Engineering of copper sulfide mediated by phototherapy performance.

Copper sulfide based phototherapy, including photothermal therapy and photodynamic therapy, is an emerging minimally invasive treatment of tumor, which the light was converted to heat or reactive oxygen to kill the tumor cells. Compared with conventional chemotherapy and radiation therapy, Cu2-x S based phototherapy is more efficient and has fewer side effects. However, considering the dose-dependent toxicity of Cu2-x S, the performance of Cu2-x S based phototherapy still cannot meet the requirement of the clinical application to now. To overcome this limitation, engineering of Cu2-x S to improve the phototherapy performance by increasing light absorption has attracted extensive attention. For better guidance of Cu2-x S engineering, we outline the currently engineering method being explored, including (1) structural engineering, (2) compositional engineering, (3) functional engineering, and (4) performance engineering. Also, the relationship between the engineering method and phototherapy performance was discussed in this review. In addition, the further development of Cu2-x S based phototherapy is prospected, including smart materials based phototherapy, phototherapy induced immune microenvironment modulation et al. This review will provide new ideas and opportunities for engineering of Cu2-x S with better phototherapy performance. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Phloretin-induced STAT3 inhibition suppresses pancreatic cancer growth and progression via enhancing Nrf2 activity.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a malignant pancreatic tumor charactered by a rapid progression and high lethal rate. Hyperactivation of STAT3 signaling exerts a vital effect on the growth and progression of PDAC. While dietary flavonoid phloretin has anti-inflammatory and antioxidant activities, it remains unclear whether phloretin has anti-tumor effects on PDAC. PURPOSE: The focus of the present study is to elucidate the effects of phloretin on PDAC and investigate its underlying molecular mechanisms. STUDY DESIGN AND METHODS: Effect of phloretin were assessed in the pancreatic cancer cells (PCCs) by colony formation assay, real-time cell analysis, flow cytometry, Immunofluorescence staining, and cell migration assay. The expressions of mRNA and protein were respectively analyzed by quantitative PCR and Western blotting. A xenograft model was used to appraise the antitumor efficacy of phloretin. RESULTS: Phloretin treatment significantly restrained cell viability and metastasis, induced DNA injury and ROS accumulation, and triggered mitochondrial-dependent apoptosis in PCCs. Mechanistically, phloretin exhibits anti-tumor potential via inactivating STAT3 signaling and enhancing Nrf2 activity. STAT3 overexpression and Nrf2 silencing partially relieved phloretin-induced inhibition on cell growth and metastasis in PCCs. Phloretin remarkably blocked pancreatic tumor growth and metastasis in vivo. CONCLUSIONS: Phloretin suppresses pancreatic cancer growth and progression through inhibition of STAT3 mediated by enhancing Nrf2 activity. Phloretin may serve as a promising therapeutic agent for PDAC.

Engineering of an endogenous hydrogen sulfide responsive smart agent for photoacoustic imaging-guided combination of photothermal therapy and chemotherapy for colon cancer.

INTRODUCTION: Photothermal therapy can be synergistically combined with chemotherapy to improve the therapeutic effect for colon cancer. However, conventional therapeutic agents have side effects in normal tissues, limiting their application. OBJECTIVES: To reduce these side effects, a smart agent (Cur@HKUST-1@PVP) whose functionality is triggered by the high content of endogenous hydrogen sulfide in colon tumors was engineered for photoacoustic imaging-guided combination of photothermal therapy and chemotherapy for colon tumors. METHODS: After reacting with hydrogen sulfide, Cur@HKUST-1@PVP simultaneously generates CuS and releases curcumin. The generated CuS serves as an imaging agent for both photothermal therapy and photoacoustic imaging, while the released curcumin is used for chemotherapy. RESULTS: In vivo photoacoustic imaging experiments demonstrated that Cur@HKUST-1@PVP can be used for selectively imaging colon cancer tumors. In vivo experiments in mice for treatment suggested that the endogenous hydrogen sulfide-activated combination of photothermal therapy and chemotherapy has a better treatment effect that photothermal therapy or chemotherapy treatment alone. CONCLUSION: The endogenous hydrogen sulfide-activated Cur@HKUST-1@PVP agent developed herein shows great potential for the accurate diagnosis and effective treatment of colon cancer.

