[Accumulation Characteristics and Health Risk Assessment of Heavy Metals in Soil-Crop System Based on Soil Parent Material Zoning].

This study used both the element occurrence form analysis and the chronic health risk assessment method to investigate the accumulation characteristics of heavy metals in the soil-crop system and the health risk assessment of agricultural products in northeastern Yunnan, which is a typical area of Southwest China where heavy metals are enriched in soil. Based on the study of 1137 groups of agricultural products and corresponding root soils, the results showed that the soil cadmium (Cd) and lead (Pb) in the lead-zinc ore concentration area were higher than the risk-intervention values of the "Soil Environmental Quality Risk control standard for soil contamination of agricultural land" (GB 15618-2018), whereas the soil Cd in the other parent material areas was within the screening-intervention buffer zone, and Pb was below the minimum risk-screening value. According to the National Food Safety Standard of China (GB 2762-2017), the heavy metal Cd in potatoes and soybeans in the area seriously exceeded the standard, the heavy metal Pb in tartary buckwheat and walnut exceeded the limit value, and the exceeding rate of heavy metal Cd in crops from these parent material areas showed: clastic rock>basalt>lead-zinc ore>carbonate ≈ Quaternary sedimentary>sand (mud) rock. According to the U.S. Environmental Protection Agency's assessment method for the chronic health risk of heavy metal intake by humans, the grains and potatoes, staple foods, and fruits had low chronic health risks of heavy metal intake. Agricultural products from the parent material area of clastic rock, sand (mud) rock, Quaternary sedimentary, and lead-zinc ore concentration showed health risks; with the change in soil physical and chemical properties and the increase in the types of edible crops, the risk will gradually increase. Based on this research, it is urgent to carry out real-time monitoring of agricultural products in the area.

Effect of drug combination on tacrolimus target dose in renal transplant patients with different CYP3A5 genotypes.

Various factors, including genetic polymorphisms, drug-drug interactions, and patient characteristics influence the blood concentrations of tacrolimus in renal transplant patients. In the present study, we established a population pharmacokinetic model to explore the effect of combined use of Wuzhi capsules/echinocandins and the patients' biochemical parameters such as haematocrit on blood concentrations and target doses of tacrolimus in renal transplant patients with different CYP3A5 genotypes. The aim of the study was to propose an individualised tacrolimus administration regimen for early renal transplant recipients.In this retrospective cohort study, we included 240 renal transplant recipients within 21 days of surgery (174 males and 66 females, mean age 39.4 years), who received tacrolimus alone (n = 54), in combination with Wuzhi capsules (99) or caspofungin (57) or micafungin (30). We collected demographic characteristics, clinical indicators, CYP3A5 genotypes, and 1950 steady-state concentrations of tacrolimus and included them in population pharmacokinetic model. An additional 110 renal transplant recipients and 625 steady-state concentrations of tacrolimus were included for external validation of the model. The population pharmacokinetic model was established and Monte Carlo was used to simulate probabilities for achieving the target concentration for individual tacrolimus administration.A two-compartment model of first-order absorption and elimination was developed to describe the population pharmacokinetics of tacrolimus. CYP3A5 genotypes and co-administration of Wuzhi capsules, as well as time after renal transplantation and haematocrit, were important factors affecting the clearance of tacrolimus. We found no obvious change in trend in the scatter plot of tacrolimus clearance rate vs. haematocrit. The Monte Carlo simulation indicated the following recommended doses of tacrolimus alone: 0.14 mg⋅kg-1⋅d-1 for genotype CYP3A5*1*1, 0.12 mg⋅kg-1⋅d-1 for CYP3A5*1*3, and 0.10 mg⋅kg-1⋅d-1 for CYP3A5*3*3. For patients receiving the combination with Wuzhi capsules, the recommended doses of tacrolimus were 0.10 mg⋅kg-1⋅d-1 for CYP3A5*1*1, 0.08 mg⋅kg-1⋅d-1 for CYP3A5*1*3, and 0.06 mg⋅kg-1⋅d-1 for CYP3A5*3*3 genotypes. Caspofungin or micafungin had no effect on the clearance of tacrolimus in renal transplant recipients.The population pharmacokinetics of tacrolimus in renal transplant patients was evaluated and the individual administration regimen of tacrolimus was simulated. For early kidney transplant recipients receiving tacrolimus treatment, not only body weight, but also CYP3A5 genotypes and drugs used in combination should be considered when determining the target dose of tacrolimus.

