ZD 7288,an HCN channel blocker,attenuates chronic visceral pain in irritable bowel syndrome-like rats

AIM:To investigate the effects of ZD 7288,a hyperpolarization-activated cyclic nucleotide-gated(HCN)channel blocker,on rats with chronic visceral pain.METHODS:Rats with visceral hypersensitivity were generated using neonatal colon irritation during postnatal days 8-15 as described previously.Visceral hypersensitivity was evaluated using electromyographic(EMG)responses of abdominal external oblique muscles to 20-80 mmHg colorectal distentions(CRD).Abdominal withdrawal reflex(AWR)scores and pain thresholds were also detected in adult rats.Different doses of ZD7288(25,50,and 100 nmol/L)were intrathecally administered in rats to study the role of spinal HCN channel in chronic visceral hypersensitivity.RESULTS:EMG responses to 20-80 mmHg CRD and AWR scores under 20-60 mmHg CRD significantly increased in rats with visceral hypersensitivity compared to control rats(P<0.05).The pain threshold in rats with visceral hypersensitivity significantly decreased compared to control rats(P<0.05).Treatment with50-100 nmol/L ZD 7288 significantly inhibited EMG responses(16%-62%,80-20 mmHg CRD,P<0.05)and AWR scores(24%-37%,40-20 mmHg CRD,P<0.05;12%-61%,80-20 mmHg CRD,P<0.05,respectively),and significantly increased pain thresholds(32%-77%,P<0.05).CONCLUSION:Spinal HCN channels may play an important role in chronic visceral hypersensitivity.     

海博刀与三角刀在经口内镜下肌切开术中疗效的回顾性队列研究

目的 比较海博刀与三角刀在经口内镜下肌切开术(POEM)中的临床疗效。方法 采用回顾性队列研究设计，纳入2012年6月至2014年7月因贲门失弛缓症在南方医科大学南方医院接受POEM治疗的患者，术中使用海博刀者为海博刀组，使用注射针和三角刀者为三角刀组，比较两组手术相关参数、术后症状缓解及并发症发生率。结果 共纳入57例患者，其中海博刀组25例，三角刀组32例。两组患者基线特征比较差异无统计学意义（P>0.05）。海博刀组平均手术时间短于三角刀组[(55.3±17.7)min比(69.5±9.4)min，P=0.038)]；术中平均器械交换次数少于三角刀组[(4.5±1.5)次比(10.7±1.7)次，P=0.000]。所有患者无严重不良事件发生。在1年的随访中，海博刀组治疗成功率92.0%(23/25)，三角刀组96.9%(31/32)，差异无统计学意义（P=0.576)。结论 海博刀能显著缩短POEM手术时间，并且获得与三角刀相似的治疗成功率。     

Effects of Crede's method on urine voiding within the first 8 h after surgery among post‐haemorrhoidectomy patients: a comparison study

Urinary retention is a common complication among patients after haemorrhoidectomy. Although Crede's method is recommended for urinary retention in nursing practice textbooks, its effects require further examination. The purpose of this study was to investigate the rate of urine voiding within the first 8 h following haemorrhoidectomy and to examine the effects of Crede's method on this postoperative outcome. A two‐group comparison study was conducted. All participants were over 20 years of age, and each had undergone haemorrhoidectomy. Outcome measurements included patients' self‐reported urine voiding within 8 h of surgery, personal demographics and disease‐related data. Before the surgical procedure, participants were divided into Crede's group and non‐Crede's group, and written educational materials were given. Patients in the Crede's group were taught Crede's method for application in the event that they were unable to void urine after haemorrhoidectomy. The non‐Crede's group patients were taught traditional methods without Crede's method. We examined urine voiding within the first 8 h after haemorrhoidectomy. The mean rate of urine voiding within 8 h of surgery was 60·9% overall, with 91·3% (21/23) in the Crede's group and 30·4% (7/23) in the non‐Crede's group reporting successful voiding. After controlling for the two groups' personal characteristics and disease‐related variables, age, educational level and perioperative fluid administration were treated as covariates and included in the multinomial logistic regression model. The odds ratio of urine voiding within the first 8 h after surgery was 52·70‐fold higher in the Crede's group than in the non‐Crede's group (p < 0·01). This study shows that Crede's method is an effective strategy to aid in urine voiding within the first eight postsurgical hours among patients following haemorrhoidectomy. Clear and concise information about urinary retention and related management strategies should be given to patients before haemorrhoidectomy.     

