Comprehensive analysis of insulin products complex disulfide bonds structure by high resolution mass spectrum / 药学学报

The correct pairing of disulfide bonds maintains the correct folding mode and high-level structure formation of peptides and protein drugs, which is crucial for the quality control of products. In order to ensure that the disulfide bonds are correctly paired, disulfide bond analysis is an essential part of peptides and protein drug characterization. Mass spectrometry can be used to analyze disulfide bonds. However, insulin and its analogues have two pairs of disulfide bonds without restriction enzyme cutting site. Conventional collision-induced dissociation (CID) and high-energy induced cleavage (HCD) cannot accurately locate the complex disulfide bond. In our study, three methods were used to localize the complex disulfide, including enzyme digestion combined with key peptide fragment in source decay (ISD) fragmentation method, enzyme digestion combined with partial reduction alkylation method, intact protein source ISD and electron transfer dissociation (ETD) cleavage method, The applicability of insulin aspart, insulin lispro and insulin glargine were also investigated. This study provides a new way for the quality control of disulfide bonding mode of insulin and its analogues, and also provides a reference for the disulfide bond localization of peptides or proteins containing this complex disulfide bond.

STABILITY TOLERANCE OF SUNFLOWER OIL -IN-WATER EMULSION EMULSIFIED BY SOYA LECITHIN FOR FOOD GRADE ACIDS

Oil-in-water emulsion has promised values in food, pharmaceutical, drug, cosmetic and allied industries. The stable emulsion with long shelf life increases its utility. Many avouring agents are used to increase shelf life as preservative or commercial value. Food grade acids are used to in the emulsion preparation which enhances the taste or avour. The present study focuses the usage of acetic acid, phosphoric acid and oxalic acid. The emulsions for different acids are prepared ranging concentration from 0.001 to 0.003M using lecithin as emulsier and sunower oil. Experiments were done to study organoleptic properties with respect to basicity and dissociation constant values. The colour of the primary emulsion was creamy white and sustainable for acetic acid emulsion to 28 day at experimental temperature 10, 25 and 40 0C. Oxalic acid is recorded a low pH value 1.88 for 0.003 M emulsion solution in compare with acetic acid (3.63) and phosphoric acid (2.32).The relative conductance measurement for oxalic acid shows a very high value 5.6mS to acetic acid 0.257mS and phosphoric acid 0.247 mS. The rst dissociation constant value 5.6x10-2 of oxalic acid is larger relatively compare to phosphoric acid 7.5 x 10-3 and acetic acid 1.8 x10-5. Basicity of acids increases from acetic acid (mono basic), oxalic acid (dibasic) to phosphoric acid (tri-basic).These results strongly supports that basicity and dissociation constant values of acids conspicuously inuence the stability of the emulsion. Higher value of dissociation constant value and basicity, lower the stability of the emulsion.

Dissociative Experiences Scale: Psychometric Analysis in Puerto Rico and Contributions to the Discussion of the Factor Structure / Escala de Experiencias Disociativas: Análisis Psicométrico en Puerto Rico y Aportaciones a la Discusión sobre la Estructura Factorial

Introduction: The Dissociative Experiences Scale (DES-II) is a widely used psychometric tool to assess dissociative symptoms. Over the years, it has been the subject of numerous studies and research in various fields of psychology and psychiatry. Numerous studies have supported the validity and reliability of the DES-II as a reliable measure of dissociative experiences. The most problematic aspect of the DES-II is the inconsistency in its factor structure. Objective: This research aimed to examine the psychometric properties of the DES-II in a clinical and non-clinical sample from Puerto Rico. Method: This research had an instrumental design. An availability sampling of 341 adult participants was used. Several competing models of the DES-II were analyzed, including a bifactor model. Result: Psychometric analyses concluded that the scale has a unidimensional structure, strong reliability, and construct validity. All 28 items met adequate discrimination values. Participants with dissociative disorders obtained higher means on the DES-II than the other diagnostic groups. Furthermore, the more adverse experiences in childhood, the more dissociative experiences in adulthood. Conclusion: The DES-II should be treated and interpreted as a unidimensional dissociation index rather than a multidimensional instrument. This study will advance further research on dissociation and dissociative disorders in Puerto Rico and Latin America.

