Randomised clinical trial: the effectiveness of Lactobacillus reuteri ATCC 55730 rectal enema in children with active distal ulcerative colitis

Background Intestinal microbiota manipulation, one of the pathogenetic components of inflammatory bowel disease (IBD), has become an attractive therapy for ulcerative colitis (UC). Aim To assess in children with active distal UC the effectiveness of Lactobacillus (L) reuteri ATCC 55730 enema on inflammation and cytokine expression of rectal mucosa. Methods A total of 40 patients (median age: 7.2 years range 6–18) with mild to moderate UC were enrolled in a prospective, randomised, placebo‐controlled study. They received an enema solution containing 10¹⁰ CFU of L. reuteri ATCC 55730 or placebo for 8 weeks, in addition to oral mesalazine. Clinical endoscopic and histological scores as well as rectal mucosal expression levels of IL‐10, IL‐1β, TNFα and IL‐8 were evaluated at the beginning and at the end of the trial. Results Thirty‐one patients accomplished the trial (17 males, median age 13 year, range 7–18). Mayo score (including clinical and endoscopic features) decreased significantly in the L. reuteri group (3.2 ± 1.3 vs. 8.6 ± 0.8, P < 0.01) compared with placebo (7.1 ± 1.1 vs. 8.7 ± 0.7, NS); furthermore, histological score significantly decrease only in the L. reuteri group (0.6 ± 0.5 vs. 4.5 ± 0.6, P < 0.01) (placebo: 2.9 ± 0.8 vs. 4.6 ± 0.6, NS). At the post‐trial evaluation of cytokine mucosal expression levels, IL‐10 significantly increased (P < 0.01) whereas IL‐1β, TNFα and IL‐8 significantly decreased (P < 0.01) only in the L. reuteri group. Conclusions In children with active distal ulcerative colitis, rectal infusion of L. reuteri is effective in improving mucosal inflammation and changing mucosal expression levels of some cytokines involved in the mechanisms of inflammatory bowel disease.     

Treatment of left-sided ulcerative colitis with butyrate enemas: a controlled trial

Background : The colonic mucosa is highly dependent upon the presence of luminal nutrients. This dependence is most marked in the distal colon. The major luminal nutrients are short chain fatty acids that are produced as a by-product of colonic fermentation of carbohydrates. Butyrate appears to be the short chain fatty acid most avidly metabolized by the colonic mucosa. It has been suggested that ulcerative colitis is, at least in part, related to an energy deficiency state of the colonic mucosa which may be secondary to impaired short chain fatty acid production, uptake or utilization. The objective of this study was to determine if butyrate given as enema therapy is effective in the treatment of active distal ulcerative colitis.
Methods : Thirty-eight patients with distal ulcerative colitis were randomly assigned to receive nightly butyrate ( n =19) or saline/placebo ( n =19) enemas. Butyrate enemas consisted of 60 mL of 80 m m sodium butyrate titrated to a pH of 7.0. Patients were assessed clinically and endoscopically at baseline and at 3 and 6 weeks follow-up. Pre- and post-treatment mucosal biopsies were assessed histologically. Response to therapy was determined by changes in a 12-point clinical disease activity index score based on patient symptoms, endoscopic mucosal appearance and physicians' global assessment.
Results : Clinical improvement was noted in seven of 19 (37%) butyrate-treated patients and nine of 19 (47%) placebo-treated patients ( P =0.51). Clinical remission was achieved in three patients in each group (16%). No toxicity was observed in either treatment arm.
Conclusions : The results suggests that once nightly 60 mL butyrate enemas (80 mmol/L) are not efficacious in the treatment of distal ulcerative colitis.     

Clinical trial: controlled,open, randomized multicentre study comparing the effects of treatment on quality of life,safety and efficacy of budesonide or mesalazine enemas in active left‐sided ulcerative colitis

