Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).

Objective: Explore the relationship between tip of the left bundle branch pacing lead and anatomic location of left bundle branch as well as the mechanism of left bundle branch current of injury. To clarify the clinical value of left bundle branch current of injury during operation. Methods: The pacing leads were implanted in the hearts of two living swines. Intraoperative electrophysiological study confirmed that the left bundle branch or only the deep left ventricular septum was captured at low output. Immediately after operation, the gross specimen of swine hearts was stained with iodine to observe the gross distribution of His-purkinje conduction system on the left ventricular endocardium and its relationship with the leads. Subsequently, the swine hearts were fixed with formalin solution, and the pacing leads were removed after the positions were marked. The swine hearts were then sectioned and stained with Masson and Goldner trichrome, and the relationship between the anatomic location of the conduction system and the tip of the lead was observed under a light microscope. Results: After iodine staining of the specimen, the His-purkinje conduction system was observed with the naked eye in a net-like distribution, and the lead tip was screwed deeply and fixed in the left bundle branch area of the left ventricular subendocardium in the ventricular septum. Masson and Goldner trichrome staining showed that left bundle branch pacing lead directly passed through the left bundle branch when there was left bundle branch potential with left bundle branch current of injury, while it was not directly contact the left bundle branch when there was left bundle branch potential without left bundle branch current of injury. Conclusion: The left bundle branch current of injury observed on intracardiac electrocardiogram during His-purkinje conduction system pacing suggests that the pacing lead directly contacted the conduction bundle or its branches, therefore, the captured threshold was relatively low. Left bundle branch current of injury can be used as an important anatomic and electrophysiological evidence of left bundle branch capture.
Animals ; Swine ; Bundle of His/physiology* ; Ventricular Septum ; Cardiac Pacing, Artificial ; Heart Conduction System ; Electrocardiography ; Iodine

Objective: Explore the relationship between tip of the left bundle branch pacing lead and anatomic location of left bundle branch as well as the mechanism of left bundle branch current of injury. To clarify the clinical value of left bundle branch current of injury during operation. Methods: The pacing leads were implanted in the hearts of two living swines. Intraoperative electrophysiological study confirmed that the left bundle branch or only the deep left ventricular septum was captured at low output. Immediately after operation, the gross specimen of swine hearts was stained with iodine to observe the gross distribution of His-purkinje conduction system on the left ventricular endocardium and its relationship with the leads. Subsequently, the swine hearts were fixed with formalin solution, and the pacing leads were removed after the positions were marked. The swine hearts were then sectioned and stained with Masson and Goldner trichrome, and the relationship between the anatomic location of the conduction system and the tip of the lead was observed under a light microscope. Results: After iodine staining of the specimen, the His-purkinje conduction system was observed with the naked eye in a net-like distribution, and the lead tip was screwed deeply and fixed in the left bundle branch area of the left ventricular subendocardium in the ventricular septum. Masson and Goldner trichrome staining showed that left bundle branch pacing lead directly passed through the left bundle branch when there was left bundle branch potential with left bundle branch current of injury, while it was not directly contact the left bundle branch when there was left bundle branch potential without left bundle branch current of injury. Conclusion: The left bundle branch current of injury observed on intracardiac electrocardiogram during His-purkinje conduction system pacing suggests that the pacing lead directly contacted the conduction bundle or its branches, therefore, the captured threshold was relatively low. Left bundle branch current of injury can be used as an important anatomic and electrophysiological evidence of left bundle branch capture.
Animals ; Swine ; Bundle of His/physiology* ; Ventricular Septum ; Cardiac Pacing, Artificial ; Heart Conduction System ; Electrocardiography ; Iodine

