Identification of ligustrazine-based analogs of piperlongumine as potential anti-ischemic stroke agents.

Piper longum has a specific aroma and spicy taste. In addition to edible value, current studies have shown that piper longum also has pharmacological activities such as anti-platelet aggregation, anti-inflammation, anti-cancer, anti-diabetes and anti-depression. Piperlongumine is an alkaloid isolated from Piper longum. Based on our previous studies, four Piperlongumine analogs were synthesized, and their anti-platelet aggregation activities were evaluated. Among them, compound 8 has the strongest anti-platelet aggregation activity. Therefore, compound 8 was docked with stroke-related protein targets, and it was found that compound 8 had good binding affinity to MRTF-A complex and Bcl-2. Through animal experiments, it was found that compound 8 could significantly improve the pathological damage of brain tissue after ischemia and could increase the expression of MRTF-A and Bcl-2 in cerebral cortex in rats. These results suggest that compound 8 may have a good inhibitory effect on apoptosis and tissue structurel disorders induced by cerebral ischemia-reperfusion, so as to reduce the injury caused by ischemic stroke.

Effects on vibration perception threshold and the quality of life in the patients of high-risk diabetic foot treated with the pestle needling therapy / 中国针灸

OBJECTIVE@#To evaluate the effects of the pestle needling therapy on the vibration perception threshold (VPT) and the quality of life (QOL) in the patients of high-risk diabetic foot.@*METHODS@#A total of 132 patients of high risk diabetic foot were randomized into an observation group and a control group, 66 cases in each one. In the control group, the routine treatment and nursing for diabetes were applied. In the observation group, on the base of the treatment as the control group, the pestle needling therapy was used at , , , Zusanli (ST 36), Yongquan (KI 1), Sanyinjiao (SP 6) and Taixi (KI 3). The intervention with the pestle needling therapy was given once every day, consecutively for 4 weeks. The follow-up visit was conducted in 3 months and 6 months after the intervention. Vibration perception threshold (VPT) was observed before and after intervention in the two groups. Separately, before intervention, at the end of intervention, 3 months after intervention and 6 months after intervention, the type 2 diabetes mellitus quality life scale (DMQLS), the revised edition was adopted to compare the QOL between the two groups. The effects were evaluated in the two groups.@*RESULTS@#After intervention, the VPT and QOL were all improved in the two groups (<0.01, <0.05). In the observation group, after intervention, VPT at the first toes and the dorsum of the feet was lower than the control group at the same time point (all <0.01). In the observation group, the total scores and the score of each dimension item in the DMQLS of the revised edition were all lower than the control group correspondently at the end of intervention, 3 months after intervention and 6 months after intervention (<0.01, <0.05). The repeated ANOVA results showed that the differences were significant in the total scores and the score of each dimension in the aspects of time, inter-group and interaction effect (<0.01, <0.05). The total scores and score of each dimension item in the DMQLS were lower than those the earlier time point (<0.01, <0.05). The total effective rate was 100.0% in the observation group, which was superior to 95.1% (59/62) in the control group (<0.05).@*CONCLUSION@#The pestle needling therapy reduces the foot VPT and improves the sensory nerve function of the foot and the QOL in the patients of high-risk diabetic foot.

Research progress in study on chemical constituents in plants of Incarvillea Juss. and their pharmacological activities / 中草药

The genus Incarvillea Juss. (Bignoniaceae) consists of about fifteen species distributed in the regions stretching from Central to East Asia along Himalaya Mountains, including eleven species in China. The plants of Incarvillea Juss. are annual or perennial herbs with attractive flowers, most of which are used as traditional folklore medicines for the treatments of stomachache, hepatitis, and abnormal menstruation. Phytochemical studies on the plants in Incarvillea Juss. have disclosed the presence of monoterpene alkaloids, cyclohexyl-ethanol, iridoids, phenylpropanoid, etc. Pharmacological activities include analgesic, anti-oxidant, and anti-inflammatory activities. In this review, the chemical constituents and their biological activities of medicinal plants from Incarvillea Juss. are comprehensively discussed.

