A pyrimidine metabolism-related signature for prognostic and immunotherapeutic response prediction in hepatocellular carcinoma by integrating analyses.

BACKGROUND: Hepatocellular carcinoma (HCC), with discouraging morbidity and mortality, ranks as one of the most prevalent tumors worldwide. Pyrimidine metabolism is a critical process that regulates DNA and RNA synthesis in cells. It is imperative to investigate the significance of pyrimidine metabolism in liver cancer. METHODS: Transcriptome and clinical data were downloaded from the TCGA database and the GEO database. The genes related to pyrimidine metabolism were sourced from the MSigDB. The pyrimidine metabolism-related signature (PMRS) was constructed through Cox regression and Lasso regression and then verified in the external validation set from the ICGC database. Functional enrichment, immune infiltration analysis, drug sensitivity, and Immunophenoscore (IPS) were further implemented to predict the response to immunotherapy. The role of PMRS in the malignant phenotype of hepatocellular carcinoma was explored by conducting a series of in vitro experiments. RESULTS: Our study developed a four-genes PMRS which demonstrates a substantial correlation with the prognosis of HCC patients, serving as an independent predictor in clinical practice. The result of risk-stratified analysis yielded evidence that low-risk patients experienced more favorable clinical outcomes. The nomogram exhibited remarkable prognostic predictive value. The subsequent results revealed that low-risk patients manifested a more promising response to immunotherapy. Moreover, the results of cell experiments demonstrated that the downregulation of DCK markedly inhibited the malignant phenotype of hepatocellular carcinoma. CONCLUSIONS: Our pyrimidine metabolism-centered prognostic signature accurately predicts overall survival, immune status, and treatment response in hepatocellular carcinoma (HCC) patients, offering innovative insights for precise diagnosis, personalized treatment, and improved prognosis.

A comprehensive analysis of the prognostic and immunotherapeutic characteristics of KIFC1 in pan-cancer and its role in the malignant phenotype of pancreatic cancer.

BACKGROUND: Kinesin family member C1 (KIFC1) is an essential member of the motor protein family, which is critically involved in various cellular events, such as mitosis, meiosis, and macromolecular transport, but also in carcinogenesis, malignant progression, and tumor recurrence. METHODS: The analysis determined the relationship between KIFC1 expression, prognosis significance, immune characteristics landscape, and genetic alterations in pan-cancer with the data extracted from web-based platforms and databases, including but not limited to UCSC, NCBI, GEPIA2, HPA, cBioPortal, SangerBox, UALCAN, GEO and TCGA. Additionally, the expression of KIFC1 in pancreatic cancer tumor tissues and adjacent normal tissues was evaluated through immunohistochemistry. In vitro Edu, colony formation, wound healing, and Transwell assay were done to elucidate the biological functions of KIFC1 in pancreatic cancer cells. RESULTS: The analysis revealed that KIFC1 is upregulated in most cancers, and its increased expression is significantly associated with reduced overall survival and disease-free survival in multiple cancer types. Additionally, strong correlations between KIFC1 expression and tumor immunotherapy were observed across various malignancies. Through univariate and multivariate Cox regression analyses using TCGA data, KIFC1 was identified as an independent predictor of prognosis in pancreatic cancer cases. Furthermore, cellular experiments demonstrated that knockdown of KIFC1 resulted in the suppression of cell proliferation, migration, and invasive ability. CONCLUSIONS: Our study indicated that KIFC1 harbors the potential to be a prognostic and immunotherapeutic biomarker of tumors, and it can have an impact on the metastasis and the cell cycle of pancreatic cancer cells.

Establishment of a fast discriminant model with electronic nose for Polygonati Rhizoma mildew based on odor variation / 中国中药杂志

