A severe form of autosomal recessive spinocerebellar ataxia associated with novel PMPCA variants

Spinocerebellar ataxia, autosomal recessive 2 (SCAR2) [MIM:213200] is a rare autosomal recessive disease of spinocerebellar ataxia associated with degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR2 is characterized by onset of impaired motor development and ataxic gait in early childhood. Recently, several PMPCA gene variants have been reported in SCAR2 patients with mild and non-progressive symptoms. PMPCA codes frataxin, which is crucial for iron biosynthesis in cells. We report a case of a 15-year-old Japanese girl with infancy-onset, very severe and progressive developmental delay, cerebellar ataxia, and extrapyramidal symptoms. Brain magnetic resonance imaging showed cerebellar atrophy and excessive brain iron accumulation in the bilateral globus pallidi and substantia nigra. Based on the clinical phenotypes and imaging, neurodegeneration with brain iron accumulation was suspected. Whole-exome sequencing on the proband and her parents revealed novel compound heterozygous variants at c.667C > T (p.Arg223Cys) and c.853del (p.Asp285llefs*16) in PMPCA. Thus, her disease was diagnosed as SCAR2. Phenotype in our case was different from ones previously reported for SCARs in the points of much severer clinical presentations with extrapyramidal signs and imaging suspected iron accumulation, and might overlap neurodegeneration with brain iron accumulation or NBIA subtypes. Our case might provide a new insight into PMPCA gene-related disorders and expand the disease concept.     

Platinum accumulation in oxaliplatin‐induced peripheral neuropathy

Oxaliplatin‐induced peripheral neuropathy (OIPN) is a common and dose‐limiting toxic effect that markedly limits the use of oxaliplatin and affects the quality of life. Although it is common, the underlying mechanisms of OIPN remain ambiguous. Recent studies have shown that the platinum accumulation in peripheral nervous system, especially in dorsal root ganglion, is a significant mechanism of OIPN. Several specific transporters, including organic cation transporters, high‐affinity copper uptake protein1 (CTR1), ATPase copper transporting alpha (ATP7A) and multidrug and toxin extrusion protein 1 (MATE1), could be associated with this mechanism. This review summarizes the current research progress about the relationship between platinum accumulation and OIPN, as well as suggests trend for the future research.     

产前超声五趾-跖-跟骨足底平面筛查足畸形的价值

目的 探讨产前超声五趾-跖-跟骨足底平面在筛查胎儿足畸形中的价值。方法 连续性选取10 015胎14~40孕周高危胎儿作为研究对象,产前超声检查采用五趾-跖-跟骨足底平面筛查足畸形,并与随访结果进行比较。结果 胎儿足长随孕周增加而增大(F=8.2,P<0.01),单纯先天性马蹄内翻足胎儿的患侧足长变短(χ²=49.1,P <0.01)。五趾-跖-跟骨足底平面超声诊断胎儿足畸形准确率为99.60%(9975/10 015),敏感度为85.29%(116/136),特异度为99.80%(9859/9879),阳性预测值为85.29%(116/136),阴性预测值为99.80%(9859/9879)。结论 五趾-跖-跟骨足底平面可用于胎儿足畸形的产前超声筛查,并可提高诊断水平。     

