Objective To evaluate the inhibiting effect of selective and non-selective cyclo-oxygenase-2(COX-2) inhibitor on growth of colon cancer cell lines in vitro and its signal transduction pathway. Methods The proliferation of colon cancer cells was determined by MTT assay. COX-2, nuclear factor(NF)-?Bp65, extracellular-signal regulated kinase(ERK), phospho ERK(pERK) protein expressed in colon cancer cell lines were analyzed by Western blot. Activator protein(AP)-1 and NF-?B binding activity influenced by non-steroidal anti-inflammatory was detected by electrophoretic mobility sift assay. Results Aspirin and celecoxib could inhibit the proliferation of HT-29, SW480 and LS174-T cells and showed a dose-dependent manner. Western blot analysis showed that expression of COX-2, pERK, NF-?Bp65 protein in colon cancer cells were down-regulated by celecoxib or aspirin in some degree but not effect in total ERK expression. AP-1 and NF-?B binding activity could be stimulated by 20% fetal calf serum or tumor necrosis factor-?. Both aspirin and celecoxib could inhibit fetal calf serum-induced AP-1 activation in HT-29 and SW480 cells. Celecoxib could also inhibit tumor necrosis factor induced NF-?B binding activity, but aspirin had little effects on SW480 cells. Conclusion NSAIDs are able to potentially inhibit the growth of colon cell lines in vitro and the mechanism may relate to AP-1 and NF-?B signal transduction pathway.

Objective To investigate the clinical features of small bowel Crohn's disease(CD).Methods From January 2009 to September 2012,a total of 138 patients diagnosed as CD who underwent examinations of colonoscopy,digestive tract radiography,capsule endoscopy,double-balloon enteroscopy and computed tomography (CT) enterography were enrolled.According to the Montreal Classification criteria,the disease was typed by the age at diagnosis,location of the lesions and behavior of the disease.The clinical symptoms,laboratory examinations,diagnostic methods and recurrence condition were also evaluated.Through the comparison of the clinical features of ileocolonic and colonic CD,the clinical features of small bowel CD were analyzed.Measurement data were analyzed with t-test,analysis of variance or non parametric test.Chi square test was performed for count data.Spearman's correlation analysis was used for correlation analysis and multivariate Logistic regression analysis was used for risk factors screening.Results A total of 62 (44.9％) cases were simple small bowel CD.Fifty-three patients (85.5％) were male,and the mean age at diagnosis was 35.3 years old.The age of 67.7％(42/62) of small bowel CD patients were less than 40 years old when diagnosed.The ratio of stricture in small bowel CD group (35.5％,22/62) was significantly higher than that of ileocolonic (18.8％,6/32) and colonic CD group (13.9％,5/36) (x2=6.594,P=0.037).Jejunal involvement was an independent risk factor for structure in CD (OR=3.481,95％ CI:1.250 to 9.693).The patients with obstructive symptoms as primary symptom in small bowel CD (38.7％,24/62) were more than those with colonic CD (16.7％,6/36) (x2 =5.210,P=0.022).However,patients with diarrhea as primary symptom in small bowel CD (21.0％,13/62) were less than those with ileocolonic (37.5％,12/32) and colonic CD (44.4％,16/36) (x2=6.512,P=0.039).Patients with two or more extraintestinal manifestations in small bowel CD (3.2％,2/62) were also significantly less than those with ileocolonic (15.6％,5/32) and colonic CD (19.4％,7/36) (x2=7.957,P=0.019).The score of CD activity index was generally low,and with no statistical correlation to serum inflammation markers such as C reaction protein.The average time duration between induction of remission and clinical recurrence of small bowel CD ((23.64 ± 17.08) months) was shorter than that of ileocolonic type ((35.07±29.84) months,t=-4.285,P=0.002) and colonic CD ((32.35 ± 28.46) months,t =-3.700,P =0.004).However,there was no significant difference in the rate of clinical recurrence between small bowel CD and ileocolonic,colonic CD.Conclusions Patients with small bowel CD account for a large proportion in patients with CD,especially in males.Stricture is more common in jejunum CD.The time duration between induction of remission and clinical recurrence of small bowel CD is short.

