Rheum palmatum L. and Salvia miltiorrhiza Bge. Alleviates Acute Pancreatitis by Regulating Th17 Cell Differentiation: An Integrated Network Pharmacology Analysis, Molecular Dynamics Simulation and Experimental Validation.

OBJECTIVE: To identify the core targets of Rheum palmatum L. and Salvia miltiorrhiza Bge., (Dahuang-Danshen, DH-DS) and the mechanism underlying its therapeutic efficacy in acute pancreatitis (AP) using a network pharmacology approach and validate the findings in animal experiments. METHODS: Network pharmacology analysis was used to elucidate the mechanisms underlying the therapeutic effects of DH-DS in AP. The reliability of the results was verified by molecular docking simulation and molecular dynamics simulation. Finally, the results of network pharmacology enrichment analysis were verified by immunohistochemistry, Western blot analysis and real-time quantitative PCR, respectively. RESULTS: Sixty-seven common targets of DH-DS in AP were identified and mitogen-activated protein kinase 3 (MAPK3), Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), protein c-Fos (FOS) were identified as core targets in the protein interaction (PPI) network analysis. Gene ontology analysis showed that cellular response to organic substance was the main functions of DH-DS in AP, and Kyoto Encyclopedia of Genes and Genomes analysis showed that the main pathway included Th17 cell differentiation. Molecular docking simulation confirmed that DH-DS binds with strong affinity to MAPK3, STAT3 and FOS. Molecular dynamics simulation revealed that FOS-isotanshinone II and STAT3-dan-shexinkum d had good binding capacity. Animal experiments indicated that compared with the AP model group, DH-DS treatment effectively alleviated AP by inhibiting the expression of interleukin-1ß, interleukin-6 and tumor necrosis factor-α, and blocking the activation of Th17 cell differentiation (P<0.01). CONCLUSION: DH-DS could inhibit the expression of inflammatory factors and protect pancreatic tissues, which would be functioned by regulating Th17 cell differentiation-related mRNA and protein expressions.

Dietary pectin attenuates Salmonella typhimurium-induced colitis by modulating the TLR2-NF-κB pathway and intestinal microbiota in mice.

The role of dietary pectin on microbial-induced colitis, oxidative status, barrier function, and microbial composition, as well as the underlying mechanisms, is scarce. In this study, we aimed to investigate whether dietary pectin alleviates Salmonella typhimurium-induced colitis in mice. Male C57BL/6J mice fed an isocaloric and isofibrous diet with 7% pectin or cellulose were administered sterile water or Salmonella typhimurium to induce colitis, which is equal to a human food dose of 0.57% (5.68 g/kg). Dietary pectin alleviated Salmonella typhimurium-induced colitis and oxidative stress as shown by the reduced disease activity index score, decreased colon shortening and histological damage score, colonic hydrogen peroxide, malondialdehyde concentrations, and relative mRNA expressions of coenzyme Q-binding protein COQ10 homologue B (Coq10b), Ccl-2, Ccl-3, Ccl-8, Tnf-α, Il-1ß, Ifn-γ, Ifn-ß, and serum TNF-α protein level. Moreover, pectin administration ameliorated the downregulated colonic abundances of occludin, zonula occludens-1, zonula occludens-2, and the upregulated abundances of TLR2 and p-NF-κB in Salmonella-infected mice. Additionally, 16S rRNA analysis demonstrated that pectin altered the microbial beta-diversity and reduced Salmonella levels. Collectively, pectin ameliorated Salmonella typhimurium-induced colitis, oxidative stress, and tight junction, which may be related to the inactivation of TLR2-NF-κB signalling and reduced abundance of Salmonella.

Selenium nanoparticles improve nickel-induced testosterone synthesis disturbance by down-regulating miR-708-5p/p38 MAPK pathway in Leydig cells.

