BACKGROUND: In the interim analysis of MONARCH plus, adding abemaciclib to endocrine therapy (ET) improved progression-free survival (PFS) and objective response rate (ORR) in predominantly Chinese postmenopausal women with HR+/HER2- advanced breast cancer (ABC). This study presents the final pre-planned PFS analysis. METHODS: In the phase III MONARCH plus study, postmenopausal women in China, India, Brazil, and South Africa with HR+/HER2- ABC without prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) were randomized (2:1) to abemaciclib (150 mg twice daily [BID]) or placebo plus: anastrozole (1.0 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg on days 1 and 15 of cycle 1 and then on day 1 of each subsequent cycle) (cohort B). The primary endpoint was PFS of cohort A. Secondary endpoints included cohort B PFS (key secondary endpoint), ORR, overall survival (OS), safety, and health-related quality of life (HRQoL). RESULTS: In cohort A (abemaciclib: n  = 207; placebo: n  = 99), abemaciclib plus a non-steroidal aromatase inhibitor improved median PFS vs . placebo (28.27 months vs . 14.73 months, hazard ratio [HR]: 0.476; 95% confidence interval [95% CI]: 0.348-0.649). In cohort B (abemaciclib: n  = 104; placebo: n  = 53), abemaciclib plus fulvestrant improved median PFS vs . placebo (11.41 months vs . 5.59 months, HR: 0.480; 95% CI: 0.322-0.715). Abemaciclib numerically improved ORR. Although immature, a trend toward OS benefit with abemaciclib was observed (cohort A: HR: 0.893, 95% CI: 0.553-1.443; cohort B: HR: 0.512, 95% CI: 0.281-0.931). The most frequent grade ≥3 adverse events in the abemaciclib arms were neutropenia, leukopenia, anemia (both cohorts), and lymphocytopenia (cohort B). Abemaciclib did not cause clinically meaningful changes in patient-reported global health, functioning, or most symptoms vs . placebo. CONCLUSIONS: Abemaciclib plus ET led to improvements in PFS and ORR, a manageable safety profile, and sustained HRQoL, providing clinical benefit without a high toxicity burden or reduced quality of life. TRIAL REGISTRATION ClinicalTrials.gov (NCT02763566).
Humans ; Female ; Fulvestrant/therapeutic use* ; Breast Neoplasms/metabolism* ; Aminopyridines/therapeutic use* ; Benzimidazoles/therapeutic use* ; Middle Aged ; Aromatase Inhibitors/therapeutic use* ; Aged ; Receptor, ErbB-2/metabolism* ; Adult ; Letrozole/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Anastrozole/therapeutic use*

Objective:To investigate the clinical features of patients with chronic obstructive pulmonary disease (COPD) and serum-positive specific IgE (SIgE).Methods:This study was a retrospective cohort study. A total of 105 stable COPD patients with allergic features and completed serum SIgE testing were included, and all of them were from Capital Medical University, Beijing Tong Ren Hospital from September 2022 to October 2023. Those with at least one positive result of SIgE testing were classified as positive SIgE COPD group, and those with negative SIgE were classified as negative SIgE COPD group. There were 32 cases (30.5%) in the positive SIgE COPD group and 73 cases (69.5%) in the negative SIgE COPD group. Differences in laboratory tests, pulmonary function, chronic obstructive pulmonary symptom scores, incidence of severe acute exacerbation events in the past year, and drug therapy were compared between the two groups. The risk factors for positive SIgE COPD were analyzed, and the best predictive value for the diagnosis of positive SIgE COPD was analyzed using the area under the curve (AUC) of receiver operating characteristic (ROC).Results:Compared with the negative SIgE COPD group, the percentage of positive SIgE COPD group with rhinitis, sinusitis, sinusitis with nasal polyps, eczema, and a history of drug or food allergy were higher (all P<0.05) and the percentage of those who had quit smoking were higher ( P<0.05); the percentage of IgE above normal thresholds, the level of IgE, the percentage of peripheral blood eosinophil (EOS%), the count of EOS, and fractional exhaled nitric oxide (FeNO) were higher (all P<0.05), and the percentage of those who had severe and above severe Global Strategy for the Diagnosis, Management, and Prevention of COPD (GOLD) pulmonary function classification were higher, while the percentage of forced expiratory volume in one second (FEV 1% predicted), 25% maximal expiratory flow (MEF 25%) and MEF 75/25% were lower, and FEV 1/FVC was higher (all P<0.05). The positive SIgE COPD group had higher modified British medical research council (mMRC) scores and COPD assessment test (CAT) scores, and a higher incidence of severe acute exacerbation events over the past year (all P<0.05), and the use of short-acting β 2 receptor agonists (SABA) or short-acting muscarinic antagonist (SAMA), inhaled corticosteroid (ICS), theophylline and oral hormone therapy were more frequent (all P<0.05). EOS% ( OR=1.252, 95% CI: 1.039-1.508) was a risk factor for SIgE positivity in COPD ( P<0.05), and having quit smoking ( OR=0.385, 95% CI: 0.197-0.751) was a protective factor ( P<0.05). The AUC value of the ROC curve of EOS%>2.5% for the diagnosis of SIgE positivity was 0.647 (95% CI: 0.543-0.752), with a sensitivity and specificity of 52.8% and 73.1%, respectively. Conclusions:Positive SIgE COPD has sever clinical symptoms, high risk of acute exacerbation and deficiencies in treatment. The elevate of EOS% is a risk factor for the development of positive SIgE in COPD patients; positive SIgE COPD meets the diagnostic criteria for allergic COPD phenotype, and EOS% over 2.5% is suggestive of the clinical detection of allergic COPD phenotype.

