Curcumin affects autophagy of prolactinoma cells by upregulating miR-206 to exert antitumor effects.

We explored the effects of curcumin on the aberrant biological behaviors of prolactinoma cells and the downstream pathways through which curcumin exerts its antitumor effects. We used quantitative reverse transcription-polymerase chain reaction assays to measure miR-206 expression levels in peripheral blood samples from patients with prolactinoma before and after curcumin treatment. We also investigated the proliferation level, viability, and invasion ability of groups of cells treated with different concentrations of curcumin using 3-(4,5)-dimethylthiahiazo (-z-y1)-3-di-phenytetrazoliumromide (MTT) assays, cell cloning assays, and Transwell assays, respectively. Furthermore, we determined the levels of autophagy-related proteins and protein kinase B/mammalian target of the rapamycin (Akt/mTOR) signaling pathway-related proteins in each group of treated cells by western blot. Curcumin treatment upregulated miR-206 expression levels in the peripheral blood of patients with prolactinoma and in GH3 cells. Knockdown of miR-206 expression enhanced the proliferation and invasive ability of GH3 cells, while curcumin treatment effectively inhibited the aberrant biological behavior of GH3 cells enhanced by miR-206 knockdown. miR-206 knockdown also activated the Akt/mTOR signaling pathway and inhibited autophagy in GH3 cells, and these changes were effectively reversed by curcumin treatment. Thus, curcumin inhibited the Akt/mTOR signaling pathway and promoted cell autophagy by miR-206 upregulation, resulting in antitumor effects that inhibited prolactinoma cell proliferation and invasion.

Deep learning of pretreatment multiphase CT images for predicting response to lenvatinib and immune checkpoint inhibitors in unresectable hepatocellular carcinoma.

Objectives: Combination therapy of lenvatinib and immune checkpoint inhibitors (CLICI) has emerged as a promising approach for managing unresectable hepatocellular carcinoma (HCC). However, the response to such treatment is observed in only a subset of patients, underscoring the pressing need for reliable methods to identify potential responders. Materials & methods: This was a retrospective analysis involving 120 patients with unresectable HCC. They were divided into training (n = 72) and validation (n = 48) cohorts. We developed an interpretable deep learning model using multiphase computed tomography (CT) images to predict whether patients will respond or not to CLICI treatment, based on the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1). We evaluated the models' performance and analyzed the impact of each CT phase. Critical regions influencing predictions were identified and visualized through heatmaps. Results: The multiphase model outperformed the best biphase and uniphase models, achieving an area under the curve (AUC) of 0.802 (95% CI = 0.780-0.824). The portal phase images were found to significantly enhance the model's predictive accuracy. Heatmaps identified six critical features influencing treatment response, offering valuable insights to clinicians. Additionally, we have made this model accessible via a web server at http://uhccnet.com/ for ease of use. Conclusions: The integration of multiphase CT images with deep learning-generated heatmaps for predicting treatment response provides a robust and practical tool for guiding CLICI therapy in patients with unresectable HCC.

NRP1 regulates autophagy and proliferation of gastric cancer through Wnt/ß-catenin signaling pathway.

Gastric cancer possesses high lethality rate, and its complex molecular mechanisms of pathogenesis lead to irrational treatment outcomes. Autophagy plays a dual role in cancer by both promoting and suppressing the cancer. However, the role of autophagy in gastric cancer is still vague. Therefore, in this study, we first obtained autophagy-related genes from the Human Autophagy Database, and then applied consensus clustering analysis to analyse the molecular subtypes of gastric cancer samples in the TCGA database. The genes obtained after subtyping were then applied to construct risk prognostic model. Following this, PCA and tSNE assessed risk scores with good discriminatory ability for gastric cancer samples. The results of Cox regression analysis and time-dependent ROC curve analysis indicated that the model had good risk prediction ability. Finally, NRP1 was selected as the final study subject in the context of expression pairwise analysis, Kaplan-Meier curves and external validation of the GEO dataset. In vitro experiments showed that NRP1 has the ability to regulate the proliferation and autophagy of gastric cancer cells by affecting the Wnt/ß-catenin signalling pathway. Similarly, in vivo experiments have shown that NRP1 can affect tumour growth in vivo. We therefore propose that NRP1 can be used as both a prognostic factor and a therapeutic target through the regulation of autophagy in gastric cancer.

