1,25(OH)2D3 alleviates oxidative stress and inflammation through up-regulating HMGCS2 in DSS-induced colitis.

BACKGROUND: Previous study found that supplements with active vitamin D3 alleviated experimental colitis. The objective of this study was to investigate the possible role of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), a ketone synthase, on vitamin D3 protecting against experimental colitis. METHODS: HMGCS2 and vitamin D receptor (VDR) were measured in UC patients. The effects of vitamin D deficiency (VDD) and exogenous 1,25(OH)2D3 supplementation on experimental colitis were investigated in dextran sulfate sodium (DSS)-treated mice. DSS-induced oxidative stress and inflammation were analyzed in HT-29 cells. HMGCS2 was detected in 1,25(OH)2D3-pretreated HT-29 cells and mouse intestines. HMGCS2 was silenced to investigate the role of HMGCS2 in 1,25(OH)2D3 protecting against experimental colitis. RESULTS: Intestinal HMGCS2 downregulation was positively correlated with VDR reduction in UC patients. The in vivo experiments showed that VDD exacerbated DSS-induced colitis. By contrast, 1,25(OH)2D3 supplementation ameliorated DSS-induced colon damage, oxidative stress and inflammation. HMGCS2 was up-regulated after 1,25(OH)2D3 supplementation both in vivo and in vitro. Transfection with HMGCS2-siRNA inhibited antioxidant and anti-inflammatory effects of 1,25(OH)2D3 in DSS-treated HT-29 cells. CONCLUSION: 1,25(OH)2D3 supplementation up-regulates HMGCS2, which is responsible for 1,25(OH)2D3-mediated protection against oxidative stress and inflammation in DSS-induced colitis. These findings provide a potential therapeutic strategy for alleviating colitis-associated oxidative stress and inflammation.

The protective effect of puerarin-loaded mesoporous silicon nanoparticles on alcoholic hepatitis through mTOR-mediated autophagy pathway.

Puerarin, a bioactive flavone compound isolated from Pueraria (Wild.), provides hepatoprotection by anti-inflammatory, anti-alcoholism, and regulating mechanistic target of rapamycin (mTOR). Building evidence suggests that the activation of mTOR reduces liver injuries associated with alcohol consumption and metabolism. However, the poor water solubility, low bioavailability, and short half-life of puerarin hinder its clinical application. The utility of mesoporous silicon nanoparticles (MSNs) can improve traditional Chinese medicine limitations. Stober methods were used to fabricate MSNs@Pue, and the size, zeta potentials and drug encapsulation efficiency were characterized by a series of analytical methods. IVIS Imaging System demonstrated liver-targeted bio-distribution, and then high-throughput sequencing, immunoproteomics and ultrastructure methods indicated autophagy related protective mechanism, followed by curative effect evaluation for the treatment efficacy. An acute-on chronic ethanol-drinking according to Gao-binge model induced alcoholic hepatitis (AH) pathology and resulted in hepatic hyper-autophagy, which was improved with MSNs@Pue administration (puerarin: 30 mM, 42 mg/kg; intravenously [i.v.]). Ethanol-fed mice were found to have increased expression of autophagy-related proteins (Atg3, Atg7, LC3 and p62). In contrast, MSNs@Pue administration significantly decreased the expression of these proteins and alleviated fatty droplets infiltration in damaged liver. Furthermore, acute-on-chronic ethanol feeding also resulted in the activiation of ERK activation and mTOR expression, which were reversed with MSNs@Pue administration and better than the usage of puerarin alone. Results point to MSNs@Pue mediated ERK/mTOR signaling pathway activation as a possible protective strategy to improve AH, which provides a strategy and evidence for treating liver disease using an MSN delivery system.

Metabolic Behaviors of Aconitum Alkaloids in Different Concentrations of Aconiti Lateralis Radix Praeparata and Effects of Aconitine in Healthy Human and Long QT Syndrome Cardiomyocytes.