The odor fingerprint of Pollygonati Rhizoma samples with different mildewing degrees was analyzed and the relationship between the odor variation and the mildewing degree was explored. A fast discriminant model was established according to the response intensity of electronic nose. The α-FOX3000 electronic nose was applied to analyze the odor fingerprint of Pollygonati Rhizoma samples with different mildewing degrees and the radar map was used to analyze the main contributors among the volatile organic compounds. The feature data were processed and analyzed by partial least squares discriminant analysis(PLS-DA), K-nearest neighbor(KNN), sequential minimal optimization(SMO), random forest(RF) and naive Bayes(NB), respectively. According to the radar map of the electronic nose, the response values of three sensors, namely T70/2, T30/1, and P10/2, increased with the mildewing, indicating that the Pollygonati Rhizoma produced alkanes and aromatic compounds after the mildewing. According to PLS-DA model, Pollygonati Rhizoma samples of three mildewing degrees could be well distinguished in three areas. Afterwards, the variable importance analysis of the sensors was carried out and then five sensors that contributed a lot to the classification were screened out: T70/2, T30/1, PA/2, P10/1 and P40/1. The classification accuracy of all the four models(KNN, SMO, RF, and NB) was above 90%, and KNN was most accurate(accuracy: 97.2%). Different volatile organic compounds were produced after the mildewing of Pollygonati Rhizoma, and they could be detected by electronic nose, which laid a foundation for the establishment of a rapid discrimination model for mildewed Pollygonati Rhizoma. This paper shed lights on further research on change pattern and quick detection of volatile organic compounds in moldy Chinese herbal medicines.

Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn's disease in Asia

The Asia-Pacific Working Group on inflammatory bowel disease (IBD) was established in Cebu, Philippines, under the auspices of the Asian Pacific Association of Gastroenterology with the goal of improving IBD care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn's and Colitis. With biologic agents and biosimilars becoming more established, it is necessary to conduct a review on existing literature and establish a consensus on when and how to introduce biologic agents and biosimilars in the conjunction with conventional treatments for ulcerative colitis (UC) and Crohn's disease (CD) in Asia. These statements also address how pharmacogenetics influence the treatments of UC and CD and provide guidance on response monitoring and strategies to restore loss of response. Finally, the review includes statements on how to manage treatment alongside possible hepatitis B and tuberculosis infections, both common in Asia. These statements have been prepared and voted upon by members of IBD workgroup employing the modified Delphi process. These statements do not intend to be all-encompassing and future revisions are likely as new data continue to emerge.

The association between new generation oral contraceptive pill and the development of inflammatory bowel diseases

BACKGROUND/AIMS: To examine the association between use of oral contraceptive pills (OCPs) and the risk of developing inflammatory bowel diseases (IBD), in a modern cohort. METHODS: A prospective nested case-control study across sites in the Asia-Pacific region was conducted; involving female IBD cases and asymptomatic controls. Subjects completed a questionnaire addressing questions related to OCP use. Primary outcome was the risk of development of IBD of those exposed to OCP versus non-exposure. Secondary outcomes were development of Crohn's disease (CD) versus ulcerative colitis (UC), and whether age of first use of OCP use may be associated with risk of IBD. RESULTS: Three hundred and forty-eight female IBD cases (41% CD, median age: 43 years) and 590 female age-matched controls were recruited. No significant association was found between OCP use and the risk of IBD (odds ratio [OR], 1.65; 95% confidence interval, 0.77–3.13; P=0.22), CD (OR, 1.55) or UC (OR, 1.01). The lack of association persisted when results were adjusted for age and smoking. IBD cases commenced OCP use at a younger age than controls (18 years vs. 20 years, P=0.049). CONCLUSIONS: In this large cohort of subjects from the Asia-Pacific region, we found a modest but not significantly increased risk of developing IBD amongst OCP users.

Focal nonspecific ileocecum inflammation: a follow-up study of 66 cases / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the natural disease course of nonspecific ileocecum inflammation (FNICI) and the possibility of early diagnosis of Crohn's disease (CD).</p><p><b>METHODS</b>The patients with an established diagnosis of FNICI at our hospital in the past 4 years were retrospectively analyzed for clinical manifestations, endoscopical, readigraphic and histopathological findings and laboratory data. The patients were followed up regularly for their outcomes.</p><p><b>RESULTS</b>Our analysis included 66 patients with FNICI (with a male-to-female ratio of 34:32 and a mean age of 39 years old). The patients were followed up for 10.5 months on average, and 8 (12.1%) patients developed CD. Among these 8 patients, the initial endoscopic examination upon admission revealed ulcers involving the ileocecum valve, and biopsy results showed focal active chronic mucosal inflammation. Laboratory tests showed that the patients who finally developed CD had significantly higher erythrocyte sedimentation rate (P=0.013) and C reaction protein (P<0.01) than the patients who eventually had full recovery.</p><p><b>CONCLUSION</b>FNICI is a common lesion caused by multiple factors and has not specific endoscopic or histopathological features, which makes its definite diagnosis difficult. The patients with persistent ulcer and elevated erythrocyte sedimentation rate and C reactive protein should be closely followed up for early diagnosis of CD.</p>

[Therapeutic effect and mechanisms study of Bawei Xilei Powder on ulcerative colitis patients].

