[Association of sleep duration and risk of frailty among the elderly over 80 years old in China: a prospective cohort study].

Objective: To explore the association between sleep duration and the risk of frailty among the elderly over 80 years old in China. Methods: Using the data from five surveys of the China Elderly Health Influencing Factors Follow-up Survey (CLHLS) (2005, 2008-2009, 2011-2012, 2014, and 2017-2018), 7 024 elderly people aged 80 years and above were selected as the study subjects. Questionnaires and physical examinations were used to collect information on sleep time, general demographic characteristics, functional status, physical signs, and illness. The frailty state was evaluated based on a frailty index that included 39 variables. The Cox proportional risk regression model was used to analyze the correlation between sleep time and the risk of frailty occurrence. A restricted cubic spline function was used to analyze the dose-response relationship between sleep time and the risk of frailty occurrence. The likelihood ratio test was used to analyze the interaction between age, gender, sleep quality, cognitive impairment, and sleep duration. Results: The age M (Q1, Q3) of 7 024 subjects was 87 (82, 92) years old, with a total of 3 435 (48.9%) patients experiencing frailty. The results of restricted cubic spline function analysis showed that there was an approximate U-shaped relationship between sleep time and the risk of frailty. When sleep time was 6.5-8.5 hours, the elderly had the lowest risk of frailty; Multivariate Cox proportional risk regression model analysis showed that compared to 6.5-8.5 hours of sleep, long sleep duration (>8.5 hours) increased the risk of frailty by 13% (HR: 1.13; 95%CI: 1.04-1.22). Conclusion: There is a nonlinear association between sleep time and the risk of frailty in the elderly.

[Efficacy and safety of endothelin receptor antagonists combined with phosphodiesterase 5 inhibitor in the treatment of pulmonary arterial hypertension: a network meta-analysis].

Objective: To examine the efficacy and safety of endothelin receptor antagonists (ERA) combined with phosphodiesterase 5 inhibitors (PDE5i) in the treatment of pulmonary artery hypertension (PAH). Methods: Computer-based retrieval was performed on PubMed, Cochrane Library, CNKI, Wanfang, and VIP database (up to February 12th, 2021). Randomized controlled trials about endothelin receptor antagonists (ERAs) or PDE5i in patients with PAH were collected. The change of 6-minute walking distance (6MWD) in 12-16 weeks was used as primary outcome index. Case fatality rate, worsening clinical events, WHO functional class (FC) improvement, adverse events (AEs), serious adverse events (SAE) were the key secondary outcomes indicators. STATA 16.0 software was used for network meta-analysis, and the pooled estimates of odds ratios (ORs) or weighted mean differences (WMDs) and 95% confidence intervals (CIs) of the results were shown. To help explain ORs and WMDs, we used the surface under the cumulative ranking curve (SUCRA) to calculate the probability of each intervention. Results: We included 29 trials with 5 949 participants. In network meta-analysis, Bosentan combined with Sildenafil (WMD=53.93, 95%CI=6.19-101.66) had shown the greatest improvement in 6MWD compared with placebo, followed by Bosentan combined with Tadalafil (WMD=50.84, 95%CI=7.05-94.62), Ambrisentan combined with Tadalafil (WMD=46.67, 95%CI=15.88-77.45), Bosentan (WMD=29.44, 95%CI=5.86-53.02), Ambrisentan (WMD=23.90, 95%CI=0.31-47.48) and Macitentan (WMD=21.57, 95%CI=2.45-40.69). According to SUCRA, the effects of different intervention measures on improving 6MWD in patients with arterial pulmonary hypertension were as follows: Bosentan+Sildenafil (82.9%)>Bosentan+Tadalafil (78.4%)>Ambrisentan+Tadalafil (77.1%)>Bosentan (49.2%)>Sildenafil (48.5%)>Ambrisentan (40.3%)>Macitentan (37.3%)>Tadalafil (33.0%)>Placebo (3.3%). For the WHO functional class, Sildenafil (OR=2.90, 95%CI=1.04-8.08) was optimal compared with placebo, followed by Bosentan (OR=2.15, 95%CI=1.15-4.04), and there was no significant difference in the rest. For clinical worsening, Bosentan combined with Tadalafil (OR=0.08, 95%CI=0.01-0.49) performed best compared with placebo, followed by Bosentan (OR=0.20, 95%CI=0.11-0.38), Bosentan combined with Sildenafil (OR=0.21, 95%CI=0.09-0.46), Ambrisentan combined with Tadalafil (OR=0.27, 95%CI=0.15-0.50), Sildenafil (OR=0.33, 95%CI=0.17-0.66) and Tadalafil (OR=0.44, 95%CI=0.21-0.90). There was no statistical difference between all interventions and placebo in terms of the incidence of adverse events and serious adverse events. For case fatality rate, Ambrisentan (OR=0.28, 95%CI=0.11-0.74) was statistically superior to placebo and there was no statistics difference in the rest. Conclusions: The combination therapy of ERAs and PDE5i performed well in the short-term improvement of motor function. Furthermore, there was no significant difference with monotherapy in terms of safety. However, it is worth emphasizing that the choice of treatment should be based on the patient's individualized situation and the patient's requirements.