A sponge heated by electromagnetic induction and solar energy for quick, efficient, and safe cleanup of high-viscosity crude oil spills.

Frequent oil spills have caused severe environmental and ecological damage. Effective cleanup has become a complex challenge owing to the poor flowability of viscous crude oils. The current method of solar heating to reduce the viscosity of heavy oil is only suitable during sunny days, while the use of Joule heating is limited by the risk of direct exposure to high-voltage electricity. Herein, we demonstrate a noncontact electromagnetic induction and solar dual-heating sponge for the quick, safe, and energy-saving cleanup of ultrahigh-viscosity heavy oil. The resulting sponge with magnetic, conductive, and hydrophobic properties can be rapidly heated to absorb heavy oil under alternating magnetic fields, solar irradiation, or both of these conditions. By constructing theoretical models and fitting the actual data, an in-depth analysis of induction and solar heating processes is carried out. The sponge has excellent resilience and stability, indicating its reusability, fast and continuous adsorption (16.17 g in 10 s), and large capacity (75-81 g/g, the highest value ever) for soft asphalt (a highly viscous crude oil). This work provides a new noncontact dual-heating strategy for heavy oil cleanup, in which absorbents use induction heating during an emergency and then switch to partial or full solar heating to save energy in sunny conditions. ENVIRONMENTAL IMPLICATION: Heavy oils stranded on the beach or floating on water can kill underwater plants by blocking sunlight, or trap water birds and other animals. Heavy oil also contains aromatic substances that are toxic to aquatic organisms. Although oil spills near shallow water cannot be cleaned up by fences or other machinery, an oil adsorbent can deal with this problem. However, common adsorbents cannot effectively absorb high-viscosity oils, such as heavy oil. In this paper, an induction and solar dual-heating sponge is developed for the effective cleanup of high-viscosity oil.

Caveolin-1 in spinal cord modulates type-2 diabetic neuropathic pain through the Rac1/NOX2/NR2B signaling pathway.

OBJECTIVE: The present study determines whether Cav-1 modulates the initiation, development and maintenance of type-2 DNP via the Rac1/NOX2-NR2B signaling pathway. METHODS: After regular feeding for three days, these rats were randomly divided into two groups: control group with normal-diet (maintenance feed) (n=8); type-2 DM group (n=8). In the type-2 DM group, the rats were fed with a high-fat and high-sugar diet, and received a single intraperitoneal streptozotocin (STZ) injection (35 mg/kg). At two weeks after STZ injection, these diabetic neuropathic pain (DNP) rats were treated with daidzein (0.4 mg/kg/day) and N-tert-Butyl-α-phenylnitrone (PBN, 100 mg/kg/day) for 14 days. After the type-2 DNP model was successfully established, the rats were assigned into four groups: DNP group, DNP+Da group (DNP rats with Cav-1 specific inhibitor daidzein), DNP+PBN group (DNP rats treated with ROS scavenger PBN), and SC group (solvent control group). Then, the mechanical and thermal hyperalgesia were assayed to evaluate the function of the caveolin 1-Recombinant Human Ras-Related C1/nicotinamide adenosine diphosphate oxidase 2-NR2B gene (Cav-1-Rac1/NOX2-NR2B) signaling pathway. In the mechanism study, the protein expression levels of p-Caveolin-1, Rac1, NOX2, p-NR2B and t-NR2B, the production of ROS, and the distribution of Cav-1 and NOX2 in the spinal cord were observed. RESULTS: The present study revealed that p-Cav-1 was persistently upregulated and activated in the spinal cord microglia in type-2 DNP rats. The use of the pharmacological inhibitor of Cav-1 and a ROS scavenger resulted to a significantly relieved mechanical allodynia and thermal hyperalgesia. In addition, it was demonstrated that Cav-1 promoted ROS generation via the activation of Rac1-dependent NADPH oxidase (NOX). CONCLUSION: The present data suggests that Cav-1 in the spinal cord modulates type-2 DNP via regulating the Rac1/NOX2-NR2B pathway.