Therapeutic effects and mechanisms of Zhen-Wu-Bu-Qi Decoction on dextran sulfate sodium-induced chronic colitis in mice assessed by multi-omics approaches.

BACKGROUND: Zhen-Wu-Bu-Qi Decoction (ZWBQD), a traditional Chinese medicine formula comprising Poria, Radix Paeoniae Alba, Rhizoma Atractylodis Macrocephalae, Rhizoma Zingiberis Recens, Radix Codonopsis and Rhizoma Coptidis, is used for treating ulcerative colitis (UC). In a previous study, we have reported ZWBQD mitigates the severity of dextran sulfate sodium (DSS)-induced colitis in mice. HYPOTHESIS: In this study, we aimed to understand the systemic actions and underlying mechanisms of ZWBQD on experimental colitis in mice. METHODS: We used multi-omics techniques and immunoblotting approach to study the pharmacological actions and mechanisms of ZWBQD in DSS-induced chronic colitic mice. RESULTS: We showed that ZWBQD exhibited potent anti-inflammatory properties and significantly protected DSS-induced colitic mice against colon injury by regulating the PI3K-AKT, MAPK signaling pathway and NF-κB signaling pathways. We also revealed that ZWBQD significantly ameliorated gut microbiota dysbiosis and abnormalities of tryptophan catabolites induced by DSS. CONCLUSIONS: We demonstrated that the therapeutic effects of ZWBQD on experimental colitis are mediated by regulating multiple signaling pathways and modulation of gut microbiota. Our study employed an integrative strategy to elucidate novel mechanisms of ZWBQD, which provides new insights into the development of Chinese herbal medicine-based therapeutics for UC.

Methylenetetrahydrofolate Reductase Gene Polymorphism C677T is Associated with Increased Risk of Coronary Heart Disease in Chinese Type 2 Diabetic Patients.

Objective Chronic cardiovascular diseases induced by long-term poor blood glucose control are the main cause of death in patients with type 2 diabetes mellitus (T2DM). Previous researches report that methylenetetrahydrofolate reductase gene (MTHFR) polymorphisms might influence the occurrence of coronary heart disease (CHD) in T2DM patients. The purpose of this study was to evaluate whether MTHFR C677T and A1298C mutations are associated with the risk of CHD in T2DM patients. Methods A total of 197 subjects with T2DM were studied, of which 95 patients with CHD. The genotypes of MTHFR C677T and A1298C were analyzed by using dideoxy chain-termination method, and compared between patients with CHD and those without CHD. Results We found that the frequency of the 677T allele was significantly higher in T2DM patients with CHD than those without CHD (P=0.011). However, there was no significant difference in any of the examined haplotypes between T2DM patients with and without CHD. Furthermore, the 677T allele was associated with a higher risk of CHD development in diabetic patients with lower homocysteine (Hcy) levels (≤15 µmol/L) (P=0.006), while no effect of MTHFR gene polymorphism on the incidence of CHD was found in patients with higher Hcy levels (>15 µmol/L) (P=0.491). Conclusion The MTHFR C677T gene polymorphism is associated with the risk of CHD of diabetic patients and could be used as an effective marker for CHD in Chinese diabetic populations with normal Hcy levels.

