Efficacy and safety of Shenbai Granules for recurrent colorectal adenoma: A multicenter randomized controlled trial.

BACKGROUND: Colorectal adenoma is benign glandular tumor of colon, the precursor of colorectal cancer. But no pharmaceutical medication is currently available to treat and prevent adenomas. PURPOSE: To evaluate efficacy of Shenbai Granules, an herbal medicine formula, in reducing the recurrence of adenomas. STUDY DESIGN: This multicenter, randomized, double-blind, placebo-controlled clinical trial was conducted by eight hospitals in China. METHODS: Patients who had received complete polypectomy and were diagnosed with adenomas within the recent 6 months were randomly assigned (1:1) to receive either Shenbai granules or placebo twice a day for 6 months. An annual colonoscopy was performed during the 2-year follow-up period. The primary outcome was the proportion of patients with at least one adenoma detected in the modified intention-to-treat (mITT) population during follow-up for 2 years. The secondary outcomes were the proportion of patients with sessile serrated lesions and other specified polypoid lesions. The data were analyzed using logistic regression. RESULTS: Among 400 randomized patients, 336 were included in the mITT population. We found significant differences between treatment and placebo groups in the proportion of patients with at least one recurrent adenoma (42.5 % vs. 58.6 %; OR, 0.47; 95 % CI, 0.29-0.74; p = 0.001) and sessile serrated lesion (1.8 % vs. 8.3 %; OR, 0.20; 95 % CI, 0.06-0.72; p = 0.01). There was no significant difference in the proportion of patients developing polypoid lesions (70.7 % vs. 77.5 %; OR, 1.43; 95 % CI, 0.88-2.34; p = 0.15) or high-risk adenomas (9.0 % vs. 13.6 %; OR, 0.63; 95 % CI, 0.32-1.25; p = 0.18). CONCLUSION: Shenbai Granules significantly reduced the recurrence of adenomas, indicating that they could be an effective option for adenomas. Future studies should investigate its effects in larger patient populations and explore its mechanism of action to provide more comprehensive evidence for the use of Shenbai Granules in adenoma treatment.

Guar gum-enhanced emission of gold nanoclusters for α-glucosidase activity detection and anti-diabetic agents screening in plant extracts.

The development of efficient fluorescent methods for α-glucosidase (α-Glu) detection and α-Glu inhibitor screening plays a critical role in the therapy of type 2 diabetes (T2D). Herein, guar gum (GG), a high-abundant and non-toxic natural polymer originated from the seeds of a drought-tolerant plant, Cyamposis tetragonolobus, was found to be able to enhance the fluorescence emission of gold nanoclusters (AuNCs) probe. The emission enhancement effect was achieved by using GG at very low concentrations (<1.0 wt%) and presented in a viscosity-dependent manner through increasing solvent reorientation time and inhibiting intramolecular motions of AuNCs. Furthermore, the enhanced emission of the AuNCs was quenched by Fe3+via dynamic quenching and then restored by α-Glu. Accordingly, a fluorimetric method was proposed for the determination of α-Glu. Owing to the fluorescence enhancement effect of GG on the AuNCs probe, the detection limit of the approach was 0.13 U L-1 and the detection range was up to 5 orders of magnitude from 0.2 to 4000 U L-1, which was much better than most current α-Glu detection methods. The approach was further applied to α-Glu inhibitors screening from natural plant extracts, providing great prospects for the prevention and treatment of T2D.

Shenlingcao oral liquid for patients with non-small cell lung cancer receiving adjuvant chemotherapy after radical resection: A multicenter randomized controlled trial.