OBJECTIVE: To investigate the efficacy and mechanisms of Bawei Xilei Powder (BXP) in treating ulcerative colitis (UC). METHODS: Totally 103 patients with left hemicolon mild to moderate UC in the active phase at the outpatient clinics of West China Hospital from June 2009 to October 2010 were randomly assigned to the treatment group (55 cases) and the control group (48 cases). Patients in the treatment group were treated with BXP (adding 1 g in 60 mL worm boiled water) and those in the control group received by 50 mg/60 mL hydrocortisone edema solution (once every evening before sleep). The therapeutic course for all was 4 weeks. The disease activity degree (Mayo scoring), endoscopic, and histologic manifestations were compared between post-and pre-treatment in the two groups. The expression of toll-like receptor-4 (TLR4), nuclear factor-kappaB (NF-kappaB), and Occludin were detected. RESULTS: The clinical remission rate and the response rate in the treatment group were 78.2% and 89.1% respectively, higher than those of the control group (58.3% and 72.9%, P < 0.05).The endoscopically mucosal healing rate was 50.9% in the treatment group and 31.3% in the control group (P < 0.05). The histological remission rate and the effective rate in the treatment group were 32.7% and 65.5% respectively, but higher than those of the control group (27.1% and 58.3%, P > 0.05). The rate of adverse events was 3.8% in the treatment (occurred in 2 cases) and 4.3% in the control group (occurred in 2 cases, P > 0.05). Compared with pre-treatment, the expression of TLR4 and NF-kappaB p65 significantly decreased (P < 0.05), while the expression of Occludin significantly increased (P < 0.05). CONCLUSIONS: BXP was effective and safe in patients with active mild to moderate UC. Its effects might be involved in regulating the expression of inflammatory factors and enhancing mucosa barrier functions. ulcerative colitis; Bawei Xilei Powder; enema therapy

Inhibitory effect of polydatin on expression of toll-like receptor 4 in ischemia-reperfusion injured NRK-52E cells / 中国中药杂志

Polydatin is a monocrystaline compound isolated from Polygonum cuspidatum Sieb. et Zucc. (Polygonaceae) with biological properties, such as anti-inflammation, anti-oxidative and nephroprotective effects. Increasing number of studies have demonstrated the protective effect of polydatin on renal ischemia reperfusion injury. However, the possible mechanisms of this protection are not fully elucidated. This study aimed to investigate the effect of polydatin on ischemia-reperfusion induced expression of toll-like receptor4 (TLR4) in rat renal tubular epithelia cells (NRK-52E), and analyze the mechanism of polydatin on TLR4 signal pathway. The cultured NRK-52E cells were incubated in three gas incubators for a period of 6 h at hypoxia and 24h at reoxygenation to simulate the ischemia-reperfusion injury in vitro. TLR4 mRNA level was analyzed by real-time-PCR, and the protein expression of TLR4 and NF-κB by Western blotting, while TNF-α and IL-1β proteins expressions were detected by ELISA. Polydatin downregulated I/R induced mRNA and protein expressions of TLR4, and decreased the protein expression of NF-κB, TNF-α and IL-1β. The TLR4 blocker partially antagonized the effect of I/R on NF-κB signaling, and such inhibitory effect was markedly enhanced by polydatin. In the present study, polydatin protects NRK-52E cells from I/R injury possibly by relieving the inflammatory response through regulation of TLR4/NF-κB signaling pathway.