Methylenetetrahydrofolate Reductase Gene Polymorphism C677T is Associated with Increased Risk of Coronary Heart Disease in Chinese Type 2 Diabetic Patients / 中国医学科学杂志(英文版)

Objective Chronic cardiovascular diseases induced by long-term poor blood glucose control are the main cause of death in patients with type 2 diabetes mellitus (T2DM). Previous researches report that methylenetetrahydrofolate reductase gene (

Author Correction: Cyclocarya paliurus tea leaves enhances pancreatic ß cell preservation through inhibition of apoptosis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

[Ecological Risk Assessment of Heavy Metals at Township Scale in the High Background of Heavy Metals, Southwestern, China].

Heavy metals (HMs) are naturally occurring elements that have high natural background levels in the environment. Therefore, it is important to conduct ecological risk assessment and identify potential sources of HMs. In the past, studies were conducted at the regional scale. The accuracy of those studies could not meet the needs of spatial planning and natural resource management. Therefore, it is necessary to conduct ecological risk assessment at the township scale. In this study, 1092 soil samples (from 0-20 cm depth) were collected in the town of Reshui, an area with high background levels of soil HMs with the parent material of carbonatite, which is commonly found in Southwest China. The town of Reshui is a multi-ecological risk superimposed area where the ecological risk is high. In this study, concentrations of HMs (Cd, Cr, As, Hg, Pb, Cu, Zn, and Ni) in the topsoil were analyzed, and statistical analysis (SA), geographic information system (GIS) modeling, and positive matrix factorization (PMF) analysis were performed. The geoaccumulation index (Igeo) and potential ecological risk index (PERI) were applied for the ecological risk assessment and quantification of the sources of the soil HMs. The mean values of HM concentrations in the topsoil were 18.1, 1.18, 174.1, 202.2, 0.09, 71.1, 34.9, and 167.2 mg ·kg-1for As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn, respectively, which were considerably higher than the average background value (ABV) in soils in Yunnan Province except for As and Pb. The average concentrations of Cd, Cr, Cu, and Ni exceeded the screening values specified in the soil contamination risk in agricultural land (GB 15618-2018) by 5.82, 1.16, 4.04, and 1.02 times, respectively. The Igeo value shows that the major pollutant is Cu in the surface soil of the study area, followed by Cr, and Cd. Speciation analysis of HMs indicates that HMs (Cr, As, Pb, Cu, Zn, and Ni) mainly exist in the residual form, mostly from the geological background with low bioavailability. The potential effective components of Hg have higher levels, but the total amount of Hg and its pollution risk are lower. Cd has a high bioavailability ratio, is easy to enter the soil solution and be absorbed by crops, and is the HM with the highest pollution risk in the study area. The PERI shows that the proportions of low ecological risk, moderate risk, and high risk soil samples are 44.23%, 54.40%, and 1.37% of the total number of samples, respectively. Hg and Cd were the major sources of risk because of their high toxicity coefficient. The PMF analysis indicates that there are four major sources of HMs in the study area: human activity, natural sources, coal mining and traffic emissions, and agricultural sources with the risk contribution ratios of 9.29%, 53.67%, 11.23%, and 25.81%, respectively. The PMF analysis effectively quantified the ecological risk from these sources, providing a reference for further pollution control and prevention measures.

Berberine Suppresses Colonic Inflammation in Dextran Sulfate Sodium-Induced Murine Colitis Through Inhibition of Cytosolic Phospholipase A2 Activity.