BACKGROUND: Low quality of life (QoL) in patients with non-small cell lung cancer (NSCLC) receiving adjuvant chemotherapy after radical resection is a major global health issue. High-quality evidence for the effectiveness of Shenlingcao oral liquid (SOL) as a complementary treatment in this patients is lacking at present. PURPOSE: To determine whether complementary SOL treatment in NSCLC patients receiving adjuvant chemotherapy would yield greater improvements in QoL than chemotherapy alone. STUDY DESIGN: We conducted a multicenter, randomized controlled trial of stages IIA-IIIA NSCLC patients undergoing adjuvant chemotherapy in seven hospitals. METHODS: Using stratified blocks, participants were randomized in a 1:1 ratio to receive SOL combined with conventional chemotherapy or conventional chemotherapy alone. The primary outcome was the change in global QoL from baseline to the fourth chemotherapy cycle, and intention-to-treat analysis was applied with a mixed-effect model. Secondary outcomes were functional QoL, symptoms, and performance status scores at the 6-month follow-up. Missing data were handled with multiple imputation and a pattern-mixture model. RESULTS: Among 516 randomized patients, 446 (86.43%) completed the study. After the fourth chemotherapy cycle, in comparison with the control group, patients receiving SOL showed a lower reduction in mean global QoL (-2.76 vs. -14.11; mean difference [MD], 11.34; 95% confidence interval [CI], 8.28 to 14.41), greater improvement in physical function (MD, 11.61; 95% CI, 8.57 to 14.65), role function (MD, 10.15; 95% CI, 5.75 to 14.54), and emotional function (MD, 4.71; 95% CI, 1.85 to 7.57), and greater improvements in lung cancer-related symptoms (e.g., fatigue, nausea/vomiting, and appetite loss) and performance status during the 6-month follow-up period (treatment main effect, p < 0.05). CONCLUSION: SOL treatment for NSCLC patients receiving adjuvant chemotherapy can significantly improve QoL and performance status within 6 months after radical resection. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03712969.

Efficient PAM-Less Base Editing for Zebrafish Modeling of Human Genetic Disease with zSpRY-ABE8e.

CRISPR/Cas9 technology has increased the value of zebrafish for modeling human genetic diseases, studying disease pathogenesis, and drug screening, but protospacer adjacent motif (PAM) limitations are a major obstacle to creating accurate animal models of human genetic disorders caused by single-nucleotide variants (SNVs). Until now, some SpCas9 variants with broad PAM compatibility have shown efficiency in zebrafish. The application of the optimized SpRY-mediated adenine base editor (ABE), zSpRY-ABE8e, and synthetically modified gRNA in zebrafish has enabled efficient adenine-guanine base conversion without PAM restriction. Described here is a protocol for efficient adenine base editing without PAM limitation in zebrafish using zSpRY-ABE8e. By injecting a mixture of zSpRY-ABE8e mRNA and synthetically modified gRNA into zebrafish embryos, a zebrafish disease model was constructed with a precise mutation that simulated a pathogenic site of the TSR2 ribosome maturation factor (tsr2). This method provides a valuable tool for the establishment of accurate disease models for studying disease mechanisms and treatments.

Use of statistical methods among acupuncture randomized controlled trials was far from satisfactory.

OBJECTIVES: To examine whether appropriate statistical methods were used in acupuncture randomized controlled trials (RCTs). STUDY DESIGN AND SETTING: We searched PubMed to identify acupuncture RCTs with continuous outcome as primary outcome published in the core clinical journals and complementary and alternative medicine (CAM) journals between January 2010 and December 2019 (10 years). We compared statistical characteristics of included trials published in core clinical journals and CAM journals. RESULTS: We included 262 RCTs, including 46 published in core clinical journals and 216 in CAM journals. Of included RCTs, only 132 (50.4%) clearly predefined the primary outcome, 72 (27.5%) specified the use of intention to treat or modified intention to treat population for primary analysis. In the 167 trials reported missing participant data (MPD), 118 (70.7%) used suboptimal methods (e.g., complete case analysis) for dealing with MPD; 11 (6.6%) conducted sensitivity analysis regarding MPD. Among the 161 trials with repeated measures design, only 21 (13.0%) used advanced statistical models (e.g., mixed-effects models) for handling repeated-measure data in the primary analysis. In the 72 trials involving multiple acupuncturists, only 4 (5.6%) adjusted acupuncturist variable or considered the clustering by acupuncturist in analysis. Trials in core clinical journals were more likely to predefine primary outcome (78.3% vs. 44.4%, P < 0.001), use multiple imputations for handling MPD (40% vs. 1.5%, P < 0.001), and use statistically advanced methods for assessing treatment effect at a single time point (26.1% vs. 2%, P = 0.001). CONCLUSION: The use of statistical methods among acupuncture RCTs is far from satisfactory. Our findings highlighted the need for researchers to carefully use the optimal statistical methods and for journal editors to strengthen the use of statistical methods.

Specification of interventions and selection of controls in randomized controlled trials of acupuncture: a cross-sectional survey.

