Diagnosis of an intermediate case of maple syrup urine disease:A case report

BACKGROUND Maple syrup urine disease(MSUD)is an autosomal recessive genetic disorder caused by defects in the catabolism of the branched-chain amino acids(BCAAs).However,the clinical and metabolic screening is limited in identifying all MSUD patients,especially those patients with mild phenotypes or are asymptomatic.This study aims to share the diagnostic experience of an intermediate MSUD case who was missed by metabolic profiling but identified by genetic analysis.CASE SUMMARY This study reports the diagnostic process of a boy with intermediate MSUD.The proband presented with psychomotor retardation and cerebral lesions on magnetic resonance imaging scans at 8 mo of age.Preliminary clinical and metabolic profiling did not support a specific disease.However,whole exome sequencing and subsequent Sanger sequencing at 1 year and 7 mo of age identified bi-allelic pathogenic variants of the BCKDHB gene,confirming the proband as having MSUD with non-classic mild phenotypes.His clinical and laboratory data were retrospectively analyzed.According to his disease course,he was classified into an intermediate form of MSUD.His management was then changed to BCAAs restriction and metabolic monitoring conforming to MSUD.In addition,genetic counseling and prenatal diagnosis were provided to his parents.CONCLUSION Our work provides diagnostic experience of an intermediate MSUD case,suggesting that a genetic analysis is important for ambiguous cases,and alerts clinicians to avoid missing patients with non-classic mild phenotypes of MSUD.

Protective effects of honey compound syrup on busulfan-induced azoospermia in male rats

Objective:To evaluate the protective effects of honey compound syrup on sperm count and testis tissue in rats.Methods:Thirty rats were randomly assigned to five groups.The control group received 1 mL normal saline with dimethyl sulfoxide intraperitoneally;the busulfan group received busulfan 10 mg/kg body weight at the first and twenty-first days of the experiment via intraperitoneal injection;the last three groups received busulfan 10 mg/kg body weight to induce azoospermia,and then received 1.0,1.5,or 2.0 mg/kg honey compound syrup,respectively,after induction of azoospermia.After administration,the testis and epididymis of all rats were removed.Then,reproductive organ weight and sperm parameters(sperm concentration,epididymal sperm reserve and daily sperm production)were measured.After hematoxylin-eosin staining,seminiferous tubule cells and diameters were assessed.Results:Busulfan damaged the testis tissue and impaired spermatogenesis.Administration of honey compound syrup in three doses improved testis tissue and spermatogenesis.The protective effects of honey compound syrup may relate to the antioxidant properties of honey and other compounds in this syrup.Conclusions:Administration of honey compound syrup could be an ameliorative agent for the side effects of chemotherapy drugs such as busulfan on the male reproductive system.

Identification of syrup type using fourier transform-near infrared spectroscopy with multivariate classification methods

This research aimed to establish near infrared(NIR)spectroscopy models for identification ofsyrup types in which the maple syrup was discriminated from other syrup types.Thirty syruptypes were used in this research;the NIR spectra of each type were recorded with 10 replicates.The repeatability and reproducibility of NIR scamning were perfomed,and the absorbance atG940cn-1 was used for calculation,.Principal component analysis was used to group the syruptype.Identification models were developed by soft independent modeling by,class analogy(SIMCA)and partial least-squares diseriminant analysis(PLS.DA),The SiMCA models of alsyrup types exhibited accuracy percentage of 93.3-100%for identifying syrup types,whereasmaple syrup discrimination models showed percentage of accuracy between 83.2%and 100%.The PLS-DA technique gave the accuracy of syrup types classification bet ween 96.6%and 100%and presented ability on discrimination of maple syrup form other types of syrup with accuracyof 100%.The finding presented the potential of NIR spectroscopy for the syrup typeidentification.

