Primary study on the effects and mechanisms of separate and combined decoctions of Scutellaria baicalensis Georgi - Coptis chinensis Franch extracts in relieving acute alcoholic liver injury in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Scutellaria baicalensis Georgi (SBG) and Coptis chinensis Franch (CCF) are traditional herbal medicine pairs used for clearing heat and eliminating dampness, stopping diarrhea, and detoxification. Traditionally, these two herbs are combined and decocted together, but the modern preparation procedures separate them to avoid the large amount of precipitation generated from co-decoction. Thus, a conflict lies between the traditional and modern extraction processes of Scutellaria baicalensis Georgi - Coptis chinensis Franch (SBG-CCF). AIM OF STUDY: There is a conflict between traditional medical practices of SBG-CCF and the modern formulation industry. In this study, we investigated the differences in the effects and mechanisms of SBG-CCF extracted by decocting separately and combining decoctions, as well as the scientific effectiveness of traditional and modern treatment methods on both. Acute alcoholic liver injury (ALI) rats were used as the pathological model. MATERIALS AND METHODS: SD rats were divided into 8 groups, including blank group, model group, low, medium, and high dose groups of SBG-CCF separated decoction, low, medium, and high dose groups of SBG-CCF combined decoction. Acute alcoholic liver injury model was induced in rats by gradually increasing the dose of alcohol through gavage everyday using white wine with an alcohol content 52%. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), triglyceride (TG), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH) were used as indicators to assess the intervention effect of SBG-CCF. And the potential active ingredients of SBG-CCF and the targets related to ALI were screened using network pharmacology, and the prediction results of network pharmacology were verified by quantitative real-time fluorescence PCR (qRT-PCR). RESULTS: SBG-CCF decoction alone and six combinations of decoctions have different degrees of improvement on alcoholic liver injury, with significant efficacy in the middle-dose group, and the combined decoction was superior to the individual decoction. SBG-CCF gavage can reduce the activity of AST, ALT, TC, TG, LDH, and MDA in the serum and liver of ALI rats, while increasing the levels of SOD and GSH. Network pharmacological analysis identified 39 active components, mainly flavonoids and alkaloids. Enrichment analysis suggested that SBG-CCF may treat ALI through the regulation of tumor necrosis factor (TNF), mitogen-activated protein kinase (MAPK), interleukin-17 (IL-17), apoptosis, and the Toll-like receptor signaling pathways. The key targets in the Disease-Signaling Pathway-Target Network were MAPK8, IKBKB, MAPK10, MAPK3, MAPK1, and AKT1. qRT-PCR results indicated that targets regulating inflammation and lipid metabolism are MAPK8, MAPK10, MAPK3, and AKT1. CONCLUSION: SBG-CCF separately extracts and combines decoction can alleviate acute alcoholic liver injury, and the effect of combined decoction is more significant than separate decoction, implying that the precipitate produced by the combination of the two is also an active substance. The resistance mechanism of SBG-CCF ALI may be related to the modulation of lipid metabolism, inhibition of lipid peroxidation, and oxidative stress. SBG-CCF has the characteristics of multi-component, multi-pathway, and multi-target resistance to ALI.

Research on the effectiveness and material basis of Ligusticum chuanxiong in alleviating acute liver injury.

