[Thalidomide in refractory Crohn's disease: long-term efficacy and safety].

Objective: To analyze the long-term efficacy and safety of thalidomide on refractory Crohn's disease (CD). Methods: A total of 79 patients with refractory CD in the First Affiliated Hospital of Sun Yat-sen University treated with thalidomide were enrolled in this retrospective study from September 2005 to July 2018. Clinical effects and adverse drug reactions were recorded and assessed. Results: In this cohort,69 patients were treated with thalidomide for ≥6 months. Sixty-eight patients among the 69 patients achieved complete clinical remission and were followed up for a median 33.5 months (range, 7-110 months). Seventeen cases relapsed during follow-up. The cumulative probabilities of remaining in remission at 12, 24, 60 months were 88.6% (95%CI 80.6%-96.6%), 80.7% (95%CI 70.3%-91.1%), 53.7% (95%CI 32.1%-75.3%) respectively. Disease activity was the only variable associated with relapse risk, with a hazard ratio (HR) of 3.559 for Crohn's disease activity index (CDAI) ≥220(95%CI 1.213-10.449, P<0.05). Adverse reactions were recorded in 42 (53.2%) patients including12 (15.2%) leading to discontinuation of thalidomide. No serious side effects were observed in all subjects. Conclusions: This study suggests a long-term benefit of maintenance treatment with thalidomide in refractory CD.Moderate to severe patients have an increased risk of relapse. The high incidence of drug adverse reactions may restrain the clinical application of thalidomide.

Primary antibiotic resistance of Helicobacter pylori in Chinese patients: a multiregion prospective 7-year study.

OBJECTIVES: To explore the characteristics of Helicobacter pylori resistance in China and the association between antibiotic resistance and several clinical factors. METHODS: H. pylori strains were collected from patients in 13 provinces or cities in China between 2010 and 2016. Demographic data including type of disease, geographic area, age, gender and isolation year were collected to analyse their association with antibiotic resistance. Antibiotic resistance was detected using the Etest test and the Kirby-Bauer disc diffusion method. RESULTS: H. pylori were successfully cultured from 1117 patients. The prevalence of metronidazole, clarithromycin (CLA), azithromycin, levofloxacin (LEV), moxifloxacin, amoxicillin (AMO), tetracycline and rifampicin resistance was 78.2, 22.1, 23.3, 19.2, 17.2, 3.4, 1.9 and 1.5%, respectively. No resistance to furazolidone was observed. The resistance rates to LEV and moxifloxacin were higher in strains isolated from patients with gastritis compared to those with duodenal ulcer and among women. Compared to patients ≥40 years old, younger patients exhibited lower resistance rates to CLA, azithromycin, LEV and moxifloxacin. The resistance rates to CLA and AMO were higher in strains isolated more recently, and we also found that the prevalence of resistance to metronidazole, CLA, azithromycin and AMO were significantly different among different regions of China. CONCLUSIONS: The resistance rates to metronidazole, CLA and LEV were high in China. Patient age, gender, disease and location were associated with the resistance of H. pylori to some antibiotics. Furazolidone, AMO and tetracycline are better choices for H. pylori treatment in China.

TLR3 preconditioning enhances the therapeutic efficacy of umbilical cord mesenchymal stem cells in TNBS-induced colitis via the TLR3-Jagged-1-Notch-1 pathway.

