Action Mode of Gut Motility, Fluid and Electrolyte Transport in Chronic Constipation.

Chronic constipation is a common gastrointestinal disorder, with a worldwide incidence of 14-30%. It negatively affects quality of life and is associated with a considerable economic burden. As a disease with multiple etiologies and risk factors, it is important to understand the pathophysiology of chronic constipation. The purpose of this review is to discuss latest findings on the roles of gut motility, fluid, and electrolyte transport that contribute to chronic constipation, and the main drugs available for treating patients. We conducted searches on PubMed and Google Scholar up to 9 February 2021. MeSH keywords "constipation", "gastrointestinal motility", "peristalsis", "electrolytes", "fluid", "aquaporins", and "medicine" were included. The reference lists of searched articles were reviewed to identify further eligible articles. Studies focusing on opioid-induced constipation, evaluation, and clinic management of constipation were excluded. The occurrence of constipation is inherently connected to disorders of gut motility as well as fluid and electrolyte transport, which involve the nervous system, endocrine signaling, the gastrointestinal microbiota, ion channels, and aquaporins. The mechanisms of action and application of the main drugs are summarized; a better understanding of ion channels and aquaporins may be helpful for new drug development. This review aims to provide a scientific basis that can guide future research on the etiology and treatment of constipation.

[Identification of quality markers of Qixuehe Capsules based on analytic hierarchy process and entropy weight methods].

Qixuehe Capsules is a compound Chinese patent medicine developed for treating the disorder of Qi and blood(a common etiology of gynecological disease), which has remarkable effects on smoothing liver and regulating Qi, activating blood circulation, and relieving pain. However, due to its complex prescriptions(15 herbs) and multiple effects, the quality control of Qixuehe Capsules has always been a bottleneck problem limiting its sustainable development. Therefore, this study adopted the traditional Chinese medicine Q-markers quantitative identification system established previously by our research group based on the combination of analytic hierarchy process and entropy weight methods. With the different effects of Qixuehe Capsules as the entry point, the comprehensive scores of chemical ingre-dients in Qixuehe Capsules under the items of effectiveness(smoothing liver and regulating qi, activating blood circulation, and relieving pain), testability and specificity were calculated and integrated, respectively. Subsequently, through the analysis of compatibility relationship of Qixuehe Capsules, 15 active ingredients with high comprehensive scores were found to be the top Q-mar-kers of Qixuehe Capsules, including ferulic acid, quercetin, caffeic acid, kaempferol, rutin, Z-ligustilide, senkyunolide Ⅰ, vanillic acid, protocatechuic acid, chlorogenic acid, rosmarinic acid, senkyunolide A, gallic acid, tetrahydropalmatine and eugenol. Collectively, this study not only provided scientific evidence for further research on the improvement and standardization of quality standards of Qixuehe Capsules but also provided methodological references for the quantitative identification of Q-markers of multi-effect traditional Chinese medicine formulae.

An integrated strategy for discovering effective components of Shaoyao Gancao decoction for treating neuropathic pain by the combination of partial least-squares regression and multi-index comprehensive method.

ETHNOPHARMACOLOGICAL RELEVANCE: Neuropathic pain, the incidence of which ranges from 5 to 8% in the general population, remains challenge in the treatment. Shaoyao Gancao decoction (SGD) is a Chinese classical formula used to relieve pain for thousands of years and has been applied for neuropathic pain nowadays. However, the effective components of SGD for the treatment of neuropathic pain remains unclear. AIMS OF STUDY: To investigate the effect and potential mechanism of SGD against neuropathic pain and further reveal the effective components of SGD in the treatment of neuropathic pain. MATERIALS AND METHODS: Spared nerve injury (SNI) model rats of neuropathic pain were orally given SGD to intervene, the components in vivo after SGD administration were determined, behavior indicators, biochemical parameters, and metabolomics were applied for assessing the efficacy. Then correlation between components and biomarkers was analyzed by pearson correlation method. To further measure the contribution of components to efficacy, the combination of partial least-squares regression (PLSR) and multi-index comprehensive method was carried out, according to the corresponding contribution degree of the results, the components with large contribution degree were considered as the effective components. RESULTS: SGD exhibited a significant regulatory effect on neuropathic pain, which could increase the pain threshold and decrease the levels of SP, ß-EP, PGE2 and NO. With the high resolution of UPLC-Q-TOF/MS technology, a total of 128 compounds from SGD were identified and 44 of them were absorbed in blood. Besides, 40 serum biomarkers were identified after intervention of SGD and the metabolic pathways were constructed. The key metabolic pathways including Glycerophospholipid metabolism, Linoleic acid metabolism, Alpha-linolenic acid metabolism, Glycosylphosphatidylinositol-anchor biosynthesis and Arachidonic acid metabolism may be related to the regulation of neuropathic pain. Metabolomics combined with PLSR and multi-index comprehensive method was utilized to discover 5 components including paeonol, DL-Arabinose, benzoic acid, hispaglabridin A and paeonilactone C as effective components of SGD in the treatment of neuropathic pain. This strategy was used to explore the effective components of SGD and elucidate its possible analgesic mechanism. CONCLUSION: This study demonstrate that SGD significantly relieved neuropathic pain and elucidated the effective components of SGD for treating neuropathic pain, the strategy as an illustrative case study can be applied to other classical formula and is beneficial to improve the quality and efficacy.

