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Severe fever with thrombocytopenia syndrome virus (SFTSV) is a newly emerging tick-borne virus with a case fatality rate between 12% and 50%. Currently, effective vaccines or antiviral drugs are not available, and a diagnostic method for detecting SFTSV is urgently needed. The monoclonal (MAb) and polyclonal antibodies (PAb) against SFTSV were prepared by immunizing animals with SFTSV nucleocapsid protein (NP), and using both monoclonal and polyclonal antibodies as capture antibodies against NP, we developed two different double-antibody sandwich enzyme-linked immunosorbent assays (DAS-ELISAs) for detecting the NP of SFTSV. Both methods were applicable for the diagnosis of SFTSV-infected patients, as confirmed by quantitative polymerase chain reaction. Furthermore, the sensitivity and specificity of two assays for diagnosing SFTS were both 100%, and had no reaction to recombinant Dabieshan NP or recombinant Dengue virus NS1 subtype 1 and 2 proteins. In addition, two standard curves were established for quantitative detection of the NP, and the monoclonal antibody-based ELISA (MAb-based ELISA) test had a lower limit of detection than the polyclonal-based ELISA (PAb-based ELISA) test. Therefore, the MAb-based ELISA could be employed for detecting SFTSV in a convenient and effective way.

This meta-analysis was designed to assess the association between two loco-regional therapies, regional nodal irradiation (RNI) and axillary lymph node dissection (ALND), and breast cancer-related lymphoedema (BCRL). We searched PubMed, Science Direct, Embase, and BMJ databases for clinical studies published between January 1, 2010 and January 1, 2020, which assessed risk factors and incidence/prevalence of BCRL. Two investigators independently selected articles to extract relative data and calculate corresponding exact binomial 95% confidence intervals (CIs). In total, 93 articles were reviewed, from which 19 studies were selected. The extracted data were pooled using a random-effects mixed model. The incidence of lymphedema in the selected studies ranged from 3% to 36.7%, with a pooled incidence of 14.29% (95% CI 13.79–14.79). The summary odds ratio/risk ratio (OR/RR) of ALND vs. no-ALND was 3.67 (95% CI 2.25–5.98) with a heterogeneity (I2) of 81% (P

BACKGROUND: Triple negative breast cancer (TNBC), accounting for 15% of all breast cancer cases, was usually considered as the most aggressive subtype. The present study evaluated the prognosis of T1a TNBC and the impact of tumor size on T1 TNBC survival in large-scale population. METHODS: This retrospective study enrolled T1a/T1b/T1c TNBC and HER2(+)/hormone receptor (HoR)(−) patients diagnosed between 2010 to 2012 from the Surveillance, Epidemiology, and End Results database. The following information was extracted for further analyses: demographic variables including age at diagnosis, race, marital status, laterality, histological grade, T/N stage, American Joint Committee on Cancer (AJCC) stage, radiation therapy, survival and cause of death. Kaplan-Meier method and Cox regression were engaged for breast cancer specific survival (BCSS) and overall survival (OS) analyses. RESULTS: In all, the present study enrolled 6,953 TNBC and 2,648 HER2(+)/HoR(−) patients. T1a TNBC which generally omitted adjuvant chemotherapy had worse prognosis than T1a HER2(+)/HoR(−) [BCSS: hazard ratio (HR) 3.23, 95% confidence interval (CI): 1.05–9.09, P=0.03; OS: HR 2.63, 95% CI: 1.25–5.56, P=0.01] and T1b HER2(+)/HoR(−) (BCSS: HR 5.26, 95% CI: 1.61–16.7, P=0.006; OS: HR 3.03, 95% CI: 1.27–7.14, P=0.013) tumors which both were recommended by the National Comprehensive Cancer Network (NCCN) guideline to have chemotherapy. T1a TNBC also showed a trend with poorer prognosis than T1b TNBC, but did not reach statistical significance. CONCLUSIONS: T1a TNBC had the worst prognosis among all small tumors (

Background Gastrointestinal symptoms are not rare among coronavirus disease 2019 (COVID-19) patients, but there have been no reports regarding convalescent plasma therapy for the recovery of gastrointestinal problems in COVID-19 patients. Case presentation We present two cases of patients with COVID-19-associated recurrent diarrhea and positive fecal occult blood who successfully recovered after a one-time convalescent plasma administration. Conclusion When COVID-19 patients develop recurrent or refractory gastrointestinal symptoms and fail to respond to the available treatment, alternative therapy with convalescent plasma administration may be considered.

Purpose At present, there are few studies on the mechanisms underlying postoperative recurrence of liver cancer, and the mechanism of action of miR-602 in postoperative recurrence of liver tumors is not clear. Our goals were to investigate the effects of miR-602 on the expression of the Ras-associated domain family 1A (RASSF1A) gene and the regulation of primary and recurrent hepatic tumors to clarify the molecular mechanisms of miR-602 in postoperative hepatocellular carcinoma. Methods We constructed a mouse liver orthotopic tumor model and a mouse liver recurrent tumor model. We measured the expression levels of the RASSF1A gene and then analyzed the effects of miR-602 on the regulation of RASSF1A. We transiently transfected the miR-602 gene into cells that stably overexpressed RASSF1A and examined relevant indicators to elucidate the mechanisms by which miR-602 regulates the RASSF1A/c-Jun N-terminal kinase (JNK) pathway in recurrence and dormancy in liver cancer. Results RASSF1A expression was inversely related to that of JNK, activating transcription factor 2 (ATF-2), and c-Jun in SMMC7721 cells stably transfected with the RASSF1A gene and in recurrent mouse tumor tissues. After transient transfection of cells with miR-602 mimic or miR-602 inhibitor, the expression of miR-602 was inversely related to that of RASSF1A. Conclusion MiR-602 might inhibit the JNK signaling pathway by inhibiting the expression of RASSF1A, thereby promoting recurrence of liver cancer after surgery. The low expression levels of miR-602 in liver cancer tissues were closely related to postoperative recurrence; they could be used as a marker to judge the prognosis of patients with liver cancer.

Background BRCA1/2 mutation is associated with a high risk of breast cancer, which may preclude breast cancer patients with BRCA1/2 mutation from breast-conserving therapy (BCT) [breast-conserving surgery (BCS), followed by radiotherapy, BCT]. It is debatable whether BCT could be a rational choice for Chinese breast cancer patients with a BRCA1/2 mutation. Methods The study comprised a cohort of women with invasive breast cancer either receiving BCT or mastectomy following the criteria for the germline BRCA1/2 mutation test. Germline DNA for BRCA1/2 testing was derived from blood samples. Survival analyses were performed. The correlations were analyzed between survival and distinct types of surgery. To compare the survival between different surgical management, Kaplan-Meier univariate analysis and multivariate Cox regression was used. Results In BRCA1/2 mutation carriers (N=176) and noncarriers (N=293), 25% and 27.3% of the patients received BCT, respectively (P=0.675). Patients receiving mastectomy (without radiotherapy or followed by radiotherapy) have larger tumor size (P