Lumbar Spine Bone Mineral Density Measurement: Comparison of Dual-Energy X-Ray Absorptiometry and Fat Content Evaluation by Dixon Chemical Shift MRI.

Background: To assess whether the fat signal intensity and fat fraction (FF) of the lumbar vertebrae as measured on the Dixon chemical shift magnetic resonance imaging (MRI) technique can be correlated with the lumbar vertebra bone mineral density (BMD) measured using dual-energy X-ray absorptiometry (DXA). Methods: Forty-five patients were retrospectively collected, and 180 lumbar vertebral bodies (L1-L4) were included. All patients underwent DXA and MRI examinations of the lumbar spine. Taking the T value of DXA as the gold standard and using the diagnostic criteria of the World Health Organization: T score ≥ -1.0SD as normal, -1.0 ~ -2.5SD as osteopenia, and ≤ -2.5SD as osteoporosis. Meanwhile, the signal intensity on T2WI was measured, and FF of L1-L4 vertebral bodies was calculated on MRI images. Bone marrow fat FF calculation formula: FF = [Mfat/(Mfat + Mwater)] × 100% (Mwater and Mfat refer to the total pixel signal intensity value of the region of interest in water image and lipid image, respectively). Finally, the association of signal intensity and FF with DXA was evaluated. Results: Totally 180 vertebral bodies in 45 patients were enrolled. According to the T value, they were divided into the normal group (n = 70), osteopenia group (n = 40), and osteoporosis group (n = 70). The fat signal intensity of the normal group, osteopenia group, and osteoporosis group were 96.6 ± 21.8, 154.5 ± 48.7, 216.3 ± 92.6, and the FF were 30.1 ± 6.2%, 52.6 ± 7.6%, 77.5 ± 7.9%, respectively. Among the three groups, the lumbar T2 fat signal intensity and FF had statistical differences (P < 0.01). Besides, the lumbar fat signal intensity and FF were negatively related to DXA (r =-0.65 and -0.93, P < 0.01). Conclusion: The fat content calculated using the Dixon chemical shift MRI had an inverse relation with BMD. Moreover, the Dixon chemical shift MRI might provide complementary information to osteoporosis-related research fields.

Hyaluronic acid-coated Bi:Cu2O: an H2S-responsive agent for colon cancer with targeted delivery and enhanced photothermal performance.

BACKGROUND: Endogenous hydrogen sulfide (H2S)-responsive theranostic agents have attracted extensive attention due to their specificity for colon cancer. However, the development of such agents with high enrichment in tumors and excellent photothermal performance remains challenging. RESULTS: We prepared hyaluronic acid (HA)-coated Bi-doped cuprous oxide (Bi:Cu2O@HA) via a one-pot method. The HA specifically targets colon cancer tumor cells to improve the enrichment of Bi:Cu2O@HA at tumor sites, while the doped Bi both enhances the photothermal performance of the H2S-triggered Cu2O and serves as an agent for tumor imaging. The results in this work demonstrated that the Bi:Cu2O@HA nanoparticles exhibit good biocompatibility, target colon cancer tumor cells, facilitate computed tomography imaging, and enhanced H2S-responsive photothermal therapy performance, resulting in an excellent therapeutic effect in colon cancer. CONCLUSIONS: The novel Bi:Cu2O@HA nanoparticles exhibit excellent tumor targeting and photothermal therapeutic effects, which provide new strategies and insights for colon cancer therapy.

Shikonin inhibited glycolysis and sensitized cisplatin treatment in non-small cell lung cancer cells via the exosomal pyruvate kinase M2 pathway.