A retrospective analysis of azathioprine in the treatment of 24 patients with refractory ulcerative colitis / 中华内科杂志

Objective To evaluate the efficacy and safety of azathioprine (AZA) in the treatment of refractory ulcerative colitis (UC).Methods Retrospective analysis of the clinical improvement,endoscopic improvement and mucosal healing rate,inflammation marker improvement after AZA administration and its safety in 24 refractory UC patients were performed,who were recruited between January 2007 and December 2011 in West China Hospital,Sichuan University,China.Results Twenty-four patients were enrolled,with a median age of 36 years old and a median course of 4 years.Among them,14 cases were moderate UC and 10 cases were severe UC.The patients were treated with AZA in a dose of (1.23 ±0.34) mg· kg-1 · d-1 from 7 weeks to 42 months.Efficacy was judged by Mayo disease activity index.At 3 months,6 months and 1 year after treatment,the effective rates were 73.9％ ( 17/23),81.8％(18/22) and 14/16 respectively,and the remission rates were 17.4％ (4/23),54.5％ (12/22) and 12/16respectively.Both ESR and C reactive protein level after treatment for 6 months and 1 year were significantly lower than those before treatment [ (9.3 ±8.9) mrn/1h,(10.9 ±7.3) mm/1h vs (22.3 ± 10.7) mm/1h;2.5(1.0-22.3) mg/L,2.3(1.0-28.0) mg/L vs 18.4(3.6-137.0) mg/L; all P ＜0.05].Corticosteroid withdrawal rates at 3 months and 1 year after AZA treatment were 16/18 and 15/16,respectively.At 6 months and 1 year after AZA treatment,the endoscopic improvement rates were 85.7％ ( 18/21 ) and 13/15 respectively; the cndoscopic remission rates were 61.9％ ( 13/21 ) and 11/15 respectively; and the mucosal healing rates were 61.9％ ( 13/21 ) and 11/15 respectively.Adverse effects were occurred in 8 patients.Leukopenia was the most common adverse effect,followed by liver function injury,alopecia and epigastric discomfort.Conclusions AZA is effective in the treatment of refractory UC patients with a low dose of ( 1.23 ± 0.34) mg· kg - 1 · d - 1,especially in the steroid withdrawing,maintaining remission and mucosal healing without severe adverse effects.

Study on the ReHo in treatment-naïve of temporal lobe epilepsy patients with depressive symptoms using resting functional-MRI (fMRI) / 生物医学工程学杂志

Epilepsy is a common neurological disease accompanied with laden economic burdens and heavy social resources consuming. Temporal lobe epilepsy (TLE) is an important subtype of the epilepsies. Our experiment was aimed to characterize the regional brain function alteration among the treatment na? ve TLE patients using ReHo. We found that elevated regional ReHo was in the left insula in the TLE patients, and the right one was cingulated, while the decreasing ReHo was in right putamen. Our result demonstrated that the key components associated with the epilepsy symptoms had altered the regional function in the TLE patients, and the disruption of cortex-thalamus-striatum loop. Our experiment provides evidence on the pathophysiological alteration in treatment na? ve TLE patients.

Primary intestinal non-Hodgkin's lymphoma: a retrospective study of 85 cases / 南方医科大学学报

<p><b>OBJECTIVE</b>To review the clinical characteristics and treatment outcomes of primary intestinal non-Hodgkin's lymphomas (PINHL) and analyze the differences between T-cell and B-cell lymphomas.</p><p><b>METHODS</b>The characteristics of PINHL patients treated in our hospital between January 2003 and December 2010 were reviewed for their clinical manifestations, diagnosis, endoscopic findings, treatments and outcomes.</p><p><b>RESULTS</b>Eighty-five cases of PINHL meeting the Dawson's criteria were identified. The median age of the patients at the time of diagnosis was 52 years and the male: female ratio was 3.05:1; 58 cases (68.2%) had B-lineage and 27 cases (31.8%) had T-cell lineage lymphomas. Compared to those with B-cell lymphoma, patients with T-cell lymphomas showed a younger age of disease onset (32 vs 56 years, P<0.01) and presented with a greater incidence of such symptoms as fever, hematochezia, diarrhea and night sweats (P<0.05); T-cell lymphoma showed more multifocal and ulcerative/ulcero-infiltrative lesions under endoscope with a longer diagnosis time (4 vs 2 months, P<0.01) and a greater likeliness of misdiagnosis (16/27 vs 12/58, P<0.01) and poor prognosis. Extranodal NK/T-cell lymphoma was the most common type of T-cell lymphomas.</p><p><b>CONCLUSION</b>In our cases, T-cell lymphoma appeared to be more common than B-cell lymphoma with a younger onset age, more difficult diagnosis, a greater likeliness of misdiagnosis, poorer prognosis and more extranodal NK/T-cell lymphoma.</p>