Aliment Pharmacol Ther 2010; 32: 368–376

Summary

Background Therapy for active left‐sided ulcerative colitis usually involves topical application of mesalazine (mesalamine) or budesonide. Aim To compare the efficacy and safety of budesonide enema and mesalazine enema in the treatment of active left‐sided ulcerative colitis. Methods A total of 237 patients with mild–moderate ulcerative colitis were randomized open 1:1 to receive either budesonide (n = 118) or mesalazine enemas (n = 119) for 8 weeks. Efficacy variables were clinical activity index, endoscopic, histological index and IBDQ scores after 4 and 8 weeks. Results Clinical remission (intention‐to‐treat analysis) at week 4 was 63.5% for budesonide enemas and 77.2% for mesalazine enemas (P < 0.05). The respective values for the per protocol population (PP) were 59.9% examined in the budesonide group and 77.5% in the mesalazine group (P < 0.02). At the final visit (W8), clinical remission was diagnosed in the ITT analysis for 64.4% of the budesonide group and 77.4% of the mesalazine group (P < 0.05). The respective values for the PP analysis were 59.5% in the budesonide group and 75.3% in the mesalazine group (P < 0.02). Conclusions Compared with budesonide, mesalazine enema was associated with a significantly higher remission rate; this was supported by favourable trends in endoscopic, histological remission rates and the IBDQ score.     

Prednisolone metasulphobenzoate foam retention enemas suppress the hypothalamo-pituitary-adrenal axis

Background: Corticosteroid enemas represent effective treatment for ulcerative proctitis, but absorption into the systemic circulation may have undesirable metabolic consequences. Prednisolone metasulphobenzoate, a lipophobic corticosteroid derivative, is designed to be absorbed poorly through the recto-sigmoid mucosa, but the effects of foam enema preparations upon the hypothalamo-pituitary-adrenal axis have not been examined. Methods: Nine patients suffering from active ulcerative proctitis underwent four weeks of therapy with prednisolone metasulphobenzoate foam enemas. The hypothalamo-pituitary-adrenal axis, denned using the modified single-dose metyrapone test, glucose homeostasis and lipid profiles were studied before and after treatment. Results: The hypothalamo-pituitary-adrenal axis was significantly depressed after the treatment period; mean stimulated plasma Cortisol concentration fell from 384 ± 244 (s.d.) to 288±252 nmol/L, P < 0.02; stimulated mean plasma 11-deoxyCortisol concentration fell from 677 ± 333 to 407 ± 326 nmol/L, P < 0.01. Mean fasting plasma glucose, insulin, C-peptide, fructosamine and triglyceride concentration were unchanged, whilst the mean serum cholesterol concentrations rose from 5.6 ± 1.1 to 6.0± 1.2 mmol/L (not significant). Conclusion: Prednisolone metasulphobenzoate foam enemas have significant systemic and endocrine metabolic effects, which could assume importance with long-term therapy.     

Abnormal glycosylated hemoglobin as a predictive factor for glucose metabolism disorders in antipsychotic treatment

The aim of this study was to observe the changes in glucose metabolism after antipsychotic (APS) therapy, to note the influencing factors, as well as to discuss the relationship between the occurrence of glucose metabolism disorders of APS origin and abnormal glycosylated hemoglobin (HbA₁c) levels. One hundred and fifty-two patients with schizophrenia, whose fasting plasma glucose (FPG) and 2-h plasma glucose (2hPG) in the oral glucose tolerance test (2HPG) were normal, were grouped according to the HbA₁c levels, one normal and the other abnormal, and were randomly enrolled into risperidone, clozapine and chlorpromazine treatment for six weeks. The FPG and 2hPG were measured at the baseline and at the end of the study. In the group with abnormal HbA₁c and clozapine therapy, 2HPG was higher after the study [(9.5 ± 1.8) mmol/L] than that before the study [(7.2 ± 1.4) mmol/L] and the difference was statistically significant (P < 0.01). FPG had no statistically significant difference before and after the study in any group (P > 0.05). HbA₁c levels and drugs contributing to 2HPG at the end of study had statistical cross-action (P < 0.01). In the abnormal HbA₁c group, 2HPG after the study was higher in the clozapine treatment group [(9.5 ± 1.8) mmol/L] than in the risperidone treatment group [(7.4 ± 1.7) mmol/L] and the chlorpromazine treatment group [(7.3 ± 1.6) mmol/L]. The differences were statistically significant (P < 0.01). In the normal HbA₁c group there was no statistically significant difference before and after the study in any group (P > 0.05). 2HPG before [(7.1 ± 1.6) mmol/L] and after the study [(8.1 ± 1.9) mmol/L] was higher in the abnormal HbA₁c group than in the normal HbA₁c group [(6.2 ± 1.4) mmol/L vs (6.5 ± 1.4) mmol/L] with the difference being statistically significant (P < 0.01 vs P < 0.001). As compared with normal HbA₁c group, the relative risk (RR) of glucose metabolism disease occurrence was 4.7 in the abnormal HbA₁c group with the difference being statistically significant (P < 0.001). Patients with abnormal HbA₁c are more likely to have a higher risk of having glucose metabolism disorders after APS treatment. Translated from Chinese Journal of Psychiatry, 2006, 39(1): 1–4 [译自: 中华精神科杂志]     