Physicochemical, Proximate and Sensory Properties of Pineapple (<i>Ananas</i>sp.) Syrup Developed from Its Organic Side-Stream

A major economical industrial challenge from pineapple (Ananas sp.) processing contributing to environmental pollution is the organic side-streams of pineapple. The physicochemical, proximate and sensory properties of organic sidestream pineapple syrup (OSPS) developed from Smooth cayenne, Sugar loaf and MD2 pineapple varieties were evaluated. Organic side-stream pineapple syrup developed from MD2 recorded the highest moisture content with a corresponding water activity. The colour change in OSPS was significant among the three varieties and Sugar loaf variety deviated from the standard yellow colour more than Smooth cayenne and MD2 varieties. This was buttress by the high Total Soluble Solids in 10% and 20% dilutions of Sugar loaf. The OSPS was acidic. In bread, incorporating 5% OSPS (w:w) of Sugar loaf recorded the highest percentage acceptability among the pineapple varieties. Interestingly, in the production of cakes with 15%, 20% and 30% OSPS, MD2 recorded the highest percentage overall acceptance. For bread and cake, there was varied significance (P 2 and 5% Sugar loaf was more acceptable.

The effects of 90-day feeding of D-psicose syrup in male wistar rats

D-Psicose is a rare sugar present in small quantities in natural products. In a previous study, we showed that D-psicose suppresses increase in plasma glucose and reduces body fat accumulation in rats. Based on acute and chronic toxicity testing in rats, D-psicose is classified as an ordinary and safe substance. Recently, we developed a high D-psicose syrup (PS) made from high fructose corn syrup (HFCS) by the alkaline isomerization method. However, the safety of PS as a food additive has not been demonstrated. In this study, we investigated the effects of 90-day feeding of PS in male Wistar rats. The rats were fed diets containing 3% D-psicose (control) or 4.3% PS for 90 days. The body weight gain and intra-abdominal adipose tissue weight did not differ between the control and PS group. The weights of the tissues did not differ between the two dietary groups. In clinical chemistry and hematological analyses, no differences were found between the control and PS groups. No gross pathological findings were evident at dietary doses of 4.3% PS. Therefore, the present study found no adverse effects of PS in rats fed a diet containing 4.3% PS for 90 days.

Brain magnetic resonance imaging findings and radiologic review of maple syrup urine disease:Report of three cases

BACKGROUND Maple syrup urine disease(MSUD)is a rare autosomal-recessive disorder that affects branched-chain amino acid(BCAA)metabolism and is named after the distinctive sweet odor of affected infants’urine.This disease is characterized by the accumulation of BCAAs and corresponding branched-chain ketoacids of leucine,isoleucine,and valine in the plasma,urine,and cerebrospinal fluid.However,the mechanisms of MSUD-induced brain damage remain poorly defined.The accumulation of BCAAs in the brain inhibits the activity of pyruvate dehydrogenase andα-ketoglutarate,disrupting the citric acid cycle and consequently impacting the synthesis of amino acids,causing cerebral edema and abnormal myelination.CASE SUMMARY We report three neonates admitted to our hospital with the classic subtype of MSUD.All three patients,with a transient normal period,presented with poor feeding,vomiting,poor weight gain,and increasing lethargy after birth.Laboratory testing revealed metabolic acidosis.The serum tandem mass spectrometry amino acid profile showed elevated plasma levels of BCAAs(leucine,isoleucine,and valine).Brain magnetic resonance imaging(MRI)presented abnormal signals mainly involving the globus pallidus,thalamus,internal capsule,brainstem,and cerebellar white matter,which represent the typical myelinated areas in normal full-term neonates.CONCLUSION In our patients,MRI showed typical features,in concordance with the available literature.Early detection and timely treatment are very helpful for the prognosis of MSUD patients.Therefore,we discuss the neuroimaging features of MSUD to enhance the knowledge of pediatricians about this disease.