Toll-like receptor-3 (TLR3) priming may enhance mesenchymal stem cell (MSC) immunosuppressive activity, but this mechanism has not been investigated in the context of inflammatory bowel disease. Thus, we assessed the immunosuppressive properties of TLR3-primed MSCs using a trinitrobenzene sulfonate (TNBS)-induced mouse model of colitis. Intraperitoneally injected polyribocytidylic acid (poly (I:C)- (a ligand of TLR3) primed human umbilical cord-derived MSCs (hUC-MSCs) migrated to the inflamed colon and effectively improved clinical and pathological manifestations in colitic mice compared with mice treated with unstimulated hUC-MSCs (UCMs). Poly (I:C)-MSCs decreased a wide range of inflammatory cytokines and increased systemic interleukin-10 (IL-10) levels in colonic tissues. Poly (I:C)-MSCs also impaired T-helper type 1/17 (Th1/17) cell expansion and enhanced the suppressive effects of regulatory T cells (Treg) in vitro and in vivo. Poly (I:C)-MSCs suppressed the proliferation of activated mesenteric lymph node (MLN) cells via the overproduction of prostaglandin E2 (PGE2) and upregulation of Jagged-1. PGE2 produced by hUC-MSCs in response to poly (I:C) increased the production of IL-10 and promoted the differentiation of Treg, which could be reversed by inhibition of Notch-1. Collectively, preconditioning MSCs with poly (I:C) enhanced the therapeutic effects of hUC-MSCs in TNBS-induced colitis, and TLR3-activated Notch-1 signaling regulated the immune suppression of hUC-MSCs through the production of PGE2.

[Nutritional risk screening in patients with Crohn's disease].

OBJECTIVE: To screen the nutritional risk in patients with Crohn's disease (CD), to explore the prevalence and characteristics of nutritional risk in CD patients, and to identify the possible risk factors. METHOD: A cross-sectional study was performed in 712 patients who was diagnosed as CD in the Center for Inflammatory Bowel Disease of First Affiliated Hospital of Sun Yat-sen University between January 2003 and January 2014. Montreal classification was used to classify CD, Crohn's Disease Activity Index (CDAI) was used to evaluate disease activity, and Nutritional Risk Screening 2002 (NRS2002) was used to assess the nutritional risk in each patient. Reappraisal with NRS 2002 was conducted in patients followed up for 1 year to identify the possible effect of treatment on nutritional risk of the CD patients. RESULTS: The prevalence of nutritional risk was 65.2% (464/712) in the enrolled CD patients. The prevalence of nutritional risk was significantly different among patients with different disease activity (χ(2)=117.169, P<0.001), also significantly different among patients of different age at diagnosis (χ(2)=11.256, P=0.004), with different lesion location (χ(2)=18.841, P=0.001) and different disease behavior (χ(2)=15.793, P<0.001), but not significantly different in patients of different sex (χ(2)=0.601, P=0.245). Multivariate Logistic regression showed that the independent predictive risk factors for nutritional risk included abdominal tenderness (OR=1.895, 95%CI: 1.080-3.324); mild (OR=1.846, 95%CI: 1.179-2.890), moderate (OR=4.410, 95%CI: 2.701-7.200) and severe (OR=14.069, 95%CI: 1.718-115.192) disease activity; B2 (stricturing) (OR=1.620, 95%CI: 1.034-2.538) and B3 (penetrating) (OR=1.920, 95%CI: 1.025-3.596) types of disease behavior; and high level with erythrocyte sedimentation rate (ESR) (OR=1.024, 95%CI: 1.015-1.034). On the other hand, >40 years at diagnosis (A3 type) (OR=0.332, 95%CI: 0.135-0.814) and high albumin level (OR=0.962, 95%CI: 0.934-0.990) were independent protective factors for nutritional risk. After 1-year follow-up, nutritional risk was eliminated in 32.0%(111/347)of the patients, and the rate was higher in patients received surgery than in those treated with medicine alone (42.9%(54/126)vs 25.8%(57/221), χ(2)=10.742, P=0.001). CONCLUSIONS: Two thirds of CD patients may have nutritional risk at diagnosis, which may differ with disease activity and Montreal classification. Abdominal tenderness, disease activity, B2 and B3 types of disease behavior, and high ESR may be independent risk factors for nutritional risk, whereas A3 type of age at diagnosis and high albumin level may be independent protective factors.

Systematic review with meta-analysis: magnetic resonance enterography vs. computed tomography enterography for evaluating disease activity in small bowel Crohn's disease.

