Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.

Endocrine-resistance remains a major challenge in estrogen receptor α positive (ERα⁺) breast cancer (BC) treatment and constitutively active somatic mutations in ERα are a common mechanism. There is an urgent need to develop novel drugs with new mode of mechanism to fight endocrine-resistance. Given aberrant ERα activity, we herein report the identification of novel covalent selective estrogen receptor degraders (cSERDs) possessing the advantages of both covalent and degradation strategies. A highly potent cSERD 29c was identified with superior anti-proliferative activity than fulvestrant against a panel of ERα⁺ breast cancer cell lines including mutant ERα. Crystal structure of ERα‒ 29c complex alongside intact mass spectrometry revealed that 29c disrupted ERα protein homeostasis through covalent targeting C530 and strong hydrophobic interaction collied on H11, thus enforcing a unique antagonist conformation and driving the ERα degradation. These significant effects of the cSERD on ERα homeostasis, unlike typical ERα degraders that occur directly via long side chains perturbing the morphology of H12, demonstrating a distinct mechanism of action (MoA). In vivo, 29c showed potent antitumor activity in MCF-7 tumor xenograft models and low toxicity. This proof-of-principle study verifies that novel cSERDs offering new opportunities for the development of innovative therapies for endocrine-resistant BC.

To enhance the learning stickiness, improve low completion rate of online teaching, and promote teaching quality has become the key to solve the contradiction in online teaching. In this paper, taking the teaching of biochemistry as example, based on the trigger mechanism, maintenance mechanism and migration mechanism of sticky learning, guided by the three-dimensional goal of "knowledge and skills, process and method, emotional attitude and values", the BOPPPS (bridge-in, objective, pre-assessment, participatory-learning, post-assessment, summary) teaching model was combined with online teaching. According to the interactive behavior in the course learning space, the Spearman rank correlation analysis was performed by SPSS 18.0 software to comprehensively evaluate the learning stickiness degree. The research has found that, due to its "micro but refined, compact structure and student-centered" characteristics, BOPPPS combining with online teaching can effectively make up for the time and space limitations of offline teaching and the excessively broad online teaching, bring benefits from the perspectives of "inclusion, attraction and production", promote students' active learning, and practically improve learning stickiness. The research provides a new idea for creating online "golden" courses.

Background::Weight gain during chemotherapy in patients with breast cancer contributes to their poor prognosis. However, a growing number of studies have found that metabolic disorders seem to play a more important role in breast cancer prognosis than weight gain. This study aimed to explore the prognostic effects of body mass index (BMI), weight gain, and metabolic disorders on the overall survival (OS) and prognosis of patients with breast cancer who underwent chemotherapy.Methods::Data from the inpatient medical records of patients with breast cancer who underwent chemotherapy at the Beijing Cancer Hospital Breast Cancer Center from January to December 2010 were retrospectively collected, and the patients were followed up until August 2020.Results::A total of 438 patients with stages I to III breast cancer met the inclusion and exclusion criteria. Forty-nine (11.19%) patients died, while 82 (18.72%) patients had tumor recurrence and metastasis at the last follow-up (August 2020). From the time of diagnosis until after chemotherapy, no significant differences were observed in the body weight ( t = 4.694, P < 0.001), BMI categories ( χ2 = 19.215, P = 0.001), and incidence of metabolic disorders ( χ2 = 24.841, P < 0.001); the BMI categories and weight change had no effect on the OS. Both univariate ( χ2 = 6.771, P = 0.009) and multivariate survival analyses (hazard ratio = 2.775, 95% confidence interval [CI]: 1.326-5.807, P = 0.007) showed that low high-density lipoprotein cholesterol (HDL-C) levels at diagnosis had a negative impact on the OS. The multivariate logistic regression analysis showed that the HDL-C level at diagnosis (odds ratio [OR] = 2.200, 95% CI: 0.996-4.859, P = 0.051) and metabolic disorders after chemotherapy (OR= 1.514, 95% CI: 1.047-2.189, P = 0.028) are risk factors for poor prognosis in patients with breast cancer. Conclusions::Chemotherapy led to weight gain and aggravated the metabolic disorders in patients with breast cancer. Low HDL-C levels at diagnosis and metabolic disorders after chemotherapy may have negative effects on the OS and prognosis of patients with breast cancer.