Background: Non-alcoholic fatty liver disease (NAFLD) was a common disease and a frequent side effect of endocrine therapy for breast cancer patients. This was the first meta-analysis to investigate the impact of NAFLD on breast cancer survival. Material and Methods: We searched Pubmed, Embase and Cochrane Central Register of Controlled Trials database for relevant studies that investigated the correlation between NAFLD and breast cancer survival. Fixed- and random-effect meta-analyses were conducted according to the heterogeneity of enrolled studies. Subgroup analyses were based on whether NAFLD was induced by Selective-estrogen receptor modulator (SERM) administration. Results: Six cohorts from five studies including 935 NAFLD and 2102 non-NAFLD patients were enrolled. NAFLD was significantly associated with advanced age (p< 0.001), obesity (p< 0.001), lymph node metastasis (p = 0.003), hormone receptor positivity (p < 0.001) and human epidermal growth factor receptor 2 positivity (p = 0.008). NAFLD had no significant impact on disease free survival(DFS) [hazard ratio (HR) 0.95, 95% confidence interval (CI) = 0.48-1.87, p = 0.87] and overall survival (OS) (HR 1.28, 95% CI = 0.59-2.78, p = 0.53). In subgroup analyses, SERM-associated NAFLD showed no significant impact on DFS and OS. Nonetheless, non-SERM-associated NAFLD had a strong prognostic correlation with poor OS (HR 1.92, 95% CI = 1.09-2.06, p = 0.02). Conclusion: NAFLD had no significant impact on breast cancer survival. However, non-SERM-associated NAFLD implied increasing death risk. Future large-scale studies are warranted to further elucidate the correlation between NAFLD and breast cancer prognosis. Keywords: breast cancer; non-alcoholic fatty liver disease; selective estrogen receptor modulator; liver metastasis TABLES Table 1. Characteristics of studies enrolled in meta-analysisStudyCountryDesignNMedian follow-up (month)TNM StageNAFLD AssessmentLiver Metastasis AssessmentClinical EndpointsHormone ReceptorRelationship Between SERM-treatment and NAFLDDuran(2015)TurkeyRC107NAIVContrast-enhanced/ Non-Contrast CTNAOSNANon-SERM-associated NAFLDYan(2017)ChinaRC64664(7-91)I-IIIUSGUSGDFS, OSER+ and/or PR+SERM-associated NAFLDWu(2017)ChinaRC123030.7±24.9 32.4±26.3I-IIIUSGUSG/CT/MRILiver-MFSER/PR+799 ER/PR- 331NAZheng(2015)ChinaRC78576(14-122)I-IIIUSGNADFS, OSER/PR+SERM-associated NAFLDYang(2015) Cohort A*KoreaRC28NAII/IIIUSG/ Non-Contrast CT/ Contrast CTNADFS, OSNANon-SERM-associated NAFLDYang(2015) Cohort B*KoreaRC24NAII/IIIUSG/ Non-Contrast CT/ Contrast CTNADFS, OSNANon-SERM-associated NAFLDRC, retrospective cohort; NA, not available; CT, computed tomography; OS, overall survival; DFS, disease free survival; SERM, selective estrogen receptor modular; USG, ultrasonography; MRI, Magnetic resonance imaging; MFS, metastasis free survival.*Study by Yang et al. included two cohorts Table 2. Correlation Between NAFLD Presence and Clinicopathological FeaturesNAFLD(%)Non-NAFLD(%)P valueAge (years)50397(32.4%)829(67.6)BMI (kg/m2)25320(43.2%)421(56.8%)Tumor Size (mm)5080(30.3%)184(69.7%)LN MetastasisYes540(40.9%)780(59.1%)0.003*No281(36.6%)486(63.4%)MenopausePre153(33.5%)304(66.5%)0.766Post96(32.4%)200(85.9%)ER/PR StatusER/PR +630(34.9%)1173(65.1%) Citation Format: Yu Song, Changjun Wang, Wei Huang, Yidong Zhou, Ziyuan Chen, Hanjiang Zhu, Feng Mao, Yan Lin, Xiaohui Zhang, Songjie Shen, Ying Zhong, Xin Huang, Chang Chen, Qiang Sun. The impact of pre-existed and SERM-induced non-alcoholic fatty liver disease on breast cancer survival: A meta-analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-12-14.

In the current issue of Blood, Xia et al evaluate the use of convalescent plasma for the treatment of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19).1,2 SARS-CoV-2 has spurred a global crisis. To date, there are limited treatment options for COVID-19 and no proven prophylactic therapies for those who have been exposed to SARS-CoV-2.

Background: Non-alcoholic fatty liver disease (NAFLD) is a common disorder and a frequent side effect of endocrine therapy (ET) for breast cancer treatment. This was the first meta-analysis to investigate the impact of NAFLD on breast cancer survival. Material and Methods: We searched Pubmed, Embase and Cochrane Central Register of Controlled Trials database for relevant studies that investigated the correlation between NAFLD and breast cancer survival. Fixed- and random-effect meta-analyses were conducted according to the heterogeneity of enrolled studies. Subgroup analyses were performed based on whether NAFLD was induced by ET administration Results: Eight cohorts from six studies including 3684 breast cancer patients were enrolled. NAFLD was significantly associated with advanced age (p < 0.001), obesity (p < 0.001), lymph node metastases (p = 0.003) and hormone receptor positivity (p < 0.001). NAFLD had no significant impact on disease free survival (DFS) [hazard ratio (HR) 1.07, 95% confidence interval (CI) = 0.64-1.77, p = 0.81] and overall survival (OS) (HR 1.29, 95% CI = 0.68-2.44, p = 0.44). In subgroup analyses, ET-associated NAFLD showed no significant impact on DFS and OS. Nonetheless, non-ET-associated NAFLD had a strong prognostic correlation with poor OS (HR 1.92, 95% CI = 1.09-3.41, p = 0.02). Conclusion: NAFLD had no significant impact on breast cancer survival. However, non-ET-associated NAFLD implied increasing death risk. Future large-scale studies are warranted to further elucidate the correlation between NAFLD and breast cancer prognosis.

Physical signs of patients indicate crucial evidence for diagnosing both location and nature of the disease, where there is a sequential relationship between the two tasks. Thus their joint learning can utilize intrinsic association by transferring related knowledge across relevant tasks. Choosing the right time to transfer is a critical problem for joint learning. However, how to dynamically adjust when tasks interact to capture the right time for transferring related knowledge is still an open issue. To this end, we propose a Task-Coupling Elastic Learning (TCEL) framework to model the task relatedness for classifying disease-location and disease-nature based on physical sign images. The main idea is to dynamically transfer relevant knowledge by progressively shifting task-coupling from loose to tight during the multi-stage training. In the early stage of training, we relax the constraints of modeling relations to focus more in learning the generic task-common features. In the later stage, the semantic guidance will be strengthened to learn the task-specific features. Specifically, a dynamic sequential module (DSM) is proposed to explicitly model the sequential relationship and enable multi-stage training. Moreover, to address the side effect of DSM, a new loss regularization is proposed. The extensive experiments on these two clinical datasets show the superiority of the proposed method over the baselines, and demonstrate the effectiveness of the proposed task-coupling elastic mechanism.

Background Aberrant expression of circular RNA(circRNA)is involved in the occurrence of various diseases and tumor development, in which plays a vital role, including hepatocellular carcinoma (HCC). Nevertheless, the regulation mechanism and biological function of circITCH in hepatocellular carcinoma (HCC) remain unclear. Methods The expression level of circular RNA itchy E3 ubiquitin protein ligase (circ-ITCH) was identified and validated by real-time polymerase chain reaction (RT-qPCR) in HCC cell lines. The stability of circITCH was confirmed by Ribonuclease R (RNase R) assay. Subsequently, through silencing and overexpression of circITCH to investigate the functional roles of circITCH in HCC proliferation, invasion and apoptosis. We also carried out bioinformatics analysis, luciferase reporter assays to define the relationship between microRNA (miR)-184 and circITCH. Results CircITCH (hsa_circ_0001141) was a stable circRNA and downregulated in HCC cells. Overexpression of circITCH inhibited cell proliferation, migration, invasion and promoted apoptosis in vitro, whereas knockdown of circITCH had the opposite effects. Mechanistically, miR-184 could be sponged by circITCH, and its overexpression could mitigate the suppressive effects of circITCH overexpression on HCC progression. Through biological website to predict the target genes of miR-184 may be combined. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to investigate mRNAs with significant functional enrichment and pathways, also which its relationship with HCC related pathway and immune cells. Conclusions Our findings reveal that circITCH served as a repressor to restrain HCC malignancy via miR-184. Therefore, circITCH may serve as a potential prognostic marker and therapeutic target for HCC.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces new-onset diabetes and severe metabolic complications of pre-existing diabetes. The pathogenic mechanism underlying this is incompletely understood. Here, we provided evidence linking circulating GP73 with the exaggerated gluconeogenesis triggered by SARS-CoV-2 infection. We found that SARS-CoV-2 infection or glucotoxic conditions increased GP73 production and secretion. Secreted GP73 then trafficked to the liver and kidney to stimulate gluconeogenesis through the cAMP/PKA pathway. By using global phosphoproteomics, we found a drastic remodeling of the PKA kinase hub exerted by GP73. Notably, plasma GP73 levels were elevated and positively correlated with blood glucose in patients with COVID19 and diabetes. Neutralization of circulating GP73 in serum of individuals infected with SARS-CoV-2 or with diabetes reduced excessive gluconeogenesis in cultured hepatocytes, and lowered blood glucose levels in animal models of diabetes. Ablation of GP73 from whole animals has a profound glucose-lowering effect secondary to reduced gluconeogenesis. Thus, GP73 is a key glucogenic hormone contributing to SARS-CoV-2-induced glucose abnormality.

SummarySevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces new-onset diabetes and severe metabolic complications of pre-existing diabetes. The pathogenic mechanism underlying this is incompletely understood. Here, we provided evidence linking circulating GP73 with the exaggerated gluconeogenesis triggered by SARS-CoV-2 infection. We found that SARS-CoV-2 infection or glucotoxic condition increased the cellular secretion of GP73. Secreted GP73 trafficked to the liver and kidney to stimulate gluconeogenesis through cAMP/PKA pathway. By using global phosphoproteomics, we found a drastic remodeling of PKA kinase hub exerted by GP73. Notably, COVID-19 patients showed pathologically elevated plasma GP73, and neutralization of the secreted GP73 inhibited enhanced PKA signaling and glucose production associated with SARS-CoV-2 infection. GP73 blockade also reduced gluconeogenesis and lowered hyperglycemia in type 2 (T2D) diabetic mice. Therefore, our findings provide novel insight into the roles of GP73 as a key glucogenic hormone and mechanistic clues underlying the development of SARS-CoV-induced glucose abnormalities.