The present study was designed to investigate the role of miR-708-5p/p38 mitogen-activated protein kinase (MAPK) pathway during the mechanism of selenium nanoparticles (Nano-Se) against nickel (Ni)-induced testosterone synthesis disorder in rat Leydig cells. We conducted all procedures based on in vitro culture of rat primary Leydig cells. After treating Leydig cells with Nano-Se and NiSO4 alone or in combination for 24 h, we determined the cell viability, reactive oxygen species (ROS) levels, testosterone production, and the protein expression of key enzymes involved in testosterone biosynthesis: steroidogenic acute regulatory (StAR) and cytochrome P450 cholesterol side chain cleavage enzyme (CYP11A1). The results indicated that Nano-Se antagonized cytotoxicity and eliminated ROS generation induced by NiSO4 , suppressed p38 MAPK protein phosphorylation and reduced miR-708-5p expression. Importantly, we found that Nano-Se upregulated the expression of testosterone synthase and increased testosterone production in Leydig cells. Furthermore, we investigated the effects of p38 MAPK and miR-708-5p using their specific inhibitor during Nano-Se against Ni-induced testosterone synthesis disorder. The results showed that Ni-inhibited testosterone secretion was alleviated by Nano-Se co-treatment with p38 MAPK specific inhibitor SB203580 and miR-708-5p inhibitor, respectively. In conclusion, these findings suggested Nano-Se could inhibit miR-708-5p/p38 MAPK pathway, and up-regulate the key enzymes protein expression for testosterone synthesis, thereby antagonizing Ni-induced disorder of testosterone synthesis in Leydig cells.

Schisandrin C enhances cGAS-STING pathway activation and inhibits HBV replication.

ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra Chinensis (Turcz.) Baill. is a long-term used traditional Chinese medicine with the functions of tonifying the kidney and calming the heart, tonifying qi and engendering fluid. It can be used to treat insomnia and dreaminess, spermatorrhea, coughs, as well as liver and kidney deficiency of Yin or Yang Syndrome. Modern pharmacological studies have shown that Schisandra Chinensis regulates host immunity and exhibits anti-cancer, antiviral and liver-protecting effects. However, the specific mechanism by which Schisandra Chinensis modulates antiviral immunity is unknown. AIM OF THE STUDY: We sought to explore the therapeutic effect of the active components of Schisandra Chinensis on anti-viral immunity and further investigate the underlying mechanism. MATERIALS AND METHODS: Immunoblotting, quantitative real-time PCR, enzyme-linked immunosorbent assay, immunofluorescence, and immunoprecipitation were used to investigate the effect of schisandrin C (SC), one of the most abundant and biologically active components of Schisandra Chinensis, on the activation of cGAS-STING signaling pathway and the underlying mechanism. In addition, CMA-mediated STING activation and hydrodynamic injection-mediated HBV-replicating mouse model were used to investigate the effect of SC on the activation of STING signaling pathway and its antiviral effect in vivo. RESULTS: SC promoted cGAS-STING pathway activation, accompanied by increased production of interferon ß (IFN ß) and downstream gene expression. Moreover, SC also exerted anti-HBV effects, reducing HBeAg, HBcAg, HBsAg, and HBV DNA levels in hydrodynamic injection-mediated HBV-replicating mouse model and elevating the production of IFN ß and expression of interferon-stimulated genes (IFIT1, ISG15, and CXCL10). Mechanistically, SC could facilitate the interaction between TANK-binding kinase 1 (TBK1) and STING, which is important for IRF3 phosphorylation and production of IFN ß. CONCLUSIONS: Our study confirmed that SC enhances cGAS-STING pathway activation and inhibits HBV replication, as well as provides clues for chronic hepatitis B and other infectious diseases treated by SC.

Protective effect of glucosamine on zearalenone-induced reproductive toxicity and placental dysfunction in mice.