Five new ent-kaurane diterpenes from Annona squamosa L. pericarps.

In the present study, five new ent-kaurane diterpenes including 4α-hydroxy-17,19-dinor-ent-kaurane-16-one (1), 4ß-hydroxy-16ß-H-18-nor-ent-kaurane-17-oic acid (2), 4ß,17-dihydroxy-16α-acetoxy-18-nor-ent-kaurane (3), Annosquamosin Z (4) and 16α-H-ent-kaurane-17,18-dioic acid, 17-methy ester (5) were isolated from Annona squamosa L. pericarp. The compounds were also evaluated for their cytotoxic activities against SMMC-7721 and HepG2 cell lines, among which compound 3 exhibited potent cytotoxicity with IC50 value of less than 20 µM.

Eight new cytotoxic annonaceous acetogenins from the seeds of Annona squamosa.

Eight new annonaceous acetogenins, squamotin A-D (1-4), annosquatin IV-V (5 and 6), muricin O (7) and squamosten B (8), together with four known ones (9-12) were isolated from the seeds of Annona squamosa. Their structures were elucidated by chemical methods and spectral data. The inhibitory activities of compound 1-9 against three multidrug resistance cell lines were evaluated. All tested compounds showed strong cytotoxicity.

Mechanism of the JAK2/STAT3-CAV-1-NR2B signaling pathway in painful diabetic neuropathy.

PURPOSE: The aim of the present study was to further elucidate the role of JAK2/STAT3-CAV-1-NR2B on painful diabetic neuropathy. METHODS: In vivo, the mechanical withdrawal threshold and thermal withdrawal latency were measured to evaluate neuropathic pain behaviors (n= 8), while western blot (n= 5) and an immunofluorescence double staining experiment (n= 6) were performed to understand the molecular mechanism. In vitro, the individual culture of BV2 mouse microglia cell lines, the co-culture of BV2 mouse microglia cell lines and PC12 rat neuron cell lines, and western blot analysis were performed to understand the molecular mechanism between microglia and neurons. RESULTS: The expression of p-JAK2, p-STAT3, t-CAV-1, and p-NR2B was upregulated in the dorsal horn of DNP rats throughout the experiment. Through the immunofluorescence double staining experiment, it was found that p-STAT3 was mainly expressed in activated microglia, and this condition can be stably maintained for approximately 2 weeks after the establishment of the DNP model. The intrathecal injection of JAK2 inhibitor AG490 can relieve the abnormal expression of p-JAK2, p-STAT3, t-CAV-1, and p-NR2B, and relieve pain. The remission of AG490 began on the third day, and it could be stably sustained for 14 days. In vitro high-glucose induced the activation of p-STAT3 in microglia, thereby upregulating the expression of p-CAV-1 and p-NR2B in neurons in the co-culture system. JAK2 inhibitor AG490 can alleviate the abnormal expression of these proteins in the JAK2/STAT3-CAV-1-NR2B signaling pathway in vitro. CONCLUSIONS: Microglial JAK2/STAT3 signaling probably contributes to neuropathic pain by activating the CAV-1-NR2B pathway.

Effects of arsenic disulfide on apoptosis, histone acetylation, toll like receptor 2 activation, and erythropoiesis in bone marrow mononuclear cells of myelodysplastic syndromes patients in vitro.