Ulcerative colitis (UC) causes chronic inflammation and damage to the colonic mucosal layer. Recent studies have reported significant changes in phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) in UC patients and oral administration of PC has considerable therapeutic effects against UC, suggesting the metabolism of phosphatidylcholine may be involved in the UC development. Our previous work has demonstrated that berberine effectively suppresses inflammation and protects colonic mucosa injury in DSS-induced colitic mice. However, whether the therapeutic effects of berberine are attributed to its action on the PC metabolism remains unknown. In the present study, we have shown that berberine significantly reduces the lysophosphatidylcholine (LPC) levels in the sera of DSS-induced experimental colitis mice and LPS-stimulated macrophage RAW 264.7 cells. The cytosolic phospholipase A2a (PLA2G4A), an enzyme for hydrolyzing PC to LPC, was found to be up-regulated in the colon tissue of experimental colitis mice and inflamed macrophage RAW 264.7 cells. We then demonstrated berberine inhibits the phosphorylation of cytosolic phospholipase A2a (PLA2G4A) in the colon tissue of experimental colitis mice and inflamed macrophage RAW 264.7 cells. Subsequently, we revealed berberine suppressed the expression of pro-inflammatory factors including TNF-alpha and IL-6 through regulating PLA2G4A dysfunction in macrophage RAW 264.7 cells. Mechanistically, we found that berberine directly binds to PLA2G4A and inhibits MAPK/JNK signaling pathway to inhibit PLA2G4A activity in inflammatory status. Therefore, we concluded that berberine inhibits colonic PLA2G4A activity to ameliorate colonic inflammation in experimental colitic mice, suggesting modulation of the PC metabolism via PLA2G4A might be beneficial for establishing new therapies strategy for UC.

Pharmacogenetics of statins treatment: Efficacy and safety.

WHAT IS KNOWN AND OBJECTIVE: Statins are widely used worldwide in the prevention and treatment of coronary atherosclerotic heart disease and ischaemic stroke. However, in clinical application, statins have shown great individual differences in terms of the efficacy and safety, some of which are related to genetic factors. The purpose of this article was to summarize the recent advances about the correlation between gene polymorphisms and the efficacy/safety of statins. METHODS: We searched the databases including PharmGKB and PubMed (published before June 2019) using the keywords such as 'statin', 'gene polymorphism' and 'SNP' and obtained more than 100 articles. In this review, we described the clinical studies of genetic variants associated with both the efficacy and adverse reactions of statins. We also clarified the importance of taking pharmacogenetic variation into account to improve the clinical application of statins. RESULTS AND DISCUSSION: The available data were collected and analysed to present the polymorphisms of candidate genes encoding the most promising proteins including SLCO1B1 (encoding uptake transporters); ABCB1, ABCC2, ABCG2 (encoding effluent transporter); APOE, APOA5 (encoding apolipoprotein); genes encoding cytochrome P450 enzyme system; KIF6, HMGCR, LDLR, LPA, PCSK9, COQ2, CETP, etc These genes were proved to be related to the pharmacodynamics and pharmacokinetics of statins, thus affecting the efficacy and safety. WHAT IS NEW AND CONCLUSION: In this paper, the correlation between gene polymorphisms and the efficacy/safety of statins was summarized. The authors reached a consensus that the variants of the genes encoding uptake and effluent transporters have the most effect on the efficacy/safety of statins. It pointed out that it is desirable to do genetic testing of these transporter genes to reduce the incidence of myopathy or to achieve better outcomes before patients use statins, especially in the regions with high frequency of risk allele.

Simultaneous UPLC-TQ-MS/MS determination of six active components in rat plasma: application in the pharmacokinetic study of Cyclocarya paliurus leaves.

BACKGROUND: Cyclocarya paliurus (Batal.) Ijinskaja (CP) is a monotypic genus plant, also called sweet tea tree that belongs to the Juglandaceae family, which is mainly distributed in the subtropical highlands in China. Our previous work has verified that CP leaves exhibit a potent hyperglycemic effect by inhibiting pancreatic ß cell apoptosis through the regulation of MPAK and Akt signaling pathways. However, the components that contribute to this potential health benefit remain undiscovered. METHOD: A sensitive, reliable, and validated ultra-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry (UPLC-TQ-MS/MS) method was developed to simultaneously determine the presence of six active components (neochlorogenic acid, chlorogenic acid, quercetin-3-O-glucuronide, kaempferol-3-O-rhamnoside, quercetin, and kaempferol) in rat plasma after a single oral administration (in a dosage of 10.5 g/kg) of an extract of CP leaves to rats. The separation was performed on a Waters ACQUITY BEH C18 column (50 mm × 2.1 mm, 1.7 µm). The detection was conducted by multiple reaction monitoring (MRM) in negative ionization mode. The two highest abundant MRM transitions without interference were optimized for each analyte. Acetonitrile and formic acid aqueous solution (0.1%) was used as the mobile phase at a flow rate of 0.3 ml/min. RESULT: The precision, accuracy, and recovery all satisfied the criteria of international guidance (Bioanalytical Method Validation Guidance for Industry, Food and Drug Administration), and the analytes were stable in plasma for all tested conditions. The main pharmacokinetic parameters were calculated by plasma concentration versus time profiles using the pharmacokinetics program. CONCLUSION: The pharmacokinetic parameters of each compound can facilitate future clinical studies.