Clinical and colonoscopic characteristics of Crohn disease and intestinal tuberculosis / 中华消化内镜杂志

ObjectiveTo unify the definitions of colonoscopic characteristics of Crohn disease (CD) and intestinal tuberculosis ( ITB),and to evaluate colonoscopic and clinical features in the differential diagnosis of CD and ITB.MethodsA collaborative group composed of 10 experts from 5 hospitals voted to identify and confirm the colonoscopic characteristics.Clinical and colonoscopic characteristics were analyzed,thereafter,characteristics were scored based on different diagnostic specificity.ROC curve was used for determining the cutoff point to differentiate CD from ITB.ResultsFirstly,standard endoscopic images and descriptions were determined.Secondly,colonoscopic parameters which were significantly different between the CD and ITB patients included the follows:involvement of more than four intestinal segments,anorectal involvement,longitudinal ulcers,cobblestone appearance and transverse ulcers.Clinical findings which were significantly different between the CD and ITB patients included active pulmonary tuberculosis,PPD-test strong positive,anal fistula/perianal abscess and extra-intestinal manifestations in CD.4.4％(6/136) patients were confirmed by histological evidence of caseating granulomas.By using our scoring system,39.7％ (54/136) confirmed diagnoses and 18.4％ (25/136) suspected diagnoses were made in patients without histological evidence.ConclusionIdentification of colonoscopic characteristics and unification of the colonscopic diagnostic criteria were helpful in the differential diagnosis between CD and ITB.The differential diagnosis rate could he improved by using the scoring system.Half cases could not be confirmed even with combined pathology and the scoring system,so a more comprhensive scoring system would be warranted.

Effects of total glucosides of paeony on the ulcerative colitis in rats / 中华临床营养杂志

@#Objective To investigate the effects of total glucosides of paeony (TGP) on mice with experimental ulcerative colitis and the underlying mechanisms. Methods Forty-eight mice were equally randomized into 6 groups ( n = 8): normal control group, model group, salicylazosulfapyridine (SASP) group, low-dose TGP group one day after enama, the mice were treated with corresponding agent by oral gavage for3 days. The disease activity index (DAI) score was evaluated every day. After all the mice were scarified, the macroscopic and histological scores were evaluated. The tumor necrosis factor-α (TNF-α) level of the colon mucosa was measured by ELISA and the colonic expression of nuclear factor-κB (NF-κB) p65 was detected by immunohistochemistry. Results Compared with the normal control group, the DAI score was significantly higher in the model group (P ＜0. 01 ),but was similar to that in low-dose TGP group ( P ＞ 0.05 ). Compared with the model group, the DAI score was significantly decreased in SASP group, medium-dose TGP group, and high-dose TGP group (all P ＜ 0. 05). The macroscopic score, histological score, TNF-α level, and expression of NF-κB p65 were significantly higher in model group than in normal control group, SASP group, medium-dose TGP group, and high-dose TGP group ( all P ＜0. 01 ), but was similar to that in low-dose TGP group (P ＞ 0. 05). The efficacy of TGP was higher in high-dose TGP group than in SASP group. Conclusions TGP has certain therapeutic effects on experimental ulcerative colitis,which may be achieved by its inhibitory effect on the activation of NF-κB and the production of TNF-α.

Analysis of surgical treatment for severe ulcerative colitis / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the role of different procedures in the treatment of severe ulcerative colitis (UC) requiring colectomy.</p><p><b>METHODS</b>A total of 29 UC inpatients who underwent colectomy at the West China Hospital between January 1996 and December 2008 were included in this study. Except two cases who underwent partial colectomy, patients were divided into total colectomy group (TC group, n=7) and total proctocolectomy group (TPC group, n=20), meanwhile divided into ileal pouch-anal anastomosis (IPAA, n=8) group, straight end-to-end anastomosis (ileoanal or ileorectal and ileostomy) group (n=14)and ileostomy group (n=5). Quality of life (QOL) was assessed using the Cleveland Global Quality of Life (CGQL) instrument.</p><p><b>RESULTS</b>The complication rate was 60.0% in TPC group and 57.1% in TC group (P>0.05). The recurrence rate was 15.0% in TPC group and 57.1% in TC group (P<0.05). The complication rate was 6/8 in IPAA group and 50.0% (7/14) in straight end-to-end anastomosis group (P>0.05). The frequency of daily bowel movements in IPAA group was significantly lower than that in straight end-to-end anastomosis group at 1 year after the surgery (5.6+/-1.7 versus 9.1+/-2.9, P<0.05). QOL was significantly improved postoperatively for all the patients(P<0.01). Patients who underwent IPAA had a better QOL than those of straight end-to-end anastomosis group (P>0.05).</p><p><b>CONCLUSIONS</b>TPC-IPAA is the ideal procedure of severe UC with acceptable complication rate, satisfactory quality of life and functional outcome.</p>

