Lipopolysaccharide (LPS) up-regulates the expression of haem oxygenase-1 in mouse placenta

Haem oxygenase-1 (HO-1) is an inducible enzyme that catalyses the rate-limiting step in the degradation of haem to biliverdin, carbon monoxide and iron. There is increasing evidence that HO plays important roles in the cellular defence against oxidative stress and the deleterious effects of pro-inflammatory cytokines. In the present study, we investigated the effects of lipopolysaccharide (LPS) on the expression of HO-1 in mouse placenta. When a single dose of LPS (75 microg/kg, i.p.) was administered to the pregnant mice, the expression of HO-1 in mouse placenta was markedly increased at 12 h after LPS treatment and remained elevated up to 48 h after LPS administration. The expression of HO-2, the constitutive form, did not change at the various time points observed. LPS-induced up-regulation of placental HO-1 was blocked after the pregnant mice were pre-treated with alpha-phenyl-N-t-butylnitrone (PBN), a free radical spin trapping agent. Correspondingly, PBN pre-treatment significantly inhibited LPS-induced lipid peroxidation and glutathione (GSH) depletion in mouse placenta. Furthermore, pentoxifylline (PTX), an inhibitor of tumour necrosis factor alpha (TNF-alpha) synthesis, also significantly attenuated LPS-induced up-regulation of placental HO-1. However, aminoguanidine (AG), a selective inhibitor of inducible nitric oxide synthase (iNOS), had little effect on LPS-induced up-regulation of HO-1 in mouse placenta. Taken together, these results indicate that LPS up-regulates the expression of HO-1 in mouse placenta. LPS-induced up-regulation of placental HO-1 is probably mediated, at least in part, by reactive oxygen species (ROS) and TNF-alpha, rather than nitric oxide.     

Mutation analysis of NANOS3 in 80 Chinese and 88 Caucasian women with premature ovarian failure

NANOS3 encodes an RNA-binding protein and has a conserved function in germ cell development. Our objective was to investigate whether mutations in NANOS3 were present in Chinese and Caucasian women with premature ovarian failure. A known synonymous single-nucleotide polymorphism (rs 2016163) in exon 1 was identified through sequencing 80 Chinese and 88 Caucasian women with premature ovarian failure. No additional single-nucleotide polymorphisms or mutations were found in exons encoding for NANOS3. Our findings suggest that mutations in NANOS3 exons are rare in both Chinese and Caucasian women with premature ovarian failure.     

妊娠期糖代谢异常孕妇血脂水平与围产结局的关系

目的 分析妊娠期糖代谢异常孕妇血脂水平与围产结局的关系。方法选 择确诊为妊娠期糖代谢异常的孕妇358例,包括妊娠合并糖尿病（DM）28例（DM组）,妊娠期糖尿病（GDM）178例（GDM组）,妊娠期糖耐量受损（GIGT）152例（GIGT组）,用Beckman—CX9型全自动生化分析仪测定血清总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL—C）及低密度脂蛋白胆固醇（LDL—C）,详细记录各组孕妇确诊时血脂水平及孕妇年龄、孕周、检测时间、治疗方法、并发症等。结果 （1）GIGT组与GDM组TG分别为（2．7±0．7）mmoL／L和（2．9±0．7）mmoL／L,TC分别为（6．2±1．1）mmol／L和（6．7±1．9）mmol／L,HDL—C分别为（1．78±0．22）mmol／L和（1．64±0．31）mmol／L,LDL-C分别为（3．8±0．9）mmol／L和（3．7±0．8）mmol／L,两两比较,差异均无统计学意义（P〉0．05）;DM组TG和LDL—C分别为（3．6±0．9）mmol／L和（4．8±0．6）mmol／L,均高于GIGT组和GDM组,而HDL-C[（1．24±0．19）mmol／L]低于GIGT组和GDM组,差异均有统计学意义（P〈0．05）。（2）DM组、GDM组、GIGT组,子痫前期发生率分别为35．7％（10／28）、16．8％（30／178）和14．5％（22／152）;早产发生率分别为39．3％（11／28）、16．8％（30／178）和19．7％（30／152）,分别比较,差异均有统计学意义（P均〈0．05）;羊水过多、胎膜早破发生率3组比较,差异无统计学意义（P〉0．05）;胎儿窘迫发生率GDM组低于GIGT和DM组,分别为9．8％（15／152）、20．2％（36／178）和21．4％（6／28）;GDM组和GIGT组巨大儿发生率高于DM组,分别为11．2％（20／178）、14．5％（22／152）和3．5％（1／28）,分别比较,差异均有统计学意义（P〈0．05）。结论 妊娠期糖代谢异常孕妇血脂水平是监测围产结局的有效指标之一,有效降低血脂水平能降低子痫前期和早产的发生率。     

