This paper summarizes professor YANG Chunbo's clinical experience in treating refractory constipation （RC） complicated with melanosis coli （MC） from the perspective of damp-heat theory. Internal accumulation of damp-heat is considered as the core pathogenesis of this condition， and the therapeutic principles should focus on clearing， transforming， tonifying， and resolving. Self-formulated Qinghua Beverage （清化饮） is developed to clear and transform damp-heat， regulate qi， and soothe collaterals. In clinical practice， RC complicated with MC is classified into damp-heat with qi stagnation syndrome and damp-heat with stasis obstruction syndrome. Qinghua Beverage is used as the base prescription with modifications according to syndrome differentiation. For damp-heat with qi stagnation syndrome， medicinals that promote qi movement and unblock the bowels， activate blood and clear collaterals are added， while for damp-heat with stasis obstruction syndrome， herbs that resolve stasis and unblock collaterals are incorporated， with simultaneous consideration of nourishing blood and supporting collaterals.

Objective To investigate the therapeutic effect and mechanisms of live combined bifidobacterium and lactobacillus tablets on slow transit constipation(STC)rats.Methods A total of 30 SPF grade Wistar adult female rats were blinded and divided into control group,model group,live combined bifidobacterium and lactobacillus tablets low-dose(0.270g/kg),live combined bifidobacterium and lactobacillus tablets medium dose group(0.540g/kg),live combined bifidobacterium and lactobacillus tablets high-dose group(1.080g/kg),and positive drug group(prucalopride succinate tablet)(0.180mg/kg),with 5 rats in each group.A rat model of STC was established by gavage of loperamide hydrochloride.After successful modeling,medication was administered by gavage for 14 consecutive days on the basis of continued modeling.Observe the changes in general physical signs,fecal water content,and calculate intestinal motility in each group of rats.Using HE staining to observe pathological changes in colon tissue,immunohistochemical methods were used to detect the protein expression of receptor tyrosine kinase(c-Kit),5-hydroxytryptamine(5-HT),5-hydroxytryptamine 3 receptor(5-HT3R),and 5-hydroxytryptamine 4 receptor(5-HT4R)in rat colon tissue.Results Compared with control group,frequency of defecation,fecal water content and intestinal propulsion speed of STC model rats were significantly decreased.The expression levels of proteins such as c-Kit,5-HT,5-HT3R,and 5-HT4R in intestinal tissues were significantly reduced in STC model rats.Compared with STC model group,rats treated with low,medium and high doses of live combined bifidobacterium and lactobacillus tablets and positive drug groups showed a significant increase in bowel frequency,fecal water content,and intestinal motility after intervention.Compared with STC model group,frequency of defecation,fecal water content,intestinal propulsion rate and protein expression of c-Kit,5-HT,5-HT3R and 5-HT4R in rat intestinal tissues were significantly increased after intervention of live combined bifidobacterium and lactobacillus tablets low,medium and high dose groups.Conclusion This study confirms that probiotic preparation live combined bifidobacterium and lactobacillus tablets effectively improves slow transit constipation by promoting the proliferation of Cajal interstitial cells in the colon,increasing the expression of 5-HT,5-HT3R,and 5-HT4R,enhancing intestinal peristalsis,and achieving the therapeutic effect on STC rats.

Objective To investigate the therapeutic effect and mechanisms of live combined bifidobacterium and lactobacillus tablets on slow transit constipation(STC)rats.Methods A total of 30 SPF grade Wistar adult female rats were blinded and divided into control group,model group,live combined bifidobacterium and lactobacillus tablets low-dose(0.270g/kg),live combined bifidobacterium and lactobacillus tablets medium dose group(0.540g/kg),live combined bifidobacterium and lactobacillus tablets high-dose group(1.080g/kg),and positive drug group(prucalopride succinate tablet)(0.180mg/kg),with 5 rats in each group.A rat model of STC was established by gavage of loperamide hydrochloride.After successful modeling,medication was administered by gavage for 14 consecutive days on the basis of continued modeling.Observe the changes in general physical signs,fecal water content,and calculate intestinal motility in each group of rats.Using HE staining to observe pathological changes in colon tissue,immunohistochemical methods were used to detect the protein expression of receptor tyrosine kinase(c-Kit),5-hydroxytryptamine(5-HT),5-hydroxytryptamine 3 receptor(5-HT3R),and 5-hydroxytryptamine 4 receptor(5-HT4R)in rat colon tissue.Results Compared with control group,frequency of defecation,fecal water content and intestinal propulsion speed of STC model rats were significantly decreased.The expression levels of proteins such as c-Kit,5-HT,5-HT3R,and 5-HT4R in intestinal tissues were significantly reduced in STC model rats.Compared with STC model group,rats treated with low,medium and high doses of live combined bifidobacterium and lactobacillus tablets and positive drug groups showed a significant increase in bowel frequency,fecal water content,and intestinal motility after intervention.Compared with STC model group,frequency of defecation,fecal water content,intestinal propulsion rate and protein expression of c-Kit,5-HT,5-HT3R and 5-HT4R in rat intestinal tissues were significantly increased after intervention of live combined bifidobacterium and lactobacillus tablets low,medium and high dose groups.Conclusion This study confirms that probiotic preparation live combined bifidobacterium and lactobacillus tablets effectively improves slow transit constipation by promoting the proliferation of Cajal interstitial cells in the colon,increasing the expression of 5-HT,5-HT3R,and 5-HT4R,enhancing intestinal peristalsis,and achieving the therapeutic effect on STC rats.

Objective To investigate the expression status of A Disintegrin and Metalloproteinase with Thrombospondin motifs 5(ADAMTS5 )and its clinical significance in primary human gastric cancer(GC). Meth-ods ADAMTS5 protein expression in 176 GC tissues and 24 adjacent normal tissues was detected by immunohisto-chemistry(IHC),and its correlation to clinicopathological features and prognosis in patients with gastric cancer was analyzed. Results ADAMTS5 expression was lower in GC tissues compared with adjacent normal tissues. Moreover,low expression of ADAMTS5 was associated with gender,histologic type,degree of differentiation,M stage,TNM stage and vascular invasion,which was also an independent indicator for poor prognosis for GC pa-tients. Conclusions ADAMTS5 expression was lower in GC tissues,which was associated with clinicopathological features and prognosis,suggesting a novel potential prognostic indicator and therapeutic target in GC.

Objective To investigate the effect of a disintegrin and metalloprotease domain(ADAM8)gene on colon cancer HCT8 cell proliferation and proliferation signal transduction pathways PI3K-Akt-mTOR. Methods Colon cancer HCT8 cells were cultured in vitro,and transfected with ADAM8 overexpression plasmid and RNA interfering plasmid. Cell proliferation were detected by EdU and MTS method assays. PI3K activity was measured by PI3K activity detection kit,Western Blot method was performed to detect the ratio of Akt and p-Akt and expression of mTOR. Results Compared with control group(1.00 ±0.12),the cell proliferation in ADAM8 overexpression group(1.22 ±0.13)was significantly higher (P<0.05)and in RNA interfering group(0.78 ±0.11)was significantly lower while PI3K activity had no significant changes in three groups. After ADAM8 overexpression,and the ratio of p-Akt/Akt and mTOR expression were increased significantly,while reduced significantly after RNA interferered. Conclusion ADAM8 can promote HCT8 cell proliferation through enhancing the phosphorylation of Akt and promoting the expression of mTOR.