Magnesium protects against sepsis by blocking gasdermin D N-terminal-induced pyroptosis.

Hypomagnesemia is a significant risk factor for critically ill patients to develop sepsis, a life-threatening disease with a mortality rate over 25%. Our clinic data analysis showed that hypomagnesemia is associated with a decreased monocyte count in septic patients. At the cellular level, we found that Mg2+ inhibits pyroptosis. Specifically, Mg2+ limits the oligomerization and membrane localization of gasdermin D N-terminal (GSDMD-NT) upon the activation of either the canonical or noncanonical pyroptotic pathway. Mechanistically, we demonstrated that Ca2+ influx is a prerequisite for the function of GSDMD-NT. Mg2+ blocks Ca2+ influx by inhibiting the ATP-gated Ca2+ channel P2X7, thereby impeding the function of GSDMD-NT and inhibiting lipopolysaccharide (LPS)-induced noncanonical pyroptosis. Furthermore, Mg2+ administration protects mice from LPS-induced lethal septic shock. Together, our data reveal the underlying mechanism of how Mg2+ inhibits pyroptosis and suggest potential clinic applications of magnesium supplementation for sepsis prevention and treatment.

Clinical parameters and outcomes of necrotizing soft tissue infections secondary to gastrointestinal fistulas.

BACKGROUND: Necrotizing soft tissue infections (NSTIs) is severe surgical infections which can occur following trauma or abdominal surgery. NSTIs secondary to gastrointestinal (GI) fistula is a rare but severe complication. METHODS: A retrospective cohort study was performed on all subjects presenting with GI fistulas associated NSTIs were included. Clinical characteristics, microbiological profile, operations performed, and outcomes of patients were analyzed. RESULTS: Between 2014 and 2017, 39 patients were finally enrolled. The mean age were 46.9 years and male were the dominant. For the etiology of fistula, 25 (64.1%) of the patients was due to trauma. Overall, in-hospital death occurred in 15 (38.5%) patients. Microbiologic findings were obtained from 31 patients and Klebsiella pneumoniae was the most common species (41.0%). Eight patients were treated with an open abdomen; negative pressure wound therapy was used in 33 patients and only 2 patients received hyperbaric oxygen therapy. Younger age and delayed abdominal wall reconstruction repair were more common in trauma than in non-trauma. Non-survivors had higher APACHE II score, less source control< 48 h and lower platelet count on admission than survivors. Multiple organ dysfunction syndrome, multidrug-resistant organisms and source control failure were the main cause of in-hospital mortality. CONCLUSIONS: Trauma is the main cause of GI fistulas associated NSTIs. Sepsis continues to be the most important factor related to mortality. Our data may assist providing enlightenment for quality improvement in these special populations.

Polymicrobial Bacteremia Involving Klebsiella pneumoniae in Patients with Complicated Intra-Abdominal Infections: Frequency, Co-Pathogens, Risk Factors, and Clinical Outcomes.

Background: Klebsiella pneumoniae has gained notoriety because of its high antibiotic resistance and mortality. We compared the clinical features and outcomes of polymicrobial bacteremia involving K. pneumoniae (PBKP). Patients and Methods: A retrospective observational study of patients with polymicrobial and monomicrobial bacteremia involving K. pneumoniae from January 2012 to December 2016 was performed. The expression of resistance and virulence genes of 27 strains was also compared by polymerase chain reaction (PCR). Results: Among the polymicrobial group, the most common accompanying micro-organism was Escherichia coli. No differences in the expression of resistance and virulence genes was found among the 27 strains collected from the group. The analysis of the outcomes revealed that the patients with PBKP were more likely to have recurrent blood stream infections (p = 0.038), longer intensive care unit (ICU) lengths of stay (p = 0.043), and a higher total hospitalization cost (p = 0.045). However, no substantial differences in mortality were found between the two groups. The multivariable analysis revealed that a longer hospital stay prior to the onset of bacteremia (>20 days) was an independent risk factor for PBKP (p = 0.034), and the Sequential Organ Failure Assessment (SOFA) score upon onset of infection (p = 0.013), the adequacy of source control (p < 0.001), and iron supplementation (p = 0.003) were identified as independent predictors of mortality in patients with KP bacteremia. Conclusions: The development of septic shock and the concomitant use of iron supplementation are associated with higher mortality in patients with KP bacteremia, and PBKP did not increase the mortality of these patients, possibly because of the ability of K. pneumoniae to obscure the effects of other bacteria. Thus, adequate source control is more important than high-dose antibiotic therapy and is linked to higher survival.

