烧伤小鼠IFIT1表达的初步观察

目的 观察烧伤小鼠干扰素诱导表达蛋白IFIT1的表达变化，初步探究其表达变化的原因。方法 实验小鼠致TBSA 15％Ⅱ度烧伤，1d及7d后处死，取肝、肺及脾组织。脂多糖掺入小鼠腹腔巨噬细胞株RAW264．7的培养基中，至终浓度0．1～1．0μg/ml，作用6h。提取组织及细胞RNA，进行半定量逆转录-聚合酶链式反应，提取组织及细胞裂解上清，进行免疫印迹检测。结果 小鼠肝、肺、脾组织IFIT1的转录在烧伤后1d升高，伤后7d恢复至伤前水平；肝、肺、脾IFIT1的蛋白水平在伤后1d一致升高，伤后7d仍能检出升高。体外实验，细菌脂多糖显著激活RAW264．7细胞的IFIT1转录及蛋白表达。结论 烧伤小鼠伤后早期IFIT1表达迅速升高，此变化与同期的内毒素血症引起的细胞应激有关。

Prevalence of minimal hepatic encephalopathy and quality of life evaluations in hospitalized cirrhotic patients in China

AIM:To investigate the prevalence of minimal hepatic encephalopathy(MHE)and to assess corresponding health-related quality of life(HRQoL)in hospitalized cirrhotic patients in China.METHODS:This multi-center cross-sectional study included 16 teaching hospitals,which were members of "Hepatobiliary Cooperation Group,Society of Gastroenterology,Chinese Medical Association",from different areas of China carried out between June and October in 2011.All the eligible hospitalized cirrhotic patients(n = 538)were required to complete triplicate number connection tests combined with one digit symbol test for diagnosing MHE.Patients' clinical examination data were complemented by a modified questionnaire assessing HRQoL.Written informed consent was obtained from each patient.RESULTS:Male was predominant(68.6%)in 519 patients who met the criteria of the study,with a mean age of 49.17 ± 11.02 years.The most common cause of liver cirrhosis was chronic hepatitis B(55.9%).The prevalence of MHE was 39.9% and varied by ChildPugh-Classification score(CPC-A:24.8%,CPC-B:39.4% and CPC-C:56.1%,P < 0.01).MHE(P < 0.01)and higher CPC scores(P < 0.01)were associated with a high HRQoL scores(reflecting poorer quality of life).The prevalence of MHE was proportionate to CPC(P = 0.01)and high quality of life scores(P = 0.01).CONCLUSION:Hospitalized cirrhotic patients have a high prevalence of MHE that is proportionate to the degree of liver function and HRQoL impairment.

Efficacy and safety of bevacizumab plus chemotherapy in Chinese patients with metastatic colorectal cancer:a randomized phase Ⅲ ARTIST trial

The efficacy and safety of bevacizumab with modified irinotecan,leucovorin bolus,and 5-fluorouracil intravenous infusion(mIFL) in the first-line treatment of metastatic colorectal cancer(mCRC) has not been well evaluated in randomized clinical trials in Chinese patients.We conducted a phrase Ⅲ trial in which patients with previously untreated mCRC were randomized 2:1 to the mIFL [irinotecan(125 mg/m2),leucovorin(20 mg/m2) bolus,and 5-fluorouracil intravenous infusion(500 mg/m2) weekly for four weeks every six weeks] plus bevacizumab(5 mg/kg every two weeks) group and the mIFL group,respectively.Co-primary objectives were progression-free survival(PFS) and 6-month PFS rate.In total,214 patients were enrolled.Our results showed that addition of bevacizumab to mIFL significantly improved median PFS(4.2 months in the mIFL group vs.8.3 months in the bevacizumab plus mIFL group,P < 0.001),6-month PFS rate(25.0% vs.62.6%,P < 0.001),median overall survival(13.4 months vs.18.7 months,P = 0.014),and response rate(17% vs.35%,P = 0.013).Grades 3 and 4 adverse events included diarrhea(21% in the mIFL group and 26% in the bevacizumab plus mIFL group) and neutropenia(19% in the mIFL group and 33% in the bevacizumab plus mIFL group).No wound-healing complications or congestive heart failure occurred.Our results suggested that bevacizumab plus mIFL is effective and well tolerated as first-line treatment for Chinese patients with mCRC.Clinical benefit and safety profiles were consistent with those observed in pivotal phase Ⅲ trials with mainly Caucasian patients.