Identification of α-glucosidase inhibitors from cyclocarya paliurus tea leaves using UF-UPLC-Q/TOF-MS/MS and molecular docking.

Leaves of Cyclocarya paliurus (CP) have a potential antihyperglycemic effect, but its active compositions responsible for the beneficial properties remain unclear. The CP extract exhibited remarkable α-glucosidase inhibitory activity with an IC50 value of 31.5 ± 1.05 µg mL-1, much lower than that of the positive control acarbose (IC50 = 296.6 ± 1.06 µg mL-1). To identify the specific α-glucosidase inhibitors from the CP extract, affinity ultrafiltration coupled with ultra-performance liquid chromatography and quadrupole-time-of-flight mass spectrometry (UF-UPLC-Q/TOF-MS/MS) was developed and 11 potential α-glucosidase inhibitors from CP extract were identified. In vitro α-glucosidase inhibitory assay verified that quercetin-3-O-glucuronide, kaempferol-3-O-rhamnoside, quercetin, kaempferol, asiatic acid and genistein were primarily responsible for the α-glucosidase inhibitory activity of the CP extract. Further, a hypoglycemia test also verified that these α-glucosidase inhibitors had the potential to reduce post-prandial hyperglycaemia in C57BL/6 mice. Moreover, the molecular docking study revealed that these identified α-glucosidase inhibitors more easily occupy the active sites of α-glucosidase than does the positive control acarbose. These findings suggest the CP tea leaves are the potential source of a hypoglycaemic agent.

Efficacy of MaZiRenWan, a Chinese Herbal Medicine, in Patients With Functional Constipation in a Randomized Controlled Trial.

BACKGROUND & AIMS: The Chinese herbal medicine, MaZiRenWan (MZRW), has been used for more than 2000 years to treat constipation, but it has not been tested in a randomized controlled trial. We performed a trial to evaluate the efficacy and safety of MZRW, compared with the stimulant laxative senna or placebo, for patients with functional constipation (FC). METHODS: We performed a double-blind, double-dummy, trial of 291 patients with FC based on Rome III criteria, seen at 8 clinics in Hong Kong from June 2013 through August 2015. Patients were observed for 2 weeks and then assigned randomly (1:1:1) to groups given MZRW (7.5 g, twice daily), senna (15 mg daily), or placebo for 8 weeks. Patients were then followed for 8 weeks and evaluated at baseline and weeks 4, 8 (end of treatment), and 16 (end of follow up). Participants recorded information on stool form and frequency, feeling of complete evacuation, and research medication taken. Data on individual bowel symptoms, global symptom improvement, and adverse events were collected. A complete response was defined as an increase ≥1 complete spontaneous bowel movement (CSBM)/week from baseline (the primary outcome). Secondary outcomes included response during the follow-up period, colonic transit, individual and global symptom assessments, quality of life measured with 36-item short form Chinese version, and adverse events. RESULTS: Although there was no statistically significant difference in proportions of patients with a complete response to MZRW (68%) vs. senna (57.7%) (P = .14) at week 8, there was a statistically significant difference vs. placebo (33.0%) (P < .005). At the 16-week timepoint (after the 8-week follow-up period), 47.4% of patients had a complete response to MZRW, 20.6% had a complete response to senna, and 17.5% had a complete response to placebo (P < .005 for MZRW vs. placebo). The group that received MZRW group also had significant increases in colonic transit and reduced severity of constipation, straining, incomplete evacuation, and global constipation symptoms compared with the groups that received placebo or senna in (P < .05 for all comparisons). CONCLUSIONS: In a randomized controlled trial of 291 patients with FC, we found MZRW to be well-tolerated and effective in increasing CSBM/week. MZRW did not appear to be more effective than senna and might be considered as an alternative to this drug. ClincialTrials.gov no: NCT01695850.