[Association between sleep duration and activity of daily living in the elderly aged 65 years and older in China].

Objective: To investigate the association between sleep duration and activity of daily living (ADL) in the elderly aged 65 years and older in China. Methods: A total of 11 247 subjects aged 65 and above were included in the Chinese Elderly Health Factors Tracking Survey from March 29, 2005 to April 8, 2019. Self-made questionnaire was used to collect the data of population sociological characteristics, health status and disease status. ADL status was assessed by basic activities of daily living. The association between sleep duration and ADL impairment was assessed by Cox proportional risk regression model. The dose-response relationship between sleep duration and ADL impairment was analyzed using restricted cubic spline function. Results: The age of the subjects was (79±10) years, including 5 793(51.5%) females. The incidence of ADL impairment was 33.3% (3 747/11 247). Subjects were divided into short, medium, and long sleep groups according to sleep duration of fewer than seven hours, seven to eight hours, or more than eight hours. The number of short, medium and long sleepers was 2 974 (26.4%), 4 922 (43.8%) and 3 351(29.8%), respectively. The intermediate sleep group had the lowest incidence of impaired ADL (4.98/100 person-years). Cox proportional risk regression model analysis showed that: taking the intermediate sleep group as reference, after adjustment of gender, age, marital status, educational level, place of residence, living with family, smoking, drinking, exercise, frequency of fruit consumption, vegetable intake frequency, sleep quality, factors such as hypertension, diabetes, heart disease and cerebrovascular disease, the long sleep time increased the risk of impaired ADL [HR (95%CI): 1.148 (1.062-1.241)]. Subgroup analysis showed a weak positive multiplicative interaction between sleep duration and age [HR (95%CI): 1.004 (1.000-1.009)], but no multiplicative interaction between sleep duration and sex [HR(95%CI): 0.948 (0.870-1.034)]. Longer sleep duration increased the risk of ADL impairment in women [HR (95%CI): 1.195 (1.074-1.329)], but not in men [HR (95%CI): 1.084 (0.966-1.217)]. Longer sleep duration increased the risk of ADL impairment in people aged 80 years and older [HR (95%CI): 1.185 (1.076-1.305)], but not in people younger than 80 years [HR (95%CI): 1.020 (0.890-1.169)]. There was a non-linear dose-response relationship between sleep duration and ADL damage (P=0.007), and the risk of ADL damage was lowest when sleep duration was 7.5 h. Conclusion: Sleep duration was positively correlated with the risk of ADL impairment in the elderly in a nonlinear dose-response relationship.

[Change of innate lymphoid cell subsets in peripheral bloods and ascites in liver cirrhotic patients complicated with spontaneous bacterial peritonitis].

Objective: To investigate the change of innate lymphoid cells (ILC) subsets in peripheral blood and ascites in liver cirrhotic patients complicated with spontaneous bacterial peritonitis (SBP). Methods: The data of 62 patients with liver cirrhosis admited to the Zhumadian Central Hospital from November 2019 to November 2020 were analyzed. Among them, 41 cases were complicated with untainted ascites (untainted ascites group), while the other 21 cases were complicated with SBP (SBP group). Meanwhile, 20 cases of controls who received healthy examination in the same period were also enrolled (control group). Peripheral blood mononuclear cell (PBMC) was isolated from peripheral blood of all patients and controls. Mononuclear cell in ascites was isolated from patients with liver cirrhosis. The percentage of ILC1, ILC2, and ILC3 subsets in PBMC and mononuclear cell in ascites were measured by flow cytometry. CD3-CD19-CD20-CD14- cells (lin-cells) were purified from ascites and were stimulated with lipopolysaccharide (LPS) for 24 h. The transcription factor T-bet, GATA3, and RORγt mRNA relative level in lin-cells was semi-quantified by real-time PCR. Cytokine level in the supernatants was measured by enzyme linked immunosorbent assay. Differences of ILC subsets in peripheral blood and ascites were compared among groups. Results: There were twenty-nine males and twelve females in untainted ascites group, aged M(Q1,Q3) 49(33, 78) years. There were twelve males and nine females in SBP group, aged 50(37, 76) years. There were eleven males and nine females in control group, aged 48(32, 69) years. lin-CD45+CD161+CD127+ ILC cells could be detected in both peripheral blood and ascites. There was no significant difference in total ILC percentage within PBMC among untainted ascites group, SBP group, and control group (P=0.235). There was also no significant difference of total ILC percentage within mononuclear cells in ascites between untainted ascites group and SBP group (P=0.232). The differences were not statistically significant of peripheral CD117-CRTh2-ILC1, CRTh2+ILC2, or CD117+CRTh2-ILC3 within peripheral ILC among untainted ascites group, SBP group, and control group (all P>0.05). ILC1 percentage in ascites was up-regulated in SBP group compared with untainted ascites group (35.69%±3.39% vs 26.40%±3.85%, P<0.001), while ILC2 in ascites was down-regulated in SBP group (36.83%±7.70% vs 48.35%±9.45%, P<0.001). There was no statistical difference in ILC3 percentage in ascites between the two groups (P=0.230). T-bet mRNA relative level and IFN-γ production by lin- cells from ascites were elevated in response to LPS stimulation in SBP group compared with untainted ascites group (both P<0.001). GATA3 mRNA relative level and IL-5/IL-13 secretion by lin-cells from ascites were reduced in SBP group compared with untainted ascites group (both P<0.05). There was no significant difference of RORγt mRNA relative level or IL-17/IL-22 expression between the two groups (both P>0.05). Conclusion: Peripheral ILC subsets do not change in liver cirrhosis patients with SBP. ILC1 percentage is up-regulated, and ILC2 percentage is down-regulated in ascites in liver cirrhosis patients with SBP.

