头颈部鳞癌程序性死亡配体-1的共表达基因及 调控网络的生物信息学分析

目的 运用生物信息学的方法绘制头颈部鳞癌（HNSCC）中程序性死亡配体-1（PD-L1）共表达基因关系网络,筛选潜在的PD-L1的协同标志物,寻找可能的PD-L1基因调控肿瘤免疫状态的基因和通路。方法 利用癌症和肿瘤基因图谱（TCGA）中的大样本HNSCC的转录组学数据,在cBioPortal数据平台进行基因集的检索,筛选PD-L1共表达基因,在R语言的clusterProfiler中进行GO-BP和KEGG富集分析,再进行分子关系网络分析,提取重要节点基因（hub基因）,再进行生存分析。结果 筛选出共表达基因117个,共表达基因主要富集在免疫调节和病毒反应过程。网络节度分析得到了10个hub基因,依次为STAT1、IFNG、CXCL10、CCR5、FCGR3A、CXCL9、GBP5、CD86、GZMB、IRF1。生存分析显示：CCR5、CXCL9、GZMB是HNSCC预后相关的重要基因。这些基因均参与了免疫过程,其表达与PD-L1相关（Pearson相关系数为0.30、0.35、0.39,P值均小于0.01）。这些基因高表达在HNSCC中均为保护因素。结论 HNSCC中的PD-L1共表达的主要基因均为免疫相关基因,其中CCR5、CXCL9、GZMB与PD-L1存在共表达关系,与预后相关,其可能与程序性死亡受体-1（PD-1）/PD-L1介导的肿瘤免疫逃避相关,为进一步研究PD-1/PD-L1的作用机制和精准靶向治疗提供了新的参考。     

Refining amyloid complete hematological response: Quantitative serum free light chains superior to ratio

Response assessment in light chain (AL) amyloidosis is based on serum and urine monoclonal protein studies. Newly diagnosed patients (n = 373) who achieved very good partial response or complete response (CR) to first line therapy were assessed for the survival impact of each of the monoclonal protein studies. At end of therapy (EOT), negative serum/urine immunofixation (IFE) was achieved in 61% of patients, 72% achieved normal serum free light chain ratio (sFLCR), and the median involved free light chain (iFLC) and difference between involved to uninvolved light chain (dFLC) were 17 mg/L and 5 mg/L, respectively. Overall, 46% of patients achieved a CR at EOT. At EOT, iFLC ≤20 mg/L and dFLC ≤10 mg/L were additive in survival discrimination to negative serum/urine IFE and were independent predictors of overall survival. In contrast, normalization of sFLCR did not add survival discrimination to serum/urine IFE and was not independent predictor of survival. We propose a new definition for hematological CR to include serum/urine IFE negativity plus iFLC ≤20 mg/L or dFLC ≤10 mg/L, instead of the current definition of serum/urine IFE negativity and normal sFLCR. Complete response using dFLC ≤10 mg/L had the best performance in those with significant renal dysfunction and by light chain isotype, making it the preferred partner to IFE. Validation of these results in a multicenter cohort is warranted.     