Chinese Herbal Medicine (MaZiRenWan) Improves Bowel Movement in Functional Constipation Through Down-Regulating Oleamide.

In a prospective, randomized, three-arms, controlled clinical study, Chinese Herbal Medicine MaZiRenWan (MZRW, also known as Hemp Seed Pill) demonstrates comparable efficacy with Senna for functional constipation (FC) during an 8-week treatment period. Both MZRW and Senna are better than a placebo; relative to Senna and a placebo, MZRW displayed a more sustained effect during the 8-week follow-up period. The characteristic pharmacological mechanism responsible for this observation is still unclear. To explore this, we collected pre- and post-treatment serum samples of 85 FC patients from MZRW/Senna/placebo treatment groups for pharmacometabolomic analysis. An ultrahigh-performance liquid chromatography-mass spectrometer (UPLC-MS) was used for metabolic profiling and quantification. In vivo studies were conducted in constipated C57BL/6J mice to verify the effects and corresponding mechanism(s) of the action of MZRW. Pearson correlation analysis, paired t-test, one-way ANOVA analysis, χ2 test, and Student t-test were used to interpret the clinical and preclinical data. Changes in levels of circulating oleamide and its derivatives negatively correlate with improvement in complete spontaneous bowel movement (CSBM) in the MZRW group (Pearson r = -0.59, p = 0.00057). The same did not hold true for either Senna or placebo groups. Oleamide is a known regulator of intestinal motility. MZRW treatment resulted in reduced levels of circulating oleamide in FC patients. Experimental verification showed that MZRW attenuated oleamide-induced slow intestinal motility in mice. MZRW decreased oleamide levels in serum, ileum, and colon in normal mice, but increased expression of colonic fatty acid amide hydrolase (FAAH). In conclusion, MZRW improved bowel movement in FC by down-regulating oleamide, possibly by enhancing FAAH-mediated degradation. Our findings suggest a novel therapeutic strategy for FC.

Psychological burden prediction based on demographic variables among infertile men with sexual dysfunction / 亚洲男科学杂志(英文版)

There has been increasing interest in the psycho-socio-relational and sexual disorders of infertility, as the risk of psychological burden among infertile men with sexual dysfunctions is significant. The purpose of this study was to develop and to validate a predictive model to estimate individual psychological burden among infertile men with sexual dysfunction and study the association between them. Comprehensive data were collected for infertile men (n = 480) who sought treatment for infertility in a reproductive medicine center between June 2012 and December 2013. Using independent predictors of psychological burden from the least absolute shrinkage and selection operator, univariable and multivariable analyses were developed into two models. Predictive accuracy was compared between the models. We explored the association between sexual dysfunction and psychological burden. A total of 480 patients were analyzed using 10-fold cross-validation. Independent predictors of psychological burden were incorporated into a model to measure anxiety (corrected-area under curve (AUC): 77.3%) and a model to measure depression (corrected-AUC: 70.2%). Anxiety and depression were both associated with erectile dysfunction (P < 0.05), with anxiety demonstrating the strongest association. Only anxiety was associated with premature ejaculation (P < 0.05). Premature ejaculation was not found to be associated with depression (P > 0.05). Predictive models for psychological burden among infertile men with sexual dysfunction are presented, and we found that there is an association between psychological burden and sexual dysfunction. According to the models, proper counseling and treatment of sexual dysfunction in infertile men may reduce the psychological burden, help attain natural pregnancy, and improve the quality of life.

