双黄连口服液辅助治疗儿童口腔溃疡心脾积热证45例临床观察

目的观察双黄连口服液辅助治疗儿童口腔溃疡心脾积热证的临床疗效。方法选取2016年4月至2018年4月温州市中西医结合医院口腔科收治的90例口腔溃疡心脾积热证患儿,按照随机数字表法分为对照组和治疗组,各45例。2组均给予复合维生素B片、维生素C片及溃疡面清洁等常规治疗,对照组在常规治疗的基础上予康复新液口服,治疗组在对照组治疗方法的基础上予双黄连口服液口服,2组均7 d为1个疗程,1个疗程后观察临床疗效。结果治疗前,2组血清炎性因子白细胞介素-2(IL-2)、白细胞介素-6(IL-6)及肿瘤坏死因子-α(TNF-α)水平比较,差异均无统计学意义(P>0.05),具有可比性。治疗后,2组IL-2水平显著升高,IL-6、TNF-α水平显著下降,与同组治疗前比较,差异均有统计学意义(P<0.05),且治疗组升高或下降更显著(P<0.05)。治疗前,2组视觉模拟评分法(VAS)评分比较,差异无统计学意义(P>0.05),具有可比性;治疗后,2组VAS评分显著降低(P<0.05),与同组治疗前比较,差异有统计学意义(P<0.05),且治疗组降低更显著(P<0.05)。治疗组溃疡愈合时间显著短于对照组,差异有统计学意义(P<0.05)。治疗组总有效率为97.78%,对照组为80.00%,2组比较,差异有统计学意义(P<0.05)。治疗后,2组患儿均无任何药物相关不良反应,且肝肾功能检查均正常。结论双黄连口服液辅助治疗儿童口腔溃疡心脾积热证,能明显减轻患儿炎性反应,缓解疼痛,促进溃疡愈合,临床疗效显著,且安全性高,值得临床推广应用。     

FXR信号通路介导何首乌导致脂质沉积的作用及机理研究

目的 探索何首乌对肝细胞脂质沉积的影响及其机制。方法 利用永生化肝细胞系LO2,采用1 mmol/L游离脂肪酸（FFA）处理,建立脂肪肝沉积细胞模型。同时加入不同浓度的何首乌提取物处理（0、2.5、5、10 μg/mL）,采用油红O染色以观察何首乌对LO2细胞脂肪沉积的作用;采用实时荧光定量PCR进行实验组LO2细胞内法尼酯X受体（FXR）基因及其下游通路胆盐输出泵（BSEP）、小分子异源二聚体伴侣（SHP）、胆固醇7α-羟化酶1（CYP7A1）关键基因的检测;并采用蛋白免疫印迹法检测FXR及其下游通路关键蛋白的表达水平。结果 何首乌处理后的LO2细胞中,油红O的染色量会随着药物浓度增加而增加;FXR的mRNA表达下降,而FXR蛋白诱导促进的下游基因BSEP、SHP的表达相应下降,而其下游抑制基因CYP7A1的表达则上升（P均<0.05）。何首乌处理的LO2肝细胞中,FXR的蛋白水平明显降低,蛋白激酶C （PKC）蛋白磷酸化水平明显降低,而PKC总蛋白表达水平无明显改变,SHP的蛋白水平也明显下降。结论 何首乌可通过抑制FXR-PKC/SHP信号转导通路,从而促进LO2肝细胞内的脂质沉积。为何首乌导致胆汁淤积所引起的肝损伤的治疗提供新的理论依据。     

Effect of BMP-9 and its derived peptide on the differentiation of human white preadipocytes

Several studies have shown that bone morphogenetic proteins (BMPs) can influence adipogenic and osteogenic cell lineages. We have shown that a peptide derived from BMP-9 (pBMP-9) at 400 ng/ml inhibits the proliferation of preosteoblasts and induces differentiation. We have now determined the effects of pBMP-9 (400 ng/ml) and equimolar concentrations of BMP-2 (100 ng/ml), BMP-9 (84.6 ng/ml) and pBMP-9 (9.04 ng/ml) on human white preadipocytes (HWP). pBMP-9 dose dependently reduced the proliferation of HWP without affecting the number of apoptotic cells. Incubation of the cells for 1 h with BMP-2, BMP-9 or pBMP-9 activated the Smad1/5/8 pathway, while incubation for 7 days in adipocyte differentiation (AD) serum-free medium containing ciglitazone and equimolar concentrations of BMP-2, BMP-9 or pBMP-9 enhanced the levels of mRNA of the adipogenic markers aP2 and adipoQ and increased the number of lipid vesicles. Thus, pBMP-9, like BMP-9, can increase the AD of HWP in AD serum-free medium.     

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.     

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。     

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.     

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。