Astragalus membranaceus Polysaccharide Regulates Small Intestinal Microbes and Activates IL-22 Signal Pathway to Promote Intestinal Stem Cell Regeneration in Aging Mice.

Aging can cause degenerative changes in multiple tissues and organs. Gastrointestinal diseases and dysfunctions are common in the elderly population. In this study, we investigated the effects of Astragalus membranaceus polysaccharide (APS) and Astragalus membranaceus ethanol extract (AEE) on age-related intestinal dysfunction and gut microbiota dysbiosis in naturally aging mice. The energy expenditure and physical activity of 23-month-old C57BL6/J mice were recorded using a metabolic cage system. Pathological changes in the intestine were evaluated using Alcian blue staining. The protein levels of leucine-rich repeats containing G protein-coupled receptor 5 (Lgr5) and Stat3 in the small intestine were determined using immunohistochemistry. The intestinal cell migration distance was assessed using bromodeoxyuridine (BrdU) immunofluorescence staining. The gene transcription levels of intestinal stem cell (ISC) markers and ISC-related signaling pathways were detected using quantitative real-time PCR (qRT-PCR). Microbiota analysis based on 16S rDNA was performed to evaluate the composition of the gut microbiota. APS and AEE improved a series of aging phenotypes in female but not in male aging mice. APS and AEE ameliorate intestinal dysfunction and histopathological changes in aging mice. APS had a more significant anti-aging effect than AEE, particularly on intestinal dysfunction. APS promotes ISC regeneration by activating the IL-22 signaling pathway. Cohousing (CH) experiments further confirmed that APS induced the IL-22 signaling pathway by increasing the abundance of Lactobacillus, thereby promoting the regeneration of ISCs. Our results show that APS may serve as a promising agent for improving age-related intestinal dysfunction.

Malignant melanoma of the prostate: Primary or metastasis? A case report.

BACKGROUND: Malignant melanoma of the prostate is rare. Twenty-five studies describing 45 cases have been reported. Prostate melanoma is characterized by an insidious onset and poor prognosis. The prognosis and treatment vary according to primary or secondary melanoma. CASE SUMMARY: A 75-year-old man attended the hospital due to low back pain of 2 mo duration. He denied a history of trauma or abnormal urinary symptoms. Digital rectal examination showed indentation in the left lobe of the prostate, 1 cm in diameter. His prostate-specific antigen was 5.6 ng/mL and 18F-fluorodeoxyglucose positron emission tomography computed tomography (18F-FDG-PET/CT) showed focal glucose metabolism in the left lobe. Imaging showed bone metastases to T12 and bilateral ribs. Transperineal prostate biopsy was done and three tissue specimens on the left side showed prostate adenocarcinoma (Gleason score 3 + 3 = 6), but the specimen on the right side showed malignant melanoma. The patient underwent T12 tumor resection and pathology findings indicated metastatic malignant melanoma. The patient underwent gastroscopy and colonoscopy, and gastroscopy revealed multiple mucosal black spots in the gastric body and fundus. The patient was diagnosed with secondary malignant prostate melanoma and primary gastric disease. CONCLUSION: Diagnosis of primary prostate melanoma requires caution and 18F-FDG-PET/CT may result in false-negative detection of melanoma.

IL-10-dependent Effect of Chinese Medicine Abelmoschus manihot on Alleviating Intestinal Inflammation and Modulating Gut Microbiota.