Cyclocarya paliurus Leaves Tea Improves Dyslipidemia in Diabetic Mice: A Lipidomics-Based Network Pharmacology Study.

Hyperlipidemia and hepatic steatosis afflict over 75% of patients with type 2 diabetes, causing diabetic dyslipidemia. Cyclocarya paliurus (CP) leaf is a herbal tea which has long been consumed by the Chinese population, particularly people suffering from obesity and diabetes. CP appears to exhibit a hypolipidemic effect in lipid loaded mice (Kurihara et al., 2003), although the detailed mechanisms and active ingredients for this hypolipidemic effect have not yet been answered. In this study, we investigated the beneficial effects of CP and predicted the mechanisms by utilizing lipidomics, serum-pharmacochemistry and network pharmacology approaches. Our results revealed that serum and hepatic levels of total triglyceride (TG), total cholesterol (T-CHO), low-density lipoproteins (LDL) and high-density lipoproteins (HDL), as well as 30 lipids including cholesterol ester (CE), diglyceride (DG), phosphatidylethanolamine (PE), phosphatidylcholine (PC), and sphingomyelin (SM) in CP-treated mice were improved in comparison with untreated diabetic mice. In parallel, 14 phytochemical compounds of CP were determined in mice serum after CP administration. Mechanistically, the network pharmacology analysis revealed the predicted targets of CP's active ingredients ALOX12, APP, BCL2, CYP2C9, PTPN1 and linked lipidome targets PLD2, PLA2G(s), and PI3K(s) families could be responsible for the CP effects on diabetic dyslipidemia. In conclusion, this study revealed the beneficial effects of CP on diabetic dyslipidemia are achieved by reducing accumulation of hepatic lipid droplets and regulating circulatory lipids in diabetic mice, possibly through PI3K signaling and MAPK signaling pathways. GRAPHICAL ABSTRACTWork flow of the evaluation of the effects and mechanisms of Cyclocarya paliurus leaves tea on dyslipidemia in diabetic mice.

Approaches in studying the pharmacology of Chinese Medicine formulas: bottom-up, top-down-and meeting in the middle.

Investigating the pharmacology is key to the modernization of Chinese Medicine (CM) formulas. However, identifying which are the active compound(s) of CM formulas, which biological entities they target, and through which signaling pathway(s) they act to modify disease symptoms, are still difficult tasks for researchers, even when equipped with an arsenal of advanced modern technologies. Multiple approaches, including network pharmacology, pharmaco-genomics, -proteomics, and -metabolomics, have been developed to study the pharmacology of CM formulas. They fall into two general categories in terms of how they tackle a problem: bottom-up and top-down. In this article, we compared these two different approaches in several dimensions by using the case of MaZiRenWan (MZRW, also known as Hemp Seed Pill), a CM herbal formula for functional constipation. Multiple hypotheses are easy to be proposed in the bottom-up approach (e.g. network pharmacology); but these hypotheses are usually false positives and hard to be tested. In contrast, it is hard to suggest hypotheses in the top-down approach (e.g. pharmacometabolomics); however, once a hypothesis is proposed, it is much easier to be tested. Merging of these two approaches could results in a powerful approach, which could be the new paradigm for the pharmacological study of CM formulas.

Erectile dysfunction is associated with subclinical carotid vascular disease in young men lacking widely-known risk factors / 亚洲男科学杂志(英文版)

