Background Occupational burnout in physicians is prevalent and can have many negative effects. The purposes of this study were to explore the prevalence of occupational burnout and to analyze the effects of social support and role stress on occupational burnout among Chinese physicians. Methods Using multistage-stratified cluster random sampling, physicians were selected to participate in the study and completed three questionnaires: the Chinese Maslach Burnout Inventory; the Cross-Cultural Role Conflict, Ambiguity and Overload Scale; and the Social Support Rating Scale. A path analysis was run to test the effects of role stress and social support on occupational burnout. Results Of 2530 physicians, 864 (34.2%) were experiencing moderate occupational burnout and 140 (5.5%) were experiencing severe occupational burnout. The path analysis results indicated that role conflict had direct positive effects on emotional exhaustion (EE) and depersonalization (DP), and role ambiguity had direct positive effects on DP and decreased personal accomplishment (DPA). Coworker support had direct negative effects on EE and positive effects on DP, family support had direct negative effects on DP and DPA. Coworker support mediated the effects of role ambiguity on EE and DP, and family support mediated the effects of role ambiguity on DP and DPA. Conclusions These findings suggest that occupational burnout is common in Chinese physicians, and that role stress and social support play important roles in occupational burnout. Interventions that aim to reduce role stress and increase social support can be effective approaches to prevent occupational burnout among physicians.

PurposeQuantification of mRNA has historically been done by reverse transcription polymerase chain reaction (RT-PCR). Recently, a robust method of detection of mRNA utilizing in situ hybridization has been described that is linear and shows high specificity with low background. Here we describe the use of the AQUA method of quantitative immunofluorescence (QIF) for measuring mRNA in situ using ESR1 (the estrogen receptor alpha gene) in breast cancer to determine its predictive value compared to Estrogen Receptor α (ER) protein.MethodsMessenger RNA for ER (ESR1) and Ubiquitin C (UbC) were visualized using RNAscope probes and levels were quantified by quantitative in situ hybridization (qISH) on two Yale breast cancer cohorts on tissue microarrays. ESR1 levels were compared to ER protein levels measured by QIF using the SP1 antibody.Results ESR1 mRNA is reproducibly and specifically measurable by qISH on tissue collected from 1993 or later. ESR1 levels were correlated to ER protein levels in a non-linear manner on two Yale cohorts. High levels of ESR1 were found to be predictive of response to tamoxifin.ConclusionQuantification of mRNA using qISH may allow assessment of large cohorts with minimal formalin fixed, paraffin embedded tissue. Exploratory data using this method suggests that measurement of ESR1 mRNA levels may be predictive of response to endocrine therapy in a manner that is different from the predictive value of ER.

Pre-analytic variables, specifically cold ischemic time, have been implicated as key variables in the measurement of proteins by immunohistochemistry. To determine the significance and magnitude of antigenic loss due to pre-analytic variables, we have compared protein antigenicity in core needle biopsies, with essentially no cold ischemic time, to that in routinely processed tumor resection specimens. Two cohorts of matched core needle biopsies and tumor resections were collected with 20 matched pairs and 14 matched pairs, respectively. Both series were analyzed by quantitative immunofluorescence using the AQUA® method. Antibodies to phospho-ERK, total ERK, phospho-AKT, total AKT, phospho-S6K1, total S6K1, Estrogen Receptor, Ki67, cytokeratin and GAPDH were measured. Detection levels for all phospho-epitopes were significantly decreased in tumor resections compared to biopsies while no significant change was seen in the corresponding total proteins. Of the other four proteins examined, Estrogen Receptor and cytokeratin showed significant loss of antigenicity. This data suggests that measurement of phospho-protein antigenicity in formalin-fixed tissue by immunological methods is dramatically affected by pre-analytic variables. This study suggests that core needle biopsies are more accurate for assessment of tissue biomarkers.