PurposeTo evaluate the cost-effectiveness of adding ribociclib to endocrine therapy for pre/perimenopausal women with hormone receptor-positive (HR+), human epidermal receptor 2-negative (HER2-) advanced breast cancer from the US payer perspective.MethodsA partitioned survival analysis model with three health states (progression-free, progressed disease, and death) was developed to compare the cost and effectiveness of ribociclib in combination with endocrine therapy versus endocrine therapy alone based on clinical data from the MONALEESA-7 phase 3 randomized clinical trials. Life years (LYs), quality-adjusted life-years (QALYs), and total costs were estimated and used to calculate incremental cost-effectiveness ratio (ICER) over a lifetime. Deterministic and probabilistic sensitivity analyses were conducted to test the uncertainties of model inputs. Additional scenario analyses were performed.ResultsIn the base-case, ribociclib plus endocrine therapy was more effective than endocrine therapy with an additional 1.39 QALYs but also more costly with an ICER of $282,996/QALY. One-way deterministic sensitivity analysis showed that overall survival associated with the treatments and the cost of ribociclib had the greatest impact on the ICER. The probabilistic sensitivity analysis showed that only beyond a willingness-to-pay (WTP) threshold of $272,867, ribociclib plus endocrine therapy would surpass endocrine therapy alone as a cost-effective option.ConclusionsFrom the US payer perspective, ribociclib plus endocrine therapy for pre/perimenopausal patients with HR+/HER2- advanced breast cancer is not cost-effective at a WTP threshold of $100,000 or $150,000 per QALY in comparison of endocrine therapy alone.

Background and aims Patients with multiple metabolic diseases are at high risk for the occurrence and death of COVID-19. Little is known about patients with underweight and metabolically healthy obesity. The aim of this study is to evaluate the impact of BMI and COVID-19 mortality in hospitalized patients, and also explore the association in different metabolically healthy (MHS) and unhealthy status (MUS). Methods and results A retrospective cohort study based on 3019 inpatients from Wuhan was conducted. Included patients were classified into four groups according the BMI level (underweight, normal weight, overweight and obesity), and patients with at least one of the metabolic abnormalities (diabetes, hypertension, dyslipidemia) was defined as MUS. Multiple Cox model was used to calculate the hazard ratio (HR). Compared to patients with normal weight, the HRs of overweight and obesity for COVID-19 mortality were 1.91 (95%CI:1.02–3.58) and 2.54 (95%CI:1.22–5.25) respectively in total patients, and 2.58 (95%CI:1.16–5.75) and 3.89 (95%CI:1.62–9.32) respectively in the elderly. The HR of underweight for COVID-19 mortality was 4.58 (95%CI:1.56–13.48) in the elderly. For different metabolic statuses, both underweight, overweight and obesity had obviously negative association with COVID-19 mortality in total and elderly patients with MUS. However, no significance was found in non-elderly and patients with MHS. Conclusion Not only overweight or obesity, but also underweight can be associated with COVID-9 mortality, especially in the elderly and in patients with MUS. More large-scale studies are needed for patients with underweight and metabolically healthy overweight or obesity.

BACKGROUND In previous studies, higher expression of PREX1 (PtdIns (3,4,5)P3-dependent Rac exchanger 1) has been detected in some subsets of breast cancer, and activation of PREX1 has been associated with tumor progression in vivo. However, an association between PREX1 and breast cancer prognosis has not been examined. MATERIAL AND METHODS In this study, we investigated the expression and correlation of PREX1 with important clinical factors and prognosis of patients with breast cancer. Immunohistochemical staining was performed for 121 tumor tissue specimens obtained from primary breast cancer lesions. RESULTS We found that 55 tissues exhibited positive staining for PREX1. Moreover, tumors positive for PREX1 were found to have significant association with recurrence rate (P=0.000) and metastasis rate (P=0.001). Univariate and multivariate regression analyses also identified PREX1 expression as an independent variable of disease-free survival. Our analyses indicate that high levels of PREX1 expression were related to longer disease-free survival in patients with breast cancer (P=0.013). CONCLUSIONS PREX1 is a favorable variable of prognosis for breast cancer patients, these study results need to be confirmed in larger research studies.

Purpose Human epidermal growth factor receptor 2 (HER2) status is both an independent prognostic factor and a predictive factor for the efficacy of targeted therapy for breast cancer, so it is critical to accurately detect HER2 protein expression and/or gene amplification. According to the recommendations of the 2013 American Society of Clinical Oncology and College of American Pathologists (ASCO/CAP) guidelines for HER2 breast cancer testing, an additional test should be pursued on a different block from the same tumor as one of the options for patients with immunohistochemistry (IHC) 2+ and a HER2/CEP17 ratio of

The objective of this paper is to investigate the energy conservation and resource utilization in the smelting process of ferrochrome pellets. Based on the laws of mass and energy conservation, the material and energy flows model has been established in the smelting process of steel belt sintering-submerged arc furnace. To better understand the smelting process from disorder state to order state under energy conservation and resource utilization, the synergy model related to the material and energy has been developed. The state change depends on the fluctuations to the energy critical point. The fluctuations are defined as order parameters, which satisfy all the smelting processes. The value of synergy degree is set as the evaluating indicator to assess the smelting process. The results show that the energy efficiencies of three smelting equipments are 42.89%, 66.17% and 61.44%, respectively. Also, the energy efficiency of the smelting process is 49.15%. The value of synergy degree is 0.584. Several suggestions for the smelting process are proposed based on the synergy model. The synergy degree of the suggestions is 0.632. The present work has a potential to improve the smelting process in efficiency.

Background The incidence of bilateral breast cancer (BBC) is increasing nowadays comprising 2%‐11% of all breast cancer (BC). According to the interval time between the first and second cancer, BBC could be divided into synchronous (SBBC) and metachronous (MBBC). However, this interval time is quite different across studies. It remains controversial whether the survival of BBC, SBBC, and MBBC is similar or worse compared to that of unilateral breast cancer (UBC), and whether the survival of SBBC is similar or worse compared to MBBC. To better understand the survival of UBC, BBC, SBBC, and MBBC and how the interval time would influence the prognosis of SBBC and MBBC, we performed this meta‐analysis on studies from recent 10 years (2008‐2018). Methods Databases of PubMed, Embase, and Web of Science were searched for relevant studies within recent 10 years. Hazard ratio (HR) was adopted to evaluate the difference of overall survival (OS) of UBC, BBC, SBBC, and MBBC. HR of OS comparisons were performed between BBC vs UBC, SBBC vs UBC, MBBC vs UBC, and SBBC vs MBBC with 3, 6, 12 months as the interval time, respectively. Results There were 15 studies of 72 302 UBC and 2912 BBC included in the meta‐analysis. The summary HR of OS comparison between BBC vs UBC was 1.68 (95% CI: 1.28‐2.20), SBBC vs UBC was 2.01 (95% CI: 1.14‐3.55), MBBC vs UBC was 3.22 (95% CI: 0.75‐13.78). When 3, 6, 12 months were used as the interval time, the summary HR of the OS comparison between of SBBC vs MBBC were 0.64 (95% CI: 0.44‐0.94), 1.17 (95% CI: 0.84‐1.63) and 1.45 (95% CI: 1.10‐1.92), respectively. Conclusion BBC and SBBC showed worse prognosis in terms of OS compared to UBC while MBBC manifested similar or non‐superior survival as UBC. The OS comparison between SBBC and MBBC changed with different interval time used. The longer the interval time used, the worse the survival of SBBC. SBBC with interval of 3‐12 months between the two cancers had the worst prognosis. When 6 months was used to differentiate SBBC from MBBC, these two clinical entities showed similar OS.