UGT1A1 predicts outcome in colorectal cancer treated with irinotecan and fluorouracil

AIM:To evaluate effects of UDP-glucuronosyltransferase1A1(UGT1A1) and thymidylate synthetase(TS) gene polymorphisms on irinotecan in metastatic colorectal cancer(mCRC).METHODS:Two irinotecan-and fluorouracil-based regimens,FOLFIRI and IFL,were selected as second-line therapy for 138 Chinese mCRC patients.Genomic DNA was extracted from peripheral blood samples before treatment.UGT1A1 and TS gene polymorphisms were determined by direct sequencing and restriction fragment length polymorphism,respectively.Gene polymorphisms of UGT1A1*28,UGT1A1*6 and promoter enhancer region of TS were analyzed.The relationship between genetic polymorphisms and clinical outcome,that is,response,toxicity and survival were assessed.Pharmacokinetic analyses were performed in a subgroup patients based on different UGT1A1 genotypes.Plasma concentration of irinotecan and its active metabolite SN-38 and inactive metabolite SN-38G were determined by high performance liquid chromatography.Differences in irinotecan and its metabolites between UGT1A1 gene variants were compared.RESULTS:One hundred and eight patients received the FOLFIRI regimen,29 the IFL regimen,and one irinotecan monotherapy.One hundred and thirty patients were eligible for toxicity and 111 for efficacy evaluation.One hundred and thirty-six patients were tested for UGT1A1*28 and *6 genotypes and 125 for promoter enhancer region of TS.Patients showed a higher frequency of wild-type UGT1A1*28(TA6/6) compared with a Caucasian population(69.9% vs 45.2%).No significant difference was found between response rates and UGT1A1 genotype,although wild-type showed lower response rates compared with other variants(17.9% vs 24.2% for UGT1A1*28,15.7% vs 26.8% for UGT1A1*6).When TS was considered,the subgroup with homozygous UGT1A1*28(TA7/7) and non-3RG genotypes showed the highest response rate(33.3%),while wild-type UGT1A1*28(TA6/6) with non-3RG only had a 13.6% response rate,but no significant difference was found.Logistic regression showed treatment duration was closely linked to clinical response.In toxicity comparison,UGT1A1*28 TA6/6 was associated with lower incidence of grade 2-4 diarrhea(27.8% vs 100%),and significantly reduced the risk of grade 4 neutropenia compared with TA7/7(7.8% vs 37.5%).Wild-type UGT1A1*6(G/G) tended to have a lower incidence of grade 3/4 diarrhea vs homozygous mutant(A/A) genotype(13.0% vs 40.0%).Taking UGT1A1 and TS genotypes together,lower incidence of grade 2-4 diarrhea was found in patients with non-3RG TS genotypes,when TA6/6 was compared with TA7/7(35.3% vs 100.0%).No significant association with time to progression(TTP) and overall survival(OS) was observed with either UGT1A1 or TS gene polymorphisms,although slightly longer TTP and OS were found with UGT1A1*28(TA6/6).Irinotecan PK was investigated in 34 patients,which showed high area under concentration curve(AUC) of irinotecan and SN-38,but low AUC ratio(SN-38G /SN-38) in those patients with UGT1A1*28 TA7/7.CONCLUSION:A distinct distribution pattern of UGT1A1 genotypes in Chinese patients might contribute to relatively low toxicity associated with irinotecan and 5-fluorouracil in mCRC patients.

