ABSTRCT Purpose To explore the evolution of HER2 nega-tive subgroups(IHC Null,Ultra-low and 1+)in breast cancer with hormone receptor(HR)positive before and after neoadju-vant therapy,and the relationship with clinical pathological fea-tures.Methods There were 255 patients who did not achieve pathological complete response(pCR)consecutively after neoad-juvant therapy.Immunohistochemistry was used to detect the ex-pression of ER,PR,HER2 and Ki67 and to evaluate the evolu-tion of HER2-negative subgroups after neoadjuvant therapy and its relationship with clinicopathological characteristics.Results Among the 255 patients included in this study,HER2 expression was 0 and 1+in 116 cases(45.5％)and 139 cases(54.7％)respectively before neoadjuvant therapy,and then HER2 0 was further divided into Null group(61 cases,23.9％)and Ultra-low group(55 cases,21.6％).After neoadjuvant therapy,HER2 expression was 0 and 1+in 117 cases(45.9％)and 138 cases(54.1％)respectively,and then HER2 0 was further di-vided into Null group(64 cases,25.1％)and Ultra-low group(53 cases,20.8％).HER2 status changed in 121 patients(47.5％)after neoadjuvant therapy.The highest conversion rate was from HER2 Ultra-low before neoadjuvant therapy to 1+after neoadjuvant therapy,with a conversion rate of 11.76％(30/255),followed by HER2 1+to the Ultra-low,with a conversion rate of 10.98％(28/255).After the neoadjuvant therapy,44 of 55 cases had transformation in the HER2 Ultra-low group,with the conversion rate of as high as 80％.Chi-square test showed that HER2 expression before neoadjuvant therapy was correlated with the maximum tumor diameter(≤2 cm,＞2cm)after neo-adjuvant therapy(x2=6.106,P=0.047);the tumor of HER21+before neoadjuvant therapy was mostly 2 cm or less in the di-ameter.The HER2 status after neoadjuvant therapy was correla-ted with the tumor thrombus(x2=6.975,P=0.029).Patients with HER2 Ultra-low after treatment were more likely to have vascular invasion.Conclusion In HR positive breast cancer,when the HER2 0 cases are divided into Ultra-low and Null sub-groups,the HER2 conversion rate increases significantly after neoadjuvant therapy,in which the Ultra-low conversion rate is the highest,indicating that the HER2 Ultra-low cases are highly unstable after neoadjuvant therapy.It is important to detect HER2 expression in residual lesions after neoadjuvant therapy and to identify the Ultra-low HER2 expression subgroup.

BACKGROUND: Breast cancer patients who are positive for hormone receptor typically exhibit a favorable prognosis. It is controversial whether chemotherapy is necessary for them after surgery. Our study aimed to establish a multigene model to predict the relapse of hormone receptor-positive early-stage Chinese breast cancer after surgery and direct individualized application of chemotherapy in breast cancer patients after surgery. METHODS: In this study, differentially expressed genes (DEGs) were identified between relapse and nonrelapse breast cancer groups based on RNA sequencing. Gene set enrichment analysis (GSEA) was performed to identify potential relapse-relevant pathways. CIBERSORT and Microenvironment Cell Populations-counter algorithms were used to analyze immune infiltration. The least absolute shrinkage and selection operator (LASSO) regression, log-rank tests, and multiple Cox regression were performed to identify prognostic signatures. A predictive model was developed and validated based on Kaplan-Meier analysis, receiver operating characteristic curve (ROC). RESULTS: A total of 234 out of 487 patients were enrolled in this study, and 1588 DEGs were identified between the relapse and nonrelapse groups. GSEA results showed that immune-related pathways were enriched in the nonrelapse group, whereas cell cycle- and metabolism-relevant pathways were enriched in the relapse group. A predictive model was developed using three genes ( CKMT1B , SMR3B , and OR11M1P ) generated from the LASSO regression. The model stratified breast cancer patients into high- and low-risk subgroups with significantly different prognostic statuses, and our model was independent of other clinical factors. Time-dependent ROC showed high predictive performance of the model. CONCLUSIONS A multigene model was established from RNA-sequencing data to direct risk classification and predict relapse of hormone receptor-positive breast cancer in Chinese patients. Utilization of the model could provide individualized evaluation of chemotherapy after surgery for breast cancer patients.
Humans ; Female ; Breast Neoplasms/genetics* ; East Asian People ; Neoplasm Recurrence, Local/genetics* ; Breast ; Algorithms ; Chronic Disease ; Prognosis ; Tumor Microenvironment

