[Efficacy and safety of Kangbingdu granules in the treatment of influenza: a randomized, double-blind, double-dummy, positive-drug parallel control multicenter clinical trial].

Objective: To observe the efficacy and safety of Kangbingdu granules (KBD) in the treatment of influenza. Methods: A multicenter, randomized, double-blind, double-dummy, and positive-drug parallel control trial was conducted in 27 Grade ⅢA hospitals in China and the subjects were randomly assigned to the KBD test group or the oseltamivir phosphate capsule control group at a ratio of 1∶1. 200 subjects were planned to be enrolled in each group. The experimental group was given KBD (18g each time, 3 times a day) and oseltamivir phosphate simulator orally, while the control group was given oseltamivir phosphate capsule (75 mg each time, twice a day) and KBD simulator orally for 5 days. The primary efficacy indicators included the remission time of major clinical symptoms and the time of complete defervescence. The secondary efficacy indicators included dosage of acetaminophen, the change of traditional Chinese medicine (TCM) syndrome score and the remission time of other important clinical symptoms. The efficacy of KBD in the test group and Oseltamivir phosphate control group were compared. Adverse events or adverse reactions were observed at the same time to evaluate the safety of KBD Granules. Results: A total of 393 subjects from 27 Grade ⅢA hospitals in China were enrolled. The experimental group included 195 subjects and 191 subjects (97.95%) completed the trial, While the control group included 198 subjects and 195 subjects (98.48%) completed the trial. There was no significant difference in the shedding rate and rejection rate between the two groups (P>0.05). In the Full Analysis Set (FAS), the mean age of the experimental group was (34.9±14.4) years old, with 83 males (42.78%). The mean age of the control group was (33.3±13.5) years old, with 78 males (39.59%). There were no statistically significant differences between the two groups in demographic data, physical examination, viral pathogen detection, total score of TCM syndromes and scores of each symptom at baseline (P>0.05). In the FAS, the remission time M (Q1, Q3) of major clinical symptoms was 3.0 (3.0, 4.0) days in the experimental group and 3.0 (3.0, 4.0) days in the control group, and the difference was not statistically significant (P>0.05). The time M (Q1, Q3) of complete defervescence was 34.0 (20.3, 49.0) hours in the experimental group and 36.5 (19.6, 48.8) hours in the control group, and the difference was not statistically significant (P>0.05). KBD granules had the same effect as Oseltamivir phosphate capsule (P>0.05) in terms of acetaminophen dosage, TCM syndrome effect and disappearance rate of most important clinical symptoms. Meanwhile, the disappearance rate of dizziness and chest distress on day 3 in the KBD granules group was better than that of oseltamivir phosphate capsule (P<0.05). Conclusion: KBD granules have the same efficacy as Oseltamivir Phosphate capsule in the treatment of influenza and the drug safety is good.

[Therapeutic effect of ginkgo biloba extract on postoperative delirium in aged patients].

Objective: To observe whether Ginkgo biloba extract (EGb761) can improve postoperative delirium in elderly patients. Methods: Eighty elderly patients undergoing tumor surgery at Zhejiang Cancer Hospital and complicated with postoperative delirium(POD) between June 2013 and July 2016 were randomly divided into treatment group (group A) and control group (group B) according to the random number table method. Patients in group A received ginkgo biloba extract (EGb761) drops oral treatment (3 times/d, 80 mg each time) in addition to oxygen inhalation and appeasement treatment. Patients in group B underwent routine oxygen inhalation and appeasement treatment. POD assessment was performed twice between the hours of 8: 00 am and 8: 00 pm daily after the diagnosis of POD. Observed indicators include sex ratio, age, body mass index (BMI), educated level, type of surgery, anesthesia method, duration of surgery, intraoperative mean arterial blood pressure, intraoperative blood loss, type of POD, visual analogue scale (VAS) scores when diagnosis of POD, the onset time of POD, initial RASS scores, duration of POD. Results: A total of 80 patients with POD were enrolled, 23 patients were excluded for did not cooperate with the tests of POD or refused to participate in the study. Finally, 57 elderly patients completed the study, 29 patients in the medication group (A group) and 28 patients in the control group (B group). There was no significant difference in sex ratio, age, BMI, education level, operation type, anesthesia method, operation duration, intraoperative mean arterial pressure, intraoperative blood loss, POD type and VAS score (all P>0.05). There was no significant difference between the two groups in POD onset time and initial RASS score (all P>0.05). The duration of POD in group A and group B was 16 (16)h and 48 (35) h respectively, the difference was statistically significant (U=161.500, P<0.001). Conclusion: Ginkgo biloba extract (EGb761) can shorten the course of POD in elderly patients.

