[Preparation of evodiamine-glycyrrhizic acid micelles with glycyrrhizic acid as carrier and their anti-hepatic fibrosis activity].

This study aimed to prepare evodiamine-glycyrrhizic acid(EVO-GL) micelles to enhance the anti-hepatic fibrosis activity of evodiamine. Firstly, EVO-GL micelles were prepared with use of thin film dispersion method. With particle size, encapsulation efficiency, loading capacity of micelles and the solubility of evodiamine as the indexes, the effect of different factors on micelles was observed to screen the optimal preparation methods and process. Then the pharmaceutical properties and the therapeutic effects of EVO-GL micelles prepared by optimal process were evaluated on CCl_4-induced hepatic fibrosis. The results showed that the micelles prepared by the thin film dispersion method had an even size, with an average particle size of(130.80±12.40)nm, Zeta potential of(-41.61±3.12) mV, encapsulation efficiency of 91.23%±1.22%, drug loading of 8.42%±0.71%, high storage stability at 4 ℃ in 3 months, and slow in vitro release. Experimental results in the treatment of CCl_4-induced hepatic fibrosis in rats showed that EVO-GL micelles had a synergistic anti-hepatic fibrosis effect, which significantly reduced the liver function index of hepatic fibrosis rats. In conclusion, the EVO-GL micelles prepared with glycyrrhizic acid as a carrier would have a potential application prospect for the treatment of hepatic fibrosis.

Serum Trimethylamine N-Oxide Concentration Is Positively Associated With First Stroke in Hypertensive Patients.

Background and Purpose- Trimethylamine N-oxide (TMAO)-a gut derived metabolite-has been shown to be atherogenic. It remains unknown whether TMAO is associated with the risk of first stroke. We aimed to determine the association between serum TMAO levels and first stroke in hypertensive patients without major cardiovascular diseases and examine any possible effect modifiers. Methods- We used a nested case-control design, using data from the CSPPT (China Stroke Primary Prevention Trial), including 622 patients with first stroke and 622 matched controls. The study was conducted from May 2008 to August 2013. The primary outcome was a first stroke. Results- After adjusting for choline, L-carnitine, and other important covariates, including baseline systolic blood pressure and time-averaged systolic blood pressure, during the treatment period, the risk of first stroke increased with each increment of TMAO level (per natural log [TMAO] increment: odds ratio, 1.22; 95% CI, 1.02-1.46). Consistently, compared with participants in the lowest tertile (<1.79 µmol/L) of serum TMAO levels, a significantly higher risk of first stroke was found in those in higher TMAO tertiles (≥1.79 µmol/L; odds ratio, 1.34; 95% CI, 1.00-1.81) or in TMAO tertile 3 (≥3.19 µmol/L; odds ratio, 1.43; 95% CI, 1.02-2.01). In the exploratory analysis, we observed an interaction between TMAO and folate levels (≥7.7 [median] versus <7.7 ng/mL) on first stroke ( P for interaction, 0.030). Conclusions- Higher TMAO levels were associated with increased risk of first stroke in hypertensive patients. Our finding, if further confirmed, calls for a carefully designed clinical trial to further evaluate the role of higher TMAO levels on outcomes in hypertensive patients. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT00794885.

[Pharmacokinetics and oral bioavailability of palmatine and jatrorrhizine in Huangteng in rats].

In this study, the total alkaloids of Huangteng were given to the rats by the methods of intragastric administration and tail vein. After the concentration changes of palmatine and jatrorrhizine in the plasma of rats were determined by RP-HPLC, pharmacokinetic parameters and oral bioavailability were calculated by 3P97 software. After the rats were pre-treated with total alkaloid 60 mg•kg⁻¹ by the methods of intragastric administration and tail vein, the main pharmacokinetic parameters were determined as follows： in the intragastric administration group, the Cmax of palmatine and jatrorrhizine were (0.91±0.06), (0.70±0.08) mg•L⁻¹; tmax of palmatine and jatrorrhizine were (35.24±0.83), (47.76±1.24) min; t1/2 of palmatine and jatrorrhizine were (187.03±1.53), (105.64±16.99) min, AUC of palmatine and jatrorrhizine were (280.30±18.69), (144.36±1.06) mg•min•L⁻¹; in the intravenous injection group, the t1/2 of palmatine and jatrorrhizine were (172.18±12.38), (147.26±1.82) min; AUC of palmatine and jatrorrhizine were (2 553.14±214.91), (328.83±10.81) mg•min•L⁻¹. The oral bioavailability of palmatine was 10.98% and jatrorrhizine was 43.90%.