Objective: To analyze the efficacy of sinonasal adenoid cystic carcinoma (ACC) with perineural invasion (PNI), and explore the prognostic value of PNI on sinonasal adenoid cystic carcinoma. Methods: The clinical data of 105 patients with sinonasal ACC admitted to Cancer Hospital, Chinese Academy of Medical Sciences from January 2000 to December 2016 were retrospectively reviewed. All patients were restaged according to American Joint Committee on Cancer 8th edition. Follow-up visits were conducted to obtain information of treatment failure and survival outcome. The Log rank test was used for univariate analysis of prognostic factors, and Cox regression model was used for multivariate prognostic analysis. Results: The maxillary sinus (n=59) was the most common primary site, followed by the nasal cavity (n=38). There were 93 patients with stage Ⅲ-Ⅳ. The treatment modalities included surgery alone (n=14), radiotherapy alone (n=13), preoperative radiotherapy plus surgery (n=10), and surgery plus postoperative radiotherapy (n=68). The median follow-up time was 91.8 months, the 5-year local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) rates were 72.6%, 73.0%, 52.9% and 78.0%, respectively. There were 33 patients (31.4%) with PNI-positive. The 5-year DMFS, PFS, and OS rates of PNI-positive group were 53.7%, 29.4% and 56.5%, respectively, which were significantly inferior to those of PNI-negative group (80.8%, 63.0% and 86.8%, respectively, P<0.05), while there was no significant difference in the 5-year LC rate between both groups (64.5% vs 76.5%, P=0.273). The multivariate Cox regression analysis showed PNI was one of the poor prognostic factors of DMFS (HR=3.514, 95%CI: 1.557-7.932), PFS (HR=2.562, 95%CI: 1.349-4.866) and OS (HR=2.605, 95%CI: 1.169-5.806). Among patients with PNI-positive, the 5-year LC, PFS and OS rates of patients received surgery combined with radiotherapy were 84.9%, 41.3% and 72.7%, respectively, which were significantly higher than 23.3%, 10.0% and 26.7% of patients receiving surgery or radiotherapy alone (P<0.05). Conclusion: The presence of PNI increases the risk of distant metastasis in patients with sinonasal ACC. Compared with patients with PNI-negative, the prognosis of patients with PNI-positive is relatively poor, and surgery combined with radiotherapy for PNI-positive sinonasal ACC results in good clinical outcomes.
Carcinoma, Adenoid Cystic/pathology* ; Humans ; Paranasal Sinus Neoplasms/therapy* ; Prognosis ; Proportional Hazards Models ; Retrospective Studies

Background: The detection of glutamic acid decarboxylase 65 (GAD65) autoantibodies is essential for the prediction and diagnosis of latent autoimmune diabetes in adults (LADA). The aim of the current study was to compare a newly developed electrochemiluminescence (ECL)-GAD65 antibody assay with the established radiobinding assay, and to explore whether the new assay could be used to define LADA more precisely. Methods: Serum samples were harvested from 141 patients with LADA, 95 with type 1 diabetes mellitus, and 99 with type 2 diabetes mellitus, and tested for GAD65 autoantibodies using both the radiobinding assay and ECL assay. A glutamic acid decarboxylase antibodies (GADA) competition assay was also performed to assess antibody affinity. Furthermore, the clinical features of these patients were compared. Results: Eighty-eight out of 141 serum samples (62.4%) from LADA patients were GAD65 antibody-positive by ECL assay. Compared with ECL-GAD65 antibody-negative patients, ECL-GAD65 antibody-positive patients were leaner (P<0.0001), had poorer β-cell function (P<0.05), and were more likely to have other diabetes-associated autoantibodies. The β-cell function of ECLGAD65 antibody-positive patients was similar to that of type 1 diabetes mellitus patients, whereas ECL-GAD65 antibody-negative patients were more similar to type 2 diabetes mellitus patients. Conclusion Patients with ECL-GAD65 antibody-negative share a similar phenotype with type 2 diabetes mellitus patients, whereas patients with ECL-GAD65 antibody-positive resemble those with type 1 diabetes mellitus. Thus, the detection of GADA using ECL may help to identify the subtype of LADA.

