Spinal cord astrocyte P2X7Rs mediate the inhibitory effect of electroacupuncture on visceral hypersensitivity of rat with irritable bowel syndrome.

This study explored the role of P2X7 receptors in spinal cord astrocytes in the electroacupuncture-induced inhibition of visceral hypersensitivity (VH) in rats with irritable bowel syndrome (IBS). Visceral hypersensitivity of IBS was intracolonically induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). Visceromotor responses to colorectal distension (CRD-20,40,60,80 mmHg) and abdominal withdrawal reflex scoring (AWRs) were recorded after electroacupuncture at bilateral Zusanli (ST36) and Sanyinjiao (SP6) acupoints to evaluate the analgesic effect of electroacupuncture on visceral pain in rats with IBS. Fluorocitric acid (FCA), an astrocyte activity inhibitor, was injected intrathecally before electroacupuncture intervention and AWRs were recorded. Western blot and real-time qPCR were used to detect the expression of NMDA and P2X7 receptor to observe the regulation effect of electroacupuncture on NMDA receptor in the spinal cord of rats with visceral hypersensitivity. Intrathecal injection of P2X7 agonist or antagonist was administered before electroacupuncture treatment. To observe the effect of P2X7 receptor in spinal astrocytes on the inhibition of visceral hyperalgesia by electroacupuncture, the changes of AWR score, NMDA receptor in the spinal cord, and GFAP expression in astrocytes were detected. Inflammation of the colon had basically subsided at day 21 post-TNBS; persistent visceral hypersensitivity could be suppressed by electroacupuncture. This analgesic effect could be inhibited by FCA. The analgesic effect, downregulation of NMDA receptor NR1 subunit, and P2X7 protein of electroacupuncture were all reversed by FCA. P2X7 receptor antagonist A740003 can cooperate with EA to carry out analgesic effect in rats with visceral pain and downregulate the expression of NR1, NR2B, and GFAP in spinal dorsal horn. However, the P2X7 receptor agonist BzATP could partially reverse the analgesic effect of EA, inhibiting the downregulatory effect of EA on the expression of NR1, NR2B, and GFAP. These results indicate that EA may downregulate the expression of the NMDA receptor by inhibiting the P2X7 receptor in the spinal cord, thereby inhibiting spinal cord sensitization in IBS rats with visceral pain, in which astrocytes are an important medium.

Dihydromyricetin Alleviates H9C2 Cell Apoptosis and Autophagy by Regulating CircHIPK3 Expression and PI3K/AKT/mTOR Pathway.

OBJECTIVE: To investigate the effect and potential mechanism of dihydromyricetin (Dmy) on H9C2 cell proliferation, apoptosis, and autophagy. METHODS: H9C2 cells were randomly divided into 7 groups, namely control, model, EV (empty pCDH-CMV-MCS-EF1-CopGFP-T2A-Puro vector), IV (circHIPK3 interference), Dmy (50 µ mol/L), Dmy+IV, and Dmy+EV groups. Cell proliferation and apoptosis were detected by cell counting kit-8 assay and flow cytometry, respectivley. Western blot was used to evaluate the levels of light chain 3 II/I (LC3II/I), phospho-phosphoinositide 3-kinase (p-PI3K), protein kinase B (p-AKT), and phospho-mammalian target of rapamycin (p-mTOR). The level of circHIPK3 was determined using reverse transcriptase polymerase chain reaction. Electron microscopy was used to observe autophagosomes in H9C2 cells. RESULTS: Compared to H9C2 cells, the expression of circHIPK in H9C2 hypoxia model cells increased significantly (P<0.05). Compared to the control group, the cell apoptosis and autophagosomes increased, cell proliferation rate decreased significantly, and the expression of LC3 II/I significantly increased (all P<0.05). Compared to the model group, the rate of apoptosis and autophagosomes in IV, Dmy, and Dmy+IV group decreased, the cell proliferation rate increased, and the expression of LC3 II/I decreased significantly (all P<0.05). Compared to the control group, the expressions of p-PI3K, p-AKT, and p-mTOR in the model group significantly reduced (P<0.05), whereas after treatment with Dmy and sh-circHIPK3, the above situation was reversed (P<0.05). CONCLUSION: Dmy plays a protective role in H9C2 cells by inhibiting circHIPK expression and cell apoptosis and autophagy, and the mechanism may be related to PI3K/AKT/mTOR pathway.