聚焦超声治疗外阴上皮内非瘤样病变的近远期疗效及其影响因素

目的 探讨聚焦超声治疗外阴上皮内非瘤样病变的近远期疗效及并发症,并初步分析其预后影响因素。方法 选择经病理检查证实为外阴上皮内非瘤样病变患者共76例,采用聚焦超声进行治疗。术后定期随访局部瘙痒症状的改善情况,采用阴道镜检查方法观察体征的变化。结果 聚焦超声治疗后平均随访28．3个月（24～60个月）,有39例患者治愈（27例为鳞状上皮增生型,12例为硬化性苔癣型）,总治愈率为51％（39／76）,总有效率达95％（72／76）,累计复发率为36％（26／72）。对复发病例在间隔一段时间后进行再次聚焦超声治疗,同样可以获得显著的临床治疗效果,18例复发后再治疗患者中,6例完全恢复正常,12例症状明显减轻或缓解。76例患者中,4例（2例鳞状上皮增生型,2例硬化性苔癣型）于治疗后2～4h出现治疗区皮肤少量水疱,经抗炎、对症治疗后均痊愈。另有2例（1例鳞状上皮增生型,1例硬化性苔癣型）在治疗后2周出现治疗区局部皮肤浅表溃疡,经抗炎、对症及促表皮生长等治疗3周后痊愈。76例患者经24～60个月的临床观察未发现有远期并发症。不同的麻醉方式及不同的病理类型对聚焦超声治疗效果的影响比较,差异无统计学意义（P〉0．05）,但病程越短、年龄越小,聚焦超声治疗的临床效果越好。结论 聚焦超声用于治疗外阴上皮内非瘤样病变安全有效,无远期并发症发生。     

Inhibiting DNA methylation alleviates cisplatin-induced hearing loss by decreasing oxidative stress-induced mitochondria-dependent apoptosis via the LRP1–PI3K/AKT pathway

Cisplatin-related ototoxicity is a critical side effect of chemotherapy and can lead to irreversible hearing loss. This study aimed to assess the potential effect of the DNA methyltransferase (DNMT) inhibitor RG108 on cisplatin-induced ototoxicity. Immunohistochemistry, apoptosis assay, and auditory brainstem response (ABR) were employed to determine the impacts of RG108 on cisplatin-induced injury in murine hair cells (HCs) and spiral ganglion neurons (SGNs). Rhodamine 123 and TMRM were utilized for mitochondrial membrane potential (MMP) assessment. Reactive oxygen species (ROS) amounts were evaluated by Cellrox green and Mitosox-red probes. Mitochondrial respiratory function evaluation was performed by determining oxygen consumption rates (OCRs). The results showed that RG108 can markedly reduce cisplatin induced damage in HCs and SGNs, and alleviate apoptotic rate by protecting mitochondrial function through preventing ROS accumulation. Furthermore, RG108 upregulated BCL-2 and downregulated APAF1, BAX, and BAD in HEI-OC1 cells, and triggered the PI3K/AKT pathway. Decreased expression of low-density lipoprotein receptor-related protein 1 (LRP1) and high methylation of the LRP1 promoter were observed after cisplatin treatment. RG108 treatment can increase LRP1 expression and decrease LRP1 promoter methylation. In conclusion, RG108 might represent a new potential agent for preventing hearing loss induced by cisplatin via activating the LRP1-PI3K/AKT pathway.KEY WORDS: Cisplatin, DNMT, Apoptosis, Hair cell, Spiral ganglion neurons, RG108, Mitochondrial dysfunction, ROS     

高温联合辐射对仔鼠神经系统与行为的影响

目的探讨高温联合辐射对仔鼠神经系统与行为的影响。方法将130只孕鼠按随机抽签法分为13组,每组10只。在孕鼠妊娠第8、9d分别接受60Co及γ-射线全身照射各1次,照射剂量1．0Gy;第10d各置温箱中,分别使其肛温保持在37、±0．5℃,41±0．5℃,42±0．5℃,并持续3、4、5min。移出温箱2h后,每组随机取5只,单笼饲养,待其自然分娩,观察仔鼠体格发育、生理发育、神经反射、活动能力等神经行为指标。结果孕鼠经高温联合辐射后,其仔鼠的生理发育、早期反射、感觉功能、活动能力均显著滞后于对照组(P<0．01)。结论高温联合辐射具有复合作用,可增强对仔鼠神经系统的不良影响。     