Effects of Bawei Xilei San on mice with oxazolone-induced colitis and the mechanisms / 中西医结合学报

Objective: To investigate the therapeutic effects of Bawei Xilei San (BWXLS), a compound traditional Chinese herbal medicine, on mice with oxazolone-induced colitis and to explore the mechanisms. Methods: Thirty-two BALB/c mice were randomly divided into 4 groups (8 for each): normal control group, untreated group, hydrocortisone group and BWXLS group. Except for the mice in the normal control group, all mice were intrarectally administered with 3.0% oxazolone to induce colitis. Then the mice in the normal control group and untreated group were administered with 0.9% carboxymethyl cellulose sodium solution. Mice in the BWXLS group were intrarectally administered with 0.2 mg/g BWXLS and hydrocortisone group with 0.02 mg/g respectively for 5 days. The body weight and stool consistency and occult or gross blood were recorded to calculate the disease activity index (DAI). The mice were sacrificed at the 6th day. The macroscopic and histological changes of the colon were evaluated. The expressions of Toll-like receptor 4 (TLR4), nuclear factor-kappaB (NF-kappaB), and epithelial tight junction protein occludin were assessed by immunohistochemical method. The level of tumor necrosis factor-alpha (TNF-alpha) in colonic mucosa was evaluated by enzyme-linked immunosorbent assay. Results: The DAI, and macroscopic and histological changes in the BWXLS group were improved as compared with those in the untreated group (P0.05). Conclusion: Up-regulating the expression of occludin and down-regulating the expressions of TLR4 and NF-kappaB, and hence inhibiting TNF-alpha expression and improving the mucosa barrier function may be part of the mechanisms of BWXLS in treating oxazolone-induced colitis in mice.

The role of COX-2 in the regulation of Wnt signal pathway / 中华内科杂志

Objective Wnt signal is very important to control the gastrointestinal mucosal proliferation, but its role in the gastric mucosal proliferation after acidified ethanol injury is not clear yet,neither is the relationship with cyclooxygenase 2 (COX-2). Methods X-gal staining was used to measure the expression of Wnt signaling; Western blot and RT-PCR were used to measure the expression of TCF4 and P-Catenin in the gastric mucosa before and after acidified ethanol injury. We also used TOP/flash plasmid to further indentify the relationship between COX-2 and Wnt signal pathway. Results After acidified ethanol injury, the expression of LacZ signal, β-Catenin and TCF4 increased only in the wild type mouse. The expression of β-Catenin and TCF4 protein increased about (3.52 ±0.52) times and (3.02 ±0.62) times separately, and the expression of β-Catenin and TCF4 mRNA increased about (19. 85 ±3.63) times and (17.82 ±4.82) times separately. Without ethanol injury, the expression of TOP/flash plasmid was inhibited by COX-2 inhibitor (NS398) about 80% and promoted by prostaglandin E2(PGE2) about 50%.After 1% ethanol injury, the expression of plasmid was inhibited by NS398 about 25% ; on the contrary,PGE2 promoted the expression about 10%. Conclusion Wnt signal in gastric mucosa is activated after acidified ethanol injury. COX-2 may work through modulating Wnt signal to control the proliferation of gastric mucosa.