Aconiti Lateralis Radix Praeparata (Fu Zi) is the processed lateral root of Aconitum carmichaelii Debx, which is widely used in emergency clinics. Poisoning incidents and adverse reactions occur with the improper intake of Fu Zi. Metabolic characteristics of aconitum alkaloids of Fu Zi may vary, and the effects of Fu Zi in healthy and Long QT syndrome (LQTS) patients is unknown. In this experiment, 24 Sprague Dawley rats were randomly divided into three groups: 2.0, 1.0, and 0.5 g/kg dose groups, and blood samples were collected after the oral administration of Fu Zi extract. We used an ultra-high performance liquid chromatography-tandem mass spectrometry system to detect the concentrations of six aconitum alkaloids. Cell toxicity, calcium imaging, and patch-clamp recordings of human induced pluripotent stem cells-cardiomyocytes (hiPSC-CMs) of aconitine in healthy and LQTS were observed. We found that the AUC(0-48h), Cmax, and t1/2 of the six compounds increased with the multiplicative dosages; those in the high group were significantly higher than those in the low group. Aconitine concentration-dependently decreased the amplitude, which has no significant effect on the cell index of normal hiPSC-CMs. Aconitine at 5.0 µM decreased the cell index between 5-30 min for LQTS hiPSC-CMs. Meanwhile, aconitine significantly increased the frequency of calcium transients in LQTS at 5 µM. Aconitine significantly shortened the action potential duration of human cardiomyocytes in both normal and LQTS groups. These results show metabolic behaviors of aconitum alkaloids in different concentrations of Fu Zi and effects of aconitine in healthy and LQTS patients.

[Trans-Douglas Retzius' space-sparing robot-assisted simple prostatectomy for large-volume benign prostate hyperplasia].

OBJECTIVE: To report the safety and efficacy of trans-Douglas Retzius' space-sparing robot-assisted simple prostatectomy (RSS-RASP) in the treatment of large-volume BPH. METHODS: This retrospective study included 24 cases of large-volume (>80 ml) BPH treated by trans-Douglas RSS-RASP from August 2019 to June 2021. The patients ranged in age from 55 to 80 (mean 68.5) years, with an average body mass index of 25.1 (20.5－34.9) kg/m2 , median prostate volume of 132.4 (85.6－235.7) ml, and preoperative tPSA of 10.8 (0.5－37.9) ng/ml, IPSS of 25 (3－35) and quality of life (QOL) score of 5 (3－8). Before surgery, 12 of the patients received catheterization for urinary retention, 1 underwent cystostomy, 2 were complicated with hydronephrosis, 1 had stones and diverticulum in the bladder, and 14 were excluded from the cases of PCa by prostatic biopsy. The operation time, intraoperative blood loss, hemoglobin level on the first day after surgery, blood transfusion, and intra- and postoperative complications were recorded. The patients were followed up for 3 to 21 months postoperatively. Comparisons were made before and after operation in the IPSS, maximum urinary flow rate (Qmax), postvoid residual volume (PVR), QOL score, IIEF score and Male Sexual Health Questionnaire (MSHQ) score. RESULTS: Trans-Douglas RSS-RASP was successfully completed in all the 24 cases, with a mean operation time of 175 (100－285) min, intraoperative blood loss of 200 (50－800) ml, hemoglobin decrease of 25 (4－57) g/L on the first day after surgery, postoperative drainage tube indwelling of 3 (2－7) d, and urinary catheterization of 12 (4－18) d. Six (25%) of the patients received intraoperative blood transfusion, 1 underwent transurethral electrocoagulation hemostasis 1 month after surgery because of postoperative bleeding, and 1 received transurethral resection of the cicatrical adhesive tissue of the bladder neck 12 months after surgery. No other complications occurred postoperatively. The IPSS (3 ［1－7］), Qmax (19.6 ［9.9－32.1］ ml/s), PVR (0 ［0－34.9］ ml) and QOL score (2 ［0－3］) of the patients were significantly improved after surgery (P < 0.05), but no statistically significant differences were observed in the IIEF (20 ［19－24］) and MSHQ scores (14 ［13－14］) as compared with the baseline (P > 0.05). CONCLUSION: Trans-Douglas RSS-RASP is a safe and effective minimally invasive method for the treatment of large-volume (>80 ml) BPH, which can improve the urinary function of the patient after operation.

[Nucleic acid aptamer-based traditional Chinese medicine application:therapy,targeting and diagnosis].