This study was conducted to determine the effects of glucosamine (GlcN) on zearalenone (ZEA)-induced reproductive toxicity and placental dysfunction in mice. The pregnant mice were randomly divided into one of the four groups, such as the control group, the ZEA group, the GlcN group, and the GlcN plus ZEA group. Reproductive toxicity was induced by consecutive gavages of ZEA at 5 mg/kg body weight during gestational days (GDs 0-14) and in the presence or absence of oral administration of GlcN (0.5 mM). The results showed that GlcN significantly alleviated the decrease of growth performance induced by ZEA exposure of pregnant mice. Meanwhile, ZEA ingestion significantly reduced the number and weight of fetuses, and reduction of placenta weight. Moreover, results of blood biochemical markers indicated that ZEA exposure led to increased oxidative stress levels in pregnant mice. Further analyses demonstrated that ZEA inhibited placental development, resulted in placental inflammation, increased the expression of pro-apoptotic proteins, and decreased the expression of placental tight junction proteins, which were reversed by the administration of GlcN. Results of western blot revealed that GlcN reversed ZEA-mediated phenotype by activating PI3K, while inhibiting MAPK signaling pathway. All these findings showed that GlcN was effective in the protection against ZEA-induced placental dysfunction and reproductive toxicity in pregnant mice. Supplementation of GlcN might be potential nutritional intervention with an ability to alleviate ZEA-induced toxicity in pregnant mice.

The yin-yang of immunity: Immune dysregulation in myelodysplastic syndrome with different risk stratification.

Myelodysplastic syndrome (MDS) is a heterogeneous group of myeloid clonal diseases with diverse clinical courses, and immune dysregulation plays an important role in the pathogenesis of MDS. However, immune dysregulation is complex and heterogeneous in the development of MDS. Lower-risk MDS (LR-MDS) is mainly characterized by immune hyperfunction and increased apoptosis, and the immunosuppressive therapy shows a good response. Instead, higher-risk MDS (HR-MDS) is characterized by immune suppression and immune escape, and the immune activation therapy may improve the survival of HR-MDS. Furthermore, the immune dysregulation of some MDS changes dynamically which is characterized by the coexistence and mutual transformation of immune hyperfunction and immune suppression. Taken together, the authors think that the immune dysregulation in MDS with different risk stratification can be summarized by an advanced philosophical thought "Yin-Yang theory" in ancient China, meaning that the opposing forces may actually be interdependent and interconvertible. Clarifying the mechanism of immune dysregulation in MDS with different risk stratification can provide the new basis for diagnosis and clinical treatment. This review focuses on the manifestations and roles of immune dysregulation in the different risk MDS, and summarizes the latest progress of immunotherapy in MDS.

The yin-yang effects of immunity: From monoclonal gammopathy of undetermined significance to multiple myeloma.

Multiple myeloma (MM) is the third most common malignant neoplasm of the hematological system. It often develops from monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) precursor states. In this process, the immune microenvironment interacts with the MM cells to exert yin and yang effects, promoting tumor progression on the one hand and inhibiting it on the other. Despite significant therapeutic advances, MM remains incurable, and the main reason for this may be related to the complex and variable immune microenvironment. Therefore, it is crucial to investigate the dynamic relationship between the immune microenvironment and tumors, to elucidate the molecular mechanisms of different factors in the microenvironment, and to develop novel therapeutic agents targeting the immune microenvironment of MM. In this paper, we review the latest research progress and describe the dual influences of the immune microenvironment on the development and progression of MM from the perspective of immune cells and molecules.

[Effect of moxibustion on M2 and P2X3 receptors of bladder tissue in rats with neurogenic bladder of detrusor areflexia after lumbar-sacral spinal cord injury].