首发精神分裂症患者IL-1β的血清蛋白水平及PBMC mRNA表达

目的从基因转录和蛋白水平,观察精神分裂症中IL-1β的动态变化情况,了解其免疫状态,并探讨IL-1β与精神病理的关系。方法采用病例对照研究方法,精神分裂症组为根据DSM—Ⅳ诊断为精神分裂症的本地汉族患者83例,单一应用利培酮治疗,在治疗前后评定PANSS量表;对照组为健康志愿者65例。应用ELISA和RT—PCR方法,同时检测血清IL-1β蛋白水平和PBMC中IL-1β mRNA表达。结果（1）精神分裂症组治疗前、后与对照组血清IL--1β水平相比,均明显增高,差异有显著性（P〈0．05）。精神分裂症组治疗后血清IL—-1β水平与治疗前相比明显下降,差异有显著性（P〈0．05）。（2）IL-1β治疗前后的差值与PANSS量表降分率呈显著正相关（r=0．388,P〈0．05）。（3）精神分裂症组治疗前、后PBMC中IL-1β mRNA表达与对照组相比明显增高,差异有显著性（P〈0．05）。精神分裂症组治疗后PBMC中IL-1β mRNA表达与治疗前相比明显下降,差异有显著性（P〈0．05）。结论（1）精神分裂症患者存在免疫激活,IL-1β水平的变化可作为病情缓解的一个灵敏指标。（2）精神分裂症患者PBMC呈激活状态,是IL-1β的主要来源之一,探讨影响PBMC细胞因子mRNA表达的因素,有助于反映对机体的免疫状况的影响。     

经尿道射精管切开术治疗射精管梗阻的效果(附60例报告)

目的：探讨经尿道射精管切开术（transurethral resection of ejaculatory duct, TURED）治疗射精管梗阻（ejaculatory duct obstruction, EDO）的效果。方法：2004年10月至2010年10月期间收治60例EDO患者,常规采用精液分析、精浆果糖和经直肠超声检查对其进行诊断,必要时行输精管造影检查。60例EDO患者均行TURED治疗,术后随访其疗效。结果：60例EDO患者的精液量为0.2~3.5 mL,平均(1.10±0.76) mL,pH值5.8~7.6,平均6.5±1.4;精浆果糖为一次射精0~51.4 μmol,平均为(5.86±2.19) μmol。经直肠超声检查结果为：单纯射精管扩张者15例,前列腺囊肿6例,单纯双侧精囊扩张10例,单侧精囊扩张4例,精囊扩张并射精管扩张10例,精囊扩张合并前列腺囊肿5例,单侧精囊扩张并对侧精囊发育不良或缺乏2例,精囊扩张并射精管扩张和钙化3例,单侧精囊扩张并射精管扩张和对侧精囊发育不良或缺乏5例。所有患者均完成手术,术后随访6~78个月。60例EDO患者行TURED术后,51例(85.0%)精液检查有不同程度的改善,16例(26.7%)妻子妊娠。结论：TURED是治疗EDO的一种简单、微创和有效的方法。     

糖性白内障大鼠晶状体水不溶性蛋白的改变

用D一半乳糖诱发了大鼠白内障,分析了其膜固有蛋白和尿素溶蛋白的改变。对正常大鼠晶状体纤维细胞膜蛋白电泳图谱的分析表明,其26KDa的主要膜固有蛋白(MIP26)约占膜固有蛋白总量的42.9％,22KDa的膜固有蛋白约占6.4％。糖性白内障大鼠晶状体纤维细胞膜固有蛋白以22KDa为主,约占30.5％,MIP26几乎消失。并在24KDa处有一深染区带。在白内障发病过程中18KDa的膜蛋白的相对含量无明显改变。这些结果提示在糖性白内障发病过程中MIP26发生了降解,产生了22KDa的降介产物。 以每克湿重计,白内障晶状体尿素溶蛋白降低约22.5％。但白内障晶状体尿素溶蛋白占总蛋白的比例升高。正常大鼠尿素溶蛋白电泳图谱主要显示四条区带,其近似分子量分别为22.5KDa、22.4KDa、20.6KDa和19.2KDa。白内障晶状体20.6KDa和19.2KDa的二条区带所占的比例明显减小。这个结果提示正常晶状体尿素溶蛋白主要含有α—和β—晶体蛋白,而且白内障晶状体尿素溶蛋白则主要含有β—晶体蛋白。