ETHNOPHARMACOLOGICAL RELEVANCE: As an effective medicinal plant, Ligusticum chuanxiong (L. chuanxiong) is traditionally used in China to treat various kinds of dysesthesia caused by liver qi stagnation, chest paralysis and heart pain caused by liver blood stagnation, and bruises and injuries caused by blood stasis. Recent research has confirmed the efficacy of L. chuanxiong in treating liver injury. AIM OF THE STUDY: L. chuanxiong has significant hepatoprotective effects, but its material basis and mechanism of action are still ambiguous. This work was to reveal the potential active ingredients (parts) of L. chuanxiong for liver protection and to investigate the pharmacological mechanism of its liver protection. MATERIALS AND METHODS: The hepatoprotective substance basis and mechanism of L. chuanxiong were investigated using network pharmacology, and the active components of L. chuanxiong extract were studied using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) analytical techniques. Molecular docking was adopted to verify the interaction between the active ingredients in L. chuanxiong and the key targets involved in liver injury. To confirm the hepatoprotective effects of the effective part in L. chuanxiong, a carbon tetrachloride (CCl4)-induced acute liver injury model in mice was used. RESULTS: As a result, network pharmacological analysis techniques were used to screen out potential active ingredients such as ferulic acid, caffeic acid, and p-coumaric acid, which were concentrated in the organic acid site and acted on 19 key targets related to liver protection. The biological process involved the positive regulation of nitric oxide biosynthesis, and various signaling pathways were implicated, including the Toll-like receptor signaling pathway, the NOD-like receptor signaling pathway, the TNF signaling pathway, and others. LC-MS and GC-MS qualitatively analyzed the effective components from L. chuanxiong extract, and 50 active components were identified. The molecular docking of key components with the core targets showed good activity, which validated the predicted results. In the final analysis, a mouse model of acute liver injury induced by CCl4 further verified the greater protective effect of the organic acid fraction of L. chuanxiong on liver injury in mice compared with other parts. CONCLUSION: The results reveal that L. chuanxiong may relieve liver damage, and the organic acids were the main active part in it. Its mechanism of alleviating liver injury is related to positive regulation of nitric oxide biosynthesis, the Toll-like receptor signaling pathway, the NOD-like receptor signaling pathway, the TNF signaling pathway, and so on.

Preliminary study on the effective site and mechanism of action of Meconopsis quintuplinervia Regel in alleviating acute alcoholic liver injury in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Meconopsis quintuplinervia Regel (MQR) belongs to the opium poppy tree plant species, and it has heat purging, detoxification, diuretic, anti-inflammatory, and analgesic effects. AIM OF STUDY: MQR has liver-protective properties and can alleviate liver heat. Therefore, this study aimed to observe the effect of MQR extract on acute alcoholic liver injury in mice and explore the mechanism of action of ethyl acetate extract of MQR (MQR-E) on alcohol-induced liver injury in combination with the network pharmacology. MATERIALS AND METHODS: To induce acute alcoholic liver injury, 52% of edible wine was administered at 12 mL/kg for 14 days. The pharmacodynamic results were used to screen the active site. MQR-E composition was analyzed based on UPLC-Q-TOF-MS, and relevant MQR-E and alcoholic liver disease (ALD) targets were screened using an online database. Then, Venn analysis of drug and disease-related targets was performed to obtain cross-targets. We investigated the protein-protein interaction network (PPI) of overlapping targets, the core targets were screened using the STRING database, and the DAVID database was chosen for GO and KEGG enrichment analysis of the central targets. RESULTS: Each of the four MQR extracts ameliorated alcoholic liver injury to varying degrees; the best results were achieved with MQR-E. MQR-E reduces liver index, serum transaminases, and fat accumulation, and attenuates ethanol-induced histopathological changes. The activities of hepatic superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) were increased, the content of malondialdehyde (MDA) was significantly reduced compared to the EtOH group, and MQR-E effectively mitigated the oxidative stress induced by ethanol in the liver. Thirty-six compounds were identified, and flavonoids were the most abundant. PPI network topology analysis was employed to assess 32 core targets: IL-6, TNF, STAT3, PPARA, and other inflammation and lipid metabolism related genes. Pathway analysis of GO and KEGG enrichment showed that the regulation of inflammatory factors and lipid metabolism were primarily involved. CONCLUSION: We concluded that MQR-E had protective effects against acute alcohol-induced liver injury in mice, and the mechanism could be linked to the inhibition of lipid peroxidation and oxidative stress. The mechanism by which MQR-E ameliorated ALD primarily involved regulating inflammatory factors and lipid metabolism based on the prediction of the network pharmacology.

Antioxidant effects of Se-glutathione peroxidase in alcoholic liver disease.