Introducción: La Escala de Experiencias Disociativas (DES-II) es una herramienta psicométrica ampliamente utilizada para evaluar síntomas disociativos. A lo largo de los años, ha sido objeto de numerosos estudios e investigaciones en diversos campos de la psicología y la psiquiatría. Numerosos estudios han respaldado la validez y la fiabilidad de la DES-II como una medida confiable de las experiencias disociativas. El aspecto más problemático del DES-II es la inconsistencia de su estructura factorial. Objetivo: Esta investigación tuvo como objetivo examinar las propiedades psicométricas de la DES-II en una muestra clínica y no clínica de Puerto Rico. Método: Esta investigación tuvo un diseño instrumental. Se utilizó un muestreo por disponibilidad compuesto por 341 participantes adultos. Se analizaron varios modelos competitivos de la DES-II, incluyendo un modelo bifactorial. Resultados: Los análisis psicométricos concluyeron que la escala posee una estructura unidimensional y una sólida confiabilidad y validez de constructo. Los 28 ítems cumplieron con valores adecuados de discriminación. Los participantes con trastornos disociativos obtuvieron medias más altas en la DES-II que los otros grupos diagnósticos. Además, a mayores experiencias adversas en la infancia, mayores experiencias disociativas en la adultez. Conclusión: La DES-II debería tratarse e interpretarse como un índice unidimensional de disociación y no como un instrumento multidimensional. Este estudio permitirá el avance de nuevas investigaciones sobre disociación y trastornos disociativos en Puerto Rico y América Latina.

Development of flow cytometry and its application in plant research / 生物工程学报

Flow cytometry is a multi-parameter, rapid and efficient method for qualitative analysis and quantitative determination of various fluorescently labeled particles in liquid flow. Flow cytometry has been applied in multiple disciplines such as immunology, virology, molecular biology, cancer biology and infectious disease monitoring. However, the application of flow cytometry in plant research is hampered due to the special composition and structure of plant tissues and cells, such as cell walls and secondary metabolites. In this paper, the development, composition and classification of flow cytometry were introduced. Subsequently, the application, research progress and application limitations of flow cytometry in plant field were discussed. At last, the development trend of flow cytometry in plant research was prospected, which provides new perspectives for broadening the potential application scope of plant flow cytometry.

Pharmacological inhibition of BAP1 recruits HERC2 to competitively dissociate BRCA1-BARD1, suppresses DNA repair and sensitizes CRC to radiotherapy

Radiotherapy is widely used in the management of advanced colorectal cancer (CRC). However, the clinical efficacy is limited by the safe irradiated dose. Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation. The BRCA1-BARD1 complex has been demonstrated to play a critical role in homologous recombination (HR) DSB repair, and its functions may be affected by HERC2 or BAP1. Accumulated evidence illustrates that the ubiquitination-deubiquitination balance is involved in these processes; however, the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn't been defined. Through activity-based profiling, we identified PT33 as an active entity for HR repair suppression. Subsequently, we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen. Mechanistically, pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction, interrupting HR repair. Consequently, PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo. Overall, these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain.

Muito além do trauma: uma investigação sobre o papel das reações peritraumáticas sobre o transtorno de estresse pós-traumático / Beyond the trauma: an investigation of the role of peritraumatic reactions on posttraumatic stress disorder

