Objective:To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults.Methods:A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test.Results:A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI: 2.23-3.88) points ( P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI: 4.03-5.37) points ( P<0.001). Ba Duan Jin showed significant improvement ( P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions:This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.

COVID-19 associated fundus lesions are mostly vascular occlusion or inflammatory changes. The affected vessels include both retinal macrovessels and microvessels, and the inflammatory changes are mainly autoimmune lesions. Clinically, the different lesions present as various fundus diseases, with varying degrees of impact on visual function. The mechanism of these lesions is considered to be related to direct injury of SARS-CoV-2, abnormal coagulation or inflammatory response caused by SARS-CoV-2. Awareness of fundus lesions associated to COVID-19 is helpful to figure out the pathophysiological mechanism of COVID-19 and promote in-depth studies for a deeper and complete understanding of the occurrence and full impact of COVID-19, emphasizing the importance of early prevention and control of the disease, and highlighting the significance of early intervention of the fundus diseases caused by COVID-19.

Digital therapeutics(DTs)refers to a non-drug intervention method that uses electronic devices such as computers,smartphones,and wearable devices to evaluate and intervene through software programs and Internet technologies.It has been confirmed that there is a good therapeutic effect on a variety of mental disorders.Digital therapeutics can improve the insomnia problems of insomniacs,enhance the attention and work memory ability of patients with attention deficit hyperactivity disorder,and can also alleviate symptoms such as depression and anxiety disorder.Digital therapy will develop towards personalized treatment,popular treatment,fragmented treatment,and entertainment treatment in the future and have broad development prospects.

BACKGROUND: Coronary artery disease (CAD) is the commonest cause of heart failure (HF), whereas pulmonary hypertension (PH) has not been established or reported in this patient population. Therefore, we assessed the prevalence, risk factors, and survival in CAD-associated HF (CAD-HF) complicated with PH. METHODS: Symptomatic CAD-HF patients were continuously enrolled in this prospective, multicenter registry study. Echocardiography, coronary arteriography, left and right heart catheterization (RHC), and other baseline clinical data were recorded. Patients were followed up and their survival was recorded. RESULTS: One hundred and eighty-two CAD-HF patients were enrolled, including 142 with HF with a preserved ejection fraction (heart failure with preserved ejection fraction [HFpEF]; left ventricular ejection fraction [LVEF] ≥50%) and 40 with a reduced ejection fraction (heart failure with reduced ejection fraction [HFrEF]; LVEF < 50%). PH was diagnosed with RHC in 77.5% of patients. Patients with PH showed worse hemodynamic parameters and higher mortality. HFrEF-PH patients had worse survival than HFpEF-PH patients. CAD-HF patients with an enlarged left ventricular end-diastolic diameter and reduced hemoglobin were at higher risk of PH. Nitrate treatment reduced the risk of PH. Elevated creatinine and mean pulmonary arterial pressure (mPAP), diastolic pressure gradient (DPG) ≥7 mmHg, and previous myocardial infarction (MI) entailed a higher risk of mortality in CAD-HF patients with PH. CONCLUSIONS: PH is common in CAD-HF and worsens the hemodynamics and survival in these patients. Left ventricle enlargement and anemia increase the risk of PH in CAD-HF. Patients may benefit from nitrate medications. Renal impairment, elevated mPAP, DPG ≥7 mmHg, and previous MI are strong predictors of mortality in CAD-HF-PH patients. TRIAL REGISTRATION ClinicalTrials.gov, NCT02164526.
Coronary Artery Disease/epidemiology* ; Creatinine ; Heart Failure/complications* ; Humans ; Hypertension, Pulmonary/complications* ; Nitrates ; Prevalence ; Prognosis ; Prospective Studies ; Registries ; Risk Factors ; Stroke Volume ; Ventricular Function, Left

