Electrocardiogram score for the selection of reperfusion strategy in early latecomers with ST-segment elevation myocardial infarction.

OBJECTIVE: The clinical benefit of percutaneous coronary intervention (PCI) is controversial in ST-segment elevation myocardial infarction (STEMI) patients presenting 12-72 hours after symptom onset. Several studies suggested this conflicting result was associated with myocardial area at risk (MaR) of enrolled patients. MaR could be estimated by the electrocardiogram (ECG) score. Our objective was to evaluate the benefits of PCI in STEMI latecomers with different MaR. METHODS: We constructed a prospective cohort involving 436 patients presenting 12-72 hours after STEMI onset and who met an inclusion criteria. 218 underwent PCI and 218 received the optimal medical therapy (OMT) alone. Individual MaR was quantified by the combined Aldrich ST and Selvester QRS score. The primary endpoint was a composite of cardiovascular death, reinfarction or revascularization within two years. RESULTS: The 2-year cumulative primary endpoint rate was respectively 9.2% in PCI group and 5.3% in OMT group when MaR<35% (adjusted hazard ratio for PCI vs. OMT, 1.855; 95% confidence interval [CI], 0.617-5.575; P=0.271), and was 12.8% in PCI group and 23.1% in OMT group when MaR ≥35% (adjusted hazard ratio for PCI vs. OMT, 0.448; 95% CI, 0.228-0.884; P=0.021). CONCLUSION: The benefit of PCI for the STEMI latecomers was associated with the MaR. PCI, compared with OMT, could significantly reduce the 2-year primary outcomes in patients with MaR≥35%, but not in ones with MaR<35%.

Use of lectin microarray to differentiate gastric cancer from gastric ulcer.

AIM: To investigate the feasibility of lectin microarray for differentiating gastric cancer from gastric ulcer. METHODS: Twenty cases of human gastric cancer tissue and 20 cases of human gastric ulcer tissue were collected and processed. Protein was extracted from the frozen tissues and stored. The lectins were dissolved in buffer, and the sugar-binding specificities of lectins and the layout of the lectin microarray were summarized. The median of the effective data points for each lectin was globally normalized to the sum of medians of all effective data points for each lectin in one block. Formalin-fixed paraffin-embedded gastric cancer tissues and their corresponding gastric ulcer tissues were subjected to Ag retrieval. Biotinylated lectin was used as the primary antibody and HRP-streptavidin as the secondary antibody. The glycopatterns of glycoprotein in gastric cancer and gastric ulcer specimens were determined by lectin microarray, and then validated by lectin histochemistry. Data are presented as mean ± SD for the indicated number of independent experiments. RESULTS: The glycosylation level of gastric cancer was significantly higher than that in ulcer. In gastric cancer, most of the lectin binders showed positive signals and the intensity of the signals was stronger, whereas the opposite was the case for ulcers. Significant differences in the pathological score of the two lectins were apparent between ulcer and gastric cancer tissues using the same lectin. For MPL and VVA, all types of gastric cancer detected showed stronger staining and a higher positive rate in comparison with ulcer, especially in the case of signet ring cell carcinoma and intra-mucosal carcinoma. GalNAc bound to MPL showed a significant increase. A statistically significant association between MPL and gastric cancer was observed. As with MPL, there were significant differences in VVA staining between gastric cancer and ulcer. CONCLUSION: Lectin microarray can differentiate the different glycopatterns in gastric cancer and gastric ulcer, and the lectins MPL and VVA can be used as biomarkers.

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 Child-Pugh-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.

Effect of ionizing radiation on transcription of colorectal cancer MDR1 gene of HCT-8 cells.

OBJECTIVE: To discuss effect of ionizing radiation on transcription of colorectal cancer multidrug resistance (MDR) 1 gene of HCT-8 cells. METHODS: Total RNA was extracted by guanidine thiocyanate one-step method. Northern blot was applied to detect transcription level of MDR1 gene. The expression of P-gp protein was detected by flow cytometry. RESULTS: The expression of MDR1 of normal colorectal cancer HCT-8 cells was low. It was increased by 8.35 times under stimulus with 2 Gy. When treated with low doses in advance, high expressed MDR was decreased significantly under 0.05, 0.1 Gy, which was 69.00%, 62.89% in 2 Gy group and 5.77 times, 5.25 times in sham irradiation group. No obvious difference was detected between (0.2+2) Gy group and 2 Gy group. Compared with sham irradiation group, the percentage of P-gp positive cells after radiation of a high 2 Gy dose was increased significantly (P<0.01). When treated with high radiation dose following low radiation dose (0.05 Gy, 0.1 Gy) in advance, the percentage of P-gp positive cells were also increased significantly. The percentage of P-gp positive cells were increased obviously in 0.2 Gy and 2 Gy groups. Compared with simple high radiation 2 Gy group, the percentage of P-gp positive cells was decreased significantly (P<0.05). CONCLUSIONS: Low radiation dose can reverse multidrug resistance of colorectal cancer cells caused by high radiation dose.