Pulse Pressure Variation Adjusted by Respiratory Changes in Pleural Pressure, Rather Than by Tidal Volume, Reliably Predicts Fluid Responsiveness in Patients With Acute Respiratory Distress Syndrome.

OBJECTIVES: 1) To evaluate the ability of pulse pressure variation adjusted by respiratory changes in pleural pressure to predict fluid responsiveness compared with pulse pressure variation alone. 2) To identify factors explaining the poor performance of pulse pressure variation in acute respiratory distress syndrome. DESIGN: Prospective study. SETTING: Forty-bed university hospital general ICU. PATIENTS: Ninety-six mechanically ventilated acute respiratory distress syndrome patients requiring fluid challenge. INTERVENTIONS: Fluid challenge, 500 mL saline over 20 minutes. MEASUREMENTS AND MAIN RESULTS: Before fluid challenge, esophageal pressure was measured at the end-inspiratory and end-expiratory occlusions. Change in pleural pressure was calculated as the difference between esophageal pressure measured at end-inspiratory and end-expiratory occlusions. Hemodynamic measurements were obtained before and after the fluid challenge. Patients were ventilated with tidal volume 7.0 ± 0.8 mL/kg predicted body weight. The fluids increased cardiac output by greater than 15% in 52 patients (responders). Adjusting pulse pressure variation for changes in pleural pressure (area under the receiver operating characteristic curve, 0.94 [0.88-0.98]) and the ratio of chest wall elastance to total respiratory system elastance (area under the receiver operating characteristic curve, 0.93 [0.88-0.98]) predicted fluid responsiveness better than pulse pressure variation (area under the receiver operating characteristic curve, 0.78 [0.69-0.86]; all p < 0.01). The gray zone approach identified a range of pulse pressure variation/changes in pleural pressure values (1.94-2.1) in 3.1% of patients for whom fluid responsiveness could not be predicted reliably. On logistic regression analysis, two independent factors affected the correct classification of fluid responsiveness at a 12% pulse pressure variation cutoff: tidal volume (adjusted odds ratio 1.57/50 mL; 95% CI, 1.05-2.34; p = 0.027) and chest wall elastance/respiratory system elastance (adjusted odds ratio, 2.035/0.1 unit; 95% CI, 1.36-3.06; p = 0.001). In patients with chest wall elastance/respiratory system elastance above the median (0.28), pulse pressure variation area under the receiver operating characteristic curve was 0.94 (95% CI, 0.84-0.99) compared with 0.76 (95% CI, 0.61-0.87) otherwise (p = 0.02). CONCLUSIONS: In acute respiratory distress syndrome patients, pulse pressure variation adjusted by changes in pleural pressure is a reliable fluid responsiveness predictor despite the low tidal volume (< 8 mL/kg). The poor predictive ability of pulse pressure variation in acute respiratory distress syndrome patients is more related to low chest wall elastance/respiratory system elastance ratios than to a low tidal volume.

The 100 most-cited articles on cardiovascular diseases from Mainland China.

