Effects of Iron Supplementation on Testicular Function and Spermatogenesis of Iron-Deficient Rats

Iron deficiency is the most common micronutrient deficiency in the world. Previous studies have shown that iron deficiency increases oxidative stress and decreases antioxidant enzymes, and studies of male infertility indicated that oxidative stress may affect male reproductive functions. The aim of this study was to investigate the effects of iron supplementation on spermatogenesis and testicular functions in iron-deficient rats. Three-week-old male Sprague Dawley (SD) rats were randomly divided into two groups: an iron-adequate control (AI group, 35 ppm FeSO₄) and an iron-deficient group (ID group, <5 ppm FeSO₄). After three weeks, the iron-deficient group was divided into an original iron-deficient group and five iron-supplemented groups, the latter fed diets containing different doses of FeSO₄ (6, 12, 18, 24, and 35 ppm). After five weeks, blood and testis tissue were analyzed. We presented as median (interquartile range, IQR) for continuous measurements and compared their differences using the Kruskal–Wallis test followed by the Mann–Whitney U test among groups. The results showed that as compared with the AI group, the ID group had significantly lower serum testosterone and poorer spermatogenesis (The medians (QR) were 187.4 (185.6–190.8) of AI group vs. 87.5 (85.7–90.4) of ID group in serum testosterone, p < 0.05; 9.3 (8.8–10.6) of AI group vs. 4.9 (3.4–5.4) of ID group in mean testicular biopsy score (MTBS], p < 0.05); iron supplementation reversed the impairment of testis tissue. In the testosterone biosynthesis pathway, iron supplementation improved the lowered protein expressions of hydroxysteroid dehydrogenases caused by iron deficiency. Additionally, decreased activities of glutathione peroxidase and catalase, and increased cleaved-caspase 8 and caspase 3 expression, were found in the iron-deficient rats. The iron-supplemented rats that received > 12 ppm FeSO₄ exhibited improvements in antioxidant levels. In conclusion, iron supplementation can abrogate testis dysfunction due to iron deficiency through regulation of the testicular antioxidant capacity.     

困难滤器回收策略

下腔静脉滤器作为预防肺栓塞的重要手段,已得到广泛应用。随着滤器置入数量逐年增加,滤器回收过程中暴露的问题逐渐引起关注。不仅滤器回收率偏低,而且长期留置容易诱发各种滤器相关并发症,滤器倾斜和超期置入等原因造成的回收困难也增加手术操作的复杂性和失败率。术者有必要熟悉滤器的特点,掌握多种回收技术,以提高滤器回收的成功率。该文根据现有滤器类型和特点,分析了造成滤器回收困难的常见原因,系统总结了导丝指引技术、球囊扩张技术、导管修正技术、导丝成襻技术、支气管钳或活检钳技术、准分子激光技术、圈套器切割技术以及一些非腔内手术方式等多种滤器回收策略。     

耳穴压豆法治疗失眠症的护理研究

目的:探讨耳穴压豆法治疗失眠症的效果及方法。方法:将我院失眠症患者60例采用耳穴压豆法实施护理,追踪随访临床效果。结果:治疗后患者入睡时间小于30分钟人数明显多于治疗前,比较差异具有统计学意义(P<0.05)。治疗后患者睡眠时间大于6h人数明显多于治疗前,比较差异具有统计学意义(P<0.05)。本组总有效率达98.33%。结论:耳穴压豆法治疗失眠症的效果明确,值得应用。     

7,7'-Dimethoxyagastisflavone-induced apoptotic or autophagic cell death in different cancer cells

7,7'-Dimethoxyagastisflavone (DMGF), a biflavonoid isolated from the needles of Taxus × media cv. Hicksii, was evaluated for its antiproliferative and antineoplastic effects in three human cancer cell lines. Interestingly, DMGF caused cell death via different pathways in different cancer cells. DMGF induced apoptosis, activated caspase-3 activity and changed the mitochondrial membrane potential in HT-29 human colon cancer cells. However, the apoptotic pathway is not the major pathway involved in DMGF-induced cell death in A549 human lung cancer cells and HepG2 human hepatoma cells. Treatment with 3-MA, an inhibitor of autophagy, significantly decreased DMGF-induced cell death in HepG2 and A549 cells, but did not affect DMGF-induced cell death in HT-29 cells. Following DMGF treatment, the HepG2 cells increased expression of LC3B-II, a marker used to monitor autophagy in cells. Thus, DMGF induced apoptotic cell death in HT-29 cells, triggered both apoptotic and autophagic death in A549 cells and induced autophagic cell death in HepG2 cells.     

