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Background The triple digital divide refers to the lack of internet access, use and knowledge among specific populations. In China, middle-aged and older adults and those living in rural areas or various regions of the country are more likely to have limited internet access and skills and, thus, have less accessibility to internet services. Few longitudinal studies have explored the association between the digital divide and the progression of depressive symptoms among middle-aged and older Chinese adults. Significantly, none of the existing studies have estimated this long-term relationship from a disparity perspective.Aims This study investigates the association between the triple digital divide and depressive symptom trajectories among middle-aged and older adults in China during a 10-year follow-up period from 2011 to 2020.Methods The sample for this secondary analysis comprises 3019 urban and 10 427 rural respondents selected from the China Health and Retirement Longitudinal Study baseline survey in 2011. Depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale. Employing longitudinal mixed-effects models, this study explored the association between the triple digital divide and depressive symptom trajectories among middle-aged and older Chinese adults by examining gender, rural–urban and regional disparities in this relationship.Results Our findings revealed a significant association between the triple digital divide and increasing trajectories of depressive symptoms, showing significant disparities based on gender, rural–urban dwelling and regional location. Notably, for both male and female participants who resided in urban areas or the central region of the country, their ability to use the internet, coupled with enhanced internet skills and greater access to internet services, was found to have a mitigating effect on the increasing trajectories of depressive symptoms.Conclusions To alleviate some of the confounding influences on the trajectory of depression in middle-aged and older adults, policymakers in China should continue to prioritise the development of internet technology, foster easy access to the internet to ensure it is ‘elder-friendly’, provide internet skill training platforms for this population and broaden access to various internet services appropriate for them. Additionally, the implementation of tailored interventions to address depression, especially targeting the more vulnerable cohorts, such as middle-aged and older women, those residing in rural areas and the western regions, is crucial. Such tailored approaches are essential for addressing the disparities and challenges associated with the triple digital divide.

Introduction The escalating consumption of ultra-processed foods (UPFs) among school-aged children in developing countries poses a significant threat to public health, contributing to the dual burden of malnutrition. In Malawi, where undernutrition coexists with a burgeoning obesity epidemic, understanding the determinants of UPF consumption and its impact on children’s nutritional status is imperative. This study, conducted in Lilongwe, Malawi, aimed to investigate the association between UPF consumption, sociodemographic factors and the nutritional status of school-aged children.Materials and methods 511 children aged 7–14 were recruited from 2 densely populated townships using systematic random sampling. Data on sociodemographic factors, UPF consumption and nutritional status were collected through face-to-face interviews and anthropometric measurements. UPF consumption was assessed using a validated Food Frequency Questionnaire while multinomial logistic regression was employed to analyse associations.Results Results revealed alarmingly high UPF consumption among children, particularly those high in sugar. Multinomial logistic regression identified significant predictors of malnutrition outcomes. Notably, children consuming UPFs more than three times a week were more likely to be malnourished. Overweight status was positively associated with sausage intake (β=0.226, adjusted OR 1.254, 95% CI 1.004 to 1.566, p=0.046) and age (β=0.020, adjusted OR=0.257, 95% CI 0.156 to 0.28, p=0.003). Conversely, underweight status was linked with residential location (β=4.507, adjusted OR 0.01, 95% CI 0.000 to 0.281, p=0.006) and fizzy drinks (β=1.071, adjusted OR 2.919, 95% CI 1.413 to 6.028, p=0.004).Conclusion The high prevalence of UPF consumption among school-aged children is significantly associated with malnutrition. Moreover, sociodemographic factors influence UPF consumption, highlighting the need for targeted interventions to reduce malnutrition. These findings may inform public health policies to mitigate malnutrition among children in Malawi’s urban communities.

Introduction Whether gastric cancer (GC) patients with deficient mismatch repair or microsatellite instability-high (dMMR/MSI-H) benefit from perioperative (neoadjuvant and/or adjuvant) chemotherapy is controversial. This protocol delineates the planned scope and methods for a systematic review and meta-analysis that aims to compare the efficacy of perioperative chemotherapy with surgery alone in resectable dMMR/MSI-H GC patients.Methods and analysis This study protocol is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols-P guideline. PubMed, Embase, Cochrane (CENTRAL), and the Web of Science databases will be searched, supplemented by a secondary screening of relevant records. Both randomised controlled trials and non-randomised studies will be included in this study. The primary and secondary outcomes under scrutiny will be overall survival, disease-free survival and progression-free survival. Two reviewers will independently screen studies, extract data and assess the risk of bias. We will analyse different treatment settings (eg, neoadjuvant or adjuvant or combined as perioperative chemotherapies) separately and conduct sensitivity analyses.Ethics and dissemination No ethics approval is required for this systematic review and meta-analysis, as no individual patient data will be collected. The findings of our study will be published in a peer-reviewed journal.Prospero registration number CRD42023494276.

