Mechanism of Chuanxiong Rhizoma intervention on central sensitization of Panx1-Src-NMDAR-2B signaling pathway in neuropathic pain model rats / 中国中药杂志

Excitatory toxicity(ET) is an important factor of neuropathic pain(NPP) induced by central sensitization(CS), and the association of pannexin-1(Panx1)-Src-N-methyl-D-aspartate receptor subunit 2 B(NMDAR-2 B) is an important new pathway for ET to initiate CS. The present study confirmed whether the central analgesic effect of Chuanxiong Rhizoma extract(CRE) was achieved through the synchronous regulation of the brain and spinal pathways of Panx1-Src-NMDAR-2 B. In this study, dynamic and simulta-neo-us microdialysis of the brain and spinal cord in vivo combined with behavioristics, high performance liquid chromatography(HPLC)-fluorescence detection, microdialysis analysis(ISCUS~(flex)), ultrasensitive multifactorial electrochemiluminescence immunoassay, ELISA, and Western blot was employed to investigate the protein expression of NMDAR-2 B, Src, and Panx1, extracellular excitatory amino acids, cytokines, energy metabolites, and substance P in spinal dorsal horn(SDH) and anterior cingulate cortex(ACC) after CRE intervention with the rat model of spared sciatic nerve injury(SNI) as the experimental tool. Compared with the sham group, the SNI group exhibited diminished mechanical withdrawal threshold(MWT)(P<0.01), increased cold spray scores(P<0.01), glutamate(Glu), D-serine(D-Ser), and glycine(Gly) in extracellular fluids of ACC, and Glu, D-Ser, interleukin-1β(IL-1β), and lactic acid(Lac) in extracellular fluids of SDH(P<0.05), dwindled tumor necrosis factor(TNF-α)(P<0.05), and elevated protein levels of NMDAR-2 B, Src, and Panx1 in ACC(P<0.05). Compared with the SNI model rats, high-and medium-dose CRE(CRE-H/M) could potentiate the analgesic activity as revealed by the MWT test(P<0.05) and CRE-M enabled the decrease in cold spray scores(P<0.05). CRE-H/M could inhibit the levels of Glu, D-Ser and Gly in the extracellular fluids of ACC(P<0.05), and the levels of Glu in the extracellular fluids of SDH(P<0.05) in SNI rats. CRE-M significantly increased the levels of glucose(Gluc), Lac, interferon-gamma(IFN-γ), keratinocyte chemoattractant/human growth-regulated oncogenes(KC/GRO), and IL-4 in extracellular fluids of SDH in SNI rats(P<0.05). CRE-H/M/L could also inhibit the levels of NMDAR-2 B, Src and Panx1 in ACC and SDH in SNI rats(P<0.05). The central analgesic effect of CRE is presumedly related to the inhibited release of excitatory amino acid transmitters(Glu, D-Ser and Gly) in ACC and SDH of SNI rats, decreased protein expression of NMDAR-2 B, Src and Panx1 in the two regions, and the regulation of the Panx1-Src-NMDAR-2 B pathway in the spinal cord and brain. The above findings partially clarified the scientific basis of clinical analgesic effect of Chuanxiong Rhizoma.

The Impacts of Simulated Microgravity on Rat Brain Depended on Durations and Regions / 生物医学与环境科学（英文）

OBJECTIVE@#To explore the dynamic impacts of simulated microgravity (SM) on different vital brain regions of rats.@*METHODS@#Microgravity was simulated for 7 and 21 days, respectively, using the tail-suspension rat model. Histomorphology, oxidative stress, inflammatory cytokines and the expression of some key proteins were determined in hippocampus, cerebral cortex and striatum.@*RESULTS@#21-day SM decreased brain derived neurotrophic factor and induced neuron atrophy in the cerebral cortex. Strong oxidative stress was triggered at day 7 and the oxidative status returned to physiological level at day 21. Inflammatory cytokines were gradually suppressed and in striatum, the suppression was regulated partially through c-Jun/c-Fos.@*CONCLUSION@#The results revealed that the significant impacts of SM on rat brain tissue depended on durations and regions, which might help to understand the health risk and to prevent brain damage for astronauts in space travel.