Objective:Intensive physicians have relatively insufficient knowledge and experience in treating patients with decompensated schistosomiasis cirrhosis (DSC) admitted in intensive care unit (ICU), but are relatively familiar with patients with decompensated alcoholic cirrhosis (DAC). For this purpose, the clinical characteristics and prognosis of these patients were compared and analyzed.Methods:A retrospective analysis was performed from January 2013 to May 2019 in our hospital and Quzhou People’s hospital. The demographic data, laboratory examination, liver function, Child-Pugh classification, complications of cirrhosis, ultrasonic imaging gastroscopy manifestations were recorded and analyzed. In addition, the treatments and prognosis were also compared.Results:A total of 30 patients (12 males and 18 females) with DSC (aged 57-88) and 31 patients with DAC (aged 41-75) were collected. Compared with patients with DAC, DSC patients were more likely to have coronary heart disease, lower proportion of hyponatremia and lower need of ventilator support. Although the incidences of jaundice and hepatic encephalopathy were significantly reduced ( P<0.05), but parameters of liver function and coagulation were no significant differences in both groups ( P>0.05). B-mode ultrasound of liver in patients with DSC displayed more proportion of patchy and diffuse echo changes and liver volume reduction ( P<0.05), whereas the manifestations of gastroscope in both groups were similar. No significant difference in main treatment measures like uses of somatostatin and three-chamber and two-capsule tube was observed. After treatment, the stop time of gastrointestinal bleeding was similar between groups of DAC and DSC [1.25 (0.5-4.125) days vs. 1.75 (1-2.375) days] ( P>0.05). In addition, the length of ICU stay in DAC group was similar to DSC group [(4.96±3.58) days vs. (3.82±1.99) days], so did the 28-day mortality [14.29% (2/14) vs. 18.18% (2/11)] (both P>0.05). Conclusions:In genenal, patients with decompensated schistosomiasis cirrhosis have the similar clinical characteristics, major biochemical indicators and accessory examination results like ultrasound and gastroscopic examinations to patients with decompensated alcoholic cirrhosis. After timely treatments, both of these patients could achieve a good prognosis.

Objective To evaluate the relationship between sevoflurane-induced cognitive impairment and α1B adrenoceptors (ADRA1B) and ADRA1D in the cerebral cortex of rats.Methods Forty-eight SPF adult Sprague-Dawley rats (half male,half female),weighing 220-260 g,were divided into control group (C group,n =24) and sevoflurane group (S group,n =24) using a random number table method.Group C and group S inhaled air and 3％ sevoflurane,respectively,for 5 h.Eight rats in each group were sacrificed immediately after anesthesia,and the cerebral cortex was removed.Eight rats in each group were selected on days 1 and 7 after anesthesia and underwent Barnes maze test.The rats were then sacrificed,and the cerebral cortex was removed.The expression of ADRA1B and ADRA1D protein and mRNA in cerebral cortex tissues was detected by Western blot and fluorescent quantitative real-time polymerase chain reaction,respectively.Results Compared with group C,the number of entering incorrect holes was significantly increased at 1 and 7 days after anesthesia,the latency and total distance to enter the target hole were prolonged,and the expression of ADRA1B and ADRA1D protein and mRNA in cerebral cortex was down-regulated immediately after anesthesia and at 1 and 7 days after anesthesia in group S (P＜0.05).Conclusion The mechanism underlying sevoflurane-induced cognitive impairment may be related to the down-regulated expression of ADRA1B and ADRA1D in cerebral cortex of rats.