[Status of diagnosis and management of acute appendicitis in 2017: a national multi-center retrospective study].

OBJECTIVE: To analyze the current status of diagnosis and management of acute appendicitis (AA) in China. METHODS: Questionnaire survey was used to retrospectively collect data of hospitalized patients with AA from 43 medical centers nationwide in 2017 (Sort by number of cases provided: Jinling Hospital of Medical School of Nanjing University, The First Affiliated Hospital of Xinjiang Medical University, Lu'an People's Hospital, Tengzhou Central People's Hospital, Dalian Central Hospital, The Affiliated Hospital of Xuzhou Medical University, Dongying People's Hospital, Jinjiang Hospital of Traditional Chinese Medicine, Huangshan Shoukang Hospital, Xuyi People's Hospital, Nanjing Jiangbei People's Hospital, Lanzhou 940th Hospital of PLA, Heze Municipal Hospital, The First College of Clinical Medical Science of China Three Gorges University, Affiliated Jiujiang Hospital of Nanchang University, The Second People's Hospital of Hefei, Affiliated Central Hospital of Shandong Zaozhuang Mining Group, The Third People's Hospital of Kunshan City, Xuzhou First People's Hospital, The 81st Group Army Hospital of PLA, Linyi Central Hospital, The General Hospital of Huainan Eastern Hospital Group, The 908th Hospital of PLA, Liyang People's Hospital, The 901th Hospital of Joint Logistic Support Force, The Third Affiliated Hospital of Chongqing Medical University, The Fourth Hospital of Jilin University, Harbin Acheng District People's Hospital, The First Affiliated Hospital of Zhengzhou University, Nanjing Luhe People's Hospital, Taixing Municipal People's Hospital, Baotou Central Hospital, The Affiliated Hospital of Nantong University, Linyi People's Hospital, The 72st Group Army Hospital of PLA, Zaozhuang Municipal Hospital, People's Hospital of Dayu County, Taixing City Hospital of Traditional Chinese Medicine, Suzhou Municipal Hospital, Beijing Guang'anmen Hospital, Langxi County Hospital of Traditional Chinese Medicine, Nanyang Central Hospital, The Affiliated People's Hospital of Inner Mongolia Medical University).The diagnosis and management of AA were analyzed through unified summary. Different centers collected and summarized their data in 2017 and sent back the questionnaires for summary. RESULTS: A total of 8 766 AA patients were enrolled from 43 medical centers, including 4 711 males (53.7%) with median age of 39 years and 958 (10.9%) patients over 65 years old. Of 8 776 patients, 5 677 cases (64.6%) received one or more imaging examinations, and the other 3 099 (35.4%) did not receive any imaging examination. A total of 1 858 (21.2%) cases received medical treatment, mainly a combination of nitroimidazoles (1 107 cases, 59.8%) doublet regimen, followed by a single-agent regimen of non-nitroimidazoles (451 cases, 24.4%), a nitroimidazole-free doublet regimen (134 cases, 7.2%), a triple regimen of combined nitroimidazoles (116 cases, 6.3%), nitroimidazole alone (39 cases, 2.1%) and nitroimidazole-free triple regimen (3 cases, 0.2%). Of the 6 908 patients (78.8%) who underwent surgery, 4 319 (62.5%) underwent laparoscopic appendectomy and 2589 (37.5%) underwent open surgery. Ratio of laparotomy was higher in those patients under 16 years old (392 cases) or over 65 years old (258 cases) [15.1%(392/2 589) and 10.0%(258/2 589), respectively, compared with 8.5%(367/4 316) and 8.0%(347/4 316) in the same age group for laparoscopic surgery, χ²=91.415, P<0.001; χ²=15.915,P<0.001]. Patients with complicated appendicitis had higher ratio of undergoing open surgery as compared to those undergoing laparoscopic surgery [26.7%(692/2 589) vs. 15.6%(672/4 316), χ²=125.726, P<0.001].The cure rates of laparoscopic and open surgery were 100.0% and 99.8%(2 585/2 589) respectively without significant difference (P=0.206). Postoperative complication rates were 4.5%(121/2 589) and 4.7%(196/4 316) respectively, and the difference was not statistically significant (χ²=0.065, P=0.799). The incidence of surgical site infection was lower (0.6% vs. 1.7%, χ²=17.315, P<0.001), and hospital stay was shorter [6(4-7) days vs. 6(5-8) days, U=4 384 348.0, P<0.001] in the laparoscopic surgery group, while hospitalization cost was higher (median 12 527 yuan vs. 9 342 yuan, U=2 586 809.0, P<0.001). CONCLUSIONS: The diagnosis of acute appendicitis is still clinically based, supplemented by imaging examination. Appendectomy is still the most effective treatment at present. Laparoscopic appendectomy has become the main treatment strategy, but anti-infective drugs are also very effective.