OBJECTIVE: To observe the effect of moxibustion at "Guanyuan" (CV 4) and "Shenque" (CV 8) on acetylcholine (Ach), adenosine triphosphate (ATP) and muscarinic-type choline receptor (M2) and purine receptor P2X3 in bladder tissue in the rats with neurogenic bladder (NB) of detrusor areflexia after lumbar-sacral spinal cord injury and explore the underlying mechanism of moxibustion for promoting detrusor contraction. METHODS: Sixty SD rats were randomly divided into a model preparation group (n=45) and a sham-operation group (n=15). In the model preparation group, the modified Hassan Shaker spinal cord transection method was used to prepare the model of NB. In the sham-operation group, the spinal cord transection was not exerted except laminectomy and spinal cord exposure. Among the rats with successfully modeled, 30 rats were selected and divided randomly into a model group and a moxibustion group, with 15 rats in each one. On the 15th day after the operation, moxibustion was applied at "Guanyuan" (CV 4) and "Shenque" (CV 8) in the moxibustion group, 10 min at each acupoint, once a day. The consecutive 7-day treatment was as one course and the intervention for 2 courses was required. Urodynamic test was adopted to evaluate bladder function in rats. Using HE staining, the morphological changes in bladder tissue were observed. The content of Ach and ATP in bladder tissue was measured with biochemical method, and the protein and mRNA expression levels of M2 and P2X3 receptors in bladder tissue were detected with Western blot and real-time fluorescence quantification PCR method. RESULTS: Compared with the sham-operation group, the maximum bladder capacity, leakage point pressure and bladder compliance were increased in the rats of the model group (P<0.05). Compared with the model group, the maximum bladder capacity, the leakage point pressure and bladder compliance were decreased in the rats of the moxibustion group (P<0.05). In the model group, the detrusor fibres were arranged irregularly, bladder epithelial tissues were not tightly connected and cell arrangement was disordered, combined with a large number of vacuolar cells. In the moxibustion group, compared with the model group, the detrusor fibres were arranged regularly, bladder epithelial cells were well distributed and vacuolar cells were reduced. Compared with the sham-operation group, the content of Ach and ATP in bladder tissue was decreased (P<0.05), the protein and mRNA expression levels of M2 and P2X3 receptors were reduced (P<0.05) in the model group. In the moxibustion group, the content of Ach and ATP in bladder tissue was increased (P<0.05) and the protein and mRNA expression levels of M2 and P2X3 receptors were increased (P<0.05) as compared with the model group. CONCLUSION: Moxibustion at "Guanyuan" (CV 4) and "Shenque" (CV 8) may effectively improve bladder function in the rats with NB of detrusor areflexia after lumbar-sacral spinal cord injury and its underlying mechanism is related to promoting the release of Ach and up-regulating the expression of M2 receptor, thereby enhancing the release of ATP and increasing the expression of P2X3 receptor. Eventually, detrusor contraction is improved.

Integrative genomic analysis of PPP3R1 in Alzheimer's disease: a potential biomarker for predictive, preventive, and personalized medical approach.

Alzheimer's disease (AD) is associated with abnormal calcium signaling, a pathway regulated by the calcium-dependent protein phosphatase. This study aimed to investigate the molecular function of protein phosphatase 3 regulatory subunit B (PPP3R1) underlying AD, which may provide novel insights for the predictive diagnostics, targeted prevention, and personalization of medical services in AD by targeting PPP3R1. A total of 1860 differentially expressed genes (DEGs) from 13,049 background genes were overlapped in AD/control and PPP3R1-low/high cohorts. Based on these DEGs, six co-expression modules were constructed by weight gene correlation network analysis (WGCNA). The turquoise module had the strongest correlation with AD and low PPP3R1, in which DEGs participated in axon guidance, glutamatergic synapse, long-term potentiation (LTP), mitogen-activated protein kinase (MAPK), Ras, and hypoxia-inducible factor 1 (HIF-1) signaling pathways. Furthermore, the cross-talking pathways of PPP3R1, such as axon guidance, glutamatergic synapse, LTP, and MAPK signaling pathways, were identified in the global regulatory network. The area under the curve (AUC) analysis showed that low PPP3R1 could accurately predict the onset of AD. Therefore, our findings highlight the involvement of PPP3R1 in the pathogenesis of AD via axon guidance, glutamatergic synapse, LTP, and MAPK signaling pathways, and identify downregulation of PPP3R1 as a potential biomarker for AD treatment in the context of 3P medicine-predictive diagnostics, targeted prevention, and personalization of medical services. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13167-021-00261-2.

