A drug-eluting Balloon for the trEatment of coronarY bifurcatiON lesions in the side branch: a prospective multicenter ranDomized (BEYOND) clinical trial in China / 中华医学杂志(英文版)

BACKGROUND@#Treatment of coronary bifurcation lesions remains challenging; a simple strategy has been preferred as of late, but the disadvantage is ostium stenosis or even occlusion of the side branch (SB). Only a few single-center studies investigating the combination of a drug-eluting stent in the main branch followed by a drug-eluting balloon in the SB have been reported. This prospective, multicenter, randomized study aimed to investigate the safety and efficacy of a paclitaxel-eluting balloon (PEB) compared with regular balloon angioplasty (BA) in the treatment of non-left main coronary artery bifurcation lesions.@*METHODS@#Between December 2014 and November 2015, a total of 222 consecutive patients with bifurcation lesions were enrolled in this study at ten Chinese centers. Patients were randomly allocated at a 1:1 ratio to a PEB group (n = 113) and a BA group (n = 109). The primary efficacy endpoint was angiographic target lesion stenosis at 9 months. Secondary efficacy and safety endpoints included target lesion revascularization, target vessel revascularization, target lesion failure, major adverse cardiac and cerebral events (MACCEs), all-cause death, cardiac death, non-fatal myocardial infarction, and thrombosis in target lesions. The main analyses performed in this clinical trial included case shedding analysis, base-value equilibrium analysis, effectiveness analysis, and safety analysis. SAS version 9.4 was used for the statistical analyses.@*RESULTS@#At the 9-month angiographic follow-up, the difference in the primary efficacy endpoint of target lesion stenosis between the PEB (28.7% ± 18.7%) and BA groups (40.0% ± 19.0%) was -11.3% (95% confidence interval: -16.3% to -6.3%, Psuperiority <0.0001) in the intention-to-treat analysis, and similar results were recorded in the per-protocol analysis, demonstrating the superiority of PEB to BA. Late lumen loss was significantly lower in the PEB group than in the BA group (-0.06 ± 0.32 vs. 0.18 ± 0.34 mm, P < 0.0001). For intention-to-treat, there were no significant differences between PEB and BA in the 9-month percentages of MACCEs (0.9% vs. 3.7%, P = 0.16) or non-fatal myocardial infarctions (0 vs. 0.9%, P = 0.49). There were no clinical events of target lesion revascularization, target vessel revascularization, target lesion failure, all-cause death, cardiac death or target lesion thrombosis in either group.@*CONCLUSIONS@#In de novo non-left main coronary artery bifurcations treated with provisional T stenting, SB dilation with the PEB group demonstrated better angiographic results than treatment with regular BA at the 9-month follow-up in terms of reduced target lesion stenosis.@*TRIAL REGISTRATION@#ClinicalTrials.gov, NCT02325817; https://clinicaltrials.gov.

Retrospective analysis of nutritional risk and nutritional treatment options in inflammatory bowel disease / 肠外与肠内营养

Objective:To understand the nutritional risk in patients with IBD,its related factors and nutritional treatment options.Methods:IBD patients treated in Peking University first hospital from January 2006 to December 2015 were studied.Using the Nutritional risk screening 2002 (NRS2002) nutritional risk assessment of the patients were evaluated.According to the body mass index (BMI),patients were divided into normal BMI group (BMI 18.5 ～ 23.9),low BMI group (BMI ＜ 18.5) and high BMI group (BMI ≥ 24).We analyzed the nutritional risk related factors and compared the difference of nutritional therapy options,regarding the UC and CD patients respectively.Results:A total of 388 patients with IBD were enrolled in the study,with UC 306 and CD 82 patients.The total nutritional risk was 49.5％.Although there was no difference in BMI distribution between UC and CD,CD was more likely to have nutritional risk than UC (CD 64.6％,UC 45.4％,(P =0.002).The nutritional risk of low BMI group was 95.7％.There were no differences in age,sex,and family history in IBD patients for the occurrence of nutritional risk.The more frequently recurrence,severe of disease activity,and the wider rang of disease bring the higher nutritional risk for UC patients.But for CD patients,penetrating type,having a history of surgery and severe of disease activity had higher nutritional risk.Adequate caloric nutrition therapy in patients with CD was 77.4％ higher than that of UC 46.8％,(P ＜ 0.001).It was a main principle of our center that UC patients with severe recurrence should not emphasize enteral nutrition and CD patients should first deal with the contraindications before starting enteral nutrition.Conclusions:IBD patients have a high nutritional risk and CD is more obvious than UC,particularly in low BMI patients.The nutritional risk of patients with UC and CD has its own associated factors.It is safe to treat IBD patients with enteral nutrition as long as the indications and contraindications were well controlled.