AuNPs-PCL nanocomposite accelerated abdominal wound healing through photothermal effect and improving cell adhesion.

Accelerating wound healing with modified biomaterial has been an attracting field in both material science and medicine. Enhanced cell adhesion could be acquired by improving surface hydrophilicity, which contributes to accelerating wound healing. Chemical reaction has been used for surface modification, but this study used a simple and nontoxic method to improve the hydrophilicity. Polycaprolactone (PCL) scaffold has been regarded as promising material for wound healing while its surface is hydrophobic. Our study demonstrated enhanced hydrophilicity of PCL with AuNPs coating. AuNPs has good biocompatibility and excellent photothermal effect. The coating of AuNPs not only improved the cell adhesion, but also gave PCL the ability to inhibit the growth of bacteria. Animal study showed that the nanocomposites decreased lymphocytes and neutrophils, increased neovascularization and accelerated the abdominal wound healing, which was attributed to improved hydrophilicity and the antibacterial ability. In conclusion, we demonstrated that the nanocomposite could be used as a potential scaffold for cell adhesion and wound healing, and the role of AuNPs was highlighted as a kind of outstanding supplement.

Cordyceps sinensis preserves intestinal mucosal barrier and may be an adjunct therapy in endotoxin-induced sepsis rat model: a pilot study.

BACKGROUND: Cordyceps sinensis (C. sinensis), a traditional Chinese medicine, exhibits various pharmacological activities such as reparative, antioxidant, and apoptosis inhibitory effects. Intestinal barrier dysfunction plays a vital role in the progression of sepsis. We aimed to explore the effect of C. sinensis on the gut barrier and evaluate its efficacy in sepsis. METHODS: A murine model of gut barrier dysfunction was created by intraperitoneal injection of endotoxin. C. sinensis or saline was administered orally after the induction of sepsis. Alterations of intestinal barrier were evaluated and compared in terms of epithelial cell apoptosis, proliferation index (PI), intercellular tight junction (TJ) and proliferating cell nuclear antigen (PCNA). RESULTS: C. sinensis significantly decreased the percentage of apoptotic cells and promoted mucosal cells proliferation indicated by enhanced PI and PCNA expression in the intestinal mucosa compared to control group. The TJs between epithelial cells which were disrupted in septic rats were also restored by treatment of C. sinensis. In survival studies, C. sinensis was demonstrated to confer a protection against the lethal effect of sepsis. CONCLUSION: These results suggest that C. sinensis has gut barrier-protection effect in endotoxin-induced sepsis by promoting the proliferation and inhibiting the apoptosis of intestinal mucosal cells, as well as restoring the TJs of intestinal mucosa. C. sinensis may have the potential to be a useful adjunct therapy for sepsis.