Chinmedomics strategy to discover effective constituents and elucidate action mechanism of Nanshi capsule against kidney-yang deficiency syndrome / 中国中药杂志

The chinmedomics method was used to explore the effect of Nanshi capsule on endogenous metabolites of rats with kidney-yang deficiency syndrome, investigate the metabolites and metabolic pathways closely related to kidney-yang deficiency syndrome (KYDS)and identify the therapeutic basis of Nanshi capsule(NPC)as well as its action mechanism for KYDS. The routine biochemical indexes of serum were detected and histomorphology was observed. Based on the chinmedomics technology platform, discriminatory analysis in multivariate modes was conducted for rat blood and urine, thus to investigate the biomarkers of KYDS and the therapeutic effect of NPC against KYDS. Meanwhile, the main constituents of NPC in rat serum were also detected to analyze its correlation between the constituents in vivo and the biomarkers of KYDS, and determine the potential effective compounds for therapeutic effect. Eleven biomarkers of KYDS were identified in the rat models, involving steroid hormone biosynthesis, tryptophan metabolism and tyrosine metabolism. It was found that NPC could regulate steroid hormone biosynthesis, tryptophan metabolism and tyrosine metabolism; PCMS analysis showed that caffeic acid, 2-hydroxy-1-methoxy-anthraquinone, 1-hydroxy-2-methoxyanthraquinone, ferulic acid glucuronide conjugation, deacetylasperulosidic acid, cynaroside, betaine and umbelliferone were the main effective compounds of NPC for KYDS. In this study, cynaroside, betaine, umbelliferone and other compounds in NPC could integrally regulate the disturbance of metabolic profile in KYDS by improving the hormone synthesis, hormone synthesis pathway, hormone synthesis and release pathway in tyrosine metabolism and linoleic acid synthesis pathway in linoleic acid metabolism. These results indicated that the NPC had the characteristics of multi-pathway, multi-target and overall regulation in the treatment of KYDS. Chinmedomics approach can provide methodology support to discover innovative drug from traditional Chinese medicine.

Esophageal and gastric variceal bleeding in the prevention of early rebleeding given enteral nutrition value after endoscopic variceal ligation and treatment / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To observe liver cirrhosis with esophageal and gastric variceal bleeding (GEVB) after endoscopic variceal ligation and treatment of early oral nutrition liquid in patients administered to reduce the risk of early rebleeding.</p><p><b>METHODS</b>Seventy-eight patients with cirrhosis who received therapeutic endoscopy after GEVB and who suffered from malnutrition were randomly divided into a treatment group (oral solution group, n=40) and a control group (regular diet group, n=38).Both of the two groups received food at 12 hours after therapeutic endoscopy.After 14 days, the rates of early rebleeding rate and liver function recovery were compared for the two groups. T-test, rank test, chi-square test and Fisher's exact test were used for statistical analyses.</p><p><b>RESULTS</b>Compared with the control group, less patients in the treatment group experienced rebleeding (0/40 vs. 5/38; x2=5.624, P=0.018); the treatment group also showed significantly improved indexes of liver function (all P less than 0.05).</p><p><b>CONCLUSION</b>s GEVB after endoscopic treatment with early oral nutrition liquid administration can reduce in the early rebleeding risk and improve function and malnutrition status.</p>

Influence of As2O3-lipiodol emulsion via transarterial embolization on a VX2 liver tumor model in rabbits / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the anticancer efficacy and the hepatic and renal toxicity of As2O3-lipiodol emulsion via transarterial embolization in a rabbit VX2 liver tumor model.</p><p><b>METHODS</b>VX2 tumors were implanted in rabbit livers successfully, followed by transarterial embolization with high-dose As2O3(5 mg/kg with 0.2 mL lipiodol, n=10), low-dose As2O3(1 mg/kg with 0.2 mL lipiodol, n=10), and control(0.2 mL lipiodol, n=10). The growth ratios and microvessel densities(MVDs) of the tumors were estimated by multi-row spiral CT and CD34 immunohistochemical staining, respectively. Hepatic and renal function was also evaluated by means of blood biochemical analysis.</p><p><b>RESULTS</b>The growth ratios of the tumors differed significantly among three groups(P<0.01). The high-dose and low dose group showed significantly lower tumor growth ratios[44.05%(-36.40%~64.60%), 95.20%(-11.60%~159.40%)] than control group[145.55%(98.90%~250.30%), all P<0.05]. The MVDs of the tumors were significantly lower in the high-dose(21.4±10.6) and low-dose group(34.1±12.0) than those in control group(57.9±16.1,all P<0.05). The levels of blood ALT and AST obtained 28 days after transarterial embolization were significantly lower in the high-dose[(25.50±12.37)U/L,(24.25±10.89)U/L] and low-dose group[(45.00±14.04)U/L,(35.22±11.86)U/L] than in control group[(79.12±30.52)U/L,(75.25±25.89)U/L, all P<0.05].</p><p><b>CONCLUSION</b>As2O3-lipiodol emulsion via transarterial embolization has anticancer effect without significant hepatic and renal functional damage in rabbit VX2 liver tumors.</p>