BACKGROUND: China, as a rapidly developing country with the largest population of cardiologist in the world, has an increasing importance in the field of cardiology. However, the quantity and quality of research production in the field of cardiology is unclear. AIMS: To analyze the characteristics of the high-level articles published on cardiovascular diseases in Mainland China, and to provide information about achievements and development in cardiovascular research. METHODS: We searched the Science Citation Index Expanded for citations of cardiovascular articles originating in mainland China from 2004 to 2015. For the 100 most frequently cited articles (T100), we evaluated the number of citations, publication time, province of origin, journal, impact factor, topic or subspecialty of the research, and publication type. RESULTS: The most frequently cited article received 703 citations at the most, while 50 at the least (mean 91.6 citations per article). T100 originated from 16 provinces, the plurality (n = 34) being from the Beijing. Sixty-seven percent were published during 2006-2009. The publications were in 29 different journals of which Circulation published the most (n = 14). Leading general medical journals Journal of the American Medical Association (n = 1), Lancet (n = 0) and New England Journal of Medicine (n = 0) featured only 1 published article, despite their extremely high impact factors. Of the T100 articles, there were 50 basic researches, 44 clinical researches, 5 meta-analyses and 1 review article. Clinical researches had the highest mean citations (mean 102.6 citations per article). CONCLUSIONS: This study provides a historical perspective on the scientific progress, and the trends in cardiovascular medicine in Mainland China.

Clinical management of organophosphate poisoning in pregnancy.

BACKGROUND: Acute organophosphorus pesticide poisoning during pregnancy may lead to spontaneous abortion. Now, there is no definite strategy focused on maintaining pregnancy. METHOD: This is a retrospective analysis of 2 cases of organophosphorus poisoning during pregnancy. All patients received penehyclidine hydrochloride injection,until the tracheobronchial tree is cleared of the secretions, and most secretions were dried. In addition, magnesium sulfate was used in one woman for the correction of hyperdynamic uterine activity. RESULTS: Two women all survived, one fetus died of spontaneous abortion, and one fetus died of incoordinate uterine action. The 2 women had no significant complications during postpartum period. CONCLUSION: Penehyclidine hydrochloride and magnesium sulfate may be used to treat organophosphorus during pregnancy. However, futher study and new experimental need to be designed.

Optimization of paeonol-loaded microparticle formulation by response surface methodology.

In this study, a central composite rotatable design based on response surface methodology (RSM) was employed to design and formulate an appropriate paeonol microparticle formulation. Five levels of a three-factor, rotatable, central composite design were used to evaluate the critical formulation variables. The optimum conditions for preparing paeonol-loaded microparticles were predicted to be: polyvinyl alcohol (PVA) content (2.84%), the ratio of drug to polymer (6.88) and the stirring rate (1007.59 rpm). The optimized responses for production yield and loading efficiency were found to be 68.86% and 55.90%, respectively, and the particle size were 23.27 ± 0.76 µm and the sorting coefficient (σ) was 0.732. Furthermore, in vitro release study suggested that microparticle could be a suitable delivery system in treating skin disease for its sustained release of drug. In conclusion, RSM can be successfully used to optimize the effect of formulation variables.

Bioavailability enhancement of paclitaxel via a novel oral drug delivery system: paclitaxel-loaded glycyrrhizic acid micelles.

Paclitaxel (PTX, taxol), a classical antitumor drug against a wide range of tumors, shows poor oral bioavailability. In order to improve the oral bioavailability of PTX, glycyrrhizic acid (GA) was used as the carrier in this study. This was the first report on the preparation, characterization and the pharmacokinetic study in rats of PTX-loaded GA micelles The PTX-loaded micelles, prepared with ultrasonic dispersion method, displayed small particle sizes and spherical shapes. Differential scanning calorimeter (DSC) thermograms indicated that PTX was entrapped in the GA micelles and existed as an amorphous state. The encapsulation efficiency was about 90%, and the drug loading rate could reach up to 7.90%. PTX-loaded GA micelles displayed a delayed drug release compared to Taxol in the in vitro release experiment. In pharmacokinetic study via oral administration, the area under the plasma concentration-time curve (AUC0→24 h) of PTX-loaded GA micelles was about six times higher than that of Taxol (p < 0.05). The significant oral absorption enhancement of PTX from PTX-loaded GA micelles could be largely due to the increased absorption in jejunum and colon intestine. All these results suggested that GA would be a promising carrier for the oral delivery of PTX.