Chemoprevention of Barrett's esophagus by celecoxib in rats / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To examine the chemopreventive effect of selective cyclooxygenase-2 (COX-2) inhibitor celecoxib for Barrett's esophagus in rats.</p><p><b>METHODS</b>Fifty 8-week-old male Sprague Dawley rats underwent esophagojejunostomy to induce Barrett's esophagus model. Four weeks after operation the animals were given celecoxib 10 mg/(kg*d(-1))(celecoxib group), or saline 1 ml (control group). Another 10 rats were sham operation group. All animals were sacrificed at 20 week after surgery. The degree of inflammation, Barrett's esophagus, adenocarcinoma, COX-2 expression and PGE(2) of animals were assessed.</p><p><b>RESULT</b>Among 60 rats, 6 rats died in celecoxib group, 8 rats died in control group, 1 rat died in sham operation group, and 45 (75%) rats completed the study. The incidence of mild, moderate and severe degree esophageal inflammation in celecoxib group and control group was 14/19(73.68%), 4/19(21.05%), 1/19(5.26%); 4/17(23.53%), 5/17(29.41%), 8/17(47.06%)(P<0.05), respectively. The incidence of Barrett's esophagus was 7/19(36.84%), 13/17(76.47%) in two group respectively(P<0.05); The incidence of Barrett's esophagus with dysplasia was 2/19(10.53%), 8/17(47.06%)(P<0.05), respectively. The expression of COX-2 was 1/7(14.29%), 10/13(76.92%)(P<0.05) in two groups. PGE2 content was significantly lower in the celecoxib group than that in control group(P<0.001). No esophageal pathological changes were found in sham operation group.</p><p><b>CONCLUSION</b>Selective COX-2 inhibitors celecoxib can inhibit inflammations, development of Barrett's esophagus and esophagus adenocarcinoma.</p>

Expression and function of interleukin-23/17 axis in trinitrobenzene sulphonic acid induced colitis in mouse / 中华消化杂志

Objective To study the expression and the role of interleukin (IL)-23/IL-17 axis in colonic tissue of trinitrobenzene sulphonic acid (TNBS) induced eolitic mice.Methods Mice were divided into four groups:control (n=24),TNBS (n= 24),TNBS 48 hours + mlL-17 antibodies (n=24),TNBS 48 hours + normal rat blood-serum (n= 24).TNBS-induced colitis model was constructed.The mice in control group and TNBS colitis group were sacrificed at 24 hours,48 hours,7th day,respectively.In TNBS 48 hours + mlL-17 antibodies group and TNBS 48 hours + normal rat blood-serum group,a single injection with the polyclonal mlL-17 antibodies or serum were given intraperitoneally at two hours before enema with TNBS,respectively,and the mice were killed at 48 hours after enema with TNBS.The histological score of colon and myeloperoxidase (MPO) activity of colonic tissue were evaluated in each group.IL-23p19 and IL-17 concentrations in colonic tissue were measured by enzyme-linked immunosorbent assay (ELISA).Expression of nuclear factor (NF)-κBp65in colonic tissue was detected by immunohistochemistry method.Expression of IL-23p19,IL-17 and IL-12p35 mRNA in colonic tissue were detected by real-time fluorescent quantitative reverse transcriptase polymerase chain reaction (RT-PCR) with SYBR Green I.Results The protein levels of IL-23p19 in colonic tissue in TNBS colitis groups at 24 hours,48 hours and 7 days were (15.53±3.32),(31.16±4.98) and (14.03±3.56) ng/mg,respectively,and their mRNA level were (4.09±0.34),(3.39±0.46) and (6.54±1.82),respectively.The protein levels of IL-17 were (0.35±0.06),(0.38±0.08),and (0.26±0.05) ng/mg,respectively,and their mRNA level were (4.21±2.61),(2.65±0.91) and (5.63±1.43),respectively.The expression levels of IL-23p19 and IL-17 in colitis model were significantly higher than those in control group and the peak was at 48 hours.Moreover,expression of IL-23p19 and IL-17 and their mRNA were positively correlated to their mRNA levels.In TNBS 48 hours + mIL-17 antibodies group,the expression levels of NF-κBp65,the microscopic scores and MPO (1.86 % ± 0.36 %,0.63 ± 0.52,0.40 ± 0.03 U/g,respectively) were significantly lower than those in TNBS 48 hours group (4.35% ±0.37%,5.13±0.64,2.29±0.40 U/g tissue,respectively).Neutralization of IL-17 was significantly protected against TNBS-induced colonic inflammation and MPO and expression of NF-κB p65.The results indicated that neutralization of IL-17 significantly reduced colonic inflammation and suppressed NF-κBp65 activation.This protection occurred in the presence of equivalent induction of local IL-23 p19 and high levels of IL-12p35 in the polyclonal raiL-17 antibodies-treated mice.Conclusions IL-23/IL-17 axis plays a critical role at the early acute phase of TNBS-induced inflammation.IL-17 may represent a new target for therapeutic intervention for inflammatory bowel disease.