Oxidative damage induced by ethanol and its metabolites is one of the factors that fuels the development of alcoholic liver disease (ALD). Selenium (Se) is an effective cofactor for glutathione peroxidase (GPx), and has antioxidant effects that improve ALD. In patients with ALD, ethanol-induced oxidative damage inhibits the synthesis of related Se-containing proteins such as: selenoprotein P (Sepp1), albumin (ALB), and GPx in the liver, thus decreasing the overall Se level in patients. Both Se deficiency and excess can affect the expression of GPx, resulting in damage to the antioxidant defense system. This damage enhances oxidative stress by increasing the levels of reactive oxygen species (ROS) in the body, which aggravates the inflammatory response, lipid metabolism disorder, and lipid peroxidation and worsens ALD symptoms. A cascade of oxidative damages caused by ALD will deplete selenium deposition in the body, stimulate the expression of Gpx1, Sepp1, and Gpx4, and thus mobilize systemic selenoproteins, which can restore GPx activity in the hepatocytes of ALD patients, reduce the levels of reactive oxygen species and alleviate oxidative stress, the inflammatory response, lipid metabolism disorder, and lipid peroxidation, thus helping to mitigate ALD. This review provides a reference for future ALD studies that evaluate the regulation of Se levels and contributes to studies on the potential pathological mechanisms of Se imbalance in ALD.

Variation in the Efficacy of Anti-Ulcerative Colitis Treatments Reveals the Conflict Between Precipitating Compatibility of Traditional Chinese Medicine and Modern Technology: A Case of Scutellaria-Coptis.

Scutellariae and Coptidis compose a classical drug pair applied in clinical practice to dispel heat, dryness, and dampness, and they are also precipitation compatible drug pairs. With modern technology, Scutellaria-Coptis is mostly prepared by decocting its components separately, while in the traditional method, it is predominantly prepared as a combined decoction. The present study investigated the effects and mechanisms of separate and combined application of Scutellaria-Coptis decoction on ulcerative colitis (UC) in mice induced by the administration of dextran sulfate sodium (DSS). Changes in body weight, colon length, and Disease Activity Index scores were also evaluated. Hematoxylin and eosin staining and other methods were used to evaluate the overall condition of animals in each group. Intestinal microflora was analyzed using 16S rRNA sequencing, while colon inflammation and antioxidant capacity were evaluated based on the levels of interleukin-6 (IL-6), IL-10, IL-1ß, tumor necrosis factor-α, superoxide dismutase, malondialdehyde, and reduced glutathione. The results revealed that Scutellaria-Coptis significantly relieved colon inflammation in mice, and the combined decoction of Scutellaria-Coptis exerted a significant effect on UC. Notably, the protective effect of Scutellaria-Coptis against colon inflammation was weakened when the antibiotic mixture was partially consumed by the gut microbiota. The results of 16S rRNA sequencing showed that the group treated with combined decoction of Scutellaria-Coptis exhibited a higher intestinal microbial diversity and intestinal flora composition than the separated decoction group. Treatment of mice with UC by administering Scutellaria-Coptis decoction through intestinal flora removal (ABX) and fecal microbial transplantation (FMT) was closely associated with intestinal flora composition. In conclusion, Scutellaria-Coptis can relieve UC with an excellent effect especially when taken as a combined decoction, alleviating colon inflammation incurred by intestinal microbes to a certain extent.

[Powder modificationfor improving content uniformity of Ziyin Yiwei Capsules].

Based on the defects in powder properties of the contents of Ziyin Yiwei Capsules, this study screened out the main medicinal slice powders causing the poor powdery properties, and introduced the powder modification process to improve the powdery properties of these slice powders, the pharmaceutical properties of the capsule contents, and the content uniformity of Ziyin Yiwei Capsules, so as to provide a demonstration for the application of powder modification technology to the preparation of Chinese medicinal solid preparations. Through the investigation on the powder properties of the contents of Ziyin Yiwei Capsules, it was clarified that the pulverized particle size of the capsule contents had a good correlation with the pulverization time. According to the measurement results of the powder fluidity and wettability, the quality defects of the capsule contents were caused by the fine powders of Taraxaci Herba and Lungwortlike Herba. "Core-shell" composite particles were prepared from medicinal excipients magnesium stearate and fine powders of Taraxaci Herba and Lungwortlike Herba slices after ultra-fine pulverization to improve the powder properties of the problematic fine powders. Powder characterization data including fluidity and wettability were measured, followed by scanning electron microscopy(SEM) and infrared ray(IR) detection. It was determined that the optimal dosage of magnesium stearate was 2%, and the compositing time was 3 min. The composite particles were then used as content components of the Ziyin Yiwei Capsules. The powder characteristics between the original capsule and the modified composite capsule including the particle size, fluidity, wettability, uniformity of bulk density, and uniformity of chromatism as well as the content uniformity and in vitro dissolution were compared. The results showed that the powder characteristics and content uniformity of the prepared composite capsule were significantly improved, while the material basis of the preparation was not changed before and after modification. The preparation process was proved to be stable and feasible. The powder modification technology solved the pharmaceutical defects that were easy to appear in the preparation of traditional capsules, which has provided experimental evidence for the use of powder modification technology for improving the quality of Chinese medicinal solid preparations and promoting the secondary development and upgrading of traditional Chinese medicinal dosage forms such as capsules.