BACKGROUND: Magnetic resonance enterography (MRE) has been proposed as a non-ionising alternative method to computed tomography enterography (CTE). Some studies have directly compared CTE and MRE in patients with small bowel Crohn's disease (CD) with variable results. AIM: To compare the overall diagnostic accuracy in assessing the activity of small bowel and complications. METHODS: MEDLINE, EMBASE and Cochrane databases were searched for studies on the accuracy of MRE and CTE, as compared with a pre-defined reference standard. Pooled sensitivity, specificity, the weighted area under the curve (AUC), incremental yield (IY) and other diagnostic indices were evaluated. RESULTS: A total of 290 CD patients from six different studies were analysed. The pooled sensitivity and specificity for MRE in detecting active small bowel CD was 87.9% [95% confidence interval (CI), 81.8-92.5] and 81.2% (95% CI: 71.9-88.4) respectively. The AUC under the summary receiver-operating characteristic (sROC) of MRE was 0.905 (SEM 0.03, standard error of the mean). Likewise, the pooled sensitivity and specificity of CTE in detecting active small bowel CD was 85.8% (95% CI: 79.2-90.9) and 83.6% (95% CI: 75.3-90.1) with the AUC of 0.898. The AUC of MRE in detecting fistula, stenosis and abscess was 0.936, 0.931 and 0.996, respectively, compared to 0.963, 0.616 and 0.899 of CTE. No statistically significant IY for MRE vs. CTE was found (fixed model, P > 0.05). CONCLUSIONS: Magnetic resonance enterography has a diagnostic effectiveness comparable to computed tomography enterography, thus may serve as a radiation-free alternative for evaluation of patients with Crohn's disease.

Peroxisome proliferator-activated receptor-gamma Pro12Ala polymorphism, Helicobacter pylori infection and non-cardia gastric carcinoma in Chinese.

BACKGROUND: Peroxisome proliferator-activated receptor gamma inhibits the growth and induces apoptosis of gastric cancer cells. A common polymorphism at codon 12 of this gene (Pro12Ala) has been shown to confer protection against diabetes and colorectal cancer. AIM: To study the association between peroxisome proliferator-activated receptor gamma gene polymorphism, Helicobacter pylori infection and gastric cancer in Chinese. METHODS: One hundred and four consecutive patients with non-cardia gastric adenocarcinoma and 104 matched controls were examined. Peroxisome proliferator-activated receptor gamma Pro12Ala polymorphism was analysed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The frequency of peroxisome proliferator-activated receptor gamma G (Ala12) allele was significantly higher among cancer patients (19.2%) than in control (8.7%; OR 2.5, 95% CI 1.1-5.8). While H. pylori infection was more prevalent in gastric cancer patients (OR 3.0; 95% CI 1.6-5.7), the combination of peroxisome proliferator-activated receptor gamma G allele and H. pylori infection further increased the risk of gastric cancer (OR 12.8, 95% CI 3.2-50.5). The presence of the Ala12 did not increase the risk of gastric cancer in H. pylori-negative subjects. CONCLUSION: Our study suggests the potential association between peroxisome proliferator-activated receptor gamma polymorphism and H. pylori infection in the development of non-cardia gastric cancer.

Chemoprevention of gastric cancer by celecoxib in rats.

BACKGROUND: Overexpression of cyclooxygenase 2 (COX-2) is frequently detected in gastric cancer and is believed to play a crucial role in gastric carcinogenesis. AIM: We examined the chemopreventive effect of a COX-2 inhibitor in an animal model of stomach carcinogenesis. METHODS: Eighty six male Wistar rats were divided into six different treatment groups: group A, water alone (n = 5); group B, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG 100 micro g/ml) (n = 16); group C, indomethacin (3 mg/kg/day) (n = 16); group D, celecoxib (5 mg/kg/day) (n = 17); group E, celecoxib (10 mg/kg/day) (n = 16); and group F, celecoxib (20 mg/kg/day) (n = 16). Group B-F animals were treated with 10% sodium chloride (in the initial six weeks) and MNNG in drinking water to induce adenocarcinoma in the stomach. All animals received treatment for 40 weeks, and were sacrificed after death or at 48 weeks. Gastric neoplasm was evaluated by histology. RESULTS: The incidences of gastric cancer were 0% in group A, 75% in group B, 68.8% in group C, 70.6% in group D, 18.8% in group E, and 31.3% in group F (p = 0.002, ANOVA). Compared with MNNG controls, treatment with celecoxib 10 mg/kg/day also showed lower tumour multiplicity (0.19 (0.40) v 1.00 (0.73); p = 0.004) and lower mean tumour volume (2.4 v 2805 mm(3); p = 0.02). Although tumours had significantly higher COX-2 expression than their adjacent normal tissues (p<0.02), there was no significant difference in COX-2 levels among tumours in the different treatment groups. The lowest tumour prostaglandin E(2) level was found in the indomethacin treated group, suggesting that the chemopreventive effect of celecoxib may be mediated by a COX independent pathway. CONCLUSION: While treatment with indomethacin had no significant effect on tumour development, treatment with celecoxib reduced gastric cancer incidence and growth in rats.