Meta-analysis of NOD2/CARD15 polymorphisms with psoriasis and psoriatic arthritis

Psoriasis and psoriatic arthritis (PsA) is a complex autoimmune disease. NOD2/CARD15 gene has been suggested to play an important role in the pathogenesis of psoriasis and PsA. This study aims to assess the association between NOD2/CARD15 polymorphisms and the susceptibility to psoriasis/PsA. A meta-analysis was performed to survey studies on the NOD2/CARD15 polymorphisms and psoriasis/PsA using comprehensive PubMed, Embase, and Web of Science citation search. A total of 9 published studies were involved. Meta-odds ratios (ORs) and 95% confidence intervals (CIs) based on fixed effects models or random effects models were depended on Cochran’s Q-statistic. Potential publication bias was evaluated by Egger’s linear regression test. As for R702W, the pooled ORs were 1.041 (95% CI 0.854–1.268, P?=?0.693; 2,081 patients vs. 2,717 controls) for C allele and 0.886 (95% CI 0.565–1.391. P?=?0.600; 1,222 patients vs. 1,818 controls) for genotype. Then for G908R, the pooled ORs were 1.042 (95% CI, 0.761–1.426, P?=?0.799; 2,053 patients vs. 2,743 controls) for C allele and 0.942 (95% CI 0.708–1.254, P?=?0.683; 1,226 patients vs. 1,824 controls) for the homozygous wild type. Then for Leu1007fsinsC allele polymorphism and genotype, the pooled ORs were 1.160 (95% CI, 0.893–1.507, P?=?0.266; 2,279 patients vs. 3,067 controls) and 1.266 (95% CI 0.897–1.789, P?=?0.180; 1,979 patients vs. 1,607 controls), respectively. No obvious publication bias was shown in the results. The association between NOD2/CARD15 polymorphisms and psoriasis/PsA was not found. Taken together, our results suggest that NOD2/CARD15 might not be a susceptibility gene for psoriasis and psoriatic arthritis.     

Serial measurement of hepatic lipids during chemotherapy in patients with colorectal cancer: a 1H MRS study

Hepatic steatosis is a hallmark of chemotherapy‐induced liver injury. We made serial ¹H MRS measurements of hepatic lipids in patients over the time course of a 24‐week chemotherapeutic regimen to determine whether ¹H MRS could be used to monitor the progression of chemotherapy‐induced steatosis. Thirty‐four patients with stage III or IV colorectal cancer receiving 5‐fluorouracil, folinic acid and oxaliplatin (n = 21) or hepatic arterial infusion of floxuridine with systemic irinotecan (n = 13) were studied prospectively. ¹H MRS studies were performed at baseline and after 6 and 24 weeks of treatment. A ¹H MR spectrum was acquired from the liver during a breath hold and the ratio of fat to fat + water (FFW) was calculated to give a measure of hepatic triglycerides (HTGCs). The methodology was histologically validated in 18 patients and the reproducibility was assessed in 16 normal volunteers. Twenty‐seven patients completed baseline, 6‐week and 24‐week ¹H MRS examinations and one was censored. Thirteen of 26 patients (50%) showed an increase in FFW after completion of treatment. Six patients (23%) developed hepatic steatosis and two patients converted from steatosis to nonsteatotic liver. Patients whose 6‐week hepatic lipid levels had increased significantly relative to baseline also had a high probability of lipid elevation relative to baseline at the completion of treatment. Serial ¹H MRS is effective for the monitoring of HTGC changes during chemotherapy and for the detection of chemotherapy‐associated steatosis. Six of 26 patients developed steatosis during chemotherapy. Lipid changes were observable at 6 weeks. Copyright © 2012 John Wiley & Sons, Ltd.     