The Involvement of Ca(2+) Signal Pathways in Distal Colonic Myocytes in a Rat Model of Dextran Sulfate Sodium-induced Colitis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Disrupted Ca2+ homeostasis contributes to the development of colonic dysmotility in ulcerative colitis (UC), but the underlying mechanisms are unknown. This study aimed to examine the alteration of colonic smooth muscle (SM) Ca2+ signaling and Ca2+ handling proteins in a rat model of dextran sulfate sodium (DSS)-induced UC.</p><p><b>METHODS</b>Male Sprague-Dawley rats were randomly divided into control (n = 18) and DSS (n = 17) groups. Acute colitis was induced by 5% DSS in the drinking water for 7 days. Contractility of colonic SM strips (controls, n = 8 and DSS, n = 7) was measured in an organ bath. Cytosolic resting Ca2+ levels (n = 3 in each group) and Ca2+ transients (n = 3 in each group) were measured in single colonic SM cells. Ca2+ handling protein expression was determined by Western blotting (n = 4 in each group). Differences between control and DSS groups were analyzed by a two-sample independent t-test.</p><p><b>RESULTS</b>Average tension and amplitude of spontaneous contractions of colonic muscle strips were significantly enhanced in DSS-treated rats compared with controls (1.25 ± 0.08 g vs. 0.96 ± 0.05 g, P= 0.007; and 2.67 ± 0.62 g vs. 0.52 ± 0.10 g, P= 0.013). Average tensions of carbachol-evoked contractions were much weaker in the DSS group (1.08 ± 0.10 g vs. 1.80 ± 0.19 g, P= 0.006). Spontaneous Ca2+ transients were observed in more SM cells from DSS-treated rats (15/30 cells) than from controls (5/36 cells). Peak caffeine-induced intracellular Ca2+ release was lower in SM cells of DSS-treated rats than controls (0.413 ± 0.046 vs. 0.548 ± 0.041, P= 0.033). Finally, several Ca2+ handling proteins in colonic SM were altered by DSS treatment, including sarcoplasmic reticulum calcium-transporting ATPase 2a downregulation and phospholamban and inositol 1,4,5-trisphosphate receptor 1 upregulation.</p><p><b>CONCLUSIONS</b>Impaired intracellular Ca2+ signaling of colonic SM, caused by alteration of Ca2+ handing proteins, contribute to colonic dysmotility in DSS-induced UC.</p>

Effect of the 5-HT4 receptor and serotonin transporter on visceral hypersensitivity in rats

Visceral hypersensitivity plays an important role in motor and sensory abnormalities associated with irritable bowel syndrome, but the underlying mechanisms are not fully understood. The present study was designed to evaluate the expression of the 5-HT4 receptor and the serotonin transporter (SERT) as well as their roles in chronic visceral hypersensitivity using a rat model. Neonatal male Sprague-Dawley rats received intracolonic injections of 0.5% acetic acid (0.3-0.5 mL at different times) between postnatal days 8 and 21 to establish an animal model of visceral hypersensitivity. On day 43, the threshold intensity for a visually identifiable contraction of the abdominal wall and body arching were recorded during rectal distention. Histological evaluation and the myeloperoxidase activity assay were performed to determine the severity of inflammation. The 5-HT4 receptor and SERT expression of the ascending colon were monitored using immunohistochemistry and Western blot analyses; the plasma 5-HT levels were measured using an ELISA method. As expected, transient colonic irritation at the neonatal stage led to visceral hypersensitivity, but no mucosal inflammation was later detected during adulthood. Using this model, we found reduced SERT expression (0.298 ± 0.038 vs 0.634 ± 0.200, P < 0.05) and increased 5-HT4 receptor expression (0.308 ± 0.017 vs 0.298 ± 0.021, P < 0.05). Treatment with fluoxetine (10 mg·kg-1·day-1, days 36-42), tegaserod (1 mg·kg-1·day-1, day 43), or the combination of both, reduced visceral hypersensitivity and plasma 5-HT levels. Fluoxetine treatment increased 5-HT4 receptor expression (0.322 ± 0.020 vs 0.308 ± 0.017, P < 0.01) but not SERT expression (0.219 ± 0.039 vs 0.298 ± 0.038, P = 0.654). These results indicate that both the 5-HT4 receptor and SERT play a role in the pathogenesis of visceral hypersensitivity, and its mechanism may be involved in the local 5-HT level.