Association of interleukin 1B gene polymorphism and gastric cancers in high and low prevalence regions in China.

AIM: Our aim was to study the relationship between interleukin 1B (IL-1B) polymorphism, Helicobacter pylori infection, and gastric cancer in high prevalent (Shanxi) and low prevalent (Guangdong) regions in China. METHOD: Genomic DNA was extracted from peripheral blood of 192 healthy volunteers, 84 gastric cancer patients from Guangdong and 169 healthy volunteers, and 86 gastric cancer patients from Shanxi. Polymorphisms in IL-1B that encodes IL-1beta and IL-1RN that encodes IL-1 receptor antagonist were analysed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). These polymorphic sites include promoter regions of IL-1B at positions +3954, -511 (C-T transition), and -31 (T-C transition), and IL-1RN variable tandem repeats. RESULTS: In the low prevalence region, the frequencies of the IL-1B +3954 T/T and IL-1RN *2/*2 genotypes were similar. IL-1B -511T/T genotype frequency was significantly higher among patients with gastric cancer (25.0%) than control subjects (12.5%) (chi2=6.7, p=0.01). In the high prevalence region, the frequencies of the IL-1B +3954T/T and -511T/T genotypes and the IL-1RN *2/*2 genotype in the cancer and control groups were similar. IL-1B -31C/C genotype frequency was significantly higher among patients with gastric cancer (90.0%) than controls (78.0%) (chi2=5.0, p=0.025). Compared with the low prevalence region, control subjects from the high prevalence region had a higher frequency of the IL-1B -511T/T genotype (23.0% v 12.5%; chi2=7.0, p<0.008). While H pylori infection alone had only a modest effect on the risk of gastric cancer development (odds ratio (OR) 5.0 (95% confidence interval (CI) 1.5-16.3)), combined with the IL-1B -511T/T genotype the risk was markedly elevated (OR 17.1, 95% CI 3.8-76.4). CONCLUSION: IL-1B -511T/T genotypes are associated with gastric cancer in China. The effect of IL-1B polymorphism is less obvious in areas of high prevalence for gastric cancer.

[Separation of DNA fragments from halobacterium halobium by capillary electrophoresis with non-gel sieving media].

The optimum electrophoresis separation conditions of Lambda DNA/EcoR I + Hind III fragments were investigated using the capillary column DB-1 coated with polysiloxane. When hydroxyethylcellulose (HEC, 1.0%, mass percentage) was used as the only non-gel sieving medium solution, some Lambda DNA fragments could not be separated. After polyvinylpyrrolidone (PVP, 2%, mass percentage) being added into the medium solution, PVP and HEC formed a network colloidal solution in buffer, and changed the network hole size of sieving media. In addition, the results showed that PVP could restrain the adsorption of capillary to DNA, reduced electroosmotic flow, and improved the selectivity of separation. For the first time, all fragments of Lambda DNA marker was separated completely under the same condition of mixed sieving medium solution. The method was applied to separate two groups of DNA fragments of halobacterium halobium, and the base pair number was conjectured.

Synthesis and characteristics of [60]fullerene polysiloxane stationary phase for capillary gas chromatography.