O Transtorno de Estresse Pós-Traumático (TEPT) é uma condição debilitante que impacta significativamente a qualidade de vida dos seus portadores. Dentre vários fatores de risco para o TEPT, as reações peritraumáticas (RP), como a imobilidade tônica peritraumática (ITP), dissociação (DP) e reações físicas de pânico (RFP), estão entre as mais investigadas. No entanto, a maioria dos estudos avaliou essas RP separadamente, e o elo entre elas e o TEPT ainda não foi bem compreendido. Portanto, essa tese teve como objetivos: (i) estimar simultaneamente o efeito das três RP sobre o TEPT utilizando um instrumento validado; e (ii) avaliar se há efeito indireto da ITP sobre o TEPT mediado pelo sentimento de culpa/vergonha. Utilizamos modelagem de equações estruturais para analisar dados de 3211 participantes do Rio de Janeiro e de São Paulo. Tratamos as RP como variáveis latentes, selecionando desconfundidores específicos para cada reação. Nossas exposições foram as RP, sendo TEPT o desfecho. Calculamos odds ratios e intervalos de confiança de 95%. Utilizamos o Bayesian Information Criterion para comparar o ajuste de modelos não aninhados. Quando analisadas separadamente, todas as RP alcançaram significância estatística. No entanto, apenas DP (ORDP=1,8; IC95%:1,3-2,4) e RFP (ORRFP=2,5; IC95%:1,8-3,4) permaneceram estatisticamente significativas quando incluímos as três reações em um modelo com seus respectivos desconfundidores e correlações entre elas. Os resultados sugeriram um possível efeito da ITP sobre o TEPT (ORITP=1,4; IC95%:1,0-1,9). As interações entre as RP não foram estatisticamente significativas. Ao investigarmos o sentimento de culpa/vergonha como mediador entre ITP e TEPT, o efeito indireto alcançou apenas significância estatística limítrofe (ORITP(TNIE)=1,1; IC95%:1,0-1,2). Os efeitos direto (ORITP(PNDE)=1,3; IC95%: 0,8-1,8) e total (ORITP(TE)=1,4; IC95%:0,9-1,9) para ITP perderam significância quando todas as RP, seus desconfundidores e correlações entre elas fizeram parte do mesmo modelo. As demais RP, no entanto, permaneceram estatisticamente significativas (ORDP=1,7; IC95%:1,3-2,3 e ORRFP=2,5; IC95%:1,8-3,4). Nossos resultados mostraram que a DP e as RFP aumentaram o risco de TEPT mesmo quando consideradas em conjunto. A ITP pode ter efeito sobre o risco de TEPT, mas esse achado deve ser interpretado com cautela devido a significância limítrofe dessa RP em nosso modelo final. Também não identificamos uma mediação significativa entre ITP e TEPT pelos sentimentos de culpa/vergonha. Contudo, a significância limítrofe encontrada para o efeito indireto demanda investigações adicionais. Nossos achados reforçam a ideia de que as reações peritraumáticas devem ser analisadas e compreendidas como ocorrências simultâneas. Também seria oportuno que estudos envolvendo culpa/vergonha, ITP e TEPT focalizassem traumas caracterizados por aprisionamento e impossibilidade de escapar, dado que estas experiências são apontadas como mais susceptíveis para desencadear a ITP. (AU)

Posttraumatic stress disorder (PTSD) is a debilitating condition that greatly impacts quality of life. Among several PTSD risk factors, peritraumatic reactions (PR) such as peritraumatic tonic immobility (PTI), dissociation (PD) and physical panic reactions (PPR) are some of the most investigated. However, several studies have assessed these PR separately, and the pathway connecting them to PTSD is not well understood. Therefore, this thesis aimed to: (i) simultaneously estimate the effect of the three PR on PTSD using a validated instrument; and (ii) assess if there is an indirect effect of PTI on PTSD mediated by feelings of guilt/shame. We used structural equation modelling to analyse data from 3211 participants from Rio de Janeiro and São Paulo. We treated the PR as latent variables and selected specific confounders for each reaction. Our exposures were the PR, and PTSD was the outcome. We calculated odds ratios and 95% confidence intervals for each analysis. We also employed the Bayesian Information Criterion to compare the goodness of fit between non-nested models. Separately, all PR achieved statistically significant results. However, only PD (ORPD=1.8; 95%CI:1.3-2.4) and PPR (ORPPR=2.5; 95%CI:1.8-3.4) remained statistically significant when all three were included in a model with their respective confounders and correlations among all PR. Our findings suggested a possible effect of PTI on PTSD (ORPTI=1.4; 95%CI:1.0-1.9). Interactions between the PR were not statistically significant. When we investigated feelings of guilt/shame as the mediator between PTI and PTSD, the indirect effect achieved a borderline statistical significance (ORPTI(TNIE)=1.1; 95%CI:1.0-1.2). Direct (ORPTI(PNDE)=1.3; 95%CI:0.8-1.8) and total (ORPTI(TE)=1.4; 95%CI:0.9-1.9) effects lost their significance when all PR, their confounders and correlations were included in the same model. The other PR remained statistically significant (ORPD=1.7; 95%CI:1.3-2.3 and ORPPR=2.5; 95%CI:1.8-3.4). Our findings showed PD and PPR to increase the risk of PTSD even when considered in tandem. PTI could have an effect on PTSD, but this must be considered cautiously, as this PR only reached borderline significance in our final model. Feelings of guilt/shame did not significantly mediate PTI's effect on PTSD. However, a borderline statistical significance in the indirect effects warrants further investigation. Our findings reinforce the hypothesis that peritraumatic reactions should be analysed and understood as simultaneous occurrences, not as separate entities. It would also be appropriate for studies concerning guilt/shame, PTI and PTSD to focus on traumas characterized by imprisonment and feelings of inescapability, given that these experiences are allegedly more likely to trigger PTI. (AU)

A rare young case of Foix Chavany Marie syndrome

Foix Chavany Marie syndrome, also called as bilateral opercular syndrome (OPS) was first described in 1837 by Magnus and further defined by Foix, Chavany and Marie in 1926 after whom it was named so. Here, we present a case of 37-year-old female, with known recurrent CVA who presented with sudden onset aphasia, dysphagia and difficulty in opening and closing her mouth and drooling of saliva. On imaging, patient was found to have ischemia of bilateral operculum.