Nucleic acid aptamers, broad-spectrum target-specific single-stranded oligonucleotides, serve as molecules in targeted therapy, targeted delivery and disease diagnosis for the treatment of tumor or microbial infection and clinical detection. Due to the existence of components in the use of traditional Chinese medicine(TCM), the target is difficult to concentrate and the specificity of treatment is poor. The effective components of TCM are toxic components, so a highly sensitive detection method is urgently needed to reduce the toxicity problem at the same time. The combined application of TCM and modern medical treatment strategy are difficult and cannot improve the therapeutic effect. Aptamers, advantageous in biosensors, aptamer-nanoparticles for targeted drug delivery, and aptamer-siRNA chimeras, are expected to connect Chinese medicinals with nanotechnology, diagnostic technology and combined therapies. We summarized the preparation, screening, and modification techniques of nucleic acid aptamers and the biomedical applications and advantages in therapy, targeting, and diagnosis, aiming at providing a reference for the in-depth research and development in TCM.

Metschnikowia bicuspidate associated with a milky disease in Eriocheir sinensis and its effectitve treatment by Massoia lactone.

The pathogenic yeast strain LIAO causing the milky disease in the Chinese mitten crab belonged to one member of Metschnikowia bicuspidate which could grow well at different temperatures from 28 to 4 °C. It was also found that the pathogenic yeast strain LIAO could grow in the extracts of the muscle, gill, heart tissues, intestinal tracts of the healthy Chinese mitten crabs by using the reducing sugars, amino acids and other nutrients in them. Massoia lactone released from liamocins produced by Aureobasidium melanogenum had high anti-fungal activity against the pathogenic yeast strain LIAO and M. bicuspidate WCY isolated from the diseased marine crabs. The minimal inhibitory concentrations (MIC) and the minimal fungicidal concentration (MFC) in the liquid culture against the pathogenic yeast strain LIAO were 0.15 mg/mL and 0.34 mg/mL, respectively. Massoia lactone as a bio-surfactant could damage the cell membrane, even break the whole cells of the pathogenic yeast strain LIAO and cause cellular necrosis of the pathogenic yeast LIAO. Therefore, Massoia lactone could be used to effectively kill the pathogenic yeast strains and as an effectitve treatment for milky disease in the Chinese mitten crab.

Nucleic acid aptamer-based traditional Chinese medicine application:therapy,targeting and diagnosis / 中国中药杂志

Nucleic acid aptamers, broad-spectrum target-specific single-stranded oligonucleotides, serve as molecules in targeted therapy, targeted delivery and disease diagnosis for the treatment of tumor or microbial infection and clinical detection. Due to the existence of components in the use of traditional Chinese medicine(TCM), the target is difficult to concentrate and the specificity of treatment is poor. The effective components of TCM are toxic components, so a highly sensitive detection method is urgently needed to reduce the toxicity problem at the same time. The combined application of TCM and modern medical treatment strategy are difficult and cannot improve the therapeutic effect. Aptamers, advantageous in biosensors, aptamer-nanoparticles for targeted drug delivery, and aptamer-siRNA chimeras, are expected to connect Chinese medicinals with nanotechnology, diagnostic technology and combined therapies. We summarized the preparation, screening, and modification techniques of nucleic acid aptamers and the biomedical applications and advantages in therapy, targeting, and diagnosis, aiming at providing a reference for the in-depth research and development in TCM.

Longxuetongluo capsule alleviates lipopolysaccharide-induced neuroinflammation by regulating multiple signaling pathways in BV2 microglia cells.

BACKGROUND: Longxuetongluo capsule (LTC), derived from the total phenolic compounds of Chinese dragon's blood, is now used in the treatment of ischemic stroke in convalescence. The aim of this study is to explore the neuroprotective effect of LTC from the perspective of neuroinflammation. METHODS: Cell viability and lactate dehydrogenase (LDH) release were measured by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) and LDH assay kit. Proinflammatory mediators and cytokines production including Nitric Oxide (NO), prostaglandin E2, (PGE2), interleukin (IL-ß), IL-6, and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA) assay. In addition, western blot was used to detect the expression of inflammatory proteins associated with the mitogen-activated protein kinases (MAPKs), janus kinase/signal transducer and activator of tranions (JAK/STAT), nuclear transcription factor κB (NF-κB), and nuclear factor erythroid-2-related actor 2/heme oxygenase 1 (Nrf2/HO-1) signaling pathways. Moreover, immunofluorescence assay and electrophoretic mobility shift assays (EMSA) were performed to determine the Nrf2 translocation and the binding-DNA activity of NF-κB, respectively. RESULTS: LTC at 0.5 to 2 µg/mL significantly increased cell viability and decreased LDH, NO, PGE2, IL-1ß, IL-6, and TNF-α production in oxygen-glucose deprivation/reoxygenation (OGD/R) and lipopolysaccharide (LPS)-induced BV2 microglia cells. Meanwhile, LTC not only decreased the protein expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) but also down-regulated phosphorylation of extracellular signal-regulated kinase (ERK)1/2, p38, and up-regulated HO-1 expression via nuclear translocation of Nrf2. LTC can significantly inhibit the phosphorylation of JAK1/STAT3 and reduce the translocation of NF-κB from cytosol to nucleus as well as the binding-DNA activity. PC12 cell pretreated with LTC-condition medium (CM) significantly alleviated LPS-induced neurotoxicity and increased PC12 cell viability in a dose-dependent manner. CONCLUSION: The present study showed that LTC exhibited a strong antineuroinflammatory activity and neuroprotective effects on LPS-stimulated BV2 microglial cells and PC12 cells.