Psychometric hepatic encephalopathy score for diagnosis of minimal hepatic encephalopathy in China

AIM:To construct normal values for the tests of the psychometric hepatic encephalopathy score(PHES)and to evaluate its usefulness in the diagnosis of minimal hepatic encephalopathy(MHE)among Chinese individuals with cirrhosis.METHODS:The five tests of PHES,number connection test-A(NCT-A),number connection test-B,serial dotting test,line tracing test and digit symbol test(DST),were administered to all enrolled subjects in a quiet room with sufficient light.Cirrhotic subjects with overt HE were excluded by the West-Haven criteria and a detailed neurological examination.Based on the nomograms of healthy volunteers,the patients were classified as having MHE when their PHES was less than-4.RESULTS:In total,146 healthy volunteers completed all the PHES tests.Age and education years were confirmed to be predictors of all five tests.In total,53patients with liver cirrhosis completed the PHES.Of the patients with liver cirrhosis,24(45.3%),22(41.5%)and 7(13.2%)had Child-Pugh grades A,B and C,respectively.MHE was diagnosed in 26 patients(49.1%).Compared with compensated cirrhotic patients(Child A),decompensated cirrhotic patients(Child B and C)had a higher proportion of MHE(65.5%vs 29.2%).No differences in age and education years were found between the MHE and non-MHE groups.NCT-A and DST were able to diagnose MHE with a sensitivity of 76.9%and a specificity of 96.3%(AUC=0.866,K=0.735).CONCLUSION:The proportion of MHE is associated with liver function.NCT-A and DST are simple tools that can be used for the diagnosis of MHE in China.

Assessment of T staging and mesorectal fascia status using high-resolution MRI in rectal cancer with rectal distention

AIM: To determine the accuracy of high-resolution magnetic resonance imaging (MRI) using phased- array coil for preoperative assessment of T staging and mesorectal fascia infiltration in rectal cancer with rectal distention. METHODS: In a prospective study of 67 patients with primary rectal cancer, high-resolution magnetic resonance imaging (in-plane resolution, 0.66 × 0.56) with phased-array coil were performed for T-staging and measurement of distance between the tumor and the mesorectal fascia. The assessment of MRI was compared with postoperative histopathologic findings. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were evaluated. RESULTS: The overall magnetic resonance accuracy was 85.1% for T staging and 88% for predicting mesorectal fascia involvement. Magnetic resonance sensitivity, specificity, accuracy, positive predictive value, and negative predictive value was 70%, 97.9%, 89.6%, 93.3% and 88.5% for ≤ T2 tumors, 90.5%, 76%, 85.1%, 86.4% and 82.6% for T3 tumors, 100%, 95.2%, 95.5%, 62.5% and 100% for T4 tumors, and 80%, 90.4%, 88%, 70.6% and 94% for predicting mesorectal fascia involvement, respectively. CONCLUSION: High-resolution MRI enables accurate preoperative assessment for T staging and mesorectal fascia infiltration in rectal cancer with rectal distention.

Severe irinotecan-induced toxicity in a patient with UGT1A1*28 and UGT1A1*6 polymorphisms

Many studies have demonstrated the impact of UGT1A1 on toxicity of irinotecan. In particular, patients bear-ing UGT1A1*28 (TA 7/7) have a higher risk of severe neutropenia and diarrhea. Based on this, prescribers of irinotecan are advised that patients with UGT1A1*28 (TA 7/7) should start with a reduced dose of irinotecan, although a particular dose is not specified. Research in Asian countries has shown a lower incidence of UG-T1A1*28 (TA 7/7), while UGT1A1*6 (A/A) is more often found and is associated with severe irinotecan-related neutropenia. We report here a case of a metastatic colorectal cancer patient who is heterozygous for the UGT1A1*28 polymorphism (TA 6/7) as well as the UG-T1A1*6 polymorphism (G/A). The patient was treated with FOLFIRI for 9 cycles and underwent two irinote-can dose reductions according to pharmacokinetic data regarding exposure to the active metabolite, SN-38. Simultaneous heterozygous UGT1A1*28 and UGT1A1*6 polymorphisms may produce higher exposure to SN-38 and a higher risk of adverse effects related to irinote-can. Additional studies will be necessary to determine the optimal starting dose of irinotecan for patients with both UGT1A1*28 and UGT1A1*6 polymorphisms.

