Enzyme-linked immunosorbent assays for quantification of MMMAE-conjugated ADCs and total antibodies in cynomolgus monkey sera / 药物分析学报

Antibody-drug conjugates(ADCs)are commonly heterogeneous and require extensive assessment of exposure-efficacy and exposure-safety relationships in preclinical and clinical studies.In this study,we report the generation of a monoclonal antibody against monomethyl auristatin E(MMAE)and the development,validation,and application of sensitive and high-throughput enzyme-linked immunosor-bent assays(ELISA)to measure the concentrations of MMAE-conjugated ADCs and total antibodies(tAb,antibodies in ADC plus unconjugated antibodies)in cynomolgus monkey sera.These assays were suc-cessfully applied to in vitro plasma stability and pharmacokinetic(PK)studies of SMADC001,an MMAE-conjugated ADC against trophoblast cell surface antigen 2(TROP-2).The plasma stability of SMADC001 was better than that of similar ADCs coupled with PEG4-Val-Cit,Lys(m-dPEG24)-Cit,and Val-Cit linkers.The developed ELISA methods for the calibration standards of ADC and tAb revealed a correlation be-tween serum concentrations and the OD450 values,with R2 at 1.000,and the dynamic range was 0.3-35.0 ng/mL and 0.2-22.0 ng/mL,respectively;the intra-and inter-assay accuracy bias％ranged from-12.2％to-5.2％,precision ranged from-12.4％to-1.4％,and the relative standard deviation(RSD)was less than 6.6％and 8.7％,respectively.The total error was less than 20.4％.The development and validation steps of these two assays met the acceptance criteria for all addressed validation parameters,which suggested that these can be applied to quantify MMAE-conjugated ADCs,as well as in PK studies.Furthermore,these assays can be easily adopted for development of other similar immunoassays.

Analysis of differences between middle school and high school students help-seeking behaviors and association with non-suicidal self-injury / 中国学校卫生

Objective@#To understand and compare the differences in help-seeking behavior among junior high school students and senior high school students and their association with non-suicidal self-injury to provide a basis for the prevention and control of non-suicidal self-injury among middle school students.@*Methods@#Three middle schools in Nanchang were selected,and the survey were conducted among 4 434 students through the General Situation Questionnaire, the Ottawa Self-injury Judgment Entry, and the Middle School Students Help Seeking Behavior Questionnaire, and SPSS 22.0 was used for statistical analysis.@*Results@#The NSSI detection rate among middle school students was 33.3% , and junior high school students detection rate(36.0%) were higher than high school students(29.6%) (χ 2=19.41，P<0.01). Differences in willingness to ask for help, asking for help from family and teachers, and talking face-to-face for help were statistically significant (all P<0.01) among NSSI participants and non-NSSI participants, for both junior high school and high school students. Females (OR=1.45), class cadres (OR=1.26), urban household registration (OR=1.45), frequent scolding by elders (OR=1.98) and a high academic burden (OR=1.39) all possible increased the risk of NSSI in junior high school students, while assistance to family members (OR=0.95) or teachers (OR=0.95) possible reduced the risk of NSSI in junior high school students. Females (OR=1.50), class cadres (OR=1.34), only children (OR=1.45), fathers with college education and above (compared to junior high school and below) (OR=1.56), frequent scolding by elders (OR=2.08), frequent corporal punishment from elders (OR=4.12) and high academic burden (OR=1.38) possibly increased the risk of NSSI among high school students, while willingness to ask for help (OR=0.82), asking for help from family (OR=0.95) and teachers (OR=0.96) possible reduced the risk of NSSI among high school students.@*Conclusion@#There are some differences in help-seeking behavior between junior and high school students, and school and parents should actively focus on middle school students help-seeking behavior and encourage them to seek help.

Prevalence of suicidal plans among college students in mainland China: a Metaanalysis / 中国学校卫生

Objective@#The metaanalysis aims to estimate the prevalence of suicide plan among college students in mainland China, and to provide more clues and reference for control and prevention of suicide.@*Methods@#The relevant studies were systematically searched via electronic databases (PubMed，Embase，CNKI，Wan Fang Data，VIP). We only selected original articles that either reported on Chinese retrieval words of "college students" "undergraduate" "university" "college" "colleges and universities" "suicide plans" "detection rate" "prevalence" "report rate", and the English retrieval words of "undergraduate" "college" "university" "suicide" "suicidality" "suicide plans" "suicidal plans suicide intending" "prevalence" "report rate" "detection rate" "China" "Chinese". And Stata 12.0 software was used to make a metaanalysis of the data.@*Results@#A total of 18 eligible studies, with 47 071 college students, were finally included. The maximum and minimum reported prevalence of suicidal plan among college students in China mainland was 4.4%(95%CI: 3.4%-5.4%).Subgroup analyses showed that the pooled estimate of suicidal plan of boys(5.4%) was higher than girls’(4.2%); The prevalence among college students from earth, middle and west areas were 5.1%，2.7%，4.5%, respectively; The prevalence among college students in 2010 and after (4.4%)was higher than that before 2010(4.3%), The prevalence among college students of life time suicide plan (4.9%)was higher than that during the past 12 months(4.0%), but there was no statistical significance in the subgroup(P>0.05) . Sensitivity analysis suggested that the results of metaanalysis were relatively stable, while funnel plot analysis suggested that publication bias might exist.@*Conclusion@#Prevalence of suicidal plans among college students in mainland China is respectively low, and there was no statistical significance in gender, region, the period of time and simple size.