Analysis of treatment and prognosis in 34 patients with anorectal malignant melanoma / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the prognostic factors of anorectal malignant melanoma (ARMM).</p><p><b>METHODS</b>Medical records and follow-up data of 34 patients with ARMM treated in the Chinese PLA General Hospital from March 1993 to November 2011 were analyzed retrospectively.</p><p><b>RESULTS</b>There were 26 abdominoperineal resections(APR) and 8 wide local excisions (WLE). Twenty patients underwent postoperative adjuvant therapy, including chemotherapy in 14 cases, radiotherapy in 2 cases, traditional Chinese medicine therapy in 4 cases and immunotherapy in 16 cases. Postoperative follow-up was carried out in all the patients and the mean follow-up period was 27 months. The 1-, 3- and 5-year overall survival rates were 76.3%, 39.6% and 20.6% respectively, while the 1-, 3- and 5-year disease-free survival rates were 60.6%, 30.8% and 12.8% respectively. APR and postoperative immunotherapy could significantly reduce the local recurrence rate. According to the Kaplan-Meier method, gross type of tumor, mural involvement, lymph metastasis, and clinical staging had significant effects on overall survival, while lymph metastasis and postoperative immunotherapy on disease-free survival. Cox proportional hazards model indicated that the clinical staging and postoperative immunotherapy were significant predictive factors.</p><p><b>CONCLUSIONS</b>Early diagnosis and correct choice of surgical method are the keys to the treatment. Postoperative immunotherapy can prolong disease-free survival.</p>

Fas and FasL expression in the spinal cord following cord hemisection in the monkey.

The changes of endogenous Fas/FasL in injured spinal cord, mostly in primates, are not well known. In this study, we investigated the temporal changes in the expression of Fas and FasL and explored their possible roles in the ventral horn of the spinal cord and associated precentral gyrus following T(11) spinal cord hemisection in the adult rhesus monkey. A significant functional improvement was seen with the time going on in monkeys subjected to cord hemisection. Apoptotic cells were also seen in the ventral horn of injured spinal cord with TUNEL staining, and a marked increase presents at 7 days post operation (dpo). Simultaneously, the number of Fas and FasL immunoreactive neurons in the spinal cords caudal and rostral to injury site and their intracellular optical density (OD) in the ipsilateral side of injury site at 7 dpo increased significantly more than that of control group and contralateral sides. This was followed by a decrease and returned to normal level at 60 dpo. No positive neurons were observed in precentral gyrus. The present results may provide some insights to understand the role of Fas/FasL in the spinal cord but not motor cortex with neuronal apoptosis and neuroplasticity in monkeys subjected to hemisection spinal cord injury.

Correlation between chirp auditory brainstem response and behavioral hearing threshold in children / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the correlation between thresholds in the chirp-ABR and behavior audiogram in order to find out if it is possible to be used as an clinical application of the chirp-ABR in estimating hearing sensitivity.</p><p><b>METHODS</b>Twenty-two cases with hearing loss or normal hearing were enrolled in the study. The behavior audiogram and the response thresholds of chirp ABR (including chirp ABR, L-chirp ABR and U-chirp ABR) were obtained from 35 ears.</p><p><b>RESULTS</b>Twenty-two cases were of both genders. The age was between 3.3- 6.5-years-old with the average age of 4.8-years-old. Divided by the degree of hearing loss, in the 35 ears, there were 6 with normal hearing, 2 with slightly hearing loss, 4 with moderate hearing loss, 10 with severe hearing loss and 13 with profound hearing loss. The Pearson correlation coefficients were 0.939, 0.900 and 0.930, respectively, which got from the data between the average of 0.5 - 4 kHz and chirp ABR respond threshold, 0.5 kHz and L-chirp ABR, and the average of 1 - 4 kHz and U-chirp ABR.</p><p><b>CONCLUSION</b>As an objective test, the response threshold of chirp-ABR and the behavior audiogram were a highly correlated with each other, but more application in more subjects is needed.</p>