The active ingredient of the traditional Chinese medicine comfrey is shikonin, a naphthoquinone compound. The focus of this study was to investigate the effect of shikonin on the proliferation, invasion, migration, and chemoresistance of non-small cell lung cancer (NSCLC) cells, and to explore its underlying molecular biological mechanisms. The results show that shikonin inhibited the viability, proliferation, invasion, and migration of NSCLC cells A549 and PC9, and induced apoptosis. As the inhibitor of pyruvate kinase M2 (PKM2), a key enzyme in glycolysis, shikonin inhibited glucose uptake and the production of lactate, the final metabolite of aerobic glycolysis. In vivo chemotherapeutic assay showed that shikonin reduced the tumor volume and weight in NSCLC mice model and increased the sensitivity to cisplatin chemotherapy. Histoimmunology experiments showed the combination of shikonin and cisplatin downregulated the expression of PKM2 and its transcriptionally regulated downstream gene glucose transporter 1 (Glut1) in tumor tissue. In an assessment of glucose metabolism, micro-PET/CT data showed a combination of shikonin and cisplatin inhibited the fluorodeoxy glucose (18F-FDG) uptake into tumor. Since exosomal PKM2 affected the sensitivity to cisplatin in NSCLC cells, we also demonstrated shikonin could inhibit exosome secretion and exosomal PKM2 through the administration of exosomal inhibitor GW4869. Furthermore, shikonin sensitized cisplatin treatment by reducing the extracellular secretion of exosomal PKM2. In conclusion, we suggest that shikonin not only inhibits PKM2 intracellularly but also reduces glycolytic flux and increases cisplatin sensitivity through the exosomal pathway.

Altered thalamic functional connectivity and cerebral blood flow in insomnia disorder: a resting-state functional magnetic resonance imaging study.

BACKGROUND AND PURPOSE: The thalamus plays a crucial role in sleep regulation, but few studies have examined functional connectivity of the thalamus in insomnia disorder. This study aimed to investigate the connectivity patterns and perfusion of the thalamus in patients with insomnia disorder using resting-state functional connectivity and three-dimensional arterial spin labeling (3D ASL). MATERIALS AND METHODS: In total, 56 patients with insomnia disorder and 59 healthy control participants with a similar age-, gender-, and education lever distribution underwent resting-state functional magnetic resonance imaging (rs-fMRI) and 3D-ASL. The thalamus was selected as the seed region. Whole-brain connectivity was assessed using rs-fMRI. Cerebral blood flow (CBF) of the bilateral thalamus was measured with 3D-ASL using region-of-interest (ROI) analysis. All participants completed a series of neuropsychological assessments. Sleep parameters were assessed via polysomnography (PSG). The relationships between imaging parameters and clinical variables were assessed with Pearson correlation analysis. RESULTS: Compared with healthy controls, patients with insomnia disorder exhibited increased connectivity between the left thalamus and right precentral gyrus, and right thalamus and left middle frontal gyrus (MFG), right superior parietal lobule (SPL) and right superior frontal gyrus (SFG). Whereas decreased connectivity was noted between the right thalamus and left posterior cerebellar lobe including Crus I, Crus II, and VII b/VII. Connectivity between the right thalamus and left Crus I was positively correlated with MoCA scores (r = 0.286, P = 0.036) in insomnia disorder. CONCLUSIONS: Our findings illustrate functional abnormalities in brain connectivity and their relationship with cognitive impairments in insomnia disorder, providing novel insight into the neural mechanisms of insomnia disorder.

Hydrazine Hydrate Accelerates Neocuproine-Copper Complex Generation and Utilization in Alkyne Reduction, a Significant Supplement Method for Catalytic Hydrogenation.

