Clinical outcomes and 5-year follow-up results of keratosis pilaris treated by a high concentration of glycolic acid

BACKGROUNDKeratosis pilaris is a hereditary abnormal keratosis of the hair follicle orifice. Gray-brown keratotic plugs in the pores and dark red keratotic papules at the openings of hair follicles can be seen, which contain coiled hair and are often accompanied by perifollicular erythema and pigmentation. Glycolic acid can correct the abnormalities of hair follicular duct keratosis and eliminate excessive accumulation of keratinocytes. It also promotes skin metabolism and accelerates the melanin metabolism. The therapeutic effect is related to the glycolic acid concentration.AIMTo evaluate the efficacy and safety of a high concentration of glycolic acid in the treatment of keratosis pilaris, and to observe the outcomes at 5-year of follow-up.METHODSTwenty-five participants were recruited and areas with typical keratosis pilaris were selected as testing sites. High concentrations of glycolic acid (50% or 70%) were applied to a circular area (d = 8 cm, S = 50 cm²) and repeated four times, on days 0, 20, 40 and 60. Before each treatment and 20 d after the last treatment, on days 0, 20, 40, 60, and 80 and at a 5-year follow-up, The number of follicular keratotic papules were counted and the extent of perifollicular erythema and pigmentation was determined. At the same time, the participants provided subjective evaluations of treatment efficacy and safety.RESULTSTreatment effectiveness was indicated by the percentage of keratotic papules in the test site, on days 20, 40, 60 and 80, which were 8%, 12%, 36%, and 60%, respectively. Compared with day 0, each difference was significant (P < 0.05). Compared with day 0, differences in melanin content (M) in the skin and skin lightness (L) on days 40, 60 and 80, the were statistically significant (P < 0.05); skin hemoglobin content (E) on days 60 and 80 was statistically different as compared with before treatment (P < 0.05). There were no significant differences in the number of keratotic papules, M, L, and E in 9 participants at the 5-year follow-up compared with before treatment (P > 0.05%).CONCLUSIONA high concentration of glycolic acid significantly improved skin roughness as well as follicular hyperpigmentation of patients with keratosis pilaris. The treatment was relatively safe, but there was no significant difference at the 5-year follow-up compared to before treatment.     

临床分离2型登革病毒突变株E蛋白N端158氨基酸基序免疫原性初探

目的:Ⅱ型登革病毒临床分离突变株(B株)E基因区部分序列的原核表达载体构建,蛋白表达、复性和纯化,及其免疫原性的初探。方法:将B株E基因1～476bp序列克隆入原核表达载体pET28a(+),经酶切、测序鉴定正确后转入表达菌,IPTG诱导后将包涵体变性,复性,纯化后的蛋白免疫C57BL/6和BALB/c小鼠制备多克隆抗体,并通过Western blot和ELISA进行抗体鉴定。结果:成功构建了pET28a(+)-B-E原核表达载体,在表达菌中以包涵体形式稳定高表达,分子量为20kD。利用蛋白的His标签进行Western blot鉴定确定该蛋白为重组B-E蛋白,得到的可溶蛋白纯度大于90%。B-E蛋白免疫BALB/c和C57BL/6小鼠均可以得到有效的多克隆抗体。结论:B-E蛋白对BALB/c和C57BL/6小鼠具有免疫原性,其中ELISA鉴定免疫C57BL/6小鼠抗体的滴度为1∶12800,Western blot鉴定免疫BALB/c小鼠抗体滴度为1∶500。     

乳腺癌调强放射治疗和常规切线野治疗的三维剂量学研究

背景与目的:乳房保留治疗已在早期乳腺癌患者中逐渐推广应用,其中全乳根治性放疗的标准技术通常采用常规切线野技术。调强放射治疗(intensity-modulatedradiotherapy,IMRT)技术有望在保障相同疗效的同时进一步减少放疗并发症,提高生活质量。本研究利用三维计划系统评价全乳IMRT的剂量学优势与适应证。方法:选择10例接受保乳手术的Tis～2N0M0早期乳腺癌病例,利用三维治疗计划系统为每例患者设计两种全乳放射治疗计划,切线野常规计划与IMRT计划,处方剂量均为5000cGy。用剂量体积直方图(dosevolumehistograms,DVH)来比较各种计划中计划靶体积(planningtargetvolume,PTV)、危及器官(organsatrisks,OARs)的剂量学差异。结果:靶区覆盖率在两种计划中相似,分别为98.3%和97.7%。与常规计划比较,IMRT计划的PTV接受<95%处方剂量与>103%处方剂量的体积百分比之和(inhomogeneityindex,IHI)从29.9%减少到2.9%,PTV接受至少105%处方剂量照射的体积百分比(V105%)从28.2%减少到0.6%;IMRT计划改善IHI和减少V105%的平均值在PTV较大的患者中优势更明显。左侧患者中冠状动脉的最大剂量(Dmax)以及心脏的平均剂量(Dmean)分别从5057.1cGy减少到4832.9cGy和从629.8cGy到450.7cGy;右侧患者肝脏的Dmean从283.9cGy减少到172.0cGy;所有患者中同侧肺的Dmean、至少接受20Gy照射的体积百分比(V20)分别从925.2cGy减少到765.9cGy,从16.0%到15.3%,Dmean与V20的平均值在IMRT计划中减少的百分比在不同射野中心肺厚度(centrallungdistance,CLD)亚组中分别是14.7%与20.9%,7.0%与12.9%;对侧乳腺和对侧肺的Dmean也分别从75.4cGy减少到20.3cGy和从30.9cGy到16.1cGy。结论:全乳IMRT的剂量学优势主要在于保证靶区覆盖率的前提下,显著改善靶区的剂量分布均匀性并一定程度上降低OARs的受照剂量与容积。乳房体积和CLD较大的病例可以通过IMRT技术获得更好的剂量学结果。     