Vitamin D prevents the intestinal fibrosis via induction of vitamin D receptor and inhibition of transforming growth factor-beta1/Smad3 pathway.

BACKGROUND AND AIMS: Vitamin D deficiency in patients with inflammatory bowel disease (IBD) is associated with greater disease activity and lower quality of life. Intestinal fibrosis is a main complication of IBD. However, the effect of vitamin D on intestinal fibrosis remains unclear. We investigated the prophylactic effect and the underlying mechanism of vitamin D on the intestinal fibrosis in vitamin D-deficient mice with chronic colitis. METHODS: Vitamin D-deficient mice were randomized into two groups receiving the vitamin D-deficient or vitamin D-sufficient diet from weaning (week 4). Intestinal fibrosis was induced by six-weekly 2,4,6-trinitrobenzene sulfonic acid administrations from week 8. At week 14, the productions of extracellular matrix (ECM) and total collagen were measured in the colons, and TGF-ß1/Smad3 signal transduction was examined in isolated colonic subepithelial myofibroblasts (SEMF). The expression of vitamin D receptor (VDR), α-SMA and Collagen I in normal SEMF and VDR-null SEMF exposed to TGF-ß1 and/or 1,25(OH)2D3 was measured. RESULTS: Vitamin D significantly reduced the histological scoring, ECM and collagen productions in the colons and decreased the levels of TGF-ß1, Smad-3, p-Smad3 and Collagen I in SEMF. 1,25(OH)2D3-induced VDR expression and decreased TGF-ß1-stimulated α-SMA and Collagen I expressions in SEMF. Knocking down VDR expression in SEMF abolished the effect of 1,25(OH)2D3. CONCLUSIONS: Vitamin D has prophylactic effect on intestinal fibrosis in the vitamin D-deficient mice with chronic colitis, which may be associated with the inhibited activation of TGF-ß1/Smad3 pathway in the SEMF via VDR induction.

Fistula output microorganism-susceptible antimicrobial prophylaxis is associated with a lower risk of surgical site infection in gastrointestinal fistula patients undergoing one-stage definitive surgery.

BACKGROUND: Empiric broad-spectrum antimicrobial prophylaxis (AMP) may not be sufficient to minimize the risk of surgical site infections (SSIs) after definitive surgical treatment of gastrointestinal (GI) fistula. This study investigates whether AMP targeted toward fistula microbiology is associated with a lower risk of SSIs in GI fistula patients undergoing one-stage definitive surgery. METHODS: Fistula output was sampled from the abdominal fistula opening for microbial growth and drug sensitivity prior to surgery. The primary outcome measure was the overall incidence rate of SSIs. RESULTS: A total of 191 patients were examined. Pre-operative microbial culture identified microbial growth in 149 patients (76.0%). Post-operative SSIs occurred in 51 patients (26.7%). Risk index category, abdominal incision length, and time of peritoneal drain removal had significantly negative impacts on SSIs frequency. Sensitive AMP agents were associated with a significantly lower risk of SSIs, compared with insensitive AMP agents, but with a similar risk to indefinite AMP agents (23.2% vs. 45.2% vs. 23.1%; odds ratio [95% confidence interval]: 2.724 [1.063, 6.979], p=0.034; 1.008 [0.467-2.177], p=0.984). CONCLUSIONS: Antimicrobial prophylaxis targeted toward fistula output AMP may minimize the occurrence of SSIs after one-stage definitive surgical treatment of GI fistula.

Exclusive enteral nutritional therapy can relieve inflammatory bowel stricture in Crohn's disease.