Two novel nornemoralisin-type diterpenoids from Aphanamixis polystachya (Wall.) R. Parker.

Two novel heptanornemoralisin-type diterpenoids nornemoralisins A (1) and B (2), together with two known compounds nemoralisin (3) and nemoralisin A (4), were isolated from the stem bark and leaves of Aphanamixis polystachya (Wall.) R. Parker. Their structures were established through comprehensive analyses of NMR spectroscopic data and high resolution mass spectrometric (HR-ESI-MS) data. The absolute configurations of carbon stereocenters were elucidated by circular dichroism (CD) analyses. The four compounds were tested for their potential cytotoxic effects against ACHN, HeLa, SMMC-7721, and MCF-7 cell lines. Nornemoralisins A (1) and B (2) exhibited significant cytotoxicity on ACHN with an IC50 value of 13.9 ± 0.8 and 10.3 ± 0.4 µM, respectively, and other compounds failed to reveal obvious cytotoxicity on the tested cell lines, compared to positive control vinblastine (IC50, 28.0 ± 0.9 µM).

[Effects of Xuesaitong injection on inflammation induced by OGD/reoxygenation in BV2 microglia].

The present study aims to investigate the effects of Xuesaitong (XST)injection on inflammation induced by OGD/reoxygenation in BV2 microglia cell and explore the underlying mechanisms.The effects of XST injection were evaluated in terms of cell viability, secretion of TNF-α, IL-1ß, IL-6 and IL-10 into culture media, protein expression of p-ERK1/2, p-JNK and p-p38, and nuclear translocation of NF-κB p65. The results showed that XST injection significantly increased cell viability, suppressed release of TNF-α, IL-1ß, IL-6 and IL-10 and down-regulated p-JNK1/2 and p-p38 MAPK expression in BV2 microglia cells induced by OGD/R injury, whereas it had no effect on p-ERK1/2 expression. Furthermore, XST injection suppressed nuclear translocation of NF-κB p65 in BV2 microglia after OGD/R injury. These data indicate that the neuroprotective effects of XST injection on OGD/R injury are associated with its inhibition of pro-inflammatory mediator production, down-regulation of JNK1/2 and p38 MAPK activation, and suppression of NF-κB p65 nuclear translocation in BV2 microglia cells.

Consensus on the integrated traditional Chinese and Western medicine criteria of diagnostic classification in polycystic ovary syndrome (draft) / 中西医结合学报

Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder of women, with complex pathogenesis and heterogeneous manifestations. Professor Jin Yu recently wrote an article entitled "Proposal of Diagnosis and Diagnostic Classification of PCOS in Integrated Traditional Chinese and Western Medicine."From this, the Obstetrics and Gynecology branches of the Chinese Association of Integrative Medicine and the China Association of Chinese Medicine collaborated with the Gynecology branch of the Chinese Association for Research and Advancement of Chinese Medicine to draft a report on the consensus of criteria for the diagnosis and classification of PCOS in integrated traditional Chinese and Western medicine. The diagnosis for PCOS includes all three features: (1) oligo-ovulation or anovulation; (2) clinical and/or laboratory evidence of hyperandrogenism;(3) PCOS is classified into four types: types Ia,Ib, IIa, and IIb. Syndrome differentiation types for PCOS in traditional Chinese medicine are as follows: Kidney deficiency with phlegm blockage syndrome, Kidney Yin deficiency with phlegm blockage and blood stasis syndrome, and Kidney deficiency with Liver Qi stagnation syndrome.

[Pharmacokinetics and brain distribution of NMD/TMP-nanoparticles].