脑功能损害危重患儿经颅多普勒超声监测的临床研究

目的 应用经颅多普勒超声(transcranial Doppler ultrasonography,TCD)观察脑功能损害患儿脑血流动力学变化,探讨TCD在监测与评估脑损害患儿预后中的价值.方法 以大脑中动脉为靶血管,检测脑功能损害组20例及无脑损害组(对照组)20例患儿的脑血流动力学参数[收缩期峰流速(Vs)、平均血流速度(Vm)、舒张期流速(Vd)、搏动指数(PI)、阻力指数(RI),对比两组患儿各参数间的差异.脑功能损害组患儿按Glasgow评分、预后再分组,比较不同Glasgow评分(≤6分组和7~13分组)、不同预后患儿的TCD各参数的差异.每日动态监测脑功能损害组患儿的TCD直至TCD参数正常,将TCD参数达正常时间与Glasgow评分、意识障碍持续时间进行相关分析.对比脑功能损害组不同Glasgow评分、不同预后患儿TCD达正常时间的差异.结果 (1)脑功能损害组大脑中动脉的Vs、PI、RI均较对照组高,Vd较对照组低,差异均有统计学意义(P均<0.05).(2)脑功能损害组Glasgow评分≤6分患儿的PI(0.91±0.21)高于Glasgow评分7~13分患儿(0.83±0.14),两组比较差异有统计学意义(P<0.05);而Vs、Vd、RI两组比较差异均无统计学意义(P均>0.05).脑功能损害组不同预后患儿间的大脑中动脉血流动力学各参数比较差异均无统计学意义(P均>0.05).(3)脑功能损害组患儿TCD参数达正常时间与入院当日Glasgow评分呈负相关(r=-0.653,P<0.01);TCD参数达正常时间与意识障碍持续时间呈正相关(r=0.923,P<0.01).不同Glasgow评分、不同预后患儿的TCD参数达正常时间差异均有统计学意义,Glasgow评分≤6分、预后差患儿的TCD达正常时间更长(P均<0.05).结论 脑功能损害患儿的脑血流动力学异常,脑损害程度越重者,PI越高,TCD参数恢复正常的时间越长;动态监测TCD可反映脑血流变化,对评估病情和预后有一定价值.     

“Pincer movement”: Reversing cisplatin resistance based on simultaneous glutathione depletion and glutathione S-transferases inhibition by redox-responsive degradable organosilica hybrid nanoparticles

The therapeutic efficacy of cisplatin has been restricted by drug resistance of cancers. Intracellular glutathione (GSH) detoxification of cisplatin under the catalysis of glutathione S-transferases (GST) plays important roles in the development of cisplatin resistance. Herein, a strategy of “pincer movement” based on simultaneous GSH depletion and GST inhibition is proposed to enhance cisplatin-based chemotherapy. Specifically, a redox-responsive nanomedicine based on disulfide-bridged degradable organosilica hybrid nanoparticles is developed and loaded with cisplatin and ethacrynic acid (EA), a GST inhibitor. Responding to high level of intracellular GSH, the hybrid nanoparticles can be gradually degraded due to the break of disulfide bonds, which further promotes drug release. Meanwhile, the disulfide-mediated GSH depletion and EA-induced GST inhibition cooperatively prevent cellular detoxification of cisplatin and reverse drug resistance. Moreover, the nanomedicine is integrated into microneedles for intralesional drug delivery against cisplatin-resistant melanoma. The in vivo results show that the nanomedicine-loaded microneedles can achieve significant GSH depletion, GST inhibition, and consequent tumor growth suppression. Overall, this research provides a promising strategy for the construction of new-type nanomedicines to overcome cisplatin resistance, which extends the biomedical application of organosilica hybrid nanomaterials and enables more efficient chemotherapy against drug-resistant cancers.KEY WORDS: Cancer therapy, Cisplatin, Drug resistance, Glutathione depletion, Glutathione S-transferases, Disulfide bonds, Organosilica hybrid nanoparticles, Ethacrynic acid     