Diimine (HN═NH) is a strong reducing agent, but the efficiency of diimine oxidized from hydrazine hydrate or its derivatives is still not good enough. Herein, we report an in situ neocuproine-copper complex formation method. The redox potential of this complex enable it can serve as an ideal redox catalyst in the synthesis of diimine by oxidation of hydrazine hydrate, and we successfully applied this technique in the reduction of alkynes. This reduction method displays a broad functional group tolerance and substrate adaptability as well as the advantages of safety and high efficiency. Especially, nitro, benzyl, boc, and sulfur containing alkynes can be reduced to the corresponding alkanes directly, which provides a useful complementary method to traditional catalytic hydrogenation. Besides, we applied this method in the preparation of the Alzheimer's disease drug CT-1812 and studied the mechanism.

Toxicity of Melastoma dodecandrum Lour. and its effects on lipopolysaccharide-induced inflammation and oxidative stress.

Melastoma dodecandrum Lour. (MDL) is component used in traditional Chinese medicine that is widely distributed throughout southern China. MDL has been long utilized in clinical treatment for various conditions, such as inflammation. However, the toxicity and underlying anti-inflammatory mechanism of MDL remain to be elucidated. In the present study, Sprague-Dawley rats received intragastric administration of MDL for 2 months, and the toxicity of MDL was investigated. The rats were treated with lipopolysaccharide (LPS) for 8 h to determine the potential anti-inflammatory mechanism of MDL. The results demonstrated that MDL alone did not affect the expression levels of factors associated with inflammation (IL-1ß, IL-6 and TNF-α) and oxidative stress [malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide (NO)] in the rat serum and exerted no effects on rat liver and kidneys. By contrast, MDL attenuated LPS-induced inflammation and oxidative stress by regulating specific cytokines, such as IL-1ß, IL-6, TNF-α, MDA, SOD and NO in the rat serum and alleviated LPS-induced liver and kidney damage. Additionally, compared with the LPS group, MDL inhibited CD4+ T cell differentiation into Th1 and Th17 cells and enhanced CD4+ T cell differentiation into Th2 and Treg cells. MDL also suppressed reactive oxygen species (ROS) production and mitochondrial apoptosis by modulating mitochondrial apoptosis-related proteins in spleen CD4+ T cells. In conclusion, the results of the present study demonstrated the non-toxic nature of MDL and revealed that it alleviated LPS-induced inflammation and oxidative stress by regulating differentiation and ROS production in CD4+ T cells.

Moxibustion therapy for treating psoriasis vulgaris: A protocol for systematic review and meta-analysis.

BACKGROUND: Psoriasis vulgaris (PV) is an immune-mediated skin disease, which has seriously affected the quality of life of patients. At present, moxibustion therapy has been widely used in the treatment of PV. The purpose of this study is to provide high-quality evidence-based medicine to evaluate the effectiveness and safety of moxibustion for PV. METHODS: We will search the following Electronic databases from their inceptions to February 2021 without any language limitation: PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, WangFang Database, Chinese Science Journal Database, Chinese Biomedical Literature Database. What's more, the grey literature and the references of all included literature will also be retrieved manually. Any clinical randomized controlled trials (RCTs) related to moxibustion therapy for PV will be taken into. In order to complete data synthesis and assess the risk of bias, we will use the RevMan V.5.3 software. RESULTS: This systematic review will provide an assessment of the current state of moxibustion for PV, aiming to assess the efficacy and safety of moxibustion for patients with PV. CONCLUSION: This systematic review will establish convincing evidence to prove the effectiveness and safety of moxibustion for PV. INPLASY REGISTRATION NUMBER: INPLASY202120008.

Fire needle therapy for blood stasis syndrome of plaque psoriasis: A protocol for systematic review and meta-analysis.