Study on quality standard of Danmu exract syrup

Objective:To establish the quality standard of Danmu exract syrup.Methods:TLC method was used to qualitatively identify Nauclea officinalis in Danmu exract syrup.The content of strictosamide and chlorogenic acid in Danmu exract syrup was determined by high efficiency axillary chromatography.Results:The spots were clear and there was no negative interference.The linear relationship of strictosamide was good in the range of 100~300ug/ml(R^(2)=0.9997).The average recovery was 99.1%and RSD was 1.16%(n=9).Chlorogenic acid had a good linear relationship in the range of 6.7~20.2ug/ml(R^(2)=0.9991).The average recovery was 99.9%and RSD was 1.10%(n=9).Conclusion:The standard is safe and reasonable,the method is simple,accurate and reproducible,and it can be used for the quality control of Danmu exract syrup.

Evaluation of the Palatability of Dry Syrups and the Bitterness Intensities of Dry Syrups Mixed with Various Beverages

The purpose of this study was to evaluate the palatability of dry syrups for pediatric use by human gustatory sensation testing and the artificial taste sensor. The bitterness intensities of dry syrups mixed with various beverages were also evaluated using the taste sensor. Twenty dry-syrup formulations of antibacterial and anti-allergic drugs containing bitter active ingredients, frequently used in pediatric medicine in Japan, were selected for testing. The main factors influencing palatability were determined by factor analysis of data from human gustatory sensation testing using the semantic differential method. It was shown that the bitterness intensity of dry syrups in water could be predicted by the artificial taste sensor. The influence of different beverages (orange juice, milk or cocoa) mixed with the dry syrups was evaluated using the artificial taste sensor. Taste and texture were found to be the principal factors influencing the palatability of dry syrups. While the bitterness intensities of some dry syrups were increased by mixing with orange juice, the bitterness intensities of most dry syrups were decreased by mixing with milk or cocoa. This suggests that one or more constituents of milk or cocoa may reduce the bitterness intensities of dry syrups.

Design, Development and Phytochemical Evaluation of a Poly Herbal Formulation Linkus Syrup

The present work has been carried out on polyherbal formulation named as Linkus Syrup. The herbal formulation consists of Glycyrrhiza glabra, Hyssopus officinalis, Piper longum and Alpinia galangal. The Linkus syrup physico-chemical evaluation such as pH, density, identification of polysaccharide, tanning agents, ascorbic acid and shelf life was complied. The TLC and quantitative determination of alkaloid were quantified. Determination of biomarker has been validated for the analysis of vasicine. The study result revealed that Linkus syrup formulation was well standardized at different levels such as physic-chemical consistency and assay of bio marker compound.

Grape Syrup

Grape syrup is a new type of healthdrink produced by the Zhuguang Drink Factoryin Wuhai City,Inner Mongolia. Grapes contain protein,amino acids,tartrate,vitamins and multi-minerals.Thisgrape syrup is prepared from the big Wuhaigrapes,quality mineral water and the extractof seaweed.It contains 30% grape juice.With rich nutrients and sweet and refreshingtaste,it has the effect of nourishing

Protective Effects of Danmu Extract Syrup on Acute Lung Injury Induced by Lipopolysaccharide in Mice through Endothelial Barrier Repair