妊高症患者血液中核因子κB介导的PTX3和CRP的表达及意义

目的：研究核因子（NF）κB介导的 PTX3和 CRP通路,是否可作为治疗妊高症的潜在靶点并分析其临床意义。方法选取2012年3月至2014年12月收治的妊高症患者（NH BPEP 标准）60例作为观察组,其中妊高症20例[血压（131.2±17.4）／（79.7±10.0）mmHg],轻度先兆子痫20例[血压（141.2±15.6）／（89.5±11.2）mmHg],重度先兆子痫20例[血压（150.3±17.6）／（97.6±14.8）mmHg];选取同期入院血压正常的晚期妊娠妇女20例作为对照组,采用全自动生化分析仪检测两组对象外周单个核细胞PTX3和 CRP水平,采用免疫印迹杂交检测 NF-κB的水平;加入 NF-κB抑制剂（PTDC）,观察 PTX3和 CRP表达水平的变化;同时观察其与患者血压波动的关系。结果观察组 PTX3和 CRP随血压升高而升高,均明显高于对照组,组内、组间差异均有统计学意义（ P ＜0.05）;加入 PTDC后,PTX3和 CRP水平均降低,与对照组比较,差异无统计学意义（P ＞0.05）。重度先兆子痫患者NF-κB表达最高[（25.8±4.9）％],应用 PTDC 后降低[（13.9±4.9）％],与对照组[（13.5±3.6）％]比较,差异无统计学意义（P ＞0.05）。结论血浆PTX3和CRP是核因子κB的下游因子,在妊高症患者中表达升高,该通路可作为药物治疗妊高症的潜在靶点。     

心脑宁胶囊治疗血脂代谢异常的临床疗效及安全性观察

目的：观察心脑宁胶囊治疗血脂代谢异常的临床疗效及安全性。方法将86例血脂代谢异常的患者随机分为治疗组（44例）和对照组（42例）。两组均予相同的基础治疗,对照组加用辛伐他汀（40 mg,晚间服）,治疗组加用心脑宁胶囊（每次3粒,每日3次）,1个疗程均为12周,观察记录治疗前后血脂指标及症状积分的变化。结果治疗组总有效率为88.6%,显著高于对照组（69.0%,掊2=6.58,P<0.01）。治疗后治疗组TC、TG、LDL-C的降低程度显著优于对照组,HDL-C升高程度显著优于对照组,差异均有统计学意义（P<0.05）。治疗组症状积分改善情况优于对照组（掊2=9.89,P<0.01）。治疗组未出现毒副反应。结论心脑宁胶囊改善血脂代谢指标疗效显著、安全可靠,且能更好地减轻临床症状。     

脑梗死患者出生日期的运气规律探析

目的探讨脑梗死患者出生日期的五运六气分布特点。方法对3 222例脑梗死患者出生日期的天干、岁运、主气、客气等运气要素进行描述性统计分析,并通过卡方检验判断其间差异性。结果脑梗死患者出生时的天干、主气分布具有一定的差异性,且差异具有统计学意义(P0.05),其中出生在乙年(金运不及)者罹患率最高,己年(土运不及)者最低;出生在四之气(主气太阴湿土)者罹患率最高,终之气(主气太阳寒水)者最低。脑梗死患者出生时的岁运、客气分布差异没有统计学意义(P0.05)。结论出生时天干、主气的运气特征对后天脑梗死的罹患存在一定影响。     

Liver fat accumulation measured by high-speed T2-corrected multi-echo magnetic resonance spectroscopy can predict risk of cholelithiasis

