Evaluation of the MHSeqTyper47 kit for forensically challenging DNA samples

Microhaplotypes have been highly regarded for forensic mixture DNA deconvolution because they do not experience interference from stutters in the same way as short tandem repeat markers, and they tend to be more polymorphic than single nucleotide polymorphism markers. However, forensic microhaplotype kits have not been reported. The MHSeqTyper47 kit genotypes 47 microhaplotype loci. In this study, MiSeq FGx sequencing metrics for MHSeqTyper47 were presented, and the genotyping accuracy of this kit was examined. The sensitivity of MHSeqTyper47 reached 62.5 pg, and full genotyping results were obtained from degraded DNA samples with degradation indexes ≤ 3.00. Full genotypes were obtained in the presence of 100 ng/μL tannin, 50 μM heme, 25 ng/μL humic acid, and 1.25 μg/μL indigo dye. In DNA mixture studies, a minimum of 31 loci of the minor contributor were correctly genotyped at 1:99 or 99:1 mixing ratios, with the cumulative random matching probability of these loci reaching 4.54 × 10⁻²⁵. Mixing ratios could be reliably predicted from two-donor DNA mixtures based on the loci with four called alleles. Taken together, these data showed that the MHSeqTyper47 kit was effective for forensically challenging DNA analysis.     

Bayesian consensus clustering for multivariate longitudinal data

In clinical and epidemiological studies, there is a growing interest in studying the heterogeneity among patients based on longitudinal characteristics to identify subtypes of the study population. Compared to clustering a single longitudinal marker, simultaneously clustering multiple longitudinal markers allow additional information to be incorporated into the clustering process, which reveals co-existing longitudinal patterns and generates deeper biological insight. In the current study, we propose a Bayesian consensus clustering (BCC) model for multivariate longitudinal data. Instead of arriving at a single overall clustering, the proposed model allows each marker to follow marker-specific local clustering and these local clusterings are aggregated to find a global (consensus) clustering. To estimate the posterior distribution of model parameters, a Gibbs sampling algorithm is proposed. We apply our proposed model to the primary biliary cirrhosis study to identify patient subtypes that may be associated with their prognosis. We also perform simulation studies to compare the clustering performance between the proposed model and existing models under several scenarios. The results demonstrate that the proposed BCC model serves as a useful tool for clustering multivariate longitudinal data.     

肠炎清合剂治疗慢性复发型溃疡性结肠炎大肠湿热证的临床观察

目的:观察肠炎清合剂对慢性复发型溃疡性结肠炎(UC)大肠湿热证患者诱导缓解效果及维持治疗对复发的影响,并从神经-内分泌-免疫炎症网络方面探讨了其作用机制。方法:将112例符合要求的患者随机分成对照组55例和观察组57例。对照组内服美沙拉嗪肠溶片,1.0 g/次,4次/d;Mayo评分系统≥7分者,加服醋酸泼尼松片,0.75 mg·kg^-1·d^-1;加用双歧杆菌活菌散剂,1包/次,2次/d,餐后温水冲服。观察组在对照组治疗的基础上服用肠炎清合剂,1包/次,分早晚2次服用。两组疗程均为连续治疗6周,再每周门诊复诊1次。进入缓解期后,两组患者均给予美沙拉嗪肠溶片,0.5 g/次,3次/d,维持治疗;观察组仍内服肠炎清合剂内服,至大肠湿热证评分减少≥90%以上。记录进入6周内缓解期的人数和缓解时间;进行治疗前后结肠镜检查,并进行Geboes指数和Baron法评价;进行治疗前后大肠湿热证评分和Mayo评分;检测治疗前后外周血白细胞介素-6(IL-6),IL-8,IL^-10,IL^-17,血管活性肠肽(VIP),胃动素(MTL)和神经肽Y(NPY);随访24周,记录复发情况。结果:经6周治疗后,观察组临床有效率为100%,黏膜愈合率为96.4%,均分别高于对照组的89.09%和81.82%(P<0.05),两组患者内镜应答率均为100%;经6周治疗后,观察组临床缓解率为91.23%,高于对照组的76.36%(χ2=4.581,P<0.05),观察组平均缓解时间短于对照组(P<0.01);治疗后观察组结肠黏膜评分,Geboes指数、大肠湿热证评分和Mayo评分均低于对照组(P<0.01);观察组患者外周血IL-6,IL-8和IL^-17水平均低于对照组(P<0.01),IL^-10水平高于对照组(P<0.01);观察组患者外周血VIP,MTL水平均低对照组(P<0.01),NPY水平高于对照组(P<0.01);观察组复发率为17.54%,低于对照组的38.18%(χ2=5.955,P<0.05);观察组平均复发时间长于对照组(P<0.01)。结论:在常规西医治疗的基础上,肠炎清合剂用于慢性复发型UC大肠湿热证的治疗,可诱导病情缓解,缩短病程,并能降低复发率,推迟复发时间,并对神经-内分泌-免疫炎症网络具有调节作用,从而可改善病情。     