Trauma y amnesia disociativa: la visión de Pierre Janet / Trauma and dissociative amnesia: Pierre Janet's vision

RESUMEN Se señala la importancia de reconsiderar el trabajo de Pierre Janet en trauma y amnesia disociativa, como elementos importantes en el estudio actual del trastorno de estrés postraumático (TEPT). Los objetivos de esta revisión histórica no sistemática y comparativa son: a) explicar, desde la perspectiva de Janet: el concepto de Idea Fija, que hoy denominamos trauma b) describir los diferentes tipos de amnesia en las cuales se basa el DSM para su clasificación actual y c) a través de un caso clínico descrito por Janet, mostrar su concordancia con lo que actualmente diagnosticamos como TEPT complejo, que denominó en su época: "una de las formas que puede tomar la histeria después de un accidente emocional". Esta revisión se basa principalmente en algunos capítulos originales de Janet publicados en Francés.

The present article gives emphasis in reconsidering the work of Pierre Janet in trauma and dissociative amnesia, as important aspects for the contemporary study of posttraumatic stress disorder (PTSD). The purpose of this non systematic historical review is to explain the following ideas under Janet´s perspective: a) the concept of fixed idea, denominated in our contemporary nomenclature as trauma, b) to describe the different types of amnesia described by Janet and its relation with DSM clasiffication for this penomenon, and c) to show through the analysis of a clinical case described by Janet, how a concordance exists between the current denomination of complex PTSD and what Janet nominated "one of the forms in which hysteria can presents after an emotional accident". This article is mainly based in some original chapters from Janet´s work published in French.

A rare presentation of Guillain-Barre syndrome with GQ1b positivity: A case report

Rationale: To report a case of cervicobrachial variant of acute inflammatory demyelinating polyneuropathy presenting with papilledema and GQ1b positivity. Patient concern: A 35-year-old female, 68 days postpartum, presented with headache, vomiting, and gait difficulty in swallowing with bilateral upper limb weakness and difficulty in walking, 13 days after ChAdOx1 nCoV-19 vaccination. Diagnosis: Guillain-Barre syndrome with GQ1b positivity. Intervention: Five cycles of plasmapheresis were given. Outcome: The patient's clinical condition improved. Palatal weakness improved and she could walk without support. There were mild sensory symptoms involving upper limbs which gradually improved. Lessons: AIDP should be considered in case of weakness following ChAdOx1 nCoV-19 vaccination. Albumino-cytological dissociation and anti-GQ1b positivity are needed to confirmed the diagnosis.

Experiências mediúnicas e dissociativas em Fernando Pessoa e C. G. Jung à luz da psicologia analítica e da psicologia anomalística / Mediumistic and dissociative experiences in Fernando Pessoa and C. G. Jung in light of analytical psychology and anomalistic psychology / Expériences médiumniques et dissociatives chez Fernando Pessoa et C. G. Jung à la lumière de la psychologie analytique et de la psychologie anomalistique / Experiencias mediúmnicas y disociativas en Fernando Pessoa y C. G. Jung a la luz de la psicología analítica y de la psicología anómala

Resumo O poeta Fernando Pessoa e o psiquiatra C. G. Jung desenvolveram suas obras em consonância com suas biografias. Ambos descreveram episódios que podem ser interpretados como mediúnicos, buscando, também, compreendê-los psicologicamente. Na literatura psicológica atual, a mediunidade pode ser entendida por meio do conceito de dissociação da personalidade. Dessa maneira, este artigo buscou examinar as relações entre dissociação e mediunidade a partir de episódios biográficos de Pessoa e de Jung, à luz da psicologia analítica e da psicologia anomalística. Hipotetiza-se que eles vivenciaram experiências dissociativas criativas e não patológicas, embora algum nível de sofrimento estivesse envolvido. Em Pessoa, as experiências dissociativas são relacionadas com sua produção hetoronímica, enquanto em Jung e suas investigações, com o desenvolvimento de seu modelo psicológico, que oferece elementos para um estudo psicobiográfico e artístico do poeta.

Abstract Poet Fernando Pessoa and psychiatrist C. G. Jung developed their works consonant with their biographies. Both described episodes that can be interpreted as mediumistic, seeking to understand them psychologically. In current psychological literature, mediumship is associated to the concept of personality dissociation. In this regard, this article examines the relationship between dissociation and mediumship based on Pessoa's and Jung's biographical episodes, in light of analytical psychology and anomalistic psychology. It is hypothesized that they experienced creative, non-pathological dissociations, although some level of suffering was involved. Pessoa's experiences are related to his hetoronymic production, whereas Jung's are tied with the development of his psychological model, which offers elements for a psychobiographical and artistic study of the poet.