BACKGROUND: Plaque psoriasis (PSO) is a common clinical chronic inflammatory skin disease. The incidence rate is increasing year by year due to the fast pace of work and unhealthy diet. Fire needle has been widely used in the treatment of PSO. However, the efficacy of fire needle for PSO is uncertain. Thus, the purpose of this systematic review is to evaluate the effectiveness and safety of fire needle for PSO (blood stasis syndrome). METHODS: The following electronic databases will be searched from inception to October 2020:PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure, WangFang Database, Chinese Science Journal Database, Chinese Biomedical Literature Database. In addition, other documents that meet the requirements will be manually searched, including conference papers, dissertations, etc. All randomized controlled trials using fire needle to treat PSO (blood stasis syndrome) that meet the criteria for inclusion will be included. The primary outcomes are clinical efficacy, Psoriasis area and severity index. Secondary outcomes include Itchy, TCM evaluation standard syndrome score, Dermatological quality of life index, and adverse events. To complete data synthesis and assess the risk of bias, we will use the RevMan V.5.3 software. RESULTS: The review results will be published in a peer-reviewed journal. CONCLUSION: This study will provide high-quality evidence based medicine to evaluate the effectiveness and safety of fire needle for PSO (blood stasis syndrome), and further seek its scientific and effective chinese medicine treatment methods. INPLASY REGISTRATION NUMBER: INPLASY202120007.

Arsenic Dispensing Powder Promotes Erythropoiesis in Myelodysplastic Syndromes via Downregulation of HIF1A and Upregulation of GATA Factors.

Traditional Chinese Medicine (TCM) is a practical medicine based on thousands of years of medical practice in China. Arsenic dispensing powder (ADP) has been used as a treatment for MDS patients with a superior efficacy on anemia at Xiyuan Hospital of China Academy of Chinese Medical Sciences. In this study, we retrospectively analyzed MDS patients that received ADP treatment in the past 9 years and confirmed that ADP improves patients' anemia and prolongs overall survival in intermediate-risk MDS patients. Then, we used the MDS transgenic mice model and cell line to explore the drug mechanism. In normal and MDS cells, ADP does not show cellular toxicity but promotes differentiation. In mouse MDS models, we observed that ADP showed significant efficacy on promoting erythropoiesis. In the BFU-E and CFU-E assays, ADP could promote erythropoiesis not only in normal clones but also in MDS clones. Mechanistically, we found that ADP could downregulate HIF1A in MDS clones through upregulation of VHL, P53 and MDM2, which is involved in two parallel pathways to downregulate HIF1A. We also confirmed that ADP upregulates GATA factors in normal clones. Thus, our clinical and experimental studies indicate that ADP is a promising drug to promote erythropoiesis in both MDS and normal clones with a superior outcome than current regular therapies. ADP promotes erythropoiesis in myelodysplastic syndromes via downregulation of HIF1A and upregulation of GATA factors.

NIR-laser-triggered gadolinium-doped carbon dots for magnetic resonance imaging, drug delivery and combined photothermal chemotherapy for triple negative breast cancer.

BACKGROUND: Owing to high genetic diversities of tumor cells and low response rate of standard chemotherapy, patients with triple negative breast cancer (TNBC) have short progression-free survivals and poor outcomes, which need to explore an effective approach to improve therapeutic efficacy. METHODS: Novel gadolinium doped carbon dots (Gd@CDs) have been designed and prepared through hydrothermal method with 3,4-dihydroxyhydrocinnamic acid, 2,2'-(ethylenedioxy)bis(ethylamine) and gadolinium chloride. The synthesized nanostructures were characterized. Taking advantage of good biocompatibility of Gd@CDs, a nanoplatform based on Gd@CDs has been developed to co-deliver chemotherapy drug doxorubicin hydrochloride (Dox) and a near-infrared (NIR) photothermal agent, IR825 for magnetic resonance imaging (MRI) guided photothermal chemotherapy for TNBC. RESULTS: The as-synthesized Dox@IR825@Gd@CDs displayed favorable MRI ability in vivo. Upon NIR laser irradiation, Dox@IR825@Gd@CDs could convert the NIR light to heat and efficiently inhibit tumor growth through photothermal chemotherapy in vitro and in vivo. Additionally, the impact of photothermal chemotherapy on the murine motor coordination was assessed by rotarod test. Dox@IR825@Gd@CDs presented low toxicity and high photothermal chemotherapy efficiency. CONCLUSION: A noble theranostic nanoplatform (Dox@IR825@Gd@CDs) was developed that could be tailored to achieve loading of Dox and IR825, intracellular delivery, favorable MRI, excellent combination therapy with photothermal therapy and chemotherapy to enhance therapeutic effect against TNBC cells. This study will provide a promising strategy for the development of Gd-based nanomaterials for MRI and combinational therapy for TNBC.