Objective:To investigate the effects of Danmu Extract Syrup(DMS) on lipopolysaccharide(LPS)-induced acute lung injury(ALI) in mice and explore the mechanism.Methods:Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table(n=12),including control(normal saline),LPS(5 mg/kg),LPS+DMS 2.5 mL/kg,LPS+DMS 5 mL/kg,LPS+DMS 10 mL/kg,and LPS+Dexamethasone(DXM,5 mg/kg) groups.After pretreatment with DMS and DXM,the ALI mice model was induced by LPS,and the bronchoalveolar lavage fluid(BALF) were collected to determine protein concentration,cell counts and inflammatory cytokines.The lung tissues of mice were stained with hematoxylin-eosin,and the wet/dry weight ratio(W/D) of lung tissue was calculated.The levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-6 and IL-1βin BALF of mice were detected by enzyme linked immunosorbent assay.The expression levels of Claudin-5,vascular endothelial(VE)-cadherin,vascular endothelial growth factor(VEGF),phospho-protein kinase B(p-Akt) and Akt were detected by Western blot analysis.Results:DMS pre-treatment significantly ameliorated lung histopathological changes.Compared with the LPS group,the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment(P<0.05 or P<0.01).The number of cells in BALF and myeloperoxidase(MPO) activity decreased significantly after DMS pretreatment(P<0.05 or P<0.01).DMS pre-treatment decreased the levels of TNF-α,IL-6 and IL-1β(P<0.01).Meanwhile,DMS activated the phosphoinositide 3-kinase/protein kinase B(PI3K/Akt) pathway and reversed the expressions of Claudin-5,VE-cadherin and VEGF(P<0.01).Conclusions:DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier.It might be a potential therapeutic drug for LPS-induced lung injury.

基于JAK2/STAT3信号通路探究利咽糖浆对慢性咽炎大鼠咽喉组织损伤及咽黏膜修复的影响

目的:基于Janus激酶2(JAK2)/信号转导和转录激活因子3(STAT3)信号通路探究利咽糖浆对慢性咽炎大鼠咽喉组织损伤及咽黏膜修复的影响。方法:取SD大鼠随机分为对照组、模型组、利咽糖浆组、RO8191(JAK2/STAT3激活剂)组、利咽糖浆+RO8191组,模型组与药物干预组大鼠采用氨水刺激咽部构建慢性咽炎模型,对照组大鼠咽部注射等剂量生理盐水,经利咽糖浆与RO8191干预后,检测大鼠一般情况及咽部表观状态,并进行咽部表观状态评分;HE染色检测大鼠咽部病理形态变化;流式细胞术检测大鼠外周血T淋巴细胞亚群CD4^(+)T与CD8^(+)T表达、CD4^(+)T/CD8^(+)T;试剂盒检测大鼠血清肿瘤坏死因子-α(TNF-α)、IL-6、IL-10、丙二醛(MDA)、活性氧(ROS)、总抗氧化能力(T-AOC)水平;以免疫印记法检测大鼠咽部组织JAK2/STAT3通路相关蛋白表达。结果:与对照组比较,模型组大鼠咽部组织出现明显病理形态损伤,外周血CD4^(+)T与CD4^(+)T/CD8^(+)T、IL-10、血清T-AOC水平降低(P<0.05),咽部表观状态评分、CD8^(+)T、血清TNF-α、IL-6、MDA与ROS水平、咽部组织p-JAK2/JAK2与p-STAT3/STAT3水平升高(P<0.05);与模型组、利咽糖浆+RO8191组相比,利咽糖浆组大鼠咽部组织病理形态损伤减轻,外周血CD4^(+)T表达与CD4^(+)T/CD8^(+)T、IL-10、血清T-AOC水平均升高(P<0.05),咽部表观状态评分、CD8^(+)T、血清TNF-α、IL-6、MDA与ROS水平、咽部组织p-JAK2/JAK2与p-STAT3/STAT3水平均降低(P<0.05);RO8191组大鼠各指标变化趋势与利咽糖浆组相反。结论:利咽糖浆可通过抑制JAK2/STAT3信号激活减轻炎症及氧化应激,增强抗炎及抗氧化能力,缓解慢性咽炎大鼠咽喉组织损伤,修复咽黏膜。