Parameter-specific analgesic effects of electroacupuncture mediated by degree of regulation TRPV1 and P2X3 in inflammatory pain in rats.

AIMS: Observing the parameter-specific anti-hyperalgesic effects of EA with different stimulation times and frequencies on painful hyperalgesia mediated by the level of TRPV1 and P2X3 expression in DRG after CFA injection. MAIN METHODS: The model was induced by the injection of CFA in each rat's right hind paw. EA treatment was applied to the bilateral ST36 and BL60. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were tested with Von Frey filaments and the radiant heat source of the test instrument, respectively. TRPV1 and P2X3 expressions were measured by immunofluorescence and western blot. αß-meATP and capsaicine combined with EA were further utilized to investigate the change in PWL. KEY FINDINGS: Different stimulation times (20, 30, 45 min) combined with different frequencies (2 Hz, 100 Hz, 2/100 Hz) of EA have analgesic effects on the PWT and PWL; however, the level of the hypoalgesic efficacy of EA was primarily associated with EA frequency. The analgesic effect of EA was better at 100 Hz than at 2 Hz. The level of regulation of 100 Hz EA on TRPV1 and P2X3 in DRG was greater than that of 2 Hz. Furthermore, both TRPV1 agonist and P2X3 agonist may impair the level of EA analgesia. SIGNIFICANCE: EA has a parameter-specific effect on chronic inflammatory pain relief, which primarily depend on the stimulation frequency and not on the stimulation time at a certain stimulation time. The parameter-specific analgesic effect of EA is at least partially related to mediation of the protein level of TRPV1 and P2X3 expression in DRG of CFA rats.

Effects of nutritional support on short-term clinical outcomes and immune response in unresectable locally advanced oesophageal squamous cell carcinoma.

This retrospective study investigated the efficiency of nutritional support in unresectable locally advanced oesophageal squamous cell carcinoma (LAOSCC) patients who received concurrent chemoradiotherapy (CCRT) based on 5-fluorouracil and cisplatin. In the routine care group, 63 patients served as historical controls and received nutrition support in a reactive manner. In addition, 57 patients in the nutritional support group received timely diet counselling, oral nutritional supplements, enteral nutrition and/or parenteral nutrition during CCRT. This support was based on scores from nutritional risk screening 2002 (NRS-2002) after June 2014. The nutritional support group had significant advantages over the routine care group with respect to the incidence of neutropenia, the objective response rate, the change in serum albumin and the lengths of hospital stay. In addition, the nutritional support group had significantly higher levels of IgG and IL-2, higher proportions of NK, CD3+ and CD4+ cells as well as a higher ratio of CD4+ /CD8+ cells than the routine care group (p < .05). In contrast, the nutritional support group had a significantly lower level of IL-6. In conclusion, the current nutritional care programme could bring benefits of improving treatment compliance, reducing toxicity and lengths of hospital stay and enhancing the immune response.

Expression and clinical significance of rhubarb on serum amylase and TNF-alpha of rat model of acute pancreatitis.