MAGNESIUM SUPPLEMENTATION IN MILD HYPERTENSIVE PATIENTS ON A MODERATELY LOW SODIUM DIET

1. The effect of oral magnesium supplementation was assessed in a group of untreated, mild hypertensive subjects who were following a moderately low sodium diet (baseline urinary sodium 86 ± 6 mmol/day). 2. Thirteen patients were allocated placebo and 12 were allocated magnesium aspartate (10 mmol/day) in a double blind fashion for 8 weeks. 3. There was no fall in blood pressure with magnesium supplementation and no significant difference in blood pressure between groups at the end of the study. 4. In the magnesium group there was an increase in urinary magnesium (4.4 ± 0.6 to 6.1 ± 1 mmol/day P < 0.001), and urinary calcium (4.3 ± 0.7 to 5.5 ± 0.9 mmol/day P < 0.01). There was no change in plasma or red cell magnesium or plasma renin activity with supplementation. 5. Magnesium supplementation does not appear to have an additive hypotensive effect in mild hypertensive subjects on a reduced sodium intake.     

EFFECT OF CROSS-FOSTERING ON NEONATAL SODIUM BALANCE AND ADULT BLOOD PRESSURE IN THE SPONTANEOUSLY HYPERTENSIVE RAT

1. The aim of the present study was to compare electrolyte handling in naturally reared neonatal spontaneously hypertensive rats (SHR) with those reared by a Wistar-Kyoto (WKY) rat foster mother (denoted SHRX), as cross-fostering SHR pups to a WKY rat dam lowers adult blood pressure in the SHR. 2. The electrolyte content of WKY rat and SHR dams’ milk was determined and electrolyte intake and urinary excretion rates were calculated in both naturally reared and cross-fostered WKY rat and SHR pups. 3. The milk sodium concentration fell in both strains (WKY rat: 31.8 ± 2.0 to 15.2 ± 1.2 mmol/L; SHR 31.9 ± 2.5 to 18.2 ± 1.6 mmol/L; P < 0.001), as did potassium (P < 0.001), over lactation, but there were no differences between strains. Calcium and magnesium concentrations increased (P< 0.001), although SHR dam's milk contained less calcium (P < 0.001) than that of WKY rat dams during the third week of lactation. 4. Spontaneously hypertensive rat pups ingested less milk (P<0.05) than WKY rat pups; therefore, their cumulative sodium intake over postnatal days 4–15 was significantly lower than that of WKY rat pups (WKY rat vs SHR: 84.4 ± 3.6 vs 59.7 ± 2.6 μmol/g bodyweight, respectively; P < 0.05) and fostered SHRX pups (77.7 ± 7.0 μmol/g bodyweight; P < 0.05). Potassium and magnesium intakes were comparable between SHR, WKY rat and SHRX pups, but SHR pups ingested significantly less calcium than either WKY rat pups (136.1 ± 6.4 vs 200.1 ± 9.5p, mol/g bodyweight, respectively; P<0.05) or SHRX pups (200.0 ± 18.0 μmol/g bodyweight; P<0.05). 5. These data show that the neonatal SHR experiences a period of sodium deficiency during the developmental stage when cross-fostering is effective in lowering blood pressure. This is consistent with the reported up-regulation of the renin-angiotensin system observed in SHR at this time and may have a long-term influence on blood pressure.     

Impact of Custodiol-N cardioplegia on acute kidney injury after cardiopulmonary bypass

