[Rapid identification and differential markers of Curcumae Radix decoction pieces of different sources based on Heracles Neo ultra-fast gas phase electronic nose].

Since Curcumae Radix decoction pieces have multiple sources, it is difficult to distinguish depending on traditional cha-racters, and the mixed use of multi-source Curcumae Radix will affect its clinical efficacy. Heracles Neo ultra-fast gas phase electronic nose was used in this study to quickly identify and analyze the odor components of 40 batches of Curcumae Radix samples from Sichuan, Zhejiang, and Guangxi. Based on the odor fingerprints established for Curcumae Radix decoction pieces of multiple sources, the odor components was identified and analyzed, and the chromatographic peaks were processed and analyzed to establish a rapid identification method. Principal component analysis(PCA), discriminant factor analysis(DFA), and soft independent modeling cluster analysis(SIMCA) were constructed for verification. At the same time, one-way analysis of variance(ANOVA) combined with variable importance in projection(VIP) was employed to screen out the odor components with P<0.05 and VIP>1, and 13 odor components such as ß-caryophyllene and limonene were hypothesized as the odor differential markers of Curcumae Radix decoction pieces of diffe-rent sources. The results showed that Heracles Neo ultra-fast gas phase electronic nose can well analyze the odor characteristics and rapidly and accurately discriminate Curcumae Radix decoction pieces of different sources. It can be applied to the quality control(e.g., online detection) in the production of Curcumae Radix decoction pieces. This study provides a new method and idea for the rapid identification and quality control of Curcumae Radix decoction pieces.

[Quality value transmitting of substance benchmarks of Zhuru Decoction].

A total of 18 batches of Zhuru Decoction samples were prepared. Chromatographic fingerprints were established for Zhuru Decoction and single decoction pieces, the content of which was then determined. The extraction rate ranges, content, and transfer rate ranges of puerarin, liquiritin, and glycyrrhizic acid, together with the common peaks and the similarity range of the fingerprints, were determined to clarify key quality attributes of Zhuru Decoction. The 18 batches of Zhuru Decoction samples had 25 common peaks and the fingerprint similarity higher than 0.95. Puerariae Lobatae Radix, Glycyrrhizae Radix et Rhizoma, and Zingiberis Rhizoma Recens had 21, 3, and 1 characteristic peaks, respectively. The 18 batches of samples showed the extraction rates within the range of 18.45%-25.29%. Puerarin had the content of 2.20%-3.07% and the transfer rate of 38.5%-45.9%; liquiritin had the content of 0.24%-0.85% and the transfer rate of 15.9%-37.5%; glycyrrhizic acid had the content of 0.39%-1.87% and the transfer rate of 16.2%-32.8%. In this paper, the quality value transmitting of substance benchmarks of Zhuru Decoction was analyzed based on chromatographic fingerprints, extraction rate, and the content of index components. A scientific and stable method was preliminarily established, which provided a scientific basis for the quality control and formulation development of Zhuru Decoction.

Efficacy and Safety of Mulberry Twig Alkaloids Tablet for Treatment of Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Multicenter Clinical Study.