The aim of this study was to evaluate the therapeutic effect of rhubarb extract on acute pancreatitis. Ninety-six healthy Sprague Dawley rats, weighing 301±5.12 g were randomly divided into 4 groups: sham surgery (group A), acute pancreatitis model (group B), acute pancreatitis with normal saline (group C), and acute pancreatitis model with rhubarb (group D). The levels of serum amylase (AMY) and TNF-α were measured at 1st, 6th, 12th and 24th hour after modeling, and the pancreatic tissue were used to observe the pathologic changes. Compared to the sham group, the serum AMY and serum tumor necrosis factor (TNF-α) levels were significantly increased in the other groups (p <0.05). Compared to the model group and the saline group, the serum AMY, serum TNF-α level and pathological changes of rats in the rhubarb group were significantly lower (p <0.05). The serum AMY and TNF-α levels increased in acute pancreatitis. The rhubarb reduced the serum AMY and TNF-α level in rats with acute pancreatitis and reduced the pathological changes of pancreas and other tissues.

Systems Pharmacology-Based Discovery of Natural Products for Precision Oncology Through Targeting Cancer Mutated Genes.

Massive cancer genomics data have facilitated the rapid revolution of a novel oncology drug discovery paradigm through targeting clinically relevant driver genes or mutations for the development of precision oncology. Natural products with polypharmacological profiles have been demonstrated as promising agents for the development of novel cancer therapies. In this study, we developed an integrated systems pharmacology framework that facilitated identifying potential natural products that target mutated genes across 15 cancer types or subtypes in the realm of precision medicine. High performance was achieved for our systems pharmacology framework. In case studies, we computationally identified novel anticancer indications for several US Food and Drug Administration-approved or clinically investigational natural products (e.g., resveratrol, quercetin, genistein, and fisetin) through targeting significantly mutated genes in multiple cancer types. In summary, this study provides a powerful tool for the development of molecularly targeted cancer therapies through targeting the clinically actionable alterations by exploiting the systems pharmacology of natural products.

Acute ischemic stroke and abnormal blood hemoglobin concentration.

OBJECTIVES: This study examines whether low or high blood hemoglobin concentration (HGB) is associated with stroke severity, worse clinical outcomes, and poorer prognosis after acute ischemic stroke (AIS). METHODS: This retrospective cohort study included data from the Ontario Stroke Registry on consecutive patients with AIS who were admitted between July 2003 and March 2008. We excluded patients taking anticonvulsants or iron supplement; patients with cancer, renal failure, history of gastro-intestinal or genitourinary bleeding, and pregnancy. Patients were divided into groups as follows: low HGB, normal HGB, and high HGB. Outcome measures included the frequency of greater degree of disability at discharge (modified Rankin score: 3-6), 7-day, 30-day and 90-day mortality, and length of stay in the acute stroke care hospital. RESULTS: Hemoglobin levels higher than the upper limit of normal are associated with a greater disability at discharge (OR = 1.49, 95% CI: 1.03-2.15, P = 0.0331), and higher 30-day mortality (HR = 1.98, 95% CI: 1.44-2.74, P < 0.0001) after adjustment for major potential confounders. The Kaplan-Meier curves indicate that abnormal HGB levels are associated with higher mortality after AIS (P < 0.0001). HGB levels below the lower limit of normal are associated with longer lengths of stay in the acute care hospital (OR = 1.11, 95% CI: 1.02-1.22, P = 0.017). Elevated HGB was associated with greater neurological deficit on admission (OR = 1.45, 95% CI: 1.06-1.95, P = 0.0195). CONCLUSIONS: Our results suggest that an elevated HGB on the initial admission is associated with more severe strokes, greater disability at discharge, and higher 30-day mortality after AIS. A low HGB on admission is associated with longer stay in the acute care hospital.

Effect of intra-operative autonomic nerve stimulation on pelvic nerve preservation during radical laparoscopic proctectomy.