UHPLC quantification and brain permeability study of sinomenine and ligustrazine in CQM after single intravenous administration / 药学学报

Chuanxiong Qingfengteng mixture (CQM) is an analgesic developed based on clinical evidence and traditional Chinese medicine theory, which majorly consists of Ligusticum chuanxiong and Sinomenium acutum extracts. The current study aims to establish an UHPLC-UV method for the quantification of sinomenine and ligustrazine after CQM administration to rats, mice and cells, and to study the brain permeability of sinomenine and ligustrazine. The selectivity, linearity, accuracy, precision and stability of the established method demonstrated that it was suitable for the determination of sinomenine and ligustrazine in biological samples such as plasma, brain tissue and cellular fluid. After CQM was intravenously administered to rats and mice, both sinomenine and ligustrazine were detected in the brain from 5 min-2 h. The CSF/plasma partition coefficients (Kp, C/P) of each component were higher than those of brain tissue/plasma partition coefficient (Kp, B/P), the Kp, C/P and Kp, B/P of ligustrazine were higher than those of sinomenine. The concentrations between CSF and brain tissue were strongly correlated (Pearson's R>0.86, P<0.001). The unbound fraction in plasma of sinomenine and ligustrazine was 78.92% and 34.07%, respectively. The plasma protein binding rates displayed concentration-independent behavior within their respective in vivo concentration ranges. After CQM co-cultured with Caco-2 cell monolayers, the apparent permeability coefficient (Papp) of sinomenine and ligustrazine were 1.30×10-6 and 3.64×10-6 cm·s-1, respectively, following into the range of the intermediate and high permeability compounds. The efflux ratio (Papp(basolateral→apical)/Papp(apical→basolateral)) of sinomenine and ligustrazine were 0.67 and 0.85, respectively. When combined with P-glycoprotein inhibitor, the Papp of each component did not increase. In conclusion, the UHPLC-UV assay was successfully applied for the brain permeability study of CQM, the components of CQM can be quickly distributed to cerebrospinal fluid and pass through the blood-brain barrier. The brain permeability of ligustrazine is higher than that of sinomenine. The transmembrane transport of sinomenine and ligustrazine may not be affected by efflux transporters. All animal care and use complied with the Regulations for the Administration of Affairs Concerning Experimental Animals approved by the State Council of the People's Republic of China. All animal studies were implemented according to protocols, which were reviewed and approved by the Institutional Animal Care and Use Committee at Experimental Research Center, China Academy of Chinese Medical Sciences.

Application of bone-retaining femoral stem prosthesis in young patients with Dorr C femoral medullary cavity / 中国骨伤

OBJECTIVE@#To assess the clinical efficacy of Tri-Lock bio-short prosthesis in artificial total hip arthroplasty(THA) in young patients with Dorr type C femoral medullary cavity.@*METHODS@#From January 2010 to January 2014, 35 young patients(37 hips) with in the chimney-like femoral medullary cavity received Tri-Lock BPS prosthesis of THA, including 18 males(20 hips) and 17 females with an average age of (32.2±3.0) years old ranging from 21.2 to 38.5 years old. There were 16 cases of rheumatoid hip arthritis (17 hips), 8 cases of rheumatoid arthritis (9 hips), and 11 cases of aseptic necrosis of femoral head (11 hips). All cases were complicated with different degrees of osteoporosis. According to Singh index, 26 cases were classified as Grade III and 9 cases as Grade II. Biological prostheses were used for the acetabulum, with ceramic lining and full ceramic femoral head. The proximal femoral medullary cavity was Dorr type C on anteroposterior X-ray. After replacement, X-ray examination was performed to locate the prosthesis stem. Engh and Harris criteria were used to evaluate the stability of bone-prosthesis interface and hip function, respectively. Changes of hip movement pre-operation and at last follow-up were compared.@*RESULTS@#All patients were followed up for 18 to 45 months(means 33.8 months). Harris hip scores in 35 cases (37 hips) increased significantly from preoperative 61.8±3.0 (51.2 to 73.5) to 93.3±6.5 (92.5 to 98.8) points at last follow-up (=54.745, <0.01). The hip mobility increased from (46.5±8.0)°(0° to 55°) before surgery to(101.2±10.5)°(85° to 130°) at the last follow-up, the difference was statistically significant(=133.091, <0.01). Immediately after surgery, the prostheses were tightly packed with the medullary cavity. At the final follow-up, 17 hips had significant femur cortical bone thickening;12 hips had varying degrees of stress occlusal bone resorption at proximal femoral, including 9 degree I(low femur density, round and blunt) and 3 degree II(involving small rotor) hips. Meanwhile, 15 hips had significant femur cortical bone thickening without thigh pain.@*CONCLUSIONS@#The cone-shaped short Tri-lock biological short-stem can fill Dorr C chimney-like medullary cavity and effectively retain good proximal femoral bone mass. Titanium microporous coating on the surface can effectively increase the friction of the prosthesis. The short-stem end in the medullary cavity can effectively avoid the occurrence of coxa varus.