Intravenous tissue plasminogen activator for acute ischemic stroke in patients with renal dysfunction.

OBJECTIVE: This study used the Taiwan Stroke Registry data to evaluate the efficacy and safety of intravenous tissue plasminogen activator (tPA) in treating acute ischemic stroke in patients with renal dysfunction. DESIGN: We identified 3525 ischemic stroke patients and classified them into two groups according to the estimated glomerular filtration rate (eGFR) at the emergency department: ≥60, and <60 ml/min/1.73 m2 or on dialysis and by the propensity score from August 2006 to May 2015. The odds ratio of poor functional outcome (modified Rankin Scale ≥2) was calculated for patients with tPA treatment (N = 705), compared to those without tPA treatment (N = 2820), by eGFR levels, at 1, 3 and 6 months after ischemic stroke. We also evaluated the risks of intracerebral hemorrhage, upper gastrointestinal bleeding, mortality, between the two groups by eGFR levels. RESULTS: Among patients with eGFR levels of <60 ml/min/1.73 m2, tPA therapy reduced the odds ratio of poor functional outcome to 0.60 (95% confidence interval = 0.42-0.87) at 6 months after ischemic stroke. The tPA therapy was not associated with increased overall risk of upper gastrointestinal bleeding, but with increased risk of intracerebral hemorrhage. The low eGFR was not a significant risk factor of intracerebral hemorrhage among ischemic stroke patients receiving tPA treatment. CONCLUSIONS: tPA for acute ischemic stroke could improve functional outcomes without increasing the risks of upper gastrointestinal bleeding for patients with or without renal dysfunction. The low eGFR was not a significant risk factor for intracerebral hemorrhage among patients receiving tPA treatment.

[Predictive value of serum ferritin and a new predictive model for intravenous immunoglobulin resistance in Kawasaki disease].

Objective: To evaluate the predictive value of serum ferritin (SF) and construct a novel predictive model for intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) (IVIGRKD). Methods: The clinical data of 422 children with KD from January 2017 to December 2019 in Quanzhou Women's and Children's Hospital were retrospectively analyzed. According to the response to IVIG, they were divided into IVIG-resistant group and IVIG-sensitive group. Forty-one clinical indicators including general characteristics and laboratory results were compared between the two groups. Comparisons between groups were performed with unpaired Student t test or Mann-Whitney U test or chi-square test. Receiver operating characteristic (ROC) curve was applied to evaluate the predictive value of SF for IVIGRKD. Binary Logistic regression analysis was used to test whether SF was an independent risk factor for IVIGRKD. Meanwhile, a novel predictive scoring system was established. The comparisons between the new predictive scoring system with four commonly used prediction scoring systems were conducted. Results: A total of 422 KD cases (285 males and 137 females, 17.0 (9.0,29.0) years of age) were enrolled and divided into IVIG-resistant group (n=57) and IVIG-sensitive group (n=365). Seventeen clinical indicators differed significantly between the two groups. SF level of the IVIG-resistant group was significantly higher than that of the sensitive group (245.0 (131.0, 519.0) vs. 145.0 (92.5, 232.5) µg/L, Z=-5.109, P<0.05). ROC curve showed that the Youden index of SF for predicting IVIGRKD was 0.326 (cutoff value 403.5 µg/L). Binary logistic regression analysis showed that SF, days of illness at initial IVIG treatment, cervical lymphadenopathy, pleomorphic rash, white blood cell, C-reactive protein (CRP), activated partial thromboplastin time (APTT), alanine transaminase (ALT) and creatinine were independent risk factors for IVIGRKD. A novel prediction model was constructed, and the cutoff points and score points were as follows: pleomorphic rash, 2 points; cervical lymphadenopathy, 1 point; SF≥ 403.5 µg/L, 1 point; white blood cell ≥ 18.3×109/L, 1 point; CRP≥83.1 mg/L, 1 point; APTT≥25.3 s, 1 point; ALT≥37.5 U/L, 1 point. And patients with scores of 4 or more were at high-risk for IVIGRKD. The Youden index of the four commonly used scoring systems ranged from 0.315 to 0.512. However, the Youden index of the new scoring system was 0.695 (sensitivity 0.772, specificity 0.923) and was the highest among the five scoring systems. Conclusions: SF shows well predictive efficiency for IVIGRKD and is an independent risk factor for IVIGRKD. SF can be used as a new predictor of IVIGRKD.