Introduction Pulmonary vein isolation (PVI) is the cornerstone of radiofrequency (RF) ablation for atrial fibrillation (AF). However, a single ablation strategy does not always achieve the desired therapeutic effect in all patients with persistent AF, and individualised strategies are required for different clinical characteristics.Methods and analysis This study aimed to determine the optimal catheter ablation strategy for persistent AF by comparing the efficacy of PVI and BCXL (BC: big circles encircling pulmonary vein isolation; XL: unfixed number of lines based on the left atrial substrate). The BCXL-AF study (clinical trial no. ChiCTR2200067081) was designed as a prospective, randomised, parallel-controlled, single-blinded clinical trial. Overall, 400 patients with persistent AF were randomised in a 1:1 ratio into PVI-only and BCXL-individualised ablation groups. Patients randomised to the individualised ablation group will be further categorised into risk strata according to their clinical condition using the actual ablation method determined by the strata. Seven postoperative visits were conducted from discharge to 24 months of age. The primary observation endpoint will be the incidence of atrial tachyarrhythmia (including AF, atrial flutter and atrial tachycardia with a duration of ≥30 s) without using antiarrhythmic drugs after a blank period of 3 months following a single ablation procedure. The BCXL-AF study will assess an optimal approach for persistent AF RF ablation and evaluate the effectiveness of individualised RF ablation strategies in reducing the recurrence rate of AF.Ethics and dissemination The study protocol was reviewed, and ethical approval was obtained from the Army Medical University Human Ethics Committee (approval number: 2022-484-01). All the participants provided written informed consent. This study was conducted according to the principles of the Declaration of Helsinki and its amendments. The results of this study will be disseminated through manuscript publication and conference presentations.Trial registration number ChiCTR2200067081.

Background As an emerging treatment strategy for triple-negative breast cancer (TNBC), immunotherapy acts in part by inducing ferroptosis. Recent studies have shown that protein arginine methyltransferase 5 (PRMT5) has distinct roles in immunotherapy among multiple cancers by modulating the tumor microenvironment. However, the role of PRMT5 during ferroptosis, especially for TNBC immunotherapy, is unclear.Methods PRMT5 expression in TNBC was measured by IHC (immunohistochemistry) staining. To explore the function of PRMT5 in ferroptosis inducers and immunotherapy, functional experiments were conducted. A panel of biochemical assays was used to discover potential mechanisms.Results PRMT5 promoted ferroptosis resistance in TNBC but impaired ferroptosis resistance in non-TNBC. Mechanistically, PRMT5 selectively methylated KEAP1 and thereby downregulated NRF2 and its downstream targets which can be divided into two groups: pro-ferroptosis and anti-ferroptosis. We found that the cellular ferrous level might be a critical factor in determining cell fate as NRF2 changes. In the context of higher ferrous concentrations in TNBC cells, PRMT5 inhibited the NRF2/HMOX1 pathway and slowed the import of ferrous. In addition, a high PRMT5 protein level indicated strong resistance of TNBC to immunotherapy, and PRMT5 inhibitors potentiated the therapeutic efficacy of immunotherapy.Conclusions Our results reveal that the activation of PRMT5 can modulate iron metabolism and drive resistance to ferroptosis inducers and immunotherapy. Accordingly, PRMT5 can be used as a target to change the immune resistance of TNBC.