Hepatocyte growth factor-induced amelioration in renal interstitial fibrosis is associated with reduced expression of alpha-smooth muscle actin and transforming growth factor-beta1.

Several studies have shown that hepatocyte growth factor (HGF) ameliorates renal interstitial fibrosis, but the mechanism is not fully clear. This study was designed to examine whether HGF can relieve renal interstitial injury in 5/6 nephrectomized rats, and to confirm whether this function was associated with decrease in alpha-smooth muscle actin (alpha-SMA) and transforming growth factor-betal (TGF-beta1) expression. The animals were randomized into 8 groups comprising 6 animals (n = 6) each: control (group I), PCI-neo (group II, 900 microg), sham-operation (group III, not nephrectomy), model or 5/6 nephrectomy group (group IV), lotensin group (an angiotensin converting enzyme inhibitor, group V, 0.6 mg/100 g/day for 5 weeks), low-dose PCI-neo-HGF group (group VI, 690 microg), high-dose PCI-neo-HGF group (group VII, 1380 microg) and lotensin + high-dose PCI-neo-HGF group (group VIII, 0.6 mg/100 g/day for 5 weeks, 1380 microg). The animals were sacrificed in the 5th week after 5/6 nephrectomy. The specimens of kidneys were used for pathological examination (hematoxylin-eosin staining), detection of alpha-SMA and TGF-beta1 mRNA (Reverse transcriptase-polymerase chain reaction) and protein (Western blot and immunohistochemistry) expression. The results showed that in 5/6 nephrectomized rats blood urea nitrogen (BUN), serum creatinine (CRE) and 24 h urinary albumin excretion (UAE) were increased, renal interstitium was injured seriously and alpha-SMA, TGF-beta1 mRNA and protein expression were elevated compared with those of control. The above changes were ameliorated and alpha-SMA and TGF-beta 1 expression was reduced by both PCI-neo-HGF and lotensin. The lotensin + high-dose PCI-neo-HGF group rats exhibited the most significant therapeutic effect both in decreasing the BUN, CRE and 24 h UAE and in relieving renal interstitial injury. In conclusion, the study demonstrated that HGF can relieve renal interstitial injury and this protection was associated with down-regulation of a-SMA and TGF-beta 1 expressions.

Vitamin D receptor gene polymorphism and ulcerative colitis susceptibility in Han Chinese.

OBJECTIVE: Specific polymorphisms in the vitamin D receptor (VDR) gene have been associated with genetic susceptibility to inflammatory bowel disease (IBD) in different ethnic populations. METHODS: A total of 218 ulcerative colitis (UC) patients and 251 healthy controls were genotyped for VDR gene polymorphisms using PCR-restriction fragment length polymorphism (PCR-RFLP) assay. VDR gene polymorphisms (Apa I, Taq I, Bsm I and Fok I) were analyzed for both genotypic and phenotypic susceptibilities. RESULTS: Among the four examined VDR gene polymorphisms, the Bsm I polymorphism showed a slightly higher distribution in our study population than that in the previous studies. We also found that the increased frequency of the Bb genotype of the Bsm I VDR gene polymorphism was associated with UC in Han Chinese, as compared with healthy controls (28.4% vs. 18.7%, χ(2) = 6.044, P = 0.014, OR = 1.739, 95% CI = 1.122-2.697). Moreover, Bsm I polymorphic allele (B) frequency was significantly increased in the UC cases, as compared to the healthy controls (14.7% vs. 7.8% χ(2) = 6.222, P = 0.013; OR = 1.670, 95% CI = 1.113-2.506). In contrast, the other three VDR gene polymorphisms (Apa I, Taq I and Fok I) were not associated with UC susceptibility in the Han Chinese cohort. In addition, none of these four VDR polymorphisms had statistical association with clinicopathological parameters of these UC patients. CONCLUSION: This study demonstrated a probable association of the Bsm I polymorphism of the VDR gene with ulcerative colitis susceptibility in Han Chinese.

[Regulatory effect of diammonium glycyrrhizinate on Th1/Th2 deviation in bronchial asthma: experiment with rats].