Molecular, Pathological, Clinical, and Therapeutic Aspects of Perihematomal Edema in Different Stages of Intracerebral Hemorrhage.

Acute intracerebral hemorrhage (ICH) is a devastating type of stroke worldwide. Neuronal destruction involved in the brain damage process caused by ICH includes a primary injury formed by the mass effect of the hematoma and a secondary injury induced by the degradation products of a blood clot. Additionally, factors in the coagulation cascade and complement activation process also contribute to secondary brain injury by promoting the disruption of the blood-brain barrier and neuronal cell degeneration by enhancing the inflammatory response, oxidative stress, etc. Although treatment options for direct damage are limited, various strategies have been proposed to treat secondary injury post-ICH. Perihematomal edema (PHE) is a potential surrogate marker for secondary injury and may contribute to poor outcomes after ICH. Therefore, it is essential to investigate the underlying pathological mechanism, evolution, and potential therapeutic strategies to treat PHE. Here, we review the pathophysiology and imaging characteristics of PHE at different stages after acute ICH. As illustrated in preclinical and clinical studies, we discussed the merits and limitations of varying PHE quantification protocols, including absolute PHE volume, relative PHE volume, and extension distance calculated with images and other techniques. Importantly, this review summarizes the factors that affect PHE by focusing on traditional variables, the cerebral venous drainage system, and the brain lymphatic drainage system. Finally, to facilitate translational research, we analyze why the relationship between PHE and the functional outcome of ICH is currently controversial. We also emphasize promising therapeutic approaches that modulate multiple targets to alleviate PHE and promote neurologic recovery after acute ICH.

Diet-Induced High Serum Levels of Trimethylamine-N-oxide Enhance the Cellular Inflammatory Response without Exacerbating Acute Intracerebral Hemorrhage Injury in Mice.

Trimethylamine-N-oxide (TMAO), an intestinal flora metabolite of choline, may aggravate atherosclerosis by inducing a chronic inflammatory response and thereby promoting the occurrence of cerebrovascular diseases. Knowledge about the influence of TMAO-related inflammatory response on the pathological process of acute stroke is limited. This study was designed to explore the effects of TMAO on neuroinflammation, brain injury severity, and long-term neurologic function in mice with acute intracerebral hemorrhage (ICH). We fed mice with either a regular chow diet or a chow diet supplemented with 1.2% choline pre- and post-ICH. In this study, we measured serum levels of TMAO with ultrahigh-performance liquid chromatography-tandem mass spectrometry at 24 h and 72 h post-ICH. The expression level of P38-mitogen-protein kinase (P38-MAPK), myeloid differentiation factor 88 (MyD88), high-mobility group box1 protein (HMGB1), and interleukin-1ß (IL-1ß) around hematoma was examined by western blotting at 24 h. Microglial and astrocyte activation and neutrophil infiltration were examined at 72 h. The lesion was examined on days 3 and 28. Neurologic deficits were examined for 28 days. A long-term choline diet significantly increased serum levels of TMAO compared with a regular diet at 24 h and 72 h after sham operation or ICH. Choline diet-induced high serum levels of TMAO did not enhance the expression of P38-MAPK, MyD88, HMGB1, or IL-1ß at 24 h. However, it did increase the number of activated microglia and astrocytes around the hematoma at 72 h. Contrary to our expectations, it did not aggravate acute or long-term histologic damage or neurologic deficits after ICH. In summary, choline diet-induced high serum levels of TMAO increased the cellular inflammatory response probably by activating microglia and astrocytes. However, it did not aggravate brain injury or worsen long-term neurologic deficits. Although TMAO might be a potential risk factor for cerebrovascular diseases, this exploratory study did not support that TMAO is a promising target for ICH therapy.