Noninvasive circulating tumor DNA (ctDNA) can be used to predict breast cancer recurrence and prognosis. In this study, we detected 226 and 114 somatic variants in tumor DNA from 70 primary breast cancer (PBC) patients (98.59%) and ctDNA from 48 patients (67.61%), respectively. Gene frequencies of tumor DNA and ctDNA significantly correlated (R 2 = 0.9532, P

AIM To evaluate the effectiveness and safety of combined ursodeoxycholic acid and percutaneous transhepatic balloon dilation for management of gallstones after expulsion of common bile duct (CBD) stones. METHODS From April 2014 to May 2016, 15 consecutive patients (6 men and 9 women) aged 45-86 (mean, 69.07 ± 9.91) years suffering from CBD stones associated with gallstones were evaluated. Good gallbladder contraction function was confirmed by type B ultrasonography. Dilation of the CBD and cystic duct was detected. Percutaneous transhepatic balloon dilation of the papilla was performed, ursodeoxycholic acid was administered, and all patients had a high-fat diet. All subjects underwent repeated cholangiography, and percutaneous transhepatic removal was carried out in patients with secondary CBD stones originating from the gallbladder. RESULTS All patients underwent percutaneous transhepatic balloon dilation with a primary success rate of 100%. The combined therapy was successful in 86.7% of patients with concomitant CBD stones and gallstones. No remaining stones were detected in the gallbladder. Transient adverse events include abdominal pain (n = 1), abdominal distension (n = 1), and fever (n = 1). Complications were treated successfully via nonsurgical management without long-term complications. No procedure-related mortality occurred. CONCLUSION For patients with concomitant CBD stones and gallstones, after percutaneous transhepatic removal of primary CBD stones, oral ursodeoxycholic acid and a high-fat diet followed by percutaneous transhepatic removal of secondary CBD stones appear to be a feasible and effective option for management of gallstones.

Background HER2+ and hormone receptor (HoR)‐negative breast cancer usually associated with poor outcome. However, it remained elusive for the prognosis of small (T1a‐T1c) HER2+/HoR‐ breast cancer. The present study retrospectively analyzed the Surveillance, Epidemiology, and End Results (SEER) database to explore the clinicopathological characteristics and prognosis of T1a‐T1c HER2+/HoR‐ breast cancer. Material and Methods Data for patients diagnosed with either HER2‐/HoR+or HER2+/HoR‐ T1a‐T1c breast cancer between 2010 and 2012 were obtained from SEER program. Survival analyses were conducted by Kaplan‐Meier method and Cox proportion hazard regression. Results Totally, 2648 HER2+/HoR‐ and 56387 HER2‐/HoR+T1a‐T1c breast cancer patients were enrolled. There was a clear trend that tumor size had a positive correlation with advanced AJCC stage (P

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes a broad clinical spectrum of coronavirus disease 2019 (COVID-19). The development of COVID-19 may be the result of a complex interaction between the microbial, environmental, and host genetic components. To reveal genetic determinants of susceptibility to COVID-19 severity in the Chinese population, we performed a genome-wide association study on 885 severe or critical COVID-19 patients (cases) and 546 mild or moderate patients (controls) from two hospitals, Huoshenshan and Union hospitals at Wuhan city in China. We identified two loci on chromosome 11q23.3 and 11q14.2, which are significantly associated with the COVID-19 severity in the meta-analyses of the two cohorts (index rs1712779: odds ratio [OR] = 0.49; 95% confidence interval [CI], 0.38–0.63 for T allele; P = 1.38 × 10−8; and index rs10831496: OR = 1.66; 95% CI, 1.38–1.98 for A allele; P = 4.04 × 10−8, respectively). The results for rs1712779 were validated in other two small COVID-19 cohorts in the Asian populations (P = 0.029 and 0.031, respectively). Furthermore, we identified significant eQTL associations for REXO2, C11orf71, NNMT, and CADM1 at 11q23.3, and CTSC at 11q14.2, respectively. In conclusion, our findings highlight two loci at 11q23.3 and 11q14.2 conferring susceptibility to the severity of COVID-19, which might provide novel insights into the pathogenesis and clinical treatment of this disease.

Background: Circulating tumor DNA (ctDNA) provides a promising noninvasive alternative to evaluate the efficacy of neoadjuvant chemotherapy (NCT) in breast cancer. Methods: Herein, we collected 63 tissue (aspiration biopsies and resected tissues) and 206 blood samples (baseline, during chemotherapy (Chemo), after chemotherapy (Post-Chemo), after operation (Post-Op), during follow-up) from 32 patients, and preformed targeted deep sequencing with a customed 1,021-gene panel. Results: As the results, TP53 (43.8%) and PIK3CA (40.6%) were the most common mutant genes in the primary tumors. At least one tumor-derived mutation was detected in the following number of blood samples: 21, baseline; 3, Chemo; 9, Post-Chemo; and 5, Post-Op. Four patients with pathologic complete response had no tissue mutation in Chemo and Post-Chemo blood. Compared to patients with mutation-positive Chemo or Post-Chemo blood, the counterparts showed a superior primary tumor decrease (median, 86.5% versus 54.6%) and lymph involvement (median, one versus 3.5). All five patients with mutation-positive Post-Op developed distant metastases during follow-up, and the sensitivity of detecting clinically relapsed patients was 71.4% (5/7). The median DFS was 9.8 months for patients with mutation-positive Post-Op but not reached for the others (HR 23.53; 95% CI, 1.904–290.9; p < 0.0001). Conclusions: Our study shows that sequential monitoring of blood ctDNA was an effective method for evaluating NCT efficacy and patient survival. Integrating ctDNA profiling into the management of LABC patients might improve clinical outcome.Trial registration: This prospective study recruited LABC patients at Peking Union Medical College Hospital (ClinicalTrials.gov Identifier: NCT02797652).

Background: Differences in genomic profiling and immunity-associated parameters between germline BRCA and non-BRCA carriers in TNBC with high tumor burden remain unexplored. This study aimed to compare the differences and explore potential prognostic predictors and therapeutic targets. Methods: The study cohort included 21 consecutive TNBC cases with germline BRCA1/2 mutations and 54 non-BRCA carriers with a tumor size ≥ 2 cm and/or ≥1 affected lymph nodes. Differences in clinicopathological characteristics and genomic profiles were analyzed through next-generation sequencing. Univariate Kaplan–Meier analysis and Cox regression model were applied to survival analysis. Immunohistochemistry was used to confirm the consistency between CCNE1 amplification and cyclin E1 protein overexpression. Results: The cohort included 16 and five patients with germline BRCA1 and BRCA2 mutations, respectively. Patients with germline BRCA1/2 mutations were diagnosed at a significantly younger age and were more likely to have a family history of breast and/or ovarian cancer. Six non-BRCA carriers (11.11%) carried germline mutations in other cancer susceptibility genes, including five mutations in five homologous recombination repair (HRR) pathway genes (9.26%) and one mutation in MSH3 (1.85%). Somatic mutations in HRR pathway genes were found in 22.22 and 14.29% of the non-BRCA and BRCA carriers, respectively. PIK3CA missense mutation (p = 0.046) and CCNE1 amplification (p = 0.2) were found only in the non-BRCA carriers. The median tumor mutation burden (TMB) was 4.1 Muts/Mb, whereas none of the cases had high microsatellite instability (MSI). BRCA status did not affect disease-free survival (DFS, p = 0.15) or overall survival (OS, p = 0.52). CCNE1 amplification was an independent risk factor for DFS in non-BRCA carriers with TNBC (HR 13.07, 95% CI 2.47–69.24, p = 0.003). Consistency between CCNE1 amplification and cyclin E1 protein overexpression was confirmed with an AUC of 0.967 for cyclin E1 signal intensity. Conclusions: We found differences in genetic alterations between germline BRCA and non-BRCA carriers with TNBC and a high tumor burden. TMB and MSI may not be suitable predictors of TNBC for immune checkpoint inhibitors. Notably, CCNE1 amplification is a novel potential prognostic marker and therapeutic target for non-BRCA carriers with TNBC. Cyclin E1 may be used instead of CCNE1 to improve clinical applicability.