In vitro Preparation and Evaluation of Sustained-Release Microcapsules of Salvianolic Acid.

OBJECTIVE: This study aims to investigate the preparation of sustained-release microcapsules of salvianolic acid. METHODS: The stability of salvianolic acid microcapsules was improved, and the time of action was prolonged in the present study. This was prepared using the spray-drying method, with chitosan as the carrier. In the preparation process, the prescription and process were optimized by L9 (34) using an orthogonal design, with yield and drug loading as indexes, in order to obtain optimum conditions. RESULTS: The optimal process and prescription for the preparation of salvianolic acid microcapsules were found to be as follows: mass concentration of chitosan, 1.5%; mass ratio of salvianolic acid to chitosan, 1:3; inlet air temperature, 190°C; and peristaltic pump speed, 300 mL·h-1. The surface of the microcapsules was round, the drug loading was 25.99% ± 2.14%, the yield was 51.88% ± 2.84%, the entrapment efficiency was 86.21% ± 2.89%, and the average particle size was 105.6 ± 2.56 nm. The microcapsules in vitro had certain sustained release characteristics. The internally fitted first-order release model equation was ln(1-Q) = -0.236 t + 4.591 7, r = 0.920. In addition, the results of differential scanning calorimetry show that the properties of salvianolic acid were not changed by the microcapsules. CONCLUSION: Sustained-release microcapsules of salvianolic acid can be successfully prepared by adopting marine polysaccharide as a carrier.

Deciphering the Active Ingredients and Molecular Mechanisms of Tripterygium hypoglaucum (Levl.) Hutch against Rheumatoid Arthritis Based on Network Pharmacology.

Tripterygium hypoglaucum (Levl.) Hutch (THH) shows well clinical effect on rheumatoid arthritis (RA), but the active ingredients and molecular mechanisms remain unclear. This work was designed to explore these issues by network pharmacology. Compounds from THH were gathered by retrieving literatures. Compound-related and RA-related genes were identified using databases, and the overlapping genes were identified by Venn diagram. The active ingredients and genes of THH against RA were confirmed by dissecting interactions between overlapping genes and compounds using Cytoscape. SystemsDock website was used to further verify the combining degree of key genes with active ingredients. Pathway enrichment analysis was performed to decipher the mechanisms of THH against RA by Database for Annotation, Visualization and Integrated Discovery. A total of 123 compounds were collected, and 110 compounds-related and 1871 RA-related genes were identified, including 64 overlapping genes. The target genes and active ingredients of THH against RA comprised 64 genes and 17 compounds, the focus of which was PTGS2, triptolide, and celastrol. SystemsDock website indicated that the combing degree of PTGS2 with triptolide or celastrol was very good. The mechanisms of THH against RA were linked to 31 signaling pathways, and the key mechanism was related to inhibition of inflammation response through inactivating TNF and NF-kappa B signaling pathways. This work firstly explored the active ingredients and mechanisms of THH against RA by network pharmacology and provided evidence to support clinical effects of THH on RA.

Network Pharmacology-Based Prediction of Active Ingredients and Mechanisms of Lamiophlomis rotata (Benth.) Kudo Against Rheumatoid Arthritis.