OBJECTIVE: Specification of interventions and selection of controls are two methodological determinants for a successful acupuncture trial. However, current practice with respect to these two determinants is not fully understood. Thus, we conducted a cross-sectional survey to examine the specification of interventions and selection of controls among published randomized controlled trials (RCTs) of acupuncture. STUDY DESIGN AND SETTING: We searched PubMed for acupuncture RCTs published in core clinical journals and complementary and alternative medicine (CAM) journals from January 2010 to December 2019 (10 years) and included RCTs that assessed treatment effects of acupuncture versus any type of control. We used network meta-analyses to explore whether there were differential treatment effects in patients with chronic pain when using sham acupuncture as a control versus using waiting list or no treatment. RESULTS: Most of the 319 eligible RCTs specified well the style of acupuncture (86.8%), traditional acupuncture point locations (96.2%), type of needle stimulation (90.3%) and needle retention time (85.6%). However, other acupuncture details were less-frequently specified, including response sought (65.5%), needle manipulation (50.5%), number of needle insertions (21.9%), angle and direction of insertion (31.3%), patient posture (32.3%) and co-interventions (22.9%). Sham acupuncture (41.4%) was the most frequently used control, followed by waiting list or no treatment (32.9%). There was no differential treatment effect when using sham acupuncture versus waiting list/no treatment as a control (standardized mean difference = -0.15, 95% confidence interval: -0.91 to 0.62). CONCLUSION: Over a decade of research practice, important gaps have remained in the specification of acupuncture interventions, including response sought, needle manipulation, and co-interventions. While sham acupuncture has been widely used, waiting list or no treatment may also be considered as an appropriate control.

Comparison Between Hemodialysis and Peritoneal Dialysis in the Risks for Disease Activity in LN-ESRD Patients: A Systematic Review and Meta-analysis.

Context: End-stage renal disease (ESRD) is the advanced stage of a progressive loss of kidney function. About 10% of all patients with lupus nephritis (LN) eventually progress to ESRD, which may necessitate renal replacement therapy (RRT), such as hemodialysis (HD), peritoneal dialysis (PD), and/or kidney transplant. Research hasn't confirmed which dialysis options, prior to kidney transplantation, are beneficial to patients' prognoses. Objective: The study intended to compare the risks-related to disease activity, exercise, all-cause infection, all-cause cardiovascular events, and mortality-of the use of HD and PD for LN-ESRD adults, as the initial alternative treatment before renal transplantation. Design: The research team performed a narrative review and analyzed the data obtained about clinical outcomes for HD and peritoneal dialysis. For the review, the research team searched the PubMed, EMBASE, and SCOPUS databases. The search used the keywords: end-stage renal disease, renal replacement therapy, hemodialysis and peritoneal dialysis. Setting: The study made in Affiliated Hospital of Hebei University, China. Participants: The studies included 15 636 patients who had been diagnosed with LN-ESRD prior to renal transplantation. Outcome Measures: For the data analysis, the research team divided the data into two groups, one of which included the data on the clinical outcomes for HD patientsand one of which included the data on the clinical outcomes for PD patients. The study evaluated four types of risks: lupus-flare risks, all-cause infection risks, all-cause cardiovascular events risk, and risk of mortality. Results: The 16 studies found in the review reported one or more outcomes of interest for the two dialysis modalities, HD and PD. The analysis of the data from the 16 studies showed that HD was associated with a higher risk than PD: (1) of lupus flares, with RR = 1.23 (confidence interval: 0.82, 1.85), but the difference didn't reach statistical significance (P = .31); (2) of all-cause infection risk, with RR = 1.02 (confidence interval: 0.66, 1.59), but the difference didn't reach statistical significance (P = .92); (3) of all-cause cardiovascular events, with RR = 1.44 (confidence interval: 1.02, 2.04), and the difference reached statistical significance (P = .04); and (4) of mortality risk, with RR = 1.29 (confidence interval: 0.95, 1.75), but the difference didn't reach statistical significance (P = .10). Conclusions: The current study may have reference significance for clinical treatment of ESRD. Except for all-cause cardiovascular events in which PD was superior to HD, offering better outcomes, both treatment modalities provide more or less similar clinical outcomes as effective initial choices for RRT in LN-ESRD patients prior to renal transplant. The current research team, however, encourages further research on the question, addressing better the possible sources of biases encountered in the current study.