Expert consensus on maintenance treatment for metastatic colorectal cancer in China

The impact of maintenance therapy on progression-free survival and overall survival as well as quality of life of Chinese patients with metastatic colorectal cancer has long been under discussion.Recently,some phase III clinical trials have revealed that maintenance therapy can significantly prolong the progression-free survival while maintain an acceptable safety profile.Based on this evidence and common treatment practice in China,we now generated one Expert Consensus on Maintenance Treatment for Metastatic Colorectal Cancer in China to further specify the necessity of maintenance therapy,suitable candidates for such treatment,and appropriate regimens.

Rebamipide suppresses diclofenac-induced intestinal permeability via mitochondrial protection in mice

AIM: To investigate the protective effect and mechanism of rebamipide on small intestinal permeability induced by diclofenac in mice. METHODS: Diclofenac (2.5 mg/kg) was administered once daily for 3 d orally. A control group received the vehicle by gavage. Rebamipide (100 mg/kg, 200 mg/kg, 400 mg/kg) was administered intragastrically once a day for 3 d 4 h after diclofenac administration. Intestinal permeability was evaluated by Evans blue and the FITC-dextran method. The ultrastructure of the mucosal barrier was evaluated by transmission electron microscopy (TEM). Mitochondrial function including mitochondrial swelling, mitochondrial membrane potential, mitochondrial nicotinamide adenine dinucleotide-reduced (NADH) levels, succinate dehydrogenase (SDH) and ATPase activities were measured. Small intestinal mucosa was collected for assessment of malondialdehyde (MDA) content and myeloperoxidase (MPO) activity. RESULTS: Compared with the control group, intestinal permeability was significantly increased in the diclofenac group, which was accompanied by broken tight junctions, and significant increases in MDA content and MPO activity. Rebamipide significantly reduced intestinal permeability, improved inter-cellular tight junctions, and was associated with decreases in intestinal MDA content and MPO activity. At the mitochondrial level, rebamipide increased SDH and ATPase activities, NADH level and decreased mitochondrial swelling. CONCLUSION: Increased intestinal permeability induced by diclofenac can be attenuated by rebamipide, which partially contributed to the protection of mitochondrial function.

Effect of intravariceal sclerotherapy combined with esophageal mucosal sclerotherapy using small-volume sclerosant for cirrhotic patients with high variceal pressure

AIM:To explore the effect of intravariceal-mucosal sclerotherapy using small dose of sclerosant on the recurrence of esophageal varices.METHODS:We randomly assigned 38 cirrhotic patients with previous variceal bleeding and high variceal pressure(> 15.2 mm Hg) to receive endoscopic variceal ligation(EVL) and combined intravariceal and esophageal mucosal sclerotherapy(combined group) using small-volume sclerosant.The end-points of the study were rebleeding and recurrence of esophageal varices.RESULTS:During a median follow-up period of 16 mo,varices recurred in 1 patient in the combined group as compared with 7 patients in the EVL group(P =0.045).Rebleeding occurred in 3 patients in the EVL group as compared with 1 patient in the combined group(P=0.687).No patient died in the two groups.No significant differences were observed between the two groups with respect to serious adverse events.CONCLUSION:Intravariceal-mucosal sclerotherapy using small dose of sclerosant is more effective than EVL in decreasing the incidence of variceal recurrence for cirrhotic patients.

Transjugular intrahepatic portosystemic shunt combined with esophagogastric variceal embolization in the treatment of a large gastrorenal shunt