OBJECTIVE: To assess the efficacy and safety of mulberry twig alkaloids (Sangzhi alkaloids, SZ-A) for treatment of type 2 diabetes in a randomized, double-blind, placebo-controlled multicenter clinical trial. METHODS: A total of 200 patients were randomized to receive SZ-A (n=100) or placebo (n=100) for 16 weeks. The data analysis system for electronic data capture clinical trial central randomization system was used for randomization and dispensing of drugs. The primary outcome was the change in glycosylated hemoglobin (HbA1c) level. The secondary outcome included the proportions of cases with HbA1c <7.0% and HbA1c <6.5%, fasting blood glucose (FBG), postprandial blood glucose (PBG), area under curve for the PBG (AUC0-2h), body weight, and body mass index (BMI). Adverse events (AEs), severe adverse events (SAEs), treatment-related adverse events (TAEs), gastrointestinal disorders (GDs), blood pressure, routine blood tests, and liver and kidney function were monitored. RESULTS: Compared with baseline, the change of HbA1c at week 16 was -0.80% (95% CI: -0.98% to -0.62%) and -0.09% (95% CI: -0.27% to 0.09%) in SZ-A group and placebo group, respectively. The proportion of patients with HbA1c <7% and <6.5% was higher in the SZ-A group than in the placebo group (46.8% vs. 21.6% and 29.9% vs. 10.8%). The observed values and changes in FBG, 1 h-PBG, 2 h-PBG, and AUC0-2h differed significantly between groups (P<0.001), but differences were not significant in body weight and BMI (P>0.05). The incidence rates of AEs, TAEs, and GDs differed significantly between groups (P=0.010, P=0.005, and P=0.006, respectively), whereas the incidence rates of SAEs showed no significant differences between groups (P=1.000). CONCLUSION: SZ-A are effective and safe for treatment of type 2 diabetes. The protocol was registered in http://www.chictr.org.cn/showproj.aspx?proj=60117 (ChiCTR2000038550).

Development of weaning food with prebiotic effects based on roasted or extruded quinoa and millet flour.

Weaning is the gradual process of introducing solids or semisolid foods into an infant's diet, in order to ensure their healthy growth. This study developed two kinds of formula weaning food based on roasted or extruded quinoa and millet flour, and evaluated their quality. A fructo-oligosaccharide (FOS)/galacto-oligosaccharide (GOS) mix was added to provide the prebiotic potential. The protein contents of the roasted quinoa-millet complementary food (RQMCF) and extruded quinoa-millet complementary food (EQMCF) were 16.7% and 17.74% higher, respectively, than that of commercial millet complementary food (CMCF). Both RQMCF and EQMCF provided sufficient levels of energy and minerals. Extrusion provided the foods with a lower viscosity, and higher solubility and water absorption ability than roasting. In vitro digestion results showed that EQMCF exhibited the highest starch and protein digestibility (89.76% and 88.72%, respectively) followed by RQMCF (87.75% and 86.63%) and CMCF (83.35% and 81.54%). The digestas of RQMCF and EQMCF after in vitro digestion exhibited prebiotic effects by promoting the growth of the probiotics (Lactobacillus plantarum and Lactobacillus delbrueckii). These results will contribute to developing complementary weaning foods for infants. PRACTICAL APPLICATION: This study has shown that extrusion is an efficient and stable processing method for producing infant complementary foods with low density, balanced nutrition, and high levels of starch and protein digestibility. Extruded quinoa-millet prebiotic complementary food can also promote the proliferation of probiotics. This will provide a new direction for developing novel infant formula weaning foods.

A comparative study on the effects of resveratrol and oxyresveratrol against tyrosinase activity and their inhibitory mechanism.

Resveratrol and oxyresveratrol are two natural polyhydroxy trans-stilbene products. Previous studies have shown that both of them can effectively inhibit the activity of tyrosinase. However, little attention has been paid to study the difference of their inhibitory mechanism. To reveal this difference, in this work a comparative study on the inhibitory effects of resveratrol and oxyresveratrol against cellular tyrosinase activity and melanin content were investigated by B16F0 cells, and the inhibitory mechanism of them on tyrosinase was revealed by cell-free tyrosinase inhibition, intrinsic fluorescence spectrum, circular dichroism and molecular docking. The results showed that the inhibitory capacity of oxyresveratrol toward tyrosinase activity and melanin formation was better than that of resveratrol. The difference of their inhibitory mechanism may be closely related to the different types of inhibition, the different strength of their interaction with tyrosinase and the different number of hydrogen bonds between them. The data in this study provide a scientific basis for revealing the inhibitory mechanisms of resveratrol and oxyresveratrol toward tyrosinase, and lay an experimental foundation for further development and utilization of them.