Comparison between Ye Tianshi and Xue Shengbai in treatment of diarrfea with damp-heat / 中国中药杂志

Ye Tianshi and Xue Shengbai are two febrile disease specialists in same time, and for the treatment of dampness and heat, they have different medication ideas. With the help of traditional Chinese medicine(TCM), author has studied two specialists' consilias of dampness and heat, through the statistics and analysis of their medicine during the treatment of dampness and heat, summarizes the similarities and differences of Ye and Xue's medicine application's assoations and models. Ye Tianshi and Xue Shengbai were both thought that the reason of dampness and heat was damp heat pathogenic factors, for this reason, the spleen and stomach conduction disordered, They both treated from the middle-jiao of Yangming and Taiyin, focused on warm-natured medicine, cold-natured medicine, used less cool-natured and heat-natured medicine, and more bitter, pungent, sweet medicine; Ye Tianshi usually use Scutellariae Radix, Paeoniae Radix Alba, Coptidis Rhizoma, Polyporus, Poria, Alismatis Rhizoma; Xue Shengbai commonly use Poria, Citri Reticulatae Pericarpium, Magnoliae officinalis Cortex, Patchouli, Glycyrrhizae Radix et Rhizoma, Angelicae Sinensis Radix, Paeoniae Radix Alba, Lablab Semen Album, Puerariae Lobatae Radix, Mume Fructus, Tsaoko Fructus, Amomi Fructus, Coptidis Rhizoma and Phellodendri Chinensis Cortex. The differences between the two masters in medicine application provide a reference for the clinical treatment of dampness and heat.

Analgesic effect and central mechanisms of CQ prescription on cancer invasion induced mirror image pain in model mice / 中国中药杂志

This study aimed to analyze the analgesic effect and related central mechanisms of CQ prescription on cancer invasion induced mirror image pain (CIIMIP)in model mice.In the study, male BALB/c mice were randomly divided into normal group, operation control group (injected with 0.2 mL inactivated S180 sarcoma cell sap), model group (injected with 0.2 mL S180 sarcoma cell sap on the right leg near the greater trochanter of femur) and CQ prescription low dose group (intraperitoneally injected with CQ prescription 100 mg•kg⁻¹ on the basis of model mice), CQ prescription middle dose group (intraperitoneally injected with CQ prescription 150 mg•kg⁻¹ on the basis of model mice), and CQ prescription high dose group (intraperitoneally injected with CQ prescription 200 mg•kg⁻¹ on the basis of model mice). Mechanical withdraw threshold (MWT) of the mirror image lateral hind paws were evaluated by Von Frey hairs before modeling and after surgery. The levels of glutamate (Glu), gamma aminobutyric acid (GABA), glycine (Gly), and taurine (Tau) in the L3-L5 spinal cord were measured by the high performance liquid chromatography-fluorescence detector (HPLC-FLD); AimPlex detection technology with multiple factors was used to detect the levels of regulated on activation in normal T-cell expressed and secreted (RANTES), monocyte chemoattractant protein (MCP-3) in the L3-L5 spinal cord. Then we observed the influence of GABAa receptor antagonist (Bicuculline) on analgesic effect of CQ prescription.The results indicated that CQ prescription could remarkably increase MWT of model mice(P<0.01, P<0.05), decrease the level of Glu(P<0.01, P<0.05), improve the levels of GABA, Gly, Tau(P<0.01, P<0.05), lower the ratio of Glu/GABA(P<0.01, P<0.05), and reduce the levels of RANTES, MCP-3(P<0.05) in the L3-L5 spinal cord, and GABAa receptor antagonist significantly blocked the analgesic effect of CQ prescription at two time points(P<0.05).This study showed that CQ prescription had significant analgesic effect on CIIMIP model mice, and its mechanism was associated with regulating the balance between excitability amino acid(EAA) and inhibitory amino acid (IAA) transmitters in central nervous system, partially activating GABAa receptor, and reducing the release of RANTES and MCP-3 in the spinal cord.