Objective: To assess the current evidence regarding the efficacy, safety, and potential advantages of endoscopic compared with open salvage surgery for patients with local recurrent nasopharyngeal carcinoma. Methods: A systematic search of Pubmed/Medline, Embase, and Cochrane databases ranged between 2000 and 2017 was conducted. Included studies reported specific residual or local recurrent nasopharyngeal cancer survival data. Proportional Meta-analysis was performed on both outcomes with a random-effects model and the 95% confidential intervals were calculated by Stata 12.0 software. Results: A total of 24 case series studies were included in the Meta-analysis.The pooled 2-year overall survival rates of endoscopic and open group were 84% (95%CI:72%-93%), 68%(95%CI:59%-77%),respectively.The pooled 2-year disease-free survival rates of endoscopic and open group were 68%(95%CI:53%-81%), 65%(95%CI:54%-75%),respectively. The pooled 5-year overall survival rates of endoscopic and open group were 72%(95%CI:37%-97%), 48% (95%CI:40%-56%),respectively.The pooled 5-year disease-free survival rates of endoscopic and open group were 65%(95%CI:29%-93%), 50%(95%CI:43%-57%),respectively.The combined outcome of endoscopic was higher than open procedure. In addition, less severe complications, lower local recurrence rates(27%vs32%).The 2-year overall survival rates of endoscopic was higher than open procedure in the staging of rT1, rT2, and rT3 (93%vs87%; 77%vs63%; 67%vs53%) , but was equal to open in the staging for rT4 (35%vs35%) .Meta-regression showed that the heterogeneity was correlated with advanced tumor ratio. Conclusions The present Meta-analysis reveals that endoscopic approach offers a safe and efficient alternative to open approach with better short-term outcome and fewer postoperative complications in selecting patients strictly.

Objective To assess the characteristics of the community-dwelling elderly through a variety of objective evaluation and subjective evaluation tools and provide basis for cognitive function intervention in the community-dwelling elderly. Methods This study evaluated the global cognitive function, memory, executive function and attention and subjective memory feeling of 74 community-dwelling healthy elderly in Beijing. Results The study included 74 community-dwelling healthy elderly. The score of overall cognitive function was (27.28 ± 1.30) points. Less than 80% of participator did not acquire the total score in abstract, language, visual space and executive function. And only 9.8% acquired the total score in the delayed memory .The average score of the memory satisfaction questionnaire was (38.28 ± 9.40) points.In addition, there was no significant correlation between the scores of memory satisfaction of the elderly and the scores of cognitive function scale(r =0.038, P>0.05). The community elderly with normal general cognitive function also showed a relative decline in various cognitive areas, especially in delayed memory. In addition, there was no significant correlation between subjective memory perception and cognitive function scale (r=-0.116-0.157, P>0.05). Conclusions The community-dwelling elderly with normal global cognitive function have cognitive decline in some cognitive function domains. And the cognitive function training needs to be carried out in community. There is no relationship between subjective memory assessment and objective cognitive function. More researches about the relationship between subjective memory assessment and objective cognitive function should be carried out in the future.

OBJECTIVE:To evaluate the content validity and interrater reliability of the modified medication discrepancy tool (MDT). METHODS:According to the structure of MDT(English edition),the terms of MDT were modified,and 5 invited ex-perts used content validity indicator to test the content validity of MDT. The interrater reliability method was adopted to test the reli-ability of MDT. The interrater reliability was performed by 2 evaluators to same 20 research objects with modified MDT. RE-SULTS:Average item-level content validity index was over 0.800,and scale-level content validity index was 0.970. The item-level interrater reliability was between 0.667 and 1.000(P<0.01). The scale-level interrater reliability was 0.840(P<0.01). CONCLU-SIONS:The modified MDT has good content validity and interrater reliability,and can be used to evaluate discharged medication discrepancies in China.

Objective To apply the Chinese version of Care Transition Measure (C-CTM) in patients with chronic diseases to assess the quality of transitional care and its influencing elements in order to provide reference for improving the quality of transitional care. Methods A total of 210 patients with chronic diseases were telephoned 2 to 4 weeks after discharge using C- CTM. Results The C- CTM score of the 210 study participants was 52.37±15.45. The general self- care preparation scored the highest which was 65.48±15.07, written plan was the lowest with a median score of 16.67. Multiple regression analysis showed that education level, hospital class and Activity of Daily Living (ADL) scores upon admission were significantly positively associated with the C- CTM scores. Conclusions The overall quality of transitional care was poor, especially in written plan. Quality of transitional care was poorer in patients with lower education level, being admitted to lower class hospitals and with lower ADL scores upon admission.