[Sensitivity and specificity of nucleic acid testing in close contacts of COVID-19 cases in Guangzhou].

Objective: To analyze the sensitivity and specificity of SARS-CoV-2 nucleic acid testing in 20 348 close contacts of COVID-19 cases in different prevention and control stages in Guangzhou and to provide scientific evidence for optimizing epidemic response strategies. Methods: A total of 20 348 close contacts of COVID-19 cases in Guangzhou were traced between February 21 and September 22,2020. All the close contacts were tested for the nucleic acid of SARS-CoV-2. The sensitivity and specificity of nucleic acid testing and diagnosis in the different prevention and control stages were compared. Results: In 20 348 close contacts, 12 462 were males (61.24%), the median (P25,P75) of age of them was 31.0 years (23.0,43.0), the median number (P25,P75) of nucleic acid testing for them was 2.0 (1.0,3.0), and the median (P25,P75) of their quarantine days was 12.0 (8.0,13.0) days, respectively. A total of 256 COVID-19 cases were confirmed in the close contacts after seven nucleic acid tests. In the 1st, 2nd, 3rd and 7th nucleic acid testing, the sensitivity and specificity were 69.14% and 99.99% (177 cases confirmed), 89.84% and 99.99% (230 cases confirmed), 97.27% and 99.99% (249 cases confirmed), and 100.00% and 99.98%, respectively. In the three stages of COVID-19 prevention and control in China: domestic case stage, imported case stage, and imported case associated local epidemic stage, the sensitivity of the 1st nucleic acid testing was 70.68%, 68.00% and 67.35%, and the specificity was 99.98%, 100.00% and 100.00%, respectively. Conclusions: The sensitivity of nucleic acid testing in the close contacts at the different stages were consistent with slight decrease, which might be related to the increased proportion of asymptomatic infections in the late stage of epidemic prevention and control with COVID-19 in Guangzhou. It is suggested to give three nucleic acid tests to improve the sensitivity and reduce false negative risk.

Upregulation of miR-335 reduces myocardial injury following myocardial infarction via targeting MAP3K2.

OBJECTIVE: Acute myocardial infarction (AMI) is a serious cardiovascular disease with a high incidence worldwide and the main cause of sudden cardiac death. The aim of this article was to study the protective role of miR-335 in myocardial infarction (MI) and the underlying molecular mechanism. MATERIALS AND METHODS: Thirty Sprague Dawley (SD) rats were randomly divided into sham group, MI + NC group and MI + agomiR-335 group. The expression of miR-335 in rat myocardium was detected by quantitative Real Time-Polymerase Chain Reaction (RT-PCR). Western blot was performed to detect the expression of TNF-α, IL-6, IL-1ß, Caspase-3, Cleaved Caspase-3 (C-Caspase-3) and MAP3K2 in rat myocardium. On the 7th day of the establishment of the rat MI model, a high-resolution small animal ultrasound system was utilized to detect the cardiac function of the rats, and the heart tissues and blood samples of the rats were collected. The corresponding kits were purchased to detect the contents of LDH, CK-MB, MDA and SOD in rat serum, and HE staining was employed to observe the morphology of rat myocardial tissue. RESULTS: The expression of miR-335 in myocardial infarcted zones and border zones of MI rats decreased significantly. The upregulation of miR-335 remarkably inhibited myocardial inflammation and apoptosis after MI, thus improving the cardiac function of MI rats. Compared with the sham group, the MAP3K2 expression in the MI + NC group was observably increased, while the overexpression of miR-335 could inhibit the expression of this protein. Through the Luciferase reporter gene experiment, we found that miR-335 could directly target MAP3K2. CONCLUSIONS: The expression of miR-335 decreased in myocardial tissue after MI, and the overexpression of miR-335 reduced myocardial damage by inhibiting oxidative stress, inflammation, and apoptosis via targeting MAP3K2, thereby improving the cardiac function of MI rats.