OBJECTIVE: As the main component of traditional Chinese medicine realgar, arsenic disulfide (As2S2) is widely used in treating myelodysplastic syndromes (MDS). The goal of the current study is to assess the effects of As2S2 on bone marrow mononuclear cells (BMMNC) of MDS. METHODS: BMMNCs were obtained from 10 lower risk MDS patients, 5 higher risk MDS patients, and 3 healthy controls. Then, the cells were treated with As2S2 for 48h, using vorinostat (also known as SAHA) as control. Cell proliferation and apoptosis were detected. mRNA and protein levels of histone deacetylase-1 (HDAC1), Toll-like receptor 2 (TLR2), and erythroid transcription factor (GATA-1) were detected by quantitative real-time PCR and western blot analysis. RESULTS: After As2S2 treatment in concentrations ranging from 3.125 to 100µmol/L, cell proliferation was inhibited in both lower risk and higher risk MDS. Fifty percent inhibitory concentrations were 24.4µmol/L and 23.6µmol/L, respectively, for lower and higher risk MDS. Apoptotic cells significantly increased in both types of MDS. mRNA and protein levels of HDAC1 and TLR2 were reduced, whereas GATA-1 was increased in both types of MDS. CONCLUSIONS: As2S2 could inhibit cell proliferation and induce apoptosis through histone acetylation modulation in MDS. Similar to SAHA, As2S2 could reduce TLR2 activation and increase GATA-1 expression. Current data suggest epigenetic and immunological alternations are involved in therapeutic mechanisms of realgar in the treatment of MDS.

Coronary Heart Disease Preoperative Gesture Interactive Diagnostic System Based on Augmented Reality.

Coronary heart disease preoperative diagnosis plays an important role in the treatment of vascular interventional surgery. Actually, most doctors are used to diagnosing the position of the vascular stenosis and then empirically estimating vascular stenosis by selective coronary angiography images instead of using mouse, keyboard and computer during preoperative diagnosis. The invasive diagnostic modality is short of intuitive and natural interaction and the results are not accurate enough. Aiming at above problems, the coronary heart disease preoperative gesture interactive diagnostic system based on Augmented Reality is proposed. The system uses Leap Motion Controller to capture hand gesture video sequences and extract the features which that are the position and orientation vector of the gesture motion trajectory and the change of the hand shape. The training planet is determined by K-means algorithm and then the effect of gesture training is improved by multi-features and multi-observation sequences for gesture training. The reusability of gesture is improved by establishing the state transition model. The algorithm efficiency is improved by gesture prejudgment which is used by threshold discriminating before recognition. The integrity of the trajectory is preserved and the gesture motion space is extended by employing space rotation transformation of gesture manipulation plane. Ultimately, the gesture recognition based on SRT-HMM is realized. The diagnosis and measurement of the vascular stenosis are intuitively and naturally realized by operating and measuring the coronary artery model with augmented reality and gesture interaction techniques. All of the gesture recognition experiments show the distinguish ability and generalization ability of the algorithm and gesture interaction experiments prove the availability and reliability of the system.

LncRNA UCA1 promotes renal cell carcinoma proliferation through epigenetically repressing p21 expression and negatively regulating miR-495.