Exploring the DNA mixture deconvolution through simulation

ABSTRACT

If an unambiguous single-source DNA profile is obtained from a crime scene, then a potential person of interest can either match or not match the crime scene profile and the likelihood ratio for the single matching genotype can be easily computed. Mixed DNA profiles on the other hand are typically ambiguous and a vast number of different likelihood ratios can be obtained depending on the genotype of a potential person of interest that is compared with the mixture later. In the absence of a person of interest it can be unclear how suitable the profile is for discriminating between donors and non-donors. We introduce a simulation method to explore the range of likelihood ratios that is expected to be obtained when a non-donor or a true donor is compared with the mixed DNA profile. Sampling is conditional on the mixture deconvolution obtained using probabilistic genotyping. These simulations help to decide whether or not a (mixed) profile is suitable for comparison to a person of interest. Moreover, the methods can be used to determine whether a profile is suitable for upload to a database and whether or not potential rework could be advised.     

Preparation,characterization, and antibacterial activity of plaunotol and plaunoi extracts complexed with hydroxypropyl-β-cyclodextrin

Croton stellatopilosus (Plaunoi) leaves accumulate several diterpenes and possess various pharmacological activities. The present study aimed to prepare, characterize and assess the antibacterial activity of inclusion complexes prepared by mixing plaunotol (PL) or plaunoi extract (PE) with cyclodextrins (CD), including α-CD, β-CD, γ-CD, and hydroxypropyl-β-cyclodextrin (HP-β-CD). The inclusion complexes were characterized using SEM, XRD, DSC, and FT-IR and evaluated for aqueous solubility and thermal stability. The PL and PE lyophilized complexes with HP-β-CD were further evaluated for their antibacterial activity against acne-causing bacteria. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of PL, PE, and the inclusion complexes evaluated using the agar dilution method revealed that the MIC and MBC values of the inclusion complexes were lower than those of PL or PE alone. Interestingly, the complexes had a synergistic activity with clindamycin after testing with checkerboard assay. The hydrogel containing the inclusion complex and clindamycin were assessed for antibacterial activity using the agar well diffusion method. The results indicated that the hydrogels showed significant inhibition of bacterial growth. In conclusion, the prepared solid dispersion of PL or PE with HP-β-CD could enhance antibacterial activity by increasing the drug solubility. The hydrogels containing PL or PE complex and clindamycin could be considered as a candidate for the treatment of acne vulgaris.     

从“筋骨、痹痿、虚实、动静、刚柔”谈膝骨关节炎功能障碍的特点

膝骨关节炎(KOA)属于进展性骨关节病,其功能障碍主要表现为膝关节疼痛、僵硬、屈伸行走不利或受限,以及关节失稳、运动控制下降和本体感觉低下等。我国KOA患者众多,且还在逐年增加,引起的功能障碍严重影响着患者健康与生活质量,因此对其开展康复的研究与实践至关重要。中医康复着眼于功能,注重辨证康复,是我国康复医学的固有特色及优势。前期的研究基于KOA功能障碍的中医证候表现,本研究经大量文献梳理及多年临床实践,从“筋骨、痹痿、虚实、动静、刚柔”5个角度为切入点,提出KOA功能障碍具有“筋骨同病、痹痿并见、虚实错杂、动静失衡、刚柔失常”5个基本特点。鉴于KOA功能障碍具有早、中、晚三期的阶段性特点,在该病发生发展的不同阶段,其功能障碍在“筋骨、痹痿、虚实、动静、刚柔”之间的表现又各有所侧重。本研究从“筋骨同病、痹痿并见、虚实错杂、动静失衡、刚柔失常”5个方面分别阐释了KOA功能障碍的特点:“筋骨同病”侧重于病位,是KOA所致功能障碍的基本病机特征,贯穿于其发病的始终;“痹痿并见、虚实错杂”偏重病性,是KOA功能障碍的基本特点;“动静失衡”偏重病因,是引起KOA病情反复及加重的重要因素;“刚柔失常”则是兼具病状与病因,是膝关节失去“骨正筋柔”的表现方式,也是KOA功能障碍的重要特征。本研究旨在进一步完善KOA的中医康复理论,为其康复治疗提供参考。     