Myocardial protection during cardiopulmonary bypass (CPB) can be achieved using cardioplegic solutions. Although, acute kidney injury (AKI) is a common complication following CPB, the effects of cardioplegic solutions on AKI have rarely been investigated. Within this study, the effects of the cardioplegic solutions histidine-tryptophan-ketoglutarate (HTK; Custodiol) and HTK-N (Custodiol-N) on AKI in a large animal model were compared. Therefore, Landrace pigs underwent median sternotomy, CPB at 34°C, 90 minutes of cardiac arrest and 120 minutes of reperfusion. Animals were randomized for single-shot cardioplegia with either HTK (n = 10) or HTK-N (n = 10). Renal biopsies and sera were analyzed to determine AKI biomarkers and apoptosis. Compared to HTK, HTK-N induced a decreased extent of proximal tubule swelling (48.3 ± 1.6 µm vs 52.3 ± 1.1 µm, P = .05) and decreased cytochrome c release (0.26 ± 0.04 vs 0.46 ± 0.08, P = .04) without reaching statistical significance due to Bonferroni correction. Comparing baseline and postreperfusion levels, the hemoglobin (Hb) and blood calcium levels were lower in HTK-N (Hb_baseline: 6.0 ± 0.6 mmol/L, Hb_reperfusion: 6.2 ± 0.7 mmol/L, P = .12; Ca²⁺_baseline: 1.36 ± 0.05 mmol/L, Ca²⁺_reperfusion: 1.28 ± 0.05 mmol/L, P = .16) compared to the HTK group (Hb_baseline: 5.9 ± 0.4 mmol/L, Hb_reperfusion: 4.7 ± 0.8 mmol/L, P < .01; Ca²⁺_baseline: 1.34 ± 0.07 mmol/L, Ca²⁺_reperfusion: 1.24 ± 0.06 mmol/L, P < .01). The present study showed that HTK-N could positively affect the kidney during CPB. Hb and calcium levels were stabilized. A statistical trend was found showing that AKI-related proximal tubule swelling and cytochrome c release were diminished.     

Beclomethasone dipropionate enemas versus prednisolone sodium phosphate enemas in the treatment of distal ulcerative colitis

Aim:

To compare beclomethasone dipropionate 3 mg/60 mL enema (BDP) and prednisolone sodium phosphate 30 mg/60mL enema (PP) once daily in patients with active distal ulcerative colitis.

Methods:

One hundred and fifty-seven patients were enrolled in a multicentre, 4-week, randomized, double-blind trial. Patients were assessed at baseline, 2 and 4 weeks.

Results:

Both treatment groups showed statistically significant improvement of clinical activity after 2 and 4 weeks. Endoscopy and biopsy showed a reduction in the activity score at the end of the treatment period in both groups. No statistically significant difference was observed between the two treatment groups. After 4 weeks, 29% of patients in the BDP group and 25% in the PP group were considered to be in clinical remission; an improvement was observed in 40% of patients on BDP and in 47% on PP. Mean morning plasma cortisol levels showed a slight but significant reduction in the PP group, while the ACTH test showed that neither drug interfered with the hypothalamic–pituitary–adrenal (HPA) axis function. No significant changes were observed in the laboratory tests. Finally, there was a low incidence of adverse events in both groups.

Conclusions:

It is concluded that, in the topical treatment of active distal ulcerative colitis, BDP 3 mg enemas are as efficacious as PP 30 mg enemas, without interference with the HPA axis.

     

Effects of calcitriol on bone mineral density in patients treated with esomeprazole

Context: Proton pump inhibitor (PPI) increases the risk of decrease in bone mineral density (BMD). However, whether calcitrol improves this situation is unknown.

Objective: The current study investigates the effects of calcitriol on BMD in patients with esomeprazole therapy.

Materials and methods: Three hundred and eighty-six participants with gastrointestinal ulcerations were enrolled and randomly assigned into controlled and supplemented groups. Participants in the controlled group were prescribed esomeprazole (20?mg/qd), while the supplemented group was prescribed esomeprazole (20?mg/qd) and calcitriol (2.5?μg/qd). BMD, serum levels of calcium, carboxy-terminal collagen crosslinks (CTX), and alkaline-phosphatase (ALP) were assessed.

Results: (1) No significant between-group difference of age, gender, smoking, previous glucocorticoid use and hemoglobin level was found; (2) after 10.6?±?0.8?d of PPI therapy, BMD T score in the controlled group was slightly increased compared with initial (?1.25?±?0.08 versus ?1.28?±?0.06, p?=?0.084), while there was no change in the supplemented group (?1.25?±?0.05 versus ?1.26?±?0.03, p?=?0.308); (3) during study termination, calcium level in the supplemented group was slightly higher than the controlled group (2.05?±?0.03?mmol/L versus 2.01?±?0.05?mmol/L, p?=?0.073), while no significant differences of CTX (366.57?±?43.71?pg/mL versus 373.15?±?50.23?pg/mL, p?=?0.036) and ALP were found among these two groups (50.47?±?9.32?U/L versus 52.23?±?10.45?U/L, p?=?0.075).