Comparison between Ye Tianshi and Xue Shengbai in treatment of distention with damp-heat / 中国中药杂志

Ye Tianshi and Xue Shengbai were both epidemic febrile diseases specialists in same time of Qing dynasty. The Traditional Chinese Medicine Inheritance Support System was used to compare and analyze the therapeutic characteristics of these two specialists in treating damp-heat type fullness or distension in stomach. Distension is commonly caused by qi stagnation accompanied with damp-heat from internal and external factors. In treatment, separation of damp and heat and removing dampness and heat from sanjiao separately were their common therapeutic principles. Both Ye Tianshi and Xue Shengbai paid much greater attention to eliminating dampness, and the herbs with bitter and pungent flavor, warm in property were usually chosen to regulate qi flow and reduce dampness. Invigorating spleen, nourishing stomach and dispersing lung were the frequently used treatment to balance the organs'harmony. The difference between specialist Ye and specialist Xue was the preference of herbs. Hou Pu (Magnoliae Officinalis Cortex), Xing Ren (Armeniacae Semen Amarum), Chen Pi (Citri Reticulatae Pericarpium), and Hua Shi (Talcum) were often used in both administrations. Besides, Ye Tianshi preferred to use Ban Xia (Pinelliae Rhizoma), Huang Qin (Scutellariae Radix), Huang Lian (Coptidis Rhizoma), Fuling, et al. Xue Shengbai on the other hand enjoyed using Fu Lingpi(Poriae Cutis), Cao Guo (Tsaoko Fructus), and Guang Huoxiang (Pogostemonis Herba), et al. In herbs compatibility, both of the two specialists were fond of using Chen Pi-Hou Pu, Hou Pu-Xing Ren. Moreover, Ye Tianshi often used Ban Xia- Xing Ren, Ban Xia-Huang Qin, and Hua Shi-Xing Ren to achieve the expected outcome of the treatment. While, Chen Pi, Fu Lingpi, and Hou Pu were the common combination with each other in Xue's cases. The similarities and differences of their administration should have the guidance in current clinical Chinese medicine practice for damp-heat type fullness or distension in stomach.

Management of antibiotic-associated pseudomembranous colitis in Non-hospitalized and hospitalized patients

Proper management of antibiotic-associated pseudo membranous colitis is not clear. This article is to investigate proper treatment of antibiotic-associated pseudo membranous colitis. Data of 67 patients [aged 18-69 years, with 31 males and 46 females] with antibiotic-associated pseudo membranous colitis were retrospectively analyzed including the demography, antibiotics to induce and for treatment of the pseudo membranous colitis, and other supportive measures. All 67 patients had a positive cytotoxin test, which confirmed the pseudo membranous colitis. Antibiotics which induced the pseudo membranous colitis included clindamycin, ofloxacin, piperacillin, cefatriaxone, penbritin and ceftazidime. Once the correct diagnosis was made, the culprit antibiotics were discontinued immediately, and narrow-spectrum antibiotics like metronidazole and vancomycin were administered in combination with correction of fluid and electrolyte abnormalities, use of vitamins C and B complex to repair the intestinal mucosa, and avoidance of antispasmodic and antidiarrheal agents. After appropriate treatment for 2-20 days, all patients recovered with no sequela. Sixty-two patients were clinically cured while five [7.5%] had diarrhea recurrence within two months of the end of therapy. Retreatment with tapering and extended period of metronidazole and/or vancomycin led to complete recovery of the patients. Multiple antibiotic agents are associated with pseudo membranous colitis, and correction of fluid and electrolyte abnormalities and use of vitamins to repair the intestinal mucosa should be performed to speed up the cure process

Study on the relationship between polymorphism sites of IL-10 and the susceptibility of endometriosis / 中华预防医学杂志