Background: Lamiophlomis rotata (LR) showed favorable clinical effect and safety on rheumatoid arthritis (RA), but its active ingredients and mechanisms against RA remain unknown. The aim of this work was to explore the active ingredients and mechanisms of LR against RA by network pharmacology. Methods: Compounds from LR were identified using literature retrieval and screened by absorption, distribution, metabolism, excretion, and toxicity (ADMET) evaluation. Genes related to the selected compounds or RA were identified using public databases, and the overlapping genes between compounds and RA target genes were identified using Venn diagram. Then, the interactions network between compounds and overlapping genes was constructed, visualized, and analyzed by Cytoscape software. Finally, pathway enrichment analysis of overlapping genes was carried out on Database for Annotation, Visualization, and Integrated Discovery (DAVID) platform. Results: A total of 148 compounds in LR were identified, and ADMET screen results indicated that 67 compounds exhibited good potential as active ingredients. A total of 90 compounds-related genes and 1,871 RA-related genes were identified using public databases, and 48 overlapping genes between them were identified. Cytoscape results suggested that the active ingredients and target genes of LR against RA consisted of 23 compounds and 48 genes, and luteolin and AKT1 were the uppermost active ingredient and hub gene, respectively. DAVID results exhibited that the mechanisms of LR against RA were related to 34 signaling pathways, and the key mechanism of LR against RA might be to induce apoptosis of synovial cells by inactivating PI3K-Akt signaling pathway. Conclusion: The active ingredients and mechanisms of LR against RA were firstly investigated using network pharmacology. This work provides scientific evidence to support the clinical effect of LR on RA, and a research basis for further expounding the active ingredients and mechanisms of LR against RA.

Self-emulsifying drug delivery system improves preventive effect of curcuminoids on chronic heart failure in rats.

Several studies have reported the preventive or therapeutic effect of curcuminoids on chronic heart failure (CHF), but their application was limited due to low solubility and bioavailability. Our previous study indicates that self-emulsifying drug delivery system (SEDDS) improves the solubility and bioavailability of curcuminoids. Thus, the aim of this work was to investigate whether SEDDS could improve preventive effect of curcuminoids on CHF in rats. CHF model was were established by coronary artery ligation. Ninety rats were randomly and averagely divided into sham, model, low- or high-dose suspension or SEDDS of curcuminoids (66.68 or 266.68 mg/kg) groups. Hemodynamic indices were recorded by multipurpose polygraph. Serum oxidative indices, B-type natriuretic peptide (BNP) and heart weight index were determined by kits and electronic balance. Myocardial infarct area, ventricular dilatation degree and collagen volume fraction of myocardial interstitium were analyzed by Masson staining, picric acid and sirius red staining, light microscopy and image analysis system. Myocardial histopathology was observed by hematoxylin and eosin staining, Masson staining and light microscopy. Reduction of ventricular pump function, increase of BNP level and heart weight index, myocardial lipid peroxidation damage, myocardial infarction, myocardial fibrosis, and cardiac enlargement were detected or observed in model group relative to those in sham group. After treatment with suspension or SEDDS of curcuminoids, the above-mentioned pathological changes were obviously reversed relative to those in model group. Meanwhile, the ameliorative effect of SEDDS of curcuminoids was markedly better than that of suspension of curcuminoids. This work provides a valuable reference from pharmacodynamics for development of curcuminoids pharmaceutics.

Prevalence and influences of hepatitis B virus infection on inflammatory bowel disease: a retrospective study in southern China.

The prevalence of Hepatitis B Virus (HBV) infection in inflammatory bowel disease (IBD) has been reported differently across the world. The present study retrospectively included 675 consecutive IBD patients (449 Crohn's disease, CD and 226 ulcerative colitis,UC) from July 2006 to July 2012. The rates of HBV infection (HBsAg-positive) were 13.6%, 16.8% and 13.8% in patients with CD, UC, and general population, respectively (P = 0.418). No significant difference in clinical characters was found between HBsAg-positive and HBsAg-negative IBD patients. The rates of anti-HBc and anti-HBs were 25.4%, 31.2% in CD and 30.1%, 24.3% in UC patients respectively. Liver function was not affected by the use of immunosuppressant in HBsAg-positive IBD patients. Erythrocyte sedimentation rate (ESR), Hypersensitivity C-reactive protein (HsCRP) and platelet (PLT) counts were significantly lower in HBsAg-positive CD patients when compared with HBsAg-negative CD patients (P < 0.05). Infliximab was used less often in HBsAg-positive than HBsAg-negative CD patients (P = 0.010). Multivariate analysis showed that lower platelet counts (OR 0.992; 95% CI: 0.988-0.996, P = 0.000) and less common use of infliximab therapy (OR 0.127; 95% CI: 0.017-0.95, P = 0.045) were independent risk factors for HBV infection in patients with CD. To conclude, the prevalence rate of HBV infection in IBD patients was similar to the general population in Southern China. HBV infection does not affect the clinical characters and medicine choices in either CD or UC patients. HBsAg-positive CD patients have lower platelet counts and less common use of infliximab when compared with HBsAg-negative CD patients.