Background Tertiary lymphoid structures (TLSs) have been proposed to assess the prognosis of patients with cancer. Here, we investigated the prognostic value and relevant mechanisms of TLSs in colorectal cancer liver metastases (CRCLM).Methods 603 patients with CRCLM treated by surgical resection from three cancer centers were included. The TLSs were categorized according to their anatomic subregions and quantified, and a TLS scoring system was established for intratumor region (T score) and peritumor region (P score). Differences in relapse-free survival (RFS) and overall survival (OS) between groups were determined. Multiplex immunohistochemical staining (mIHC) was used to determine the cellular composition of TLSs in 40 CRCLM patients.Results T score positively correlated with superior prognosis, while P score negatively associated with poor survival (all p

Objectives This study estimates the effect of chronic disease diagnoses (CDDs) on elderly Chinese individuals’ alcohol consumption behaviour.Subjects and participants Our analysis was applied to a publicly available dataset that covers 5724 individuals aged 50 or above and spans 15 years (2000–2015: six waves) from the China Health and Nutrition Survey.Design The outcome variables are elderly individuals’ weekly consumption of alcoholic beverages: beer, red wine, Chinese spirits and total alcohol intake. The explanatory variable of primary interest is the number of chronic diseases diagnosed (including hypertension, diabetes, stroke and myocardial infarction). Other covariates concern sample individuals’ sociodemographic and health-related characteristics. A Chamberlain-Mundlak correlated random-effect Tobit model is adopted to simultaneously account for the clustering of ‘zeros’ in the outcome variable and endogeneity issues such as omitted variables and reverse causality.Results Our estimation suggests that, on average, an additional chronic disease diagnosed by medical doctors reduced an elderly Chinese individual’s weekly consumption of beer, red wine and Chinese spirits, respectively, by 1.49 (95% CI −2.85 to –0.13), 0.93 (95% CI −1.63 to –0.23) and 0.89 (95% CI −1.23 to –0.54) ounces. These effects translate into a reduction of 0.95 (95% CI −1.29 to –0.60) ounces in total weekly alcohol consumption and a reduction of 24% (95% CI −0.35 to –0.14) in the incidence of excessive drinking. Further explorations suggest that elderly Chinese individuals’ alcohol consumption is most responsive to diabetes and stroke diagnoses, but the effects vary across different beverages. Moreover, males, rural residents, smokers and those living with non-drinkers respond to CDDs more strongly than their respective counterparts.Conclusion While CDDs reduced alcohol consumption among elderly Chinese individuals, they failed to stop all heavy drinkers from excessive drinking. Relevant policies and measures are thus needed to urge heavy drinking patients to quit excessive drinking.

Objectives Limited research has focused on the association between work stress and health behaviours in Asian countries. We aimed to explore the effect of work stress on two health behaviours among employees aged 45 years or above in two countries with ageing populations, Korea and Japan.Design A cross-sectional study.Setting This secondary data analysis was conducted on baseline data from the Korean Longitudinal Study of Aging (KLoSA, 2006) and the Japanese Study of Aging and Retirement (JSTAR, 2007 and 2009).Participants Included in the analytical sample were 4982 responders without missing data aged 45 years or older who reported work positions and hours (KLoSA n=3478, JSTAR n=1504).Main outcome measures Work stress was represented by the short version of the effort-reward imbalance (ERI) model. We used logistic regression and multinomial logistic regression to investigate the association between work stress and smoking (binary current smoking) and between work stress and drinking (categorical volume of alcohol). Socioeconomic and work-related characteristics were taken into consideration, and we examined the potential interaction between ERI and gender.Results Work stress as measured by ERI ratio was significantly associated with both smoking and drinking in the KLoSA analysis; after the model was fully adjusted, ORs were 1.45 (95% CI 1.17 to 1.80) and 1.44 (95% CI 1.09 to 1.90), respectively. In analysis of the data from JSTAR, the ERI ratio was associated with smoking (OR 1.37, 95% CI 1.01 to 1.89) but not with drinking. No statistically significant interaction was found between ERI and gender in any model (p=0.82 in KLoSA data and p=0.19 in JSTAR data).Conclusions Statistically significant associations were found between work stress and both smoking and drinking behaviours in Korea and between work stress and smoking in Japan. Government integration of effort-reward balance programmes and health promotion programmes could effectively promote population health in these two Asian countries.