Applying the effective teaching theory to the small-class teaching of pharmacology can improve the flexibility of small-class teaching mode under the guidance of the concept of effective teaching and high efficiency. The course chapters were randomly selected for traditional teaching mode or small-class teaching mode based on effective teaching theory in the same class. Practice has proved that the small-class teaching based on AO-AMFM can enhance student analysis and make careful smart objective and teaching frame work before class, and can also reach prompt activation, multi-learning, effective feedback and multi-summary, which can significantly improve students' learning enthusiasm and learning efficiency.

Objective:To explore the effect of the X-BL mixed teaching mode on Pharmacology course. Methods:In Pharmacology course of the 2017 pharmacy major of our university, 3 teaching units were randomly selected as the control group while the rest 3 teaching units were selected as the experimental group. Traditional teaching mode was carried out in control group. In the experimental group, we designed a X-BL mixed teaching mode composed of web-based learning (WBL), case-based learning (CBL), and team-based learning (TBL). Teaching effects of the two groups were compared using online unit tests and questionnaires. Test scores were analyzed by SPSS 20.0, and differences between groups were analyzed by t test. Results:The test scores of each unit of the experimental group were significantly higher than those of the control group ( P<0.01), and the low scores were all zeroed. The questionnaires showed that the two groups showed similar learning willingness, but the experimental group students were more satisfied with teaching method, teaching quality, classroom atmosphere, teacher guidance and learning effect than the control group. Conclusion:The X-BL mixed teaching mode, which focused on case teaching and group learning, integrated online and offline teaching, and information teaching, has showed a better teaching effect than traditional teaching in the Pharmacology courses. This teaching mode may have certain promotion value in the future teaching applications.

Objective:To analyze the clinical features of severe or critical 2019 novel coronavirus pneumonia (NCP) patients.Methods:Clinical data of 58 patients with severe or critical NCP in Wuhan Union Hospital, Tongji Medical College of Huazhong University of Science and Technology from January 29 to February 26, 2020 were collected. The general information, clinical symptoms, results of blood test and chest computed tomography (CT) imagings, treatments and outcomes of patients were analyzed retrospectively.Results:Among the 58 patients, 36 patients (62.1%) were severe and 22 (37.9%) were critical, 28 (48.3%) were male and 30 (51.7%) female, with an average age of (62.12±12.95) years. Twenty-eight patients (48.2%) had previous underlying diseases, including 21 patients (36.2%) with hypertension, 11 patients (19.0%) with diabetes mellitus, 6 patietns (10.3%) with coronary heart disease, 2 patients (3.4%) with chronic renal failure, and 1 patient (1.7%) with malignant tumor. The symptoms included fever (54 cases, 93.1%), dyspnea (48 cases, 82.8%), cough (46 cases, 79.3%), muscle soreness (32 cases, 55.2%), sore throat (15 cases, 25.9%), and diarrhea (6 cases, 10.3%). Decreased or increased white blood cell count was found in 7 patients (12.1%) and 6 patietns (10.3%). Decreased percent of lymphocyte, increased percent of neutrophil, and decreased hemoglobin level were found in 35 patients (60.3%), 27 patients (46.6%), and 24 patients (41.4%), respectively. Elevated CRP, PCT and D-dimmer level were demonstrated in 38 patients (65.5%), 36 patients (62.1%), and 45 patients (77.5%). Increased level of ALT, AST, LDH and decreased serum albumin were found in 32 patients (55.2%), 25 patients (43.1%), 39 patietns (67.2%) and 43 patietns (74.1%), respectively. The main features of CT imaging were diffuse lesion in both lungs, which were mainly manifested as multiple patchy shadows and ground-glass shadows, bilateral and peripheral distribution, consolidation and interlobular septal thickening. Twenty-nine patients (50.0%) were treated with antibiotics, and 14 patients (24.1%) with systemic glucocorticoid. In addition to supportive and antivirus treatment, oxygen therapy methods including nasal catheter (9 cases, 15.5%), oxygen mask (33 cases, 56.9%), high-flow nasal catheter (8 cases, 13.3%) and invasive mechanical ventilation were adopted. Twenty-one patients (36.2%) were discharged from the hospital, 27 patients (46.6%) in remission were still in the isolation wards, 3 patients (5.2%) were transferred to the ICU for further treatment, and 7 patients (12.1%) died.Conclusions:Severe and critical NCP are at higher risk in the elderly and those having underlying diseases. Severe/critical NCP patients often show extrapulmonary abnormity as well as lung dysfunction. Comprehensive treatment as early as possible is the key to improve the prognosis and reduce the mortality.