A new species of the subgenus Stigmatochirus of Plastus Bernhauer (Coleoptera: Staphylinidae: Osoriinae) from Yunnan, China.

Plastus (Stigmatochirus) menglaius sp. nov. is described from Yunnan, China. Color images of the habitus and aedeagu of the new species are included. A key to the subgenus Stigmatochirus of World species is provided.

A new species of the genus Thoracochirus Bernhauer (Coleoptera: Staphylinidae: Osoriinae) from Yunnan, China.

Thoracochirus yunxianius sp. nov. is described from Yunnan, China. Color images of the habitus and aedeagus of the new species are included. A key to the genus Thoracochirus of mainland China species is provided.

Mechanism of low-frequency, low-intensity ultrasound modulation of the mouse retina.

Objective.Ultrasound has been shown to modulate the activity of retinal ganglion cells (RGCs) in mice, but the mechanism remains poorly understood. This study aims to address this question.Approach.Multi-electrode recordings together with pharmacological methods were used to investigate the possible cellular/circuitry mechanism(s) underlying the neuronal modulation induced by low-frequency (1 MHz), low-intensity (ISPTA0.5 W cm-2) ultrasound stimulation.Main results.We found that ultrasound activated mechanosensitive channels (transient receptor potential vanilloid 4 (TRPV4) channels are involved) in Müller cells, causing the release of glutamate, which acts on the extrasynapticN-methyl-D-aspartate receptors of RGCs, thus leading to the modulation of neuronal activity.Significance.Our results reveal a novel mechanism of low-frequency, low-intensity ultrasound modulation, involving TRPV4 as a mechanosensitive target for ultrasound and glutamate as an essential mediator of neuron-glia communication. These findings also demonstrate that the mechanical-force-mediated pathway is important for retinal signal modulation during visual processes, such as visual accommodation.

Dual effects of hydrogen sulphide on focal cerebral ischaemic injury via modulation of oxidative stress-induced apoptosis.

1. Hydrogen sulphide (H2S), one of three signalling gasotransmitters, plays an important role in oxidative stress and apoptosis. However, the effects of H2S on oxidative stress-induced apoptosis in focal cerebral ischaemic injury in rats have not been clarified. 2. In the present study, sodium hydrosulphide (NaHS) was used as the H2S donor. Eighty-four Sprague-Dawley rats were randomly divided into six groups: sham, sham + low-dose (2.8 mg/kg) NaHS, sham + high-dose (11.2 mg/kg) NaHS, infarct, infarct + low-dose NaHS and infarct + high-dose NaHS. The focal cerebral ischaemic model was created by cranially inserting a nylon thread with a rounded tip into an internal carotid artery. Rats were killed 21 h after administration of NaHS. 3. In the infarct + low-dose NaHS compared with infarct group, infarct volume was significantly decreased and injury to the mitochondria in nerve cells was mitigated. Furthermore, significant increases were seen in mitochondrial superoxide dismutase and glutathione peroxidase activity and neuronal bcl-2 protein levels, whereas mitochondrial malondialdehyde content and neuronal bax and caspase 3 protein levels were significantly decreased, in the infarct + low-dose NaHS compared with infarct group. The effects seen in the infarct group were significantly aggravated in the infarct + high-dose NaHS group. 4. The findings of the present study provide novel evidence for the dual effects of H2S on focal cerebral ischaemic injury via modulation of oxidative stress-induced apoptosis.

Low-frequency, low-intensity ultrasound modulates light responsiveness of mouse retinal ganglion cells.

