约束隐结构研究冠心病痰湿证的定量化辨证规则＊

目前在中医界已发布的冠心病痰湿证辨证标准是以主症、次症形式定性地给出，存在主观性较强的问题。本文引入约束隐结构分析，该方法将主症、次症的语义作为约束条件加入隐结构分析过程，得到含有主症、次症语义约束的定量化中医证候辨证规则。使用该方法对冠心病痰湿证患者556条无标签数据的分析，得到其约束隐结构模型，最后建立定量化痰湿证辨证规则，舌胖边有齿痕（3.16）、苔腻（3.12）、苔白滑（4.72）、胸闷（1.73）、脉濡或滑（6.04）；次症：肢体困重（0.48）、口黏（0.63）、体胖（0.49）、大便粘滞（1.38）、脘腹痞满（0.97）、面色晦浊（0.79）、嗜睡（1.18）、纳差（1.07）。与经典隐结构模型得到规则和中医界已发布的定性化辨证规则相比，约束隐结构得到的规则客观性强，具有可重复性。在证候类大小、规则的量化合理度上较好地反映了主症、次症的特点，得到的规则切合中医实际，为冠心病痰湿证辨证标准的定量化研究提供帮助和参考。     

Genetics of intervertebral disc disease: A review

Intervertebral disc disease (IVDD) is a common musculoskeletal disease affecting about 5% of all individuals. It is characterized by lumbar disc herniation, which causes nerve root irritation, either mechanically or via inflammatory mediators, and results in radiating pain, known as sciatica. Numerous studies have been conducted to identify the causes and risk factors for IVDD. Lifting heavy loads, torsional stress, and motor vehicle driving are among the best-identified environmental risk factors. However, it has become evident recently from family and twin studies that genetic factors may also be important in IVDD. This hypothesis was strengthened by the identification of two collagen IX alleles associated with sciatica and lumbar disc herniation. In addition, disc degeneration has been shown to be related to an aggrecan gene polymorphism, a Vitamin D receptor and matrix metalloproteinase-3 gene alleles. This review highlights the genetic role and occupational aspects of IVDD.     

Re‐structuring the negotiated order of the hospital

Researchers continue to lament the lack of organisational focus in the sociology of health and illness. Although studies have increasingly focused on boundaries between organizations, little such research has focused on the formal boundaries within the hospital itself. Given its dramatic compartmentalisation, and continuing prevalence in health systems, the lack of organisational perspective in hospital research limits insights into the effects (as well as the construction) of the order of health work and care. With a greater emphasis on ‘ordering’ in the concept of negotiated order, the aim of this study is to examine the manifestation and consequences of the formal boundaries of hospital departments. Fieldwork featured 12 months of ethnography, including formal and informal observations, 80 audio‐recorded, semi‐structured interviews, and 56 field interviews, in the Emergency Departments (EDs) of two tertiary referral hospitals. Compared with in‐patient hospital departments, the ED has limited legitimacy claims of organ‐specific knowledge to transfer patients out of the ED. The manifestation of specialised knowledge hierarchies in organisational structures disadvantages patients who are older and who have chronic conditions, underpinning the argument that effects as well as the negotiation of stable organisational orders deserve increased attention in the sociology of health and illness.     

Identification of polcalcin as a novel allergen of Amaranthus retroflexus pollen

IntroductionAmaranthus retroflexus (Redroot Pigweed) is one of the main sources of allergenic pollens in temperate areas. Polcalcin is a well-known panallergen involved in cross-reactivity between different plants. The aim of this study was the molecular cloning and expression of polcalcin, as well as evaluating its IgE-reactivity with A. retroflexus sensitive patients’ sera.MethodsAllergenic extract was prepared from A. retroflexus pollen and the IgE-reactivity profile was determined by ELISA and immunoblotting using sera from twenty A. retroflexus sensitive patients. Polcalcin-coding sequence was amplified by conventional PCR method and the product was inserted into pET-21b(+) vector. The recombinant protein was expressed in E. coli BL21 and purified by metal affinity chromatography. The IgE-binding capability of the recombinant protein was analyzed by ELISA and immunoblotting assays, and compared with crude extract.ResultsOf 20 skin prick test positive patients, 17 patients were positive in IgE-specific ELISA. Western blotting confirmed that approximately 53% of ELISA positive patients reacted with 10 kDa protein in crude extract. The A. retroflexus polcalcin gene, encoding to 80 amino acid residues was cloned and expressed as a soluble protein and designated as Ama r 3. The recombinant polcalcin showed rather identical IgE-reactivity in ELISA and western blotting with 10 kDa protein in crude extract. These results were confirmed by inhibition methods, too.ConclusionThe recombinant form of A. retroflexus polcalcin (Ama r 3) could be easily produced in E. coli in a soluble form and shows rather similar IgE-reactivity with its natural counterpart.     