Resumé Le poète Fernando Pessoa et le psychiatre C. G. Jung ont développé leurs œuvres en accord avec leurs biographies. Tous deux ont décrit des épisodes qui peuvent être interprétés comme médiumniques, en cherchant à les comprendre psychologiquement. Dans la littérature psychologique actuelle, la médiumnité est associée au concept de dissociation de la personnalité. À cet égard, cet article examine la relation entre dissociation et médiumnité à partir des épisodes biographiques de Pessoa et de Jung, à la lumière de la psychologie analytique et de la psychologie anomalistique. L'hypothèse est qu'ils ont fait l'expérience de dissociations créatives et non pathologiques, bien qu'un certain niveau de souffrance y ait été impliqué. Chez Pessoa, ces expériences sont liées à sa production hétéronymique, tandis que chez Jung, elles sont liées au développement de son modèle psychologique, ce qui offre des éléments pour une étude psychobiographique et artistic du poète.

Resumen El poeta Fernando Pessoa y el psiquiatra C. G. Jung desarrollaron sus obras en consonancia con sus biografías. Ambos describieron episodios que pueden interpretarse como mediúmnicos, también buscando comprenderlos psicológicamente. En la literatura de la psicología actual, la mediumnidad puede entenderse bajo el concepto de disociación de la personalidad. Así, este artículo buscó examinar la relación entre disociación y mediumnidad a partir de los episodios biográficos de Pessoa y Jung, a la luz de la psicología analítica y la psicología anomalística. La hipótesis supone que estos autores tuvieron experiencias disociativas creativas y no patológicas, aunque estas involucraron cierto nivel de sufrimiento. En Pessoa, las experiencias se relacionan con su producción de la heteronimia; y en Jung, con el desarrollo de su modelo psicológico, que ofrece elementos para un estudio psicobiográfico y artístico del poeta.

Alteraciones atípicas del líquido cefalorraquídeo en el Síndrome de Guillain-Barré: Reporte de casos / Atypical Alterations of cerebrospinal fluid in Guillain Barré Syndrome: Cases Reports

RESUMEN El síndrome de Guillain-Barré se caracteriza por presentar una disociación albúmino-citológica en la mayoría de pacientes. La presencia de pleocitosis o hipoglucorraquia puede alejar el diagnóstico, por lo que se recomienda descartar, principalmente, causas infecciosas. Se presentan tres casos cuyos estudios de líquido cefalorraquídeo mostraron pleocitosis linfocítica e hiperproteinorraquia persistente y uno de ellos, además, hipoglucorraquia; fue solamente en análisis posteriores que los tres pacientes presentaron la clásica disociación albuminocitológica. El estudio neurofisiológico en todos ellos demostró asimismo un compromiso axonal. Las alteraciones atípicas en el contexto de parálisis flácida aguda justificarían repetir el análisis de líquido cefalorraquídeo y descartar otras etiologías, pero sin posponer en modo alguno el tratamiento.

SUMMARY Guillain-Barré syndrome shows a cyto-albuminologic dissociation in most patients. Pleocytosis or hypoglycorrhachia may defer the diagnosis, a reason for which an infectious etiology must be ruled out. Three cases of Guillain-Barré are described, whose cerebrospinal fluid tests showed limphocytic pleocytosis and persistently elevated protein concentration, while one of the cases also showed hypoglycorrhachia, and the classic cyto-albuminologic dissociation was only demonstrated in subsequent analysis. The neurophysiologic evaluation revealed an axonal disruption in all the patients. The atypical alterations in the context of acute flaccid paralysis warrant a retesting of the cerebrospinal fluid in order to rule out other etiologies, but without postponing the start of treatment.