Objective:To analyze the expression level of malignant biological marker gene in locally advanced low rectal cancer tissues after neoadjuvant chemotherapy with XELOX, so as to provide guidance for clinical treatment.Methods:Based on the established inclusion and exclusion criteria, 104 patients with locally advanced low rectal cancer treated in the Surgery Department of the Affiliate Hospital of Qingdao University from January 2017 to January 2018 were included in the study. Based on the random number table method, they were divided into observation group and control group, with 52 patients in each group. Radical resection was performed in both groups, while radical resection was performed directly in the control group, and neoadjuvant chemotherapy with XELOX plus radical resection was performed in the observation group. The effect of tumor resection in the two groups was compared and analyzed, and the expression levels of tumor markers and malignant biological marker genes in the tumor tissues after surgery were determined. The 3-year postoperative survival rate of the two groups was followed up.Results:The R0 resection rate was 96.15% in the observation group and 80.77% in the control group, with statistically significant difference ( P<0.05). There were no significant differences in the serum levels of cancer antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA) and carbohydrate antigen 50 (CA50) before the operation in the two groups ( P>0.05). One week after the operation, the serum levels of CA19-9, CEA and CA50 in the observation group were significantly lower than those in the control group ( P<0.05). Through detection, the relative mRNA expression levels of PPTG and Smad4 in the postoperative observation group were higher than those in the control group, while the relative mRNA expression levels of Runx3 and APC were lower than those in the control group, with statistically significant difference ( P<0.05). The 3-year follow-up survival rate in the observation group was 90.38%, significantly higher than 78.85% in the control group ( P<0.05). Conclusions:The application of XELOX neoadjuvant chemotherapy in radical resection of locally advanced low rectal cancer has important clinical value in reducing tumor malignancy, improving tumor resection effect and improving survival.

Aim To observe the mRNA expressions of cell cycle regulators at different time points during the hypertrophic process of H9 c2 rat cardiomyoctes in-duced by angiotensin Ⅱ stimulation.Methods H9c2 myocytes were stimulated with 1.0 μmol · L-1 angio-tensin Ⅱ (Ang Ⅱ)for scheduled time.Cells were stained by Rhodamine labeled phalloidin and the cell area was measured by ImageJ software.mRNA expres-sion levels of cyclin B,D,E,cyclin dependent kinase (CDK)1,2,4,6,and CDK inhibitor p21 were de-termined by real-time PCR at different time points (0, 5,10,30 min,and 1,2,3,6,12,24,48 h).Re-sults H9 c2 cell size increased soon after stimulation of Ang Ⅱ;mRNA expressions of cyclin E,CDK4 and CDK2 all reached the peak at 5 min after stimulation of Ang Ⅱ;mRNA expression of cyclin D was increased dramatically at 10 min,followed by a decrease trend. However,the mRNA expression of cyclin B and CDK6 both showed two peaks,a p2 1 mRNA level was up to the peak at 30 min,and the expression was lowest at 3h.Although its expression increased gradually after 3h,p21 mRNA remained low level.Conclusion mRNA expression levels of the cell cycle regulators fluctuate and jointly facilitate the hypertrophic process of cardiomyocytes.