AIM: This study assessed the effect of intra-operative electrical nerve stimulation (INS) on pelvic autonomic nerve preservation (PANP) during laparoscopic resection for rectal cancer. METHOD: A total of 189 consecutive cases of radical laparoscopic proctectomy were included. PANP was assessed visually or with INS. Urinary function was evaluated by residual urine volume (RUV), International Prostatic Symptom Score (IPSS) and recatheterization rate. Erectile function was evaluated using the International Index of Erectile Function (IIEF-5) scale. RESULTS: INS successfully confirmed PANP in 65 (91.5%) patients, while direct vision confirmed PANP in only 72 (61.0%) patients. Compared with the successfully confirmed patients, failed patients in the INS group exhibited higher postoperative RUV (100.0 ± 34.6 vs 25.2 ± 13.6 ml, P = 0.003), higher IPSS (7 days, 20.0 ± 8.6 vs 6.5 ± 2.4, P = 0.012; 1 month, 13.5 ± 6.0 vs 5.3 ± 1.9, P = 0.020; 6 months, 11.7 ± 5.1 vs 4.5 ± 1.7, P = 0.018), a greater number of incidences of a micturition disorder (66.7% vs 1.5%, P = 0.000), higher recatheterization rates (33.3% vs 1.5%, P = 0.017) and a lower IIEF score at 3 months (8.25 ± 0.96 vs 10.93 ± 1.99, P = 0.012) and 6 months (12.50 ± 1.29 vs 15.63 ± 1.65, P = 0.001) postoperatively. Compared with the vision group, the INS group had less deterioration in postoperative RUV (31.5 ± 26.4 vs 54.0 ± 46.7 ml, P = 0.000), lower IPSS (7 days, 7.7 ± 5.0 vs 11.0 ± 6.6, P = 0.000; 1 month, 6.0 ± 3.3 vs 7.6 ± 5.4, P = 0.012) and higher IIEF score (3 months, 10.69 ± 2.07 vs 9.42 ± 2.05, P = 0.001; 6 months, 15.36 ± 1.85 vs 13.64 ± 2.00, P = 0.000) as well as a lower incidence of urination disorders (7.0% vs 17.8%, P = 0.038). CONCLUSION: INS is effective for the accurate evaluation of PANP during radical laparoscopic proctectomy. Combined with INS, laparoscopic proctectomy is more effective in urogenital function protection.

Suppression of Inflammatory Responses by Dihydromyricetin, a Flavonoid from Ampelopsis grossedentata, via Inhibiting the Activation of NF-κB and MAPK Signaling Pathways.

Ampelopsis grossedentata, an indigenous plant in southern China, has been used for treating pharyngitis in traditional Chinese medicine for hundreds of years. In this study, we explored the anti-inflammatory activity of dihydromyricetin (1), its major bioactive component, and the underlying mechanism of this action. We demonstrated that 1 suppressed the levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) as well as increased the level of the anti-inflammatory cytokine interleukin-10 (IL-10) in lipopolysaccharide (LPS)-treated mice. Moreover, 1 was found to markedly inhibit the production of nitric oxide (NO) and the levels of TNF-α, IL-1ß, and IL-6, whereas it increased the level of IL-10 in LPS-induced RAW 264.7 macrophage cells. Compound 1 also reduced the protein expression of inducible nitric oxide synthase (iNOS), TNF-α, and cyclooxygenase-2 (COX-2) in macrophage cells. Furthermore, 1 suppressed the phosphorylation of NF-kappa B (NF-κB) and IκBα as well as the phosphorylation of p38 and JNK but not ERK1/2 in LPS-stimulated macrophages. Taken together, the present results suggest that 1 exerts its topical anti-inflammatory action through suppressing the activation of NF-κB and the phosphorylation of p38 and JNK. Thus, 1 may be a potentially useful therapeutic agent for inflammatory-related diseases.

Endoscopic appearance and location dictate diagnostic yield of biopsies in eosinophilic oesophagitis.