BACKGROUND Liver fat accumulation is associated with increased cholesterol synthesis and hypersecretion of biliary cholesterol, which may be related to the development of cholelithiasis.AIM To investigate whether liver fat accumulation measured by high-speed T2-corrected multi-echo magnetic resonance spectroscopy(MRS) is a risk factor for cholelithiasis.METHODS Forty patients with cholelithiasis and thirty-one healthy controls were retrospectively enrolled. The participants underwent high-speed T2-corrected multi-echo single-voxel MRS of the liver at a 3 T MR scanner. The proton density fat fraction(PDFF) and R~2 value were calculated. Serum parameters and waist circumference(WC) were recorded. Spearman's correlation analysis was used to analyze the relationship between PDFF, R~2, and WC values. Multivariate logistic regression analysis was carried out to determine the significant predictors of the risk of cholelithiasis. Receiver operating characteristic curve(ROC) analysis was used to evaluate the discriminative performance of significant predictors.RESULTS Patients with cholelithiasis had higher PDFF, R~2, and WC values compared with healthy controls(5.8% ± 4.2% vs 3.3% ± 2.4%, P = 0.001; 50.4 ± 24.8/s vs 38.3 ±8.8/s, P = 0.034; 85.3 ± 9.0 cm vs 81.0 ± 6.9 cm, P = 0.030; respectively). Liver iron concentration extrapolated from R~2 values was significantly higher in the cholelithiasis group(2.21 ± 2.17 mg/g dry tissue vs 1.22 ± 0.49 mg/g dry tissue, P = 0.034) than in the healthy group. PDFF was positively correlated with WC(r = 0.502, P 0.001) and R~2(r = 0.425, P 0.001). Multivariate logistic regression analysis showed that only PDFF was an independent risk factor for cholelithiasis(odds ratio = 1.79, 95%CI: 1.22-2.62, P = 0.003). ROC analysis showed that the area under the curve of PDFF was 0.723 for discriminating cholelithiasis from healthy controls, with a sensitivity of 55.0% and specificity of 83.9% when the cut-off value of PDFF was 4.4%.CONCLUSION PDFF derived from high speed T2-corrected multi-echo MRS can predict the risk of cholelithiasis.     

雌二醇下调铁对成骨细胞活性的抑制作用

目的了解雌二醇与铁对小鼠原代成骨细胞活性的影响及活性氧(ROS)的作用。方法提取新生小鼠颅骨原代成骨细胞,经差速贴壁法纯化后传代,选取3~4代进行实验,随机分为对照组,枸橼酸铁铵(FAC)组和FAC+17β-雌二醇(FAC+E2)组,分别用2.5μmol/L FAC和10 nmol/L E2干预7 d后收集细胞,用CCK-8法检测各组细胞增殖情况;用碱性磷酸酶(ALP)活性试剂盒检测各组细胞碱性磷酸酶活性;荧光定量PCR(Q-PCR)检测成骨相关基因(Runx2、osterix、Bglap、IBSP)表达;荧光酶标仪检测各组ROS水平并在荧光显微镜下观察。结果细胞活性氧水平检测结果显示,FAC组活性氧水平明显高于其余各组,FAC+E2组与FAC组相比ROS水平降低(P0.05);FAC干预后细胞增殖能力及ALP活性明显下降(P0.05),FAC+E2组细胞增殖能力较FAC组上升(P0.05),ALP活性上升,但差异无统计学意义(P0.05);Q-PCR结果显示,与对照组相比,FAC组Runx2、osteorix表达水平明显下降(P0.05),FAC+E2组与FAC组相比,各基因表达水平均显著升高(均P0.05)。结论 FAC可能通过升高ROS水平抑制成骨细胞生物活性;雌二醇可能通过清除FAC诱导生成的ROS下调该抑制作用。     

子宫内膜异位症从蓄血证论治

[目的]探讨以《伤寒论》蓄血证理论治疗子宫内膜异位症的可行性。[方法]通过跟师学习,结合《伤寒论》中蓄血证相关理论,从病机、证候、治疗几方面阐述子宫内膜异位症与蓄血证之间的相互关系,并列举验案加以分析佐证。[结果]从临床角度看,蓄血证与子宫内膜异位症有相似之处,离经之血瘀滞,瘀热互结下焦是其病因病机,以少腹硬满胀痛、血下则缓为主要临床表现。破结逐瘀是其治疗大法,以抵当汤为治疗主方。临证施治时,根据月经周期、患者体质,在破结逐瘀泻热基础上,佐以补肾、健脾、温经、解痉,并配合针灸治疗。文中所附子宫内膜异位症病案,皆为瘀热互结下焦,从蓄血证论治,以水蛭、地鳖虫祛瘀消散离经之血,以大黄、猫爪草等泻热解毒,并防止病灶的异常出血,取得较好疗效。[结论]以《伤寒论》蓄血证理论治疗下焦瘀热互结的一类疾病,如子宫内膜异位症等,疗效良好,值得临床推广应用。