Objective. Ultrasound modulates the firing activity of retinal ganglion cells (RGCs), but the effects of lower-frequency, lower-intensity ultrasound on RGCs and underlying mechanism(s) remain poorly understood. This study aims to address these questions.Approach. Multi-electrode recordings were used in this study to record the firing sequences of RGCs in isolated mouse retinas. RGCs' background firing activities as well as their light responses were recorded with or without ultrasound stimulation. Cross-correlation analyses were performed to investigate the possible cellular/circuitry mechanism(s) underlying ultrasound modulation.Main results. It was found that ultrasound stimulation of isolated mouse retina enhanced the background activity of ON-RGCs and OFF-RGCs. In addition, background ultrasound stimulation shortened the light response latency of both ON-RGCs and OFF-RGCs, while enhancing part of the RGCs' (both ON- and OFF-subtypes) light response and decreasing that of the others. In some ON-OFF RGCs, the ON- and OFF-responses of an individual cell were oppositely modulated by the ultrasound stimulation, which suggests that ultrasound stimulation does not necessarily exert its effect directly on RGCs, but rather via its influence on other type(s) of cells. By analyzing the cross-correlation between the firing sequences of RGC pairs, it was found that concerted activity occurred during ultrasound stimulation differed from that occurred during light stimulation, in both spatial and temporal aspects. These results suggest that the cellular circuits involved in ultrasound- and light-induced concerted activities are different and glial cells may be involved in the circuit in response to ultrasound.Significance. These findings demonstrate that ultrasound affects neuronal background activity and light responsiveness, which are critical for visual information processing. These results may also imply a hitherto unrecognized role of glial cell activation in the bidirectional modulation effects of RGCs and may be critical for the nervous system.

Artemisinin biosynthesis enhancement in transgenic Artemisia annua plants by downregulation of the ß-caryophyllene synthase gene.

Artemisinin is an effective antimalarial drug isolated from the medicinal plant Artemisia annua L. Due to its increasing market demand and the low yield in A. annua, there is a great interest in increasing its production. In this paper, in an attempt to increase artemisinin content of A. ANNUA by suppressing the expression of ß-caryophyllene synthase, a sesquiterpene synthase competing as a precursor of artemisinin, the antisense fragment (750 bp) of ß-caryophyllene synthase cDNA was inserted into the plant expression vector pBI121 and introduced into A. annua by Agrobacterium-mediated transformation. PCR and Southern hybridization confirmed the stable integration of multiple copies of the transgene in 5 different transgenic lines of A. annua. Reverse transcription PCR showed that the expression of endogenous CPS in the transgenic lines was significantly lower than that in the wild-type control A. annua plants, and ß-caryophyllene content decreased sharply in the transgenic lines in comparison to the control. The artemisinin content of one of the transgenic lines showed an increase of 54.9 % compared with the wild-type control. The present study demonstrated that the inhibition pathway in the precursor competition for artemisinin biosynthesis by anti-sense technology is an effective means of increasing the artemisinin content of A. annua plants.

[Paraquat (PQ) clearance through continuous plasma perfusion in PQ poisoning patients: a clinical study].

OBJECTIVE: To examine the impact of continuous plasma perfusion on plasma PQ concentration (PPQ) in acute PQ-poisoning patients for the estimation of its PQ clearance effect. METHODS: 21 PQ-poisoned patients admitted to our poisoning center within 24 hours after the ingestion were prospectively enrolled. Continuous plasma perfusion (flow rate 180 ml/min) was performed, with plasma/blood separation at 40 ml/min and routine cartridges change every 3 hours. Urinary PQ (UPQ), urine flow rate (UFR), and PPQ level at inlet/outlet of the cartridge were obtained right before, and 1.5 hours after the start of each perfusion session for calculation of renal and plasma PQ excretion. RESULTS: In all 8 rounds (108 sessions) of plasma perfusion on the 21 patients, PQ elimination rate (ml/min) by plasma perfusion was found always higher than the renal value: [1st (21 cases) 11.14±6.13 vs. 5.33±4.33; 2nd (21 cases) 18.36±11.32 vs. 4.85±3.15; 3rd (21 cases) 16.13±10.05 vs. 0.84±0.80; 4th (17 cases) 12.86 (6.72, 17.47) vs. 0.28 (0.09, 0.60); 5th (11 cases) 14.12 (10.48, 35.20) vs. 0.10 (0.03, 0.73); 6th (7 cases) 16.47 (11.82; 20.69) vs. 0.13 (0.03, 0.40); 7th (5 cases) 13.33 (9.71, 18.75) vs. 0.33 (0.24, 0.47); 8th (5 cases) 11.27 (9.21, 16.02) vs. 0.32 (0.10, 1.22), P< 0.05 or P< 0.01]. In the study, PPQ was found negatively correlated to PQ elimination by plasma perfusion (r = - 0.4799, P< 0.0001), and positively correlated to the renal elimination ( r = 0.5060, P< 0.0001). The survivors (10 cases) showed a higher PPQ reduction rate (mg×L(-1)×h(-1)) than the non-survivors (11 cases, 0.57± 0.03 vs. 0.47±0.06,P< 0.05). CONCLUSION: Continuous plasma perfusion may be a promising therapeutic tool for its significant PPQ reduction effect, and plasma perfusion should be made available early for patients with acute PQ intoxication.