Diterpenoid and triterpenoid glycosides from Clinopodium chinense.

Two new compounds, including a diterpenoid glycoside (1) and a triterpenoid glycoside (6), along with six known compounds were isolated from Clinopodium chinense. The structures of the new compounds were determined on basis of extensive spectral analysis and chemical method. Compounds 1-8 were evaluated for their insulin resistance effect and cytotoxic activity against the A549 and HepG2 cancer cell lines. None of the compounds were cytotoxic (IC50 > 100 µM), while compounds 1-3 and 5 showed the activity of ameliorating insulin resistance in HepG2.

Pharmacodynamics of Five Anthraquinones (Aloe-emodin, Emodin, Rhein, Chysophanol, and Physcion) and Reciprocal Pharmacokinetic Interaction in Rats with Cerebral Ischemia.

(1) Background: Rhubarb anthraquinones-a class of components with neuroprotective function-can be used to alleviate cerebral ischemia reperfusion injury. (2) Methods: The three pharmacodynamic indicators are neurological function score, brain water content, and cerebral infarction area; UPLC-MS/MS was used in pharmacokinetic studies to detect plasma concentrations at different time points, and DAS software was used to calculate pharmacokinetic parameters in a noncompartmental model. (3) Results: The results showed that the pharmacodynamics and pharmacokinetics of one of the five anthraquinone aglycones could be modified by the other four anthraquinones, and the degree of interaction between different anthraquinones was different. The chrysophanol group showed the greatest reduction in pharmacodynamic indicators comparing with other four groups where the rats were administered one of the five anthraquinones, and there was no significant difference between the nimodipine group. While the Aloe-emodin + Physcion group showed the most obvious anti-ischemic effect among the groups where the subjects were administered two of the five anthraquinones simultaneously. Emodin, rhein, chrysophanol, and physcion all increase plasma exposure levels of aloe-emodin, while aloe-emodin lower their plasma exposure levels. (4) Conclusions: This experiment provides a certain preclinical basis for the study of anthraquinone aglycones against cerebral ischemia and a theoretical basis for the study of the mechanism of interaction between anthraquinones.

[Study on dryness effect of Atractylodis Rhizoma based on theory of dry-dry and dryness-induced Yin deficiency].

In order to establish a more perfect evaluation system for dryness effect of Atractylodis Rhizoma, determine the main dry parts of Atractylodis Rhizoma，and further define the mechanism of stir-baked Atractylodis Rhizoma in reducing the dryness. The healthy rats were given with different doses of water extract and volatile oil of raw Atractylodis Rhizoma and stir-baked Atractylodis Rhizoma for 21 days. Based on the theory of the dry-dry and dryness-induced Yin deficiency, the amount of drinking water, tissue morphology of submandibular glands, urine volume and the expression of aquaporin 2 (AQP2) in the kidneys, as well as blood rheology, ratio of cAMP/cGMP in serum and the content of Na⁺-K⁺-ATP enzyme were selected as the evaluation indexes. The results indicated that the rats with high dose volatile oil from raw Atractylodis Rhizoma had a significant increase in the amount of drinking water, urine volume, blood viscosity, ratio of cAMP/cGMP and content of Na⁺-K⁺-ATP enzyme in the serum（P<0.05）as compared with the soybean oil group; meanwhile, atrophy of submandibular acinar gland was obvious，and the expression of aquaporin 2 was reduced significantly（P<0.05）. There were significant differences between volatile oil high dose group of raw Atractylodis Rhizoma and volatile oil high dose group of stir-baked Atractylodis Rhizoma. There was no significant difference between the water extract groups of raw and stir-baked Atractylodis Rhizoma and the saline group. A comprehensive evaluation system for the dryness effect of Atractylodis Rhizoma was established. It was confirmed that the volatile oil part was the main dry part of Atractylodis Rhizoma. It revealed that the mechanism of dryness effect of Atractylodis Rhizoma was not only related to the decrease of the total content of the volatile oil, but also may be related to the transformation of dryness components in the volatile oil. It provides references for the study of material basis of Atractylodis Rhizoma dryness, provides an experimental basis for the clinical application of Atractylodis Rhizoma, further clarifies the mechanism of stir-baked Atractylodis Rhizoma in reducing the dryness, and provides thoughts for the evaluation of other dry traditional Chinese medicines.