Herb pair of Ephedrae Herba-Armeniacae Semen Amarum alleviates airway injury in asthmatic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Ephedrae Herba (EH, Ephedra sinica Stapf.) and Armeniacae Semen Amarum (ASA, Prunus armeniaca L. var. ansu Maxim.) have been used to treat asthma, cold, fever, and cough in China for thousands of years. AIM OF THE STUDY: In this study, we aimed to investigate the optimal ratio of EH and ASA compatibility (EAC) to reduce airway injury in asthmatic rats and its possible mechanism. METHODS: Rats were sensitized with a mixture of acetylcholine chloride and histamine bisphosphate 1 h before sensitization by intragastric administration of EAC or dexamethasone or saline for 7 days. Subsequently, the ultrastructure of rat airway epithelial tissue changes, apoptosis of the airway epithelial cells, and the expression of mRNA and protein of EGRF and Bcl-2 were detected. RESULTS: Transmission electron microscope: EAC (groups C and E) had the most prominent effect on repairing airway epithelial cells' ultrastructural changes in asthmatic rats. TUNEL: dexamethasone and EAC (groups B、C、E and F) inhibited the apoptosis of airway epithelial cells in asthmatic rats (P < 0.05). In situ hybridization: EAC (group E) inhibited the overexpression of EGFR and Bcl-2 mRNA (P < 0.05).Western Blotting: EAC (groups A、B、C、E and F) inhibited the upregulation of airway epithelial EGFR and Bcl-2 protein expression (P < 0.01). CONCLUSIONS: Our findings indicate that EAC can inhibit abnormal changes in airway epithelial structure and apoptosis of airway epithelial cells, thereby alleviating airway injury. In this study, the best combination of EH and ASA to alleviate airway epithelial injury in asthmatic rats was group E (EH: ASA = 8: 4.5).

Polycarbonate-based ultra-pH sensitive nanoparticles improve therapeutic window.

Stimuli-sensitive nanomaterials with cooperative response are capable of converting subtle and gradual biological variations into robust outputs to improve the precision of diagnostic or therapeutic outcomes. In this study, we report the design, synthesis and characterization of a series of degradable ultra-pH sensitive (dUPS) polymers that amplify small acidic pH changes to efficacious therapeutic outputs. A hydrolytically active polycarbonate backbone is used to construct the polymer with pH-dependent degradation kinetics. One dUPS polymer, PSC7A, can achieve activation of the stimulator of interferon genes and antigen delivery upon endosomal pH activation, leading to T cell-mediated antitumor immunity. While a non-degradable UPS polymer induces granulomatous inflammation that persists over months at the injection site, degradable PSC7A primes a transient acute inflammatory response followed by polymer degradation and complete tissue healing. The improved therapeutic window of the dUPS polymers opens up opportunities in pH-targeted drug and protein therapy.

Nature-derived anticancer steroids outside cardica glycosides.

Steriods which are ubiquitous in natural resources are important components of cell membranes and involved in several physiological functions. Steriods not only exerted the anticancer activity through inhibition of various enzymes and receptors in cancer cells, inclusive of aromatase, sulfatase, 5α-reductase, hydroxysteroid dehydrogenase and CYP 17, but also exhibited potential activity against various cancer forms including multidrug-resistant cancer with low cytotoxicity, and high bioavailability. Accordingly, steroids are useful scaffolds for the discovery of novel anticancer agents. This review aims to outline the advances of nature-derived steroids outside cardica glycosides with anticancer potential, covering the articles published between Jan. 2015 and Aug. 2020.