Effects of acupuncture at acupoints with lower versus higher pain threshold for knee osteoarthritis: a multicenter randomized controlled trial.

BACKGROUND: The acupoint selections impact the effects of acupuncture, and preliminary evidence showed potential connection between pain threshold (PT) and acupuncture response. This study examined whether acupuncture at acupoints with lower PT versus higher PT would yield different effects in patients with knee osteoarthritis (KOA). METHODS: In this multicenter randomized clinical trial, patients were randomly assigned (1:1:1) to receive acupuncture at acupoints with lower PT (LPT group), acupuncture at acupoints with higher PT (HPT group), and no acupuncture (waiting-list group). PT was measured with electronic von Frey detector. The primary outcome was the change in WOMAC total score from baseline to 16 weeks, and the secondary outcomes were SF-12 score, and active knee range of motion (ROM). Intention-to-treat analysis was conducted with linear mixed-effect model. RESULTS: Among 666 randomized patients, 625 (93.84%) completed the study. From baseline to 16 weeks, patients in the LPT group versus HPT group had similar effects in reducing WOMAC total score (adjusted mean difference (MD) 2.21, 95% confidence interval (CI) -2.51 to 6.92, P = 0.36), while a greater reduction in WOMAC total score was observed in LPT group (-9.77, 95% CI -14.47 to -5.07, P < 0.001) and HPT group (-11.97, 95% CI -16.71 to -7.24, P < 0.001) compared with waiting-list group. There were no differences in SF-12 score and knee ROM between LPT versus HPT groups. CONCLUSION: Our findings found that the effects of acupuncture at acupoints with lower versus higher PT were similar, both were effective for patients with KOA. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03299439. Registered 3 October 2017, https://clinicaltrials.gov/ct2/show/NCT03299439.

Long-term (1980-2015) changes in net anthropogenic phosphorus inputs and riverine phosphorus export in the Yangtze River basin.

Quantitative information on long-term net anthropogenic phosphorus inputs (NAPI) and its relationship with riverine phosphorus (P) export are critical for developing sustainable and efficient watershed P management strategies. This is the first study to address long-term (1980-2015) NAPI and riverine P flux dynamics for the Yangtze River basin (YRB), the largest watershed in China. Over the 36-year study period, estimated NAPI to the YRB progressively increased by ∼1.4 times, with NAPIA (chemical fertilizer input + atmospheric deposition + seed input) and NAPIB (net food/feed imports + non-food input) contributing 65% and 35%, respectively. Higher population, livestock density and agricultural land area were the main drivers of increasing NAPI. Riverine total phosphorus (TP), particulate phosphorus (PP) and suspended sediment (SS) export at Datong hydrological station (downstream station) decreased by 52%, 75% and 75% during 1980-2015, respectively. In contrast, dissolved phosphorus (DP) showed an increase in both concentration (∼7-fold) and its contribution to TP flux (∼16-fold). Different trends in riverine P forms were mainly due to increasing dam/reservoir construction and changes in vegetation/land use and NAPI components. Multiple regression models incorporating NAPIA, NAPIB, dam/reservoir storage capacity and water discharge explained 84% and 92% of the temporal variability in riverine DP and PP fluxes, respectively. Riverine TP flux estimated as the sum of DP and PP fluxes showed high agreement with measured values (R2 = 0.87, NSE = 0.84), indicating strong efficacy for the developed models. The model forecasted an increase of 50% and 7% and a decrease of 15% and 22% in riverine DP flux from 2015 to 2045 under developing, dam building, NAPIA and NAPIB reduction scenarios, respectively. This study highlights the importance of including enhanced P transformation from particulate to bioavailable forms due to river regulation and changes in land-use, input sources and legacy P pools in development of P pollution control strategies.