Adjuvant herbal therapy for targeting susceptibility genes to Kawasaki disease: An overview of epidemiology, pathogenesis, diagnosis and pharmacological treatment of Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) is a self-limiting acute systemic vasculitis occur mainly in infants and young children under 5 years old. Although the use of acetylsalicylic acid (AAS) in combination with intravenous immunoglobulin (IVIG) remains the standard therapy to KD, the etiology, genetic susceptibility genes and pathogenic factors of KD are still un-elucidated. PURPOSE: Current obstacles in the treatment of KD include the lack of standard clinical and genetic markers for early diagnosis, possible severe side effect of AAS (Reye's syndrome), and the refractory KD cases with resistance to IVIG therapy, therefore, this review has focused on introducing the current advances in the identification of genetic susceptibility genes, environmental factors, diagnostic markers and adjuvant pharmacological intervention for KD. RESULTS: With an overall update in the development of KD from different aspects, our current bioinformatics data has suggested CASP3, CD40 and TLR4 as the possible pathogenic factors or diagnostic markers of KD. Besides, a list of herbal medicines which may work as the adjunct therapy for KD via targeting different proposed molecular targets of KD have also been summarized. CONCLUSION: With the aid of modern pharmacological research and technology, it is anticipated that novel therapeutic remedies, especially active herbal chemicals targeting precise clinical markers of KD could be developed for accurate diagnosis and treatment of the disease.

Acupuncture and clomiphene citrate for anovulatory infertility: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the comparative effectiveness of acupuncture or acupuncture combined with clomiphene citrate (CC) versus CC alone on the outcomes of anovulatory infertility. METHODS: A literature search in eight databases yielded nine randomised controlled trials (RCTs) that evaluated the comparative effectiveness of acupuncture and CC in anovulatory infertility. Subsequently, data were extracted and the studies were assessed for the quality of their methodological designs and risk of bias. Meta-analyses of the RCT data were conducted. RESULTS: Nine trials including 1441 women were included in the meta-analysis. There were no significant differences in the rates of pregnancy (odds ratio (OR) 1.18, 95% CI 0.83 to 1.69), ovulation (OR 2.57, 95% CI 0.59 to 11.29) or pregnancy loss (OR 0.98, 95% CI 0.59 to 1.63) when acupuncture was used as an adjuvant therapy alongside CC. Although acupuncture alone did not increase the ovulation rate (OR 0.41, 95% CI 0.11 to 1.49), our review demonstrated superior effects in patients who received acupuncture as a separate treatment modality with respect to both the pregnancy rate (OR 2.34, 95% CI 1.76 to 3.10) and the maximum follicular diameter (mean difference 0.50 mm, 95% CI 0.44 to 0.56 mm) when compared with CC alone. Statistical analysis also showed a reduction in the rate of pregnancy loss when acupuncture was used as a separate treatment compared with CC alone (OR 0.19, 95% CI 0.08 to 0.45). CONCLUSIONS: Based on the above pooled results of the studies, the use of acupuncture as a monotherapy significantly improved the rate of pregnancy among the study participants compared with the use of CC alone. However, any results drawn from these studies should be interpreted with caution when considering the context of clinical practice.

[Triptolide induces autophagy of ovarian granulosa cells via PI3K/AKT/m TOR pathway].

The aim of this paper was to observe the concentration,time and mechanism of autophagy induced by triptolide( TP) in ovarian granulosa cells( OGCs). CCK-8 method was used to compare the inhibitory effects of TP at different concentrations on primary cultured rat OGCs and IC50 was calculated. The effects of TP at different concentrations and time points on the expression of OGCs autophagy factor protein and the cascade of PI3 K/AKT/m TOR pathway were detected by Western blot. The effects of TP,autophagy inducer( brefeldin A) and PI3 K/m TOR inhibitor( NVP-BEZ235) on the expression of PI3 K/AKT/m TOR cascade and autophagy related factor protein were detected by Western blot. The results show that the IC50 of different concentrations of TP on OGCs of rat ovary was14. 65 µmol·L-1,and the minimum inhibitory concentration of TP was 0. 1 µmol·L-1( 100 nmol·L-1). Compared with the control group,the expression levels of beclin1 and LC3Ⅱ in each group were significantly higher than those in the control group( P<0. 05 or P<0. 01). After 12 hours of treatment with TP,brefeldin A and NVP-BEZ235,respectively,compared with the control group,TP could significantly promote the expression level of downstream autophagy effect or molecule beclin1,LC3Ⅱ and inhibit the expression level of LC3Ⅰ,p62 protein( P<0. 05 or P< 0. 01). Moreover,the expression of beclin1 and LC3Ⅱ/LC3Ⅰ in TP group was higher than that in brefeldin A group( P<0. 05 or P<0. 01),and the expression of p62 in TP group was lower than that in brefeldin A group( P<0. 05 or P<0. 01). At the same time,TP could significantly inhibit the expression of p-PI3 K,p-AKT,p-mTOR protein,and the inhibitory effect of TP was better than that of NVP-BEZ235 group. This study suggests that 100 nmol·L-1 TP could induce OGCs autophagy successfully in cultured rat ovary for 12 h; TP may induce OGCs autophagy by inhibiting PI3 k/Akt/m TOR signaling pathway.