Effect of Oral Nutritional Supplementation on Growth in Children with Undernutrition: A Systematic Review and Meta-Analysis.

Oral nutritional supplements (ONS) are used to promote catch-up growth in children with undernutrition. We conducted a systematic review and meta-analysis to summarize the evidence of ONS intervention effects on growth for 9-month- to 12-year-old children who were undernourished or at nutritional risk. Eleven randomized controlled trials met the inclusion criteria; trials compared changes in anthropometric measures in children using ONS or ONS + DC (dietary counselling) to measures for those following usual diet or placebo or DC alone. The RCTs included 2287 children without chronic diseases (mean age 5.87 years [SD, 1.35]; 56% boys). At follow-up time points up to 6 months, results showed that children in the ONS intervention group had greater gains in weight (0.423 kg, [95% confidence interval 0.234, 0.613], p < 0.001) and height (0.417 cm [0.059, 0.776], p = 0.022) versus control; greater gains in weight (0.089 kg [0.049, 0.130], p < 0.001) were evident as early as 7-10 days. Longitudinal analyses with repeated measures at 30, 60, and 90 days showed greater gains in weight parameters from 30 days onwards (p < 0.001), a trend towards greater height gains at 90 days (p = 0.056), and significantly greater gains in height-for-age percentiles and Z-scores at 30 and 90 days, respectively (p < 0.05). Similar results were found in subgroup analyses of studies comparing ONS + DC to DC alone. For children with undernutrition, particularly those who were mildly and moderately undernourished, usage of ONS in a nutritional intervention resulted in significantly better growth outcomes when compared to control treatments (usual diet, placebo or DC alone).

Bawei Chenxiang Wan Ameliorates Cardiac Hypertrophy by Activating AMPK/PPAR-α Signaling Pathway Improving Energy Metabolism.

Bawei Chenxiang Wan (BCW), a well-known traditional Chinese Tibetan medicine formula, is effective for the treatment of acute and chronic cardiovascular diseases. In the present study, we investigated the effect of BCW in cardiac hypertrophy and underlying mechanisms. The dose of 0.2, 0.4, and 0.8 g/kg BCW treated cardiac hypertrophy in SD rat model induced by isoprenaline (ISO). Our results showed that BCW (0.4 g/kg) could repress cardiac hypertrophy, indicated by macro morphology, heart weight to body weight ratio (HW/BW), left ventricle heart weight to body weight ratio (LVW/BW), hypertrophy markers, heart function, pathological structure, cross-sectional area (CSA) of myocardial cells, and the myocardial enzymes. Furthermore, we declared the mechanism of BCW anti-hypertrophy effect was associated with activating adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor-α (PPAR-α) signals, which regulate carnitine palmitoyltransferase1ß (CPT-1ß) and glucose transport-4 (GLUT-4) to ameliorate glycolipid metabolism. Moreover, BCW also elevated mitochondrial DNA-encoded genes of NADH dehydrogenase subunit 1(ND1), cytochrome b (Cytb), and mitochondrially encoded cytochrome coxidase I (mt-co1) expression, which was associated with mitochondria function and oxidative phosphorylation. Subsequently, knocking down AMPK by siRNA significantly can reverse the anti-hypertrophy effect of BCW indicated by hypertrophy markers and cell surface of cardiomyocytes. In conclusion, BCW prevents ISO-induced cardiomyocyte hypertrophy by activating AMPK/PPAR-α to alleviate the disturbance in energy metabolism. Therefore, BCW can be used as an alternative drug for the treatment of cardiac hypertrophy.