[The relationship between resting heart rate and all-cause mortality among the Chinese oldest-old aged more than 80: a prospective cohort study].

Objective: To explore the association between resting heart rate(RHR) and all-cause mortality among the Chinese oldest-old aged more than 80. Methods: Using a total of seven surveys or follow-ups data (1998, 2000, 2002, 2005, 2008, 2011 and 2014) from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). A total of 17 886 elderly over 80 years old were selected as subjects, their resting heart rate were measured though baseline survey and the survival outcome and death time of the subjects were followed up. The subjects were divided into 6 groups according to their resting heart rate. Cox regression model was used to estimate the effect of resting heart rate on mortality risk. The interaction of age, gender and resting heart rate was also analyzed by likelihood ratio test. Results: The age of subjects M (P25, P75) was 92 (86, 100) years old, including 10 531 females (58.9%) and there were 13 598 participants died, the mortality rate was 195.5 per 1 000 person-years. Multivariate Cox regression analysis showed that compared to the control group (60-69 pbm/min), the hazard ratio of the elderly are 1.06 (95%CI: 1.02, 1.11), 1.09 (95%CI: 1.04, 1.15), 1.23 (95%CI: 1.14, 1.34), 1.25 (95%CI: 1.08, 1.44) in the group of RHR between 70-79, 80-89, 90-99 and ≥100 pbm/min and P values are all less than 0.05. Likelihood ratio test showed that RHR and age had an interaction effect. (P for interaction=0.011). Conclusion: The risk of all-cause death increased with the increase of resting heart rate and this relationship was stronger between the 80-89 years old people.

[Significance of microRNA 216a, 324-5p and 29a expression in peripheral blood in patients with acute pancreatitis and their correlation with liver injury].

Objective: To investigate the significance of microRNA (miR)-216a, miR-324-5p, miR-29a expression in peripheral blood in patients with acute pancreatitis (AP) and their correlation with liver injury. Methods: It was a case-control study design. To select 130 AP patients admitted from June 2017 to May 2019 in the First People's Hospital of Shangqiu, and the patients were divided into mild AP group (MAP group) and moderately severe AP group (SAP group) according to the disease severity, or 54 patients in the liver injury group (20 were MAP and 34 were SAP) and 76 in the non-liver injury group(all were MAP) according to liver injury. And another 40 healthy volunteers were selected as the healthy group. The expressions of miR-216a, miR-324-5p and miR-29a in peripheral blood of MAP group, SAP group, healthy group and liver injury group, non-liver injury group were compared, and the correlation between the miRNA levels and clinical indexes was analyzed. The predictive value of miRNA levels in peripheral blood for AP complicated with liver injury was analyzed by receiver operating characteristic (ROC) curve. Results: The levels of miR-216a and miR-29a in MAP group and SAP group were higher than those in healthy group, and the level of miR-324-5p was lower than that in healthy group (all P<0.01). The levels of miR-216a and miR-29a in SAP group were higher than those in MAP group, and the level of miR-324-5p was lower than that in healthy group (all P<0.01). Balthazar CT Score, acute physiology and chronic health evaluations (APACHE Ⅱ) score, C-reactive protein level, length of hospital stay were positively correlated with the levels of miR-216a and miR-29a in peripheral blood (all P<0.05), and negatively correlated with the levels of miR-324-5p (P<0.05). The levels of miR-216a and miR-29a in the peripheral blood in the liver injury group were higher than those in the non-liver injury group, and they were higher inSAP patients than those in MAP patients in the liver injury group (all P<0.05). The level of miR-324-5p in the peripheral blood in the liver injury group was lower than that in the non-liver injury group, and it was lower in SAP patients than that in MAP patientsin the liver injury group (all P<0.05). The area under ROC curve of miR-216a, miR-324-5p, and miR-29a in peripheral blood to predicate the AP complicated with liver damage was 0.694, 0.750 and 0.814, respectively. Conclusions: The levels of miR-216a and miR-29a increase in peripheral blood and the level of miR-324-5p decreases in patients with AP, and they are closely related to Balthazar CT score, APACHEⅡ score, C-reactive protein and length of hospital stay. The levels of miR-216a, miR-324-5p, miR-29a has certain predictive value for AP with liver injury, of which miR-29a has the highest predictive value.

The efficacy and safety of topical rapamycin-calcitriol for facial angiofibromas in patients with tuberous sclerosis complex: a prospective, double-blind, randomized clinical trial.