Insight into chemical basis of traditional Chinese medicine based on the state-of-the-art techniques of liquid chromatography-mass spectrometry

Traditional Chinese medicine (TCM) has been an indispensable source of drugs for curing various human diseases. However, the inherent chemical diversity and complexity of TCM restricted the safety and efficacy of its usage. Over the past few decades, the combination of liquid chromatography with mass spectrometry has contributed greatly to the TCM qualitative analysis. And novel approaches have been continuously introduced to improve the analytical performance, including both the data acquisition methods to generate a large and informative dataset, and the data post-processing tools to extract the structure-related MS information. Furthermore, the fast-developing computer techniques and big data analytics have markedly enriched the data processing tools, bringing benefits of high efficiency and accuracy. To provide an up-to-date review of the latest techniques on the TCM qualitative analysis, multiple data-independent acquisition methods and data-dependent acquisition methods (precursor ion list, dynamic exclusion, mass tag, precursor ion scan, neutral loss scan, and multiple reaction monitoring) and post-processing techniques (mass defect filtering, diagnostic ion filtering, neutral loss filtering, mass spectral trees similarity filter, molecular networking, statistical analysis, database matching, etc.) were summarized and categorized. Applications of each technique and integrated analytical strategies were highlighted, discussion and future perspectives were proposed as well.

Simulation Analysis of Occupancy Rates of Baicalein， Quercetin and Galangin on Target Sites of Xanthine Oxidase / 中国实验方剂学杂志

Objective:To simulate the occupancy rates of baicalein， quercetin and galangin on the target sites of xanthine oxidase <italic>in vivo</italic>. Method:In this experiment， the half inhibitory concentration （IC₅₀） of febuxostat， baicalein， quercetin and galangin against xanthine oxidase were determined by <italic>in vitro</italic> enzymatic reaction. Binding free energy was predicted by molecular docking technology and their association rate constant （k_on） and dissociation rate constant （k_off） were determined by surface plasmon resonance technology. Based on measured binding kinetic parameters （k_on and k_off） and extracted pharmacokinetic data， the target occupancy model <italic>in vivo</italic> was established. Result:The IC₅₀values of febuxostat， baicalein， quercetin and galangin were 0.002 7， 1.63， 0.38， 1.59 µmol·L^-1， respectively. The IC₅₀ of febuxostat was very close to that reported in the literature. The predicted curve of target occupancy rate <italic>in vivo</italic> of febuxostat was consistent with its duration of clinical efficacy. When single intragastric administration of long-circulating liposomes of quercetin with dose of 100 mg·kg^-1 in rats， the time of target occupancy rate >70% <italic>in vivo</italic> lasted for about 3.9 h. When rats were orally administered baicalein and galangin with dose of 200 mg·kg^-1， the time of target occupancy rate >50% <italic>in vivo </italic>lasted for about 10 h and 1.7 h， respectively. Conclusion:The prediction model of xanthine oxidase target occupancy constructed by drug target binding kinetics and <italic>in vivo</italic> pharmacokinetic curves can effectively evaluate the <italic>in vivo</italic> inhibitory activity of compounds against the target.

Construction of Rho GDIa-sgRNAs plasmids by clustered regularly interspaced short palindromic repeats/associated protein 9 and the effect on migration of Hepa 1-6 cell line in mouse / 解剖学报

Objective To construct the recombinant plasmids of knocking down Rho guanine dissociation inhibitor α (GDIα ) gene by using clustered regularly interspaced short palindromic repeats/associated protein 9 (CRISPR/Cas9) technique, and investigate the effect of Rho GDIα interference on the migration of Hepa 1-6 cells of mouse in order to provide the method of prevention and treatment of liver cancer. Methods To construct and identify the PX458-Rho GDIα-single guide (sg) RNAs by using CRISPR/Cas9 technique. And the Hepa 1-6 cells were transfected by liposomes with PX458-Rho GDIα-sgRNAs for 48 hours respectively, and cells treated with PX458 plasmids were used as control. The migration ability of Hepa 1-6 was checked by wound healing assay and Transwell assay, respectively. Results The expression of Rho GDIα was depressed in group of PX458-Rho GDIα-sgRNAl transfection which was detected by using RT-PCR. The migration distance of Hepa 1-6 in PX458-Rho GDIα-sgRNAl transfection group was significantly promoted comparing with the control group which was transfected with PX458 only, and the cell number of PX458-Rho GDIα-sgRNAl group was more than that in control group by using transwell assay, indicating concluded that knocking down of Rho GDIα promoted the migration ability of Hepal-6 cells. Conclusion The result is explicit that in vivo, Rho GDIα may inhibit the migration of Hepal-6 partially. Overexpression of Rho GDIα might be used as an important method to prevent the metastasize of carcinoma.