益气养阴合剂中10种有效成分的含量测定

目的：建立同时测定益气养阴合剂中丹参酮ⅡA、丹酚酸A、丹酚酸B、毛蕊异黄酮、毛蕊异黄酮葡萄糖苷、五味子醇甲、五味子醇乙、五味子甲素、五味子乙素、丹皮酚含量的方法。方法：采用Hedera C₁₈ ODS-2色谱柱（4.6 mm×250 mm，5 μm），以乙腈-0.1%磷酸水溶液梯度为流动相，柱温30℃，流速1.0 mL·min^-1，检测波长215nm。结果：毛蕊异黄酮、毛蕊异黄酮葡萄糖苷、丹皮酚、五味子醇甲、五味子醇乙、五味子甲素、五味子乙素、丹参酮ⅡA、丹酚酸A、丹酚酸B浓度分别在2.93~62.76（r=0.999 6）、2.53~54.06（r=0.999 9）、2.78~59.64（r=0.999 9）、2.72~58.38（r=0.999 2）、2.79~59.76（r=0.999 6）、2.87~61.44（r=0.999 7）、2.61~63.66（r=0.999 2）、2.28~48.78（r=0.999 6）、2.99~64.08（r=0.999 5）、2.69~57.66（r=0.999 1）范围内与峰面积呈良好的线性关系，平均回收率在93.23%~100.68%之间。结论：3批样品测定结果表明，建立的方法可以用于同时测定益气养阴合剂中10种成分的含量。     

升髓合剂防治化疗后骨髓抑制的临床研究

目的:观察患者临床症状、客观检测指标及用药期间是否出现不良反应等,评价升髓合剂对多西他赛联合顺铂方案(Docetaxel Combined with Cis-platinum,DP)化疗所致骨髓抑制的有效性及安全性。方法:将50例符合标准的恶性肿瘤患者随机分为两组,治疗组和对照组各25例。对照组:DP方案化疗同时加服地榆升白片,治疗组:在DP方案化疗基础上加用升髓合剂。2个周期后观察患者化疗后第3、7、14 d外周血细胞变化及骨髓抑制情况,化疗后中医临床症状评分及疗效以及体力状况评分(Karnofsky,KPS)、体质量变化及其不良反应。结果:①两组化疗完成率观察组明显高于对照组(P<0.05);②观察组血常规中白细胞、中性粒细胞、血小板计数治疗后1周与治疗前比较无统计学意义,(P>0.05),而对照组白细胞、中性粒细胞、血小板计数下降显著,与治疗前差异有统计学意义,(P<0.05);两组相比,化疗后1周观察组血常规白细胞、中性粒细胞、血小板水平明显高于对照组,差距有统计学意义(P<0.05);③化疗后2周观察组白细胞计数升高明显高于对照组,两组差异有显著性(P<0.05);④化疗后中医证候改善方面,观察组症状改善显著(P<0.05)。对照组症状上改善不明显(P>0.05),两组在总体症状改善率方面相比较有显著性差异,治疗组明显优于对照组(P<0.05);⑤治疗组KPS评分明显优于对照组(P<0.05);⑥治疗组不良反应的发生率明显低于对照组(P<0.05)。结论:升髓合剂对于多西他赛联合顺铂化疗方案引起的骨髓抑制等不良反应具有防治作用。     

肺力咳合剂联合糖皮质激素治疗小儿肺炎疗效观察

目的:观察肺力咳合剂联合糖皮质激素治疗小儿肺炎的疗效。方法:选取我院儿科2016年12月~2018年7月接收的肺炎患儿120例,按随机数表法分为观察组和对照组,每组60例。对照组确诊后用糖皮质激素进行治疗;观察组确诊后用糖皮质激素联合肺力咳合剂进行治疗。治疗结束后评估两组临床效果,详细记录治疗前、治疗3 d后与治疗7 d后肺部炎症的积分情况以及咳嗽消失时间、发热消失时间、胃肠道反应时间、肺啰音消失时间与X线肺部炎症吸收时间。结果:肺力咳合剂联合糖皮质激素治疗的观察组临床治疗效果明显优于仅用糖皮质激素治疗的对照组(P<0.05);观察组治疗3 d、1周后,肺部炎症积分比对照组明显降低,咳嗽消失时间、发热消失时间、胃肠道反应时间、肺啰音消失时间与X线肺部炎症吸收时间得到有效的改善(P<0.05)。结论:对小儿肺炎以肺力咳合剂联合糖皮质激素辅助治疗效果显著,利于缓解症状及体征,减少住院治疗时间,值得临床推广。