This study aims to prepare nimodipine/tetramethylpyrazine-loaded poly(D, L-lactide-co-glycolide) dual-drug nanoparticles (NMD/TMP-NPs) and investigate pharmacokinetics and brain distribution to evaluate the possibility of enhancing the drug effect of dual-drug nanoparticles. NMD/TMP-NPs were prepared via W/O/W emulsion solvent evaporation. Entrapment efficiency and drug loading of NMD/TMP-NPs were investigated by ultracentrifugation, and drug release behavior in vitro was studied by dialysis method. The pharmacokinetic and brain distribution were studied in SD mice administered intravenously with NMD/TMP-NPs in comparison with NMD-suspension, NMD/TMP-suspension and NMD-NPs, (NMD-NPs+TMP)-suspension. According to the results, the entrapment efficiency and drug loading of NMD were (79.71±0.73)%, (1.74±0.02)%, those of TMP were (40.26±1.51)% and (4.38±0.16)%. The nanoparticles showed the property of sustained release. On the basis of the major parameters for in vivo pharmacokinetic and brain distribution, t1/2ß of NMD-suspension, NMD/TMP-suspension and NMD-NPs, (NMD-NPs+TMP)-suspension, NMD/TMP-NPs were (1.097±0.146), (1.055±0.06), (1.950±0.140), (1.860±0.096), (2.497±0.475） h, CL were (0.778±0.098), (1.133±0.111), (0.247±0.023), (0.497±0.040), (0.297±0.024) h•L-1, AUC0-t in rat plasma were (514.218±60.383), (352.916±33.691), (1 618.429±240.198), (804.110±75.804), (1 349.058±215.497) µg•h•L⁻¹, respectively, and AUC0-t in brain were 0.301 9, 0.624 8, 1.068 6, 1.313 0, 1.046 5 mg•h•L⁻¹, respectively. According to the in vivo study, the pharmacokinetic behavior of NMD were markedly prolonged by adding TMP or prepared dual-drug nanoparticles.

Simulation of spatial and temporal distributions of non-point source pollution load in the Three Gorges Reservoir Region.

Non-point source (NPS) pollution has become the largest threat to water quality in recent years. Major pollutants, particularly from agricultural activities, which include nitrogen, phosphorus and sediment that have been released into aquatic environments, have caused a range of problems in the Three Gorges Reservoir Region (TGRR), China. It is necessary to identify the spatial and temporal distributions of NPS pollutants and the highly polluted areas for the purpose of watershed management. In this study, the NPS pollutant load was simulated using the Soil and Water Assessment Tool (SWAT) and the small-scale watershed extended method (SWEM). The simulation results for four typical small catchments were extended to the entire watershed leading to estimates of the NPS load from 2001 to 2009. The results demonstrated that the NPS pollution load in the western area was the highest and that agricultural land was the primary pollutant source. The similar annual variation trends of runoff and sediment loads demonstrated that the sediment load was closely related to runoff. The loads of total nitrogen (TN) and total phosphorus (TP) were relatively stable from 2001 to 2007, except for high loads in 2006. The increase in pollution source strength was an important reason for the significant upward trend of TN and TP loads from 2008 to 2009. The rainfall from April to October contributed to the largest amount of runoff, sediment and nutrient loads for the year. The NPS load intensities in each sub-basin reveal large variations in the spatial distribution of different pollutants. It was shown that the temporal and spatial distributions of pollutant loads were positively correlated with the annual rainfall amounts and with human activities. Furthermore, this finding illustrates that conservation practices and nutrient management should be implemented in specific sites during special periods for the purpose of NPS pollution control in the TGRR.

Radioprotective effect of adenine on irradiation-induced apoptosis.

AIM: To investigate the radioprotective effect of adenine on irradiated lymphocytes and discover the possible mechanisms of protection. METHODS: Lymphocytes were pretreated for 12 h with adenine (0.001-0.1 µmol·L(-1)) and then exposed to 4 Gy radiation. Cell viability was observed by the MTS assay, apoptosis was detected by Annexin V-FITC/PI, DNA ladder, and caspase 3/7 activity. Caspase-9, Bax, and Bcl-2 gene expression was investigated by RT-PCR. RESULTS: Irradiation increased cell death and DNA fragmentation. Pretreatment with adenine significantly reversed this tendency. Furthermore, several anti-apoptotic characteristics of adenine were determined, including the ability to inhibit caspase 3/7, upregulate B-cell lymphoma (Bcl-2) and downregulate Bcl-2- associated X (Bax), capase-9 gene expression in 4 Gy-irradiated AHH-1 cells. CONCLUSION: The results suggest that adenine had a radioprotective effect to inhibit apoptosis in a concentration dependent manner.