AIM: To evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt(TIPS) combined with stomach and esophageal variceal embolization(SEVE) in cirrhotic patients with a large gastrorenal vessel shunt(GRVS).METHODS: Eighty-one cirrhotic patients with gastric variceal bleeding(GVB) associated with a GRVS were enrolled in the study and accepted TIPS combined with SEVE(TIPS + SEVE), by which portosystemic pressuregradient(PPG), biochemical, TIPS-related complications, shunt dysfunction, rebleeding, and death were evaluated. RESULTS: The PPGs before TIPS were greater than 12 mmH g in 81 patients. TIPS + SEVE treatment caused a significant decrease in PPG(from 37.97 ± 6.36 mmH g to 28.15 ± 6.52 mm Hg, t = 19.22, P < 0.001). The percentage of reduction in PPG was greater than 20%from baseline. There were no significant differences in albumin, alanine aminotransferase, aspartate aminotransferase, bilirubin, prothrombin time, or Child-Pugh score before and after operation. In all patients, rebleeding rates were 3%, 6%, 12%, 18%, and 18% at 1,3, 6, 12, and 18 mo, respectively. Five patients(6.2%)were diagnosed as having hepatic encephalopathy. The rates of shunt dysfunction were 0%, 4%, 9%, 26%,and 26%, at 1, 3, 6, 12, and 18 mo, respectively. The cumulative survival rates in 1, 3, 6, 12, and 18 mo were100%, 100%, 95%, 90%, and 90%, respectively.CONCLUSION: Our preliminary results indicated that the efficacy and safety of TIPS + SEVE were satisfactory in cirrhotic patients with GVB associated with a GRVS(GVB + GRVS).

Magnetostratigraphy and ^(230)Th dating of a drill core from the southeastern Qaidam Basin:Salt lake evolution and tectonic implications

The Qarhan Salt Lake area is the Quaternary depocenter of the Qaidam Basin, and carries thick lacustrine sediments, as well as rich potassium and magnesium salt deposits. The abundant resources and thick sediments in this lake provide an ideal place for the study of biogas formation and preservation, salt lake evolution, and the uplift of the Tibetan Plateau. In this study, we attempt to construct a paleomagnetic and ^(230)Th age model and to obtain information on tectonic activity and salt lake evolution through detailed studies on a 1300-m-long drill core(15DZK01) from the northwestern margin of the Qarhan Salt Lake area(Dongling Lake). Based on gypsum ^(230)Th dating, the age of the uppermost clastic deposit was calculated to be around 0.052 Ma. The polarity sequence consist of 13 pairs of normal and reversed zones,which can be correlated with subchrons C2r.1r-C1n of the geomagnetic polarity timescale(GPTS 2012)(from ~2.070 Ma to ~0.052 Ma). Sedimentary characteristics indicate that Dongling Lake witnessed freshwater environment between ~ 2.070 Ma and 1.546 Ma. During this period, the sedimentary record reflects primarily lakeshore, shallow-water and swamp environments, representing favourable conditions for the formation of hydrocarbon source rocks. Between 1.546 Ma and ~ 0.052 Ma, the Dongling Lake was in sulphate deposition stage, which contrasts with the central Qarhan Salt Lake area, where this stage did not occur in the meantime. During this stage, Dongling Lake was in a shallow saltwater lake environment, but several periods of reduced salinity occurred during this stage. During the late Pleistocene at ~0.052 Ma, the Dongling Lake experienced uplift due to tectonic activity, and saltwater migrated through the Sanhu Fault to the central Qarhan Salt Lake area, resulting in the absence of halite deposition stage. The residual saline water was concentrated into magnesium-rich brine due to the lack of freshwater, and few potassium salt deposits occur in the Dongling Lake area.

Total and not bevacizumab-bound vascular endothelial growth factor as potential predictive factors to bevacizumab-based chemotherapy in colorectal cancer

AIM: To identify suitable biomarkers of response to bevacizumab(BV)- it remains an open question. The measurement of serum vascular endothelial growth factor(VEGF) has been proposed as a predictive factor for this drug, even if literature data are contradictory. METHODS: We prospectively evaluated the role of BV, total and not BV-bound VEGF and angiopoietin-2(Ang-2) serum levels as potential predictive factors of response for BV in combination with an oxaliplatinbased chemotherapy. BV, Ang-2, total and not BVbound VEGF levels were measured at baseline, before 2^(nd) and 5^(th) cycle of oxaliplatin-based chemotherapy in 20 consecutive metastatic colorectal cancer patients. RESULTS: Results were correlated to response to treatment. Variability in BV levels have been found, with decreased level in less responding patients. In particular, the concentration of BV increased of 3.96 ± 0.69 folds in serum of responsive patients after 3 more cycles of therapy compared to those with stable or progressive disease with a 0.72 ± 0.25 and 2.10 ± 0.13 fold increase, respectively. The determination of free and total VEGF demonstrated that the ratio between the two values, evaluated immediately before the 2^(nd) and the 5^(th) cycle of therapy, decreased from 26.65% ± 1.33% to 15.50% ± 3.47% in responsive patients and from 53.41% ± 4.75 to 34.95% ± 2.88% in those with stable disease. Conversely, in those with progression of disease, the ratio showed the opposite behavior coming up from 25.99% ± 5.23% to 51.71% ± 5.28%. The Ang-2 levels did not show any relationship. CONCLUSION: Our data show that the ratio of not BV-bound VEGF to total VEGF serum and BV plasma concentrations for predicting the response to BV plus oxaliplatin-based chemotherapy could be a promising biomarker of response to BV.