Discriminating Lamiophlomis rotata According to Geographical Origin by (1)H-NMR Spectroscopy and Multivariate Analysis.

INTRODUCTION: Lamiophlomis rotata (Duyiwei) is a folk herbal medicine that traditionally has been used in China as a hemostatic agent. Raw plant materials used for medicinal products from different geographical regions are often inconsistent in chemical composition. Metabolic fingerprinting provides a new approach for distinguishing the geographical origins of L. rotata. OBJECTIVE: To identify metabolites that contribute to the different geographical regions of L. rotata samples. METHODS: Lamiophlomis rotata metabolomics were performed by (1)H-nuclear magnetic resonance (NMR) spectroscopy and multivariate statistical analyses. The L. rotata metabolic profile was prepared for NMR measurements using methanol-d4 solvent. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) were applied to analyse the L. rotata (1)H-NMR spectroscopy data. RESULTS: Nine iridoid glycosides, one flavonoid and three phenylpropanoid glycosides were detected in L. rotata by (1)H-NMR spectroscopy. (1)H-NMR measurements and multivariate analysis were used to successfully discriminate samples from three different locations. CONCLUSION: The NMR-based analysis of L. rotata is a more comprehensive approach than traditional chromatographic methods. Simple sample preparation, rapidity and reproducibility of are additional advantages of NMR analysis.

Risk factors for surgery and postoperative recurrence: analysis of a south China cohort with Crohn's disease.

BACKGROUND AND AIMS: To investigate the risk factors for primary surgery and postoperative recurrence in a cohort of Chinese Crohn's disease (CD) patients. METHODS: Medical notes of consecutive diagnosed patients from 2003 until 2010 were reviewed. Fifty-seven postoperative patients--finished regular follow-up--were recruited for postoperative recurrence analysis. RESULTS: One hundred eleven of 323 (34.4%) patients of this cohort underwent primary surgery. The cumulative frequency of resection was 16.6%, 35.4%, 53%, and 94.5% for 1, 5, 10, and 30 years, respectively, after onset of disease. Male (OR: 1.994; 95% CI: 1.291-3.078, p = 0.002), stricture (OR: 4.832; 95% CI: 3.064-7.621, p = 0.000), or penetrating (OR: 4.923; 95% CI: 3.060-7.919, p = 0.000) were associated with an increased risk for primary surgery, while early use of immunomodulators was (OR: 0.438; 95% CI: 0.218-0.880, p = 0.020) associated with a decreased risk. Fifty-seven (21.1%) patients were diagnosed as postoperative clinical recurrence and the cumulative recurrence rates were 6.1%, 17.1%, and 36.8% for 1, 2, and 3 years, respectively. Perianal disease was associated with an increased risk for clinical recurrence (OR: 5.606; 95% CI: 1.59-19.766, p = 0.007). CONCLUSIONS: The operation frequency is high in CD. Male, penetrating, and stricture diseases are associated with an increased risk for primary surgery while early use of immunomodulators is associated with a decreased risk. The postoperative recurrence rate is also high. Patients with perianal disease are at higher risk for clinical recurrence.

[Risk factors for initial bowel resection and postoperative recurrence in patients with Crohn disease].