Inflammatory bowel disease (IBD) is a recurrent disease associated with a potential risk of colorectal cancer. Abelmoschus manihot (AM), a Chinese herbal medicine, is known to alleviate IBD. However, its mechanism of action requires further clarification. Here, we focused on the role of IL-10 and the gut microbiota in the mechanism of action of AM. The effects of AM on intestinal inflammation, mucus production, and gut microbes were evaluated in dextran sodium sulfate (DSS)-induced acute and chronic IBD models and in IL-10-deficient mice (IL-10[Formula: see text]). AM exhibited protective effects on acute and chronic models of IBD in wild-type mice by restoring body weight and colon length, promoting IL-10 secretion, and decreasing TNF-[Formula: see text] levels. Moreover, AM alleviated inflammatory infiltration, increased mucin 2 transcription, and increased the number of goblet cells in the colon. On the contrary, these effects were diminished in IL-10[Formula: see text] mice, which implied that the effect of AM on intestinal inflammation is IL-10-dependent. A gut microbial sequencing analysis showed that gut microbial dysbiosis was modulated by AM intervention. The regulatory effects of AM on Eggerthellaceae, Sutterellaceae, Erysipelotrichaceae, Burkholderiaceae, Desulfovibrionaceae, and Enterococcaceae were dependent on IL-10. These results revealed that AM ameliorated IBD and modulated gut microbes by promoting IL-10 secretion, indicating that AM has the potential to improve IBD and that AM is IL-10-dependent.

Potential roles of gut microbiota and microbial metabolites in chronic inflammatory pain and the mechanisms of therapy drugs.

Observational findings achieved that gut microbes mediate human metabolic health and disease risk. The types of intestinal microorganisms depend on the intake of food and drugs and are also related to their metabolic level and genetic factors. Recent studies have shown that chronic inflammatory pain is closely related to intestinal microbial homeostasis. Compared with the normal intestinal flora, the composition of intestinal flora in patients with chronic inflammatory pain had significant changes in Actinomycetes, Firmicutes, Bacteroidetes, etc. At the same time, short-chain fatty acids and amino acids, the metabolites of intestinal microorganisms, can regulate neural signal molecules and signaling pathways, thus affecting the development trend of chronic inflammatory pain. Glucocorticoids and non-steroidal anti-inflammatory drugs in the treatment of chronic inflammatory pain, the main mechanism is to affect the secretion of inflammatory factors and the abundance of intestinal bacteria. This article reviews the relationship between intestinal microorganisms and their metabolites on chronic inflammatory pain and the possible mechanism.

[Effect of Salviae Miltiorrhizae Radix et Rhizoma on diversity of intestinal flora in diabetic nephropathy rats].

This study aimed to explore the effect of Salviae Miltiorrhizae Radix et Rhizoma, its stems and leaves on the diversity of intestinal microflora in rats with diabetic kidney injury. Diabetic rats model was established by feeding high glucose and high fat diet and 5% glucose solution with intraperitoneal injection of 30 mg·kg~(-1) streptozocin(STZ). The rats were randomly divided into normal group, model group, irbesartan control group, Huangkui Capsules control group, as well as low, middle and high dose groups of Sal-viae Miltiorrhizae Radix et Rhizoma, its stems and leaves. After administration for 2 weeks, 16 S rRNA technique was used to analyze the diversity of intestinal microflora in the feces of each group. The results showed rats in the model group developed renal tubular epithelial vacuole degeneration and a large amount of inflammatory cell infiltration in the renal interstitium. A small amount of inflammatory cell infiltration was seen in each administration group. The kidney structure of rats in irbesartan group, Huangkui Capsules group, high-dose group of Salviae Miltiorrhizae Radix et Rhizoma and its stem water extract, as well as high dose group of Salviae Miltiorrhizae Radix et Rhizoma and its stem ethnol extract group was close to the normal group. The diversity and structure of intestinal flora in the model group were significantly different from those in the normal group. Each administration group improved the fecal flora diversity in rats with diabetic kidney injury to a certain extent, especially the high dose of Salviae Miltiorrhizae Radix et Rhizoma and its stems water extract. Different flora were found in feces of diabetic nephropathy model rats on class, order, family and genus levels. On families and genera levels, the relative abundance of Bifidobacterium, Turicibacter, Peptostreptococcaceae, Desulfovibrio, and SMB53 showed an upward trend in model group, but that of Lactobacillus, Clostridium, Rikenella, Rumen fungi showed a downward trend. The administration groups can improve the relative abundance of the above intestinal flora in the model rats to a normal-like level. The results of this study provide a reference for resource utilization and further development of Salviae Miltiorrhizae Radix et Rhizoma.