[Modulation on the P-glycoprotein in the jejunum by combined use of Glycyrrhiza inflata and Kansui].

To investigate the modulation on the P-glycoprotein in the jejunum by combined use of Glycyrrhiza inflata and Kansui with ussing chamber and rt-pcr, Rhodamine 123 (R123), a P-gp substrate and fluorescein sodium (CF), a model drug of non-P-gp substrate transported by a passive diffusion were taken as investigational drugs. Because these two drugs can be easily assayed and widely used in various research fields. The permeability of R123 or CF via Wistar rat jejunum membranes was evaluated by in vitro ussing chamber after oral administration of four different decoctions of Glycyrrhiza inflata and Kansui for 1 week. And the concentration of R123 or CF was determined by the fluorospectrophotometry in the receiving solution. Meanwhile the expression of mdr1a in P-glycoprotein was detected by real-time fluorescent quantitative PCR. After oral administration of combined decoction of the single drug, the absorptive directed permeability of R123 increased significantly (P < 0.01). On the other hand, Kansui and combine decoction of the two drugs also decrease the permeability of secretory directed transport (P < 0.05). No action of Glycyrrhiza inflata was found on the secretory transport of R123 [Papp = (2.56 +/- 0.38) x 10(-5), cm x s(-1)] across the jejunum tissues, while Papp of control group was found [Papp = (2.35 +/- 0.27) x 10(-5), cm x s(-1)]. After oral administration of Kansui decoction for 1 week and 2 weeks, the levels of mdr1a expression in Wistar rats were lower than that of the control group, but there were no significant difference in the results. Meanwhile, Glycyrrhiza inflata had no effect on transport of CF across the jejunum tissues, though the other three groups could decrease the permeability of CF, as compared with control group. Kansui may slightly inhibit P-glycoprotein function in the intestinal membrane. For another, some compositions in Kansui inhibit P-glycoprotein function, and some others strengthen the tight junction between cells in the intestinal membrane to decrease permeability of CF. As the inhibitory action to P-glycoprotein was enhanced by combination of Glycyrrhiza inflata and Kansui, based on the results, it may be one of the mechanisms of creating toxicity once co-administration of Glycyrrhiza inflata and Kansui.

[The histological changes of diabetic rats' skin and the effects on the percutaneous absorption of glucocorticoid].

To examine the histological changes of diabetic rats' skin and the effects on the percutaneous absorption of hydrocortisone (HC, a glucocorticoid), male Wistar rats were randomly divided into five groups: control group, diabetes one-week group (W1), two-week group (W2), three-week group (W3), and four-week group (W4), while each group contained 6 rats. Diabetes mellitus (DM) rat model was prepared with the method of streptozocin (STZ, 40 mg x kg(-1)) intraperitoneal injection. Abdominal skin was cut to carry out an in-vitro penetration experiment on an improved Franz diffusion cells, and phosphate buffer (PBS, pH 7.4) was used as receptor solution. The solution was analyzed with HPLC, and then the penetrating rate can be calculated. Meanwhile, rats' abdominal skins of different DM periods were HE stained and made into tissue slices to find if any histological changes occurred. The penetrating rate of control, W1, W2, W3, and W4 groups were 2.39 +/- 1.25, 3.22 +/- 1.72, 3.02 +/- 1.89, 3.63 +/- 2.02 and 5.00 +/- 3.36 microg x h(-1) x cm(-2), respectively. There was significant difference between the control and the W4 group (P < 0.05), but no significant differences were found between any other two groups (P > 0.05). The tissue slices showed that compared to the normal rats' skin, little change was observed in one-week DM rats' skin, but the skin of one-month DM rats' skin was observed thinner, and it became much thinner than that of rats with two-month diabetes, especially the epidermis. After making a rat into diabetic, the rats' skin goes through a pathological change, and this change is closely interrelated with the increase of the permeation of HC. Therefore, it is necessary to adjust the dose while some drug was applied on the skin in case of diabetes mellitus.