Studies on the anti-aging activity of a glycoprotein isolated from Fupenzi (Rubus chingii Hu.) and its regulation on klotho gene expression in mice kidney.

In this study, a novel glycoprotein with molecular weight of 22.0 kDa was isolated and purified from Fupenzi (a kind of unripe fruits of Rubus chingii Hu.) by means of anion-exchange (DEAE-52) and gel column chromatography (Sephadex G-100). The glycoprotein consists of a carbohydrate component (81.42 ±â€¯0.96%) and protein component (14.56 ±â€¯1.21%). The anti-aging capability was measured in d­galactose induced aging mice model, and the experimental data showed that the glycoprotein could significantly inhibit the formation of malondialdehyde (MDA) and raise the activities of superoxide dismutase (SOD) and catalase (CAT) in mice kidney and serum. The reverse transcription polymerase chain reaction (RT-PCR), quantitative real time polymerase chain reaction (Q-PCR) and western blots showed that the glycoprotein significantly increase the expression of anti-aging gene klotho in mice kidney. The results suggested that the anti-aging mechanism of FPZ might be achieved by improving the klotho gene expression and repairing the renal function. This study will provide a scientific basis for the view of traditional Chinese medicine that tonifying kidney is the basic way of anti-aging. In addition, the glycoprotein could be exploited as a potent dietary supplement to attenuate aging and prevent age-related diseases in humans.

Combination of quercetin, cinnamaldehyde and hirudin protects rat dorsal root ganglion neurons against high glucose-induced injury through Nrf-2/HO-1 activation and NF-κB inhibition.

OBJECTIVE: To examine the effects of the combination of quercetin (Q), cinnamaldehyde (C) and hirudin (H), a Chinese medicine formula on high glucose (HG)-induced apoptosis of cultured dorsal root ganglion (DRG) neurons. METHODS: DRG neurons exposed to HG (45 mmol/L) for 24 h were employed as an in vitro model of diabetic neuropathy. Cell viability, reactive oxygen species (ROS) level and apoptosis were determined. The expression of nuclear factor of Kappa B (NF-κB), inhibitory kappa Bα(IκBα), phosphorylated IκBα and Nf-E2 related factor 2 (Nrf2) were examined using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot assay. The expression of hemeoxygenase-1 (HO-1), interleukin-6 (IL-6), tumor necrosis factor (TNF-α) and caspase-3 were also examined by RT-PCR and Western blot assay. RESULTS: HG treatment markedly increased DRG neuron apoptosis via increasing intracellular ROS level and activating the NF-κB signaling pathway (P<0.05). Co-treatment with Q, C, H and their combination decreased HG-induced caspase-3 activation and apoptosis (P<0.05 or P<0.01). The expressions of NF-κB, IL-6 and TNF-α were down-regulated, and Nrf2/HO-1 expression was up-regulated (P<0.05 or P<0.01). QCH has better effect in scavenging ROS, activating Nrf-2/HO-1, and down-regulating the NF-κB pathway than other treatment group. CONCLUSIONS: DRG neurons' apoptosis was increased in diabetic conditions, which was reduced by QCH formula treatment. The possible reason could be activating Nrf-2/HO-1 pathway, scavenging ROS, and inhibition of NF-κB activation. The effect of QCH combination was better than each monomer or the combination of the two monomers.

BODIPY-Mn nanoassemblies for accurate MRI and phototherapy of hypoxic cancer.