Clinicopathological characteristics and prognosis of 232 patients with poorly differentiated gastric neuroendocrine neoplasms

BACKGROUND Poorly differentiated gastric neuroendocrine neoplasms(PDGNENs)include gastric neuroendocrine carcinoma(NEC)and mixed adenoneuroendocrine carcinoma,which are highly malignant and rare tumors,and their incidence has increased over the past few decades.However,the clinicopathological features and outcomes of patients with PDGNENs have not been completely elucidated.AIM To investigate the clinicopathological characteristics and prognostic factors of patients with PDGNENs.METHODS The data from seven centers in China from March 2007 to November 2019 were analyzed retrospectively.RESULTS Among the 232 patients with PDGNENs,191(82.3%)were male,with an average age of 62.83±9.11 years.One hundred and thirteen(49.34%)of 229 patients had a stage III disease and 86(37.55%)had stage IV disease.Three(1.58%)of 190 patients had no clinical symptoms,while 187(98.42%)patients presented clinical symptoms.The tumors were mainly(89.17%)solitary and located in the upper third of the stomach(cardia and fundus of stomach:115/215,53.49%).Most lesions were ulcers(157/232,67.67%),with an average diameter of 4.66±2.77 cm.In terms of tumor invasion,the majority of tumors invaded the serosa(116/198,58.58%).The median survival time of the 232 patients was 13.50 mo(7,31 mo),and the overall 1-year,3-year,and 5-year survival rates were 49%,19%,and 5%,respectively.According to univariate analysis,tumor number,tumor diameter,gastric invasion status,American Joint Committee on Cancer(AJCC)stage,and distant metastasis status were prognostic factors for patients with PDGNENs.Multivariate analysis showed that tumor number,tumor diameter,AJCC stage,and distant metastasis status were independent prognostic factors for patients with PDGNENs.CONCLUSION The overall prognosis of patients with PDGNENs is poor.The outcomes of patients with a tumor diameter>5 cm,multiple tumors,and stage IV tumors are worse than those of other patients.

Association of MYO9B gene polymorphisms with inflammatory bowel disease in Chinese Han population

AIM:To explore the association of MYO9B gene polymorphisms with clinical phenotypes and intestinal permeability of individuals with inflammatory bowel disease(IBD)in China.METHODS:A total of 442 IBD patients and 402 healthy volunteers were genotyped for two single nucleotides(rs962917 and rs1545620)using the ligase detection reaction and polymerase chain reaction.Allelic and genotype frequency analyses were performed for the two groups.Intestinal permeability was evaluated using lactulose(L)and mannitol(M)excretion.The association of MYO9B gene polymorphisms with intestinal permeability between the normal and high intestinal permeability groups was analyzed.RESULTS:Overall,there was no significant difference in the genotypic and allelic frequencies of MYO9B between IBD patients and controls.Although no association was found with ulcerative colitis in the comparison between the subgroups,the frequencies of rs962917and rs1545620 were different in the Crohn’s disease(CD)subgroup with ileocolitis(CC vs CT and TT,P=0.014;and AA vs AC and CC,P=0.022,respectively).rs1545620 variants appear to be the genetic susceptibility factor for perianal disease in CD patients(AA vs AC CC,P=0.029).In addition,the L/M ratio was significantly higher in IBD patients than in controls(0.065±0.013 vs 0.020±0.002,P=0.02),but no association was found between the MYO9B gene and the L/M ratio in IBD patients.CONCLUSION:MYO9B gene polymorphisms may influence the sub-phenotypic expression of CD in China.No association between these MYO9B polymorphisms and intestinal permeability in IBD patients was found.