Mindfulness-based cognitive therapy is associated with distinct resting-state neural patterns in patients with generalized anxiety disorder.

INTRODUCTION: Mindfulness-based cognitive therapy (MBCT) may be effective for generalized anxiety disorder (GAD); however, the neural mechanism is poorly understood. In this study, we examined the potential neural mechanisms through which MBCT may reduce anxiety in patients with mild-to-moderate GAD. METHODS: Eight weekly group MBCT sessions (2 h each) were conducted with 32 GAD patients. Resting-state functional magnetic resonance imaging (fMRI) was used, along with clinical and mindfulness profiles. A regional homogeneity (ReHo) approach was applied, and resting-state functional connectivity in the default mode network (DMN) using the posterior cingulate cortex (PCC) seed was examined. RESULTS: MBCT reduced the anxiety and increased the mindfulness abilities of patients. After MBCT, patients had reduced ReHo in broad regions of the limbic system, along with increased DMN functional connectivity in the anterior cingulate cortex (ACC) and bilateral insula. Overlapping regions of reduced ReHo and increased DMN functional connectivity were observed in the mid-cingulate cortex (MCC) and bilateral insula. The increased PCC-ACC and PCC-insula functional connectivity following MBCT were related to anxiety improvements, suggesting a potential therapeutic mechanism for mindfulness-based therapies. DISCUSSION: Group MBCT treatment appears to have effectively reduced anxiety symptoms in patients with mild-to-moderate GAD. Activation and functional connectivity appeared significantly different across some limbic regions after MBCT treatment. The salience network showed reduced ReHo and increased connectivity to the PCC. The DMN functional connectivity of the MCC may indicate reduced anxiety and improved mindfulness in GAD patients.

Constructing a DNA barcode reference library for southern herbs in China: A resource for authentication of southern Chinese medicine.

Southern Chinese Medicine (SCM) is an important sect of Traditional Chinese Medicine (TCM) with its own special cultural style. Species identification is essential for TCM quality control because authentic herbs are possibly substituted with adulterants that would threaten the health of the public or even cause death. Here, we provided the first local reference DNA barcode library based on the second internal transcribed spacer (ITS2) for the molecular identification of SCM. A total of 1512 specimens of southern herbs representing 359 species were collected under the instructions and identification of taxonomic experts. Genomic DNA was extracted, and the PCR reaction proceeded according to standard procedures. After Sanger sequencing, sequence assembling and annotation, a reliable ITS2 barcode library with 1276 sequences from 309 species of Southern herbs was constructed. The PCR efficiency of the whole samples was 84.39%. Characteristics of the ITS2 barcode were analyzed, including sequence lengths and GC contents in different taxa. Neighbor-joining trees based on Kimura 2-Parameter (K2P) genetic distances showed a 67.56% successful rate of species identification with ITS2 barcode. In addition, 96.57% of species could be successfully identified at the genus level by the BLAST method. Eleven plant species were discovered to be cryptic. In addition, we found that there is an incorrect sequence existing in the public database, making a reliable local DNA barcode reference more meaningful. ITS2 barcodes exhibit advantages in TCM identification. This DNA barcode reference library could be used in Southern Chinese Medicine quality control, thus contributing to protecting public health.

Chemical profiles and metabolite study of raw and processed Polygoni Multiflori Radix in rats by UPLC-LTQ-Orbitrap MSn spectrometry.