Salvia miltiorrhiza stems and leaves total phenolic acids combination with tanshinone protect against DSS-induced ulcerative colitis through inhibiting TLR4/PI3K/AKT/mTOR signaling pathway in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza Bge. as a traditional Asian medicinal plant, roots and rhizomes (Danshen) are used to treat chronic hepatitis and coronary heart disease. In recent years, the medicinal value of S. miltiorrhiza stems and leaves total phenolic acids extract (JF) similar to roots and rhizomes has received increasing attention. S. miltiorrhiza roots and rhizome tanshinone extract (DT) has a good anti-inflammatory effect. AIM OF THE STUDY: To explore the therapeutic effect and possible molecular mechanisms of JF and DT alone or in combination on dextran sulfate sodium (DSS)-induced colitis mice. MATERIALS AND METHODS: Colitis was induced by received 2% DSS in drinking water for 7 consecutive days. Then mice were administered orally for 7 days. Disease activity index (DAI) scores and body weight were recorded daily. After the end of the experiment, colon was removed, colon length was measured and histopathological analysis was performed. Inflammatory factors expression was determined by ELISA, its mRNA expression was detected by real-time quantitative PCR, and the expression of related proteins on TLR4/PI3K/AKT/mTOR signal was analyzed by Western blot. RESULTS: Treatment with JF and DT alone or in combination reduced DAI scores, increase body weight, improved colon shortening, and decreased colon histology scores. In addition, the expression level of inflammatory factors was inhibited. The combination of JF and DT had a better inhibitory effect on inflammatory factors compared to JF alone. We also found that DT alone and JF combined with DT inhibited TLR4/PI3K/AKT/mTOR signaling-related proteins expression levels (including TLR4, p-PI3K p110α/PI3K p110α, p-AKT (ser473)/AKT, mTOR, p-mTOR, NF-κB p65), showing an effective anti-inflammatory effect. CONCLUSIONS: We demonstrated for the first time that, JF and DT alone or in combination effectively ameliorated DSS-induced ulcerative colitis in mice, possibly by inhibiting the TLR4/PI3K/AKT/mTOR signaling pathway.

Endovascular and hybrid treatments for subclavian artery aneurysms.

OBJECTIVE: This paper retrospectively reviews our experience with endovascular and hybrid treatments for subclavian artery aneurysms (SAA). METHODS: Seventeen patients with SAAs were treated at our center between July 2011 and October 2018. Clinical and follow-up data were extracted from the hospital records and retrospectively reviewed. We routinely use endovascular treatments and stenting or axillary-axillary bypass to treat SAA if vertebral artery blood flow requires restoration. Patients were followed up at 3, 6, and 12 months after their operations and yearly thereafter. RESULTS: Median follow-up was 30.5 months. In 6 patients, the SAAs involved the ipsilateral vertebral artery. Simple coil embolization was performed for 1 patient; endovascular covered stenting and coil embolization for 4 patients; and hybrid treatment for 1 patient. In 11 patients, the SAAs did not involve the ipsilateral vertebral artery. Hybrid treatment was performed for 1 patient; thoracic aortic stent implantation with coil embolization for 1 patient; and covered stent placement in the subclavian artery for 9 patients. Among the 9 patients who were symptomatic at presentation, 8 had relief of symptoms. Leakage was observed in 1 patient, but it stopped spontaneously. Stent occlusion occurred in 18.8% (3/16), but all were asymptomatic, and no interventions were necessary. CONCLUSION: Endovascular and hybrid treatments appear to be effective for SAAs with few complications and good clinical outcomes. KEY WORDS: Covered stent, Coil embolization, Endovascular treatment, Hybrid, Subclavian artery aneurysm.

Prognostic Value of Vimentin Is Associated With Immunosuppression in Metastatic Renal Cell Carcinoma.