Conclusion: Patients with gastrointestinal ulcerations with esomeprazole therapy, calcitriol supplement showed no efficacy on BMD changes.     

Clinical trial: insulin-sensitizing agents may reduce consequences of insulin resistance in individuals with non-alcoholic steatohepatitis

Background Currently, although only a few therapies normalize the liver test abnormalities with/without improving the liver histology, no pharmacologic therapy has proved to be effective for the treatment of non‐alcoholic steatohepatitis. Aim To investigate the role of insulin sensitizers in the treatment of individuals with non‐alcoholic steatohepatitis (NASH). Methods A total of 74 individuals with NASH (male/female, 44/30; mean age, 47.2 ± 9.0 years) were enrolled. Participants were divided into two distinct groups: group 1 (n = 25) participants were administered a conventional diet and exercise programme while those in group 2 (n = 49) were administered the diet and exercise programme plus insulin sensitizers. Results With respect to baseline metabolic, biochemical and histological parameters, no significant differences were observed between the two groups (P > 0.05). Insulin sensitizers significantly improved metabolic parameters (homeostasis model assessment‐insulin resistance score, P < 0.05), serum aminotransferase levels [aspartate aminotransferase (AST): 45.9 ± 24.2 to 33.3 ± 17.7 IU/L, P < 0.01; alanine aminotransferase (ALT): 78.2 ± 46.3 to 47.3 ± 34.5 IU/L, P < 0.001] and histological features (median non‐alcoholic fatty liver disease activity score: 5.0–3.0, P = 0.01), while diet and exercise improved serum aminotransferase levels (AST: 39.3 ± 11.1 to 30.0 ± 8.6 IU/L, P < 0.01; ALT: 66.9 ± 28.9 to 42.0 ± 16.2 IU/L, P < 0.001) at the end of the 48 weeks when compared to baseline. Insulin sensitizers improved the high‐sensitivity C‐reactive protein levels (P < 0.01). No serious adverse effects of insulin sensitizers were observed. Conclusion Insulin sensitizers can lead to improvement in metabolic, biochemical and histological abnormalities of NASH as a result of improved insulin sensitivity.     

参黄降糖胶囊对糖尿病合并高血压病人血管内皮功能、血液流变学的影响

目的 探讨参黄降糖胶囊对糖尿病合并高血压病人血管内皮功能、血液流变学及血压、血糖水平的影响。方法 选取2019年5月至2020年5月在河北省沧州中西医结合医院接受治疗的糖尿病合并高血压病人98例,采用随机数字表法分为参黄降糖组（49例）和常规组（49例）,常规组给予硝苯地平及二甲双胍治疗,参黄降糖组在常规组基础上给予参黄降糖胶囊治疗,比较两组病人血管内皮功能指标[内皮素-1、一氧化氮、血管内皮生长因子（VEGF）水平]、血压水平（24 h平均舒张压、24 h平均收缩压）、血糖指标、血液流变学指标及临床疗效的变化。结果 两组病人内皮素-1水平、24 h平均舒张压、24 h平均收缩压水平、血液流变学指标、血糖指标治疗后[24 h平均舒张压：（75.52±10.27）mmHg、（91.46±10.21）mmHg;24 h平均收缩压：（112.64±20.18）mmHg、（127.52±20.21）mmHg;空腹血糖：（6.18±1.09）mmol/L、（6.92±1.24）mmol/L;餐后2 h血糖（2hPG）:(8.87±1.44)mmol/L、（10.28±2.01）mmol/L;空腹...     

检测血清尿素水平评估慢性肝炎病情

目的检测慢性肝病患者血清尿素(Urea)水平的变化,探讨其在评估慢性肝炎病情中的意义。方法采用连续监测法测定186例(分5组)慢性肝病患者及40例正常人血清Urea水平,同时测定肝功能指标,进行比较分析。结果正常对照组血清Urea水平为5.01±0.68mmol/L,慢性肝炎轻度患者为4.90±0.76mmol/L、中度患者为4.14±0.81mmol/L、重度患者为4.09±0.69mmol/L。慢性肝炎中度及重度患者血清Urea水平明显低于正常对照组(t=4.635、3.819,P<0.01)和慢性肝炎轻度患者(t=2.818、2.093,P<0.01、P<0.05)。肝硬化代偿组患者Urea(4.88±1.24mmol/L)与正常对照组比较无显著性变化(t=0.559,P>0.05),但肝硬化失代偿组患者Urea水平(6.08±2.67mmol/L)明显高于正常对照组(t=2.446,P<0.05)。结论慢性肝炎患者血清Urea水平降低,且随着病情的加重呈进行性下降,血清Urea测定可作为慢性肝炎肝脏受损的一项指标,同时对慢性肝炎病情的估计有一定价值。     