Pulmonary embolism excluded acute coronary syndrome by coronarography: a retrospective analysis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Pulmonary embolism (PE) is often mistaken as acute coronary syndromes (ACS) because of the considerable overlap in their clinical features. We evaluated the factors causing misdiagnosis of PE as ACS and factors that differentiate PE from ACS to improve the diagnosis efficacy of PE.</p><p><b>METHODS</b>The medical records of 22 consecutive PE patients, between 2001 and 2010, who were initially suspected of ACS were retrieved. ACS was ruled out by coronary artery angiography before a definite diagnosis of PE was given. Twenty-two contemporary cases of ACS matched by age and sex were recruited as controls. Clinical manifestations, electrocardiograms (ECG), and biomarkers of these patients were reviewed retrospectively. The factors causing misdiagnosis of PE as ACS and factors differentiating PE from ACS were evaluated.</p><p><b>RESULTS</b>We found two leading causes of misdiagnosis of PE as ACS. One is that PE can resemble ACS in several clinical aspects (symptoms and signs, ECG findings, plasma cardiac troponin I, and D-dimer). The other is the insufficient recognition of PE by clinicians. Risk factors for venous thromboembolism (VTE), especially deep venous thrombosis (DVT), together with signs of PE, such as unexplained dyspnea or hypoxemia, and right ventricular pressure overload on ECGs are valuable in differentiating the two diseases.</p><p><b>CONCLUSIONS</b>Differentiation between PE and ACS is sometimes challenging. Adequate awareness of the risk factors for VTE and the signs of PE are crucial in the diagnosis of PE.</p>

Protective effect of intermittent hypobaric hypoxia on cardiomyocytes injury induced by hydrogen peroxide / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To observe the protective effect and mechanism of intermittent hypobaric hypoxia (IHH) on cardiomyocytes induced by hydrogen dioxide.</p><p><b>METHODS</b>Male guinea pigs were divided randomly into two groups (n = 10): intermittent hypoxia group (IHH), and control group (non-IHH). The IHH guinea pigs were exposed to a simulated 5,000 m high altitude and hypoxia in hypobaric chamber for 28 d, 6 h/d. The control guinea pigs were kept in the same environment as IHH except hypoxia exposure. Cardiomyocytes were enzymatically isolated from left ventricle of non-CIHH or CIHH guinea pigs. The contractile was assessed in guinea pigs by a video-based motion edge-detection system. The contents and activities of malondialdehyde(MDA), lactate hydrogenase(LDH) and antioxidant enzymes were evaluated by using biochemical methods.</p><p><b>RESULTS</b>1. Hydrogen peroxide could induce contractile and diastole dysfunction, the latent period was longer in IHH cardiac myocytes. 2. After hydrogen peroxide(300 micromol/L, 10 min) perfusion, LDH and MDA contents in supernatant increased significantly in non-IHH and CIHH cardiomyocytes (P < 0.01), Whereas the contents of MDA and LDH in IHH cardiomyocytes were lower than those in non-IHH cardiomyocytes (P < 0.01). 3. The activities of superoxide dismutase (SOD) and catalase (CAT) were significantly increased in the myocardium of IHH guinea pigs, after hydrogen peroxide (300 micromol/L, 10 min) perfusion, SOD and CAT activities decreased significantly in non-IHH and CIHH cardiomyocytes (P < 0.01), whereas the activities of SOD and CAT in CIHH cardiomyocytes were still higher than those in non-IHH cardiomyocytes.</p><p><b>CONCLUSION</b>IHH had a protective effect on cardiomyocytes injury induced by hydrogen peroxide, which might relate with its antioxidation effects.</p>

Chemotaxis-related factors are expressed abnormally in bone marrow mesenchymal stem cells of multiple myeloma patients / 中国实验血液学杂志