Objectives: Earlier researches suggested patients should be routinely screened for bacteria and fungi infection after COVID-19 being confirmed. Here, we enrolled 236 patients with COVID-19 to analyze the clinical characteristics, fungal strains, mortality, and laboratory data of different groups. Design: Single center retrospective study Patients: A total of 236 COVID-19 patients from Huoshenshan Hospital were included in this study, consisting of 14(6%) died cases, 222(94%) discharged cases . Results: The result revealed that 5 mortality in positive group were all related to aspergillus infection while candida infection rarely caused death. Aspergillus was most common in non-survivors while candida was most common in survivors. In terms of interleukin-6 (IL6), viral loads, nucleic acid clearance time, etc, fungal serologically positive group had a higher level than negative group. Conclusions: Non-survivors of Covid-19 with fungal infection were almost associated with aspergillus infection. Aspergillus infection, instead of candida infection might be fatal for critical ill patients with COVID-19. There is great significance to carry out routine screening for fungal infection especially for critical patients to enable early treatment to be implemented. Keywords: coronavirus disease 2019 (COVID-19); fungal infection; aspergillus; mortality

Coronavirus disease 2019 (COVID-19) has rapidly evolved into a global pandemic. A total of 1578 patients admitted into a newly built hospital specialized for COVID-19 treatment in Wuhan, China, were enrolled. Clinical features and the levels of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin (Ig)M and IgG were analyzed. In total, 1532 patients (97.2%) were identified as laboratory-confirmed cases. Seventy-seven patients were identified as asymptomatic carriers (n = 64) or SARS-CoV-2 RNA positive before symptom onset (n = 13). The positive rates of SARS-CoV-2 IgM and IgG were 80.4% and 96.8%, respectively. The median of IgM and IgG titers were 37.0A U/ml (interquartile range [IQR]: 13.4-81.1 AU/ml) and 156.9 AU/ml (IQR: 102.8-183.3 AU/ml), respectively. The IgM and IgG levels of asymptomatic patients (median titers, 8.3 AU/ml and 100.3 AU/ml) were much lower than those in symptomatic patients (median titers, 38.0 AU/ml and 158.2 AU/ml). A much lower IgG level was observed in critically ill patients 42-60 days after symptom onset. There were 153 patients with viral RNA shedding after IgG detection. These patients had a higher proportion of critical illness during hospitalization (p

To verify whether omitting radiotherapy from breast cancer treatment for patients ≥ 70 years old following breast-conserving surgery (BCS) without axillary lymph node dissection is safe. Previous studies have shown that omitting breast radiotherapy after BCS and axillary lymph node dissection is safe for elderly breast cancer patients. We aimed to evaluate the safety of BCS without axillary surgery or breast radiotherapy (BCSNR) in elderly patients with breast cancer and clinically negative axillary lymph nodes. We performed a retrospective analysis of 481 patients with breast cancer, aged ≥ 70 years, between 2010 and 2016. Of these, 302 patients underwent BCSNR and 179 underwent other, larger scope operations. Local recurrence rate, ipsilateral breast tumor recurrence (IBTR) rate, distant metastasis rate, breast-related death, disease-free survival (DFS), and overall survival (OS) were compared between the two groups. After a median follow-up of 60 months, no significant differences in local recurrence, distant metastasis rate, breast-related death, and DFS were noted. The OS was similar (P = 0.56) between the BCSNR group (91.7%) and other operations group (93.0%). The IBTR rate was considered low in both groups, however resulted greater (P = 0.005) in the BCSNR group (5.3%) than in other operations group (1.6%). BCSNR did not affect the survival of elderly patients with breast cancer with clinically negative axillary lymph nodes. IBTR was infrequent in both groups; however, there was a significant difference between the two groups. BCSNR is a feasible treatment modality for patients with breast cancer ≥ 70 years old with clinically negative axillary lymph nodes.

Background HER2 dual-blockade combined with aromatase inhibitors (AI) is a promising strategy to improve progression-free survival (PFS) in hormone receptor (HR) positive, metastatic breast cancer (MBC). Pyrotinib is a novel irreversible epidermal growth factor receptor/HER2 dual tyrosine kinase inhibitor. However, there is scarcity of data on the effectiveness and safety of pyrotinib combined with trastuzumab and AI as first-line treatment in a metastatic setting. Methods/design The present study is a prospective, randomized, open-label trial. 198 patients with HER2+/HR+ MBC will be recruited. Eligible patients will be allocated (2:1) to either an experimental group (pyrotinib + trastuzumab + AI) or a control group (trastuzumab + AI). Allocation will be stratified by 1) time since adjuvant hormone therapy (≤ 12 months/> 12 months/no prior hormone therapy); 2) lesion sites (visceral / non-visceral). The primary endpoint is PFS. Discussion To our knowledge, this is the first prospective randomized controlled trial to assess dual HER2-blockade with pyrotinib in the metastatic setting. This study will provide valuable evidence regarding the efficacy and safety of pyrotinib when combined with trastuzumab and an AI as first-line treatment for MBC. Moreover, it will also evaluate the feasibility of endocrine therapy as an alternative to chemotherapy in providing de-escalation therapy with less toxicity for advanced HR+/HER2+ patients. Trial registration ClinicalTrials.gov, ID: NCT03910712. Registered on 10 Apr. 2019.

ObjectiveUsing the deep learning model to realize tongue image-based disease location recognition and focus on solving two problems: 1. The ability of the general convolution network to model detailed regional tongue features is weak; 2. Ignoring the group relationship between convolution channels, which caused the high redundancy of the model.MethodsTo enhance the convolutional neural networks. In this paper, a stochastic region pooling method is proposed to gain detailed regional features. Also, an inner-imaging channel relationship modeling method is proposed to model multi-region relations on all channels. Moreover, we combine it with the spatial attention mechanism.ResultsThe tongue image dataset with the clinical disease-location label is established. Abundant experiments are carried out on it. The experimental results show that the proposed method can effectively model the regional details of tongue image and improve the performance of disease location recognition.ConclusionIn this paper, we construct the tongue image dataset with disease-location labels to mine the relationship between tongue images and disease locations. A novel fully-channel regional attention network is proposed to model the local detail tongue features and improve the modeling efficiency.SignificanceThe applications of deep learning in tongue image disease-location recognition and the proposed innovative models have guiding significance for other assistant diagnostic tasks. The proposed model provides an example of efficient modeling of detailed tongue features, which is of great guiding significance for other auxiliary diagnosis applications.

The prognosis of elderly patients with hormone receptor-positive breast cancer is very good, and their survival is unaffected by performing breast-conserving surgery (BCS) without radiotherapy. Therefore, we aimed to verify that BCS without axillary lymph node dissection, sentinel lymph node biopsy, or radiotherapy (BCSNR) is safe for patients over 70 years of age with luminal-type breast cancer, as well as for those with HER2-positive and triple negative breast cancer (TNBC). This study retrospectively included 450 patients > 70-year-old with breast cancer from 2010 to 2016. The patients were divided into two groups, one treated with BCSNR and the other treated with mastectomy and axillary lymph node dissection (MALND), with a median follow-up period of 5 years. Disease-free survival (DFS), overall survival, local recurrence, distant metastasis, and ipsilateral breast tumor recurrence (IBTR) were compared between the two groups. The 5-year DFS for patients who underwent BCSNR and MALND was 90.1 and 91.3% (p = 0.903), respectively. In the BCSNR and MALND groups, respectively, the 5-year DFS for patients with luminal A type breast cancer was 99.2 and 100% (p = 0.167), that for patients with luminal B type breast cancer was 89.2 and 95.5% (p = 0.138), that for patients with HER2-positive breast cancer was 86.7 and 75.9% (p = 0.455), and that for TNBC patients was 71.7 and 89.7% (p = 0.195). IBTR significantly differed between the BCSNR and MALND groups for patients with TNBC (18.9% vs 0.0%, p = 0.040) and luminal B type patients (5.6% vs 0.0%, p = 0.043). BCSNR is not only suitable for elderly patients with luminal-type breast cancer but also for those with HER2-positive breast cancer and TNBC.

Objectives: Intravenous thrombolysis and thrombectomy are recommended for patients whose stroke onsets are within first 6 h, and very few options are available for patients whose stroke onset is more than 6 h, which includes most ischemic stroke patients. Human urinary kallidinogenase (HUK) showed potential clinical benefits in acute ischemic stroke patients. This study aims to investigate the safety and clinical benefits of HUK in ischemic stroke patients.Patients and methods: Patients were recruited for a multicenter double-blind, placebo-controlled phase II b and phase III trial. Neurophysiological outcomes were assessed by the European Stroke Scale (ESS) and the functional outcomes were assessed by the activity of daily living scale (ADL). Safety was monitored by recording adverse events.Results: The improvements in ESS scores and ADL scores in the HUK group were significantly greater than that in patients receiving placebo. Furthermore, HUK treatment was also associated with a lower rate of disable, according to ADL. HUK-related adverse events occurred at a low rate, in 1.73% of HUK-treated patients.Conclusion: HUK is safe and provides potential clinical benefits as a treatment for acute ischemic stroke. Further large post-marketing observational studies are needed.

Clinical Treatment Score post-5 years (CTS5) is a promising prognostic tool to evaluate late recurrence risk for breast cancer. Our study aimed to validate its prognostic value in large-scale population and explore the impact of menopausal and HER2 status on CTS5 model. We performed a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) database. Survival analyses were conducted to assess the prognostic value of CTS5 in different breast cancer subgroups in terms of overall survival (OS) and breast cancer specific survival (BCSS) after five years. A total of 23,168 breast cancer patients with positive hormone receptor (HoR) were enrolled. Postmenopausal and premenopausal patients were 13,686 and 9,482, respectively. Taking CTS5 score as a continuous variable, it had significant positive correlation with poor prognosis beyond five years in both postmenopausal and premenopausal subgroups. Nevertheless, for HER2+ postmenopausal patients, the model has less effective prognostic value on long-term BCSS [HR1.177 (95%CI 0.960–1.443), p = 0.117]. Using CTS5 score as a categorical variable, HER2- patients with high-risk level revealed significant poor survival in terms of both BCSS and OS, irrespective of menopausal status. Our study showed the CTS5 model could be a useful prognostic tool for predict long-term survival in HoR+/HER2- patients. And further large-scale studies are warranted to assess its prognostic value for HER2+ patients and develop novel prediction model for late recurrence risk estimation.