血脂全套分析在肾病综合征诊断中的应用价值

目的 探讨肾病综合征（NS）患者血浆总胆固醇（CHOL）、三酰甘油（TG）、高密度脂蛋白（HDL）、低密度脂蛋白（LDL）、载脂蛋白A1（Apo-A1）及载脂蛋白B （Apo-B）水平变化及临床意义。方法 选择2013年1月至2016年11月太和县人民医院收治的60例NS患者为NS疾病组,同期住院其他肾脏疾病患者30例（非NS患者）为疾病对照组,50例本院健康体检者为正常对照组,检测并比较治疗前3组对象的CHOL、TG、HDL、LDL、Apo-A1及Apo-B水平。结果 NS疾病组的CHOL、TG、HDL、LDL、Apo-A1及Apo-B水平分别为（9.18±2.50） mmol/L、（3.00±1.55） mmol/L、（1.65±0.53） mmol/L、（5.83±2.27） mmol/L、（1.66±0.42） g/L、（1.83±0.61） g/L;疾病对照组CHOL、TG、HDL、LDL、Apo-A1及Apo-B水平分别为（4.22±0.98） mmol/L、（1.89±1.35） mmol/L、（1.13±0.44） mmol/L、（2.39±0.70） mmol/L、（1.06±0.32） g/L、（0.88±0.22） g/L;正常对照组CHOL、TG、HDL、LDL、Apo-A1及Apo-B的水平分别为（4.42±0.46） mmol/L、（1.10±0.31） mmol/L、（1.33±0.21） mmol/L、（2.37±0.43） mmol/L、（1.31±0.17） g/L、（0.80±0.12） g/L。3组研究对象的生化指标差异有统计学意义（P<0.05）,且NS疾病组各指标水平均高于疾病对照组、正常对照组,差异有统计学意义（P<0.05）,而疾病对照组与正常对照组的TG、HDL和Apo-A1水平差异有统计学意义（P<0.05）。3组研究对象的CHOL、TG、HDL、LDL、Apo-A1及Apo-B的异常率差异有统计学意义（P<0.05）。结论 与正常健康人和非NS肾病患者比较,NS患者存在明显的血脂异常。     

Nicotine tartrate liquid enemas for mildly to moderately active left-sided ulcerative colitis unresponsive to first-line therapy: a pilot study

Background: Ulcerative colitis is predominantly a disease of non-smokers, and transdermal nicotine is therapeutic but often results in side-effects. Administration of nicotine as a liquid rectal enema results in less systemic nicotine absorption. Aim: To determine the safety and clinical response of nicotine tartrate liquid enemas for active left-side ulcerative colitis in a pilot study. Methods: Ten non-smoking patients with mildly to moderately active left-sided ulcerative colitis unresponsive to first-line therapy were treated in an open protocol with nightly nicotine tartrate liquid enemas at a dose of 3 mg nicotine base for 1 week then 6 mg for 3 weeks. Clinical assessments were determined at baseline and 4 weeks by endoscopy, physician assessment and a patient diary of daily symptoms. Peak and trough serum nicotine and trough plasma cotinine were determined by gas chromatography/mass spectrometry and high performance liquid chromatography, respectively. Results: After 4 weeks of treatment, 5/7 patients (71%) showed clinical and sigmoidoscopic improvement (per protocol analysis). The other three patients discontinued therapy within 7 days because of inability to retain the liquid enemas. No patients showed histologic improvement. Six of the patients who completed the 4-week study had peak and trough serum nicotine concentration determined, only 1 of 6 patients had a detectable peak nicotine concentration (value 2.3 ng/mL), and all six patients had undetectable trough nicotine concentrations. The mean trough plasma cotinine concentration was 13 ± 10 ng/mL. Transient and mild adverse events occurred in 4/10 patients (nausea, lightheadedness, tremor, sleep disturbance). Given the low or undetectable serum nicotine concentrations, these adverse events are not likely to be related to the nicotine enemas. Conclusions: Nicotine tartrate liquid enemas administrated at a dose of 3 mg nicotine base/day for 1 week and then 6 mg/day for 3 weeks are safe and appear to result in clinical improvement in some patients with mildly to moderately active, left-sided ulcerative colitis unresponsive to first-line therapy. Placebo-controlled trials are warranted to confirm these preliminary findings.     