This study was aimed to investigate the mRNA expression levels of hepatocyte growth factor (HGF), stromal cell-derived factor-1 (SDF-1), monocyte chemotactic protein-1 (MCP-1) and interleukin-8 (IL-8) in bone marrow mesenchymal stem cells (MSC) from multiple myeloma (MM) patients. The mRNA expression levels of HGF, SDF-1, MCP-1 and IL-8 in bone marrow MSC from 20 newly diagnosed MM patients were detected by real time quantitative RT-PCR and were compared with that in 9 controls. The results indicated that the mean mRNA expression level of HGF was up-regulated in MM patients, as compared with controls (p < 0.01). However, the mean mRNA expression level of SDF-1 mRNA was down-regulated in MM patients, as compared with controls (p < 0.05). There was no significant difference in the mRNA expression levels of MCP-1 and IL-8 between MM and control cohorts (p > 0.05). It is concluded that BM-MSC from MM patients express HGF, SDF-1, MCP-1, IL-8, but these chemotaxis-related factors expression of bone marrow microenvironment cellular component are dysregulated in MM patients, which may result from the interplay between MM cells and MSC.

Study on differentiation of human umbilical cord-derived mesenchymal stem cells into human sweat gland cells in vitro and the relative signal pathway / 中华烧伤杂志

<p><b>OBJECTIVE</b>To study the differentiation potential of human umbilical cord-derived mesenchymal stem cells (UCMSC) into human sweat gland cells (hSGC) and the role of extracellular signal-regulated kinase (ERK) pathway.</p><p><b>METHODS</b>UCMSC and hSGC were isolated and cultured in vitro. The former was identified with expression of CD14, CD29, CD34, CD44, CD45, CD105, cytokeratin 7 (CK7), CK19, and carcinoembryonic antigen (CEA), while the latter was identified with expression of CK19 and CEA. UCMSC with density of 5 x 10(4) cells per well placed in lower compartment of Transwell chamber were divided into control group (C, cultured with nutrient solution without any stimulation), thermal injury group (TI, treated with heat-shocked hSGC with density of 1 x 10(4) cells per well inoculated into the upper compartment of Transwell chamber for indirect co-culture), thermal injury + EGF group (TIE, treated with indirect co-culture as used in TI group, with addition of 50 ng/mL EGF), thermal injury + PD98059 group (TIP, treated with indirect co-culture as used in TI group, with addition of 10 nmol/mL ERK specific inhibitor PD98059) according to the random number table. One week after culture, the positive expression rates of CK7 and CK19 in UCMSC were detected by flow cytometry, the expression of CK19 and CEA in UCMSC were examined with immunohistochemical staining and the positive expression rate of CEA was calculated, and the expression level of phosphorylated ERK (pERK) was determined by Western blotting. Data were processed with one-way analysis of variance.</p><p><b>RESULTS</b>(1) CD29, CD44, and CD105 were highly expressed in UCMSC, accompanied by low or negative expression of CD14, CD34, CD45, CK7, CK19, and CEA. The expression of CK19 and CEA were positive in hSGC. The two results showed that UCMSC and hSGC were pure. (2) Compared with those of C group [(2.2 +/- 1.5)%, (2.2 +/- 0.7)%, (3.3 +/- 0.7)%, 0.640 +/- 0.026], the expression levels of CK7, CK19, CEA, and pERK in UCSMC of TI group [(6.4 +/- 0.7)%, (5.7 +/- 0.3)%, (7.4 +/- 1.0)%, 0.790 +/- 0.049] and TIE group [(14.3 +/- 1.0)%, (12.6 +/- 1.1)%, (17.6 +/- 2.3)%, 1.200 +/- 0.032] were significantly increased (with F value respectively 78.49, 139.36, 87.13, and 191.74, P values all below 0.01), and those of TIE group were higher than those of TI group (with F value from 50.14 to 145.47, P values all below 0.01). There were no obvious difference in the 4 indexes between TIP group and C group (with F value from 0.00 to 0.13, P values all above 0.05).</p><p><b>CONCLUSIONS</b>UCMSC co-cultured with heat-shocked hSGC can differentiate into hSGC, and ERK signal pathway participates in the process of differentiation of UCMSC into hSGC.</p>

Effect of proteasome inhibitor on migration ability and hepatocyte growth factor expression of bone marrow mesenchymal stem cells in multiple myeloma patients / 中国实验血液学杂志

This study was aimed to investigate the effect of proteasome inhibitor bortezomib on the migration ability and hepatocyte growth factor (HGF) expression of bone marrow mesenchymal stem cells (MSC) in multiple myeloma patients. Transwell assay was employed to measure the migration ability of bone marrow MSC in vitro before and after treatment with bortezomib. The HGF mRNA expression level was determined by real-time quantitative PCR. The results indicated that after treated with bortezomib of concentrations of 2.5 nmol/L for 48 hours, the migration activity of MSC decreased significantly as compared with control cohorts (p < 0.05). The HGF mRNA level in MSC after bortezomib treatment was significantly lower than that of control group (p < 0.05). It is concluded that bortezomib can inhibit the migration and down-regulate HGF mRNA expression of bone marrow MSC in multiple myeloma patients.