Long-term variation (1960-2003) and causal factors of non-point-source nitrogen and phosphorus in the upper reach of the Yangtze River.

The knowledge of long-term variation and causal factors of non-point source (NPS) pollution in large-scale watersheds is helpful in the development of water quality control programs. In this study, the Improved Export Coefficient Model and the Revised Universal Soil Loss Equation were combined to estimate the temporal and spatial variations (1960-2003) of NPS pollution in the upper reach of the Yangtze River (URYR). Two change points for NPS pollution were successfully detected. In the URYR, the dissolved nitrogen (DN) and dissolved phosphorus (DP) increased before 2000 and decreased after 2000, whereas the inflection points from increase to decline were around 1980 for the adsorbed N (AN) and adsorbed P (AP). The results also indicated that the dissolved pollutants were mainly contributed by the anthropogenic factors, while the adsorbed pollutants were primarily exported by the natural factors. By comparing the load intensities from each source, it revealed that for the dissolved pollutants, the major source of the high load intensity transferred from urban land to dry land after 1980. Simultaneously, the high load intensity areas of the adsorbed pollutants transferred from forest to orchard around 1980, which was mainly attributed to the increasing fertilizer application. These results may be useful for planning and management of the URYR and other large-scale watersheds.

Ferulic acid attenuates adhesion molecule expression in gamma-radiated human umbilical vascular endothelial cells.

Radiation induces an important inflammatory response in the irradiated organs, characterized by leukocyte infiltration and vascular changes. Since adhesion molecules play an important role in facilitating the immune response at the inflammation sites, interfering with the expression of these molecules may be an important therapeutic target of radiation induced inflammation. Many adhesion molecules such as intercellular cell adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) have been identified in radiation. Ferulic acid (FA), an effective radioprotector during radiotherapy, is widely used in endothelium protection. The present study examined the effect of FA on the induction of adhesion molecules by gamma-radiation and the mechanisms of its effect in gamma-irradiated human umbilical vein endothelial cells (HUVECs). HUVECs were pretreated for 18 h with FA and then exposed to 10 Gy radiation. The result of cell adhesion assay showed FA inhibited radiation-induced U937 adhesion to HUVECs. FA prevented induction of ICAM-1 and VCAM-1 expression in a concentration-dependent manner after stimulation with radiation at the level of mRNA and protein. Inhibitors of the extracellular signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) pathways were used to determine which pathway was involved in FA action; the result showed that the inhibitory effect of FA on adhesion molecule expression was mediated by the blockade of JNK. FA appears to be a potential therapeutic agent for treating various inflammatory disorders including radiation induced inflammation.

Ferulic acid protects human umbilical vein endothelial cells from radiation induced oxidative stress by phosphatidylinositol 3-kinase and extracellular signal-regulated kinase pathways.

Ferulic acid (FA) has been demonstrated to have a remarkable antioxidant activity, the mechanism of FA of protecting human umbilical vein endothelial cells (HUVECs) from radiation induced oxidative stress was investigated in the present study. The oxidative protection of FA was assessed by cellular glutathione (GSH) content, nicotinamide adenine dinucleotide phosphate (NADPH) levels, and reactive oxygen species (ROS) analysis. Nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation was detected using Western blotting. The upstream signaling pathway involved in FA mediated Nrf2 activation was determined by signaling inhibitors. FA significantly increased the transcription of antioxidant related genes such as GCLC (glutamate-cysteine ligase catalytic subunit), GCLM (glutamate-cysteine ligase regulatory subunit), NQO1 (NADPH quinone oxidoreductase-1) and heme oxygenase-1 (HO-1) mRNA in radiated cells, and these changes involved in a significant increase of the intracellular GSH content and the expression of NAPDH. FA evidently promoted Nrf2 translocation into nuclei and increased the intracellular GSH and NADPH levels in radiated cells. Phosphatidylinositol 3-kinase (PI3K) and extracellular signal regulated kinase (ERK) pathways were associated with FA-induced Nrf2 activation. The results suggested that FA-induced Nrf2 activation play key role in cytoprotective effect of FA against oxidative stress via PI3K and ERK signaling pathways.

Parameter uncertainty analysis of non-point source pollution from different land use types.