静脉注射丙种球蛋白治疗新生儿ABO溶血病对血糖的影响——两种测定方法比较研究

目的:探讨静脉注射丙种球蛋白(IVIG)治疗新生儿ABO溶血病对血糖的影响。方法:选取我院2012年2月至2016年2月足月新生儿明确诊断为ABO溶血病33例并给予静脉注射IVIG的患儿为研究组,其中输注IVIG后血糖正常的14例患儿为研究1组,输注IVIG后血糖增高的19例患儿为研究2组;选择同期ABO溶血病未使用IVIG的34例患儿作为对照组。比较三组患儿治疗过程中的血糖变化情况。结果:研究1组用试纸法和葡萄糖氧化酶法监测输注IVIG后2 h血糖为(5.7±0.6)mmol/L和(5.7±0.5)mmol/L,输注后4 h的血糖为(5.7±0.9)mmol/L和(5.8±0.4)mmol/L(P均>0.05);研究2组用试纸法和葡萄糖氧化酶法监测输注IVIG后2 h后血糖为(11.7±0.6)mmol/L和(7.5±0.6)mmol/L,输注后4 h血糖为(12.5±0.8)mmol/L和(8.7±0.5)mmol/L(P均<0.05);对照组在相同时间点的血糖分别为(5.5±0.4)mmol/L和(5.9±0.4)mmol/L、(5.4±0.6)mmol/L和(5.3±0.3)mmol/L(P均>0.05)。结论:新生儿ABO溶血病患儿静脉输注IVIG过程中出现部分病例血糖增高,临床输注IVIG过程中应重视血糖检测,密切检测血糖情况,以减少高血糖对小儿产生危害。     

微 RNA-124-3p在溃疡性结肠炎病人外周血中的表达及意义

目的 检测溃疡性结肠炎（UC）病人外周血中微RNA-124-3p(miR-124-3p)的表达水平,并讨论其临床意义。方法 选择121例UC病人（UC组）和60例健康体检者（对照组）作为研究对象进行前瞻性研究,UC组来源于2019年8月至2021年8月期间武汉市蔡甸区人民医院住院治疗的病人,对照组为同期来院进行健康体检的个体。采用实时荧光定量PCR(qRT-PCR)检测miR-124-3p在各组外周血中的表达水平,酶联免疫吸附实验（ELISA）法检测C-反应蛋白（CRP）在各组外周血中的表达水平。UC活动期病人外周血miR-124-3p表达水平与CRP水平的相关性采用Pearson法,与UC内镜严重指数（UCEIS）评分、改良梅奥（Mayo）评分的相关性分析采用Spearman法。结果 与对照组相比,UC组病人外周血中miR-124-3p的表达水平显著降低（0.84±0.22比0.52±0.17,P<0.05）,CRP水平显著升高[（7.08±2.52）mg/L比（9.83±2.91）mg/L,P<0.05]。与UC缓解期病人相比,活动期病人外周血中miR-124-3p的表...     

ACUTE EFFECT OF ETHANOL ON RENAL ELECTROLYTE TRANSPORT IN THE RAT

1. Despite human and animal studies, the direct effect of ethanol on renal water and electrolyte transport is poorly understood. The acute effect of increasing plasma concentrations of ethanol was evaluated in a water diuretic anaesthetized rat model which inhibits endogenous arginine vaso-pressin (AVP) release. 2. Ethanol at a plasma concentration of 1.69 ±0.28 mmol/L produced an immediate increase in urine flow (174 ± 11 μL/min pre-ethanol and 189 ± 13 and then 206 ± 12 μL/min during the ethanol infusion; P<0.001) as well as an increase in fractional sodium excretion (0.17 ± 0.04 to 0.28 ± 0.05 and 0.27 ± 0.05%; P<0.001). There was also a brief phosphaturia. These increases in electrolyte excretion had returned to control values by 20 min despite a further increase in the plasma ethanol concentration. 3. The urinary excretion of potassium, calcium and magnesium was not altered nor was glomerular filtration rate or renal plasma flow. 4. Ethanol at a mean concentration of 1.60 mmol/L did not alter the action of a maximal concentration of AVP (75 ng/kg) on water or electrolyte transport. However, the antidiuretic effect of a submaximal concentration of AVP (7.5 ng/kg) was augmented by ethanol at concentrations of 1.63 and 0.98 mmol/L. 5. These studies suggest that the ethanol induced diuresis commonly ascribed to inhibition of AVP secretion may also be due to other intrarenal effects of ethanol, possibly acting within the proximal tubule. These results also confirm recent in vitro findings that while ethanol does not inhibit the action of a maximal concentration of AVP, it does modulate the effects of lower AVP concentrations.     