BackgroundSOX2 is an embryonic developmental transcription factor, which is important in the development of the respiratory tract. SOX2 overexpression is associated with aggressive disease in several tumor types. However, SOX2 overexpression and gene amplification associates with favorable outcome in lung squamous cell carcinomas (SCC) and dissimilar results have been reported in lung adenocarcinomas (ADC). The aim of the present study was to evaluate SOX2 expression in NSCLC and determine the relationship with clinico-pathological variables and outcome.MethodsSOX2 protein levels were measured in tissue microarrays (TMAs) containing FFPE samples from two independent lung cancer cohorts (n = 340 & 307) using automated quantitative immunofluorescence (QIF). Assay validation was performed using FFPE preparations of cell lines with known SOX2 expression. Associations of SOX2 levels with main clinico-pathological characteristics and with overall survival were studied using uni-and multivariate analysis.ResultsSOX2 levels were higher in patients with SCC than in ADC in both cohorts (p value<0.0001). In the training cohort, NSCLC patients whose tumors showed high SOX2 (n = 245) had longer survival than those with low SOX2 levels (log rank p = 0.0002). Comparable results were observed in the second independent validation cohort, log rank p = 0.0113. SOX2 positive cases showed a 58% reduction in risk of death in Cox univariate analysis (hazards ratio-HR = 0.42 confidence interval-CI (0.36,0.73), p = 0.0002). SOX2 was associated with significantly longer survival independent of histology in multivariate analysis (hazards ratio-HR = 0.429 confidence interval-CI (0.295, 0.663), p = <0.001).ConclusionsSOX2 is an independent positive prognostic marker in NSCLC. Increased SOX2 levels are more frequent in SCC than in ADC, but the association with better survival is independent from the histological subtype.

Background Microtubule associated proteins (MAPs) endogenously regulate microtubule stability. Here we assess the prognostic value of stathmin, a destabilizing protein in combination with MAP-tau, a stabilizing protein, in order to assess microtubule stabilization as a potential biomarker. Methods Stathmin and MAP-tau expression levels were measured in a breast cancer cohort (n = 651) using the tissue microarray format and quantitative immunofluorescence (AQUA) technology, then correlated with clinical and pathological characteristics and disease free survival. Results Univariate Cox proportional hazards (PH) models indicated that high stathmin expression predicts worse overall survival (HR = 1.48; 95% CI = 1.119–1.966; P = 0.0061). Survival analysis showed 10-year survival of 53.1% for patients with high stathmin expression versus 67% for low expressers (log rank, P<.003). Cox multivariate analysis showed high stathmin expression was independent of age, menopausal status, nodal status, nuclear grade, tumor size, ER, PR, and HER2 expression (HR = 1.19; 95% CI= 1.03–1.37; P = 0.01). The ratio of MAP-tau to stathmin expression showed a positive correlation to disease free survival (HR = 0.679; 95% CI = 0.517–0.891; P = 0.0053) with a 10-year survival of 65.4% for patients with high MAP-tau to stathmin ratio versus 52.5% survival rate for low ratio (log rank, P = 0.0009). Cox multivariate showed MAP-tau to stathmin ratio was an independent predictor of overall survival (HR = 0.609; 95% CI = 0.422–0.879; P = 0.008). Conclusion Low stathmin and high MAP-tau are associated with increased microtubule stability and better prognosis in breast cancer.

