Predictive factors analysis of the efficacy of cyclophosphamide combined with glucocorticoids in the treatment of idiopathic membranous nephropathy

Objective To investigate the predictive factors affecting the efficacy of cyclophosphamide (CTX) combined with glucocorticoids in the treatment of idiopathic membranous nephropathy (IMN), and to evaluate the efficacy of calcineurin inhibitor (CNI) adjustment due to poor treatment. Methods A retrospective cohort study was conducted. Two hundreds and twenty-eight patients with IMN diagnosed by renal biopsy in the People's Hospital of Guangxi Zhuang Autonomous Region from January 1, 2007 to December 1, 2016 were enrolled. All subjects were treated with CTX in combination with glucocorticoids. The patients were divided into two groups: remission group and no remission group. Multivariable logistic regression analysis was used to determine the baseline clinical-pathological influencing factors for the remission of IMN in the enrolled patients. Results The number of total remission (including complete and partial remission) of the first CTX combined with glucocorticoid treatment in 228 patients with IMN was 188(82.5%). Among them, 141 patients (61.8%) had complete remission (CR), the median time for CR was 8(6, 12) months, and the median time for partial remission (PR) was 3(1, 4) months. The median follow-up time for this study was 25(13, 43) months. Compared with the remission group, the serum albumin level was lower in the non-remission group, the 24-hour urine protein content, the blood complement C3 and C4 levels were higher, and the pathological stage was milder (all P﹤0.05). Multivariate logistic regression analysis suggested that the levels of baseline serum albumin, complement C4, and pathological stage were independent predictors of clinical remission in IMN patients. Twenty-four non-remission patients were treated with CNI. The overall response rate was 66.7%(16/24) at 6 months and 77.3%(17/22) at 12 months. Conclusions The levels of baseline albumin, blood complement C4, and pathological stage were independent predictors of clinical remission in IMN patients treated with CTX plus glucocorticoids. The non-remission patients with CTX combined with glucocorticoid therapy can still achieve a higher response rate after adjusting for CNI.     

The comparison of animal models for premature ovarian failure established by several different source of inducers

The objective of this study was to compare premature ovarian failure animal models established by several different source of inducers. Female ICR mice, KM mice, and SD rats were treated by cyclophosphamide at 120 mg/kg, busulfan at 12 mg/kg, cisplatin at 3 or 4 mg/kg, 4-vinylcyclohexene diepoxide at 160 mg/kg, 35% galactose food pellet, and tripterygium glycosides at 50 mg/kg, respectively. Parameters were analyzed by body weight, serum concentration level of related hormones, ovarian and uterine pathological examination. The results indicated the body weight of mice increased very slowly following single dose of cyclophosphamide (p < 0.05) with damaged ovary; repeated doses of cisplatin could induce body weight significantly decreased (p < 0.01) with a rising trend of serum LH concentration, declining tendency of serum E2 concentration and injured ovary and uterus; 4-vinylcyclohexene diepoxide also hindered the mice growing (p < 0.05) with damaged ovary and uterus; the body weight of mice feed by 35% galactose food pellet increased slowly (p < 0.05) with dramatically higher serum concentration level of galactose, albumin, and total protein (p < 0.001) and injured ovary. Busulfan and tripterygium glycosides did not present obvious evidences. In conclusion, the inducers presented their respective features in such animal models and should be appropriately applied in preventive methods.     

Protective effects of betulinic acid on intestinal mucosal injury induced by cyclophosphamide in mice

BackgroundBetulinic acid (BA) is a plant-derived pentacyclic triterpenoid with a variety of biological activities. The purpose of this study was to assess the potential protective role of BA against intestinal mucosal injury induced by cyclophosphamide (CYP) treatment.MethodsMice were pretreated with BA daily (0.05, 0.5, and 5.0 mg/kg) for 14 days, then injected intraperitoneally with CYP (50 mg/kg) for 2 days.ResultsBA pretreatment reduced the contents of malondialdehyde (MDA) and glutathione (GSH), decreased the activity of superoxide dismutase (SOD) in small intestine, increased villus hight/crypt depth ratio and restored the morphology of intestinal villi in CYP-induced mice. Moreover, BA pretreatment could significantly down-regulate the levels of pro-inflammatory cytokines interleukin-5 (IL-5), IL-17, IL-12 (P70) and tumor necrosis factor α (TNF-α), reduced production of chemokines macrophage inflammatory protein-1α (MIP-1α), macrophage inflammatory protein-1β (MIP-1β) and regulated upon activation, normal T-cell expressed and secreted (RANTES), and enhanced the levels of anti-inflammatory such as IL-2 and IL-10 in serum, and decreased the mRNA expressions of IL-1β and TNF-α in intestine of CYP-induced mice. Furthermore, RT-PCR demonstrated that BA improved intestinal physical and immunological barrier in CYP-stimulated mice by enhancing the mRNA expressions of zonula occluden 1 (ZO-1) and Claudin-1.ConclusionsBA might be considered as an effective agent in the amelioration of the intestinal mucosal resulting from CYP treatment.     