Bats are associated with several important zoonotic viruses from different families. One example includes adeno-associated viruses (AAVs), that are extensively detected in several animals, especially primates. To understand AAVs distribution and genetic diversity in the coastal areas of Southeast China, a total of 415 intestine samples were mostly collected from two provinces of southeast China, i.e., Zhejiang and Fujian province. Intestine samples from five bat species were collected for AAVs detection. The average prevalence rate for AAV detection among these samples was 18.6% (77 positives out of 415 samples) and ranged from 11.8 to 28.9% between the five bat species. This suggests that AAVs are widely distributed in diverse bat populations in southeast coastal areas of China. Based on the genome sequence of bat adeno-associated virus-CXC1(BtAAV-CXC1) from one AAV-positive sample, the genetic diversity of the detected AAVs were assessed and analyzed. Phylogenetic analysis revealed that BtAAV-CXC1 was comparatively distant to other major AAVs from mammals and non-mammals, with only a 52.9~64.7% nucleotide identity. However, they were phylogenetically closer to Rhinolophus sinicus bat adeno-associated virus (Rs-BtAAV1), with a 74.5% nt similarity. Partial analysis of the rep and cap overlapping open reading frame (ORF) sequences from bat AAV samples revealed 48 partial rep sequences and 23 partial cap sequences from positive samples shared 86.9 to 100% and 72.3 to 98.8% nucleotide identities among themselves, respectively. This suggests that the detected AAVs had a distinctly high genetic diversity. These findings led us to conclude that diverse AAVs may be widely distributed in bat populations from the southeast regions of China.

Background. Body constitution (BC) is the abstract concept indicating the state of a person’s health in Traditional Chinese Medicine (TCM). The doctor identifies the body constitution of the patient through inspection and inquiry. Previous research simulates doctors to identify BC types according to a patient’s objective physical indicators. However, the lack of subjective feeling information can reduce the accuracy of the machine to imitate the doctor’s diagnosis. The Constitution in Chinese Medicine Questionnaire (CCMQ) is used to collect subjective information but suffers from low acquisition efficiency. Methods. This paper presents a personalized body constitution inquiry method based on a machine learning technique. It employs a random generator, a feature extractor, and a classifier to simulate the doctor inquiry and generate a personalized questionnaire. Specifically, the feature extractor evaluates and sorts the question of the constitution in the CCMQ based on the recognition results of the tongue coating image of patients. The sorted questions and relevant BC label are inputted into the classifier; the best questions are screened out for patients. Results. The experimental results show that our method can select personalized questions from the CCMQ for the patients, significantly reducing the time and the number of questions to answer. It also improves the accuracy of recognizing BC. Compared with the CCMQ, patients had 68.3% fewer questions to answer and the time occupied by answering is reduced by 80.3%. Conclusions. The proposed method can simulate the doctor's inquiry and pick out personalized questions for patients. It can act as auxiliary diagnosis tools to collect subjective patient feelings and help make further judgments on the patient’s BC types.

Objectives: Earlier researches suggested patients should be routinely screened for bacteria and fungi infection after COVID-19 being confirmed. Here, we enrolled 236 patients with COVID-19 to analyze the clinical characteristics, fungal strains, mortality, and laboratory data of different groups. Design: Single center retrospective study Patients: A total of 236 COVID-19 patients from Huoshenshan Hospital were included in this study, consisting of 14(6%) died cases, 222(94%) discharged cases. Results: The result revealed that 5 mortality in positive group were all related to aspergillus infection while candida infection rarely caused death. Aspergillus was most common in non-survivors while candida was most common in survivors. In terms of interleukin-6 (IL6), viral loads, nucleic acid clearance time, etc, fungal serologically positive group had a higher level than negative group. Conclusions: Non-survivors of Covid-19 with fungal infection were almost associated with aspergillus infection. Aspergillus infection, instead of candida infection might be fatal for critical ill patients with COVID-19. There is great significance to carry out routine screening for fungal infection especially for critical patients to enable early treatment to be implemented. Funding Statement: This study was financially supported by grants Key Foundation of Wuhan Huoshenshan Hospital (2020[18]), Key Research& Development Program of Jiangsu Province (BE2018713), Medical Innovation Project of Logistics Service (18JS005). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This study was approved by the Medical Ethical Committee of Wuhan Huoshenshan Hospital (No. HSSLL011). Written informed consent was obtained from each patient.

Background Percutaneous procedures to treat common bile duct (CBD) stones typically require access via intrahepatic bile ducts. This study aimed to describe the outcomes of a percutaneous transcystic approach that expelled the CBD stones into the duodenum after percutaneous transcystic balloon dilation of the ampulla (PTCBDA) for high-risk patients who present with acute cholecystitis and CBD stones. Methods Patients diagnosed with acute cholecystitis and CBD stones who were deemed too high-risk for surgery or general anesthesia and were treated with PTCBDA and CBD stone removal between March 2010 and November 2015 were included for further analysis. Patients underwent emergency percutaneous transhepatic gallbladder drainage under ultrasound. Staged PTCBDA and CBD stone expulsion were performed. Outcomes evaluated included the success rate, causes of failure, and complications. Results Eighteen patients met the inclusion criteria. CBD stones were successfully expelled in 16 patients. A second procedure was performed in one patient because of residual stones. The procedure failed in two patients because their stones were large. One patient developed bile peritonitis and underwent percutaneous catheter drainage. Discussion Percutaneous transcystic anterograde expulsion of CBD stones may be a feasible and effective method for treating high-risk surgical patients with acute cholecystitis and co-existing CBD stones.

This paper studies intersection signal control in which traffic arrivals from all approaches along with the queues are assumed known. The control policy minimizes the overall intersection delay by deciding the green intervals for signal phases dynamically as driven by real-time traffic but subject to a set of constraints such as min/max green time for each phase. This paper models intersection vehicle delay by assuming continuous vehicle arrival and departure, and presents the optimal condition for green signal switch. Prior to this work, there does not appear to have been a continuous model on optimal control applied to the general intersection. Two numerical algorithms are proposed: optimum based (DORAS) and queue-based heuristic (DORAS-Q) respectively. Numerical tests are conducted via discrete simulation using an actual intersection data covering peak, mid-day and mid-night hours, respectively. Comparison is conducted between actuated, DORAS, DORAS-Q and OPAC III. The tests show that the latter three methods all perform significantly better than the actuated.

Both long-term environmental durability and high broadband reflectance of protected-silver mirrors are of great importance to the developments of optical instruments for a variety of applications under harsh environments. In this paper, the dependences of spectral properties and environmental durability of protected-silver mirrors with a Sub/NiCrNx/Ag/NiCrNx/SiNx/Air structure on thickness of SiNx protective layer were investigated in details. The reflectance, transmittance, total scattering loss measurements and scanning electron microscope (SEM) imaging were employed to characterize the spectral properties and surface morphology, and accelerated environmental tests, including humidity test and salt fog test, were applied to investigate the environmental durability. Five magnetron-sputtering prepared protected-silver mirrors with SiNx layer thicknesses between 8 nm to 16 nm were tested. The results showed that both optical and corrosion-resistant properties of protected-silver mirrors were SiNx thickness dependent and the optimum SiNx thickness should be approximately 14 nm for Sub/NiCrNx/Ag/NiCrNx/SiNx/Air protected-silver mirrors to have both reasonably high reflectance in the visible spectral range and high corrosion resistance for long lifetime applications in harsh environments.

To study the characteristics of a high-energy proton beam produced by the interaction between the ultra-intense pulse laser and a composite target, we set up an experiment using the \SILEX-I" laser device. Using the CR39-type nuclear track detector (NTD), HD810-type radiochromic films (RCF), and Thomson ion spectrometer, we measure the density, space distribution, yield, and energy spectrum of the proton beam, which are mainly produced in the normal direction of the target back. The results show that the proton-beam launch direction has nothing to do with the ultra-intense laser pulse incident direction; the proton-beam space distribution is within the disc, silk or ring structure, the launch field angle of the proton beam is small, and the high-energy proton beam has a cut-off energy, which is related to the thickness of the target. These experimental results can provide important parameters and reference for the development of the laser proton imaging and treatment device.