Objective: To understand the consistency of ALK Ventana-D5F3 immunohistochemistry (IHC) interpretation in Chinese lung adenocarcinoma among histopathologists from different hospitals, and to recommend solution for the problems found during the interpretation of ALK IHC in real world, with the aim of the precise selection of patients who can benefit from ALK targeted therapy. Methods: This was a multicenter and retrospective study. A total of 109 lung adenocarcinoma cases with ALK Ventana-D5F3 IHC staining were collected from 31 lung cancer centers in RATICAL research group from January to June in 2018. All cases were scanned into digital imaging with Ventana iSCANcoreo Digital Slide Scanning System and scored by 31 histopathologists from different centers according to ALK binary (positive or negative) interpretation based on its manufacturer′s protocol. The cases with high inconsistency rate were further analyzed using FISH/RT-PCR/NGS. Results: There were 49 ALK positive cases and 60 ALK negative cases, confirmed by re-evaluation by the specialist panel. Two cases (No. 2302 and No.2701) scored as positive by local hospitals were rescored as negative, and were confirmed to be negative by RT-PCR/FISH/NGS. The false interpretation rate of these two cases was 58.1% (18/31) and 48.4% (15/31), respectively. Six out of 31 (19.4%) pathologists got 100% accuracy. The minimum consistency between every two pathologists was 75.8%.At least one pathologist gave negative judgement (false negative) or positive judgement (false positive) in the 49 positive or 60 negative cases, accounted for 26.5% (13/49), 41.7% (25/60), respectively, with at least one uncertainty interpretation accounted for 31.2% (34/109). Conclusion There are certain heterogeneities and misclassifications in the real world interpretation of ALK-D5F3 IHC test, which need to be guided by the oncoming expert consensus based on the real world data.

Objective: To analyze the expression of programmed death ligand 1 (PD-L1) in patients with advanced lung adenocarcinoma and the consistency of four PD-L1 immunohistochemical detection platforms, with an aim of establishing baseline information to predict and select patients for programmed death 1 (PD-1)/PD-L1 immune inhibitor therapy. Methods: This was a multi-center retrospective study, collecting totally 57 advanced lung adenocarcinoma biopsy specimens from four centers from August 2017 to December 2017.The mean age of 57 patients was 59 (range 34-81) years, and 29 cases were male, 28 cases were female. Four PD-L1 immunohistochemical stains were done for each case, including 22C3 (Dako), 28-8 (Abcam), SP263 (Ventana), and SP142 (Ventana). Among them, 22C3 staining was done using Dako autostainer, and for the other three antibodies, Ventana Ultraview detection system and autostainer was used. The immunohistochemical slides were read by two trained histopathologists in a double-blinded way, and the percentage of PD-L1 positive tumor cells was assessed as <1%, 1%-24%, 25%-49% and more than 50%. Results: The Dako 22C3 was used as the standard. There were eight cases in which the PD-L1 staining was more than 50% (14.0%, 8/57). The staining consistency of tumor cells was higher in 22C3, 28-8 and SP263 (ρ=0.729-0.809). The two scoring doctors had a high degree of concordance in PD-L1 positive tumor cells (ρ=0.707-0.896), and this was most noticeable in 22C3 and SP263. Conclusions 22C3, 28-8 and SP263 show high consistency in tumor cell staining. The study can provide an effective basis for screening for potential patient population that may benefit from immunotherapy.

Objective To investigate the clinical features of divergence paralysis improve the diagnostic and therapeutic ability,and evaluate the effect of surgical and non-surgical treatment.Methods It was a retrospective case series study.11 cases with complete data,diagnosed and treated as divergence paralysis in Tianjin Eye Hospital from September 2014 to January 2016,were summarized.The observation items included general date,neurologica consultation,comprehensive eye examination,and the eye position and movement,deviation degree,binocular vision,AC / A,diplopia examination of pre-treatment and post-treatment.The patients were followed up from 3 months to 1.5 yeas,averaged 6.9 months.Results In our study,1 patient was MillerFisher syndrome,3 cases had a history of hypertension,and 1 case had the history of intaking sleeping pills for about 3 months.The rest of the patients denied the nervous system disease,cardiovascular disease and other medical history.All patients complained about uncrossed diplopia only at distance.All of the 11 patients had a sudden onset of their symptoms.Each patient was examined by same neurologist,meanwhile MRI or CT were performed.All the results showed normal.All patients had refractive error.The angle of esotropia for distance of 5 meters was from + 25 △ to + 55 △ and was from + 8 △ to + 40△ for near(33 cm)before treatment while changed into-4△ ～ + 12△ for distance (5m) and to-8△ ～ +8△ for near (33 cm) after treatment.The ratio of AC / A ranged from 1.3 to 4.0,with an average of 2.6.Conclusion The clinical characteristics of divergence paralysis are a greater angle of esotropia and ipsilateral diplopia.Lateral rectns resection and non-surgical treatment have better effects on the improvement of diplopia and esotropia.