Efficacy and safety of fire needle therapy for blood stasis syndrome of plaque psoriasis: protocol for a randomized, single-blind, multicenter clinical trial.

BACKGROUND: Fire needle therapy is a characteristic treatment in traditional Chinese medicine (TCM). An increasing number of studies have indicated that fire needle treatment for psoriasis provides satisfactory results with few side effects and a low recurrence rate. We herein describe the protocol for a multicenter, randomized, single-blind, placebo-controlled trial that will provide high-quality evidence on the efficacy and safety of fire needle therapy for plaque psoriasis. METHODS: Ninety-two patients with blood stasis syndrome (BSS) of plaque psoriasis will be enrolled and randomly assigned to receive fire needle therapy (intervention group) or fire needle control therapy (control group) once a week for 4 weeks. The Psoriasis Area and Severity Index (PASI) score will serve as the major efficacy index, while the body surface area (BSA), Physician Global Assessment (PGA) score, Dermatology Life Quality Index (DLQI) score, patient-reported quality of life (PRQoL), visual analog scale (VAS) score for itching, TCM symptom score, and relapse rate will be assessed as secondary outcomes. The PASI score, BSA, PGA score, and VAS score for itching will be evaluated at baseline and during the 4-week treatment and follow-up periods. DLQI score, PRQoL, and TCM symptom score will be assessed at baseline and during the treatment period. Recurrence will be evaluated during the follow-up period. Safety assessments include vital sign monitoring, routine blood tests, blood biochemistry, routine urine tests, pregnancy tests, physical examinations, and adverse-event recording. SAS software will be used for data analysis. The data network platform will be designed by the data management center of Nanjing Ningqi Medical Technology Co., Ltd. DISCUSSION: It is believed that fire needle therapy can activate the meridians, promote blood circulation, and regulate skin immunity. BSS of plaque psoriasis is related to not only immune dysfunction but also poor or stagnant blood flow. We anticipate that the results of the trial described in this protocol will provide strong evidence for the safety and efficacy of fire needle therapy for BSS of plaque psoriasis. TRIAL REGISTRATION: Clinicaltrials.gov NCT03953885 . Registered on May 15, 2019. Name: Fire Needle Therapy on Plaque Psoriasis with Blood Stasis Syndrome.

The effect of Jiedu Huoxue decoction on rat model of experimental nonbacterial prostatitis via regulation of miRNAs.

CONTEXT: The underlying mechanisms of Jiedu Huoxue decoction (JDHXD) in treating chronic prostatitis have not been fully explored. OBJECTIVE: This study investigates the miRNAs as potential biomarkers and the effect of JDHXD on the rat model of experimental nonbacterial prostatitis. MATERIALS AND METHODS: Fifty-four Sprague-Dawley male rats were randomly divided into normal control, model, JDHXD low dose (0.5 g/kg/day), medium dose (1 g/kg/day), high dose (2 g/kg/day) and western medicine (cernilton 0.094 g/kg/day) groups, and intragastrically administered once daily for 30 days. The control and model (upon successful establishment) groups received distilled water. Differential expression of miRNAs was analysed with high-throughput miRNA sequencing and validated with qRT-PCR and Northern blot. Prediction of specific target genes and functional enrichment analysis were performed with bioinformatics. RESULTS: LD50 test showed no sign of toxicity with maximum feasible dose 4 g/kg JDHXD. Compared with control, 495 miRNAs showed expression changes in CAP/CPPS rats, of which 211 were significantly different and 37 were prostatic-related. There were 181 differentially expressed miRNAs between the model and high dose JDHXD groups, of which 23 were identical with the control and model groups. Compared with control, miR-146a, miR-423 and miR-205 expression increased significantly in the model group, decreased dose-dependently in the JDHXD groups (p < 0.05), and vice-versa for miR-96 (p < 0.05). The effect of low dose JDHXD was comparable to cernilton (p > 0.05). DISCUSSION AND CONCLUSIONS: Future studies may explore the contributions of the active components in JDHXD. The study design is generalisable. The effect can be repeatedly verified in clinical trials.