Elevation of Lower Esophageal Sphincter Pressure With Acute Transcutaneous Electrical Acustimulation Synchronized With Inspiration.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common esophageal disorder. Transcutaneous electrical acustimulation (TEA), as a needleless method of electroacupuncture (EA) has been reported to improve hypotensive lower esophageal sphincters pressure (LESP) in GERD. Synchronized TEA (STEA) with inspiration has been revealed to be more effective than TEA in enhancing vagal tone. AIM: To explore the effect of STEA on LESP in GERD and possible mechanisms involving autonomic functions. METHODS: Sixty patients were randomly allocated into a STEA group (45 patients) and sham-TEA group (15 patients). The ECG was recorded for the assessment of the autonomic function, followed with an esophageal high-resolution manometry (HRM) test. When the test was completed, the STEA or sham-TEA treatment was performed for 30 minutes. Then the HRM test was repeated. RESULTS: STEA increased LESP from 21.9 to 31.9 mmHg in GERD patients (p < 0.001). A negative correlation between the percentage of STEA-induced increase in LESP and basal LESP was observed (R = -0.471, p = 0.001). STEA reduced the number of ineffective esophageal contractions (p < 0.05). STEA rather than sham-TEA increased vagal activity (0.27 ± 0.14 vs. 0.36 ± 0.18, p < 0.001) and decreased sympathetic activity (0.73 ± 0.14 vs. 0.64 ± 0.18, p < 0.001). CONCLUSIONS: Acute STEA augments LESP in GERD and the percentage of the increase in LESP was negatively correlated with basal LESP. The effect of STEA on LESP might be mediated via autonomic function. CONFLICT OF INTEREST: The authors reported no conflict of interest.

Dihydroartemisinin induces apoptosis and inhibits proliferation, migration, and invasion in epithelial ovarian cancer via inhibition of the hedgehog signaling pathway.

Dihydroartemisinin (DHA), the primary of artemisinin extracted from the traditional Chinese medicine Artemisia annua, has been used in malaria treatment for a long time. Recently, many studies have indicated that, in addition to antimalarial effects, DHA also exhibits anticancer activity in certain types of neoplasms, including ovarian cancer. However, the precise anti-ovarian cancer mechanism of DHA is still unclear. Abnormal activation of the hedgehog (Hh) pathway is closely related to tumorigenesis and progression of ovarian cancer. We performed this study to elucidate the effects of DHA on the biological behavior of ovarian cancer cells and to determine its effects on the Hh signaling pathway. CCK8 assays and flow cytometry were used to evaluate the effects of DHA on cell viability and apoptosis in both ovarian cancer cells and HOSEPICs (human ovarian surface epithelial cells) in response to DHA treatment. Transwell membrane chambers were used to analyze the effects of DHA on the migration and invasion of epithelial ovarian cancer cells following treatment with DHA. The impact of DHA on Hh signaling was analyzed by RT-qPCR and Western blot. DHA significantly inhibited proliferation, migration, and invasion of ovarian cancer cells, and induced apoptosis in vitro. In contrast, DHA had few effects on cell proliferation and apoptosis in HOSEPICs. DHA inhibited the hedgehog signaling pathway. Furthermore, DHA inhibited purmorphamine (Hh signaling pathway agonist)-induced cell proliferation, cell migration, and cell invasion and the inhibition of apoptosis. Importantly, DHA enhanced GANT61 (hedgehog signaling pathway inhibitor)-induced apoptosis and the inhibition of cell viability, migratory capacity, and invasive ability. This study demonstrates that DHA inhibits cell viability, migration, and invasion, as well as induces apoptosis in epithelial ovarian cancer through suppression of the Hh signaling pathway.

Preventive effects of transcutaneous electrical acustimulation on ischemic stroke-induced constipation mediated via the autonomic pathway.

The aim of this study was to explore the preventive effect and possible mechanisms of transcutaneous electrical acustimulation (TEA) on stroke-induced constipation. A total of 86 ischemic stroke patients were randomly allocated to 2-wk TEA or sham-TEA group. Bowel dairy and Bristol Stool Form Scale were recorded daily. Constipation and dyspeptic symptom assessment was performed at the end of the 14-day treatment. Electrocardiogram was recorded for the assessment of autonomic function. The correlation between autonomic function at admission and stroke severity was assessed. The univariate and multivariate regression analyses were performed to investigate the risk factors for stroke-induced constipation. The cumulative incidence of stroke-induced constipation was 68.2% at the acute stage. Sympathetic nerve activity at admission was positively correlated with stroke severity ( R = 0.47, P < 0.001). Sympathetic nerve activity and stroke severity were independent risk factors for stroke-induced constipation. TEA decreased cumulative incidence of stroke-induced constipation (42.9 vs. 68.2%, P = 0.029). TEA significantly increased frequency of bowel movements (4.5 vs. 5.5, P = 0.001) and spontaneous bowel movements (3.0 vs. 4.5, P = 0.003) per week. TEA decreased straining defecations (0.2 vs. 0, P < 0.001) and laxative use (1 vs. 0, P < 0.001). TEA improved stool consistency and patients' quality of life ( P < 0.05, resp.). TEA increased vagal activity ( P < 0.001 vs. baseline) and decreased sympathetic activity ( P < 0.001 vs. baseline). Ischemic stroke patients are predisposed to autonomic function imbalance. TEA was effective in the prevention of stroke-induced constipation, and the effect was possibly mediated via the autonomic function. NEW & NOTEWORTHY This study illustrated that the brain-gut dysfunction, primarily autonomic function imbalance, was correlated with the stroke-induced constipation. This was the first study to report that transcutaneous electrical acustimulation had a preventive effect on stroke-induced constipation, suggesting a potential novel therapy for bowel problem management. The effect was possibly mediated via the autonomic function.