BACKGROUND: Acknowledging that eosinophilic esophagitis (EoE) is a disease with variable involvement throughout the oesophagus, studies have suggested a minimum of five biopsies to diagnose EoE. Although it is accepted that furrows and exudates appear to represent areas of inflammation, no research to date has looked specifically at EoE endoscopic findings to see if eosinophilic infiltrate correlates with specific endoscopic findings. AIM: To evaluate the distribution of eosinophils in EoE and determine whether endoscopic appearances predict the degree of eosinophilia at various locations of the oesophagus. METHODS: We performed a prospective cross sectional study of EoE (treated and untreated) patients to study the distribution of eosinophils according to endoscopic findings. The oesophagus of 10 EoE patients were biopsied up to 32 times in a circumferential manner. The mucosal changes were documented at the site of each biopsy. Histological determination of eosinophil counts and related histopathology of the oesophagus were then correlated with endoscopic findings. Similar biopsy assessments were made in treated (resolved) EoE patients (n = 6) to determine the permanence of specific endoscopic appearances. RESULTS: A total of 16 patients were biopsied (10 EoE, 6 treated EoE). A total of 432 biopsies were obtained in all with 294 biopsies from 10 EoE subjects. Eosinophil density was increased distally in the majority of EoE patients. Biopsies performed in areas of exudates and furrows demonstrated higher eosinophil counts. Lines and normal-appearing oesophagi in EoE subjects were not commonly associated with elevated eosinophil counts (>15 eos/HPF). Rings alone without associated furrows or plaques did not demonstrate elevated eosinophil counts and were seen in resolved EoE (Rx-EoE) as well as in active EoE patients. CONCLUSIONS: Eosinophilic esophagitis remains a variable disease with some patients manifesting extensive disease throughout the oesophagus. Characteristics of furrows and exudates found during endoscopy are associated with higher peak eosinophil counts, requiring fewer biopsies to make a diagnosis. Lines and otherwise normal appearances of the oesophagus suggest a milder mucosal eosinophilia, requiring substantial biopsies to adequately identify fields with diagnostic eosinophil counts.

An improved dosage regimen of sertraline hydrochloride in the treatment for premature ejaculation: an 8-week, single-blind, randomized controlled study followed by a 4-week, open-label extension study.

WHAT IS KNOWN AND OBJECTIVE: This study aimed at evaluating the safety and efficacy of an improved dosage regimen of sertraline in patients with premature ejaculation (PE) and to examine whether the premature ejaculation diagnostic tool (PEDT) can be used as a measure of treatment response in these patients. METHODS: A total of 218 PE patients were randomized into control (n = 61) and treatment (n = 157) groups to receive mycelium of cordyceps sinensis C4 and sertraline 50 mg daily for 8 weeks, respectively. Following this blinded stage, sixty-three patients chose to take sertraline 100 mg daily for an additional 4-week period, and 80 other patients continued treatment with sertraline 50 mg. Main outcome measures include intravaginal ejaculatory latency time (IELT), PEDT score and Clinical Global Impression of Change (CGIC) score. RESULTS: At weeks 4 and 8, mean IELT of patients who subsequently chose to take 100 mg of sertraline was significantly lower than that of patients who continued taking 50 mg of sertraline, although the IELT value was comparable between the two groups of patients at baseline. However, with an additional 4-week treatment, the mean IELT increased significantly more in the 100-mg group than in the 50-mg continuation group. Similar results were also obtained in the analyses of the PEDT and CGIC scores. Both regimens were well tolerated, and relapse rate did not differ significantly between the two groups. WHAT IS NEW AND CONCLUSION: These findings suggest that PE patients not responding to an 8-week treatment with sertraline 50 mg can benefit from an additional 4-week treatment with sertraline 100 mg and that the PEDT may be a valid measure of treatment response in PE patients.

On the efficiency of FES cycling: a framework and systematic review.