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.

OBJECTIVE: To understand the value of Child-Pugh (CP) classification and model of end-stage liver disease (MELD) score for patients with cirrhosis and their prognosis by retrospectively analyzing the two methods in hemorrhage death and non-hemorrhage death in patients with liver cirrhosis. METHODS: A total of 72 patients who died of cirrhosis (the death group) were analyzed retrospectively, and the initial data in the hospital before death were collected. The initial information of the control group (88 patients) at the same time was also obtained. The death group was divided into two subgroups: esophagus varicosity burst massive hemorrhage death group and non-hemorrhage death group. RESULTS: MELD score and CP score of the death group (22.230±13.451, 10.264±2.028) were significantly higher than those of the control group (15.370±6.201, 9.318±1.644; P<0.05). The MELD score and CP score for the massive bleeding death group were close to those of the control group. There was significant difference between the non-hemorrhage death group and the control group. The ratio of patients with CP grade A and MELD scores<20 died for massive bleeding in the death group was more than 70%, and that of CP grade C and MELD scores ≥ 30 in the death group was higher. ROC surve analysis found the accuracy of short-term predication of survival by MELD score and CP classification was improved after eliminating the risk factors of hemorrage. CONCLUSION MELD and CP play a role in evaluating the state and prognosis of patients with cirrhosis. MELD score and CP classification predict the short-term survival efficiently on the premise of excluding the risk factors of esophagus and/or stomach bottom varicosity burst massive bleeding. CP and MELD scores are deficiencies, especially for low MELD score (<20) and CP level A patients. The prognostic accuracy may be improved when combining esophageal gastric fundal varices.
End Stage Liver Disease ; diagnosis ; mortality ; Esophageal and Gastric Varices ; Humans ; Liver Cirrhosis ; diagnosis ; mortality ; Prognosis ; ROC Curve ; Retrospective Studies ; Risk Factors ; Severity of Illness Index

This study was conducted to evaluate the growth and NAG-1 gene expression effected by Non-steroidal anti-inflammatory drug (NSAID) on colon cancer cell lines in vitro. The proliferation of colon cancer cells were determined by MTT assay and COX-2 protein expression were detected by Western blot. Total RNA was isolated from three kinds of colon cancer cell lines; the expressions of NAG-1 mRNA in the cells treated with or without NSAIDs were assessed by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay. Celecoxib, meloxicam and aspirin were able to inhibit the growth of HT-29, SW480 and LS174-T cells in dose-dependent manner. COX-2 protein expressed in HT-29 and LS174-T, but not in SW480 cells. All of colon cancer cells expressed NAG-1 gene and the level of LS174-T was lower than that of the other two cell lines. NAG-1 expression was increased by treatment with some NSAIDs in all three kinds of colon cancer cells. NSAIDs were able to potentially inhibit the growth of colon cell lines. Induction of NAG-1 gene expression by NSAID was not consistent with COX-2 expression.
Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; Antineoplastic Agents ; pharmacology ; Aspirin ; pharmacology ; Celecoxib ; Cell Proliferation ; drug effects ; Cyclooxygenase 2 ; metabolism ; Gene Expression Regulation, Neoplastic ; HT29 Cells ; Humans ; Neoplasm Proteins ; metabolism ; Pyrazoles ; pharmacology ; RNA, Messenger ; metabolism ; Sulfonamides ; pharmacology ; Thiazines ; pharmacology ; Thiazoles ; pharmacology