强力枇杷露治疗慢性支气管炎模型小鼠作用机制研究

目的 探讨强力枇杷露治疗慢性支气管炎模型小鼠的作用机制。方法 将72只NIH小鼠随机分为空白对照组(A组,12只,等体积纯净水)和模型组(60只),采用烟熏联合脂多糖吸入法复制慢性支气管炎模型小鼠建模45 d后,将模型组小鼠随机分为模型对照组(B组,等体积纯净水),盐酸氨溴索组(C组,10 mL/kg),强力枇杷露低、中、高剂量组(D1组、D2组、D3组,7.5,15,30 mL/kg),各12只,雌雄各半。各组小鼠按30 mL/kg灌胃给药,每日1次,连续14 d。末次给药24 h后,采集小鼠血清,测定白细胞介素6(IL-6)、白细胞介素8(IL-8)水平;取右肺组织,测定肿瘤坏死因子-α(TNF-α)、丙二醛(MDA)及超氧化物歧化酶(SOD)含量;对左肺支气管组织进行病理组织学检查。结果 与B组比较,D1组小鼠肺组织MDA含量显著降低(P <0.01);D2组小鼠血清IL-8的水平、肺组织MDA含量均显著降低(P <0.05);D3组小鼠血清IL-8水平、肺组织TNF-α和MDA含量均显著降低(P <0.05),SOD含量显著升高(P <0.05)。与C组比较,D1组小鼠血清IL-8水平显著升高(P <0.05),肺组织SOD含量显著降低(P <0.05)。病理组织学染色结果显示,与B组比较,D1组、D2组、D3组小鼠慢性支气管炎病变程度减轻。结论 强力枇杷露治疗慢性支气管炎模型小鼠的作用机制可能与降低IL-8,TNF-α,MDA含量和升高SOD含量相关。

微滤联合大孔树脂纯化蓝莓果脯糖浆中花色苷的工艺优化

本文使用微滤技术联合大孔树脂技术对蓝莓果脯糖浆分离纯化,以回收其中的蓝莓花色苷。首先通过静态试验对大孔树脂进行筛选,并在动态试验中以花色苷回收率和总糖去除率为指标,在单因素和Box-Behnken响应面试验的基础上,优化了上样流速、乙醇浓度和洗脱流速等工艺参数。结果表明:微滤透过液中花色苷含量为6.84 mg/100 mL,总糖含量为31.76 mg/mL。AB-8、D101、HPD600三种树脂中,优选出AB-8用于蓝莓果脯花色苷的纯化,大孔树脂纯化花色苷最佳工艺条件为:上样流速2.0 mL/min、乙醇浓度83%、洗脱流速2.0 mL/min,该条件下花色苷的回收率为86.68%,总糖去除率为84.13%。花色苷解吸液经旋转蒸发浓缩后,花色苷质量浓度为5.56 mg/100 mL,总糖浓度为5.24 mg/mL,花色苷的色价为31.43,约为原料中花色苷色价的5倍。微滤联合大孔树脂纯化蓝莓果脯糖浆花色苷效果明显,本研究为蓝莓花色苷的分离纯化提供了一定的技术参考。

UPLC-MS/MS法同时测定小绿叶止咳糖浆中8种成分的含量

目的建立UPLC-MS/MS法同时测定小绿叶止咳糖浆中常春藤皂苷C、常春藤皂苷B、α-常春藤皂苷、芦丁、秦皮甲素、金丝桃苷、山柰酚-3-O-芸香糖苷、绿原酸的含量。方法分析采用Acquity UPLC BEH C_(18)色谱柱(100 mm×2.1 mm,1.7μm);流动相0.05%甲酸-乙腈,梯度洗脱;体积流量0.3 mL/min;柱温40℃;电喷雾离子源;正负离子扫描;多反应监测模式。结果8种成分在各自范围内线性关系良好(r>0.9990),平均加样回收率96.61%~101.28%,RSD 1.78%~3.82%。结论该方法快速准确,稳定灵敏,可用于小绿叶止咳糖浆的质量控制。