Introduction: Vimentin, a classical marker of epithelial-mesenchymal transition, reflects the invasiveness of cancer cells. Its role in the genesis and progression of tumor has been reported in various cancers, including renal cell carcinoma. However, the impact of vimentin on tumor microenvironment, particularly its implication with tumor-infiltrating immune cells, is unknown. Methods: We conducted this study in 231 patients with metastatic renal cell carcinoma (mRCC) to determine the potential relationship between vimentin and immune status. Using immunohistochemical staining, expression of vimentin, CD8, FOXP3, programmed cell death protein 1 (PD-1), and programmed cell death ligand 1 (PD-L1) were evaluated in resected tumor tissue. Kaplan-Meier analysis and Cox regression models were used for survival analysis. Chi-square test, Fisher exact test, and Mann-Whitney U-test were used for comparison between vimentin high and low groups. Results: High expression of vimentin, stroma PD-L1, and PD-1 indicated poor overall survival, whereas low regulatory T cell or high CD8+ T cell infiltration indicated long overall survival. Stroma PD-L1 (P = 0.030), vimentin (P = 0.026) expression, and CD8+ T cell infiltration (P < 0.001) were independent prognostic factors in mRCC. High vimentin expression was accompanied by high PD-1, PD-L1 expression, and increased regulatory T cell infiltration (all P < 0.001), indicating immunosuppression in the tumor microenvironment. Conclusions: We revealed that vimentin expression was associated with immunosuppression in mRCC, and the immune-suppressive status might be possibly posed by PD-1/PD-L1. Patients with high vimentin expression may acquire potential benefit from the recently approved PD-1/PD-L1 inhibitors. However, further clinical trials are needed to validate our findings.

Protective Effect and Mechanism of Boswellic Acid and Myrrha Sesquiterpenes with Different Proportions of Compatibility on Neuroinflammation by LPS-Induced BV2 Cells Combined with Network Pharmacology.

Frankincense and myrrha (FM), commonly used as a classical herbal pair, have a wide range of clinical applications and definite anti-inflammatory activity. However, anti-neuroinflammation effects and mechanisms are not clear. In this study, we adopted a lipopolysaccharide (LPS)-induced microglial (BV2) cell model and a network pharmacology method to reveal the anti-neuroinflammatory effects and mechanisms of boswellic acid (BA) and myrrha sesquiterpenes (MS) with different proportions of compatibility. The data showed that the different ratios of BA and MS had different degrees of inhibition of interleukin-1ß (IL-1ß), IL-6, and inducible nitric oxide synthase (iNOS) mRNA expression, down-regulated the phosphor-nuclear factor kappa B/nuclear factor kappa B (p-NF-Ò¡B)/(NF-Ò¡B), phosphorylated protein kinase b/protein kinase b (p-AKT/AKT), and Toll-like receptor 4 (TLR4) protein expression levels, and increased phospho-PI3 kinase (p-PI3K) protein expression levels. When the ratios of BA and MS were 10:1, 5:1, and 20:1, better effective efficacy was exhibited. According to the correlation analysis between the effect index and bioactive substances, it was suggested that 2-methoxy-5-acetoxy -fruranogermacr-1(10)-en-6-one (Compound 1), 3α-acetyloxylanosta-8,24-dien-21-oic acid (Compound 2), 11-keto-boswellic acid (Compound 3), and 3-acetyl-11-keto-ß -boswellic acid (Compound 4) made important contributions to the treatment of neuroinflammation. Furthermore, based on the network pharmacological analysis, it was found that these four active compounds acted on 31 targets related to neuroinflammation and were involved in 32 signaling pathways which mainly related to the immune system, cardiovascular system, and nervous system, suggesting that BA and MS could be used to treat neuroinflammation.

Comparison of Cosmetic Effect and Pain Reduction Outcomes of Modified Mini-Laparoscopy Versus Laparoendoscopic Single-Site Surgery for Adrenalectomy.