This study aimed to gain insight into the underlying pathogenesis of erectile dysfunction in young men under the age of 40 years without widely-known risk factors. Compared with normal controls, patients with erectile dysfunction had increased carotid intima-media thickness, fasting levels of blood glucose and insulin, and homeostatic model assessment index, as well as lower flow-mediated vasodilation and testosterone levels (P < 0.05), though all of these values were within their respective normal range. Multivariate logistic regression analysis identified carotid intima-media thickness, flow-mediated vasodilation, insulin level, and homeostatic model assessment index as significant predictors of erectile dysfunction. Young men with flow-mediated vasodilation <10.65% were 11.645 times more likely to have erectile dysfunction, young men with carotid intima-media thickness >0.623 mm had a 4.16-fold, and young men with homeostatic model assessment index >1.614 had a 5.993-fold greater risk of having erectile dysfunction. In conclusions, in young men with normal results from general clinical screening, an increased carotid intima-media thickness and homeostatic model assessment index and reduced flow-mediated vasodilation were associated with a higher incidence of erectile dysfunction. Erectile dysfunction may appear before the detection of traditional cardiovascular risk factors and may be the earliest clinical sign of subclinical cardiovascular disease.

Cyclocarya paliurus tea leaves enhances pancreatic ß cell preservation through inhibition of apoptosis.

Leaves of Cyclocarya paliurus are a sweet tea traditionally used to treat obesity and diabetes in China. However, its protective mechanisms against hyperglycemia remains unclear. Here, we demonstrate that the extract of C. paliurus leaves significantly decreased body loss, food intake and blood glucose level, and increased blood insulin level, ß-cell number and insulin-producing ß cells in high-fat diet-low dose STZ-induced diabetic mice. In vivo and in vitro studies also showed the extract of C. paliurus leaves significantly inhibited pancreatic ß cell apoptosis by suppressing the expression of caspase 8, caspase 9 and cleaved caspase-3, as well as Bax/Bcl-2 ratio, down-regulating p38, ERK and JNK phosphorylation, and up-regulating Akt phosphorylation. These effects were significantly enhanced by inhibitor p-38 or ERK or JNK, and counteracted by inhibitor of PI3K. In addition, the extract of C. paliurus leaves also significantly improved hepatic steatosis, nephropathy and cardiac hypertrophy of diabetic mice. Taken together, these results provide the insight into the effects of C. paliurus leaves on pancreatic ß cell preservation in standing glucolipotoxicity. Therefore, C. paliurus tea leaves may be used as a new remedy for diabetes through enhancing pancreatic ß cell preservation by inhibiting ß cell apoptosis.

[Effects of different drying methods on quality of Gastrodiae Rhizoma].

Different drying methods, including drying in the sun, sulphur fumigation, hot air drying, microwave drying, infrared drying and various coupling techniques,were used to dry fresh Gastrodiae Rhizoma. Characteristics, extracts and the contents of active components of all samples were compared to investigate the effects of different drying methods on quality of Gastrodiae Rhizoma. The results showed that the characteristics of the samples would be better with use of sulphur fumigation, hot air drying, and hot air-microwave drying. Different drying methods had little effects on extracts. Among them, the extract content was higher after hot air drying. The stilbene glycosides would transformation and the contents of Gastrodiae Rhizoma polysaccharides would decline with use of sulphur fumigation, microwave drying and infrared drying. In the comprehensive analysis of characteristics, content of active components, production cost and other factors, hot air drying or hot air-microwave drying was recommended as the first choice.

Effects of different drying methods on quality of Gastrodiae Rhizoma / 中国中药杂志

Different drying methods, including drying in the sun, sulphur fumigation, hot air drying, microwave drying, infrared drying and various coupling techniques,were used to dry fresh Gastrodiae Rhizoma. Characteristics, extracts and the contents of active components of all samples were compared to investigate the effects of different drying methods on quality of Gastrodiae Rhizoma. The results showed that the characteristics of the samples would be better with use of sulphur fumigation, hot air drying, and hot air-microwave drying. Different drying methods had little effects on extracts. Among them, the extract content was higher after hot air drying. The stilbene glycosides would transformation and the contents of Gastrodiae Rhizoma polysaccharides would decline with use of sulphur fumigation, microwave drying and infrared drying. In the comprehensive analysis of characteristics, content of active components, production cost and other factors, hot air drying or hot air-microwave drying was recommended as the first choice.