OBJECTIVE: To investigate the risk factors for the initial bowel resection and postoperative recurrence in a cohort of patients with Crohn disease(CD). METHODS: A total of 216 consecutive patients who were regularly followed up in the Department of Gastroenterology at the First Affiliated Hospital of Sun Yat-sen University between 2003 and 2009 were included. Probabilities for initial intestinal resection were calculated with Kaplan-Meier method. The influence of concomitant covariates on the cumulative probability rates was examined using Cox proportional hazard model. The risk of postoperative recurrence, including endoscopic recurrence, clinical recurrence and surgical recurrence, was also investigated during the follow-up. Logistic analysis was performed for the risk factors of recurrence. RESULTS: The median follow-up was 55 months. A total of 44 patients(20.4%) underwent bowel resection. The cumulative frequency of surgery was 11%, 25%, and 45% at 1, 5, and 10 years after initial onset. Multivariate analyses showed that age at diagnosis and disease behavior were independent risk factors for initial intestinal resection(P<0.05). All but 4 patients had complete follow-up after the surgery with a median duration of 20.4 months. Endoscopic recurrence rate was 52.6% within 1 year, and clinical recurrence rate was 22.5%. Median time to clinical recurrence was 22.6 months. Multivariate analyses showed that perianal disease was the only independent risk factor for clinical recurrence(P<0.05). During the follow-up 2 patients(5%) underwent further operation and both had the same indications for the reoperation as that for the initial surgery. CONCLUSIONS: Patients with CD have a high frequency of surgery and the postoperative recurrent rate is also high. Age at diagnosis and disease behavior are associated with the probability of initial surgery. The presence of perianal disease is associated with a higher risk of clinical recurrence.

[Self-microemulsifying drug delivery system increasing solubility and intestinal absorption in situ of tanshinones].

OBJECTIVE: Study the effect of self-microemulsifying drug delivery system(SMEDDS) on the solubility and absorption of tanshinones to guide the selection of composition of tanshinone SMEDDS. METHOD: The solubility of tanshinones in the solution of SMEDDS was determined by UV-spectrometer and the absorption of tanshinone SMEDDS was determined by HPLC as the detection method. RESULT: The solubility of tanshinones in solution of SMEDDS was 10 times in water and 2.5 times in micelle solution. The solubility of tanshinones in solution of SMEDDS was increased with the increasing of oil (MCT) in composition of tanshinone SMEDDS. The absorption constants (Ka) in SMEDDS and micelle solution was 0.479 h(-1) and 0.326 h(-1) respectively, and the absorption half life (t1/2) was 1.44 h and 2.12 h respectively. The absorption was increased with the oil increasing in composition of tanshinone SMEDDS. CONCLUSION: SMEDDS can increase the solubility and absorption of tanshinones significantly and the increasing of oil content (MCT) in SMEDDS composition promote the dissolution and absorption of tanshinones.

[Over one year follow-up report for newly diagnosed pediatric Crohn's disease].

OBJECTIVE: To explore the clinical characteristics, therapeutic responses and outcomes of pediatric Crohn's disease (CD). METHODS: From a hospital-derived incidence cohort, 20 Crohn's disease patients (aged 0.5 - 15 years old at diagnosis), diagnosed from 2003 to 2009, received a follow-up period of more than one year. The patients were phenotyped according to Montreal standards. PCDAI was introduced to assess the disease activity and the Hyams J rules adopted to evaluate the therapeutic efficacies. The treatment was individualized based on the overall evaluation of child. RESULTS: Of these 20 patients, 55% were 7 - 12 years old at the diagnosis time. The male: female ratio was 1.5:1. At the time of diagnosis, the common manifestations included abdominal pain (95.0%), fever (80.0%) and diarrhea (80.0%). Growth retardation was detected in 50% of the cases. Complicated behavior was observed in 45% patients at diagnosis. The most frequent disease location at diagnosis was terminal ileum/colon (55%). Upper GI tract involvement was quite common in children (20%). Non-penetrating non-stricture (50%) behavior was most frequent at diagnosis. Ultimately, corticosteroids plus 6-MP/AZA treatment was administrated in 11 cases. Of these, 9 (82%) successfully withdrew the corticosteroids and maintained a complete remission. Colonoscopy was repeated in 6 complete remission cases and 4 of them achieved a complete mucosa healing. The mean follow-up period was 23 months (range: 12 - 59). At the endpoint of follow-up, 15 cases achieved a complete remission, 4 had a partial remission, 1 underwent operation and none of them died. The children who successfully withdrew from corticosteroids and achieved a complete remission could catch up the height of their age group. 6-MP/AZA associated severe adverse effects were reported at 17% in this group. CONCLUSION: Growth retardation is predominant in pediatric CD and it may provide diagnostic clues. Immunosuppressant therapy may improve the natural history of this disease. It is safe under close monitoring.