Objective To explore the changes and their clinical significance of peripheral blood myeloid-derived suppressor cells (MDSC)and their subtypes in patients with inflammatory bowel disease (IBD).Methods From April 2016 to April 2017,99 hospitalized IBD patients in 2nd Xiangya Hospital of Central South University were enrolled as observation group one,which included 84 Crohn's disease (CD) (70 in active phase and 14 in remission phase)and 15 patients with ulcerative colitis(UC).At the same period,32 healthy controls were enrolled as healthy control group one.The proportion of peripheral blood MDSC and subtypes of CD patients,UC patients and healthy controls were examined.Observation group two including 62 IBD patients (47 CD and 15 UC)were selected from observation group one and 21 healthy individuals were selected from healthy control group one as healthy control.The serum levels of tumor necrosis factorα(TNF-α)and interleukin 8 (IL-8)were detected.Chi square test,t test and one-way analysis of variance were performed for statistical analysis.Pearson correlation was performed for correlation analysis.Results The proportion of MDSC in peripheral blood mononuclear cells of CD and UC patients of observation group one were both higher than that of healthy control group one ((6 .30 ± 3.97)% and (7.50±3.12)% vs.(3.94±2.25)%,respectively),and the differences were statistically significant (t＝-3.22 and -3.21,both P＜0.01).The proportion of granulocytic MDSC in peripheral blood mononuclear cells of CD patients was higher than that of UC patients and healthy control group one ((65.69±20.45)% vs.(50.93±13.56)% and (51.50±11.61)%,respectively),and the differences were statistically significant (t＝2 .93 and 3 .79 ,both P＜0 .01 ).The proportion of monocytic MDSC in peripheral blood mononuclear cells of UC patients was higher than that of CD patients and healthy control group one ((28.41±18.33)% vs.(18.38±17.43)% and (28.17±10.22)%,respectively),and the differences were statistically significant (t＝2.22 and 2.93,both P＜0.05 ).The proportion of granulocytic MDSC was higher and the proportion of monocytic MDSC was lower in peripheral blood mononuclear cells of CD patients in active phase than those of CD patients in remission phase ((67 .36 ± 2.27)% vs.(46.49±6.32)%,and (17.19±2.02)% vs.(34.33±6.12)%),and the differences were statistically significant (t＝3.60 and 3.26,both P＜0.01).The serum level of TNF-αof CD patients of observation group two was higher than that of UC patients and healthy control group two ((7.83± 6.54)ng/L vs.(4.77±2.12)ng/L and (4.40±2.05)ng/L),and the differences were statistically significant (t＝2.01 and 2.53,both P＜0.05).The serum level of IL-8 of UC patients of observation group two was higher than that of CD patients and healthy control group two ((65.80±45.14)ng/L vs. (25.80±22.32)ng/L and (26.40±22.37)ng/L),and the differences were statistically significant (t＝4.87 and 4.21,both P＜0.01).Granulocytic MDSC was positively correlated with TNF-α(r＝0.319, P＝0 .0 1 1 )and was negatively correlated with IL-8 (r＝-0 .2 9 6 ,P＝0 .0 1 9 ).Monocytic MDSC was negatively correlated with TNF-α(r＝-0.260,P＝0.040)and was positively correlated with IL-8 (r＝0.306,P＝0.016).Conclusions The proportion of granulocytic MDSC in peripheral blood mononuclear cells significantly increases in active CD patients,while the proportion of monocytic MDSC significantly increases in UC and CD patients in remission phase.Detection of MDSC and their subtypes maybe helpful in the differentiation of CD and UC as well as the diagnosis and treatment of CD.

OBJECTIVE: To analyze the characteristics of intestinal flora in Crohn's disease (CD) and intestinal tuberculosis (ITb), and to find potential identification features to differentiate these 2 diseases. METHODS: Fifteen CD patients, 23 ITb patients, and 21 healthy volunteers (controls) were enrolled from June 2007 to November 2009. Selective culturing was used for the enumeration of bacteria count. RESULTS: The intestinal flora was mainly composed of Bifidobacteria, Bacteroids, Escherichia coli and Staphylococcus aureus both in CD and ITb patients. Lactobacillus and Bifidobacteria decreased obviously but Bacteroid increased in CD patients compared with the control (P<0.01). Lactobacillus, Bifidobacteria and Escherichia coli decreased obviously (P<0.05), but Bacteroid increased in ITb patients compared with the control (P<0.01). Bacteroid increased in ITb patients compared with CD patients (P<0.05). No difference in Enterococcus, Staphylococcus aureus and Saccharomycete was found among the 3 groups (P>0.05). CONCLUSION Intestinal flora disorder occurred in either CD or ITb patients. The alteration of Bacteroid and Escherichia coli can help differentiate the 2 diseases.
Adult ; Bacteroides ; isolation & purification ; Crohn Disease ; diagnosis ; microbiology ; Diagnosis, Differential ; Escherichia coli ; isolation & purification ; Feces ; microbiology ; Female ; Humans ; Male ; Tuberculosis, Gastrointestinal ; diagnosis ; microbiology