Hypoxia promotes not only the metastasis of tumors but also therapeutic resistance. Photosensitizer-mediated consumption of O2 during photodynamic therapy (PDT) reinforces tumor hypoxia. Herein, a light-dependent attenuator of a hypoxic environment is reported for accurate MRI and phototherapy of hypoxic cancer. First, a photoresponsive Mn(ii) nanoassembly was constructed, then it was assembled with bovine serum albumin (BSA) and modified with polyethylene glycol-folic acid (PEG-FA), forming cancer targeting Mn-DBA@BSA-FA nanoassemblies, which offer T1 signals and can catalyze the water oxidation reaction under irradiation of red light emitting diode (LED) light with the generation of O2 and heat. Moreover, they could selectively penetrate through and accumulate in the tumor tissues with clear T1 magnetic resonance imaging (MRI) signals, and have remarkably eliminated the tumors in vivo, while they are of low toxicity to the healthy organs. The release of the Mn(ii) complex from the nanoparticles in an acidic environment and the in vivo biodistribution results confirm the selective cancer targeting. Our work demonstrates the potential of nanoparticles as excellent theranostic agents for MR imaging combined with phototherapy triggered by near-infrared light.

Effects of Chinese Medicinal Compound Jinmaitong on the Expression of Nitrotyrosine andNerve Growth Factor in the Dorsal Root Ganglia of Diabetic Rats.

Objective To study the effects of Chinese medicinal compound Jinmaitong(JMT) on the expressions of nitrotyrosine (NT) and nerve growth factor (NGF) in dorsal root ganglia of diabetic rats. Methods Experimental rat diabetic models were established by the intraperitoneal injection of streptozotocin. Rat models were then randomly divided into four groups including normal control group (Con group),diabetes mellitus group (DM group),Jinmaitong group(JMT group)(treated with JMT similar to the fifteen-fold dose of adult recommended dosage),and taurine group(Tau group)(treated with Taurine similar to the fifteen-fold dose of adult recommended dosage),with 10 rats in each group. The Con and DM groups were treated with distilled water at a daily dose of 1 ml/100 g. All rats were given intragastric administration for 16 weeks and then killed. Body weight and blood glucose were detected before and at the 4th,8th,12th,and 16th week after treatment. The pain threshold to mechanical stimulation with von Frey filament were carried out before death. The expressions of NT and NGF in dorsal root ganglion were detected by immunohistochemistry and Western blot analysis,respectively. Results Immunohistochemistry showed that the average optical density (AOD) of NT expression in DM group were significantly higher than those in control group (P=0.000),and the AOD of NGF was significantly lower than the control group (P=0.006).The AOD of NT(P=0.000,P=0.000) in both treatment groups decreased significantly and the AOD of NGF(P=0.000, P=0.004)significantly increased compared with DM group. The AOD of NT in JMT group was significantly lower than Tau group (P=0.004). Western blot analysis showed that the protein level of NT in DM group was significantly higher than that in control group (P=0.000),and the protein level of NGF was significantly lower than that in control group (P=0.000). Compared with the DM group,the protein level of NT in both treatment groups significantly decreased (P=0.001,P=0.000),and the protein level of NGF increased significantly (P=0.000,P=0.001). Conclusion Traditional Chinese medicine JMT can obviously up-regulate the expressions of NGF and reduce the NT levels in dorsal root ganglia of diabetic rats.

Jinmaitong alleviates the diabetic peripheral neuropathy by inducing autophagy.

