Metabolism studies on hydroxygenkwanin and genkwanin in human liver microsomes by UHPLC-Q-TOF-MS

Hydroxygenkwanin (HYGN) and genkwanin (GN) are major constituents of Genkwa Flos for the treatment of edema, ascites, cough, asthma and cancer. This is a report about the investigation of the metabolic fate of HYGN and GN in human liver microsomes and the recombinant UDP-glucuronosyltransferase (UGT) enzymes by using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS). An on-line data acquisition method multiple mass defect filter (MMDF) combined with dynamic background subtraction (DBS) was developed to trace all probable metabolites. Based on this analytical strategy, three phase I metabolites and seven glucuronide conjugation metabolites of HYGN, seven phase I metabolites and 12 glucuronide conjugation metabolites of GN were identified in the incubation samples of human liver microsomes. The results indicated that demethylation, hydroxylation and o-glucuronidation were main metabolic pathways of HYGN and GN. The specific UGT enzymes responsible for HYGN and GN glucuronidation metabolites were identified using recombinant UGT enzymes. The results indicated that UGT1A1, UGT1A3, UGT1A9, UGT1A10 and UGT2B7 might play major roles in the glucuronidation reactions. Overall, this study may be useful for the investigation of metabolic mechanism of HYGN and GN, and it can provide reference and evidence for further experiments.     

腹腔镜膀胱根治性切除术围手术期并发症分析

目的探讨腹腔镜下膀胱根治性切除术围手术期并发症发生情况。方法统计本院2016年12月至2018年12月104例膀胱癌患者行腹腔镜下根治性膀胱切除术(LRC)围手术期的并发症以及手术时间、术中出血量、术后住院时间等情况。围手术期并发症定义为手术30 d内发生的并发症。结果平均手术时间327 min,平均出血量478 mL,接受输血者16例(15.4%),平均输血量415 mL。术后平均住院时间17.9 d。尿流改道方式上,Bricker回肠膀胱术68例,输尿管皮肤造口术36例。围手术期并发症发生率47.1%(49例),包括肠梗阻、尿路感染、肺炎、下肢静脉血栓、肺栓塞等。结论腹腔镜下膀胱根治性切除术仍有较高的并发症发生率,常见并发症为肠梗阻,尿路感染等,术前应积极治疗基础疾病,术中严格操作,术后采取相应预防措施以防止出现严重并发症。并根据患者情况选择合适的手术方案。     

调强放疗联合周剂量顺铂治疗老年人食管癌临床疗效观察

目的：观察调强放疗联合周剂量顺铂治疗老年人食管癌的近期疗效和毒副反应。方法将60例局部晚期老年食管癌患者采用数字表法随机分为同步放化疗组（ CRT组）30例和单纯放疗组（ RT组）30例,两组均采用6MV－X射线调强放疗,放疗剂量：DT 60 Gy／30次／6周。 CRT组在放疗第2天开始给予顺铂20～25 mg／m^2,1次／周,共6次。结果 CRT组、RT组近期有效率分别为80．0％、63．3％,差异有统计学意义（χ^2＝5．934,P＜0．05）。不良反应主要为骨髓抑制、放射性食管炎,基本为Ⅰ～Ⅱ级,两组不良反应差异无统计学意义（P＞0．05）。结论调强放疗联合周剂量顺铂治疗老年人食管癌近期疗效显著,不良反应轻,患者耐受性好,值得临床推广。     

Peritoneal transport rate,systemic inflammation,and residual renal function determine peritoneal protein clearance in continuous ambulatory peritoneal dialysis patients

Background

Peritoneal protein clearance (Pcl) is related to the mortality of patients on continuous ambulatory peritoneal dialysis (CAPD) as well as technique failure. In this prospective observational study, we aimed to investigate factors associated with the level of Pcl.

Methods

We prospectively enrolled 344 prevalent CAPD patients. A standard peritoneal equilibrium test was conducted for each patient. Baseline demographics, biochemistry, and Pcl were recorded.

Results

The average Pcl of the patients was 97.40 ± 54.14 mL/day. Peritoneal transport level, serum high-sensitivity C-reactive protein (hsCRP), and residual glomerular filtration rate (rGFR) were independently related to Pcl. The standard β values were 0.53, 0.17, and ?0.10, respectively. Moreover, compared with non-diabetic patients, diabetic patients had a non-significantly higher level of Pcl (104.90 ± 48.65 vs. 96.15 ± 54.97 mL/day; P = 0.06).

Conclusion

Continuous ambulatory peritoneal dialysis patients lose a high amount of protein through the peritoneum each day. The Pcl value is positively related to the level of peritoneal transport and hsCRP and negatively related to the rGFR.     