Long non-coding RNAs have recently emerged as important regulators in the pathogenesis and progression of cancers. The long non-coding RNA urothelial carcinoma-associated 1 is reportedly upregulated and functions as an oncogene in some tumors. However, the role of urothelial carcinoma-associated 1 in renal cell carcinoma is not well elucidated so far. In this study, we found that urothelial carcinoma-associated 1 was overexpressed in renal cell carcinoma tissues compared with the adjacent normal tissues, and higher urothelial carcinoma-associated 1 expression levels were positively associated with advanced tumor stage and poor survival time in renal cell carcinoma patients. Further studies showed that knockdown of urothelial carcinoma-associated 1 suppressed renal cell carcinoma cell proliferation and S-phase cell number in vitro. Moreover, urothelial carcinoma-associated 1 was found to be associated with enhancer of zeste homolog 2, which suppressed p21 expression through histone methylation (H3K27me3) on p21 promoter. We also showed that knockdown of urothelial carcinoma-associated 1 increased the p21 protein expression through regulating enhancer of zeste homolog 2. In addition, bioinformatics analysis and dual-luciferase reporter assays confirmed that miR-495 was a target of urothelial carcinoma-associated 1 in renal cell carcinoma, and urothelial carcinoma-associated 1 promoted cell proliferation by negatively regulating miR-495. These findings illuminated that urothelial carcinoma-associated 1 promoted renal cell carcinoma progression through enhancer of zeste homolog 2 and interacted with miR-495. Overall, overexpression of urothelial carcinoma-associated 1 functions as an oncogene in renal cell carcinoma that may offer a novel therapeutic target for renal cell carcinoma patients.

Studies on anti-hepatoma activity of Annona squamosa L. pericarp extract.

This study investigated the anti-hepatoma activity of different extracts from A. squamosa pericarps, phytochemistry of the ethyl acetate (EtOAc) fraction and possible anti-hepatoma mechanism of active constituents. The anti-hepatoma activity of different extracts from A. squamosa pericarps were evaluated by MTT assay against SMMC-7721 cells in vitro and verified by using H22 xenografts bearing mice. Phytochemical investigation of the active pericarp extract was carried out. The pro-apoptosis and cycle arrest effects of active constituents were observed by fluorescent microscope and flow cytometry. Western blot assay was conducted to find the possible anti-hepatoma mechanisms of active constituents. The result showed that EtOAc extract was the active fraction. Two ent-kaurane diterpenoids, named ent-kauran-16-en-19-oic acid and ent-kauran-15-en-19-oic acid, were isolated from the active EtOAc fraction. The pro-apoptosis and G1 phase arrest effects of these diterpenoids were found. Western blot assay showed that ent-kauran-16-en-19-oic acid could activate caspase-3,-8,-9, up-regulate of Bax and down-regulate of Bcl-2.

Investigations on the antifatigue and antihypoxic effects of Paecilomyces hepiali extract.

Paecilomyces hepiali, one of the most valuable and effective Chinese medicinal herbs, possesses potential antioxidant, immunomodulatory, antitumor and anti­inflammatory properties. The present study aimed to investigate the antifatigue and antihypoxic effects of Paecilomyces hepiali extract (PHC) in a mouse model. Using a rotating rod, forced swimming and running assessment, the antifatigue activity of PHC was determined. PHC administration for 7 days had no effect on mouse horizontal or vertical movement, indicating no neurotoxicity at the selected doses was observed. Using a normobaric hypoxia, sodium nitrite toxicosis and acute cerebral ischemia assessments, PHC was confirmed to possess antihypoxic effects. PHC treatment for 7 days significantly enhanced the serum and liver levels of adenosine triphosphate, superoxide dismutase and glutathione peroxidase, prior to and following 60 min of swimming. The levels of antioxidant­associated proteins in the livers of the mice were analyzed using western blotting. PHC effectively increased the expression levels of phosphorylated (p)­5'­monophosphate (AMP)­activated protein kinase (AMPK), p­protein kinase B (AKT) and p­mammalian target of rapamycin (mTOR). The results of the present study demonstrated that PHC efficiently enhanced endurance from fatigue and had antihypoxic effects through elevation of the antioxidant capacity in the serum and liver, at least in part through the AMPK and AKT/mTOR pathways. These results indicate the potential of this natural product as an antioxidant in the treatment of fatigue, hypoxia and their associated diseases.

Apoptosis in human myelodysplastic syndrome CD34+ cells is modulated by the upregulation of TLRs and histone H4 acetylation via a ß-arrestin 1 dependent mechanism.