Efficacy and safety of coenzyme A versus fenofibrate in patients with hyperlipidemia: a multicenter,double-blind,double-mimic,randomized clinical trial

Abstract

Background: We investigated the lipid-lowering efficacy and safety of coenzyme A (CoA) versus fenofibrate in Chinese patients with moderate dyslipidemia.

Methods: A total of 417 subjects (aged 18–75?years) diagnosed with moderate dyslipidemia (triglyceride 2.3–6.5?mmol/L) from 13 large cardiovascular centers in China were recruited and randomly divided into a fenofibrate group (n?=?207), which received 200?mg of fenofibrate orally once daily, and a CoA group (n?=?210), which received 400?mg of CoA orally once a day. Blood lipoproteins, liver and renal function, creatine kinase, and blood glucose were measured at baseline, and after 4 and 8?weeks of treatment.

Results: The baseline triglyceride (TG) level in the fenofibrate group and the CoA group was 3.39?±?0.99?mmol/L and 3.60?±?1.11?mmol/L, respectively. After treatment for 4 and 8?weeks with fenofibrate, TG was reduced by 31.62% and 33.13%. In the CoA group, TG was reduced by 17.29% and 23.80%. Compared with baseline, total cholesterol (TC) was significantly decreased in both groups after either 4 or 8?weeks of treatment (p?<?.05). CoA increased high-density lipoprotein cholesterol (HDL-C) after 4?weeks of treatment, whereas it had no significant effect on HDL-C after 8?weeks of treatment. Low-density lipoprotein cholesterol (LDL-C) was not modified in either group. The incidence of side effects was significantly lower in the CoA group compared with the fenofibrate group (p?<?.05).

Conclusions: Compared with fenofibrate, CoA has less effect on reducing plasma TG levels in subjects with moderate dyslipidemia. However, it has fewer adverse effects.     

Effects of garlic polysaccharide on alcoholic liver fibrosis and intestinal microflora in mice

Context: Alcoholic liver fibrosis (ALF) is treatable and reversible consequence of liver disease. Intestinal microflora plays an important role in the progression of liver disease. Garlic (Allium sativum L. [Amaryllidaceae]) has been consumed as a traditional medicine to treat liver injury.

Objective: To investigate the effects of garlic polysaccharide (GP) on ALF and intestinal microflora in mice.

Materials and methods: KM mice were orally administered with alcohol (56%, 6?mL/kg) for 30?d to establish ALF model, and divided into four groups together with control group (water only). Hugan tablet (60?mg/kg) or GP (250 and 150?mg/kg) were given 5?h after each dose of alcohol. Biochemical markers in serum and liver homogenate were determined with kits. Alteration of intestinal microflora, and protein expressions of TGF-β1, TNF-α and decorin were detected.

Results: In GP-H group, ALT and AST decreased to 18.85?±?4.71?U/L and 40.84?±?7.89?U/L. MDA, TC, TG and LDL-C decreased to 2.32?±?0.86?mmol/mg, 0.21?±?0.12?mmol/L, 0.96?±?0.31?mmol/L and 0.084?±?0.027?mmol/L. SOD, GSH-Px and GSH increased to 118.32?±?16.32?U/mg, 523.72?±?64.20?U/mg and 0.56?±?0.05?mg/g. Ratios of TGF-β1 and TNF-α decreased to 0.608?±?0.170 and 1.057?±?0.058, decorin increased to 2.182?±?0.129. Lachnospiraceae and Lactobacillus increased, Facklamia and Firmicutes decreased with GP pretreatment.

Discussion and conclusions: Intestinal microflora provides novel insight into the mechanisms of GP that may be used to treat ALF and intestinal microflora dysbiosis.