Through resources investigation and sample collection,a total number of 392 Dendrobium officinale from 38 different populations,9 provinces were processed for measuring and observing.Fourteen agronomy characterizations like stem height,stem diameter,number of node in stem were selected for further classification.The cluster analysis was performed using Ward and Euclidean method.The results showed that the threshold of genetic distance was 2.77.Thirtyeight populations were divided into 6 groups.The factor analysis showed that,the leaf shape,stem shape,pitch length and leaf color were very important factors for classification.This study establish the foundation for analyzing the genetic relationship of D.officinale from different populations.
Cluster Analysis ; Dendrobium ; anatomy & histology ; classification ; Plant Leaves ; Plants, Medicinal ; anatomy & histology ; classification

Background: Nasopharyngeal carcinoma (NPC) is sensitive to radiotherapy (RT). However, neurocognitive complications such as memory loss and learning and attention deficits emerge in the survivors of NPC who received RT. It remains unclear how radiation affects patient brain function. This pilot study aimed at finding cerebral functional alterations in NPC patients who have received RT. Methods: From September 2014 to December 2016, 42 individuals, including 22 NPC patients and 20 normal volunteer controls in National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College, were recruited in this study. All patients received resting-state functional magnetic resonance imaging scans and neurocognitive tests 1 day before the initiation of RT (baseline) and 1 day after the completion of RT; the 20 normal controls were also subjected to the same scans and tests. The amplitude of the low-frequency fluctuations (ALFF) in blood oxygen level-dependent signals and functional connectivity (FC) were used to characterize cerebral functional changes. Independent t test, paired t test, and analysis of variances were used to obtain statistical significance across groups. Results: After RT, NPC patients showed significantly decreased ALFF values in the calcarine sulcus, lingual gyrus, cuneus, and superior occipital gyrus and showed significantly reduced FC mainly in the default mode network (P < 0.05, corrected by AlphaSim). Relative to the controls, ALFF was decreased in the lingual gyrus, calcarine sulcus, cingulate cortex, medial prefrontal gyrus (P < 0.05, corrected by AlphaSim), and FC reduction was found in multiple cerebellar–cerebral regions, including the cerebellum, parahippocampus, hippocampus, fusiform gyrus, inferior frontal gyrus, inferior occipital gyrus, precuneus, and cingulate cortex (P < 0.001, corrected by AlphaSim). Conclusions Cerebral functional alterations occur immediately after RT. This study may provide an explanation for the cognitive deficits in the morphologically normal-appearing brains of NPC patients after RT and may contribute to the understanding of the complex mechanism of RT.

BACKGROUNDPharmacological therapy for congestive heart failure (CHF) with ventricular arrhythmia is limited. In the study, our aim was to evaluate the effects of Chinese traditional medicine Shensong Yangxin capsules (SSYX) on heart rhythm and function in CHF patients with frequent ventricular premature complexes (VPCs).

METHODSThis double-blind, placebo-controlled, multicenter study randomized 465 CHF patients with frequent VPCs to the SSYX (n = 232) and placebo groups (n = 233) for 12 weeks of treatment. The primary endpoint was the VPCs monitored by a 24-h ambulatory electrocardiogram. The secondary endpoints included the left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter, N-terminal pro-brain natriuretic peptide (NT-proBNP), New York Heart Association (NYHA) classification, 6-min walking distance (6MWD), Minnesota Living with Heart Failure Questionnaire (MLHFQ) scores, and composite cardiac events (CCEs).

RESULTSThe clinical characteristics were similar at baseline. SSYX caused a significantly greater decline in the total number of VPCs than the placebo did (-2145 ± 2848 vs. -841 ± 3411, P < 0.05). The secondary endpoints of the LVEF, NYHA classification, NT-proBNP, 6MWD, and MLHFQ scores showed a greater improvements in the SSYX group than in the placebo group (ΔLVEF at 12th week: 4.75 ± 7.13 vs. 3.30 ± 6.53; NYHA improvement rate at the 8th and 12th week: 32.6% vs. 21.8%, 40.5% vs. 25.7%; mean level of NT-proBNP in patients with NT-proBNP ≥125 pg/ml at 12th week: -122 [Q1, Q3: -524, 0] vs. -75 [Q1, Q3: -245, 0]; Δ6MWD at 12th week: 35.1 ± 38.6 vs. 17.2 ± 45.6; ΔMLHFQ at the 4th, 8th, and 12th week: -4.24 ± 6.15 vs. -2.31 ± 6.96, -8.19 ± 8.41 vs. -3.25 ± 9.40, -10.60 ± 9.41 vs. -4.83 ± 11.23, all P < 0.05). CCEs were not different between the groups during the study period.