Deciphering the Active Compounds and Mechanisms of Qixuehe Capsule on Qi Stagnation and Blood Stasis Syndrome: A Network Pharmacology Study.

BACKGROUND: Qixuehe capsule (QXH), a Chinese patent medicine, has been demonstrated to be effective in the treatment of menstrual disorders. In traditional Chinese medicine (TCM) theory, qi stagnation and blood stasis syndrome (QS-BSS) is the main syndrome type of menstrual disorders. However, the pharmacodynamic effect of QXH in treating QS-BSS is not clear, and the main active compounds and underlying mechanisms remain unknown. METHODS: A rat model of QS-BSS was established to evaluate the pharmacodynamic effect of QXH. Thereafter, a network pharmacology approach was performed to decipher the active compounds and underlying mechanisms of QXH. RESULTS: QXH could significantly reduce the rising whole blood viscosity (WBV) and plasma viscosity (PV) but also normalize prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FIB) content in QS-BSS rats. Based on partial least-squares-discriminant analysis (PLS-DA), the low-dose QXH-intervened (QXH-L) and the high-dose QXH-intervened (QXH-H) groups seemed the most effective by calculating the relative distance to normality. Through network pharmacology, QXH may improve hemorheological abnormality mainly via 185 compounds-51 targets-28 pathways, whereas 184 compounds-68 targets-28 pathways were associated with QXH in improving coagulopathy. Subsequently, 25 active compounds of QXH were verified by UPLC-Q/TOF-MS. Furthermore, 174 active compounds of QXH were shared in improving hemorheological abnormality and coagulopathy in QS-BSS, each of which can act on multiple targets to be mainly involved in complement and coagulation cascades, leukocyte transendothelial migration, PPAR signaling pathway, VEGF signaling pathway, and arachidonic acid metabolism. The attribution of active compounds indicated that Angelicae Sinensis Radix (DG), Paeoniae Radix Rubra (CS), Carthami Flos (HH), Persicae Semen (TR), and Corydalis Rhizoma (YHS) were the vital herbs of QXH in treating QS-BSS. CONCLUSION: QXH can improve the hemorheology abnormality and coagulopathy of QS-BSS, which may result from the synergy of multiple compounds, targets, and pathways.

[Quantity and function of T cell subsets in patients with paroxysmal nocturnal hemoglobinuria].