A new type of fullerene-containing polysiloxane was synthesized by reacting [60]fullerene with azidopropyl polysiloxane directly. The polysiloxanes have been used successfully as stationary phases for capillary gas chromatography. They displayed high column efficiency, wide operational temperature and high thermostability, and exhibited unique selectivity for many organic substances, such as alkanes, alcohols, ketones and aromatic compounds. The stationary phase was especially suitable for separation of high boiling-point compounds like polycyclic aromatic hydrocarbons and phthalic esters, etc. It was also found that some alcoholic or aromatic positional isomers could be well separated on the column. The influence of the fullerene content on the separation was also investigated.

Hydroxy-dibenzo crown ether stationary phase for capillary gas chromatography using sol-gel technology.

A new kind of crown ether, OH-dibenzo-14-crown-4 (OH-DB14C4), is prepared and coated onto the fused silica capillary by sol-gel process. Chromatographic characteristics including column efficiency (> 3,000 plates/m), thermal stability (to 330 degrees C) and ability of deactivation are studied. The selectivity of new stationary phase is superior to sol-gel OH-terminal silicone oil (OH-TSO) for positional isomers of some aromatic compounds such as xylene, dichlorobenzene, nitrotoluene, nitrochlorobenzene. The new stationary phase has high sample capacity for separation of small molecular mass compounds: low-molecular-mass alcohols, ethers and ketones, short-chain fatty acids and volatile amines.

[Preparation and chromatographic characteristics of linear [60] fullerene polysiloxane stationary phase for capillary gas chromatography].

Hydrosilylation of polymethylhydrosiloxane (active hydrogen content was 0.05%) and reactions with allylbromide (or undecenyl bromide), sodium azide and [60] fullerene in their given orders is described. Two kinds of fullerene-containing polysiloxanes were obtained [polymer(3)]. Their [60] fullerene contents were 30 mg (C60-PSO-1) and 60 mg (C60-PSO-2) respectively. These polymers (3) were characterized by FT-IR, 1H-NMR, UV-V, 13C-NMR and used as stationary phase for capillary chromatography. Two fused-silica capillary columns (0.25 mm i.d.) were coated with a 5 g/L solution of polymer (3) in dichloromethane by the static method. The column efficiencies were 3,450 plates/m (C60-PSO-1) and 3,020 plates/m (C60-PSO-2), for naphthalene at 120 degrees C. The average polarities of these columns, represented by the McReynold's Constant, were 79 and 93 respectively. The polarity of C60-PSO-2 was a little higher than that of C60-PSO-1, which was in turn a little higher than that of SE-30(43). These columns showed wide operation temperature range (100-360 degrees C) and outstanding thermostability. It could be used at 360 degrees C with a baseline drift of 30-40 fA. Grob test mixtures eluted on these columns in the ordre of 1,3-butanediol, n-decane, 1-octanol, n-undecane, 2,6-dimethylphenol, n-dodecane, 2,4-dimethylaniline, naphthalene, indicating that the strong pi-pi interaction of [60] fullerene with aromatic moieties played an important role in separation mechanism. The columns exhibited unique selectivity for many organic compounds, such as alkanes, alcohols, ketones and anilines. It can well separate benzene homologues, naphthalene homologues and polyaromatic hydrocarbons(PAHs) due to the pi-pi interaction of three-dimensional pi system of C60 and aromatic hydrocabons. And the columns are especially good for the separation of positional isomers(nonanol, butanediol, nitrotoluene, nitrochlorobenzene, nitroethylbenzene, dinitrobenzene, chlorophenol). The columns also have excellent thermostability and are particularly suitable for the separation of high boiling compounds. For example, polycyclic aromatic hydrocarbons and fatty acid methyl esters are well separated on them.

Arrhythmia during extracorporeal shock wave lithotripsy.

A prospective study of arrhythmia during extracorporeal shock wave lithotripsy (ESWL) was performed in 50 patients, using an EDAP LT01 piezoelectric lithotriptor. The 12-lead standard ECG was recorded continuously for 10 min before and during treatment. One or more atrial and/or ventricular ectopic beats occurred during ESWL in 15 cases (30%). The occurrence of arrhythmia was similar during right-sided and left-sided treatment. One patient developed multifocal ventricular premature beats and ventricular bigeminy; another had cardiac arrest for 13.5 s. It was found that various irregularities of the heart rhythm can be caused even by treatment with a lithotriptor using piezoelectric energy to create the shock wave. No evidence was found, however, that the shock wave itself rather than vagal activation and the action of sedo-analgesia was the cause of the arrhythmia. For patients with severe underlying heart disease and a history of complex arrhythmia, we suggest that the ECG be monitored during treatment. In other cases, we have found continuous monitoring of oxygen saturation and pulse rate with a pulse oximeter to be perfectly reliable for raising the alarm when depression of respiration and vaso-vagal reactions occur.