Objective We investigated whether cirrhotic patients with upper gastrointestinal hemorrhage should be stratified for antibiotic prophylaxis based on Child-Pugh scores and etiology,to estimate risks of nosocomial infection,six-week re-bleeding,and mortality,and whether antibiotics prophylaxis have equal effects on patients of all Child-Pugh classes and etiologies.Methods A total of 316 hospitalized patients of cirrhosis patients with upper gastrointestinal hemorrhage were analyzed.The patients were classified as antibiotic group and control group,according to the patients whether received antibiotic prophylaxis or not.The two groups were monitored nosocomial infection rates,six-week re-bleeding rates and mortality rates.Results (1) Antibiotic prophylaxis reduces rates of nosocomial infection,six-week re-bleeding.(2)According to the etiology,cirrhosis can be divided into viral cirrhosis (VC) group and alcoholic cirrhosis (AC) group.The nosocomial infection rates and six-week re-bleeding rates of the VC group were lower in the antibiotic group.The nosocomial infection rates and the six-week re-bleeding rates of the AC group were lower in the antibiotic group.(3) According to Child-Pugh classification,patients were divided into Child-Pugh class A,B,C three groups.Child-Pugh class A group:the nosocomial infection rates,six-week re-bleeding rates and mortality rates had no significant difference between the antibiotic group and control group.Child-Pugh class B group:the nosocomial infection rates and six-week re-bleeding rates were lower in the antibiotic group.Child-Pugh class C group:the nosocomial infection rates and six-week re-bleeding rates were lower in the antibiotic group.Conclusion Antibiotic prophylaxis reduces rates of nosocomial infection,six-week re-bleeding in cirrhosis patients with upper gastrointestinal hemorrhage,so the writer suggests short-term antibiotic prophylaxis.Antibiotics prophylaxis have equal effects on cirrhosis patients of different etiologies.While antibiotics prophylaxis have no equal effects on cirrhosis patients of all Child-Pugh classes.The nosocomial infection rates,six-week-rebleeding rates and mortality rates of Child-Pugh class A are low.The recommendation for routine antibiotic prophylaxis for this subgroup requires further evaluation.

Three new sesquiterpene glycosides, named codonopsesquilosides A-C (1-3), were isolated from an aqueous extract of the dried roots of Codonopsis pilosula. Their structures including absolute configurations were determined by spectroscopic and chemical methods. These glycosides are categorized as C15 carotenoid (1), gymnomitrane (2), and eudesmane (3) types of sesquiterpenoids, respectively. Compound 1 is the first diglycoside of C15 carotenoids to be reported. Compound 2 represents the second reported example of gymnomitrane-type sesquiterpenoids from higher plants. The absolute configurations were supported by comparison of the experimental circular dichroism (CD) spectra with the calculated electronic CD (ECD) spectra of 1-3, their aglycones, and model compounds based on quantum-mechanical time-dependent density functional theory. The influences of the glycosyls on the calculated ECD spectra of the glycosidic sesquiterpenoids, as well as some nomenclature and descriptive problems with gymnomitrane-type sesquiterpenoids are discussed.

The implementation of cancer genome scientific program has promoted the diagnosis, prevention and tar-get treatment of diseases at molecular level with massive cancer genome data accumulated. Effective mining and use of cancer genome data have thus become the focus in the field of cancer genome. The cancer genome was annotated and demonstrated according to the mining of high-throughput cancer genome data from American National Cancer Research Center, namely the disease-named entity and drug-named entity were identified from the gene function descriptive text and the mined high-throughput data were annotated from their clinical application, in order to help scientific workers to find the relationship between diseases, drugs and genes in scientific literature.

Four new acetylenes (1-4) and one new unsaturated ω-hydroxy fatty acid (5), together with 5 known analogues, were isolated from an aqueous extract of Codonopsis pilosula roots. Their structures were determined by spectroscopic and chemical methods. The new acetylenes are categorized as an unusual cyclotetradecatrienynone (1), tetradecenynetriol (2), and rare octenynoic acids (3 and 4), respectively, and 3 and 4 are possibly derived from oxidative metabolic degradation of 1 and/or 2. The absolute configuration of 1 was assigned by comparison of the experimental circular dichroism (CD) spectrum with the calculated electronic circular dichroism (ECD) spectra of stereoisomers based on the quantum-mechanical time-dependent density functional theory, while the configuration of 2 was assigned by using modified Mosher׳s method based on the MPA determination rule of Δδ RS values for diols.

A data link-based information aggregation model was established by analyzing the dimensions, approaches, model and its application scope of case specific information aggregation according to the link between information characteristics and the link between information use processes followed by a substantial evidence analysis of information aggregation with Middle East Respiratory Syndrome as an example, which showed that the model can be used in case analysis of health field.