// Yan Lin 1, * , Shengsheng Wang 2, * , Xiaohui Zhang 1 , Changjun Wang 1 , Guangliang Shan 3 , Yidong Zhou 1 , Feng Mao 1 , Jinghong Guan 1 , Xin Huang 1 , Ying Zhong 1 , Qiang Sun 1 1 Department of Breast Disease, Peking Union Medical College Hospital, Peking Union Medical College, Beijing 100730, China 2 Physical Examination Center, Peking Union Medical College Hospital, Peking Union Medical College, Beijing 100730, China 3 Department of Epidemiology, Institute of Basic Medical Sciences, Peking Union Medical College, Beijing 100730, China * These authors have contributed equally to this work Correspondence to: Qiang Sun, email: pumclinyan@163.com Keywords: breast cancer, case-control study, striking life events Abbreviations: BMI: body mass index; CI: confidence intervals; ORs: odds ratios. Received: November 15, 2016 Accepted: March 19, 2017 Published: June 27, 2017 ABSTRACT The current case-control study investigated the relationship between striking life events and breast cancer in Chinese women. A total of 265 primary breast cancer patients and 265 controls were enrolled with matching for age and completed questionnaires. Logistic regression analysis was used. Thirty-nine breast cancer patients reported striking life events and twenty-four of the controls reported striking life events. The number of striking life events was significantly greater in patients ( p = 0.04). It indicated a striking life event led to a 1.726-fold increased HR (95% CI 1.005-2.965, p < 0.05) for breast cancer with adjustment for age, and a 1.811-fold increased HR (95% CI 1.021 - 3.212, P < 0.05) with adjustment for age, BMI, and late age at menopause. High BMI (OR: 1.680, 95% CI: 1.258-2.196, p < 0.05) and a family history of breast cancer (OR: 2.244, 95% CI: 1.065-4.729, p < 0.05, respectively) increased the risk of breast cancer, and late age at menopause decreased the risk for breast cancer (OR: 0.513, 95% CI: 0.303-0.868, p < 0.05). Our findings indicate a significant association between striking life events and breast cancer in Chinese women, especially in the subpopulation with high BMI or family history of breast cancer.

Background: Apocrine carcinoma was a rare subtype of breast cancer. Due to its rarity and lack of standardized diagnostic criteria, there was no consensus on its biological behaviors. The present study retrospectively analyzed the Surveillance, Epidemiology, and End Results (SEER) database to clarify the impact of apocrine feature on breast cancer prognosis. Materials and Methods: Patient data for invasive apocrine (aBC), mucinous (mBC) or ductal (IDC) breast cancer between 2010 and 2012 were obtained from SEER program. Kaplan-Meier method and Cox proportion hazard regression were adopted for breast cancer-specific survival (BCSS) and overall survival (OS) analyses. Results: There were totally 306 aBC, 2733 mBC and 120127 IDC enrolled. Compared with IDC, aBC tended to occur in elderly patients with higher histological grade, more triple-negative breast cancer (TNBC) and less radiation therapy. Except univariate analysis revealed aBC had shortened BCSS than mBC (HR 5.020, p< 0.001), neither mBC nor IDC revealed BCSS or OS advantage over aBC. As for TNBC, aBC was associated with prolonged BCSS (univariate: HR 0.329, p = 0.020; multivariate: HR 0.183, p = 0.017) and OS (univariate: HR 0.445, p = 0.028; multivariate: HR 0.338, p = 0.016) over IDC. This finding was consistent with the results for hormone receptor negative breast cancers. Conclusion: aBC had the trend with worse BCSS than mBC and comparable prognosis as IDC. Morphological apocrine features indicated favorable prognosis for TNBC and hormone receptor negative subtype. Future studies were warranted to further evaluate the prognostic value of different histological types. Table 1. Clinicopathological characteristics of patients with aBC and IDCCharacteristicsaBC (N=306)IDC (N=120127)p value cMedian Follow-up (months)(IQR)22.0 (10.0-35.8)21.0 (10.0-33.0)Age (Mean ± SD)60.7 ± 11.357.8 ± 11.8< 0.001RaceWhite225 (73.8%)93483 (78.3%)0.108Black39 (12.8%)13690 (11.5%)Others a41(13.4%)12145 (10.2%)Marital StatusMarried166 (57.2%)70109 (61.4%)0.164Not Married b124 (42.8%)44086 (38.6%)LateralityLeft136 (44.4%)60705 (50.5%)0.038Right170 (55.6%)59410 (49.5%)GradeI19 (6.4%)24345 (20.8%)< 0.001II159 (53.9%)48323 (41.3%)III / IV117 (39.7%)44294 (37.9%)AJCC StageI154 (50.3%)64223 (53.5%)0.334II109 (35.6%)41978 (34.9%)III43 (14.1%)13926 (11.6%)T StageT1187 (61.1%)75070 (62.5%)0.358T289 (29.1%)36385 (30.3%)T319 (6.2%)5755 (4.8%)T411 (3.6%)2917 (2.4%)N StageN0202 (66.0%)81605 (68.0%)0.589N173 (23.9%)28830 (24.0%)N220 (6.5%)6413 (5.3%)N311 (3.6%)3228 (2.7%)Molecular SubtypeHER2-/ER+62 (20.3%)83840 (69.8%)0.001HER2+/ER+27 (8.8%)14194 (11.8%)HER2+/ER-54 (17.6%)6331 (5.3%)Triple Negative163 (53.3%)15762 (13.1%)SurgeryBCS156 (53.1%)67965 (58.5%)0.067Mastectomy138 (46.9%)48214 (41.5%)RadiationYes139 (48.4%)64981 (56.4%)0.008No148 (51.6%)50270 (43.6%) Table 2. Clinicopathological characteristics of patients with aBC and mBCCharacteristicsaBC (N=306)mBC (N=2733)p value cMedian Follow-up (months)(IQR)22.0 (10.0-35.8)21.0 (9.0-34.0)Age (Mean ± SD)60.7 ± 11.362.5 ± 12.30.018RaceWhite225 (73.8%)2050 (75.5%)0.709Black39 (12.8%)342 (12.6%)Others a41(13.4%)322 (11.9%)Marital StatusMarried166 (57.2%)1454 (56.1%)0.756Not Married b124 (42.8%)1138 (43.9%)LateralityLeft136 (44.4%)1397 (51.1%)0.031Right170 (55.6%)1335 (48.9%)GradeI19 (6.4%)1538 (60.7%)< 0.001II159 (53.9%)887 (35.0%)III / IV117 (39.7%)110 (4.3%)AJCC StageI154 (50.3%)1773 (64.9%)< 0.001II109 (35.6%)851 (31.1%)III43 (14.1%)109 (4.0%)T StageT1187 (61.1%)1825 (66.8%)0.002T289 (29.1%)741 (27.1%)T319 (6.2%)136 (5.0%)T411 (3.6%)31 (1.1%)N StageN0202 (66.0%)2465 (90.2%)< 0.001N173 (23.9%)221 (8.1%)N220 (6.5%)33 (1.2%)N311 (3.6%)14 (0.5%)Molecular SubtypeHER2-/ER+62 (20.3%)2544 (93.1%)< 0.001HER2+/ER+27 (8.8%)22 (0.8%)HER2+/ER-54 (17.6%)151 (5.5%)Triple Negative163 (53.3%)16 (0.6%)SurgeryBCS156 (53.1%)1769 (66.3%)< 0.001Mastectomy138 (46.9%)898 (33.7%)RadiationYes139 (48.4%)1473 (55.1%)0.037No148 (51.6%)1201 (44.9%) Table 3. Comparison of BCSS and OS between aBC and IDC by multivariate Cox proportional hazard model according to different molecular subtypesUnivariateMultivariateHazard ratio (95% CI)ap valuebHazard ratio (95% CI)ap valuebAll BCSS1.224 (0.611 - 2.450)0.5680.726 (0.180 - 2.933)0.652OS1.100 (0.624 - 1.939)0.7420.394 (0.098 - 1.585)0.190ER+BCSS2.773 (0.893 - 8.609)0.0661.764 (0.440 - 7.092)0.423OS1.358 (0.438 - 4.214)0.5951.012 (0.253 - 4.049)0.987ER-BCSS0.378 (0.157 - 0.910)0.0240.241 (0.077 - 0.751)0.014OS0.517 (0.268 - 0.995)0.0440.409 (0.194 - 0.864)0.019ER+/HER2-BCSS3.961 (1.275 - 12.30)0.0102.370 (0.590 - 9.524)0.224OS1.912 (0.616 - 5.932)0.2541.370 (0.342 - 5.495)0.656ER+/HER2+ cBCSSNANANANAOSNANANANAER-/HER2+BCSS0.601 (0.084 - 4.287)0.6080.840 (0.117 - 6.061)0.862OS0.854 (0.213 - 3.431)0.8241.120 (0.277 - 4.525)0.874TNBCBCSS0.329 (0.123 - 0.880)0.0200.183 (0.046 - 0.736)0.017OS0.445 (0.212 - 0.935)0.0280.338 (0.140 - 0.816)0.016 Table 4. Comparison of BCSS and OS between aBC and mBC by multivariate Cox proportional hazard model according to different molecular subtypesUnivariateMultivariateHazard ratio (95% CI)ap valuebHazard ratio (95% CI)ap valuebAll BCSS5.020 (2.106 - 11.97) Citation Format: Changjun Wang, Yu Song, Hanjiang Zhu, Yidong Zhou, Feng Mao, Yan Lin, Yanna Zhang, Xiaohui Zhang, Songjie Shen, Ying Zhong, Xin Huang, Qiang Sun. Morphological apocrine and mucinous features of breast carcinoma: Does histology matter for survival? [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-06-31.