Land use type is one of the most important factors that affect the uncertainty in non-point source (NPS) pollution simulation. In this study, seventeen sensitive parameters were screened from the Soil and Water Assessment Tool (SWAT) model for parameter uncertainty analysis for different land use types in the Daning River Watershed of the Three Gorges Reservoir area, China. First-Order Error Analysis (FOEA) method was adopted to analyze the effect of parameter uncertainty on model outputs under three types of land use, namely, plantation, forest and grassland. The model outputs selected in this study consisted of runoff, sediment yield, organic nitrogen (N), and total phosphorus (TP). The results indicated that the uncertainty conferred by the parameters differed among the three land use types. In forest and grassland, the parameter uncertainty in NPS pollution was primarily associated with runoff processes, but in plantation, the main uncertain parameters were related to runoff process and soil properties. Taken together, the study suggested that adjusting the structure of land use and controlling fertilizer use are helpful methods to control the NPS pollution in the Daning River Watershed.

Prelimary exploration on Chinese medicine syndrome type distribution in patients with polycystic ovary syndrome / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the Chinese medicine syndrome type distribution in patients with polycystic ovary syndrome (PCOS) and its relationship with sexual hormones.</p><p><b>METHODS</b>Chinese medicine syndrome types of 212 PCOS patients were differentiated and sorted by adopting fuzzy mean C clustering method, and their relationship with the indices of sexual hormones detected on the 3rd to 5th day of menstrual cycle was analyzed, with the values got from 20 healthy women for controls.</p><p><b>RESULTS</b>Intermingling syndromes were commonly seen in PCOS patients. Shen-deficiency syndrome (presented in 64 patients) and Gan-qi stagnancy syndrome (61 patients) were the dominance, accounting for 30.2% and 28.8% respectively, significantly higher than that of other syndromes (P < 0.05), which were Pi-deficiency syndrome (41 patients, 19.3%), phlegm-dampness syndrome (33 patients, 15.6%) and blood stasis syndrome (13 patients, 6.1%). Levels of estradiol (E2), testosterone (T), luteinzing hormone (LH), dehydroiso-androsterone (DHEA-S) and prolactin (PRL) were higher, while the level of sexual hormone binding protein (SHBG) was lower in PCOS patients than those in control, follicular stimulating hormone (FSH) level in patients of Shen-deficiency syndrome and phlegm-dampness syndrome was high than that in control (P < 0.05 and P < 0.01). However, no significant differences were found in comparing the various sexual endocrinal indices between patients with different syndrome types (P > 0.05). Besides, the level of PRL was positively correlated with LH and E2 levels in patients.</p><p><b>CONCLUSION</b>Chinese medicine syndromes presented in patients with PCOS are mostly intermingling, Shen-deficiency and Gan-stagnancy are the basic syndromes, and there is some correlation between syndrome type and sexual hormone levels.</p>

Parameter uncertainty analysis of the non-point source pollution in the Daning River watershed of the Three Gorges Reservoir Region, China.

The generation and formation of non-point source pollution involves great uncertainty, and this uncertainty makes monitoring and controlling pollution very difficult. Understanding the main parameters that affect non-point source pollution uncertainty is necessary to provide the basis for the planning and design of control measures. In this study, three methods were adopted to do the parameter uncertainty analysis with the Soil and Water Assessment Tool (SWAT). Based on the results of parameter sensitivity analysis by the Morris screening method, the ten parameters that most affect runoff, sediment, organic N, nitrate, and total phosphorous (TP) were chosen for further uncertainty analysis. First-order error analysis (FOEA) and the Monte Carlo method (MC) were used to analyze the effect of parameter uncertainty on model outputs. FOEA results showed that only a few parameters had significantly affected the uncertainty of the final simulation results, and many parameters had little or no effect. The SCS curve number was the parameter with significant uncertainty impact on runoff, sediment, organic N, nitrate and TP, and it showed that the runoff process was mainly responsible for the uncertainty of non-point source pollution load. The uncertainty of sediment was the biggest among the five model output results described above. MC results indicated that neglecting the parameter uncertainty of the model would underestimate the non-point source pollution load, and that the relationship between model input and output was non-linear. The uncertainty of non-point source pollution exhibited a temporal pattern: It was greater in summer than in winter. The uncertainty of runoff was smaller compared to that of sediment, organic N, nitrate, and TP, and the source of uncertainty was mainly affected by parameters associated with runoff.