Excessive apoptosis of hematopoietic precursors in the bone marrow underlies the ineffective hematopoiesis characteristic of myelodysplastic syndrome (MDS). Toll-like receptor (TLR) signaling is abnormally activated in MDS and may be involved in excessive programmed cell death in the pathogenesis of MDS. TLRs expression and global histone H3/H4 acetylation were analyzed in bone marrow (BM) CD34+ cells from 20 lower-risk and 20 higher-risk MDS patients and 10 healthy controls. Apoptosis of BM CD34+ cells was examined by flow cytometry, and its correlation to histone acetylation and the expression of TLR2 and ß-arrestin1 (ß-arr1), measured by enzyme-linked immunosorbent assay and qRT-PCR, was assessed. TLR1, TLR2 and TLR6 expression and H4 acetylation levels were higher in lower-risk MDS patients than in higher-risk MDS patients or controls, and TLR2 expression and H4 acetylation levels were positively correlated with an increased rate of apoptosis. Lower-risk MDS was associated with increased ß-arr1 expression and histone acetyltransferase p300 activity. In in vitro-cultured primary normal and lower-risk MDS CD34+ cells, TLR2 activation-induced apoptosis was mediated by the upregulation of ß-arr1 leading to the recruitment of p300 and increased histone H4 acetylation. The nuclear accumulation of ßarr1 following TLR2 activation promote H4 acetylation at specific target gene promoters and may thus affect transcription of target genes in BM CD34+ cells. The mechanisms underlying the deregulation of TLR2 and increased apoptosis in MDS may involve the ß-arr1 mediated recruitment of p300 leading to increased levels of histone H4 acetylation.

[Research Advances on Pathogenesis of Myelodysplastic Syndrome].

Myelodysplastic syndrome (MDS) is a clonal marrow stem cell disorder, characterized by ineffective haemopoiesis leading to blood cytopenias. As a disease of grey zone, along with the development of research, the exploration on its pathogenesis have been shifted from molecular genetics and the feature of immunophenotype to the epigenetic and micro environment. But at present, the pathogenesis of MDS is still not clear, the research of the molecular genetics and immunophenotype can not meet the needs of experimental and clinical application any longer. The hematopoietic stem cells, cytokines, epigenetic studies, however, have made a lot of achievements. Targeted medicine such as azacitidine and decitabine had promising response in treating MDS patients. In this article the abnormality of stromal cells, cytokines and epigenetic changes in hematopoietic microenvironment of MDS are reviewed in order to optimize the monitoring MDS progress and guide its clinical medication strategy.

Near Infrared Spectroscopic Combined with Partial Least Squares and Radial Basis Function Neural Network to Analyze Paclitaxel Concentration in Rat Plasma.

Paclitaxel is known as one of the most effective anticancer drugs. Near Infrared Spectroscopy (NIRS), a rapid, precise and non-destructive approach of analysis, has been widely used for qualitative and quantitative detection. The present study aims to analyze the plasma paclitaxel concentration with NIRS. Various batches of plasma samples were prepared and the concentration of paclitaxel was determined via high performance liquid chromatography tandem mass spectrometry (LC-MS/MS). The outliers and the number of calibration set were confirmed by Monte Carlo algorithm combined with partial least squares (MCPLS). Since NIR spectra may be contaminated by signals from background and noise, a series of preprocessing were performed to improve signal resolution. Moving window PLS and radical basis function neural network (RBFNN) methods were applied to establish calibration model. Although both PLS and RBFNN models are well-fitting, RBFNN-established model displayed better qualities on stability and predictive ability. The correlation coefficients of calibration curve and prediction set (Rc(2) and Rp(2)) are 0.9482 and 0.9544, respectively. Moreover, independent verification test with 20 samples confirmed the well predictive ability of RBFNN model.

Study of the analgesic activities, chronic toxicity and addictive potential of Jia-Yuan-Qing pill in rats.