OBJECTIVE: To observe the deregulation of autophagy in diabetic peripheral neuropathy (DPN) and investigate whether Jinmaitong ( JMT) alleviates DPN by inducing autophagy. METHODS: DPN models were established by streptozotocin-induced diabetic rats and Schwann cells (SCs) cultured in high glucose medium. The pathological morphology was observed by the improved Bielschowsky's nerve fiber axonal staining and the Luxol fast blue-neutral red myelin staining. The ultrastructure was observed by the transmission electron microscopy. Beclin1 level was detected by immunohistochemistry and Western blot. The proliferation of cultured SCs was detected by methylthiazolyldiphenyl-tetrazolium bromide. RESULTS: Diabetic peripheral nerve tissues demonstrated pathological morphology and reduced autophagic structure, accompanied with down-regulation of Beclin1. JMT apparently alleviated the pathological morphology change and increased the autophagy [in vivo, Beclin1 integral optical density (IOD) value of the control group 86.6±17.7, DM 43.9±8.8, JMT 73.3 ±17.8, P<0.01 or P<0.05, in vitro Beclin1 IOD value of the glucose group 0.47±0.25 vs the control group 0.88±0.29, P<0.05]. Consequently, inhibition of autophagy by 3-methyladenine resulted in a time- and concentration-dependent decrease of the proliferation of SCs (P<0.05, P<0.01). CONCLUSIONS: Down-regulation of autophagy in SCs might contribute to the pathogenesis of DPN. JMT alleviates diabetic peripheral nerve injury at least in part by inducing autophagy.

Simultaneous determination and pharmacokinetics of five rhubarb anthraquinones in dog plasma by HPLC after orally administration the rhubarb extract.

Rhubarb is widely used in the treatment of obstipation, gastrointestinal indigestion and other diseases in China and other Asian countries for thousands of years. Anthraquinones are the major group of polyphenol constituents including aloe-emodin, rhein, emodin, chrysophanol and physcion. In order to evaluate the pharmacokinetics of five rhubarb anthraquinones, a high-performance liquid chromatography with fluorescence detection (HPLC-FLD) method for simultaneous determination of aloe-emodin, rhein, emodin, chrysophanol and physcion in dog plasma was established. Solid phase extraction (SPE) was applied to the extraction and purification of samples. The calibration curves of five anthraquinones showed good linearity with r greater than 0.9925. The average extraction recoveries, examined at three concentration levels, carried from 92.1% to 102.3%, and the accuracies ranged from 87.7% to 102.5% with precision (RSD) <10%. The pharmacokinetic paremeters of five anthraquinones were investigated systematically after orally administration the rhubarb extract. Five anthraquinones were rapidly absorbed and Tmax for aloe-emodin, rhein, emodin, chrysophanol and physcion was at 0.75, 1.50, 0.75, 1.0 and 2.0 h respectively. The Cmax of five anthraquinones was 0.031, 3.39, 0.27, 0.036 and 0.032 µg/mL while the AUC of five anthraquinones was 0.35 ± 0.058, 32.22 ± 8.29, 2.97 ± 0.66, 0.43 ± 0.10 and 0.41 ± 0.12 mg h/L, respectively.

Effects of Jinmaitong Capsule () on ciliary neurotrophic factor in sciatic nerves of diabetes mellitus rats.