Self-assembled sonogels formed from 1,4-naphthalenedicarbonyldinicotinic acid hydrazide

In this paper, we report self-assembled sonogels formed from 1,4-naphthalenedicarbonyldinicotinic acid hydrazide (NDC-NN3) in some liquids including ethanol, tetrahydrofuran (THF), 1,4-dioxane, n-propanol, n-butanol and n-pentanol. When the clear solution of NDC-NN3 in the selected liquids mentioned above at a suitable concentration was irradiated with ultrasound waves at room temperature, a sonogel was formed. Upon heating, the sonogel dissolved gradually and finally became a clear solution again. Upon cooling the hot solution to room temperature, the solution state did not change even after standing for a few days. Nevertheless, if the solution underwent sonication for a certain time, a stable gel was obtained again. The critical gelation concentrations (CGCs) of NDC-NN3 in ethanol, THF, 1,4-dioxane, n-propanol, n-butanol and n-pentanol are 10, 8, 6, 8, 6 and 8 mg mL⁻¹, respectively. The obtained sonogels display excellent mechanical properties. The crystal structure of NDC-NN3 suggests that the naphthalene ring, hydrazide group and the position of N in the pyridine ring mediate the self-assembly process. Upon sonication, the formation of suitable π–π stacking and intermolecular hydrogen bonding drives the gelator molecules to self-assemble into fibers, spheres and micro-burdock-shaped balls in various solvents, which ultimately confine the liquids.

Ultrasound-induced gelation of a novel type of gelator, 1,4-naphthalenedicarbonyl- dinicotinic acid hydrazide, is reported. The gelator self-assembled into various architectures in different solvents.     

大剂量甲氨蝶呤静脉给药时间对淋巴瘤患者脑脊液中药物浓度的影响

背景与目的:甲氨蝶呤(methotrexate,MTX)在脑脊液中高于最小有效治疗浓度是治疗中枢淋巴瘤的必要条件,目前尚不明确大剂量MTX(high doseMTX,HD-MTX)静脉给药时间对MTX穿透血脑屏障的影响.本研究探索HD-MTX静脉不同给药时间对脑脊液中MTX浓度的影响,以获得更好的中枢淋巴瘤防治效果并尽可能减少MTX外周毒性.方法:34例非霍奇金淋巴瘤患者分别接受MTX 1～3g/m2 6 h持续静脉给药或24 h持续静脉给药,其中17例交替使用两种给药方法;采用高效液相色谱法检测MTX停药0 h、24 h、48 h的MTX血清浓度,及停药0 h后脑脊液中MTX浓度;比较两组血中和脑脊液中MTX浓度以及毒性反应,并对影响MTX浓度的因素进行相关分析.结果:给药结束时6 h给药组的MTX血清浓度显著高于24 h给药组:自身对照结果6 h给药组的脑脊液中MTX浓度为0.70 Ixmol/L,明显高于24 h给药组的0.49 Ixmol/L(校正值,P=0.044).MTX的脑脊液浓度与血清浓度呈正相关,中枢侵犯患者脑脊液MTX浓度显著高于无中枢侵犯的患者.自身对照结果6 h组和24 h组Ⅱ～Ⅳ度粘膜炎的发生率分别15.4%和37.8%.Ⅲ～Ⅳ度骨髓抑制的发生率分别为46.2%和67.6%.结论:在提高MTX的中枢浓度和降低外周毒性方面,HD-MTX 6 h给药方案优于24 h给药方案.