Crohn′s disease (CD) is a chronic, progressive and destructive inflammatory disease affecting the entire digestive tract. Changes in the intestinal microbiota, particularly a decrease in gut microbiome diversity, are thought to be associated with chronic intestinal inflammation of CD. As for the mechanism of antibiotics in CD treatment, some scholars believe that antibiotics can affect the course of disease by reducing the concentration of intestinal bacteria and changing the composition of intestinal microbiota. Different antibiotics, including ciprofloxacin, metronidazole and rifaximin, have been proved to have certain therapeutic effect on some patients with CD in clinical practice, but there are still limitations in the use of antibiotics.In this review, the relationship between intestinal flora and the incidence of CD and the application of antibiotics in CD were reviewed, providing reference and help for the standardized application of antibiotics in CD.

Objective:To evaluate the efficacy and safety of oliceridine for treatment of moderate to severe pain after surgery with general anesthesia in patients.Methods:The patients with moderate to severe pain (numeric pain rating scale ≥4) after abdominal surgery with general anesthesia from 14 hospitals between July 6, 2021 and November 9, 2021 were included in this study. The patients were assigned to either experiment group or control group using a random number table method. Experiment group received oliceridine, while control group received morphine, and both groups were treated with a loading dose plus patient-controlled analgesia and supplemental doses for 24 h. The primary efficacy endpoint was the drug response rate within 24 h after giving the loading dose. Secondary efficacy endpoints included early (within 1 h after giving the loading dose) drug response rates and use of rescue medication. Safety endpoints encompassed the development of respiratory depression and other adverse reactions during treatment.Results:After randomization, both the full analysis set and safety analysis set comprised 180 cases, with 92 in experiment group and 88 in control group. The per-protocol set included 170 cases, with 86 in experiment group and 84 in control group. There were no statistically significant differences between the two groups in 24-h drug response rates, rescue analgesia rates, respiratory depression, and incidence of other adverse reactions ( P>0.05). The analysis of full analysis set showed that the experiment group had a higher drug response rate at 5-30 min after giving the loading dose compared to control group ( P<0.05). The per-protocol set analysis indicated that experiment group had a higher drug response rate at 5-15 min after giving the loading dose than control group ( P<0.05). Conclusions:When used for treatment of moderate to severe pain after surgery with general anesthesia in patients, oliceridine provides comparable analgesic efficacy to morphine, with a faster onset.

The Ly-6 and uPAR (LU) domain-containing proteins represent a large family of cell-surface markers. In particular, mouse Ly-6A/Sca-1 is a widely used marker for various stem cells; however, its human ortholog is missing. In this study, based on a systematic survey and comparative genomic study of mouse and human LU domain-containing proteins, we identified a previously unannotated human gene encoding the candidate ortholog of mouse Ly-6A/Sca-1. This gene, hereby named LY6A, reversely overlaps with a lncRNA gene in the majority of exonic sequences. We found that LY6A is aberrantly expressed in pituitary tumors, but not in normal pituitary tissues, and may contribute to tumorigenesis. Similar to mouse Ly-6A/Sca-1, human LY6A is also upregulated by interferon, suggesting a conserved transcriptional regulatory mechanism between humans and mice. We cloned the full-length LY6A cDNA, whose encoded protein sequence, domain architecture, and exon-intron structures are all well conserved with mouse Ly-6A/Sca-1. Ectopic expression of the LY6A protein in cells demonstrates that it acts the same as mouse Ly-6A/Sca-1 in their processing and glycosylphosphatidylinositol anchoring to the cell membrane. Collectively, these studies unveil a novel human gene encoding a candidate biomarker and provide an interesting model gene for studying gene regulatory and evolutionary mechanisms.
Humans ; Membrane Proteins/genetics* ; Pituitary Neoplasms/genetics* ; Biomarkers