<p><b>OBJECTIVE</b>To explore the relationship of the endometriosis susceptibility and polymorphism of up stream of IL-10 promoter at the site of 1082(G→A), 819(C→T) and 592(C→A).</p><p><b>METHODS</b>A total of 214 patients with endometriosis and 160 healthy individuals were enrolled and divided into patient group and control group in this study. The polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) was applied to detect the base transition in the up stream of IL-10 promoter at the site of 1082(G→A), 819(C→T) and 592(C→A). SPSS11.0 software was applied to analysis frequencies of all genotypes.</p><p><b>RESULTS</b>There was no difference in polymorphism of IL-10-1082 between the endometriosis (AA: 87.90%, GA: 12.10%) and control group (AA: 87.50%, GA: 12.50%). The rate of TT, CT and CC genotype IL-10-819 was the same as the AA, CA and CC individually. There was no difference in the polymorphism of IL-10-819 or IL-10-592 between the endometriosis group (TT or AA: 41.12%, CT or CA: 47.66%, CC: 11.21%) and control group (χ(2) = 5.87, P = 0.053). However, there were significant difference in the genotype of CT of IL-10-819 or CA of IL-10-592 between the endometriosis group and control group (after adjust OR = 1.88, 95% CI = 1.10 - 3.21, χ(2) = 5.24, P = 0.021), and the allele C of IL-10-819 or IL-10-592 were close related with occurrence of endometriosis (OR = 1.42, 95%CI = 1.04 - 1.95, χ(2) = 4.81, P = 0.028). The IL-10 level in the plasma of endometriosis group with genotype of CC (CC), CT (CA) of IL-10-819(-592) were significant higher than those with TT (AA) (CA/CT: (50.12 ± 82.40) pg/ml, CC: (91.00 ± 118.23) pg/ml, TT/AA: (21.45 ± 22.10) pg/ml) (F = 2.492, P = 0.048; F = 1.852, P = 0.008).</p><p><b>CONCLUSION</b>The allele C of IL-10-819 or IL-10-592 was close related to the high level expression of IL-10, and it is the risk of the occurrence of endometriosis.</p>

Effect of Danzhi Xiaoyao Powder on neuro-immuno-endocrine system in patients with depression / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of Danzhi Xiaoyao Powder (DXP) on neuro-immuno-endocrine system in patients with depression.</p><p><b>METHODS</b>A randomized double-blinded and controlled study was conducted in 63 cases of depression. They were assigned to the DXP group (32 cases, treated with DXP) and the control group (31 cases, treated with maprotiline). The curative effect was evaluated with Hamilton's depressive scale (HAMD) before and at the end of the 2nd, 4th and 6th week of the treatment. Serum levels of serotonin (5-HT), norepinephrine (NE), brain derived neurotrophic factor (BDNF), cortisol (CORT), interleukin-6 (IL-6), and interleukin-1beta (IL-1beta) were detected before and at the 6th week of the treatment.</p><p><b>RESULTS</b>After 2 weeks of treatment, the total score of HAMD decreased remarkably in both groups (P < 0.01), and the total score, as well as the scores of the three factors, i. e. anxiety/somatization, cognitive impairment and feeling of despair, were lower in the DXP group than that in the control group respectively (P < 0.05 or P < 0.01). After 4 and 6 weeks of treatment the total score and score of the three factors all reduced significantly in both groups (P < 0.01), with insignificant difference between the groups. After 6 weeks of treatment, the serum levels of 5-HT and BDNF increased (P < 0.01), and the serum IL-6 level decreased in both groups (P < 0.05 or P < 0.01), the serum CORT level reduced in the DXP group (P < 0.01), while the serum NE level elevated in the control group (P < 0.01).</p><p><b>CONCLUSION</b>DXP is effective in improving symptoms of depression by regulating the levels of 5-HT, BDNF, CORT and IL-6.</p>

Pharmacokinetics of mangiferin in rat plasma after oral administration of a single dose of suanzaoren decoction / 药学学报