GOALS: To examine the efficiency of exclusive enteral nutrition (EEN) in relieving inflammatory bowel stricture in patients with Crohn's disease (CD). BACKGROUND: Patients with CD usually develop bowel strictures due to transmural edema of intestinal wall, which can potentially be managed with conservative medical treatment. Previous studies showed that EEN therapy could induce clinical remission through its anti-inflammation effect. METHODS: We achieved a prospective observational study. CD patients with inflammatory bowel stricture were preliminarily differentiated from a fibrous one, and further treated with EEN therapy for 12 weeks. Demographics and clinical variables were recorded. Nutritional (body mass index, albumin, pre-albumin, transferrin, etc.), inflammatory (C-reactive protein, erythrocyte sedimentation rate, white blood cell, etc.), and radiologic parameters (bowel wall thickness, luminal diameter, and luminal cross-sectional area) were evaluated at baseline, week 4, and week 12, respectively. RESULTS: Between May 2012 and January 2013, 65 patients with CD were preliminarily diagnosed with inflammatory bowel stricture and 6 patients were further excluded. Among the remaining 59 cases, 50 patients (84.7%) finished the whole EEN treatment, whereas the other 9 patients (15.3%) gained progressive bowel obstruction resulting in surgery. Intention-to-treat analyses showed that 48 patients (81.4%) achieved symptomatic remission, 35 patients (53.8%) achieved radiologic remission, and 42 patients (64.6%) achieved clinical remission. Among those patients who complete the whole EEN therapy, inflammatory, nutritional, and radiologic parameters improved significantly compared with baseline. Of note, the average luminal cross-sectional area at the site of stricture increased approximately 331% at week 12 (195.7 ± 18.79 vs. 59.09 ± 10.64 mm, P<0.001). CONCLUSIONS: EEN therapy can effectively relieve inflammatory bowel stricture in CD, which replenishes roles of enteral nutrition in the treatment of CD. Further studies are expected to investigate the underlying mechanisms of this effect in the future.

T2 enhances in situ level of Foxp3+ regulatory cells and modulates inflammatory cytokines in Crohn's disease.

BACKGROUND: Acting via IL-10 and transforming growth factor-ß (TGF-ß), t regulatory cells (Tregs) that express the Forkhead Box P3 (Foxp3) play a vital role in maintaining intestinal immune homeostasis. Many studies have found correlation between Foxp3(+) Treg cells and Crohn's disease (CD). T2, extracted from the medicinal plant Tripterygium wilfordii Hook F, has already been proved to be therapeutically effective in inducing the remission of CD. However, the mechanisms in human studies remain largely unknown. AIM: We aimed to explore the effect of T2 on the in situ levels of inflammatory cytokines and the number of Foxp3(+) Tregs in inflamed mucosa of CD. METHODS: Mucosal biopsies from 20 patients treated with T2 were taken by colonoscopy. The changes of Foxp3(+) Tregs as well as TNF-α and IL-10 in diseased tissue were visualized by immunochemistry. Western blot and ELISA were used to quantify levels of Foxp3 protein expression and inflammatory cytokines. RESULTS: T2 treatment ameliorated the pathological inflammation of CD. We observed that the significantly elevated Foxp3(+) Tregs and IL-10 levels in the mucosa of CD patients after T2 treatment concurred with the down-regulation of proinflammatory TNF-α. CONCLUSION: We confirmed the efficacy of T2 treatment in CD and showed that microscopic inflammation was attenuated by the modulation of in situ levels of inflammatory cytokines. The therapeutic mechanisms might involve the up-regulation of Foxp3(+) Tregs.

Prevention of postoperative recurrence of Crohn's disease: Tripterygium wilfordii polyglycoside versus mesalazine.

OBJECTIVES: To explore effectiveness and safety of polyglycosides of Tripterygium wilfordii (GTW) and mesalazine (5-aminosalicylic acid [5-ASA]) in preventing postoperative clinical and endoscopic recurrence of Crohn's disease. METHODS: In this prospective, single-centre, single-blind study, postoperative Crohn's disease patients in remission were randomized to receive 1 mg/kg GTW daily, orally, or 4 g 5-ASA daily, orally, for 52 weeks. Patients underwent physical examinations, ileocolonoscopies and biochemical analyses at baseline and weeks 13, 26 and 52, or when clinical recurrence was suspected. Outcome measures were proportion of patients showing clinical or endoscopic recurrence at week 52, and changes in Rutgeerts' and Crohn's Disease Activity Index (CDAI) scores. RESULTS: Twenty-one patients were assigned to receive GTW and 18 to 5-ASA; two patients on GTW and one on 5-ASA were withdrawn. Clinical and endoscopic recurrences were less common in the GTW group (n = 4) versus the 5-ASA group (n = 9). There were improvements in Rutgeerts' scores for those taking GTW. Mean between-group CDAI scores were similar. No serious adverse events were reported. CONCLUSION: These findings indicate that GTW appears to be an effective, well-tolerated prophylactic regimen, superior to oral 5-ASA, for preventing clinical and endoscopic recurrence in postsurgical Crohn's disease.