Application of the combination index (CI)-isobologram equation to research the toxicological interactions of clothianidin, thiamethoxam, and dinotefuran in honeybee, Apis mellifera.

Due to complex pest control scenarios and the needs of agricultural production, different neonicotinoids may be used in certain agricultural applications. Consequently, honeybees may be exposed to these substances through distribution throughout plant tissues via the vascular system through several pathways, such as surface water, the exudates excreted from plants, and air pollution via drift of dust as well as contaminated pollen and nectar. In the current study, the single and combined toxicity of clothianidin, dinotefuran, and thiamethoxam to honeybees was examined after 48 h exposure by the acute oral method and combination index (CI)-isobologram equation. At the 48 h interval, our results showed that 1) the order of toxicities for the single insecticides was ranked as clothianidin > thiamethoxam > dinotefuran and that 2) all binary and ternary combinations showed synergism or additive effect at the effect (fa) 0.5. Therefore, our results not only provided meaningful guidelines in evaluating the safety risk of the mixtures of the three neonicotinoids towards honeybees but also suggested that there is a significant interest in the study of mixture toxicities of neonicotinoids against honeybees because risk assessment of neonicotinoids against honeybees conducted only in individual insecticides may underestimate the realistic toxicity.

Curcumol allosterically modulates GABA(A) receptors in a manner distinct from benzodiazepines.

Inhibitory A type γ-aminobutyric acid receptors (GABAARs) play a pivotal role in orchestrating various brain functions and represent an important molecular target in neurological and psychiatric diseases, necessitating the need for the discovery and development of novel modulators. Here, we show that a natural compound curcumol, acts as an allosteric enhancer of GABAARs in a manner distinct from benzodiazepines. Curcumol markedly facilitated GABA-activated currents and shifted the GABA concentration-response curve to the left in cultured hippocampal neurons. When co-applied with the classical benzodiazepine diazepam, curcumol further potentiated GABA-induced currents. In contrast, in the presence of a saturating concentration of menthol, a positive modulator for GABAAR, curcumol failed to further enhance GABA-induced currents, suggesting shared mechanisms underlying these two agents on GABAARs. Moreover, the benzodiazepine antagonist flumazenil did not alter the enhancement of GABA response by curcumol and menthol, but abolished that by DZP. Finally, mutations at the ß2 or γ2 subunit predominantly eliminated modulation of recombinant GABAARs by curcumol and menthol, or diazepam, respectively. Curcumol may therefore exert its actions on GABAARs at sites distinct from benzodiazepine sites. These findings shed light on the future development of new therapeutics drugs targeting GABAARs.

Pharmacokinetics and tolerance of dehydroandrographolide succinate injection after intravenous administration in healthy Chinese volunteers.