OBJECTIVE: To study the regulatory effect of diammonium glycyrrhizinate (GL) on the Th1/Th2 deviation in bronchial asthma. METHODS: Thirty Wistar rats were injected intraperitoneally with antigen solution including ovalbumin (OVA), inactivated pertussis vaccine, and aluminum hydroxide for the purpose of sensitization. Fourteen days later OVA was sprayed 20 min everyday for a consecutive 5 days to evoke sensitization, thus models of asthma were established. Then the 30 rats were randomly divided into 3 equal groups: asthma model group, model+GL group, and model+DXM group. Another 10 rats were used as control group. All rats underwent tracheal intubation to perform the breathing curves. By the end of the experiment the rats were killed with their lungs taken out to undergo pathological examination. Suspension of splenocytes was prepared, the level of interferon (IFN)-gamma, a cytokine mainly secreted by Th1 cells, was detected by L929-VSV system, and the IL-4 level was detected by ELISA. RESULTS: The amplitude of the breathing curve of the GL group was similar to that of the DXM group, both significantly lower than that of the model group [(0.139+/-0.011) mV, both P<0.01] and higher than that of the control group. The respiratory rates of all groups became faster than normal. Pathology showed infiltration of inflammatory cells and proliferation of cup-shaped cells in the pneumonic tissues in the model group, and such damages were much slighter in the GL and DXM groups. The IFN-gamma level of the model group was (1.6+/-0.4) U, significantly lower than that of the control group [(3.7+/-1.0) U, P<0.05]. The IFN-gamma level of the GL group was (18.7+/-5.5) U, significantly higher than those of the DXM group [(2.1+/-0.3) U], model group and control group (all P<0.01). The IL-4 level of the model group was (305+/-36) pg, significantly higher than those of the GL group [(168+/-10) pg, P<0.01], DXM group [(213+/-47) pg], and control group [(54+/-6) pg, P<0.01], however, there was no significant difference between the GL and DXM groups. CONCLUSION: GL increases the IFN-gamma level and decreases the IL-4 level, thus promoting the polarization of Th1 cells, regulating the Th1/Th2 deviation, and alleviating asthma.

[Role of endothelium-derived hyperpolarizing factor in shear stress-induced endothelium-dependent relaxations of rats].

AIM: To investigate the role and mechanism of endothelium-derived hyperpolarizing factor (EDHF) in shear stress induced vasorelaxation of rat mesenteric artery. METHODS: The changes in vessel diameter in response to variable flow (0-300 microL.min(-1)) were continuously examined. The contribution of prostacyclin (PGI2), NO and EDHF to shear stress induced relaxation were analyzed by inhibitory effects of indomethacin, N(G)-nitro-L-arginine (L-NA) and KCl. The nature and hyperpolarizing mechanism of EDHF were examined by the inhibitory effects of inhibitors of cytochrome P450 pathway and of various K+ channels. RESULTS: The shear stress-induced relaxation were endothelium dependent and the contribution of NO was more prominent in large mesenteric arteries (400-500 microm) than that in resistance arteries (150-250 microm), whereas that of EDHF was noted in both-sized blood vessels. Tetrabutylammonium (a nonselective inhibitor of K channels) almost abolished, whereas the combination of charybdotoxin (an inhibitor of both large and intermediate-conductance Ca2+-activated K channels) and apamin (an inhibitor of small-conductance Ca2+-activated K channels) significantly inhibited the EDHF-mediated component of the shear stress-induced relaxations. CONCLUSION: EDHF plays an important role in shear stress-induced endothelium-dependent relaxations, and K channels especially calcium-activated K channels appear to be involved.

Expression of interferon-alpha/beta receptor protein in liver of patients with hepatitis C virus-related chronic liver disease.

AIM: To study the expression of interferon-alpha/beta (IFN-alpha/beta) receptor protein in liver of patients with hepatitis C virus (HCV)-related chronic liver disease and its clinical significance. METHODS: A total of 181 patients with HCV-related chronic liver disease included 56 with HCV-related liver cirrhosis (LC) and 125 with chronic hepatitis C (CHC). CHC patients were treated with five megaunits of interferon-?1b six times weekly for the first 2 weeks and then every other day for 22 wk. The patients were divided into interferon (IFN) treatment-responsive and non-responsive groups, but 36 patients lost follow-up shortly after receiving the treatment. The expression of IFN-alpha/beta receptor (IFN-alpha/betaR) protein in liver of all patients was determined with immunofluorescence. RESULTS: In liver of patients with HCV-related chronic liver disease, the expression of IFN-alpha/betaR protein in liver cell membrane was stronger than that in cytoplasm and more obvious in the surroundings of portal vein than in the surroundings of central vein. Moreover, it was poorly distributed in hepatic lobules. The weak positive, positive and strong positive expression of IFN-alpha/betaR were 40% (50/125), 28% (35/125), 32% (40/125), respectively in CHC group, and 91.1% (51/56), 5.35% (3/56), and 3.56% (2/56), respectively in LC group. The positive and strong positive rates were higher in CHC group than in LC group (P<0.01). In IFN treatment responsive group, 27.8% (10/36) showed weak positive expression; 72.2% (26/36) showed positive or strong positive expression. In the non-responsive group, 71.7% (38/53) showed weak positive expression; 28.3% (15/53) showed positive or strong positive expression. The expression of IFN-alpha/betaR protein in liver was more obvious in IFN treatment responsive group than in non-responsive group. CONCLUSION: Expression of IFN-alpha/betaR protein in liver of patients with HCV-related chronic liver disease is likely involved in the response to IFN treatment.