Efficacy of erythropoietin combined with enteral nutrition for the treatment of anemia in Crohn's disease: a prospective cohort study.

BACKGROUND: Anemia is a common and serious complication in patients with inflammatory bowel disease. The present study was dedicated to evaluate the therapeutic efficacy of erythropoietin (EPO) combined with enteral nutrition (EN) in anemic Crohn's disease (CD) patients, in terms of hemoglobin level, treatment success rate, adverse events, and predictor of this therapy. MATERIALS AND METHODS: We performed a prospective study in CD patients. On the basis of hemoglobin level, all enrolled patients were divided into anemic and nonanemic groups. The anemic group was further divided into EPO and non-EPO subgroups, depending on whether EPO was prescribed. Hematological and other parameters were measured initially and in the first 4 weeks after starting treatment. RESULTS: In total, 109 patients (49 nonanemic and 60 anemic, including 38 EPO and 22 non-EPO) were included. The prevalence of anemia in CD was 55.05%. Age, disease behavior, Crohn's Disease Activity Index scores, C-reactive protein, and erythrocyte sedimentation rate were significantly different between anemic and nonanemic groups. An increase in hemoglobin level and a significant decrease in C-reactive protein level were observed in the EPO treatment group. Treatment success rate was 63.16% in the EPO group, whereas none of patients achieved treatment success in the non-EPO group. CONCLUSION: EPO combined with EN can improve the hemoglobin level in anemic CD patients.

Clinical characteristics of non-perianal fistulating Crohn's disease in China: a single-center experience of 184 cases.

BACKGROUND: There is little information of non-perianal fistulating Crohn's disease in the consensus published by the European Crohn's and Colitis Organization in 2006 and 2010. This study was designed to demonstrate the clinical characteristics of non-perianal fistulating Crohn's disease among homogenous Chinese population. METHODS: One-hundred-and-eighty-four patients were retrospectively collected. All of these patients were diagnosed of Crohn's disease between February 2001 and April 2011. RESULTS: The male-to-female ratio was 2.7:1. The most common symptoms at onset were abdominal pain (88.0%), diarrhea (34.7%), and fever (28.3%). The most common disease location and behavior at diagnosis were small bowel (56.0%) and penetrating (51.6%). Among 324 non-perianal fistulae, the most common types were ileocolonic anastomotic (30.9%), terminal ileocutaneous (19.7%), and enteroenteric anastomotic (11.4%). One-hundred-and-thirty- eight (75.0%) patients received antibiotics, and ß-lactam (85.5%) and metronidazole (67.4%) are most frequently used. One-hundred-and-seventy-eight (96.7%) patients suffered 514 surgical operations, and the cumulative surgical rates after 1, 3, and 5 years were 38.0%, 52.2%, and 58.7% respectively. Nine patients died during the follow-up period, and the cumulative survival rates after 1, 3, and 5 years were 97.8%, 96.7%, and 96.2% respectively. CONCLUSIONS: This study displayed the clinical characteristics of non-perianal fistulating Crohn's disease in our center. Large population-based studies are required for further investigation in China.

[Research progress of anemia associated with inflammatory bowel diseases].