Effects of propranolol or propranolol plus isosorbide-5-mononitrate on variceal pressure in schistosomiasis

AIM: To compare the effects of propranolol (PR) to that of PR plus isosorbide-5-mononitrate (ISMN) on variceal pressure in patients with schistosomiasis. METHODS: Forty-eight patients with schistosomiasis who had no previous variceal bleeding were treated with PR alone or PR plus ISMN. Seven patients refused variceal pressure manometry (3 receiving PR and 4 receiving PR plus ISMN). One patient withdrew from the trial due to headache after taking ISMN. At the time of termination, twenty patients were randomly assigned to treatment with PR plus ISMN or PR alone. The dose of PR was adjusted until the resting heart rate had been reduced by 25% or was less than 55 bpm. In the PR plus ISMN group, after PR was titrated to the same target, the dose of ISMN was increased up to 20 mg orally twice a day. Variceal pressure was measured using a noninvasive endoscopic balloon technique at the end of the 6-mo treatment period. RESULTS: In 40 patients (20 in the PR group and 20 in the PR plus ISMN group), variceal pressure was measured before treatment and at the end of the 6-mo treatment period. PR or PR plus ISMN treatment caused a significant reduction in variceal pressure (PR group: from 24.15 ± 6.05 mmHg to 22.68 ± 5.70 mmHg, P = 0.001; PR plus ISMN group: from 25.69 ± 5.26 mmHg to 20.48 ± 5.43 mmHg; P < 0.001). The percentage decrease in variceal pressure was significant after PR plus ISMN compared with that after PR alone (15.93% ± 8.37% vs 6.05% ± 3.67%, P = 0.01). One patient in the PR plus ISMN group and two patients in the PR group had variceal bleeding during follow-up. There were no significant differences between the two groups regarding the incidence of variceal bleeding. In the PR plus ISMN group, three patients had headache and hypotension. The headache was mild and transient and promptly disappeared after continuation of the relevant drug in two patients. Only one patient withdrew from the trial due to severe and lasting headache after taking ISMN. No side effects occurred in the PR group. CONCLUSION: PR plus ISMN therapy may be an alternative treatment for patients with schistosomiasis who have a high risk of bleeding.

Melatonin Ameliorates Liver Fibrosis Induced by Carbon Tetrachloride in Rats via Inhibiting TGF-β1/Smad Signaling Pathway

Melatonin has been reported to inhibit hepatic fibrosis and the mechanism may be correlated to its anti-oxidant effect. Nevertheless, the mechanism is not completely identified. This study was conducted to investigate the effects of melatonin on TGF-β1/Smad signaling pathway in liver fibrosis in rats. The liver fibrosis model was made by the subcutaneous injection of CC14. The liver pathology changes were detected using hematoxylin and eosin （H＆E） staining and Van Gieson （VG） staining. Serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） activities were measured with an autoanalyzer. Glutathione peroxidase （GPx） activities and levels of malondialdehyde （MDA） and hydroxyproline （Hyp） in liver were evaluated by spectrophotometry. Expression levels of TGF-β1, Smad2/3, phosphorylated Smad2/3 （p-Smad2/3） and Smad7 in liver were detected by immunohistochemistry and Western blot analysis. Results showed that melatonin suppressed CC14-induced liver fibrosis, along with an improvement in histological changes, significant decreases in pathologic grading sores and obvious decreases in Hyp levels in liver. Melatonin improved liver function indicated by decreased serum ALT and AST activities. In addition, melatonin exerted its anti-oxidant effects, as supported by decreased MDA levels and increased GPx activities in liver. Furthermore, melatonin inhibited TGF-β1/Smad pathway, as evidenced by decreased TGF-β1, Smad2/3 and p-Smad2/3 expression and increased Smad7 expression in liver. In conclusion, melatonin may suppress CCl4-induced hepatic fibrosis in rats via inhibiting TGF-β1/Smad pathway. It is possible for melatonin to be a potential reagent to treat and cure liver fibrosis.