The association between neurocognitive functioning and clinical features of borderline personality disorder

Objective: To investigate the relationship between neurocognitive profiles and clinical manifestations of borderline personality disorder (BPD). Methods: Forty-five patients diagnosed with BPD and 35 healthy volunteers were included in the study. The BPD group was evaluated with the Borderline Personality Inventory for dissociative, impulsivity and suicidal dimensions. The Verbal Memory Processes Test and the Cambridge Neurophysiological Assessment Battery were administered to both the BPD and healthy control groups. Results: BPD patients differed from controls in sustained attention, facial emotion recognition, and deteriorated verbal memory function. A model consisting of the Dissociative Experiences Scale - Taxon (DES-T), motor impulsivity and Scale for Suicidal Behavior scores explained 52% of the variance in Borderline Personality Inventory scores. It was detected that motor impulsivity, decision-making and recognizing sadness may significantly predict DES-T scores, and response inhibition and facial emotion recognition scores may significantly predict impulsivity. Conclusion: Our findings demonstrate that the disassociation, impulsivity, and suicidality dimensions are sufficient to represent the clinical manifestations of BPD, that they are related to neurocognitive differences, and that they interact with clinical features.

Mass Spectral Character of Fentanyl Analogues / 法医学杂志

Objective To provide the reference for the identification of unknown fentanyl analogues by studying the characteristic ions and main fragmentation pathways of fentanyl analogues in the modes of collision induced dissociation （CID） and electron ionization （EI）. Methods Nine fentanyl analogues （2, 2'-difluorofentanyl, acetyl fentanyl, fentanyl, butyl fentanyl, valeryl fentanyl, acryloyl fentanyl, furan fentanyl, 4-fluorine isobutyl fentanyl, carfentanyl） were selected and analyzed with ultra-high performance liquid chromatography-quadrupole time-of-flight-mass spectrometry （UHPLC-QTOF-MS） and gas chromatography-mass spectrometry （GC-MS）. The mass spectrum obtained was analyzed. The CID and EI fragmentation routes of fentanyl analogues were speculated. Results The CID and EI fragmentation pathways were highly similar. In the CID mode, characteristic ions were formed by the carbon-nitrogen bond cleavage between the piperidine ring and the N-phenyl-amide moiety, within the piperidine ring, and between the phenethyl and piperidine ring. While in the EI mode, dissociation of the piperidine ring, as well as cleavage between the piperidine ring and the phenethyl were the main fragmentation pathways. Conclusion This study summarizes the main fragmentation pathways and characteristic ions of fentanyl analogues in the CID and EI modes, which is useful for forensic laboratories to identify and structural analyze fentanyl type new psychoactive substance in practical work.

Is There Any Association Between Childhood Traumatic Experiences, Dissociation and Psychotic Symptoms in Schziophrenic Patients?

OBJECTIVE: The aim of this study was to investigate the rates childhood traumatic experiences (CTEs) of schizophrenia patients and to examine relationship between childhood traumatic experiences, dissociation and psychotic symptoms. METHODS: One hundred schizophrenia patients who had 5 or 5 points below in Clinical Global Impression-Severity (CGI-S) and who were not in active psychotic episode and 50 healthy siblings who grew up in the same environment with the patients were included to the study. Structured Clinical Interview for DSM IV, Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms, Dissociative Experiences Scale (DES), CGI-S, Global Assessment of Functioning Scale and Childhood Trauma Questionnaire (CTQ-28) applied to the patients. RESULTS: Childhood abuse subscales and DES scores were statistically higher in the patient group (p<0.001). We determined moderately significant positive correlation between CTQ-28 and DES. We determined moderately significant positive correlation between CTQ total scores and persecutory delusions, delusions of reference, ability to feel intimacy and closeness; relationship with friends and peers. Also, there was a significant positive correlation between persecutory delusions and CTQ-total, DES-total and all subscales of CTQ-28. CONCLUSION: Clinicians should inquire about CTEs to develop comprehensive formulations and treatment plans among schizophrenia.

Emphasis on the significance of "short hepatic portal vein" anatomy in perihepatic portal surgery / 中国实用外科杂志

Perihilar area is a clinically specific anatomical area centered on the confluence of the main portal vein with the left and right branches and bounded by the "H-shaped transverse sulcus" of the liver. Its anatomical structure is complex, involving the liver, gallbladder, regional lymph nodes and luminal systems such as portal vein, hepatic artery, bile duct and inferior vena cava. It is a difficult area in hepatobiliary surgery. Therefore, a reasonable surgical approach is of great importance. The anatomical approach strategy of "Glisson intrathecal dissociation" can clearly show the anatomical structure of various luminal systems in the perihilar area, reduce the risk of surgical error injury, and contribute to the rational individualized surgical plan decision and implementation. The short hepatic portal vein is a small branch of the main, right and left branches of the portal vein and their confluence, which distributes and travels in the transverse sulcus of the liver. The anatomical characteristics of the short hepatic portal vein should not be ignored in the implementation of "Glisson intrathecal dissociation" in the perihilar area.