BACKGROUND: The efficacy of topical rapamycin is well documented for tuberous sclerosis complex (TSC)-related facial angiofibromas (FAs). Calcitriol has been shown to lessen skin fibrosis and may be therapeutically beneficial to FAs. OBJECTIVES: To evaluate whether topical rapamycin-calcitriol combination is an effective and safe treatment for TSC-related FAs. METHODS: Fifty-two patients with TSC with FAs were enrolled in this prospective study including three 12-week periods. In period 1, either topical rapamycin 0·1% or calcitriol 0·0003% single-agent therapy vs. their combination was applied in a double-blind, left-right-randomized, split-face comparison. The primary outcome was the reduction of modified Facial Angiofibroma Severity Index (mFASI) at week 12. In period 2, the patients were reassigned to use on both cheeks the ointment that resulted in the better primary outcome in period 1. The treatment was discontinued in period 3 (week 25-36) and a follow-up mFASI was scored to evaluate the degree of recurrence. RESULTS: The mean changes in mFASI at week 12 compared with baseline were -0·92, -0·44 and -1·09 for rapamycin (P ≤ 0·001), calcitriol (P = 0·039) and rapamycin-calcitriol combination (P ≤ 0·001), respectively. Although rapamycin-calcitriol combination and rapamycin had similar statistically significant decreases of mFASI at week 12, rapamycin-calcitriol combination resulted in faster improvement in erythema, greater reduction of papule elevation and longer durability after discontinuing treatment than rapamycin alone. The treatments were well tolerated. CONCLUSIONS: This randomized clinical trial demonstrates that topical rapamycin-calcitriol combination therapy is an effective and safe regimen for TSC-related FAs. What is already known about this topic? Facial angiofibromas (FAs) cause substantial psychological distress in individuals with tuberous sclerosis complex (TSC), but invasive procedural treatments are not applicable to all patients. Topical rapamycin has been demonstrated as an effective and safe treatment regimen for TSC-related FAs. What does this study add? Compared with baseline (day 0), both topical rapamycin 0·1% and rapamycin 0·1%-calcitriol 0·0003% combination ointment achieved statistically significant reductions in modified Facial Angiofibroma Severity Index at week 12. Compared with rapamycin alone, extended use of the rapamycin-calcitriol combination regimen until week 24 showed more effectiveness in decreasing papule elevation and could maintain a longer therapeutic effect after treatment discontinuation. Linked Comment: Lee. Br J Dermatol 2020; 183:604-606.

Antiplatelet agents for the secondary prevention of ischaemic stroke in patients with or without renal dysfunction.

BACKGROUND AND PURPOSE: Studies on using antiplatelet agents for secondary prevention in ischaemic stroke patients with renal dysfunction are limited. The Taiwan Stroke Registry database was used to compare the efficacy of antiplatelet agents. METHODS: From the Taiwan Stroke Registry data, 39 174 acute ischaemic stroke patients were identified and were classified into three groups by antiplatelet agent: aspirin, clopidogrel and dual antiplatelet therapy (DAPT) with a combination of aspirin and clopidogrel. The re-stroke incidence and 1-year mortality were stratified by estimated glomerular filtration rate (eGFR) levels at admission: ≥90, 60-89 and <60 ml/min/1.73 m2 or on dialysis. RESULTS: Compared to the aspirin group, the re-stroke differences were not statistically significant for the clopidogrel group [adjusted subhazard ratio 0.95, 95% confidence interval (CI) 0.84-1.08] and the DAPT group (adjusted subhazard ratio 1.03, 95% CI 0.77-1.39) after controlling for the competing risk of death. The mortality rate increased as the eGFR level declined. In addition, compared to patients taking aspirin, there was no statistically significant difference in overall 1-year mortality for the clopidogrel group (adjusted hazard ratio 1.11, 95% CI 0.95-1.29) and for the DAPT group (adjusted hazard ratio 1.01, 95% CI 0.67-1.54). The results were consistent in different subgroups stratified by eGFR levels. CONCLUSIONS: There was no difference in the risks of recurrent stroke and 1-year mortality amongst ischaemic stroke patients with or without renal dysfunction receiving antiplatelet agents with aspirin, clopidogrel or dual agents with a combination of aspirin and clopidogrel, regardless of their renal dysfunction status.

Precision Measurement of the Branching Fractions of η

Based on a sample of (1310.6±7.0)×10^{6}J/ψ events collected with the BESIII detector, we present measurements of J/ψ and η^{'} absolute branching fractions using the process J/ψ→γη^{'}. By analyzing events where the radiative photon converts into an e^{+}e^{-} pair, the branching fraction for J/ψ→γη^{'} is measured to be (5.27±0.03±0.05)×10^{-3}. The absolute branching fractions of the five dominant decay channels of the η^{'} are then measured for the first time and are determined to be B(η^{'}→γπ^{+}π^{-})=(29.90±0.03±0.55)%, B(η^{'}→ηπ^{+}π^{-})=(41.24±0.08±1.24)%, B(η^{'}→ηπ^{0}π^{0})=(21.36±0.10±0.92)%, B(η^{'}→γω)=(2.489±0.018±0.074)%, and B(η^{'}→γγ)=(2.331±0.012±0.035)%, where the first uncertainties are statistical and the second systematic.