OBJECTIVE：To provide reference for improving the continuing education system for licensed pharmacists in China by learning from the mature experience of the continuing education system of licensed pharmacists in the UK. METHODS ： Literature research method was adopted to summarize and analyze the organizational structure ，specific contents and implementation methods of the continuing education system for licensed pharmacists in the UK by combing the English and Chinese literatures ， official policies and reports of the continuing education system for licensed pharmacists in the UK. The suggestions and reflections were put forward to improve the continuing education system of licensed pharmacists in China. RESULTS & CONCLUSIONS ：The management organization of continuing education system for licensed pharmacists in the UK is mainly UK Association of Boards of Pharmacy，the organizations of which provide continuing education include pharmacy associations ，pharmaceutical education institutions，pharmaceutical colleges and universities. Continuing education system of licensed pharmacists in the UK is relatively perfect，including personal needs analysis ，systematic continuing education courses ，self-education and evaluation reflection of licensed pharmacists ，forming a systematic circulation system ；continuing education is carried out for pharmacists in different practicing fields ，with equal emphasis on theory and practice. In terms of continuing education ，the UK focuses on face-to-face ， one-to-one training ，and provides many free continuing education courses. Compared with the UK ，the continuing education system of licensed pharmacists in China still has some gaps. For example ，the self-education and self-evaluation awareness of licensed pharmacists is not strong ，the content and form of continuing education lack of pertinence and practicality ，and the re-registration management of pharmacists ’practicing qualifications is more formalistic. It is recommended that licensed pharmacists in China establish the concept of self-education ，strengthen the practicality of continuing education for pharmacists ，carry out refined continuing education for pharmacists in different fields of practice ，and strengthen the management of re-registration of licensed pharmacists，so as to form a systematic and effective circulation system for continuing education of licensed pharmacists in China.

BACKGROUND: As one of the most common endocrinal disorders for women at childbearing age, the diagnostic criteria of polycystic ovary syndrome (PCOS) have been defined differently among different international health organizations. Phenotypic heterogeneity of PCOS also brings about difficulties for its diagnosis and management assessment. Therefore, more efficient biomarkers representing the progression of PCOS are expected to be integrated into the monitoring of management process using metabolomic approaches. METHODS: In this prospective randomized controlled trial, 117 PCOS patients were enrolled from December 2016 to September 2017. Classical diagnostic parameters, blood glucose, and metabolome were measured in these patients before and at 2 months and 3 months of different medical interventions. The receiver operating characteristic (ROC) curves were built based on multivariate statistical analysis using data at baseline and 3 months' management, and combinational biomarkers with appreciable sensitivity and specificity were selected, which then validated with data collected at 2 months. RESULTS: A set of metabolites including glutamic acid, aspartic acid, 1-methylnicotinamide, acetylcarnitine, glycerophosphocholine, and oleamide were filtered out with high performance in representing the improvement through 3-month management of PCOS with high sensitivity and specificity in ROC analysis and validation with other two groups showed an appreciable area under the curve over 0.96. CONCLUSIONS: The six metabolites were representative of the remission of PCOS through medical intervention, making them a set of potential biomarkers for assessing the outcome of PCOS management. TRIAL REGISTRATION ClinicalTrials.gov, NCT03264638.
Biomarkers ; Female ; Humans ; Metabolomics ; Polycystic Ovary Syndrome/diagnosis* ; Prospective Studies ; ROC Curve

Cholangiocarcinoma (CCA) has emerged as an intractable cancer with scanty therapeutic regimens. The aberrant activation of Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are reported to be common in CCA patients. However, the underpinning mechanism remains poorly understood. Deubiquitinase (DUB) is regarded as a main orchestrator in maintaining protein homeostasis. Here, we identified Josephin domain-containing protein 2 (JOSD2) as an essential DUB of YAP/TAZ that sustained the protein level through cleavage of polyubiquitin chains in a deubiquitinase activity-dependent manner. The depletion of JOSD2 promoted YAP/TAZ proteasomal degradation and significantly impeded CCA proliferation

ObjectiveTo investigate the features and changing trend of drug-induced liver injury (DILI) in the elderly from 2009 to 2019, and to provide a reference for clinical prevention and treatment of DILI in the elderly. MethodsA retrospective analysis was performed for the clinical data of 2107 elderly patients, aged ≥60 years, who were diagnosed with DILI in The Fifth Medical Center of Chinese PLA General Hospital from January 2009 to December 2019, and they were divided into groups according to age. Related clinical data were analyzed, including age, sex, clinical features, prognosis, and regional distribution. The Chi-square test was used for comparison of categorical data between groups. ResultsAmong the 2107 patients with DILI, there were 802 male patients and 1305 female patients, with a male/female ratio of 1∶1.63. Cholestasis type was the most common clinical type and was observed in 1439 patients (68.3%). There was the highest number of patients in the 60-64 years group (942 patients, 44.7%), among whom 618(65.6%) were female, 589(62.5%) had cholestasis type, 471(50.0%) had chronic DILI, 421(44.7%) had drug-induced liver cirrhosis, and 25(2.7%) had drug-induced liver failure. There were 187 patients in the 75-79 years group, among whom 110 (58.8%) patients were male, 137(73.3%) had cholestasis type, 114(60.9%) had liver cirrhosis, 4(2.1%) had drug-induced liver failure. The results showed that chronic DILI was more common in the 60-64 years group, and liver cirrhosis was more common in the 75-79 years group. As for prognosis, in the 60-64 years group, 27 patients (2.9%) were cured, 885 (93.9%) were improved, 30(32%) had no response or died; in the 65-69 years group, 16 (2.8%) were cured, 528 (92.0%) were improved, and 30(5.2%) had no response or died; in the 70-74 years group, 9(2.8%) were cured, 305(94.1%) were improved, and 10 (3.6%) had no response or died. The results showed that there was no significant difference in mortality rate between the different age groups (P＞0.05). The proportion of elderly DILI patients among hospitalized DILI patients increased from 15.90% in 2009 to 22.05% in 2013 and 27.51% in 2019, with a 1.73-fold increase in 11 years. As for regional distribution, the patients in North China accounted for the highest proportion of 47.08% (the patients from Hebei, Shanxi, and Inner Mongolia accounted for 24.92%, 10.96%, and 10.25%, respectively), followed by those in Northeast China who accounted for 17.85%. The patients in Beijing accounted for 11.53%. ConclusionThe proportion of elderly DILI patients among hospitalized DILI patients tends to increase in these years. Cholestasis type is the most common clinical type, and most of the patients with this clinical type progress to chronic DILI and drug-induced liver cirrhosis. Early diagnosis, early intervention, and standardized treatment of elderly DILI should be taken seriously.