<p><b>AIM</b>To study the pharmacokinetics of mangiferin in rats after oral administration of a single dose of Suanzaoren decoction.</p><p><b>METHODS</b>An HPLC method was established using puerain as internal standard. Plasma samples were deproteinized with acetonitrile-acetic acid (9:1), followed by evaporation of the acetonitrile to dryness. The resultant residue was then dissolved in mobile phase and HPLC separation was achieved on a Hypersil C18 (200 mm x 4.6 mm ID, 5 microm) column at room temperature. The mobile phase consisted of acetonitrile-water (12:88) with 1% acetic acid and 1% tetrahydrofuran at a flow rate of 0.7 mL x min(-1). The UV detection wavelength was set at 320 nm.</p><p><b>RESULTS</b>The calibration curve was shown to be linear over the range from 0.536 to 26.8 microg x mL(-1) (r2 > or = 0.995). Mean recovery was determined as 92.7%. Within-day and between-day precisions were less than 9. 1% RSD. The limit of quantitation (LOQ) was 0.536 microg x mL(-1). The maximum plasma concentration (Cmax), the time to reach peak concentration (Tmax) and the apparent elimination half-life (T1/2) were (10.5 +/- 2.2) microg x mL(-1), (5.8 +/- 0.4) h and (5.0 +/- 0.3) h, respectively.</p><p><b>CONCLUSION</b>The validated HPLC method developed has been applied to take a limited view of pharmacokinetics profile of mangiferin in rat plasma after having orally taken a single dose of Suanzaoren decoction.</p>

Chronic pain impairs spatial learning and memory ability and down-regulates Bcl-2 and BDNF mRNA expression in hippocampus of neonatal rats / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the effect and possible mechanism of complete Freund's adjuvant induced chronic pain on later function of learning and memory in neonatal rats.</p><p><b>METHODS</b>Sixty Sprague-Dewley rat pups (10 litters of 6 pups) were randomly divided into control group and chronic pain group (n = 30 in each group). In the chronic pain group, left hind paws of the rats were treated with subcutaneous injection of 20 microl of CFA on postnatal day-2. The control rat pups received normal saline. The hippocampus of rats were separated on postnatal days 10 and 21 (one rat in each group from every litter, n = 10). The expression of Bcl-2 and BDNF mRNA were investigated by RT-PCR. Morris water maze tests were performed on day 21 (one rat in each group from every litter, n = 10).</p><p><b>RESULTS</b>In hidden-platform training of Morris water maze, the mean escape latency of rats in the chronic pain group were longer than that of the control rats. In spatial probe tests, the average percentages of the swimming time and distances in the platform quadrant in the pain group rats were less than those in the control group. There was no significant difference in visible-platform training between the two groups. The Bcl-2 and BDNF mRNA expressions in hippocampus of the pain group rats were lower than those in the control at day 10, but no significant difference at day 21.</p><p><b>CONCLUSION</b>Chronic pain stress induced by CFA impairs the spatial learning and memory function in neonatal rats. These effects might exert through down-regulating Bcl-2 and BDNF mRNA expression in the hippocampus.</p>

Pharmacokinetic study on spinosin in rat plasma after oral administration of suanzaoren extract at a single dose / 药学学报

<p><b>AIM</b>To study the pharmacokinetics of spinosin in rat plasma after oral administration of Suanzaoren extract using sulfamethoxazole (SMZ) as internal standard by RP-HPLC method.</p><p><b>METHODS</b>Plasma samples were deproteined with acetonitrile, followed by evaporation of the acetonitrile to dryness. The residual was then resolved in mobile phase and HPLC separation was achieved on a Hypersil C18 (5 microns, 200 mm x 4.6 mm ID) column at 35 degrees C. The mobile phase consisted of acetonitrile-water-acetic acid (15:85:1) at a flow rate of 0.7 mL.min-1. The UV detection wavelength was set at 334 nm.</p><p><b>RESULTS</b>The calibration curve was shown to be linear over the range from 18.1 to 903.5 micrograms.L-1 (r2 > or = 0.995). Mean recovery was 94.5%. Within-day and between-day precisions RSD were less than 9.0%. The limit of quantitation was 18.1 micrograms.L-1. The plasma spinosin was stable at -20 degrees C.</p><p><b>CONCLUSION</b>The simple, sensitive and accurate HPLC method developed has been applied to determine the pharmacokinetics of spinosin in rat plasma after having taken Suanzaoren extract at a single dose.</p>