儿童咳嗽变异性哮喘气道重塑发病机制及抗支糖浆作用机制研究进展

儿童咳嗽变异性哮喘是支气管哮喘的一种特殊类型,患儿临床症状呈多样性,包括干咳、喘息、胸闷、呼吸急促、呼吸困难等,如果长期得不到有效处理或治疗,会导致病情持续恶化发展。随着科技的进步,病理学检查技术不断地更新和升级,逐步证明气道重塑是儿童咳嗽变异性哮喘难以根治的原因。因此,干预气道重塑可改善患儿肺功能并提高治疗效果。抗支糖浆作为一种中成药制剂,在治疗儿童咳嗽变异性哮喘疾病中具有其独特的优势和局限性,文章对其在儿童咳嗽变异性哮喘气道重塑中的作用机制进行综述。

石榴补血糖浆对东莨菪碱诱导PC12细胞凋亡的保护作用及机制研究

目的:探讨石榴补血糖浆对东莨菪碱诱导大鼠肾上腺髓质嗜铬细胞瘤(PC12)细胞凋亡保护作用,探究石榴补血糖浆体外改善认知功能障碍的保护作用机制。方法:将不同浓度的石榴补血糖浆冻干粉细胞培养液作用于PC12细胞,采用CCK-8法检测细胞活性,根据细胞活性结果将后续实验分为空白对照组(NC)、模型组(SC)、石榴补血糖浆低、中、高剂量组(L、M、H:25、50、100μg/ml)、多奈哌齐对照组(D,10μmol/L);利用ELISA试剂盒检测细胞乙酰胆碱(Ach)、乙酰胆碱酯酶(AchE)、超氧化物歧化酶(SOD)和脂质过氧化产物丙二醛(MDA)的水平,流式凋亡术检测活性氧自由基(ROS)及细胞凋亡情况;Westernblot法检测凋亡相关蛋白Bcl-2、Bax、Caspase-3、Cleaved-Caspase-3等蛋白的表达情况。结果:石榴补血糖浆可显著增加PC12细胞的存活率,增加Ach、SOD的水平,降低ROS、MDA及AchE的水平,降低Bax/Bcl-2的比值和Cleaved-Caspase-3/Caspase-3蛋白的表达。结论:石榴补血糖浆可通过Bax/Bcl-2信号通路抑制细胞凋亡,减轻氧化应激,影响细胞内神经递质的水平发挥神经保护作用。

Identification of eight novel mutations in 11 Chinese patients with maple syrup urine disease

Background Maple syrup urine disease(MSUD)is an autosomal recessive inherited disorder that affects the degradation of branched-chain amino acids and is associated with acute and chronic brain dysfunction.This study presents 11 new patients with MSUD and describes the clinical characteristics and gene mutations reported in Chinese individuals.Methods During 2011–2018,11 pedaitric patients with MSUD from 11 Chinese families were analyzed based on clinical characteristics and mass spectrometry,with confirmation via gene sequencing.Novel mutations affecting protein function were predicted with Mutation-Taster,PolyPhen-2,CADD and SIFT software.3D models of the mutated proteins were generated by using the SWISS-MODEL online server,and the models were visualized in PyMOL.The characteristics and gene mutations in patients with MSUD were analyzed retrospectively.Results Seventeen mutations in the BCKDHA,BCKDHB and DBT genes were found,8 of which are novel:c.55C>/T,c.349C>T,c.565C>T,c.808G>A,c.859C>G,and c.1270dupC in BCKDHA;c.275-2A>G in BCKDHB;and c.1291C>T in DBT.Eight patients died.Two patients had severe mental retardation and were physically handicapped.One patient with the intermediate type had relatively good prognosis,with mild psychomotor retardation and adiposity.Four mothers underwent amniocentesis for prenatal diagnosis during their second pregnancy;two fetuses were wild type,and two were carriers of one heterozygous mutation.Conclusions Eight novel mutations were associated with MSUD in Chinese patients.Prenatal diagnosis was successfully performed by genetic analysis.Mutations in the BCKDHB gene were found in the majority of Chinese patients with MSUD.