Traditional Chinese Medicine Xihuang Wan Inhibited Lewis Lung Carcinoma in a Syngeneic Model, Equivalent to Cytotoxic Chemotherapy, by Altering Multiple Signaling Pathways.

BACKGROUND/AIM: Xihuang Wan (XHW), a traditional Chinese medicine (TCM), has been used in China for a variety of cancers including lung cancer. The present study evaluated the efficacy of XHW on a Lewis lung mouse model and explored the potential mechanism via transcriptomics. MATERIALS AND METHODS: The mice were randomized into 6 groups: 1) untreated control (n=10); 2) low-dose XHW; 3) medium-dose XHW; 4) high-dose XHW; 5) cisplatin; and 6) untreated blank (n=4). Lewis lung carcinoma (LLC) cells were injected subcutaneously except for the 4 mice in the blank group. The body weight and tumor length and width were measured every 3 days. RNA-sequencing was performed on tumors in the high-dose XHW group and the control group. RESULTS: XHW inhibited the growth of LLC in a syngeneic mouse model, without toxicity, with equivalent efficacy to cisplatin. RNA-sequencing demonstrated that many signaling pathways were involved in XHW-mediated inhibition of LLC, including tumor necrosis factor, estrogen, cyclic guanosine 3', 5'-monophosphate-protein kinase G, apelin and the peroxisome proliferator-activated receptor signaling pathways. CONCLUSION: XHW inhibited LLC carcinoma through different pathways and shows clinical promise for patients who cannot tolerate platinum-based drugs.

Herbal cake-partitioned moxibustion inhibits colonic autophagy in Crohn's disease via signaling involving distinct classes of phosphatidylinositol 3-kinases.

BACKGROUND: Autophagy is an evolutionarily conserved biological process in eukaryotic cells that involves lysosomal-mediated degradation and recycling of related cellular components. Recent studies have shown that autophagy plays an important role in the pathogenesis of Crohn's disease (CD). Herbal cake-partitioned moxibustion (HM) has been historically practiced to treat CD. However, the mechanism by which HM regulates colonic autophagy in CD remains unclear. AIM: To observe whether HM can alleviate CD by regulating colonic autophagy and to elucidate the underlying mechanism. METHODS: Rats were randomly divided into a normal control (NC) group, a CD group, an HM group, an insulin + CD (I + CD) group, an insulin + HM (I + HM) group, a rapamycin + CD (RA + CD) group, and a rapamycin + HM (RA + HM) group. 2,4,6-trinitrobenzenesulfonic acid was administered to establish a CD model. The morphology of the colonic mucosa was observed by hematoxylin-eosin staining, and the formation of autophagosomes was observed by electron microscopy. The expression of autophagy marker microtubule-associated protein 1 light chain 3 beta (LC3B) was observed by immunofluorescence staining. Insulin and rapamycin were used to inhibit and activate colonic autophagy, respectively. The mRNA expression levels of phosphatidylinositol 3-kinase class I (PI3KC1), Akt1, LC3B, sequestosome 1 (p62), and mammalian target of rapamycin (mTOR) were evaluated by RT-qPCR. The protein expression levels of interleukin 18 (IL-18), tumor necrosis factor-α (TNF-α), nuclear factor κB/p65 (NF-κB p65), LC3B, p62, coiled-coil myosin-like BCL2-interacting protein (Beclin-1), p-mTOR, PI3KC1, class III phosphatidylinositol 3-kinase (PI3KC3/Vps34), and p-Akt were evaluated by Western blot analysis. RESULTS: Compared with the NC group, the CD group showed severe damage to colon tissues and higher expression levels of IL-18 and NF-κB p65 in colon tissues (P < 0.01 for both). Compared with the CD group, the HM group showed significantly lower levels of these proteins (P IL-18 < 0.01 and P p65 < 0.05). There were no significant differences in the expression of TNF-α protein in colon tissue among the rat groups. Typical autophagic vesicles were found in both the CD and HM groups. The expression of the autophagy proteins LC3B and Beclin-1 was upregulated (P < 0.01 for both) in the colon tissues of rats in the CD group compared with the NC group, while the protein expression of p62 and p-mTOR was downregulated (P < 0.01 for both). However, these expression trends were significantly reversed in the HM group compared with the CD group (P LC3B < 0.01, P Beclin-1 < 0.05, P p62 < 0.05, and P m-TOR < 0.05). Compared with those in the RA + CD group, the mRNA expression levels of PI3KC1, Akt1, mTOR, and p62 in the RA + HM group were significantly higher (P PI3KC1 < 0.01 and P Akt1, mTOR, and p62 < 0.05), while those of LC3B were significantly lower (P < 0.05). Compared with the RA + CD group, the RA + HM group exhibited significantly higher PI3KC1, p-Akt1, and p-mTOR protein levels (P PI3KC1 < 0.01, P p-Akt1 < 0.05, and P p-mTOR < 0.01), a higher p62 protein level (P = 0.057), and significantly lower LC3B and Vps34 protein levels (P < 0.01 for both) in colon tissue. CONCLUSION: HM can activate PI3KC1/Akt1/mTOR signaling while inhibiting the PI3KC3 (Vps34)-Beclin-1 protein complex in the colon tissues of CD rats, thereby inhibiting overactivated autophagy and thus exerting a therapeutic effect.