A comparison of clinical and pathologic characteristics between Crohn's disease and intestinal tuberculosis / 中华内科杂志

Objective To search for the distinctive diagnostic features of Crohn's disease and intestinal tuberculosis in clinical manifestations with methods widely used clinically.Methods A retrospective study enrolled 33 Crohn's disease and 34 intestinal tuberculosis inpatients in West China Hospital of Sichuan University from 1996 to 2007.The clinical characteristics and key points of differential diagnosis were analyzed.All the pathological sections were studied again.Results The total duration of symptoms in patients with a diagnosis of Crohn's disease was longer than that in patients with intestinal tuberculosis ( P < 0.05 ).The incidence of eolectomy is significantly higher in Crohn' s disease than in intestinal tuberculosis because of intestinal obstruction or undefined diagnosis ( P < 0.05 ).Hematochezia,extra-intestinal manifestation and ileus occurred significantly more in Crohn's disease than in intestinal tuberculosis( P < 0.05 ).Night sweating and hypoalbuminemia occurred significantly more in intestinal tuberculosis than in Crohn's disease( P <0.05 ).The positive rate of serum antibodies to mycobacterium and increased erythrocyte sedimentation rate is higher in intestinal tuberculosis than in Crohn's disease(P < 0.05).Cobblestone sign and fissure-shape ulcers were only found in Crohn's disease,while circular ulcer occurred significantly more in intestinal tuberculosis( P <0.05).The involvement of stomach,jejunum or ileum was significantly more in Crohn's disease than in intestinal tuberculosis( P < 0.05 ).Granulomas were more common in intestinal tuberculosis than in Crohn's disease( P < 0.05 ) and the site of granulomas was valuable for differential diagnosis.In all the Crohn's disease specimens,lymphoid aggregates in the lamina propria or submucosa were significantly more in surgically reseeted specimens than in endoscopic biopsies (P <0.05).Conclusions There are definitely some different features between the two diseases.It is essential to review the whole clinical data of the patient.The frequency of granulomas and the distribution of chronic inflammation are identified as histological parameters that can be used to differentiate tuberculosis and Crolm's disease.

Expression and significance of mucosal β-defensin-2,TNFα and IL-1β in ulcerative colitis CHANG / 中华内科杂志

Objective To investigate the expression and significance of human β-defensin-2 (HBD2),TNFα and IL-1βin ulcerative colitis(UC).Methods Thirty-five patients with active UC diagnosed by the department of gastroenterology in West China Hospital were included in this study.Ulcerative colitis disease activity index(UCAI)was assessed and the pathological grades of UC were classified.Immunohistochemistry assay and real-time quantitative PCR were used for the expression of HBD2,TNFα,IL-1β in colonic mucosa of UC.Results Among the 35 patients with UC,10 cases were mild.13 moderate and 12 severe.Of the 35 cases.there were 11 with grade Ⅰ.13 grade Ⅱ and 11 grade Ⅲ lesion according to Truelove criteria.The score of UCAI had positive correlation with pathological grading (r=0.890,P＜0.01).The expressions of HBD2,TNFα,IL-1β in colonic mucosa of UC with immunohistochemistry and real-time quantitative PCR were significantly higher than those in healthy control (P＜0.05);the expressions increased gradually with the severity of pathological grade and there was a higher expression of them in inflamed area than in non-inflamed(P＜0.05).A good positive correlation was also found between HBD2 and other inflammatory cytokines.Conclusions It is shown that there is a higher expression of HBD2 in colonic mucosa as compared with healthy control.a higher expression of it in inflamed area than in non-inflamed area and a positive correlation of expression between HBD2 and pro-inflammatory cytokines such as TNFα and IL-1 β,implying that HBD2 and pro-inflammatory cytokines are interdependent and interactive playing an important role in magnifying and aggravating inflammatory injury in UC.