This study was purposed to investigate the immune state of T cells, the quantity and function of GPI(+) T cells and GPI(-) T cells in patients with paroxysmal nocturnal hemoglobinuria (PNH). 22 cases of PNH and 18 normal controls were enrolled in this study. Their T lymphocyte subsets, Th lymphocyte subsets were assayed by flow cytometry with the monoclonal antibodies concerned. The proportion of GPI(+) T cells or GPI(-) T cells in CD3(+) T cells, CD4(+) T cells, CD8(+) T cells and the expressions of CD69 on these T cells were also respectively assayed. The results showed that the proportion of CD4(+) T cells in CD3(+) T cells in PNH [(47.7670 +/- 13.91139)%] was lower than that in controls [(54.9592 +/- 7.11678)%] (p < 0.05). CD8(+) T cells in CD3(+) T cells of PNH cases [(52.2767 +/- 13.90395)%] were higher than that of controls [(45.2418 +/- 6.75306)%] (p < 0.05). The ratio of CD4(+) T cells to CD8(+) T cells was reverse in PNH. Those were more significantly in PNH-AA (0.77763 +/- 0.409153) (p < 0.05). The proportion of Th1 cells in PNH [(16.9136 +/- 6.78899)%], especially in PNH-AA [(22.8000 +/- 5.45244)%], was significantly higher than that in controls [(4.4600 +/- 1.81879)%] (p < 0.05). The proportion of Th2 cells in PNH [(4.7582 +/- 1.98441)%] had no difference from controls [(3.7960 +/- 1.13810)%]. The number of GPI(-) T cells in CD8(+) T cells and CD4(+) T cells were (14.6797 +/- 11.96718)% and (3.9241 +/- 2.46263)% respectively. The expression of CD69 on GPI(+) T cells or GPI(-) T cells in PNH [CD8(+) GPI(+) T cells (17.67881 +/- 8.562493)%, CD8(+) GPI(-) T cells (15.86575 +/- 7.279743)%, CD4(+) GPI(+) T cells (4.65431 +/- 1.984378)%, CD4(+) GPI(-) T cells (4.93181 +/- 1.730001)%]was significantly higher than that in normal controls [CD8(+) GPI(+) T cells (4.68038 +/- 1.216645)%, CD4(+) GPI(-) T cells (1.77339 +/- 0.645259)%] (p < 0.05), but the expression of CD69 on GPI(+) T cells was not different from that on GPI(-) T cells in PNH. It is concluded that high function of cytoimmunity in PNH may be responsible for bone marrow failure but not relates to the existence of PNH clone in T cell population.

Burden of abnormal hematopoietic clone in patients with myelodysplastic syndromes.

OBJECTIVE: To investigate the role of the burden of abnormal hematopoietic clone in the development of myelodysplastic syndromes (MDS). METHODS: The ratio of the bone marrow cells with abnormal chromosomes to the total counted bone marrow cells was regarded as the index of MDS clone burden. The disease severity related parameters including white blood cell count, hemoglobin, platelet count, lactate dehydrogenase level, bone marrow blast, myeloid differentiation index, micromegakaryocyte, transfusion, interleukin-2, tumor necrosis factor (TNF), CD4+ and CD8+ T cells of MDS patients were assayed, and the correlations between those parameters and MDS clone burden were also analyzed. RESULTS: The clone burden of MDS patients was 67.4% +/- 36.2%. MDS clone burden positively correlated with bone marrow blasts (r = 0.483, P < 0.05), negatively with hemoglobin level (r = -0.445, P < 0.05). The number of blasts, hemoglobin, and erythrocytes in high clone burden (> 50%) and low clone burden ( < or = 50%) groups were 7.78% +/- 5.51% and 3.45% +/- 3.34%, 56.06 +/- 14.28 g/L and 76.40 +/- 24.44 g/L, (1.82 +/- 0.48) x 10(12)/L and (2.32 +/- 0.66) x 10(12)/L, respectively (all P < 0.05). CD4+ T lymphocytes of MDS patients and normal controls were (0.274 +/- 0.719) x 10(9)/L and (0.455 +/- 0.206) x 10(9)/L, respectively (P < 0.05). CD8+ T lymphocytes of MDS patients and normal controls were (0.240 +/- 0.150) x 10(9)/L and (0.305 +/- 0.145) x 10(9)/L, respectively. The serum level of interleukin-2 of MDS patients (6.29 +/- 3.58 ng/mL) was significantly higher than normal control (3.11 +/- 1.40 ng/mL, P < 0.05). The serum level of TNF of MDS patients and normal control group were 2.42 +/- 1.79 ng/mL and 1.68 +/- 0.69 ng/mL, respectively. The ratio of CD4 to CD8 was higher in high clone burden MDS patients (1.90 +/- 0.52) than that in low clone burden patients (0.97 +/- 0.44, P < 0.05). CONCLUSION: The quantitive clonal karyotype abnormalities and deficient T cell immunity are important parameters for evaluating MDS severity and predicting its progression.