Punicalagin alleviates hepatotoxicity in rats challenged with cyclophosphamide

This study investigated the possible hepatoprotection of punicalagin in rats received cyclophosphamide (20 mg/kg/day, i.p., for 7 days). Punicalagin given at two doses, 15 and 30 mg/kg/day, p.o., for 7 days, starting the same day of cyclophosphamide administration. Punicalagin significantly and dose-dependently reduced the elevations of serum alanine aminotransferase, and liver nuclear factor-κB p65, tumor necrosis factor-α, interleukin-1β, malondialdehyde, nitric oxide, Bax/Bcl-2 ratio, inducible nitric oxide synthase, caspases 3 and 9 activities, and prevented the decrease of hepatic total antioxidant capacity. Punicalagin also attenuated the histopathological liver tissue damage, and decreased cyclooxygenase-2 expression in liver of rats received cyclophosphamide in a dose-dependent manner. It was concluded that punicalagin protected rat liver against cyclophosphamide toxicity by inhibiting oxidative/nitrosative stress, inflammation, and apoptosis.     

Astragalus polysaccharides and astragaloside IV ameliorates cyclophosphamide-induced mouse model of overactive bladder

ObjectivePrevious studies have shown that Astragalus polysaccharides (APS) and Astragaloside IV (AS-IV) protect against inflammation-related cell damage and exhibit immune enhancement. Since urothelial injury may result in an overactive bladder (OAB), the aim of this study was to investigate the efficacy of APS and AS-IV on urothelial injury in an experimental animal model.Materials and methodsThe effects of APS and AS-IV on the proliferation and migration of primary human urothelial cells (HUCs) or primary human fibroblast cells (HFCs) were assessed using an in vitro wounding model and colorimetric thiazolyl blue assays. Sixty virgin female mice were randomized into five groups: group 1–saline-injected plus treatment with H₂O, group 2–cyclophosphamide (CYP) plus treatment with H₂O, group 3–CYP plus treatment with solifenacin succinate (SS; 10 mg/kg), group 4–CYP plus treatment with AS-IV (100 mg/kg), and group 5–CYP plus treatment with APS (100 mg/kg). Cystometry assessment was conducted and cell junction-associated protein zonula occludens-2 (ZO-2) expression was measured. Voiding interval values (time between voids) were assessed in mice under anesthesia. Lastly, immunohistochemistry analysis was used to confirm the location and level, respectively, of ZO-2 expression.ResultsAPS and AS-IV did not influence the cell viability but increased migration in HFCs compared with the controls. The OAB mice showed significantly lower voiding interval values. Voiding interval values were significantly higher in the CYP plus treatment with APS (100 mg/kg) and AS-IV (100 mg/kg) groups than in the CYP-induced OAB group. Additionally, the expression of ZO-2, a tight junction protein, was increased in the CYP plus treatment APS (100 mg/kg) and AS-IV (100 mg/kg) groups compared with the CYP-induced OAB group.ConclusionThese findings suggest that APS and AS-IV modulate urothelial wound healing, which ameliorates urinary frequency of mice treated with CYP. APS or AS-IV may have the potential benefit of acting as urothelial wound healing modulators.     

周晋华运用环磷酰胺联合中药紫杉治疗晚期肺癌经验

肺癌多是邪祟之物郁结留滞致使人体气血运行不畅所致,周晋华主任认为肺癌的发生与正虚邪害密不可分,而晚期肿瘤患者虚多实少,全身为虚,当以脾虚为主,“得脾胃者得中央,得中央者得天下”,局部为实,故当以缓治,固脾胃之本培人体之元,周晋华主任运用低剂量规律口服环磷酰胺联合中药紫杉片解毒散结配伍,佐以益气健脾之法治疗晚期肺癌患者,发现对身体基础状况较差的老年肿瘤患者有良好的效果,此法是从姑息性治疗角度运用中西医结合的方法将静脉化疗药环磷酰胺改为口服,在提高老年患者对化疗药物的耐受性,减轻化疗副作用方面有一定的优势,为临床治疗晚期肺癌提供一种新思维。     