Development of a sensitive and rapid UHPLC-MS/MS method for simultaneous quantification of nine compounds in rat plasma and application in a comparative pharmacokinetic study after oral administration of Xuefu Zhuyu Decoction and nimodipine.

Xuefu Zhuyu Decoction (XFZYD) is a traditional Chinese medicine prescription used for the clinical treatment of traumatic brain injury (TBI). The purpose of this work was to develop a sensitive and rapid UHPLC-MS/MS method to simultaneously study the pharmacokinetics of nimodipine and eight components of XFZYD, namely, amygdalin, hydroxysafflor yellow A, rutin, liquiritin, narirutin, naringin, neohesperidin and saikosaponin A, in rats with and without TBI. Multiple reaction monitoring was highly selective in the detection of nine analytes and the internal standard without obvious interference. The calibration curves displayed good linearity (r > 0.99) over a wide concentration range. The mean absolute recoveries of the nine analytes were 85-106%, and all matrix effects were in the range 80-120%. The intra- and inter-day precision and accuracy were acceptable (RSD, <15%; RE%, ±20%). The validated method was successfully applied to compare the pharmacokinetics in four experimental groups, including control rats orally administered XFZYD and TBI model rats orally administered XFZYD, XFZYD and nimodipine, or nimodipine alone. The results showed that herb-drug interactions occurred between XFZYD and nimodipine in the treatment of TBI, nimodipine affected the pharmacokinetics of XFZYD, and XFZYD affected the absorption, distribution and excretion of nimodipine in vivo.

Effects of moving cupping therapy for plaque psoriasis: study protocol for a randomized multicenter clinical trial.

BACKGROUND: It is difficult to achieve a balance among safety, efficacy, and cost for the clinical treatment of plaque psoriasis. The current treatment of psoriasis often involves comprehensive therapy such as topical plasters, internal medicine, and phototherapy, which are expensive, and some of the drugs have serious side effects. Moving cupping is a type of cupping that has been used clinically for thousands of years in China. It has the advantage of being inexpensive and easy to perform. Therefore, it is widely used in public hospitals in China for psoriasis treatment. However, a comprehensive evaluation of the current clinical evidence of its efficacy is lacking. In this study, we aimed to evaluate the efficacy and safety of moving cupping to treat plaque psoriasis. METHODS: A multicenter, two-arm parallel group, single-blind, randomized, controlled trial will be conducted at six hospitals in China between August 1, 2019 and December 31, 2021. A total of 122 adult patients (aged 18-65 years) who meet the inclusion criteria are being recruited. Participants will receive either basic treatment combined with moving cupping therapy or basic treatment combined with moving cupping placebo. The treatment cycle will be 4 weeks, and the efficacy of treatment will be assessed weekly by the Psoriasis Area and Severity Index during the treatment period and follow-up visits at weeks 6 and 8. The body surface area, physician's global assessment, Dermatology Life Quality Index, patient-reported quality of life, visual analog scale, Traditional Chinese Medication syndrome scoring scale, combined medication, and adverse events will also be recorded and compared to the relative baseline values. DISCUSSION: The findings of this trial may lead to better decisions regarding the treatment of plaque psoriasis. If the trial outcomes are considered favorable, this ancient Chinese medical therapy may be worthy of widespread use because of its convenience and low cost. TRIAL REGISTRATION: This study was registered on May 15,2019 at ClinicalTrials.gov with the identifier number NCT03952676.