Lack of somatic mutations in EGFR tyrosine kinase domain in hepatocellular and nasopharyngeal carcinoma

Activating EGFR somatic mutations have been shown to predict treatment response to small molecules targeting the EGFR intracellular tyrosine kinase domain. Recent work on cell-lines and animal models had demonstrated an inhibitory effect of EGFR tyrosine kinase inhibitors in hepatocellular and nasopharyngeal carcinoma, and clinical trials in these tumour types are ongoing. There are few data on the presence or prevalence of EGFR mutations in hepatocellular and nasopharyngeal carcinomas. We studied exons 18-21 of the EGFR gene from 100 hepatocellular and 102 nasopharyngeal carcinomas, and found no exonic mutations of potential significance. Alternative mechanisms may be important for the observed activity of small molecule EGFR tyrosine kinase inhibitors in hepatocellular and nasopharyngeal carcinomas.     

Depletion of rabphilin 3A in a transgenic mouse model (R6/1) of Huntington's disease, a possible culprit in synaptic dysfunction

Huntington's disease (HD) is a hereditary neurodegenerative disorder characterized by progressive psychiatric, cognitive, and motor disturbances. We studied the expression of synaptic vesicle proteins in the R6/1 transgenic mouse model of HD. We observed that the levels of rabphilin 3A, a protein involved in exocytosis, is substantially decreased in synapses of most brain regions in R6/1 mice. The appearance of the reduction coincides with the onset of motor deficits and behavioral disturbances. Double immunohistochemistry did not show colocalization between rabphilin 3A and huntingtin aggregates in the HD mice. Using in situ hybridization, we demonstrated that rabphilin 3A mRNA expression was substantially reduced in the R6/1 mouse cortex compared to wild-type mice. Our results indicate that a decrease in mRNA levels underlie the depletion of protein levels of rabphilin 3A, and we suggest that this reduction may be involved in causing impaired synaptic transmission in R6/1 mice.     

Abundant expression of zinc transporters in Bergman glia of mouse cerebellum

Zinc transporters (ZnTs) are membrane proteins involved in zinc ion transportation in mammalian cells. Seven members of ZnT family, ZnT1-7, have been cloned and characterized. These transporter proteins have different cellular and sub-cellular locations, suggesting that they may play different roles in zinc homeostasis in normal and pathological conditions in different tissues. Cerebellum is one of the most zinc-enriched regions in the central nervous system, but little is known about zinc metabolism in the cerebellum. In the present study, we investigated the detailed distributions of four members (ZnT1, ZnT3, ZnT4 and ZnT6) of the ZnT family, in the mouse cerebellum. Immunostaining and confocal microscopic observations revealed a similar staining pattern of ZnTs in the molecular layer and the Purkinje cell layer. Double labeling with anti-S-100beta or anti-MAP2 and anti-ZnTs clearly showed that the Bergman glial cell bodies in the Purkinje cell layer and their radial processes in the molecular layer exhibited strong immunofluorescence of all the tested ZnTs. However, the somata of the Purkinje cells contained a moderate immunostaining for ZnT1, but virtually lack of other three ZnTs. In the granular layer, ZnTs appeared with different immunostaining patterns. ZnT1 was expressed in a small number of neuronal cell bodies and their primary dendrites, whereas ZnT3 and ZnT4 were present in nerve terminals but not in the neuronal somata. ZnT6 was undetectable in either the cell bodies or processes in the granular layer. The present results indicate that the Bergman glial cells may play an important role in zinc metabolism in the mouse cerebellar cortex.     

Stromal cell-derived inducing activity does not promote dopaminergic differentiation, but enhances differentiation and proliferation of neural stem cell-derived astrocytes

Previous evidence has shown that stromal cell-derived inducing activity (SDIA), produced by the mouse PA6 stromal cell line, promotes dopaminergic differentiation of mouse, monkey and human embryonic stem cells in vitro. To examine whether PA6 stromal cells can enhance the yield of dopaminergic differentiation from neural progenitors, we generated neurospheres from embryonic day 11.5 (E11.5) (midbrain and forebrain) and E14.5 (ventral mesencephalon and cortex) rat embryos and allowed them to differentiate in co-culture with PA6 cells or poly-l-lysine/laminin-coated dishes. We observed that SDIA did not promote dopaminergic differentiation of E11.5 and E14.5 neurospheres but more prominently, enhanced astrocyte differentiation, cell survival and astrocyte proliferation. Our results suggest that PA6 cells do not have a general capacity to promote differentiation into dopaminergic neurons from all types of stem cells, but that they may specifically induce dopaminergic differentiation of highly uncommitted stem cells such as embryonic stem cells.     