Cardioprotective effects of simvastatin on reversing electrical remodeling induced by myocardial ischemia-reperfusion in normocholesterolemic rabbits / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Recent studies have revealed that pretreatment with statin is effective in preventing arrhythmia, but its electrophysiological mechanism is unclear. This study was conducted to investigate the cardioprotective effects of simvastatin on reversing electrical remodeling in left ventricular myocytes of rabbit heart undergoing ischemia-reperfusion, so as to explore the ionic mechanism responsible for the anti-arrhythmic effect of statin.</p><p><b>METHODS</b>Forty-five rabbits were randomly divided into three groups: ischemic-reperfusion group (I-R), simvastatin intervention group (Statin) and sham-operated control group (CON). Anesthetized rabbits were subjected to 30-minute ischemia by ligation of the left anterior descending coronary artery and a 60-minute reperfusion after a 3-day administration of oral simvastatin of 5 mg x kg(-1) x d(-1) in the Statin group or a placebo in the I-R group. Single ventricular myocytes were isolated enzymatically from the epicardial zone of the infracted region derived from the hearts in the I-R and Statin group and the same anatomical region in the CON animals. The whole cell patch-clamp technique was used to record membrane ionic currents, including sodium current (I(Na)), L-type calcium current (I(Ca-L)) and transient outward potassium current (I(to)). Simultaneously, the level of serum cholesterol was examined.</p><p><b>RESULTS</b>There was no significant difference in the serum cholesterol concentration among the three groups. The peak I(Na) current density (at -30 mV) was significantly decreased in I-R ((-22.46+/-5.32) pA/pF, n=12) compared with CON ((-42.78+/-5.48) pA/pF, n=16, P<0.01) and Statin ((-40.66+/-5.89) pA/pF, n=15, P<0.01), while the peak I(Na) current density in the Statin group was not different from CON (P>0.05). The peak I(Ca-L) current density (at 0 mV) was significantly increased in I-R ((-4.34+/-0.92) pA/pF, n=15) compared with CON ((-3.13+/-1.22) pA/pF, n=13, P<0.05) and Statin ((-3.46+/-0.85) pA/pF, n=16, P<0.05), while the Peak I(Ca-L) current density in Statin was not different from CON (P>0.05). The I(to) current density (at +60 mV) was significantly decreased in I-R ((9.49+/-1.91) pA/pF, n=11) compared with CON ((17.41+/-3.13) pA/pF, n=15, P<0.01) and Statin ((14.54+/-2.41) pA/pF, n=11, P<0.01), although there was a slight reduction in the Statin group compared with CON (P<0.05).</p><p><b>CONCLUSIONS</b>It is implied that ischemia-reperfusion induces significant down-regulation of I(Na) and I(to) and up-regulation of I(Ca-L), which may underlie the altered electrical activity and long abnormal transmembrane action potential duration of the surviving ventricular myocytes, thus contributing to ventricular arrhythmias during acute ischemia-reperfusion period. Pretreatment with simvastatin could attenuate these changes and reverse this electrical remodeling without lowering the serum cholesterol level, contributing to the ionic mechanism of statin in treatment of arrhythmia independent of a decrease in cholesterol.</p>

Changes of Serum Brain Type Creatine Kinase Isoenzyme and Cystatin C in Neonates with Hypoxic-Ischemic Encephalopathy and Their Clinical Significance / 实用儿科临床杂志

Objective To explore the changs of serum brain type creatine kinase isoenzyme(CK-BB),cystatin C of newborns with hypoxic-ischemic encephalopathy(HIE) and assess their applications.Methods The serum concentrations of CK-BB and cystatin C were measured by turbidimertric immunoassay in 56 HIE newborns and 42 normal neonates.Results 1.Compared with controls,the concentration of serum CK-BB in moderate HIE newborns had significant differences(P