Measurement of the Dynamics of the Decays D_{s}

Using e^{+}e^{-} annihilation data corresponding to an integrated luminosity of 3.19 fb^{-1} collected at a center-of-mass energy of 4.178 GeV with the BESIII detector, we measure the absolute branching fractions B_{D_{s}^{+}→ηe^{+}ν_{e}}=(2.323±0.063_{stat}±0.063_{syst})% and B_{D_{s}^{+}→η^{'}e^{+}ν_{e}}=(0.824±0.073_{stat}±0.027_{syst})% via a tagged analysis technique, where one D_{s} is fully reconstructed in a hadronic mode. Combining these measurements with previous BESIII measurements of B_{D^{+}→η^{(')}e^{+}ν_{e}}, the η-η^{'} mixing angle in the quark flavor basis is determined to be ϕ_{P}=(40.1±2.1_{stat}±0.7_{syst})°. From the first measurements of the dynamics of D_{s}^{+}→η^{(')}e^{+}ν_{e} decays, the products of the hadronic form factors f_{+}^{η^{(')}}(0) and the Cabibbo-Kobayashi-Maskawa matrix element |V_{cs}| are determined with different form factor parametrizations. For the two-parameter series expansion, the results are f_{+}^{η}(0)|V_{cs}|=0.4455±0.0053_{stat}±0.0044_{syst} and f_{+}^{η^{'}}(0)|V_{cs}|=0.477±0.049_{stat}±0.011_{syst}.

Study of the D

Using e^{+}e^{-} annihilation data of 2.93 fb^{-1} collected at center-of-mass energy sqrt[s]=3.773 GeV with the BESIII detector, we measure the absolute branching fraction of D^{0}→K^{-}µ^{+}ν_{µ} with significantly improved precision: B_{D^{0}→K^{-}µ^{+}ν_{µ}}=(3.413±0.019_{stat}±0.035_{syst})%. Combining with our previous measurement of B_{D^{0}→K^{-}e^{+}ν_{e}}, the ratio of the two branching fractions is determined to be B_{D^{0}→K^{-}µ^{+}ν_{µ}}/B_{D^{0}→K^{-}e^{+}ν_{e}}=0.974±0.007_{stat}±0.012_{syst}, which agrees with the theoretical expectation of lepton flavor universality within the uncertainty. A study of the ratio of the two branching fractions in different four-momentum transfer regions is also performed, and no evidence for lepton flavor universality violation is found with current statistics. Taking inputs from global fit in the standard model and lattice quantum chromodynamics separately, we determine f_{+}^{K}(0)=0.7327±0.0039_{stat}±0.0030_{syst} and |V_{cs}|=0.955±0.005_{stat}±0.004_{syst}±0.024_{LQCD}.

Evidence of a Resonant Structure in the e

The cross section of the process e^{+}e^{-}→π^{+}D^{0}D^{*-} for center-of-mass energies from 4.05 to 4.60 GeV is measured precisely using data samples collected with the BESIII detector operating at the BEPCII storage ring. Two enhancements are clearly visible in the cross section around 4.23 and 4.40 GeV. Using several models to describe the dressed cross section yields stable parameters for the first enhancement, which has a mass of 4228.6±4.1±6.3 MeV/c^{2} and a width of 77.0±6.8±6.3 MeV, where the first uncertainties are statistical and the second ones are systematic. Our resonant mass is consistent with previous observations of the Y(4220) state and the theoretical prediction of a DD[over ¯]_{1}(2420) molecule. This result is the first observation of Y(4220) associated with an open-charm final state. Fits with three resonance functions with additional Y(4260), Y(4320), Y(4360), ψ(4415), or a new resonance do not show significant contributions from either of these resonances. The second enhancement is not from a single known resonance. It could contain contributions from ψ(4415) and other resonances, and a detailed amplitude analysis is required to better understand this enhancement.

Observation of D

Using a data sample corresponding to an integrated luminosity of 2.93 fb^{-1} recorded by the BESIII detector at a center-of-mass energy of 3.773 GeV, we present an analysis of the decays D^{0}→π^{-}π^{0}e^{+}ν_{e} and D^{+}→π^{-}π^{+}e^{+}ν_{e}. By performing a partial wave analysis, the π^{+}π^{-} S-wave contribution to D^{+}→π^{-}π^{+}e^{+}ν_{e} is observed to be (25.7±1.6±1.1)% with a statistical significance greater than 10σ, besides the dominant P-wave contribution. This is the first observation of the S-wave contribution. We measure the branching fractions B(D^{0}→ρ^{-}e^{+}ν_{e})=(1.445±0.058±0.039)×10^{-3}, B(D^{+}→ρ^{0}e^{+}ν_{e})=(1.860±0.070±0.061)×10^{-3}, and B(D^{+}→f_{0}(500)e^{+}ν_{e},f_{0}(500)→π^{+}π^{-})=(6.30±0.43±0.32)×10^{-4}. An upper limit of B(D^{+}→f_{0}(980)e^{+}ν_{e},f_{0}(980)→π^{+}π^{-})<2.8×10^{-5} is set at the 90% confidence level. We also obtain the hadronic form factor ratios of D→ρe^{+}ν_{e} at q^{2}=0 assuming the single-pole dominance parametrization: r_{V}={[V(0)]/[A_{1}(0)]}=1.695±0.083±0.051, r_{2}={[A_{2}(0)]/[A_{1}(0)]}=0.845±0.056±0.039.