The raw and processed roots of Plygonum multiflorum Thunb (PM) are used to treat different diseases in clinical practice. In order to clarify the influence of processing, a comparative study of chemical substance analysis was carried out. As the xenobiotics with a high enough exposure in target organs being considered as the potential effective or toxicity components, an in vivo study was also implemented to characterize the constitutes and metabolites, and meanwhile, the factor of compatibility with black bean were also considered. As a result, a total of 148 compounds were detected in PM extracts and more than 40 compounds were only detected in the processed products, which were probably new components produced during the steaming process. In in vivo study, 7 prototype components and 66 metabolites were detected or tentatively identified, 24 of which were reported for the first time. Our results indicated that processing greatly changed the chemical composition of PM and influenced the disposition of the compounds in vivo. To the best of our knowledge, this was the first global comparative study of raw and processed PM. These results expanded our knowledge about the influence of processing of PM and provided the essential data for further efficacy or toxicity studies.

[Explore microcosmic connection between autophagy mechanism and follicular development based on "kidney governing reproduction" theory].

In the theory of traditional Chinese medicine(TCM) that "kidney storing essence and governing reproduction", reproductive essence is an important part of the kidney essence and acts as the original material of offspring embryos. Sperm, oocyte and zygote should be all included in the range of reproductive essence. Ovum is the essence of reproduction from inborn. The follicles maturation depends on the quality of oocyte and the vigor of kidney essence. Meanwhile, discharge of mature ovum relies on the stimulation and promotion by kidney Qi. Autophagy almost exists in different cells stages and all various of mammalian cells. Many studies have found that autophagy not only participates in the formation of follicles, but also in every phase of the follicles development, and is involved in the occurrence and development of ovarian diseases. Recently, more and more scholars believe that autophagy is a new field to explore the microcosmic relationship between autophagy and TCM. Kidney-nourishing TCM could promote follicular growth and improve variety clinical symptoms by inhibiting the apoptosis of ovarian granulosa cells and reducing follicular atresia. Meanwhile, apoptosis of ovarian granulosa cells is closely related to autophagy of ovarian granulosa cells. In order to provide some theoretical foundation for kidney-nourishing therapy's promoting effect on follicular growth and improving effect on ovarian function, also to further explore the molecular mechanism of kidney-nourishing medicine in promoting follicular development, this paper would explain the microcosmic relationship between autophagy and follicular development based on the theory of "kidney governing reproduction". All of these would be of great significance to prevent and intervene the diseases of reproductive system timely and effectively.

[Clinical study on compound prescription with Valerianae Jatamansi Rhizoma et Radix in treatment of generalized anxiety disorder].

This study was aimed to observe the clinical efficacy of anxiolytic compound prescription with Valerianae Jatamansi Rhizoma et Radix (ACPV) in treating liver Qi stagnation and feel ill at ease type generalized anxiety disorder (GAD). Sixty-seven patients diagnosed as GAD with stagnation of liver Qi and feel ill at ease were randomly divided into treatment group and control group. Patients in treatment group (n=34) was treated with ACPV decoction, and patients in control group (n=33) were treated with deanxit. Both groups were treated with respective drugs for 4 weeks. HAMA scale, traditional Chinese medicine (TCM) symptom scale (liver Qi stagnation and feel ill at ease type) and salivary cortisol levels were measured before and 2 weeks and 4 weeks after drug treatment. The life events scale (LES) and drug safety evaluation were performed before and after 4 weeks treatment. Two patients were excluded according to LES, and 5 patients were discontinued. Sixty patients were enrolled in the study finally (30 cases in each group). As compared with baseline, HAMA scores in both groups were significantly decreased at 2 weeks and 4 weeks (P<0.05, P<0.01). After 2 weeks and 4 weeks treatment, the TCM syndrome score in both group was also significantly improved (P<0.01). Moreover, the salivary cortisol levels in both groups were also decreased at 2 weeks and 4 weeks (P<0.05, P<0.01). The total efficiency between two groups had no statistically significant difference after 2 weeks treatment and 4 weeks treatment; moreover, no statistically significant differences were observed between two groups in HAMA scores, TCM syndrome scale scores and salivary cortisol levels between two groups. The incidence of adverse reactions in the treatment group was significantly lower than that in the control group (P<0.01), and there were no obvious side effects in general physical examination during the period of treatment. Thus, anxiolytic compound prescription with Valerianae Jatamansi Rhizoma et Radix is effective for GAD (stagnation of liver Qi and feel ill at ease type).