Research and development in the art of cycling using functional electrical stimulation (FES) of the paralysed leg muscles has been going on for around thirty years. A range of physiological benefits has been observed in clinical studies but an outstanding problem with FES-cycling is that efficiency and power output are very low. The present work had the following aims: (i) to provide a tutorial introduction to a novel framework and methods of estimation of metabolic efficiency using example data sets, and to propose benchmark measures for evaluating FES-cycling performance; (ii) to systematically review the literature pertaining specifically to the metabolic efficiency of FES-cycling, to analyse the observations and possible explanations for the low efficiency, and to pose hypotheses for future studies which aim to improve performance. We recommend the following as benchmark measures for assessment of the performance of FES-cycling: (i) total work efficiency, delta efficiency and stimulation cost; (ii) we recommend, further, that these benchmark measures be complemented by mechanical measures of maximum power output, sustainable steady-state power output and endurance. Performance assessments should be carried out at a well-defined operating point, i.e. under conditions of well controlled work rate and cadence, because these variables have a strong effect on energy expenditure. Future work should focus on the two main factors which affect FES-cycling performance, namely: (i) unfavourable biomechanics, i.e. crude recruitment of muscle groups, non-optimal timing of muscle activation, and lack of synergistic and antagonistic joint control; (ii) non-physiological recruitment of muscle fibres, i.e. mixed recruitment of fibres of different type and deterministic constant-frequency stimulation. We hypothesise that the following areas may bring better FES-cycling performance: (i) study of alternative stimulation strategies for muscle activation including irregular stimulation patterns (e.g. doublets, triplets, stochastic patterns) and variable frequency stimulation trains, where it appears that increasing frequency over time may be profitable; (ii) study of better timing parameters for the stimulated muscle groups, and addition of more muscle groups: this path may be approached using EMG studies and constrained numerical optimisation employing dynamic models; (iii) development of optimal stimulation protocols for muscle reconditioning and FES-cycle training.

Immunomodulatory and anti-inflammatory properties of artesunate in experimental colitis.

BACKGROUND: Inflammatory bowel disease is a chronic and idiopathic gastrointestinal inflammation mediated by disregulated immune responses. Artemisinin (a chemical from a traditional Chinese herbal medicine Artemisia annua L.) and its derivatives have been proven to exhibit anti-inflammatory and immunomodulatory effects in the treatment of systemic lupus erythematosus and rheumatoid arthritis with low side-effects. This study is aimed to evaluate the potential therapeutic value of artesunate for inflammatory bowel disease. METHODS: Murine colitis was induced by either oral administration of dextran sulfate sodium salt (DSS) or intrarectal delivery of 2,4,6- trinitrobenzene sulfonic acid (TNBS) or oxazolone. Mice were treated with artesunate (150mg/kg/day). Peritoneal macrophages were stimulated with lipopolysaccharide (LPS) in the presence or absence of artesunate. Changes in cytokines or proteins of interests were analyzed by enzyme-linked immunosorbent assay (ELISA) or SDS-PAGE/Western blot. RESULTS: Artesunate significantly ameliorated DSS colitis and TNBS colitis (but not oxazolone colitis), including reduced weight loss and disease activity, as well as macroscopic and microscopic colonic injury. The expression of NF-κBp65 and p-IκB-α were reduced in artesunate treated TNBS colitis compared with untreated. The levels of IFN-γ, IL-17, and TNF-α were significantly decreased in artesunate treated TNBS colitis or DSS colitis. Furthermore, in vitro artesunate treatment significantly inhibited TNF-α production by LPS-activated macrophages. CONCLUSIONS: Artesunate suppresses TNF-α expression in vitro and in vivo as well as T-helper (Th)1/Th17 responses in TNBS colitis model. Our data suggest a novel clinical application of artesunate as a potential therapy for Crohn's disease.

Polybrominated diphenyl ethers in maternal serum, umbilical cord serum, colostrum and mature breast milk. Insights from a pilot study and the literature.