Endoscopic observation of different repair patterns in human traumatic tympanic membrane perforations / Observação endoscópica de diferentes padrões de reparo em perfurações humanas traumáticas da membrana timpânica

Abstract Introduction: In the last decade, there has been an increasing use of biomaterial patches in the regeneration of traumatic tympanic membrane perforations. The major advantages of biomaterial patches are to provisionally restore the physiological function of the middle ear, thereby immediately improving ear symptoms, and act as a scaffold for epithelium migration. However, whether there are additional biological effects on eardrum regeneration is unclear for biological material patching in the clinic. Objective: This study evaluated the healing response for different repair patterns in human traumatic tympanic membrane perforations by endoscopic observation. Methods: In total, 114 patients with traumatic tympanic membrane perforations were allocated sequentially to two groups: the spontaneous healing group (n = 57) and Gelfoam patch-treated group (n = 57). The closure rate, closure time, and rate of otorrhea were compared between the groups at 3 months. Results: Ultimately, 107 patients were analyzed in the two groups (52 patients in the spontaneous healing group vs. 55 patients in the Gelfoam patch-treated group). The overall closure rate at the end of the 3 month follow-up period was 90.4% in the spontaneous healing group and 94.5% in the Gelfoam patch-treated group; the difference was not statistically significant (p > 0.05). However, the total average closure time was significantly different between the two groups (26.8 ± 9.1 days in the spontaneous healing group vs. 14.7 ± 9.1 days in the Gelfoam patch-treated group, p < 0.01). In addition, the closure rate was not significantly different between the spontaneous healing group and Gelfoam patch-treated group regardless of the perforation size. The closure time in the Gelfoam patch-treated group was significantly shorter than that in the spontaneous healing group regardless of the perforation size (small perforations: 7.1 ± 1.6 days vs. 12.6 ± 3.9, medium-sized perforations: 13.3 ± 2.2 days vs. 21.8 ± 4.2 days, and large perforations: 21.2 ± 4.7 days vs. 38.4 ± 5.7 days; p < 0.01). Conclusion: In the regeneration of traumatic tympanic membrane perforations, Gelfoam patching not only plays a scaffolding role for epithelial migration, it also promotes edema and hyperplasia of granulation tissue at the edges of the perforation and accelerates eardrum healing.

Resumo Introdução: Na última década, houve um uso crescente de placas biomateriais na regeneração de perfurações traumáticas da membrana timpânica. As principais vantagens das placas de biomateriais são restaurar provisoriamente a função fisiológica da orelha média, assim melhoram imediatamente os sintomas da orelha e atuam como um suporte para a migração do epitélio. No entanto, não se sabe se há efeitos clínicos adicionais na regeneração do tímpano em relação ao fragmento de material biológico. Objetivo: Avaliar a resposta de cicatrização para diferentes padrões de reparo em perfurações de membrana timpânica traumáticas humanas por meio de observação endoscópica. Método: Foram alocados 114 pacientes com perfurações de membrana timpânica traumáticas sequencialmente para dois grupos: o de cicatrização espontânea (n = 57) e o tratado com esponja de Gelfoam (n = 57). A velocidade de fechamento, o tempo de fechamento e a taxa de otorreia foram comparados entre os grupos aos três meses. Resultados: Foram analisados 107 pacientes nos dois grupos (52 no de cicatrização espontânea e 55 no tratado com esponja de Gelfoam). A velocidade global de fechamento no fim do período de seguimento de três meses foi de 90,4% no grupo de cicatrização espontânea e de 94,5% no grupo tratado com esponja de Gelfoam; a diferença não foi estatisticamente significativa (p > 0,05). No entanto, o tempo total médio de fechamento foi significativamente diferente entre os dois grupos (26,8 ± 9,1 dias no de cicatrização espontânea versus 14,7 ± 9,1 dias no tratado com esponja de Gelfoam, p < 0,01). Além disso, a velocidade de fechamento não foi significativamente diferente entre o grupo de cicatrização espontânea e o grupo tratado com esponja de Gelfoam, independentemente do tamanho da perfuração. O tempo de fechamento no grupo tratado com esponjas de Gelfoam foi significativamente menor do que no grupo de cicatrização espontânea, independentemente do tamanho da perfuração (pequenas perfurações: 7,1 ± 1,6 dias vs. 12,6 ± 3,9, perfurações de tamanho médio: 13,3 ± 2,2 dias vs. 21,8 ± 4,2 dias e grandes perfurações: 21,2 ± 4,7 dias vs. 38,4 ± 5,7 dias; p < 0,01). Conclusão: Na regeneração de PMT traumáticas, a esponja de Gelfoam não só desempenha um papel de estrutura para a migração epitelial, mas também promove edema e hiperplasia de tecido de granulação nas bordas da perfuração e acelera a cicatrização do tímpano.