Paclitaxel and etoposide-loaded Poly (lactic-co-glycolic acid) microspheres fabricated by coaxial electrospraying for dual drug delivery

Abstract

In this study, we fabricated paclitaxel (PTX) and etoposide (ETP) loaded Poly (lactic-co-glycolic acid) (PLGA) microspheres with core–shell structures and particle sizes ranging from 1 to 4?µm by coaxial electrospraying. The microspheres were analyzed by scanning electron microscopy (SEM), transmission electron microscopy (TEM). The drug loading rate and entrapment efficiency of the microspheres were detected by high performance liquid chromatograph (HPLC). Moreover, the drug release profiles and degradation of drug-loaded PLGA microspheres in vitro were investigated, respectively. The distinct layered structure that existed in the manufactured core–shell microspheres can be observed by TEM. The in vitro release profiles indicated that the PLGA/PTX?+?ETP (PLGA/PE) microspheres exhibited the controlled release of two drugs in a sequential manner. Cell Counting Kit-8 was used to detect the toxic and side effects of the microspheres on bone tumor cells. PTX and ETP for combination drug therapy loaded microspheres had more cytotoxic effect on saos-2 osteosarcoma cells than the individual drugs. In conclusion, core–shell PLGA microspheres by electrospraying for combination drug therapy is promising for medicine applications, the PLGA/PE microspheres have some potential for osteosarcoma treatment.     

A Bayesian Meta-analysis Method for Estimating Risk Difference of Rare Events

Bayesian meta-analysis has been more frequently utilized for synthesizing safety and efficacy information to support landmark decision-making due to its flexibility of incorporating prior information and availability of computing software. However, when the outcome is binary and the events are rare, where event counts can be zero, conventional meta-analysis methods including Bayesian methods may not work well. Several methods have been proposed to tackle this issue but the prior knowledge of event rate was not utilized to increase precision of risk difference estimates. To better estimate risk differences, we propose a new Bayesian method, Beta prior BInomial model for Risk Differences (B-BIRD), which takes into account the prior information of rare events. B-BIRD is illustrated using a real data set of 48 clinical trials about a type 2 diabetes drug. In simulation studies, it performs well in low event rate settings.     

Effects of Polystyrene Microplastics on Growth and Toxin Production of Alexandrium pacificum

Microplastics (MP) widely distributed in aquatic environments have adverse effects on aquatic organisms. Currently, the impact of MP on toxigenic red tide microalgae is poorly understood. In this study, the strain of Alexandrium pacificum ATHK, typically producing paralytic shellfish toxins (PST), was selected as the target. Effects of 1 and 0.1 μm polystyrene MP with three concentration gradients (5 mg L⁻¹, 25 mg L⁻¹ and 100 mg L⁻¹) on the growth, chlorophyll a (Chl a), photosynthetic activity (F_v/F_m) and PST production of ATHK were explored. Results showed that the high concentration (100 mg L⁻¹) of 1 μm and 0.1 μm MP significantly inhibited the growth of ATHK, and the inhibition depended on the size and concentration of MP. Contents of Chl a showed an increase with various degrees after MP exposure in all cases. The photosynthesis indicator F_v/F_m of ATHK was significantly inhibited in the first 11 days, then gradually returned to the level of control group at day 13, and finally was gradually inhibited in the 1 μm MP treatments, and promotion or inhibition to some degree also occurred at different periods after exposure to 0.1 μm MP. Overall, both particle sizes of MP at 5 and 25 mg L⁻¹ had no significant effect on cell toxin quota, and the high concentration 100 mg L⁻¹ significantly promoted the PST biosynthesis on the day 7, 11 and 15. No significant difference occurred in the cell toxin quota and the total toxin content in all treatments at the end of the experiment (day 21). All MP treatments did not change the toxin profiles of ATHK, nor did the relative molar percentage of main PST components. The growth of ATHK, Chl a content, F_v/F_m and toxin production were not affected by MP shading. This is the first report on the effects of MP on the PST-producing microalgae, which will improve the understanding of the adverse impact of MP on the growth and toxin production of A. pacificum.