[Comparison of the pathogenesis of liver fibrosis induced by pig serum exposure and bile duct ligation in rats].

OBJECTIVE: To observe the occurrence and progression of liver fibrosis induced by pig serum exposure and bile duct ligation, and analyze the relationship between hepatic inflammation and liver fibrosis. METHODS: Chronically immune-mediated liver fibrosis was induced in rats by weekly injection of pig serum (IPS) into the peritoneal cavity at 3 ml/kg for 12 weeks. Cholestatic fibrosis was induced by common bile duct ligation (BDL). The Knodell score was used to evaluate the histological changes in the liver, and immunohistochemistry was performed using anti-SMA, anti-ED1, anti-CK7, and anti-CD45 antibodies. Quantitative real time PCR (qPCR) analysis was employed to quantify the mRNA expression of the genes related to inflammation, including interleukin-1beta (IL-1beta), IL-6, monocyte chemotactic protein-1, tumor necrosis factor-alpha, regulated upon activation normal T cell expressed and secreted (RANTES), transforming growth factor-beta, platelet-derived growth factor A, as well as the genes associated with fibrogenesis, namely collagen 1, alphaSMA, MMP-9 and TIMP-1. RESULTS: Knodell scores for periportal necrosis, intralobular degeneration and focal necrosis, and portal inflammation were all significantly higher in the BDL group than in the IPS group (P<0.01), whereas the scores for fibrosis was higher in the IPS group (P<0.05). Immunohistochemistry showed obvious inflammation with numerous alphaSMA-positive cells in the liver of the rats in BDL group; the liver of the rats in IPS group showed numerous alphaSMA-positive myofibroblasts with limited inflammatory cell infiltration. qPCR demonstrated a significant up-regulation of the genes related to extracellular matrix remodeling such as collagen 1 (P<0.01), alphaSMA (P<0.01), MMP-9 (P<0.01) and TIMP-1 (P<0.01) in the rat liver in IPS group compared with those in the normal control group, and the mRNA expressions of the inflammation-related cytokines, except for RANTES, were comparable with those in the control. In contrast, the BDL group showed a significant up-regulation of all the pro-inflammatory genes examined with also increased expression of the fibrogenesis-related genes (P<0.05). CONCLUSION: Liver fibrosis induced by IPS is characterized by active ECM remodeling in the absence of obvious inflammation, indicating that chronic development of liver fibrosis can be independent of active hepatic inflammation. BDL-induced liver fibrosis highlights obvious inflammation and fibrous proliferation in the liver.

[Design, optimization and quality evaluation of curcumin self-emulsifying drug delivery system (SEDDS)].

OBJECTIVE: To develop the self-emulsifying drug delivery system (SEDDS) of curcumin, and evaluate its quality in vitro. METHODS: The excipients of curcumin SEDDS were selected via its solubility study in various oils, surfactants and co-surfactants and the formulation was optimized using ternary phase diagram study and central composite design-response surface methodology (oil, surfactant and co-surfactant percentages as factors; solubility, droplet size, polydispersity index and emulsifying time as responses). The appearance, droplet size and polydispersity index after emulsifying and the emulsifying time of optimized curcumin SEDDS were studied. The solubility of curcumin in the solution of SEDDS was determined. RESULTS: Castor oil-(tween-80) -ethanol = 28: 55: 20 (w/ w/w) was selected for optimum curcumin SEDDS. The droplet size was 222. 2 nm, polydispersity index was 0. 171. The time of self-emulsifying was 10 s and the solubility of curcumin in SEDDS was 1.93 mg/mL. CONCLUSION: Curcumin SEDDS formulation is selected and optimized successfully, and the preparation of curcumin SEDDS is simple, the quality is stable.