Effects of acute caffeine, theanine and tyrosine supplementation on mental and physical performance in athletes.

BACKGROUND: A limited amount of research has demonstrated beneficial effects of caffeine and theanine supplementation for enhancement of mental performance. The purpose of this investigation was to determine whether the acute ingestion of a supplement containing caffeine, theanine and tyrosine improves mental and physical performance in athletes. METHODS: Twenty current or former male collegiate athletes (age: 20.5 ± 1.4 y; height: 1.82 ± 0.08 m; weight: 83.9 ± 12.6 kg; body fat: 13.8 ± 5.6%) completed this randomized, double-blind, placebo-controlled crossover trial. After familiarization, each participant completed two identical testing sessions with provision of a proprietary dietary supplement (SUP) containing caffeine theanine and tyrosine or a placebo (PL). Within each testing session, participants completed assessments of mental and physical performance before and after provision of SUP or PL, as well as after two rounds of exercise. Assessments were performed using a performance testing device (Makoto Arena) that evaluated multiple aspects of mental and physical performance in response to auditory and visual stimuli. Testing was performed both with the body in a static position and during dynamic movement. General linear models were used to evaluate the effects of SUP and PL on performance. RESULTS: Changes in movement accuracy during performance assessment were greater following SUP ingestion as compared to PL for both static and dynamic testing (SUP: + 0.4 to 7.5%; PL: - 1.4 to 1.4% on average; p < 0.05). For dynamic testing, the change in number of targets hit was higher and the change in average hit time was lower with SUP as compared to PL (p < 0.05). However, there were no differences between conditions for the changes in number of targets hit or average hit time during static testing. There were no differences in changes of subjective variables during either condition, and performance measures during the two rounds of exercise did not differ between conditions (p > 0.05). DISCUSSION: The present results indicate that a combination of a low-dose of caffeine with theanine and tyrosine may improve athletes' movement accuracy surrounding bouts of exhaustive exercise without altering subjective variables. Based on this finding, supplementation with caffeine, theanine and tyrosine could potentially hold ergogenic value for athletes in sports requiring rapid and accurate movements. TRIAL REGISTRATION: NCT03019523. Registered 24 January 2017.

Dietary Intakes of EPA and DHA Omega-3 Fatty Acids among US Childbearing-Age and Pregnant Women: An Analysis of NHANES 2001-2014.