Objective To assess the effect of simvastatin on secretion of VEGF in blood serum and sputum of elderly chronic ob-structive pulmonary disease(COPD)combined with PAH patients and the pulmonary function.Methods Seventy cases of elderly COPD patients combined with PAH patients were randomized in two groups,namely the normal treatment group and combined sim-vastatin group (35 cases in each group),then compare the changes of the VEGF in blood serum,sputum and lung function.Results VEGF in blood serum and sputum showed significant changes after therapies of simvastatin (P <0.05).After 4 weeks′therapy, the FEV1% pre and FEV1/FVC increased significantly (P <0.05).Conclusion Normal treatment combine with simvastatin could decrease VEGF in blood serum and sputum of elderly COPD combined with PAH patients,meanwhile improve pulmonary function.

Objective To assess the significance of elevated serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in predicting 30-day mortality rate for patients in intensive care unit (ICU).Methods A retrospective study was conducted.The clinical data of 480 patients admitted to ICU in Tianjin First Center Hospital from June 2012 to October 2013 were studied.The characteristics of patients were recorded,the acute physiology and chronic health evaluation Ⅱ (APACHE I) score was calculated,and the routine blood tests,blood biochemistry,and serum NT-proBNP level within 24 hours after admission were determined.Patients were divided into non-survival and survival groups according to 30-day outcome,and the characteristics and clinical parameters were compared between two groups,and single factor analysis affecting prognosis was analyzed.All patients were divided into four groups according to four percentile method as NT-proBNP＜280 ng/L (group Q1),280 ng/L≤NT-proBNP＜ 1 200 ng/L (group Q2),1 200 ng/L≤NT-proBNP＜1 990 ng/L (group Q3),1 990 ng/L≤NT-proBNP＜4 700 ng/L (group Q4).A Cox regression analysis was used to test the independence of the predictors.A receiver operator characteristic curve (ROC curve) was plotted to compare the power of APACHE Ⅱ score and NT-proBNP in predicting the outcome.Kaplan-Meier analysis was used to assess survival rate among different NT-proBNP patients.Results By single factor analysis it was shown that age,APACHE Ⅱ score,creatinine,NT-proBNP and severe infection were those influencing the outcome.NT-proBNP 1 200-4 700 ng/L (groups Q3 and Q4) and APACHE Ⅱ score ＞20 were independent risk factors for predicting outcome [relative risk (RR) for group Q3 was 3.624,95％ credibility interval (95％CI) was 1.258-10.138; RR for group Q4 was 5.059,95％ CI was 3.202-9.993; RR for APACHE Ⅱ score ＞20 was 2.987,95％ CI was 1.345-5.823].The area under the ROC curve (AUC) for APACHE Ⅱ score and serum NT-proBNP was similar,and it was 0.831 (95％CI 0.778-0.884) and 0.876 (95％CI 0.827-0.925),respectively.The cut-off value of NT-proBNP for predicting mortality was 1 250 ng/L.Kaplan-Meier analysis showed that groups of Q2,Q3 and Q4 had lower cumulative survival rate compared with group Q1 (26.5％,25.4％,16.2％ vs.29.6％),and group Q4 showed most significant extent of lowering of survival rate (x2=122.920,P＜ 0.05).Conclusion Elevated NT-proBNP level in ICU patients signify severity of the disease,and it is an independent predictor of death of ICU patients.

AIM: Aquaporin 3 ( AQP3 ) water channel expressed in the kidney plays a critical role in the urine concentrating mechanism. Mice with AQP3 deletion show a urinary concentrating defect. To better characterize this defect, we studied the influence and mechanism of an acute urea load in conscious AQP3 - null and wild - type mice. METHODS:Urine was collected and assayed every 2 h, from 2 h before (baseline) to 8 h after the urea load. Urine volume, urine osmolality and urea concentration were measured. RNA was isolated from the whole kidney and real - time PCR was carried out using a LightCycler. Total protein of UTs was assayed from kidney tissue by Western blotting. RESULTS: Mice of both genotypes excreted the urea loaded in ～ 4 h with the same time course. Despite their low baseline, the AQP3 - null mice raised their urine osmolality and urea concentration progressively after the urea load to the values almost equal to those in wild - type mice at 8 h. In contrast, urine non - urea solute concentration did not change. Urine volume fell in the last 4 h to about one - fourth of basal values. The urea load strongly upregulated urea transporter UT - A3 expression in both genotype mice. CONCLUSION: These observations show that lack of AQP3 does not interfere with the ability of the kidney to concentrate urea but impairs its ability to concentrate other solutes. This solute - selective response results from the capacity of AQP3 to transport not only water but also urea, suggesting a novel role for AQP3 in non - urea solute concentration in the urine.