Objective: This study was to introduce the modified mini-laparoscopic adrenalectomy and investigate the advantage of operative time, cosmetic effect, and pain reduction by comparing the modified mini-laparoscopic adrenalectomy and laparoendoscopic single-site surgery (LESS). Methods and Patients: Between May 2015 and Jun 2018, 76 consecutive patients with adrenal tumor underwent laparoscopic adrenalectomy. Of which, 36 cases were in the mini-laparoscopic surgery group (the M group) and 40 cases in the LESS group. Medical records of the consecutive patients were analyzed. The operative time, blood loss, the Visual Analog Scale (VAS) scores and the Scar Cosmesis Assessment and Rating (SCAR) Scale scores were recorded. Results: The mean operative time in the M group was significantly less than that of in the LESS group (54.75 ± 9.37 min vs. 106.48 ± 19.71 min, P < .01). Mean estimated blood loss did not differ between the 2 groups (12.22 ± 5.29 mL vs. 10.80 ± 6.66 mL, P > .05). The mean VAS scores in the M group were significantly lower than those of the LESS group on postoperative days (POD) 1 and 3. The SCAR scale scores at POD 60 were similar in the M group and the LESS group (0.86 ± 0.64 vs. 0.95 ± 0.71, P > .05). Conclusions: Modified mini-laparoscopic adrenalectomy is safe and convenient. It offered less operative time, significant cosmetic benefit, and reduced incisional pain.

The mechanism of mulberry leaves against renal tubular interstitial fibrosis through ERK1/2 signaling pathway was predicted by network pharmacology and validated in human tubular epithelial cells.

Mulberry leaf was reported that it has antidiabetic activity, although the mechanisms underlying the function have not been fully elucidated. In the present study, the results of network pharmacology suggested that mulberry leaves could regulate key biological process in development of diabetes, and the process implicates multiple signaling pathways, such as JAK-STAT, MAPK, VEGF, PPAR, and Wnt. Then, the research in vitro indicated that mulberry leaves remarkably ameliorated high glucose-induced epithelial to mesenchymal transition, which was characterized with significant reduction of intracellular reactive oxygen species (ROS) levels as well as downregulation of NADPH oxidase subunits NOX1, NOX2, and NOX4, and it was found to be connected with the ERK1/2 signaling pathway in human tubular epithelial cells (HK-2). Moreover, the results of bioinformatics and the dual luciferase report showed that ZEB1 might be a target gene of miR-302a; decreased miR-302a and increased ZEB1 expressions could significantly promote epithelial to mesenchymal transition. However, mulberry leaves could reverse these modulations. Our results demonstrated that network pharmacology could provide a guidance role for traditional Chinese medicine research, and mulberry leaves could be of benefit in preventing high glucose-induced EMT in HK-2 cells, which proved that it was related to the upregulation of miR-302a by targeting ZEB1 and the inhibition of NADPH oxidase/ROS/ERK1/2 pathway.

Modified Mini-laparoscopic Surgery Optimized the Laparoscopic Decortication of Renal Cyst.

PURPOSE: This study was to introduce the modified mini-laparoscopic surgery for renal cyst and investigate itsadvantages on operative time, cosmetic effect and pain reduction by comparison with laparo-endoscopic single sitesurgery (LESS) and conventional laparoscopic surgery. METHODS AND PATIENTS: Between May 2015 and October 2018, 140 consecutive patients with benign renal cystunderwent laparoscopic decortication of renal cyst. Of which, 48 cases were in mini-laparoscopic surgery group(M group), 56 cases in LESS group and 36 cases in conventional laparoscopic surgery group (C group). The operativetime, blood loss, visual analog scale (VAS) and Scar Cosmesis Assessment and Rating (SCAR) Scale wasrecorded. RESULTS: The mean operative time in M group (26.08±7.70 min) and C group (28.56 ± 7.99 min). was significantlyless than that in LESS group (47.32 ±10.53 min) (P < 0.01). Mean blood loss did not differ between the 3 groups(P > 0.05). Mean VAS pain scores in M group were significantly lower than that of LESS group and C group onpostoperative day (POD) 1 and 3 (P < 0.01). The SCAR scale of POD 30 in C group (6.25 ± 1.0) was significantlyhigher than that in M group (0.77 ± 0.59) and LESS group (0.98 ± 0.70). The postoperative course was uneventfulwith no morbidity within 1to 6 months of follow-up. CONCLUSION: Modified mini-laparoscopic decortication of renal cyst have more comprehensive advantages comparingwith LESS and conventional laparoscopic surgery. It is convenient and offered significant cosmetic benefitand reduced incisional pain.