OBJECTIVE: To study the effects of the Chinese medicine Jinmaitong Capsule (, JMT) on the pathomorphology of sciatic nerves, ciliary neurotrophic factor (CNTF), and the mRNA expressions of CNTF in rats with streptozotocin-induced diabetes mellitus (STZ-DM). METHODS: The animal model was established by one time intraperitoneal injection of streptozotocin. The rats were simply divided by random into 5 groups including model group, low-dose JMT group (JL), medium-dose JMT group (JM), high-dose JMT group (JH) and neurotropin group. For each of the above 5 groups, a group of 10 normal Wistar rats matched in body weight, age and gender were set as normal group. Intragastric administrations were started after the animal model established. The JL group were administered with five times the JMT dose recommended for a human adult; the JM group were administered with ten times the JMT dose recommended for a human adult; the JH group were administered with twenty times the JMT dose recommended for a human adult. The neurotropin group was administered with ten times the neurotropin dose recommended for a human adult. All rats were given intragastric administration for 16 weeks and then killed. In the 4th, 8th, 12th, 16th week, body weight and blood glucose level were detected before and after the intervention. The morphologic changes of the sciatic nerves were observed by optical microscope and transmission electron microscope. The CNTFmRNA expressions were detected by real-time fluorescent quantitative polymerase chain protein, and the CNTF protein expressions were detected by immunohistochemical method. RESULTS: The blood glucose levels of the STZ-DM rats were much higher than normal group (P<0.01), and there was no apparent difference between any treatment groups and the model group (P>0.05). Before and after the intervention in the 4th, 8th, 12th, 16th week, there were no significant differences in the body weight among all the groups (P>0.05). The sciatic nerves of STZ-DM rats might have pathomorphological changes in axons, myelin sheaths, and interstitium. The levels of CNTF and CNTF-mRNA expressions in the STZ-DM rats were both significantly decreased (P<0.01). The sciatic nerves of STZ-DM rats might have pathomorphological changes in axons, myelin sheaths, and interstitium. CONCLUSION: JMT could improve the pathomorphology of sciatic nerves by increasing CNTF's and CNTF-mRNA expressions in sciatic nerve tissues, and promote the repair and regeneration of damaged nerve fibers.

Comparative pharmacokinetics of five rhubarb anthraquinones in normal and thrombotic focal cerebral ischemia-induced rats.

A comparative oral pharmacokinetic study of five anthraquinones (aloe-emodin, emodin, rhein, chrysophanol and physcion) from the extract of Rheum palmatum L. was performed in normal and thrombotic focal cerebral ischemia (TFCI)-induced rats. The plasma samples were clarified through solid phase extraction prior to simultaneous determination of the anthraquinones with a validated high-performance liquid chromatography-fluorescence system. The results indicated that the Cmax, t(1/2) and AUC(0-t), of aloe-emodin, rhein, emodin and chrysophanol in TFCI-induced rats were nearly double, whereas the CL values were remarkably decreased (p < 0.05) over those of the normal rats. The plasma drug concentration-time data of five anthraquinones to rats fitted a two-compartment open model. The five anthraquinones in rat plasma were absorbed quickly and eliminated slowly in both groups. The obtained results could be helpful for evaluating the impact of the efficacy and safety of the drug in clinical applications.

[Clinical analysis of 15 cases of pseudohypoparathyroidism].

OBJECTIVE: To analyze the clinical characteristics, diagnosis and treatment of pseudohypoparathyroidism (PHP). METHODS: The clinical data of 15 patients with pseudohypoparathyroidism (including 9 male and 6 female patients) admitted in our hospital between January, 1990 and July, 2011 were reviewed. RESULTS: The disease course of the patients ranged from 3 days to 21 years, and such symptoms of tetany and fatigue were found in all the patients. Most of the patients had a history of seizures. Laboratory tests suggested commonly low serum calcium, hyperphosphatemia, and parathyroid hormone (PTH) elevation. Head CT indicated multiple intracranial calcifications in 9 cases, and abnormal thyroid function was found in 4 cases. No specific treatment was available for this disease, and life-long calcium and vitamin D supplementation was advised to prevent acute attacks and disease progression. CONCLUSION: PHP is a rare genetic disease with a high rate of misdiagnosis in initial diagnosis. For repeated tetany and epileptic attacks and children with congenital developmental defects, examinations of blood calcium, phosphorus, and PTH and brain CT should be ordered as soon as possible. Long-term calcium and vitamin D supplementation is suggested for the treatment, and the presence of concomitant thyroid dysfunction or hypogonadism necessitates corresponding treatments.

Inhibitory effects of salvianolic acid B on apoptosis of Schwann cells and its mechanism induced by intermittent high glucose.