我国不同地区阿片类镇痛药物在癌痛治疗中的使用情况及个人经济负担

摘 要 目的：了解我国不同地区阿片类镇痛药的使用情况与趋势,评估癌痛治疗吗啡临床需要量及满足临床需要的程度,评价个人药费可负担性,为我国合理使用阿片类镇痛药,提高癌痛控制水平和患者生活质量提出政策建议。方法：采用回顾性分析方法,分析2006~2016年我国7个片区的阿片类镇痛药使用强度（MUD）及其各阶段年复合增长率（CAGR）。基于我国7个片区肿瘤登记数据和国际疼痛标准治疗指南,测算2015年不同地区的吗啡需要量。将药品价格以DDD值标化为限定日费用(DDC),采用改进后的WHO/HAI标准调查法评价阿片类镇痛药用于癌痛治疗的个人药费可负担性。结果：全国MUD从2006年的1.45DDD/10万人天增长至2016年的6.93DDD/10万人天,整体增长率呈现为前高后低。不同地区间MUD差异较大,且MUD极差有逐年加大趋势。2016年MUD最大地区为华南（9.67DDD/10万人天）,最小为西北（3.28DDD/10万人天）。2015年,全国吗啡等效当量实际使用量仅占癌痛治疗吗啡需要量的21.5%,华东（26%）和华南（36%）等地区高于西南（11%）和西北（12%）。各类阿片类镇痛药的DDC范围为10.80～848.88元,除吗啡注射剂外,其余药品的疗程自付费用均大于1 d的日均可支配收入。结论：我国阿片类镇痛药用于癌痛治疗整体使用不足,且不同经济水平的地区使用差异较大,癌痛患者长期使用镇痛药物治疗的个人药费负担较重。应全面加快推行癌痛规范化治疗示范病房和疼痛门诊,完善相应保障体系,合理引导广大城乡居民可负担的癌痛治疗药品价格,降低个人费用负担,提高癌症患者生存质量,使更多癌痛患者得到经济有效的治疗。     

Effects of angiotensin-converting enzyme inhibitor,captopril, on bone of mice with streptozotocin-induced type 1 diabetes

There are contradictory results about the effect of angiotensin-converting enzyme inhibitors (ACEIs) on bone. This study was performed to address the skeletal renin?angiotensin system (RAS) activity and the effects of the ACEI, captopril, on the bone of streptozotocin-induced type 1 diabetic mice. Histochemical assessment on bone paraffin sections was conducted by Safranin O staining and tartrate-resistant acid phosphatase staining. Micro-computed tomography was performed to analyze bone biological parameters. Gene and protein expression were determined by real-time polymerase chain reaction and immunoblotting, respectively. Type 1 diabetic mice displayed osteopenia phenotype and captopril treatment showed no osteoprotective effects in diabetic mice as shown by the reduction of bone mineral density, trabecular thickness and bone volume/total volume. The mRNA expression of ACE and renin receptor, and the protein expression of renin and angiotensin II were markedly up-regulated in the bone of vehicle-treated diabetic mice compared to those of non-diabetic mice, and these molecular changes of skeletal RAS components were effectively inhibited by treatment with captopril. However, treatment with captopril significantly elevated serum tartrate-resistant acid phosphatase 5b levels, reduced the ratio of osteoprotegerin/receptor activator of nuclear factor-κB ligand expression, increased carbonic anhydrase II mRNA expression and the number of matured osteoclasts and decreased transforming growth factor-β and osteocalcin mRNA expression in the tibia compared to those of diabetic mice. The present study demonstrated that the use of the ACEI, captopril, has no beneficial effect on the skeletal biological properties of diabetic mice. However, this could be attributed, at least partially, to its suppression of osteogenesis and stimulation of osteoclastogenesis, even though it could effectively inhibit high activity of local RAS in the bone of diabetic mice.     

Interleukin-33 alleviates psoriatic inflammation by suppressing the T helper type 17 immune response

Psoriasis is a chronic inflammatory skin disease with unclear pathogenesis. Interleukin-33 (IL-33) is highly expressed in patients with psoriasis, but its role in psoriasis is unknown. The aim of this study was to investigate the possible role of IL-33 in the pathogenesis and treatment of psoriasis. IL-33 expression was determined using enzyme-linked immunosorbent assay, real-time fluorescent quantitative polymerase chain reaction and immunohistochemical staining. CD4⁺ T cells were sorted using magnetic beads and treated with or without IL-33. Imiquimod (IMQ) was used to induce psoriatic inflammation in mice. The frequency of immune cells was determined using flow cytometry. The cytokine level in mouse skin was measured using cytometric bead array. Our results showed that IL-33 was highly expressed in the lesional skin and serum of patients with moderate-to-severe plaque psoriasis. IL-33 inhibited the expression of IL-17 in CD4⁺ T cells of psoriasis patients. Subcutaneous injection of IL-33 alleviated the IMQ-induced psoriatic inflammation in mice, reduced tumor necrosis factor-α and IL-23 expression, and decreased the proportion of T helper type 17 (Th17) cells in the skin-draining lymph nodes in the mice. Our results suggest that IL-33 plays a protective role in the pathogenesis of psoriasis by suppressing Th17 cell differentiation and function. The potential therapeutic effect of IL-33 in treating psoriasis warrants further investigation.