Objective:To analyze the consistency of the clinical phenotype of Alport syndrome between monozygotic twins.Methods:This retrospective study included identical twins with Alport syndrome who met the inclusion and exclusion criteria and were admitted to Peking University First Hospital from January 2000 to March 2019. Their clinical data and urinary epidermal growth factor (uEGF) level were extracted from the on-line registry system of hereditary kidney diseases, and analyzed retrospectively.Results:Three pairs of monozygotic twins with X-linked Alport syndrome from three non-consanguineous families were included. The consistency of the genotype status between the twins tended to confirm their monozygotic relationship. The first twins were term infants, and the twin 1A had a normal birth weight (2 500 g) while twin 1B was small for gestational age (2 450 g) . The other two pairs of twins were preterm, with different birth weights between twins 2 (2A is 2 450 g, 2B is 1 900 g) , but similar birth weights between twins 3. Although raised in the same environment, compared with twin 1A, 1B had obvious growth retardation. However, growth rate in the remaining twins were consistent. The renal abnormalities were not exactly the same between both twins 1 and twins 2, but was almost the same in twins 3. Both 1A and 1B were characterized by massive proteinuria and renal dysfunction, whereas 1B had worse renal function. At the last follow-up, 1A was diagnosed with stage 3 of chronic kidney disease (CKD) whereas 1B was CKD stage 4. Although renal function in twins 2 were normal, 2A had prominent proteinuria(24 h urinary total protein: 0.22 g) while 2B only had microalbuminuria(urinary albumin-to-creatinine ratio: 65 mg/g). Compared with the age-matched healthy controls, the concentration of uEGF normalized by urine creatinine (uEGF/Cr) were significantly lower in these twins. Besides, the twin-boy who had lower estimated glomerular filtration rates had lower uEGF/Cr. However, the extrarenal manifestations such as ocular and acoustic abnormalities were similar between the twins. Twins 2 and 3 showed bilateral temporal retinal thinning, and twins 1 both had binaural mild mid-low frequency sensorineural deafness.Conclusions:Renal manifestations of X-linked Alport syndrome in monozygotic twins may differ from each other, whereas the extrarenal manifestations including ocular and acoustic abnormalities may be consistent. Low birth weight and growth retardation may be associated with the progression of renal dysfunction.

Noninfectious uveitis refers to a category of inflammatory diseases involving the uvea,vitreous,optic disk and retina,with the exception of infectious factors or masquerade syndrome.These kind of blinding diseases are frequently recurrent,and the diagnosis and follow-up require fundus imaging techniques.OCT angiography (OCTA) is a rapid,noninvasive and quantifiable blood flow imaging modality that provides a depiction of the microvasculature morphology of the retinal and choroidal through different segmentation and detects the abnormal blood perfusion as well as the neovascularization.OCTA plays an important role in the diagnosis,assessment and follow-up for anterior uveitis,posterior uveitis and pan-uveitis such as Vogt-Koyanagi-Harada disease,Beh(c)et's disease,ocular sarcoidosis,birdshot chorioretinopathy,serpiginous choroiditis,multifocal choroiditis,punctate inner choroidopathy,acute zonal occult outer retinopathy,acute posterior multifocal placoid pigment epitheliopathy,multiple evanescent white dot syndrome,and also provides clue about their pathophysiologic mechanisms.