Jia-Yuan-Qing pill (JYQP) composed of Porcellio laevis Latreille, Corydalis Rhizoma and Radix Cynanchi Paniculati at a ratio of 9:7:7 has been found to be an effective analgesic agent. The present study aimed to evaluate the safety, addictive potential and anti-cancer pain activity of JYQP in a rat model. During the 6-month chronic toxicity test, no significant changes in general behavior, defecation, postural abnormalities, dietary or water intake or blood biochemical parameters were observed in male and female rats. Although a high dose of JYQP (5 g/kg) caused swelling of the liver, spleen and kidney in male and female rats, no pathological changes were observed in all organs examined via hematoxylin and eosin staining. The analgesic effect of JYQP on bone cancer pain was successfully confirmed in a rat model of Walker 256 cell-induced bone cancer. In contrast to morphine, in a physical dependence test, JYQP produced no withdrawal symptoms following chronic administration. The data from this study provide experimental evidence supporting the clinical use of JYQP as an effective, safe and non-addictive agent for the treatment of bone cancer pain.

Studies on the analgesic activities of Jia-Yuan-Qing pill and its safety evaluation in mice.

The analgesic activity of Porcellio laevis Latreille, Rhizoma Corydalis, and Radix Cynanchi Paniculati have been reported in recent years. A new formula named Jia-Yuan-Qing pill (JYQP) is therefore created by combining the three herbs at 9:7:7 ratio according to traditional Chinese theories. The present study aims to evaluate the effect of JYQP as a novel painkiller in various models. Acute toxicity test was applied to evaluate the safety of JYQP. Acetic-acid-induced writhing, hot plate test, formalin test, and naloxone-pretreated writhing test were employed to elaborate the analgesic activity of JYQP and its possible mechanism. A bone cancer pain mouse model was performed to further assess the effect of JYQP in relieving cancer pain. Test on naloxone-precipitated withdrawal symptoms was conduct to examine the physical dependence of mice on JYQP. Data revealed that JYQP reduced writhing and stretching induced by acetic acid; however, this effect could not be blocked by naloxone. JYQP specifically suppressed the phase II reaction time in formalin-treated mice; meanwhile, no analgesic effect of JYQP in hot plate test was observed, indicating that JYQP exerts analgesic activity against inflammatory pain rather than neurogenic pain. Furthermore, JYQP could successfully relieve bone cancer pain in mice. No physical dependence could be observed upon long-term administration in mice. Collectively, our present results provide experimental evidence in supporting clinical use of JYQP as an effective and safe agent for pain treatment.

[Study on the detection of active ingredient contents of Paecilomyces hepiali mycelium via near infrared spectroscopy].

Partial least squares (PLS) and radial basis function neural network (RBFNN) combined with near infrared spectros- copy (NIR) were applied to develop models for cordycepic acid, polysaccharide and adenosine analysis in Paecilomyces hepialid fermentation mycelium. The developed models possess well generalization and predictive ability which can be applied for crude drugs and related productions determination. During the experiment, 214 Paecilomyces hepialid mycelium samples were obtained via chemical mutagenesis combined with submerged fermentation. The contents of cordycepic acid, polysaccharide and adenosine were determined via traditional methods and the near infrared spectroscopy data were collected. The outliers were removed and the numbers of calibration set were confirmed via Monte Carlo partial least square (MCPLS) method. Based on the values of degree of approach (Da), both moving window partial least squares (MWPLS) and moving window radial basis function neural network (MWRBFNN) were applied to optimize characteristic wavelength variables, optimum preprocessing methods and other important variables in the models. After comparison, the RBFNN, RBFNN and PLS models were developed successfully for cordycepic acid, polysaccharide and adenosine detection, and the correlation between reference values and predictive values in both calibration set (R2c) and validation set (R2p) of optimum models was 0.9417 and 0.9663, 0.9803 and 0.9850, and 0.9761 and 0.9728, respectively. All the data suggest that these models possess well fitness and predictive ability.