乌苯美司联合XEC化疗方案治疗三阴性乳腺癌的临床研究

目的探讨乌苯美司联合XEC化疗方案治疗三阴性乳腺癌患者的临床疗效及其对外周血T淋巴细胞亚群及血清骨桥蛋白(OPN)水平变化的影响。方法选取河南科技大学第一附属医院2015年6月—2017年1月收治的三阴性乳腺癌患者83例,随机分成对照组(41例)和治疗组(42例)。对照组患者给予XEC化疗方案治疗,第1天静脉滴注注射用环磷酰胺500 mg/m~2,同时静脉滴注注射用盐酸表柔比星100 mg/m~2,第1~14天口服卡培他滨片1 g/m~2,疗程为21 d。治疗组在对照组的基础上口服乌苯美司片,30 mg/次,1次/d,疗程为21 d。两组均持续治疗4个疗程。观察两组患者临床疗效,比较治疗前后两组患者SF-36评分、外周血T淋巴细胞亚群表达水平和OPN水平。结果治疗后,对照组和治疗组临床总有效率分别为75.61%、95.24%,两组比较差异具有统计学意义(P0.05)。治疗后,两组躯体疼痛、躯体功能、睡眠质量、生命活力、生理职能、心理健康等生活质量评分均显著升高,同组治疗前后比较差异具有统计学意义(P0.05);且治疗后治疗组生活质量评分显著高于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者CD~(3+)、CD~(4+)、CD~(4+)/CD~(8+)水平均显著升高,CD~(8+)水平显著下降,同组治疗前后比较差异具有统计学意义(P0.05);且治疗组T淋巴细胞亚群水平显著优于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组血清OPN水平显著下降,同组治疗前后比较差异具有统计学意义(P0.05);且治疗组血清OPN水平显著低于对照组,两组比较差异具有统计学意义(P0.05)。结论乌苯美司联合XEC化疗方案治疗三阴性乳腺癌患者效果显著,可有效改善患者外周血T淋巴细胞亚群和血清OPN水平,且安全性较高,具有一定的临床推广应用价值。     

造血干细胞移植预处理诱发口腔黏膜炎模型的建立

目的探讨建立造血干细胞移植预处理诱发口腔黏膜炎大鼠模型的可行性。方法采用马利兰和环磷酰胺预处理方案结合左颊黏膜搔刮建立大鼠口腔黏膜炎模型。设立模型组和对照组，从自然过程、口腔黏膜炎指数、血象、骨髓象、病理检查等指标动态观察口腔黏膜炎的发生、发展过程。结果模型组大鼠于第7天开始出现口腔黏膜炎表现，发生率为80．00％；口腔黏膜炎指数在第11天达到峰值（2．04±1.80），4级以上口腔黏膜炎占39．29％（11／28）；第18～21天病损基本恢复，期间大鼠体重持续下降，白细胞计数于第10天下降至最低点，骨髓增生度低下。结论成功建立了造血干细胞移植预处理诱发口腔黏膜炎的大鼠模型。     

不同剂量环磷酰胺对小鼠免疫功能的影响

目的探索不同剂量环磷酰胺(CTX)对正常小鼠免疫功能的影响,为CTX临床应用提供实验数据。方法 C57BL/6小鼠24只,随机分为对照组、低剂量组和高剂量组,分别给生理盐水(NS)、低剂量和高剂量的CTX,检测血常规、Treg比率、T细胞和B细胞增殖功能及巨噬细胞吞噬功能、细胞增殖周期及凋亡比率。结果 RBC、WBC、PLT数量在高剂量组显著降低,对照组与低剂量组无差异;Treg占CD4+T细胞的比例在低剂量组显著下降,对照组与高剂量组无差异;T、B细胞增殖指数及巨噬细胞吞噬功能在低剂量组高于对照组和高剂量组,高剂量组低于对照组;细胞凋亡比率在高剂量组明显增加,对照组与低剂量组间无差异;高剂量组细胞阻滞在S期,对照组与低剂量组间无差异。结论低剂量CTX通过下调Treg、增强免疫细胞的功能,促进机体免疫;而高剂量CTX通过抑制DNA的复制、促进细胞凋亡和降低免疫细胞功能,使机体处于免疫抑制状态。相关数据可以为CTX的临床应用提供借鉴。