BACKGROUND: The 2015­2020 Dietary Guidelines for Americans (DGA) recommend that the general population should consume about 8 ounces (oz.) per week of a variety of seafood, providing approximately 250 mg per day of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and that pregnant and lactating women should consume 8–12 oz. per week of seafood. METHODS: We determined the usual intakes, percentage not meeting recommendations, and trends in EPA and DHA intakes among childbearing-age and pregnant women (15–44 years of age) using the NHANES cycles 2001­2002 through 2013­2014. RESULTS: For the childbearing-age women, the mean usual intake of seafood was 0.44 ± 0.02 oz. equivalent per day and 100% of the population was below the DGA recommendation. Mean usual intakes of EPA, DHA, and combined EPA and DHA from foods and dietary supplements combined were 26.8 ± 1.4, 62.2 ± 1.9, and 88.1 ± 3.0 mg per day, respectively. Over 95% of the sample did not meet the daily intakes of 250 mg EPA and DHA. Similar results were observed for pregnant women. After controlling for covariates, there were slight but significant increases in EPA and DHA intakes from foods and dietary supplements over the 14-year span among childbearing-age (p = 0.005) and pregnant women (p = 0.002). CONCLUSIONS: It was estimated that a majority of U.S. childbearing-age and pregnant women consumed significantly lower amounts of seafood than what the DGA recommends, which subsequently leads to low intakes of EPA and DHA; in addition, dietary supplement use has not eliminated the nutrient shortfall.

Increasing Cancer Therapy Efficiency through Targeting and Localized Light Activation.

Currently, the potential of cancer therapy is compromised by a variety of problems related to tumor specificity, drug access, and limited efficacy. We report a novel approach to improve the effectiveness of cancer treatment utilizing a light-responsive nanoconstruct. Effectiveness is increased by enhancing drug absorption through heating and the production of free radicals. Treatment specificity is increased through chemical targeting of the nanoconstruct and localization of light delivery to the tumor. When reaching the tumor, magnetic resonance imaging is enhanced and near-infrared fluorescence is activated upon drug release, making it possible to visualize the localized treatment at both the tissue and cellular levels. This dual-modality imaging nanoconstruct enables the synergistic treatment and observable evaluation of solid tumors with dramatically improved efficacy, giving rise to a promising new approach for cancer therapy and evaluation.

Differentiated demographic histories and local adaptations between Sherpas and Tibetans.

BACKGROUND: The genetic relationships reported by recent studies between Sherpas and Tibetans are controversial. To gain insights into the population history and the genetic basis of high-altitude adaptation of the two groups, we analyzed genome-wide data in 111 Sherpas (Tibet and Nepal) and 177 Tibetans (Tibet and Qinghai), together with available data from present-day human populations. RESULTS: Sherpas and Tibetans show considerable genetic differences and can be distinguished as two distinct groups, even though the divergence between them (~3200-11,300 years ago) is much later than that between Han Chinese and either of the two groups (~6200-16,000 years ago). Sub-population structures exist in both Sherpas and Tibetans, corresponding to geographical or linguistic groups. Differentiation of genetic variants between Sherpas and Tibetans associated with adaptation to either high-altitude or ultraviolet radiation were identified and validated by genotyping additional Sherpa and Tibetan samples. CONCLUSIONS: Our analyses indicate that both Sherpas and Tibetans are admixed populations, but the findings do not support the previous hypothesis that Tibetans derive their ancestry from Sherpas and Han Chinese. Compared to Tibetans, Sherpas show higher levels of South Asian ancestry, while Tibetans show higher levels of East Asian and Central Asian/Siberian ancestry. We propose a new model to elucidate the differentiated demographic histories and local adaptations of Sherpas and Tibetans.

MRI-guided liposomes for targeted tandem chemotherapy and therapeutic response prediction.