Human serum and mother's milk are frequently used to assess exposure to polybrominated diphenyl ethers (PBDEs), including transplacental transfer to the foetus. However, little is known about the kinetics of PBDEs, especially the highly brominated BDE congeners. In this pilot study, maternal serum samples were collected from 10 women at delivery and five to six weeks post partum. Umbilical serum was also obtained. Milk was donated two to five days, and five to six weeks after delivery. The amount of PBDEs in these samples was determined using liquid-liquid extraction and GC/MS. Low, moderately and highly brominated diphenyl ethers were present in umbilical cord serum, indicating placental transfer. The lipid-adjusted levels of BDE-47, BDE-207 and BDE-209 were similar in maternal and umbilical cord serum, whereas the cord serum levels for the penta- to octa-BDEs quantified were lower than in maternal serum. Marked changes were seen in the congener pattern in breast milk during the first month of lactation, whereas maternal serum levels did not change significantly. The general pattern was an enrichment of low to moderately brominated congeners (i.e. from BDE-17 to BDE-154, with the exception of BDE-28) in colostrum compared with maternal serum. In contrast, more highly brominated congeners were found at similar, or lower levels in colostrum than in maternal serum. After the transition from colostrum to mature milk, the levels of BDE-153 and BDE-209 were substantially reduced, and BDE-209 was below the limit of detection in 6 out of 9 samples. A literature review on the design and reporting of studies on the transfer of PBDEs from mother to infant revealed a lack of transparency in many cases. The use of the recently published STROBE-ME guidelines is therefore recommended.

Biogeography and variability of eleven mineral elements in plant leaves across gradients of climate, soil and plant functional type in China.

Understanding variation of plant nutrients is largely limited to nitrogen and to a lesser extent phosphorus. Here we analyse patterns of variation in 11 elements (nitrogen/phosphorus/potassium/calcium/magnesium/sulphur/silicon/iron/sodium/manganese/aluminium) in leaves of 1900 plant species across China. The concentrations of these elements show significant latitudinal and longitudinal trends, driven by significant influences of climate, soil and plant functional type. Precipitation explains more variation than temperature for all elements except phosphorus and aluminium, and the 11 elements differentiate in relation to climate, soil and functional type. Variability (assessed as the coefficient of variation) and environmental sensitivity (slope of responses to environmental gradients) are lowest for elements that are required in the highest concentrations, most abundant and most often limiting in nature (the Stability of Limiting Elements Hypothesis). Our findings can help initiate a more holistic approach to ecological plant nutrition and lay the groundwork for the eventual development of multiple element biogeochemical models.

One-step synthesis of highly biocompatible multi-shaped gold nanostructures with fruit extract.

In this study, the authors demonstrate the synthesis of various gold nanostructures through a one-step, green and complete bio-modulation approach. Nanoparticles were successfully synthesised by the addition of gold aqueous solution to fruit extracts, including orange, papaya, peach or lemon. The particles were of various shapes and sizes with high abundance, such as sphere, marigold, triangle and hexagon. The biocompatibility of the presented gold nanostructures was examined; haemolysis tests revealed a non-toxicity result in blood cell uptake of such gold nanostructures. This study opens the exciting possibility of synthesising various multi-shaped nanoparticles through a simple and green approach, as well as paving the way for future bio-applications.

Therapeutic effects of TACI-Ig on rat with adjuvant arthritis.