[Pharmacokinetics and bioavailability of sustained-release tablets of matrine in dogs].

OBJECTIVE: To study the pharmacokinetics and bioavailability of sustained-release tablets of Matrine in dogs. METHODS: 6 dogs were randomly assigned to receive sustained-release tablets or commercial capsules 300 mg, then a crossover trial was conducted 1 week later. Plasma samples were taken at different time points and the plasma concentration of Oxymatrine and Matrine in dogs was determined by HPLC. RESULTS: The pharmacokinetic parameters of self-made sustained-release tablets versus those of its control preparation were as follows: Tmax: (6.17 +/- 2.04) (M), (3.25 +/- 0.61) (OM), (4.75 +/- 1.17) (M), (2.42 +/- 0.38) (OM) h; Cmax: (3.79 +/- 1.11) (M), (4.76 +/- 0.60) (OM), (5.35 +/- 0.72) (M), (7.04 +/- 0.47) (OM) microg/mL; AUC(0-->infinity): (45.15 +/- 11.77) (M), (32.38 +/- 4.60) (OM) and (44.71 +/- 5.52) (M), (29.11 +/- 4.41) (OM) microg x h/mL. CONCLUSION: The self-made sustained-release tablets and commercial capsules bioequivalent.

A new species of the genus Oxyporus Fabricius (Coleoptera: Staphylinidae: Oxyporinae) in Yunnan Province, China.

A new species of the genus Oxyporus Fabricius, 1775 is described based on specimens collected in Yunnan Province, China, namely Oxyporus (Oxyporus) mojiangius Li, sp. nov. from Mojiang County. The number of Oxyporus species worldwide is thus increased to 132. Color images of the habitus and aedeagus of the new species are included. A key to the Oxyporus species of Yunnan Province is provided.

A U-shaped association between serum betaine and incident risk of first ischemic stroke in hypertensive patients.

BACKGROUND & AIMS: Betaine (a micronutrient) has important biological functions (e.g., preventing premature apoptosis and serving as a methyl donor). We investigated the association between baseline serum betaine and the incident risk of first stroke in hypertensive patients. METHODS: We conducted a nested case-control study, including 622 patients with first stroke (including 502 ischemic stroke, 118 hemorrhagic stroke and 2 uncertain type of stroke) and 622 matched controls from the China Stroke Primary Prevention Trial (CSPPT). The study was conducted from May 2008 to August 2013. The study outcomes included first stroke and its subtypes: first ischemic and hemorrhagic stroke. RESULTS: There was a U-shaped association between baseline serum betaine and the risk of first ischemic stroke. The risk of first ischemic stroke decreased with the increment of betaine (per 10 µmol/L increase: OR, 0.87; 95%CI: 0.77-0.99) in patients with betaine <77.7 µmol/L, while the risk of first ischemic stroke increased with the betaine increment (OR, 1.17; 95%CI: 1.01-1.36) in patients with betaine ≥77.7 µmol/L. However, there was no significant association between serum betaine and risk of first hemorrhagic stroke (per 10 µmol/L increase: OR, 0.98; 95%CI: 0.82-1.17). CONCLUSIONS: There was a U-shaped association between baseline betaine levels and the risk of first ischemic stroke in hypertensive patients, with a turning point at about 77.7 µmol/L. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00794885.