Reconstruction of the electrocardiogram during heart surgery.

Electrocardiograms (ECG) recorded during arrhythmia surgery are used for identification of arrhythmias of different morphology. However, the interpretation of an intraoperative ECG is difficult because some leads cannot be recorded and the signals of the remaining leads often differ from those of a preoperative recording because of the sternotomy. Therefore, a method for reconstruction of a complete intraoperative ECG, which resembles a preoperatively recorded ECG, was studied in 24 patients undergoing heart surgery. The reconstruction method involves calculating coefficients for a transformation matrix, using a preoperative ECG recording and a first intraoperative ECG recording. Once this matrix has been established, further intraoperative recordings can be transformed into an ECG which strongly resembles a preoperative ECG. The correlation between reconstructed intraoperative leads and the corresponding preoperative leads was high in the leads Vx and Vy (median correlation coefficient 0.98 and 0.97) and slightly smaller in lead Vz (0.94). Further studies will prove if the method can be useful in arrhythmia surgery.

Complete atrioventricular block, retrograde atrial activation and intra-atrial block.

A case of complete atrioventricular block, retrograde atrial activation, and intra-atrial block was reported. Inhomogeneous inhibition of the atrioventricular junction and the so-called summation of impulses may both act together to make retrograde conduction possible when third-degree atrioventricular block was present. In lead 2, P waves were dome-shaped, and in lead V1, P waves were biphasic; narrow and peaked P waves intermittently appeared, denoting third-degree intra-atrial block. The peaked P waves signified that the right atrium was activated while the left atrium was not depolarized.

Atrial tachycardia, 2:1 alternate Wenckebach periodicity, and atrial standstill.

A case of atrial tachycardia, 2:1 alternate Wenckebach periodicity and atrial standstill is reported in an 80-year-old woman who complained of exertional dyspnea and occasional syncope for two years. Two blocked P' waves appeared after each Wenckebach period suggesting type B alternating Wenckebach phenomenon (Mobitz type II 2:1 A-V block distal, and Wenckebach conduction proximal).

Application of a new spatial signal averaging device for the beat-to-beat detection of cardiac late potentials.

A new high resolution digital signal averaging device was developed to record precordial late potentials. The subjects examined included 8 normals (including medical patients with normal cardiovascular status), and 21 patients with coronary artery disease (CAD) and myocarditis of probable viral origin. Late potentials were evident in 11 cases (CAD 8 cases and myocarditis in 3 cases). In 10 patients, multiple ventricular premature beats and in 3 others, attacks of ventricular tachycardia had been present. Sudden cardiac death occurred later in one patient. It was concluded that late potentials as recorded by this simple new device are predictive of ventricular arrhythmias--sometimes life threatening. As no triggering is necessary, both conventional and beat-to-beat signal averaging can be carried out and the presence of various arrhythmias is negligible.

Clinical significance of bifid T waves.

An attempt was made to analyze bifid T waves which appeared in different clinical conditions. Bifid T waves occurred in 16% of 600 normal children, 92% of 37 cases of childhood ventricular septal defect (VSD), 6 of 10 cases of tetralogy of Fallot (children) and 33% of 193 patients with cerebrovascular accidents (including 3 children). Sixteen cases of bifid T waves which appeared after amiodarone treatment were also analyzed. It was thought that in normal children, bifid T waves might be due to right ventricular preponderance. In VSD, the bifid T waves assumed a peculiar "dome and dart" appearance. In cerebrovascular accidents, autonomic imbalance might be at fault. In cases of treatment with adriamycin, myocardial toxicity is the most probable cause. The conclusion was made that bifid T waves can appear in different clinical settings, which must be considered individually.