First Measurement of the Form Factors in D_{s}

We report on new measurements of Cabibbo-suppressed semileptonic D_{s}^{+} decays using 3.19 fb^{-1} of e^{+}e^{-} annihilation data sample collected at a center-of-mass energy of 4.178 GeV with the BESIII detector at the BEPCII collider. Our results include branching fractions B(D_{s}^{+}→K^{0}e^{+}ν_{e})=[3.25±0.38(stat)±0.16(syst)]×10^{-3} and B(D_{s}^{+}→K^{*0}e^{+}ν_{e})=[2.37±0.26(stat)±0.20(syst)]×10^{-3}, which are much improved relative to previous measurements, and the first measurements of the hadronic form-factor parameters for these decays. For D_{s}^{+}→K^{0}e^{+}ν_{e}, we obtain f_{+}(0)=0.720±0.084(stat)±0.013(syst), and for D_{s}^{+}→K^{*0}e^{+}ν_{e}, we find form-factor ratios r_{V}=V(0)/A_{1}(0)=1.67±0.34(stat)±0.16(syst) and r_{2}=A_{2}(0)/A_{1}(0)=0.77±0.28(stat)±0.07(syst).

Determination of the Pseudoscalar Decay Constant f_{D_{s}

Using a 3.19 fb^{-1} data sample collected at an e^{+}e^{-} center-of-mass energy of E_{cm}=4.178 GeV with the BESIII detector, we measure the branching fraction of the leptonic decay D_{s}^{+}→µ^{+}ν_{µ} to be B_{D_{s}^{+}→µ^{+}ν_{µ}}=(5.49±0.16_{stat}±0.15_{syst})×10^{-3}. Combining our branching fraction with the masses of the D_{s}^{+} and µ^{+} and the lifetime of the D_{s}^{+}, we determine f_{D_{s}^{+}}|V_{cs}|=246.2±3.6_{stat}±3.5_{syst} MeV. Using the c→s quark mixing matrix element |V_{cs}| determined from a global standard model fit, we evaluate the D_{s}^{+} decay constant f_{D_{s}^{+}}=252.9±3.7_{stat}±3.6_{syst} MeV. Alternatively, using the value of f_{D_{s}^{+}} calculated by lattice quantum chromodynamics, we find |V_{cs}|=0.985±0.014_{stat}±0.014_{syst}. These values of B_{D_{s}^{+}→µ^{+}ν_{µ}}, f_{D_{s}^{+}}|V_{cs}|, f_{D_{s}^{+}} and |V_{cs}| are each the most precise results to date.

Measurement of the Branching Fraction For the Semileptonic Decay D

Using a data sample corresponding to an integrated luminosity of 2.93 fb^{-1} taken at a center-of-mass energy of 3.773 GeV with the BESIII detector operated at the BEPCII collider, we perform an analysis of the semileptonic decays D^{0(+)}→π^{-(0)}µ^{+}ν_{µ}. The branching fractions of D^{0}→π^{-}µ^{+}ν_{µ} and D^{+}→π^{0}µ^{+}ν_{µ} are measured to be (0.272±0.008_{stat}±0.006_{syst})% and (0.350±0.011_{stat}±0.010_{syst})%, respectively, where the former is of much improved precision compared to previous results and the latter is determined for the first time. Using these results along with previous BESIII measurements of D^{0(+)}→π^{-(0)}e^{+}ν_{e}, we calculate the branching fraction ratios to be R^{0}≡B_{D^{0}→π^{-}µ^{+}ν_{µ}}/B_{D^{0}→π^{-}e^{+}ν_{e}}=0.922±0.030_{stat}±0.022_{syst} and R^{+}≡B_{D^{+}→π^{0}µ^{+}ν_{µ}}/B_{D^{+}→π^{0}e^{+}ν_{e}}=0.964±0.037_{stat}±0.026_{syst}, which are compatible with the theoretical expectation of lepton flavor universality within 1.7σ and 0.5σ, respectively. We also examine the branching fraction ratios in different four-momentum transfer square regions, and find no significant deviations from the standard model predictions.