Anemia is a frequent and serious complication in patients with inflammatory bowel disease (IBD). One third of patients with inflammatory bowel disease suffers from recurrent anemia. Anemia is associated with a decrease in the quality of life and an increased rate of hospitalization. A number of studies have been conducted and the most relevant conclusions obtained are:(1)anemia is quite common in IBD; (2)although in many cases anemia parallels the clinical activity of the disease, many patients in remission have anemia, and iron, vitamin B12 and/or folic acid deficiency;(3)anemia, and also iron deficiency without anemia, have important consequences in the clinical status and quality of life of the patients;(4)oral iron supplement is limited by poor absorption, intolerance, and induction of oxidative stress at the site of bowel inflammation; (5) intravenous iron sucrose has a high efficiency and a significant improvement in the quality of life; (6)erythropoietin is needed in a significant number of cases to achieve normal hemoglobin levels. Combination therapy with erythropoietin leads to a faster and larger hemoglobin increase. Thus, clinicians caring for IBD patients should have a comprehensive knowledge of anemia, and apply recently published guidelines in clinical practice.

Fish oil-supplemented parenteral nutrition prolongs survival while beneficially altering phospholipids' Fatty Acid composition and modulating immune function in rat sepsis.

We investigated the therapeutic effects of parenteral fish oil (FO) on survival and fatty acid profile in plasma and erythrocyte membranes, T-lymphocyte subsets, and plasma cytokines in a rat model of sepsis. Adult male Sprague-Dawley rats were subjected to cecal ligation and puncture-induced sepsis. For recovery, central venous catheterization was performed 2 days before sepsis was induced. Rats were randomly assigned to receive normal saline (n = 20) or total parenteral nutrition (PN) containing a standard soybean oil emulsion (n = 20) or FO-supplemented TPN (n = 20) at the onset of sepsis for 5 days. In the control group, rats were challenged by sham operation and underwent appropriate control treatment (n = 10). Sepsis led to a high mortality and body weight loss compared with sham operation. Total PN supplemented with FO, but not without FO, improved the survival compared with normal saline. Furthermore, parenteral infusion of FO increased the concentrations of eicosapentaenoic acid and docosahexaenoic acid, as well as the ratio of (eicosapentaenoic acid + docosahexaenoic acid) to arachidonic acid both in plasma and erythrocyte membrane. In addition, FO-supplemented TPN improved the percentages of CD3 and CD3CD4 T cells, as well as the CD4/CD8 ratio in spleen. Meanwhile, the percentage of regulatory T cells (CD4CD25Foxp3) among CD4 T cells was reduced by FO-supplemented TPN. Fish oil-supplemented TPN attenuated the production of high-mobility group box 1 and IL-10 in plasma. Moreover, parenteral FO decreased the bacterial loads in peritoneal lavage, blood, lung, and spleen. The present study suggests that FO-supplemented TPN initiated at the onset of sepsis improves survival, beneficially alters the lipids profile in plasma and erythrocyte membrane, modulates immune function, and regulates inflammatory response in a rat model.

[Maintenance effect of polyglycosides of Tripterygium wilfordii on remission in postoperative Crohn disease].

OBJECTIVE: To observe the maintenance effect of polyglycosides of Tripterygium wilfordii (GTW) on remission in postoperative Crohn disease (CD). METHODS: From 2005 to 2007, 45 adult cases of postoperative Crohn disease were randomly divided into two groups, GTW group and mesalazine group, which received GTW and mesalazine treatment respectively. CD activity index (CDAI) and clinical markers were collected at 0, 3, 6, 12 months or at the onset of symptoms. Ileocolonoscopy was performed at the end of the trial (1 year after operation) or at the onset of symptoms, and recurrence score were recorded. RESULTS: No clinical recurrence was ascertained in both groups at 3 months. Four patients (18.2%) in GTW group relapsed and 5 (21.7%) in mesalazine group relapsed at 6 months (P=0.530). Seven patients (31.8%) in GTW group and 9 (39.1%) in mesalazine group relapsed at one year (P=0.421). Ten patients (45.5%) in GTW group had endoscopic recurrence compared with 14 (60.9%) in mesalazine group at one year(P=0.231). There were no significant differences between two groups. CONCLUSION: GTW is similar to mesalazine in maintenance of remission of postoperative Crohn disease.