Treatment of upper extremity deep vein thrombosis with apixaban and rivaroxaban

Randomized controlled trials leading to the approval of apixaban and rivaroxaban for venous thromboembolism (VTE) did not include patients with upper extremity deep vein thrombosis (UE-DVT). We sought to evaluate the safety and effectiveness of rivaroxaban and apixaban for the treatment of acute UE-DVT. Consecutive patients with VTE enrolled into the Mayo Clinic VTE Registry, between March 1, 2013 and December 31, 2019, were followed prospectively. Clinical, demographic and imaging data were collected at the time of study recruitment. Patients with a diagnosis of acute UE-DVT who received rivaroxaban, apixaban, LMWH or warfarin were included. Recurrent VTE, major bleeding, clinical-relevant non-major bleeding (CRNMB), and death were assessed at 3-month intervals. During the study period, 210 patients with acute UE-DVT were included; 63 were treated with apixaban, 39 with rivaroxaban, and 108 with LWMH and/or warfarin. Overall 51% had catheter-associated UE-DVT, 60% had a diagnosis of malignancy, and 14% had concurrent pulmonary embolism. Malignancy was more common in patients treated with LMWH/warfarin (67% vs 52%, P = .03). At 3 months of follow up, one (0.9%) recurrent VTE occurred in a patient treated with LMWH/warfarin and one (1.0%) patient treated with apixaban or rivaroxaban (P = .97). Major bleeding occurred in three patients treated with LMWH/warfarin, and in none of those treated with apixaban or rivaroxaban (P = .09). Clinical-relevant non-major bleeding occurred in one patient (0.9%) treated with LWMH/warfarin and two patients (2.0%) treated with apixaban or rivaroxaban (P = .53). Treatment of UE-DVT with apixaban or rivaroxaban appears to be as safe and effective as LMWH/warfarin.     

Sex-Typed Personality Traits and Gender Identity as Predictors of Young Adults’ Career Interests

Gender segregation of careers is still prominent in the U.S. workforce. The current study was designed to investigate the role of sex-typed personality traits and gender identity in predicting emerging adults’ interests in sex-typed careers. Participants included 586 university students (185 males, 401 females). Participants reported their sex-typed personality traits (masculine and feminine traits), gender identities (gender typicality, contentment, felt pressure to conform, and intergroup bias), and interests in sex-typed careers. Results indicated both sex-typed personality traits and gender identity were important predictors of young adults’ career interests, but in varying degrees and differentially for men and women. Men’s sex-typed personality traits and gender typicality were predictive of their masculine career interests even more so when the interaction of their masculine traits and gender typicality were considered. When gender typicality and sex-typed personality traits were considered simultaneously, gender typicality was negatively related to men’s feminine career interests and gender typicality was the only significant predictor of men’s feminine career interests. For women, sex-typed personality traits and gender typicality were predictive of their sex-typed career interests. The level of pressure they felt to conform to their gender also positively predicted interest in feminine careers. The interaction of sex-typed personality traits and gender typicality did not predict women’s career interests more than when these variables were considered as main effects. Results of the multidimensional assessment of gender identity confirmed that various dimensions of gender identity played different roles in predicting career interests and gender typicality was the strongest predictor of career interests.     

Comparison of interventions for pain control with tenaculum placement: a randomized clinical trial

Objective

Although previous studies have demonstrated that a variety of local anesthetics are effective to decrease pain associated with tenaculum placement, no studies directly compare an injection with a topical anesthetic. The objective of this study was therefore to compare mean pain scores with tenaculum placement after an intracervical lidocaine injection or topical lidocaine gel.

Study Design

A randomized, single-blinded trial of women presenting for office gynecologic procedures that required a tenaculum. Women aged 18 years or older were randomized to receive either a 1% lidocaine intracervical injection or topical application of 2% lidocaine gel to the cervix immediately prior to tenaculum placement. The primary outcome was pain at the time of tenaculum placement, measured on a 100 mm Visual Analog Scale. Secondary outcomes included pain with the intervention and satisfaction with tenaculum placement.

Results

Seventy-four women were enrolled and randomized; 35 subjects in each group met criteria for analysis. The two groups had similar socio-demographic characteristics. Women who received the injection had lower mean pain levels at tenaculum placement [12.3 mm (S.D. 17.4 mm) versus 36.6 mm (S.D. 23.0 mm), p<.001] but higher mean pain levels with study drug application [20.4 mm (S.D. 19.4 mm) versus 5.9 mm (S.D. 8.6 mm), p<.001]. Satisfaction with tenaculum placement was similar for the two groups.

Conclusion

Mean pain with tenaculum placement is lower after receiving a lidocaine injection than after receiving a topical lidocaine gel. Satisfaction with tenaculum placement is similar with both interventions.