Aspiration therapy for acute embolic occlusion of the superior mesenteric artery.

BACKGROUND: Embolic superior mesenteric artery (SMA) occlusion is associated with high mortality rates. Delayed treatment often leads to serious consequences, including intestinal necrosis, resection, and even patient death. Endovascular repair is being introduced, which can improve clinical symptoms and prognosis and decrease the incidence of exploratory laparotomy. Many reports have described successful endovascular revascularization of embolic SMA occlusion. However, most of those reports are case reports, and there are few reports on Chinese patients. In this paper, we describe the technical and clinical outcomes of aspiration therapy using a guiding catheter and long sheath technique which facilitates the endovascular repair procedure. AIM: To evaluate the complications, feasibility, effectiveness, and safety of endovascular treatment for the acute embolic occlusion of the SMA. METHODS: This retrospective study reviewed eight patients (six males and two females) from August 2013 to October 2018 at Xuanwu Hospital, Capital Medical University. The patients presented with acute embolic occlusion of the SMA on admission and were initially diagnosed by computed tomography angiography (CTA). The patients who underwent endovascular treatment with a guiding catheter had no obvious evidence of bowel infarct. No intestinal necrosis was identified by gastrointestinal surgeons through peritoneal puncture or CTA. The complications, feasibility, effectiveness, safety, and mortality were assessed. RESULTS: Six (75%) patients were male, and the mean patient age was 70.00 ± 8.43 years (range, 60-84 years). The acute embolic occlusion of the SMA was initially diagnosed by CTA. All patients had undertaken anticoagulation primarily, and percutaneous aspiration using a guiding catheter was then undertaken because the emboli had large amounts of thrombus residue. No death occurred among the patients. Complete patency of the suffering artery trunk was achieved in six patients, and defect filling was accomplished in two patients. The in-hospital mortality was 0%. The overall 12-mo survival rate was 100%. All patients survived, and two of the eight patients had complications (the clot broke off during aspiration). CONCLUSION: Aspiration therapy is feasible, safe, and beneficial for acute embolic SMA occlusion. Aspiration therapy has many benefits for reducing patients' death, resolving thrombi, and improving symptoms.

Salvia miltiorrhiza protects against diabetic nephropathy through metabolome regulation and wnt/ß-catenin and TGF-ß signaling inhibition.

Diabetic nephropathy (DN) is a complication of diabetes that is caused by uncontrolled high blood sugar. It has been reported that Salvia miltiorrhiza (SM) possesses the ability to prevent kidney damage, although the mechanisms remain unclear. The study was to investigate whether and how SM improved DN injury via regulation of metabolome and the molecular mechanisms. In this study, SD rats were fed a high glucose / high fat diet accompanied by 0.5% glucose water. Three weeks later, the rats were given one intraperitoneal injection of 30 mg/kg STZ each day for three days for DN model. The biochemical indicators and metabolomics of plasma, urine and renal tissue were analyzed. Then the western blotting analysis of renal tissue and glomerular mesangial cells were investigated. The results showed that Salvia miltiorrhiza extracts improved the renal injury and regulation of abnormal glycolipid metabolism. The metabolites in serum, urine and renal tissues have been changed significantly. The involved metabolic pathways mainly include phospholipid, arachidonic acid, and pyrimidine metabolisms. Meanwhile, SM inhibited the relative expression levels of wnt4, ß-catenin and TGF-ß in renal tissue and high-glucose induced glomerular mesangial cells.

Immunoscore System for Predicting Clinical Outcome of Metastatic Renal Cell Carcinoma Patients Treated with Tyrosine Kinase Inhibitors.