Orexin loss in Huntington's disease

Huntington's disease (HD) is a devastating neurodegenerative disorder caused by an expanded CAG repeat in the gene encoding huntingtin, a protein of unknown function. Mutant huntingtin forms intracellular aggregates and is associated with neuronal death in select brain regions. The most studied mouse model (R6/2) of HD replicates many features of the disease, but has been reported to exhibit only very little neuronal death. We describe for the first time a dramatic atrophy and loss of orexin neurons in the lateral hypothalamus of R6/2 mice. Importantly, we also found a significant atrophy and loss of orexin neurons in Huntington patients. Like animal models and patients with impaired orexin function, the R6/2 mice were narcoleptic. Both the number of orexin neurons in the lateral hypothalamus and the levels of orexin in the cerebrospinal fluid were reduced by 72% in end-stage R6/2 mice compared with wild-type littermates, suggesting that orexin could be used as a biomarker reflecting neurodegeneration. Our results show that the loss of orexin is a novel and potentially very important pathology in HD.     

环境气象因素对脂质异常型干眼发病的风险研究

目的:探讨我国东西部地区不同环境气象因素对脂质异常型干眼发病的影响。方法:多中心回顾性研究。选取2021-03-01/2022-02-28南京中医药大学附属南京中医院及新疆伊犁哈萨克自治州友谊医院眼科门诊就诊的干眼患者,统计整理一般资料(性别、年龄、就业情况、教育程度)及就诊当日室外环境气候数据(温度、湿度、空气质量指数、风力)。筛选出符合纳排的患者,应用单因素、多因素及非线性模型分析筛选出两地区脂质异常型干眼的环境相关因素。结果:南京与伊犁两地区各自不同季节脂质异常型干眼发病情况无明显差异,两地相比,伊犁地区脂质异常型干眼发病就诊人次四季均明显多于南京地区(P<0.001)。单因素研究结果显示,影响脂质异常型干眼发病的因素有：性别、就业情况、湿度、空气质量指数、风力。多因素Logistic回归分析显示：湿度、温度、空气质量指数三种环境因素有统计学意义,在调整年龄、性别、就业情况三种混杂因素后仍然有意义。非线性分析显示温度在低于10℃时,脂质异常型干眼的发生概率随温度的降低而上升;在10℃～15℃时,脂质异常型干眼的发生概率变化趋于平稳,当温度超过15℃后,脂质异常型干眼的发生概...     

GLYCEROL DEHYDRATES OEDEMATOUS AS WELL AS NORMAL BRAIN IN DOGS

1. Although the effect of glycerol on reducing intracranial pressure has been widely investigated, only a few studies have reported its dehydrating effect on brain oedema caused by infarction, ischaemia, microembolism and cold injury, but none on traumatic oedema. In this study the effects of glycerol (1 g/kg, i.v. bolus infusion at a rate of 0.04 g/kg per min) on traumatic and cryogenic cerebral oedema and on normal brain were compared in the anaesthetized dog. The tissue water content was measured with the gravimetric method. 2. Oedema resulting from mechanical trauma was initiated 4 h prior to treatment with glycerol (8 dogs) or vehicle (5 dogs) by closed head contusion with fixed force under general anaesthesia. Tissue samples underneath the region of contusion were taken, before and 1 h after infusion of glycerol or vehicle, for the measurement of water content. 3. Glycerol infusion decreased the water content in white matter of the traumatic brain model from 76.54 ± 1.70% to 70.73 ± 1.54% (P<0.001). In normal brain the reduction was from 68.42 ± 0.48% to 65.36 ± 0.39% (P<0.001). Neither vehicle nor glycerol infusion resulted in significant changes in specific gravity of the gray matter. 4. Cryogenic oedema was initiated 3 h prior to the infusion of glycerol or vehicle by applying unilaterally a brass conical cup (bottom diameter 1 cm) filled with dry ice-acetone (- 65^°C) to the exposed dura for 1 min. The contralateral hemisphere, which was not subjected to cold injury, was used for determination of water content of normal gray and white matter. 5. Glycerol infusion decreased the water content in the white matter of the cold-injured region from 75.38 ± 0.69% to 72.57 ± 0.58% (P<0.001). In the normal white matter the reduction was from 68.63 ± 0.34% to 65.48 ± 0.49% (P<0.001). 6. Our data indicate that glycerol decreases water content of the white matter in traumatic and cold-injured oedematous brain as well as in normal brain.