Liposomes are effective drug delivery systems that can be functionalized with imaging contrast agents, providing both diagnosis and monitoring of disease treatment. Here we describe the design of a theranostic liposomal drug delivery system whose biodistribution can be real time imaged by contrast enhanced MRI and can achieve tandem chemotherapy drug delivery. Because T1 relaxation of MRI depends upon the chemical structure of contrast agent as well as its interaction with neighbor environment, we rationally designed a functional liposome for in vivo T1 enhanced MRI. The liposome shows a 36-fold higher T1 relaxation rate over the commercial MRI contrast agent Omniscan® and a long circulation time up to 300min in vivo. Moreover, the multifunctional liposome carries both hydrophobic and hydrophilic chemotherapeutic drugs, can synergistically enhance therapeutic effects of multiple drugs and selectively deliver them to lung tumors, leading to lower doses, toxicity and sustained release. The nanoparticles, which exhibit favorable biodistributions to tumors, offer new possibilities for the simultaneous delivery of more than one drug and the evaluation of therapeutic response in vivo by T1 enhanced MRI. STATEMENT OF SIGNIFICANCE: Cancer cells invoke different mechanisms to resist cancer therapies, particularly when delivering a single agent in a given therapy. The combination of two (or more) thermotherapy agents provides a promising way to circumvent such situations of drug resistance, due to a favorable synergistic effect that "tricks" the drug resistance mechanism. However, challenges to the simultaneous delivery of two drugs prevail, especially with regards to the simultaneous delivery of hydrophobic and hydrophobic drugs. Furthermore, non-invasive in vivo imaging of drug distribution enables the real-time monitoring and prediction of therapeutic responses to treatment. In this study, we rationally designed a theranostic liposomal drug delivery system whose biodistribution can be imaged via T1-weighted MRI in real-time and can achieve tandem chemotherapy drug delivery. This original study will be of considerable use to the wider drug delivery community.

Identification and monitoring of metabolite markers of dry bean consumption in parallel human and mouse studies.

SCOPE: Aim of the study was to identify and monitor metabolite markers of dry bean consumption in parallel human and mouse studies that each had shown chemopreventive effects of dry bean consumption on colorectal neoplasia risk. METHODS AND RESULTS: Using LC/mass spectroscopy ± ESI and GC/mass spectroscopy, serum metabolites of dry beans were measured in 46 men before and after a 4-week dry bean enriched diet (250 g/day) and 12 mice that received a standardized diet containing either 0 or 10% navy bean ethanol extract for 6 weeks; we also investigated fecal metabolites in the mice. The serum metabolites identified in these controlled feeding studies were then investigated in 212 polyp-free participants from the Polyp Prevention Trial who self-reported either increased (≥+31 g/day from baseline), high dry bean intake of ≥42 g/day in year 3 or low, unchanged dry bean consumption of <8 g/day; serum was analyzed from baseline and year 3. Serum pipecolic acid and S-methyl cysteine were elevated after dry bean consumption in human and mouse studies and reflected dry bean consumption in the Polyp Prevention Trial. CONCLUSION: Serum levels of pipecolic acid and S-methyl cysteine are useful biomarkers of dry bean consumption.

Improving the efficacy of conventional therapy by adding andrographolide sulfonate in the treatment of severe hand, foot, and mouth disease: a randomized controlled trial.

Background. Herb-derived compound andrographolide sulfonate (called Xiyanping injection) recommended control measure for severe hand, foot, and mouth disease (HFMD) by the Ministry of Health (China) during the 2010 epidemic. However, there is a lack of good quality evidence directly comparing the efficacy of Andrographolide Sulfonate combination therapy with conventional therapy. Methods. 230 patients were randomly assigned to 7-10 days of Andrographolide Sulfonate 5-10 mg/Kg/day and conventional therapy, or conventional therapy alone. Results. The major complications occurred less often after Andrographolide Sulfonate (2.6% versus 12.1%; risk difference [RD], 0.94; 95% CI, 0.28-1.61; P = 0.006). Median fever clearance times were 96 hours (CI, 80 to 126) for conventional therapy recipients and 48 hours (CI, 36 to 54) for Andrographolide Sulfonate combination-treated patients (χ(2) = 16.57, P < 0.001). The two groups did not differ in terms of HFMD-cause mortality (P = 1.00) and duration of hospitalization (P = 0.70). There was one death in conventional therapy group. No important adverse event was found in Andrographolide Sulfonate combination therapy group. Conclusions. The addition of Andrographolide Sulfonate to conventional therapy reduced the occurrence of major complications, fever clearance time, and the healing time of typical skin or oral mucosa lesions in children with severe HFMD.