[Efficacy of polyglycosides of Tripterygium wilfordii in preventing postoperative recurrence of Crohn disease].

OBJECTIVE: To observe the efficacy of polyglycoside of Tripterygium wilfordii(GTW) in preventing postoperative recurrence of Crohn disease(CD). METHODS: Thirty-nine post-operative CD patients in whom all of the diseased gut had been removed from January 2005 to December 2006 were enrolled in a randomized, placebo-controlled trial. The patients took GTW(21 cases) or SASP(18 cases) in two weeks after operation. Crohn disease activity index(CDAI), ESR and CRP were collected at week 0, 13, 26, 52 or at the onset of symptoms. Ileocolonoscopy was performed at the end of the trial or at the onset of symptoms. RESULTS: One patient in GTW group and 2 patients in SASP group were lost and 2 patients in GTW were excluded from the trial for non-compliance. Clinical recurrence was ascertained in one patient (5.6%) received GTW and in four (25.0%) received SASP. Four of eighteen patients in GTW(22.2%) had endoscopic recurrence compared with nine of sixteen(56.2%) in SASP. There were significant differences between the two groups(P<0.05). CONCLUSION: Tripterygium wilfordii showed good efficacy in preventing recurrence of postoperative CD which can maintain remission and prevent recurrence.

Efficacy of T2 in active Crohn's disease: a prospective study report.

To date few therapies have been shown to reliably prevent the evolution of Crohn's disease (CD). The traditional Chinese medicine, Tripterygium wilfordii Hook F (TWHF), has both immunomodulatory and anti-inflammatory activities. Our aim was to investigate the potential efficacy of T2, the major constituent of extracts of TWHF, in inducing remission of active CD. Twenty adult patients with active CD were enrolled to be treated with T2 pills (60 mg daily) for 12 weeks. Plasma levels of C-reactive protein (CRP), tumor necrosis factor (TNF)-alpha, and interleukin (IL)-1beta were measured at entry and every 2 weeks thereafter until week 12. At each visit the CD Activity Index (CDAI) was calculated. The CD Endoscopic Index of Severity was measured at entry and week 12. Sixteen patients completed the study. A significant decrease in serum levels of CRP, TNF-alpha, and IL-1beta occurred rapidly after commencement of treatment. CDAI scores showed a rapid decline during the first 8 weeks and reached their lowest at week 10. Endoscopic improvements were observed at week 12. In conclusion, T2 appears to be effective for the treatment of mildly or moderately active CD. Further controlled studies are warranted for this promising drug.

Triptolide suppresses IL-1beta-induced chemokine and stromelysin-1 gene expression in human colonic subepithelial myofibroblasts.

AIM: To examine the inhibitive effects of triptolide on the expression of IL-8, monocyte chemotactic protein (MCP)-1, and matrix metalloproteinases (MMP)-3 in subepithelial myofibroblasts (SEMF) stimulated with IL-1beta. METHODS: SEMF cultures were established from normal colons in patients who underwent gut resection for colorectal carcinoma. Chemokine and MMP-3 expressions were determined by ELISA and RT-PCR. The cytosolic amount of phosphorylation of I kappa B-alpha(p-I kappa B-alpha) was determined by Western blotting. The DNA binding capacity of NF-kappa B was evaluated by electrophoretic mobility shift assays. RESULTS: IL-1beta stimulated protein and mRNA expression of IL-8, MCP-1, and MMP-3 in SEMF. Triptolide inhibited these effects of IL-1beta in a dose-dependent manner. Mechanistic studies revealed that triptolide markedly decreased IL-1beta -induced NF-kappa B DNA binding capacity and cytosolic amount of p-I kappa B-alpha. These results showed that triptolide inhibited IL-1beta -induced chemokine and MMP-3 expression in SEMF through the NF-kappa B pathway. CONCLUSION: Triptolide inhibited IL-1beta -induced chemokine and MMP-3 expression in SEMF by preventing the phosphorylation of I kappa B-alpha.