AIM: Dehydroandrographolide succinate (DAS) is extracted from herbal medicine Andrographis paniculata (Burm f) Nees. DAS injection is used in China for the treatment of viral pneumonia and upper respiratory tract infections. The aim of this study is to investigate the pharmacokinetics and tolerance of DAS injection in healthy Chinese volunteers. METHODS: This was a single-center, randomized, single-dose, three-way crossover design study. Nine eligible subjects were randomly divided into 3 groups, and each group sequentially received 80, 160, or 320 mg of DAS infusion according to a three-way Latin square design. Plasma and urine samples were collected and determined using an LC-MS/MS method. Safety and tolerability were determined via clinical evaluation and adverse event monitoring. RESULTS: For the 80, 160, and 320 mg dose groups, the mean C(max) were 4.82, 12.85, and 26.90 mg/L, respectively, and the mean AUC(0-12) were 6.18, 16.95, and 40.65 mg·L(-1)·h, respectively. DAS was rapidly cleared, with a mean T(max) of 0.94-1.0 h and a t(1/2) of approximately 1.51-1.89 h. Approximately 10.1%-15.5% of the intravenous DAS dose was excreted unchanged in urine within 24 h in the 3 groups, and more than 90% of unchanged DAS was excreted between 0 and 4 h. The pharmacokinetic profile was similar between male and female subjects. No serious or unexpected adverse events were found during the study, but one mild adverse event (stomachache) was reported. CONCLUSION: This study shows that DAS has nonlinear pharmacokinetic characteristics. To guarantee the effective concentration, mul¬tiple small doses are recommended in clinical regimens.

Determination of dehydroandrographolide succinate in human plasma by liquid chromatography tandem mass spectrometry (LC-MS/MS): Method development, validation and clinical pharmacokinetic study.

A LC-MS/MS method was developed and validated for the determination of dehydroandrographolide succinate (DAS), a traditional Chinese medicine derivative used for the treatment of pneumonia, upper respiratory tract infection, and chronic bronchitis. Following protein precipitation, DAS was detected by ion transition at m/z 531.2/99.0 in multiple reaction monitoring mode with negative electrospray ionization-tandem mass spectrometry. The limit of detection was 0.5ng/mL, and the lower limit of quantification was 10ng/mL in human plasma. Good linearity was maintained over the range of 10-5000ng/mL, and the correlation coefficient was better than 0.99. The accuracy ranged from 95.3% to 113%, RSD from 0.928% to 6.47%, for the within- and between-run analysis at all QC levels. The recovery ranged from 85.5% to 93.4% and the matrix effect from 107% to 119%. No significant carryover and good stability were found during method validation. The developed method was successfully applied to the determination of DAS in human plasma in a pharmacokinetic study following intravenous infusion of potassium sodium DAS to nine healthy volunteers.

[Pathogen identification of Pinellia ternata tuber disease and selection of fungicide].

The rotten tuber of Pinellia ternata was found as an important disease during the growing season in Tianshui production area. The isolated pathogens were tested following Koch's postulates and identified as Fusarium oxysporum. The suitable growth conditions for the F. oxysporum were 15-30 degrees C, pH 6-8, the optimal condition was 21.9 degrees C and pH 7.2. Some fungicides were demonstrated to be effective to inhibit the pathogen growth. 70% thiophanate-methyl and 58% metalaxyl MZ were most effective to inhibit the pathogen. The EC50 were 0.002 7, 0.066 2 g x L(-1), respectively.

Endocrine traits of polycystic ovary syndrome in prenatally androgenized female Sprague-Dawley rats.

Although hyperandrogenism is an important condition and is considered the possible pathogenesis behind polycystic ovary syndrome (PCOS), data supporting this is still scarce. We sought to determine whether or not prenatal androgen exposure leads to PCOS and the possible cellular mechanisms involved. To induce prenatal androgen exposure, pregnant rats were treated with daily subcutaneous injections of free testosterone (T) or dihydrotestosterone (DHT) from embryonic days 16 to 19, and their female offspring were studied as adults. The mRNA expression of the progesterone receptor (PR) in the preoptic area (POA) hypothalamus was higher in the experimental groups than in the control group after ovariectomy and stimulation with estradiol benzoate. The levels of T, P, leutinizing hormone (LH), and estradiol were higher in the experimental groups than in the control groups. The frequency and magnitude of LH secretion was increased in experimental rats as compared with the control group. The anogenital distance of the experimental groups was prolonged and the nipple number was lower than that of the control group. Almost all experimental rats had prolonged or irregular estrous cycles. The experimental groups had fewer corpus luteum and preovulatory follicles and more preantral follicles and antral follicles than the controls. Our findings are consistent with the hypothesis that excess androgen during the prenatal period may cause PCOS. Additionally, we show that hyperandrogenic interference in the release of preovulatory LH surges is mediated by the suppressive effects of androgens on PR expression in POA-hypothalamic tissue.