AIMS: To investigate protective effects of Salvianolic acid B (Sal B) on the intermittent high glucose (IHG)-induced oxidative stress, mitochondrial pathway activation and Schwann cell (SC) apoptosis in vitro. MAIN METHODS: SCs were primarily cultured and exposed to the different conditions. Apoptosis was confirmed by the Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) method and concentration of 8-hydroxy-2-deoxy Guanosine (8-OHdG) was detected by Elisa. Intracellular ROS generation and mitochondrial transmembrane potential (ΔΨm) were detected by flow cytometry analysis. Quantitative real-time reverse transcriptase PCR was performed to analyze the expression levels of Bax and BcL-2. Western blot was performed to analyze the expression levels of some important transcription factors and proteins. KEY FINDINGS: Treatment with Sal B inhibited the IHG-induced oxidative stress by reducing ROS production and 8-OHdG levels, mitochondrial depolarization and apoptosis in SCs in a dose-dependent manner. Furthermore, treatment with Sal B down-regulated the IHG-induced release of cytochrome c, AIF nuclear translocation and Bax expression, but mitigated the IHG-mediated down-regulation of BcL-2 expression in SCs. In addition, treatment with Sal B attenuated the IHG-induced activation of caspase-9 and caspase-3 and minimized the cleavage of PARP in SCs. SIGNIFICANCE: Our results indicated that IHG induced SC apoptosis in both caspase-dependent and caspase-independent pathways by activating the mitochondrial pathway. Sal B inhibited the IHG-induced oxidative stress, activation of the mitochondrial pathway and apoptosis in SCs.

Pharmacokinetic study of six flavones in rat plasma and tissues after oral administration of 'JiangYaBiFeng' using SPE-HPLC-DAD.

In this study, a high performance liquid chromatography (HPLC) coupled with diode array detection (DAD) for simultaneous determination of six flavones including baicalein, sophoricoside, rutin, baicalin, quercetin and genistein in rat plasma and tissues after oral administration of JiangYaBifeng (JYBF) tablets was developed. The investigated analytes in plasma and tissues were extracted and purified with liquid-liquid extraction and solid phase extraction (SPE). Chromatographic separation was accomplished on a DIONEX Acclaim C18 column (250mm×4.6mm, 5.0µm particle size) with a simple linear gradient elution. The calibration curves for all the flavones had good linearity in the measured range with R(2) higher than 0.9983. The relative errors (REs) of the intra- and inter-day accuracy at different flavones levels were all less than ±10%. The proposed method enables unambiguous identification and quantification of investigated flavones in vivo. This is the first report on determination of the major flavones in rat plasma and tissues after oral administration of JYBF tablets. The results provided a meaningful basis for evaluating the clinical application of this medicine.

Capillary electrophoresis coupled with end-column electrochemiluminescence for the determination of ephedrine in human urine, and a study of its interactions with three proteins.

A tris(2,2-bipyridyl)ruthenium(II) (Ru(bpy)3²âº)-based electrochemiluminescence (ECL) detection coupled with capillary electrophoresis (CE) method has been established for the sensitive determination of ephedrine for the first time. Under the optimized conditions [ECL detection at 1.15 V, 25 mmol/L phosphate buffer solution (PBS), pH 8.0, as running buffer, separation voltage 12.5 kV, 5 mmol/L Ru(bpy)3²âº with 60 mmol/L PBS, pH 8.5, in the detection cell] linear correlation (r = 0.9987) between ECL intensity and ephedrine concentration was obtained in the range 6.0 × 10⁻8-6.0 × 10⁻6 g/mL. The detection limit was 4.5 × 10⁻9 g/mL (S:N = 3). The developed method was successfully applied to the analysis of ephedrine in human urine and the investigation of its interactions with three proteins, including bovine serum albumin (BSA), cytochrome C (Cyt-C) and myoglobin (Mb). The number of binding sites and the binding constants between ephedrine and BSA, Cyt-C and Mb were 8.52, 12.60, 10.66 and 1.55 × 104 mol/L, 6.58 × 10³ mol/L and 1.59 × 104 mol/L, respectively.