行为-结构化-关系干预模式对短期住院孤独症谱系障碍儿童的疗效分析

目的 探讨以行为-结构化-关系(BSR)干预模式对短期住院孤独症谱系障碍(ASD)儿童的干预疗效,为改善ASD儿童的预后提供参考依据。方法 选取2015年12月－2016年12月确诊为ASD的2~6岁儿童141例,随机分为治疗组和对照组。治疗组ASD儿童均接受BSR模式的短期课程训练,训练课程包括个别辅导、游戏课、运动课、音乐课等,每天训练时间6 h,持续1个月;对照组ASD儿童处于干预等待,接受随访观察和评估。所有ASD儿童干预前、后均接受儿童心理教育评估(第三版)(PEP-3)来进行各方面能力变化的评估。结果 治疗组、对照组干预前各副测验的原积分差异无统计学意义(P>0.05)。两组ASD儿童干预后认知、语言理解、模仿、情感表达、社会互动、行为特征-非语言、适应行为的原积分比较,差异均有统计学意义(t=2.41、2.02、4.14、3.69、4.42、2.69、2.96,P<0.05);但小肌肉、大肌肉、自理的原积分比较,差异无统计学意义(t=-1.13、-1.05、-0.84,P>0.05)。结论 BSR干预模式能够有效改善短期住院ASD儿童的预后,可推广用于儿童ASD的治疗。     

Comparison of Acoustic Structure Quantification,Transient Elastography (FibroScan) and Histology in Patients with Chronic Hepatitis B and without Moderate to Severe Hepatic Steatosis

The purpose of this study was to compare acoustic structure quantification (ASQ) with transient elastography for staging liver fibrosis. One hundred eighty-two patients with chronic hepatitis B and without moderate to severe hepatic steatosis scheduled for liver biopsy underwent ASQ and transient elastography examinations. All ASQ parameters, including total mode, total average, red mode, red average, red standard deviation, blue mode, blue average, blue standard deviation and focal disturbance (FD) ratio and liver stiffness obtained via transient elastography were found to correlate with fibrosis stage (Spearman's r?=?0.783, 0.791, 0.750, 0.771, 0.544, 0.718, 0.691, 0.439, 0.815 and 0.814, respectively; all p values < 0.001). Among the ASQ parameters, the FD ratio had the highest correlation with the stage of fibrosis. The areas under the receiver operating characteristic curves (AUCs) of FD ratio and liver stiffness were 0.911 and 0.906 for F ≥ F1, 0.918 and 0.882 for F ≥ F2, 0.911 and 0.914 for F ≥ F3 and 0.926 and 0.978 for F?=?F4, respectively. There was no significant difference in AUCs between FD ratio and liver stiffness in predicting different stages of fibrosis (p?=?0.062–0.912). ASQ is a promising technique for assessing liver fibrosis in the absence of moderate to severe hepatic steatosis.     

Cocrystal and Salt Forms of an Imidazopyridazine Antimalarial Drug Lead

Cocrystallization and salt formation were used to produce new multicomponent forms of a novel antimalarial imidazopyridazine drug lead (MMV652103) that displayed improved physicochemical properties. The drug lead had earlier shown good in vitro potency against multidrug resistant (K1) and sensitive (NF54) strains of the human malaria parasite Plasmodium falciparum, and high in vivo efficacy in both Plasmodium berghei and Plasmodium falciparum mouse models. A major drawback of MMV652103 is its limited aqueous solubility. Various new supramolecular products, including several multicomponent solid forms, are reported here, namely 3 cocrystal forms with the dicarboxylic acid coformers adipic acid, glutaric acid, and fumaric acid, and a salt form with malonic acid. These were characterized by thermal methods and their structures elucidated by single-crystal X-ray diffraction. A customized solubility experiment was performed in fasted-state simulated intestinal fluid for comparison of the solubility behavior of each new form of the drug lead with that of the untreated starting material. All of the multicomponent forms showed an improvement in the maximum concentrations (C_max) attained by the drug lead and the rate at which it dissolved. The recorded C_max values exceeded the concentration of the untreated compound by factors in the range 4.6-5.6.     

Structural and functional characterization of β2‐glycoprotein I domain 1 in anti‐melanoma cell migration

We previously found that circulating β₂‐glycoprotein I inhibits human endothelial cell migration, proliferation, and angiogenesis by diverse mechanisms. In the present study, we investigated the antitumor activities of β₂‐glycoprotein I using structure‐function analysis and mapped the critical region within the β₂‐glycoprotein I peptide sequence that mediates anticancer effects. We constructed recombinant cDNA and purified different β₂‐glycoprotein I polypeptide domains using a baculovirus expression system. We found that purified β₂‐glycoprotein I, as well as recombinant β₂‐glycoprotein I full‐length (D12345), polypeptide domains I‐IV (D1234), and polypeptide domain I (D1) significantly inhibited melanoma cell migration, proliferation and invasion. Western blot analyses were used to determine the dysregulated expression of proteins essential for intracellular signaling pathways in B16‐F10 treated with β₂‐glycoprotein I and variant recombinant polypeptides. Using a melanoma mouse model, we found that D1 polypeptide showed stronger potency in suppressing tumor growth. Structural analysis showed that fragments A and B within domain I would be the critical regions responsible for antitumor activity. Annexin A2 was identified as the counterpart molecule for β₂‐glycoprotein I by immunofluorescence and coimmunoprecipitation assays. Interaction between specific amino acids of β₂‐glycoprotein I D1 and annexin A2 was later evaluated by the molecular docking approach. Moreover, five amino acid residues were selected from fragments A and B for functional evaluation using site‐directed mutagenesis, and P11A, M42A, and I55P mutations were shown to disrupt the anti‐melanoma cell migration ability of β₂‐glycoprotein I. This is the first study to show the therapeutic potential of β₂‐glycoprotein I D1 in the treatment of melanoma progression.