Morphological and transcriptional responses of Lycopersicon esculentum to hexavalent chromium in agricultural soil.

The carcinogenic, teratogenic, and mutagenic effects of hexavalent chromium (Cr[VI]) on living organisms through the food chain raise the immediate need to assess the potential toxicological impacts of Cr(VI) on human health. Therefore, the concentration-dependent responses of 12 Cr(VI)-responsive genes selected from a high-throughput Lycopersicon esculentum complementary DNA microarray were examined at different Cr concentrations. The results indicated that most of the genes were differentially expressed from 0.1 mg Cr/kg soil, whereas the lowest-observable-adverse-effect concentrations of Cr(VI) were 1.6 mg Cr/kg soil, 6.4 mg Cr/kg soil, 3.2 mg Cr/kg soil, and 0.4 mg Cr/kg soil for seed germination, root elongation, root biomass, and root morphology, respectively, implying that the transcriptional method was more sensitive than the traditional method in detecting Cr(VI) toxicity. Dose-dependent responses were observed for the relative expression of expansin (p = 0.778), probable chalcone-flavonone isomerase 3 (p = -0.496), and 12S seed storage protein CRD (p = -0.614); therefore, the authors propose the 3 genes as putative biomarkers in Cr(VI)-contaminated soil. Environ Toxicol Chem 2016;35:1751-1758. © 2015 SETAC.

Application of Ultra-High-Performance Liquid Chromatography Coupled with LTQ-Orbitrap Mass Spectrometry for the Qualitative and Quantitative Analysis of Polygonum multiflorum Thumb. and Its Processed Products.

In order to quickly and simultaneously obtain the chemical profiles and control the quality of the root of Polygonum multiflorum Thumb. and its processed form, a rapid qualitative and quantitative method, using ultra-high-performance liquid chromatography coupled with electrospray ionization-linear ion trap-Orbitrap hybrid mass spectrometry (UHPLC-LTQ-Orbitrap MS(n)) has been developed. The analysis was performed within 10 min on an AcQuity UPLC™ BEH C18 column with a gradient elution of 0.1% formic acid-acetonitrile at flow rate of 400 µL/min. According to the fragmentation mechanism and high resolution MS(n) data, a diagnostic ion searching strategy was used for rapid and tentative identification of main phenolic components and 23 compounds were simultaneously identified or tentatively characterized. The difference in chemical profiles between P. multiflorum and its processed preparation were observed by comparing the ions abundances of main constituents in the MS spectra and significant changes of eight metabolite biomarkers were detected in the P. multiflorum samples and their preparations. In addition, four of the representative phenols, namely gallic acid, trans-2,3,5,4'-tetra-hydroxystilbene-2-O-ß-d-glucopyranoside, emodin and emodin-8-O-ß-d-glucopyranoside were quantified by the validated UHPLC-MS/MS method. These phenols are considered to be major bioactive constituents in P. multiflorum, and are generally regarded as the index for quality assessment of this herb. The method was successfully used to quantify 10 batches of P. multiflorum and 10 batches of processed P. multiflorum. The results demonstrated that the method is simple, rapid, and suitable for the discrimination and quality control of this traditional Chinese herb.

The stability of aerobic granular sludge treating municipal sludge deep dewatering filtrate in a bench scale sequencing batch reactor.

Inoculated with mature aerobic granular sludge in a sequencing batch reactor, gradually increasing the proportion of municipal sludge deep dewatering filtrate in influent, aerobic granular sludge was domesticated after 84 days and maintained its structure during the operation. The domesticated AGS was yellowish-brown, dense and irregular spherical shape, average size was 1.49 mm, water content and specific density were 98.13% and 1.0114, the SVI and settling velocity were 40 ml/g and 46.5m/h. After 38 days, NO3(-)-N accumulated obviously in the reactor as lack of carbon sources. When adding 1-3g solid CH3COONa at 4.5 and 5.5h of each cycle from the 57th day, the removal rate of TN rose to above 90% after 20 days, where effective COD removal and denitrification were realized in a single bioreactor. Finally, the removal rates of COD, TP, TN and NH4(+)-N were higher than 95%, 88%, 96% and 99%.