β-2 Adrenergic receptor gene polymorphism and response to propranolol in cirrhosis

AIM: To evaluate the association of β-2 adrenergic receptor(β2-AR) gene polymorphism with response of variceal pressure to propranolol in cirrhosis.METHODS: Sixty-four non-related cirrhotic patients participated in this study and accepted variceal pressure measurement before and after propranolol administration. Polymorphism of the β 2-AR gene was determined by directly sequencing of the polymerase chain reaction products from the DNA samples that were prepared from the patients.RESULTS: The prevalence of Gly16-Glu/Gln27 and Arg16-Gln27 homozygotes, and compound heterozygotes was 29.7%, 10.9%, and 59.4%, respectively.Patients with cirrhosis with Gly16-Glu/Gln27 homozygotes had a greater decrease of variceal pressure after propranolol administration than those with Arg16-Gln27 homozygotes or with compound heterozygotes(22.4% ± 2.1%, 13.1% ± 2.7% and 12.5% ± 3.1%,respectively, P < 0.01).CONCLUSION: The variceal pressure response to propranolol was associated with polymorphism of β 2-AR gene. Patients with the Gly16-Glu/Gln27 homozygotes probably benefit from propranolol therapy.

Ulcerative colitis flair induced by mesalamine suppositories hypersensitivity

Mesalamine suppositories have been used widely for the treatment of distal ulcerative colitis and considered to be safer than systemic administration for its limited systemic absorption.However,previous studies have shown that mesalamine suppository occasionally causes severe hypersensitivity reactions including fever,rashes,colitis exacerbation and acute eosinophilic pneumonia.Here we present a 25-year-old woman with ulcerative colitis with bloody diarrhea accompanied by abdominal pain and fever which were aggravated after introduction of mesalamine suppositories.In light of symptom exacerbation of ulcerative colitis,increased inflammatory injury of colon mucosa shown by colonoscopy and elevated peripheral eosinophil count after mesalamine suppositories administration,and the Naranjo algorithm score of 10,the possibility of hypersensitivity reaction to mesalamine suppositories should be considered,warning us to be aware of this potential reaction after administration of mesalamine formulations even if it is the suppositories.

5-aminosalicylic acid in combination with nimesulide inhibits proliferation of colon carcinoma cells in vitro

AIM: To investigate the effects of 5-aminosalicylic acid (5-ASA) in combination with nimesulide on the proliferation of HT-29 colon carcinoma cells and its potential mechanisms. METHODS: Inhibitory effects of drugs (5-ASA,nimesulide and their combination) on HT-29 colon carcinoma cells were investigated by thiazolyl blue tetrazolium bromide (MTT) assay. Cellular apoptosis and proliferation were detected by TUNEL assay and immunocytochemical staining,respectively. RESULTS: Pretreatment with 5-ASA or nimesulide at the concentration of 10-1000 μmol/L inhibited proliferation of HT-29 colon carcinoma cells in a dose-dependent manner in vitro (t = 5.122,P < 0.05; t = 3.086,P < 0.05,respectively). The inhibition rate of HT-29 colon carcinoma cell proliferation was also increased when pretreated with 5-ASA (100 μmol/L) or nimesulide (100 μmol/L) for 12-96 h,which showed an obvious time-effect relationship (t = 6.149,P < 0.05; t = 4.159,P < 0.05,respectively). At the concentration of 10-500 μmol/L,the apoptotic rate of HT-29 colon carcinoma cells significantly increased (t = 18.156,P < 0.001; t = 19.983,P < 0.001,respectively),while expression of proliferating cell nuclear antigen (PCNA) was remarkably decreased (t = 6.828,P < 0.05; t = 14.024,P < 0.05,respectively). 5-ASA in combination with nimesulide suppressed the proliferation of HT-29 colon carcinoma cells more than either of these agents in a dose-dependent and time-dependent manner (t = 5.448,P < 0.05; t = 4.428,P < 0.05,respectively). CONCLUSION: 5-ASA and nimesulide may inhibit the proliferation of HT-29 colon carcinoma cells and coadministration of these agents may have additional chemopreventive potential.