[Brief history of percutaneous coronary intervention].

Percutaneous coronary intervention (PCI) is that delivering balloon catheter and/or equipment such as a stent to the target coronary artery bypass peripheral artery, at the same time, expanding and opening the stenosis of coronary artery. Through several decades of development, PCI has become a most effective way to rescue patients with coronary heart disease and become one of the biggest advances in the field of heart disease. Because of the development of PCI, more lives have been saved in patients with coronary heart disease. However, PCI does not meet the point of perfection, still has a lot of issues remain to be further resolved. Through a review the development of PCI, we may be able to get some insights to perfect the treatment technique for the patients of coronary heart disease.

Role of mast cells in acupuncture effect: a pilot study.

To better understand the therapeutic effectiveness of acupuncture, questions about the underlying mechanisms need to be addressed. Here we describe the impact of manual stimulation by an acupuncture needle of zusanli (stomach 36 [ST36]) on analgesia in rats. The analgesic effect was more pronounced after stimulation of ST36 than after stimulation of a sham point near the acupuncture point. At the same time, we determined in tissue slices the density of mast cells in the acupuncture points and nearby points, as well as the degree of degranulation before and after stimulation. We found that the density of mast cells from the ST36 of rats was higher than that from a nearby sham point. In addition, acupuncture resulted in a remarkable increase in degranulation of the mast cells. Pretreatment of the acupuncture point with disodium chromoglycate not only counteracted the phenomenon of degranulation but also reduced analgesic effect of acupuncture. Our experiments on inhibition of degranulation of mast cells in tissue from acupuncture points demonstrates the possible role of mast cells in acupuncture effects.

[Influence of mast cell function on the analgesic effect of acupuncture of "Zusanli" (ST 36) in rats].

OBJECTIVE: To investigate the role of mast cells in acupuncture analgesia in rats. METHODS: A total of 48 Sprague Dawley (SD) rats were divided into normal control, acupoinc Effect [("Zusanli"(ST 36)-acupuncture (Acu), non-acupoint (3 mm left to ST36), disodium cromoglycate (DSC, 0.02 gmL, for acupoint injection), normal saline (NS, for acupoint injection), DSC + Acu, NS-b+ Acu and DSC+contralach Center ral Acu groups, with 6 cases in each group. The latency of tail flick response to heat irradiation was used as the pain threshold. "Zusanli" (ST 36) was punctured with filiform needle and stimulated by lifting and thrusting the needle for 30 min. After sacrifice under anesthesia (1% embutal) c, tissues of T36 area were sampled, sliced (4 microm), and stained with Toluidine Blue for skin and Neutral Red for muscles. RESULTS: Compared with normal control group, the ratios of pain threshold increased significantly in all the 7 experimental groups (P < 0.05), and those of DSC and NS groups were significantly lower than those of acupoint-Acu, non-acupoint, DSC+ Acu, NS+ Acu and DSC + contralateral Acu groups (P < 0.05) n. Comp + Acu group, the ratios of NS+Acu and DSC+ contralateral Acu groups were evidently higher (P < 0.05, 0.01). Compared with control group, the degranulation ratio of acupoint-Acu group was significantly higher (P < 0.05, 0.001 in muscle and skin separately), and the ratio of DSC+ Acu group was markedly lower than that of acupoint-Acu group (P < 0.01 in skin). CONCLUSION: Acupuncture of ST36 has a significant analgesia and enhances the degranulation of mast apparently cells, which is weakened by injection of DSC in the acupoint area, suggesting an important role of mast cells in acupuncture-induced analgesia.