CONCLUSIONSIn this 12-week pilot study, SSYX was demonstrated to have the benefits of VPCs suppression and cardiac function improvement with good compliance on a background of standard treatment for CHF.

TRIAL REGISTRATIONwww.chictr.org.cn, ChiCTR-TRC-12002061 (http://www.chictr.org.cn/showproj.aspx?proj=7487) and Clinicaltrials.gov, NCT01612260 (https://clinicaltrials.gov/ct2/show/NCT01612260).

Objective To investigate the related factors of lymph node detection number in rectal cancer patients underwent laparoscopic surgery. Methods 98 patients with rectal cancer who underwent laparoscopic surgery were selected from January 2014 to January 2010. All the patients general information [gender, age, body mass index (BMI)], preoperative imaging findings and pathological data (tumor size, gross type, TNM stage, distant metastasis, histological differentiation and depth of invasion, et al), surgery related data (experience of surgeon, operation time) and preoperative radiotherapy and chemotherapy were collected. Results The age, BMI, tumor size, length of specimen, invasive depth, surgeon and preoperative radiotherapy and chemotherapy was correlated with the number of lymph nodes in patients with laparoscopic surgery (P < 0.05), but gender, TNM staging, general type, histological differentiation, operation time were not associated with the number of lymph nodes detected in minimally invasive surgery for rectal cancer (P > 0.05). Multiple linear regression analysis showed that BMI, tumor size, length of specimen, invasive depth, surgeon and preoperative radiotherapy and chemotherapy were the independent influencing factors of lymph node detection in patients with minimally invasive rectal cancer (P < 0.05). Conclusion The factors of patients, tumor status, surgical factors and preoperative chemoradiotherapy are related to the number of lymph nodes in patients with rectal cancer.

OBJECTIVETo evaluate the clinical efficacy and safety of Huayu Tongbi Recipe (HTR) combined methotrexate (MTX) in treating refractory rheumatoid arthritis (RRA).

METHODSTotally 167 RRA patients were assigned to the treatment group (73 cases) and the control group (94 cases) according to different therapeutic methods. Patients in the treatment group were treated with HTR combined MTX, while those in the control group were treated with leflunomide (LEF) combined MTX. Clinical signs and symptoms, RF, CRP, ESR, disease activity score 28 (DAS28), and safety indicators were compared between the two groups before treatment, at week 12 and 24 after treatment. The efficacy and safety indices were also evaluated.

RESULTSAt week 12 after treatment the total effective rate was 82.2% (60/73 cases) in the treatment group and 79.8% (75/94 cases) in the control group, showing no statistical difference between the two groups (chi2 = 0.15, P > 0.05). At week 24 after treatment the total effective rate was 78.1% (57/73 cases) in the treatment group and 755% (71/94 cases) in the control group, showing no statistical difference between the two groups (chi2 = 0.15, P > 0.05). There was statistical difference in the total effective rate between week 24 and week 12 in the control group (chi2 = 0.49, P < 0.05). Clinical signs and symptoms, RF, CRP, ESR, and DAS28 were significantly improved in the two groups after 12- and 24-week treatment (P < 0.01). There was no statistical difference in the improvement at week 12 after treatment between the two groups (P > 0.05). There was statistical difference in time of morning stiffness, tender joint numbers, swollen joint numbers, patient global assessment, RF, CRP, and DAS28 at week 24 after treatment between the two groups (P < 0.05). Besides, adverse reactions occurred less in the treatment group than in the control group (P < 0.01).

CONCLUSIONThe efficacy of HTR combined MTX was equivalent to that of LEF (10 mg per day) combined MTX, but with more stable therapeutic effects and less adverse reactions.

Antirheumatic Agents ; pharmacology ; therapeutic use ; Arthralgia ; Arthritis, Rheumatoid ; drug therapy ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Humans ; Isoxazoles ; Methotrexate ; pharmacology ; therapeutic use ; Phytotherapy ; Treatment Outcome