Treatment of chronic mallet finger deformity with minor bone anchors and palmaris longus tendon graft / 中国骨伤

<p><b>OBJECTIVE</b>To explore the clinical effects of minor bone anchors and palmaris longus tendon graft in treating chronic mallet fingers deformity.</p><p><b>METHODS</b>From January 2008 to June 2013, 26 patients with chronic mallet fingers deformity were treated with minor bone anchors and palmaris longus tendon graft. There were 18 males and 8 females, aged from 18 to 52 years old with an average of (32.0±1.3) years. Among them, 8 cases caused by machine injury, 6 cases by fall injury, 6 cases by sprain from fight, 4 cases by tendon spontaneous rupture, 2 cases by knife trauma. There was no tendon attachment of extensor tendon check in 16 cases, and with 0.3 to 0.5 cm tendon attachment in 10 cases. All patients had the flexion deformity and the disability of dorsiflexion activity. During operation, the distal interphalangeal joint was fixed in 10° to 20° dorsiflexion by a Kirshner wire, the minor bone anchor was used to reconstruct the extensor tendon insertion, the palmaris longus tendon slice was transplanted the decayed area of extensor tendon insertion. Four weeks postoperatively, the Kirshner wire was removed and the plaster external fixation was used, and the patient began function exercises. Postoperative complications were observed and fingers functions were assessed according to Dargan standard.</p><p><b>RESULTS</b>The patients were followed up from 6 to 14 months with an average of (5.0±0.3) months. Wound superficial infection occurred in 2 cases, the skin pressure ulcer in 2 cases, joint activities disability in 1 case; these symptoms got improvement after symptomatic treatment. Traumatic arthritis occurred in 2 cases, 1 case was improved after treatment, and 1 case had chronic pain for a long time. No internal fixation loosening or breakage and tendon rupture were found. According to Dargan standard to evaluate the finger function, 17 cases got excellent results, 8 good, and 1 poor.</p><p><b>CONCLUSION</b>It is an effective way to treat the chronic mallet finger deformity using minor bone anchors and palmaris longus tendon graft, and the method has advantages of reliable fixation, easy operation, satisfactory effect and less complication.</p>

A study of the related factors about acute stress responses of the military freshmen / 中华行为医学与脑科学杂志

Objective To explore the related factors about acute stress responses of the military freshmen,then built a path model among self-efficacy,social support,coping style,state-trait anxiety and acute stress responses.Methods 584 students were tested by General Self-efficacy Scale (GSES),Perceived Social Support Scale (PSSS),Coping Styles Questionnaire,State-Trait Anxiety Inventory (STAI) and Acute Stress Response Scale ( ASP S).Results ①The military freshmen in each factor of acute stress response got a lower score,especially the mean score of the changes of cognition was higher (0.21 ±0.21 ),compared with the other factors,and the changes of pathology (0.053 ±0.114) was lower.②There were significant correlations between self-efficacy,social support,positive coping,negative coping,state anxiety,trait anxiety and acute stress responses (P ＜ 0.01 ).③ Negative coping( r=0.130),trait anxiety(r=0.005) and state anxiety(r=0.002) influenced ASR directly,meanwhile,self-efficacy( r =-1.292) influenced ASR through the state anxiety indirectly,self-efficacy ( r=-7.465 ) and social support ( r =-0.294) influenced ASR indirectly through trait anxiety.Conclusion Acute stress responses of the military freshmen were directly influenced by negative coping and state-trait anxiety,and negative coping style was the main reason.

O que há de errado no tratamento da pioartrite do quadril? / What is wrong in the treatment of hip pyoarthritis?

O trabalho visa chamar a atençäo sobre a incidência da pioartrite do quadril no Departamento de Ortopedia e Traumatologia da Faculdade de Medicina da Universidade de Säo Paulo e concluimos que seu tratamento nos parece ainda insuficiente e inadequado, em face da elevada proporçäo de maus resultados