Effect of sodium carboxymethyl starch on erythrocyte rheology and oxygen carrying function / 国际药学研究杂志

Objective: To investigate the physicochemical properties of sodium carboxymethyl starch(CMS) and its effect on erythrocyte rheology and oxygen carrying function. Methods According to the requirements of Chinese Pharmacopoeia,the physicochemical properties were determined for CMS120,CMS380 and hydroxyethyl starch 130 (HES130),including pH value,osmotic pressure molar concentration and viscosity. Normal saline,CMS120,CMS380 and HES130 were mixed with whole blood(7:3,V/V),respectively,and the experimental groups were set as whole blood group,whole blood+normal saline(NSB)group,whole blood+CMS120(CMS120B)group,whole blood+CMS380 (CMS380B)group,and whole blood+HES130(HES130B)group. The colloid osmotic pressure,blood viscosity,eryth- rocyte deformation and aggregation,and the partial pressure of oxygen when blood oxygen saturation was 50%(P50)val- ue were measured for each of these groups. Results: The osmotic pressure molar concentration and the viscosity of CMS120 and CMS380 were both significantly higher than those of HES130(all P<0.05)as indicated by the determina- tion of physicochemical properties. Compared with the whole blood group,the colloid osmotic pressure was significantly increased in the CMS380B and CMS120B groups(P<0.05),which was also significantly higher than that in the HES130B group(P<0.05). At low shear rate(10/s),compared with the whole blood group,the whole blood and the plasma vis- cosities were significantly increased in the NSB,CMS380B and CMS120B groups(all P<0.05),but the whole blood viscosity was significantly decreased in the HES130B group(P<0.05). Under the conditions of shear rate 10/s,50/s and 150/s,compared with the HBS130B group,the whole blood and the plasma viscosities were both significantly in- creased in the CMS120B and CMS380 groups(all P<0.05). At the effect of high shear rate,both the CMS380 and HES130 groups showed a tendency to promote erythrocyte deformation,and the CMS120B and CMS380B groups promot- ed erythrocyte aggregation,while the HES130B group inhibited erythrocyte aggregation amplitude(P<0.05). The P50 value was significantly higher in the CMS380B group than in the HES130B group(P<0.05). Conclusion: CMS130 and CMS380 could improve the rheological properties of erythrocytes and CMS380 could also promote the oxygen release of erythrocytes.

Solitary Nodular Invasive Mucinous Adenocarcinoma of the Lung: Imaging Diagnosis Using the Morphologic-Metabolic Dissociation Sign

OBJECTIVE: To evaluate the efficacy of the morphologic-metabolic (M-M) dissociation sign based on computed tomography (CT) and fluorine-18-fluorodeoxyglucose positron emission tomography (PET)/CT in discriminating invasive mucinous adenocarcinoma (IMA) from invasive non-mucinous adenocarcinomas (ADCs) of the lung. MATERIALS AND METHODS: The Institutional Review Board approved this retrospective study. Among surgically resected solitary pulmonary nodule (SPN)-type ADCs (< 3 cm in diameter), 35 patients with IMAs and 329 with invasive non-mucinous ADCs were included. Morphologic malignancy was established if the tumor with lobulated or spiculated margin on CT presented a tumor shadow disappearance rate of < 0.5. The M-M dissociation sign was determined when a malignant-morphologic nodule on CT showed maximum standardized uptake value (SUVmax) < 3.5 on PET/CT. RESULTS: Among 35 IMAs (size: 21 ± 7 mm, SUVmax: 1.8 ± 2.0) and 329 invasive non-mucinous ADCs (size: 21 ± 6 mm, SUVmax: 4.6 ± 4.2), the M-M dissociation sign was observed in 54% of IMAs (19/35) and 10% of invasive non-mucinous ADCs (34/329) (p < 0.001). The diagnostic performance of the sign in discriminating IMA from invasive non-mucinous ADCs showed a sensitivity of 54.3% (95% confidence interval [CI], 36.7–71.2), specificity 89.7% (95% CI, 85.9–92.7), positive predictive value 35.8% (95% CI, 26.5–46.5), and negative predictive value 94.9% (95% CI, 92.8–96.4). Multivariate analyses revealed metabolic benignity (odds ratio [OR] 2.99; 95% CI, 1.01–8.93; p = 0.047) and M-M dissociation sign (OR 6.35; 95% CI, 2.76–14.62; p < 0.001) to be significant predictors of SPN-type IMAs. CONCLUSION: Identification of the absence of M-M dissociation sign is an accurate indicator for excluding IMA from SPN-type lung ADCs.