Effects of chelation therapy with succimer in young rabbits of moderate lead poisoning / 中华预防医学杂志

<p><b>OBJECTIVE</b>To explore the effect of chelation therapy with succimer (DMSA) in male rabbits of moderate lead poisoning during juvenile stage.</p><p><b>METHODS</b>Twenty-four 45-day-old male New Zealand rabbits were randomly divided into three groups (therapy group, TG; positive control group, PG and negative control group, NG, n=8). The TG and PG were orally exposed to lead acetate (5 mg x kg(-1) x d(-1)) for 6 weeks. Rabbits in TG were orally supplied DMSA 1050 mg/m2 in the first week and 700 mg/m2 in the next two weeks, while the other two groups wren't blood and urinary samples of all rabbits were collected per week. The tissues and organs of all rabbits were collected after 12 weeks. The blood lead levels (BLLs) were determined by atomic absorption spectrometer. The urine lead levels and the lead contents of tissue and organ were determined by inductively coupled plasma-mass spectrometry. Histopathology of tissue and organ was observed by light microscope.</p><p><b>RESULTS</b>Compared with PG, the lead level in the morning urine of TG with DMSA chelating was increased significantly. The level was peaked at (1246.96 +/- 157.91) microg/L on the first day after chelating. While the base line was (40.97 +/- 1.77) microg/L before chelating. Meanwhile, the BLLs were sharply declined from (429.63 +/- 10.82) microg/L to (238.50 +/- 11.82) microg/L. The urine lead levels of TG decreased through the 3-week chelating and 3-week discontinuation. The urine lead levels of these two groups were significantly different (F=2934.35, P<0.01). Compared to each two groups in these three groups, there were significant difference (P<0.01). The authors found the reversion of BLLs in first week after stop chelating. The BLLs of PG presented the slow course of declining in the same time, were (135.50 +/- 7.09) microg/L, very close to the level of TG for (149.88 +/- 11.39) microg/L. Compared with treatment discontinuation for 3 weeks, the urine lead levels and the body weight gain of the therapy group increased more than that of PG, and the BLLs and the lead concentrations in tissues and organs decreased more than that of PG, and histopathology in the liver tissues and testicle tissues were improved.</p><p><b>CONCLUSION</b>DMSA chelating for the rodent models of moderate lead poisoning might reduce the BLLs and soft tissue lead contents quickly and effectively, decrease toxic effects of lead in a short period of time, thus alleviate the impairment of lead poisoning on tissues and organs by decreasing lead burden, and bring out improvement on the growth retardation caused by lead poisoning.</p>

Role of multi-drug resistance-associated protein-1 transporter in statin-induced myopathy.

This study investigated the effects of probenecid to inhibit the multi-drug resistance-associated protein-1 (MRP-1) in mediating the efflux and myotoxicity in rat skeletal muscles, with administration of rosuvastatin. Male Sprague-Dawley rats were administered daily, for 15 days, with either rosuvastatin (50, 100 or 200 mg/kg) or probenecid (100 mg/kg) alone, or with a combination of rosuvastatin (50, 100 or 200 mg/kg) and probenecid (100 mg/kg). Skeletal muscle toxicity was elevated with probenecid administered with 200 mg/kg/day of rosuvastatin, with the elevation of creatine kinase by 12-fold, alanine aminotrasferase by 10-fold and creatinine by 9-fold at day 15, with no adverse effects observed when probenecid was given alone. Mitochondria ultrastructural damage with enlargement, disruption, cristolysis and vaculation was seen in the soleus and plantaris of animals administered with probenecid and high dosages of statin. These muscles were also expressing more succinic dehydrogenase (SDH)-positive and cytochrome oxidase (CyOX)-positive fibers. Although generally well-tolerated, statins produce a variety of adverse skeletal muscle events. Hydrophilic statins, with reduced levels of non-specific passive diffusion rates into extra-hepatic tissues, are still seen to produce myopathy. This highlights the important roles of transport mechanisms in statin transport at the skeletal muscles. Excessive influx, reduced efflux or the combination of the two could result in elevated cellular levels of statins at the skeletal muscles, resulting in toxicity. This study provides preliminary evidence that the MRP-1 transporter and efflux at skeletal muscles possibly play significant roles in statin-induced myopathy.