Background To investigate the clinical characteristics of Epstein–Barr virus (EBV) infection in the pediatric nervous system (NS). Methods We retrospectively analyzed the clinical data and follow-up results of 89 children with neurological damage caused by EBV who were hospitalized in the children’s hospital of Chongqing Medical University from January 2008 to April 2019. Results EBV infection of the NS can occur at any time of the year. The highest incidence was seen in the age group of 0–4 years. Fever is the main clinical feature (74/89, 83.1%). The main clinical types were encephalitis/meningoencephalitis (64/89, 71.9%), acute myelitis (2/89, 2.2%), acute disseminated encephalomyelitis (ADEM) (3/89, 3.4%), Guillain–Barré Syndrome (GBS) (15/89, 16.9%), neurological damage caused by EBV-hemophagocytic lymphohistiocytosis (EBV-HLH) (4/89, 4.5%), and NS-post-transplant lymphoproliferative disorder (NS-PTLD) (1/89, 1.1%). Anti-N-methyl-D-aspartate receptor encephalitis was found during the convalescence of EBV encephalitis. EBV encephalitis/meningitis showed no symptoms of tonsillitis, lymph node enlargement, skin rash, hepatosplenomegaly. Acute motor axonal neuropathy is the chief complication in GBS caused by EBV. Conclusion There were significant differences in neurological complications caused by EBV. The prognosis of EBV infection in the NS is generally good. These illnesses are often self-limiting. A few cases may show residual sequelae.

BackgroundHuman oxoguanine glycosylase 1 (hOGG1) in base excision repair (BER) pathway plays a vital role in DNA repair. Numerous epidemiological studies have evaluated the association between hOGG1 Ser326Cys polymorphism and the risk of cancer. However, the results of these studies on the association remain conflicting. To derive a more precise estimation of the association, we conducted a meta-analysis.Methodology/Principal FindingsA comprehensive search was conducted to identify the eligible studies of hOGG1 Ser326Cys polymorphism and cancer risk. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. We found that the hOGG1 Ser326Cys polymorphism was significantly associated with overall cancer risk (Cys/Cys vs. Ser/Ser: OR = 1.19, 95%CI = 1.09–1.30, P<0.001; Cys/Cys vs. Cys/Ser+Ser/Ser: OR = 1.16, 95%CI = 1.08–1.26, P<0.001). Moreover, in subgroup analyses by cancer types, the stronger significant association between hOGG1 Ser326Cys polymorphism and lung cancer risk was found (Cys/Cys vs. Ser/Ser: OR = 1.29, 95%CI = 1.16–1.44, P<0.001; Cys/Cys vs. Cys/Ser+Ser/Ser: OR = 1.22, 95%CI = 1.12–1.33, P<0.001). The significant effects of hOGG1 Ser326Cys polymorphism on colorectal, breast, bladder, prostate, esophageal, and gastric cancer were not detected. In addition, in subgroup analyses by ethnicities, we found that the hOGG1 Ser326Cys polymorphism was associated with overall cancer risk in Asians (Cys/Cys vs. Ser/Ser: OR = 1.21, 95%CI = 1.10–1.33, P<0.001).ConclusionsThis meta-analysis showed that hOGG1 326Cys allele might be a low-penetrant risk factor for lung cancer.

Background Burn-out among doctors threatens their own health, and that of their patients. To identify risk factors of the doctor burn-out is vital to improving their health and increasing the quality of healthcare services. This study aims to explore the relationship between work-family conflict (WFC) and burn-out among Chinese doctors and the mediating role of coping styles in this relationship.MethodsA cross-sectional survey was conducted in China, with a questionnaire packet which consisted of the Chinese Maslach Burnout Inventory (CMBI), WFC Scale and the Simplified Coping Style Questionnaire (SCSQ). A total of 2530 doctors participated in the survey. Correlation analysis was performed to explore the relationship between CMBI, WFC and SCSQ scores. A linear regression model was set to determine the mediating role of coping styles on the relationship between WFC and burn-out.ResultsDoctors who had higher scores on work interfering with family conflict, reported more emotional exhaustion (r=0.514, P<0.001) and had a sense of accomplishment (r=−0.149, P<0.001). Simultaneously, family interfering with work (FIW) was positively associated with all dimensions of burn-out (r=0.213, 0.504, 0.088, respectively, P<0.001). Coping styles had partial, complete and even mediating effects on the relationship between WFC and burn-out among Chinese doctors.ConclusionsWFC was correlated with burn-out, and coping style was a mediator in this relationship among Chinese doctors. Coping style was a positive resource against burn-out.