We conducted this study to determine whether immunoscore system (IS) predicts survival in patients with metastatic renal cell carcinoma (mRCC). A total of 218 mRCC patients treated with sunitinib or sorafenib in Zhongshan Hospital, Fudan University were recruited during 2007-2017, retrospectively. CD8, CD4, Treg, PD-1 and PD-L1 expression were evaluated by immunohistochemical staining of paraffin embedded slide. Kaplan-Meier method and COX regression model were used in survival analyses. Multivariate analyses demonstrated that expressions of CD8, Treg, PD-1 and stromal PD-L1 (sPD-L1) expressions were independent predictive factors for OS, thus IS was established containing these four immunological factors. Subsequent analysis revealed that performance of IS provided good differentiation of OS and PFS. Besides, multivariate analysis identified IS as an independent prognostic factor for OS (p<0.001) and PFS (p=0.002). IS, compared with International mRCC Database Consortium (IMDC) risk model, and provided better prediction ability for OS. Results suggested that IS was a powerful prognostic factor for OS and PFS in patients with mRCC treated with tyrosine kinase inhibitors. And IS can be used as essential supplement to IMDC for outcome prediction in mRCC patients.

Polysaccharides From Chrysanthemum morifolium Ramat Ameliorate Colitis Rats via Regulation of the Metabolic Profiling and NF-κ B/TLR4 and IL-6/JAK2/STAT3 Signaling Pathways.

Studies have indicated that Chrysanthemum polysaccharides (CP) could prominently ameliorate colitis rats, but its possible mechanism remains unclear. In this study, the underlying mechanism of CP was explored by the metabolic profiling analysis and correlated signaling pathways. TNBS/ethanol induced colitis was used to investigate the intervention efficacy following oral administration of CP. The levels of cytokines such as TNF-α, IL-6, IFN-γ and IL-1ß, and the activities of SOD, MPO, and MDA were determined. We also performed western-blot for p65, TLR4, p-JAK2, and STAT3 protein expression in the colon tissue to probe their mechanisms of correlated signaling pathways. What's more, the metabolic changes in plasma and urine from colitis rats were investigated based on UPLC-Q-TOF/MS combined with MetabolynxTM software. The potential biomarkers and metabolic pathways were also tentatively confirmed. The metabolic profiles of plasma and urine were clearly improved in model rats after oral administration of CP. Thirty-two (17 in serum and 15 in urine) potential biomarkers were identified. The endogenous metabolites were mainly involved in linoleic acid, retinol, arachidonic acid, glycerophospholipid and primary bile acid metabolism in plasma, and nicotinate and nicotinamide, ascorbate and aldarate, histidine and ß-alanine metabolism in urine. After polysaccharides intervention, these markers turned back to normal level at some extent. Meanwhile, the elevated expression levels of pp65, TLR4, p-STAT3, and p-JAK2 were significantly decreased after treatment. Results suggested that CP would be a potential prebiotics for alleviation of TNBS-induced colitis. The study paved the way for the further exploration of the pathogenesis, early diagnosis and curative drug development of the colitis.

[Incompatible mechanism of compatibility of Chinese medicines based on Qianjinzi and Gancao effect on intestinal flora/barrier system].

The study was based on the toxic characteristics of the compatibility between "Zaojisuiyuan" and Gancao, with intestinal tract and intestinal bacteria as subject. From the angle of intestinal barrier function, motor function, steady state of intestinal flora and metabolism genes, the toxic and side effects of the compatibility between Qianjinzi and Gancao with similar properties, bases and chemical composition and types were further explored. The results showed that the combined application of Qianjinzi and Gancao enhanced intestinal mucosa damage, and led to abnormal changes in intestinal bacteria structure and metabolic function. It improved the degradation functions of mucus and aromatic amino acids on intestinal bacteria, which may increase the risk of disease and derived from intestinal urotoxin and other toxic substances. This study considered intestinal bacteria as an important target to study the interactions of traditional Chinese medicine. The "drug-intestinal bacteria-metabolism-toxicity" was applied in the experiment. Meanwhile, it provides ideas for exploring incompatible mechanism of traditional Chinese medicines.