Idiopathic granulomatous mastitis (IGM) has a high prevalence in Asia and Africa[1]. It usually presents as a tender mass with rapid progression and has a recurrent or prolonged natural disease cou...

// Qianqian Xu 1 , Yali Xu 1 , Bo Pan 1 , Liangcai Wu 2 , Xinyu Ren 3 , Yidong Zhou 1 , Feng Mao 1 , Yan Lin 1 , Jinghong Guan 1 , Songjie Shen 1 , Xiaohui Zhang 1 , Changjun Wang 1 , Ying Zhong 1 , Liangrui Zhou 3 , Zhiyong Liang 3 , Haitao Zhao 2 , Qiang Sun 1 1 Department of Breast Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China 2 Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China 3 Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China Correspondence to: Qiang Sun, email: sunqiangpumc@126.com Haitao Zhao, email: ZhaoHT@pumch.cn Keywords: triple-negative breast cancer (TNBC), TTK, biomarker, prognostic indicator, survival analysis Received: September 20, 2016 Accepted: October 19, 2016 Published: November 09, 2016 ABSTRACT Purpose: Previous studies demonstrate that threonine and tyrosine kinase (TTK) is overexpressed in triple-negative breast cancer (TNBC), but there are conflicting results regarding its effect on TNBC survival. The purpose of this study was to assess the prognostic significance of TTK expression in primary TNBC. Results: Of 169 consecutive cases eligible for this study, 164 included follow-up information. Cytoplasm and membrane TTK staining was observed in 99.4% of cases, while 5.9% displayed whole cell immunostaining. At a discriminating threshold of 55, elevated TTK expression was associated with prolonged disease free survival (DFS) ( p < 0.001) and overall survival (OS) ( p = 0.024) in primary TNBC and prolonged DFS in individual basal-like ( p = 0.001) and non-basal-like ( p = 0.001) TNBC subtypes. In addition, Cox regression analysis demonstrated that elevated TTK expression was an independent prognostic factor for DFS in TNBC ( p < 0.001). Methods: TTK expression of 169 samples was tested by immunohistochemistry (IHC). A receiver operating characteristic (ROC) curve was used to identify a cutpoint for TTK expression, which was analyzed for its association with patients’ clinicopathological factors and survival using Chi-square, log-rank, and Cox regression analyses. Conclusions: TTK is a favorable prognostic biomarker associated with TNBC survival.

To evaluate and compare the efficacy and safety of the taxane plus anthracycline (TA) regimen vs. the taxane plus anthracycline plus cyclophosphamide (TAC) regimen as adjuvant chemotherapy in Chinese patients with node-positive breast cancer (BCa). Patients with BCa (n = 640) were recruited between January 2010 and June 2012. All patients were randomized to receive six cycles of adjuvant therapy with the TA or TAC regimen. The primary endpoint was disease-free survival (DFS). The secondary endpoints were overall survival (OS), quality of life (QoL), and chemotherapy-related toxicity. Finally, 630 patients were evaluable, with a median follow-up of 70 months. There were no differences in the 70-month median DFS and OS between the two groups (DFS: TA 79.7% vs. TAC 75.6%, P = 0.371; OS: TA vs. TAC, 85.1% vs. 87.6%, P = 0.271). The TA group had lower frequencies grade III/IV vomiting (TA vs. TAC, 11.7% vs. 18.1%, P = 0.025) and nausea (13.0% vs. 19.4%, P = 0.031). The health-related QoL score was higher in the TA group (74.1 ± 5.3 vs. 67.9 ± 4.4, P = 0.001 vs. TAC). In the adjuvant setting, compared with the TAC regimen, the TA regimen exhibits no significant difference with respect to DFS and OS in Chinese patients with node-positive BCa. On the other hand, TA is associated with less severe adverse events, lower economic burden, and better QoL.

In the location-related planning of a hydropower system, the consideration of future operations under uncertainties can make the decisions sustainable and robust. Then, it is of great importance to develop an effective approach that deals with the long-term stochasticity due to the long-lasting effects of the location selections. Thus, we propose a multistage stochastic programming model to optimize the planning decisions of cascade hydropower stations and the long-term stochastic operations in an integrated way. The first stage (i.e., the planning stage) in the model deals with the location and capacity decisions of the hydropower stations, while the subsequent stages implement the scheduling decisions under each stagewise stochastic scenario. To address the curse of dimensionality caused by the long-term stochastic operations, we further propose a novel dimensionality reduction approach based on dual equilibrium to transform the multistage model into a tractable two-stage stochastic program. The applicability of our approach is validated by a case study based on a basin of Yangtze River, China, and corresponding sensitivity analysis. Published version

Purpose. To investigate the association of ptosis, levator, and jaw winking in Marcus Gunn jaw-winking synkinesis (MGJWS), and the risk factor of preservation and outcomes of the unilateral levator excision and frontalis suspension.Methods. Clinical features of MGJWS case series from 2011 to 2018 were retrospectively reviewed. Association between jaw winking and ptosis/levator function was statistically analyzed. The patients underwent unilateral levator excision and frontalis suspension using silicone rod or autogenous fascia lata. Clinical outcomes were evaluated in operated patients and the independent risk factors of residual jaw winking were investigated after a long follow-up.Results. There were 42 MGJWS patients in 2011 to 2018, accounting for 2.87% of all congenital blepharoptosis. 80% of mild jaw winking was accompanied with mild ptosis and fair levator function, and moderate-to-severe jaw winking was often accompanied with moderate-to-severe ptosis and poor levator function (P<0.05). Ptosis showed a strong association with excursion of jaw winking (R = 0.785,P<0.01). Jaw winking was resolved in all 34 operated patients with good correction of ptosis. Severity of jaw winking is an independent risk factor for the residual synkinesis after surgery. Severe preoperative jaw winking had an 18.05 times increased risk of postoperative residual synkinesis compared with moderate jaw winking (P<0.05).Conclusions. In MGJWS eyelid excursion of jaw winking has a direct correlation with ptosis and dysfunction of levator muscle. Unilateral levator aponeurosis excision and frontalis suspension is an efficient approach for MGJWS. Severe jaw winking is a risk factor of residual eyelid synkinesis after surgery.

Background Disease caused by Bacillus anthracis is often accompanied by high mortality primarily due to toxin-mediated injury. In the early disease course, anthrax toxins are secreted; thus, antibiotic use is limited to the early stage. In this regard, antibodies against the toxin component, protective antigen (PA), play an important role in protecting against anthrax. Therefore, we developed PA21, a fully human anti-PA immunoglobulin G monoclonal antibody. Methods Combining human Fab was screened from a phage library with human heavy constant regions. Enzyme-linked immune sorbent assay, Western blot analysis and immunoprecipitation test evaluated the binding ability of PA21. Moreover, the affinity and neutralizing activity of the antibody was detected in vitro while the protective effectiveness in 60 rats was also examined in vivo. Results The Fischer 344 rats challenged with the lethal toxin can be protected by PA21 at a concentration of 0.067 mg/kg. All six rats remained alive although PA21 was injected 24 h before the toxin challenge. PA21 did not influence the binding of PA to cell receptors and that of a lethal factor to PA. Conclusion The PA21 monoclonal antibody against PA can be used for emergency prophylaxis and anthrax treatment.

Deep learning methods have been applied to Chinese named entity recognition for the online medical consultation. They require a large number of marked samples. However, no such database is available at present. This paper begins with constructing a larger labelled Chinese texts database for the online medical consultation. Second, a basic framework unit is proposed, which is pre-trained by the transfer learning from both Bidirectional language model and Mask language model trained on the larger unlabelled data. Finally, cross domains adversarial learning (CDAL) for Chinese named entity recognition is proposed to further improve the performance, which not only uses the pre-trained basic framework unit, but also uses the adversarial multi-task learning on both electronic medical record texts and online medical consultation texts. Experimental results validate the effectiveness of CDAL.