Transmembrane activator and calcium modulator and cyclophilin ligand interactor-immunoglobulin (TACI-Ig) is a human fusion protein that binds and neutralizes both B lymphocyte stimulator (BLyS), a cytokine shown to be a key regulator of B cell maturation, proliferation and survival, and a proliferation-inducing ligand (APRIL). Rat adjuvant arthritis (AA) is an experimental animal model of rheumatoid arthritis (RA), which is mainly dependent on T cells and neutrophil-mediated cytokine production. The purpose of the present study was to investigate the effects of TACI-Ig on rat AA. Rat AA was induced by intradermal injection of 0·1 ml complete Freund's adjuvant (CFA). TACI-Ig (0·7, 2·1 and 6·3 mg/kg), recombinant human tumour necrosis factor-α receptor (rhTNFR) : Fc (2·8 mg/kg) and IgG-Fc (6·3 mg/kg) were administered subcutaneously every other day from days 16 to 34 after immunization. Arthritis was evaluated by arthritis global assessment and swollen joint count (SJC). The ankle joint and spleen were harvested for histopathological examination. Spleen index and thymus index were calculated. The levels of BLyS, interleukin (IL)-17, interferon (IFN)-γ, IgG1, IgG2a and IgM in AA rat spleen were measured by enzyme-linked immunosorbent assay. Administration of TACI-Ig significantly reduced the arthritis global assessment and SJC, decreased spleen index and ameliorated histopathological manifestations of rat AA. Suppressing the levels of BLyS, IL-17, IFN-γ and Ig in AA rat spleen were observed after administration of TACI-Ig. These results showed that TACI-Ig significantly inhibited the degree of rat AA, and the inhibitory effects might be associated with its ability to reduce BLyS, proinflammatory cytokines and Ig levels in spleen.

Anti-diabetic effect of methylswertianin and bellidifolin from Swertia punicea Hemsl. and its potential mechanism.

In this study, we continued to investigate the hypoglycemic activity of Swertia punicea Helmsl., the hypoglycemic and hypolipidemic effects of methylswertianin and bellidifolin from the active ethyl acetate (EtOAc) fraction, and the potential mechanism(s) underlying the improvement of insulin resistance. Streptozotocin (STZ)-induced type 2 diabetic male BABL/c mice treated with methylswertianin and bellidifolin at different doses (orally, 200 and 100mg/kg body wt./day) for 4 weeks were analyzed in comparison to untreated mice. The results proved that methylswertianin and bellidifolin significantly reduced fasting blood glucose (FBG). The administration of both compounds also improved the oral glucose tolerance and lowered fasting serum insulin (FINS). Moreover, post-administration evaluation revealed lower serum total cholesterol (TC), low density lipoprotein cholesterol (LDL) and triglyceride (TG) levels and increased relative high density lipoprotein cholesterol (HDL) concentrations (HDL/TC). Methylswertianin and bellidifolin appeared to improve insulin resistance by enhancing insulin signaling. The expression levels of insulin-receptor alpha subunit (InsR-alpha), insulin-receptor substrate-1 (IRS-1), and phosphatidylinositol 3-kinase (PI3K) were also increased after administration. Meanwhile, methylswertianin and bellidifolin increased hepatic glycogen content, decreased glucokinase (GK) activities and increased glucose-6-phosphatase (G6Pase) activities. In conclusion, these result indicated that methylswertianin and bellidifolin could be useful for treating type-2 diabetes, likely via the improvement of insulin resistance (IR).

Two acidic polysaccharides from the flowers of Chrysanthemum morifolium.

Two new acidic polysaccharides, F4 and F5, were isolated from the flowers of Chrysanthemum morifolium. Monosaccharide analysis indicated that F4 contained arabinose, galactose and galacturonic acid units in a molar ratio of 1.0:2.3:6.8 and F5 contained arabinose, rhamnose galactose and galacturonic acid units in a molar ratio of 1.0:3.2:1.0:4.3. The results of methylation analysis, partial acid hydrolysis and NMR spectral analysis indicated that F4 had a homogalacturonan main chain with arabinogalactan side chain linked to 3 position of (1 --> 3,4)-linked galacturonan and F5 had a rhamnogalacturonan main chain with arabinogalactan side chain linked to 3 position of (1 --> 3,4)-linked galacturonan or 4 position of (1 --> 2,4)-linked rhamnose. Biological tests revealed that F4 and F5 could simulate the mitogen induced T and B lymphocyte proliferation in vitro.