[Pharmacokinetics of Mori Folium flavones and alkaloids in normal and diabetic rats].

To study the pharmacokinetic effect of Mori Folium flavones and alkaloids in normal and diabetic rats. An UPLC-TQ-MS method was developed for the simultaneous determination of rutin, isoquercitrin, astragalin, kaempferol, quercetin, chlorogenic acid, cryptochlorogenic acid, neochlorogenic acid, DNJ and fagomine in plasma of rats. The diabetic rat model was induced through intravenous injection with alloxan and high-fat diet. Samples of plasma of rats were obtained at different time points, after the rats were administrated with Mori Folium flavones and alkaloids. After the deproteinization with acetonitrile, the concentrations of Mori Foliam constituents in rats at different time points were detected by UPLC-TQ-MS method, and pharmacokinetic parameters were calculated by DAS 2.0 software. The results showed that quercetin and kaempferol reached peak at 0.333 h, indicating that Mori Folium flavonoid constituents were absorbed and distributed quickly. At about 4 h after administration, both of them reached the peak concentrations for the second time, suggesting that they stayed in intestine for a long time. DNJ and fagomine in gastrointestinal tract can be quickly absorbed into blood, and the concentration in plasma reached peak after 0.667 h, suggesting that both of them could be rapidly distributed in the systemic circulation of rats. Cryptochlorogenic acid, neochlorogenic acid, quercetin, kaempferol and rutin were found to have a higher Cmax and AUC0-t in normal rats than those in diabetic rats. The t1/2values of cryptochlorogenic acid and neochlorogenic acid were shorter in diabetic rats, while quercetin, kaempferol and rutin had a longer t1/2value in diabetic rats. Chlorogenic acid, astragalin, isoquercitrin, fagomine had a higher Cmax in diabetic rats, and the t1/2values of astragalin and fagomine were longer, which suggested differences in absorption of active ingredients under normal and diabetic conditions.

A Comprehensive Strategy to Evaluate Compatible Stability of Chinese Medicine Injection and Infusion Solutions Based on Chemical Analysis and Bioactivity Assay.

Stability of traditional Chinese medicine injection (TCMI) is an important issue related with its clinical application. TCMI is composed of multi-components, therefore, when evaluating TCMI stability, several marker compounds cannot represent global components or biological activities of TCMI. Till now, when evaluating TCMI stability, method involving the global components or biological activities has not been reported. In this paper, we established a comprehensive strategy composed of three different methods to evaluate the chemical and biological stability of a typical TCMI, Danhong injection (DHI). UHPLC-TQ/MS was used to analyze the stability of marker compounds (SaA, SaB, RA, DSS, PA, CA, and SG) in DHI, UHPLC-QTOF/MS was used to analyze the stability of global components (MW 80-1000 Da) in DHI, and cell based antioxidant capability assay was used to evaluate the bioactivity of DHI. We applied this strategy to assess the compatible stability of DHI and six infusion solutions (GS, NS, GNS, FI, XI, and DGI), which were commonly used in combination with DHI in clinic. GS was the best infusion solution for DHI, and DGI was the worst one based on marker compounds analysis. Based on global components analysis, XI and DGI were the worst infusion solutions for DHI. And based on bioactivity assay, GS was the best infusion solution for DHI, and XI was the worst one. In conclusion, as evaluated by the established comprehensive strategy, GS was the best infusion solution, however, XI and DGI were the worst infusion solutions for DHI. In the compatibility of DHI and XI or DGI, salvianolic acids in DHI would be degraded, resulting in the reduction of original composition and generation of new components, and leading to the changes of biological activities. This is the essence of instability compatibility of DHI and some infusion solutions. Our study provided references for choosing the reasonable infusion solutions for DHI, which could contribute the improvement of safety and efficacy of DHI. Moreover, the established strategy may be applied for the compatible stability evaluation of other TCMIs.