Introduction Malaria affecting the central nervous system (CM) is a major contributor to paediatric epilepsy in resource-poor settings, with 10%–16% of survivors developing epilepsy within 2 years of infection. Despite high risk for post-malaria epilepsy (PME), biomarkers indicating which CM survivors will develop epilepsy are absent. Such biomarkers are essential to identify those at highest risk who might benefit most from close surveillance and/or preventive treatments. Electroencephalography (EEG) contains signals (specifically gamma frequency activity), which are correlated with higher risk of PME and provide a biomarker for the development of epilepsy. We propose to study the sensitivity of quantitative and qualitative EEG metrics in predicting PME, and the potential increased sensitivity of this measure with additional clinical metrics. Our goal is to develop a predictive PME index composed of EEG and clinical history metrics that are highly feasible to obtain in low-resourced regions.Methods and analyses This prospective observational study being conducted in Eastern Zambia will recruit 250 children aged 6 months to 11 years presenting with acute CM and follow them for two years. Children with pre-existing epilepsy diagnoses will be excluded. Outcome measures will include qualitative and quantitative analysis of routine EEG recordings, as well as clinical metrics in the acute and subacute period, including histidine-rich protein 2 levels of parasite burden, depth and length of coma, presence and severity of acute seizures, presence of hypoglycaemia, maximum temperature and 1-month post-CM neurodevelopmental assessment scores. We will test the performance of these EEG and clinical metrics in predicting development of epilepsy through multivariate logistic regression analyses.Ethics and dissemination This study has been approved by the Boston Children’s Hospital Institutional Review Board, University of Zambia Biomedical Research Ethics Committee, and National Health Research Authority of Zambia. Results will be disseminated locally in Zambia followed by publication in international, open access, peer-reviewed journals when feasible.

Objective We aimed to detect the incidence and risk factors of type 2 diabetes mellitus (T2DM) development in the suburbs of Beijing.Design Cohort study with record linkage to incidence data.Setting We performed a 5-year follow-up study in a randomly selected suburban population including 1114 subjects aged ≥18 years living in the suburbs of Beijing.Participants 118 subjects with T2DM at baseline according to the 1999 WHO criteria were excluded, and 895 subjects attended the follow-up assessment in 2012. The non-diabetic subjects at baseline were classified into two groups: normal glucose tolerance (NGT) group (n=673) and impaired glucose regulation (IGR) group(n=222).The incidence and risk factors of diabetes development in each group were investigated.Outcome measures A structured questionnaire about sociodemographic characteristics, height, weight, waist circumference, hip circumference, blood pressure, oral glucose tolerance test and serum lipid levels.Results Out of the 895 non-diabetic subjects, 67 developed diabetes with 29 in the NGT group and 38 in the IGR group, respectively, after a 5-year follow-up, producing an overall 5-year cumulative incidence of diabetes of 13%. The incidence of diabetes was 15.5 cases per 1000 person-years, 8.9 cases per 1000 person-years in the NGT group and 35.7 cases per 1000 person-years in the IGR group (p

Abstract Background Programmed cell death protein 1 (PD-1) is a key immune checkpoint that regulates peripheral tolerance and protects against autoimmunity. Programmed death ligand-2 (PD-L2) is a less studied ligand to PD-1 and has yet to be fully explored, especially in pancreatic ductal adenocarcinoma (PDAC). Methods In this study, we performed immunohistochemistry to detect the PD-L2, CD3, CD8, transforming growth factor-β2 (TGF-β2) and FOXP3 levels in paraffin sections from 305 patients with resected PDAC as a training set. Expression levels of intratumoral and stromal immune markers were compared in relation to survival using Kaplan-Meier curves, random survival forest model and survival tree analysis. A multivariable Cox proportional-hazards model of associated markers was used to calculate the risk scores. Results PD-L2 was expressed in 71.5% of PDAC samples and showed strong correlations with CD3+, CD8+ T cells and FOXP3+ regulatory T cell densities. High levels of intratumoral PD-L2 and FOXP3 were related to poor survival; only stromal FOXP3 overexpression was associated with worse prognosis. Four patterns generated from survival tree analysis demonstrated that PD-L2low stromalFOXP3low patients had the longest survival, while PD-L2high intratumoralCD3low patients had the shortest survival (P

Introduction The NLRP3 inflammasome is closely related to diabetes and atherosclerosis. Recent studies suggest NIMA-related kinase 7 (NEK7) is necessary for NLRP3 inflammasome activation during potassium efflux. However, the expression of the NEK7/NLRP3 inflammasome pathway in diabetic lower extremity arterial disease (DLEAD) is unclear. The present study aimed to explore whether the NEK7/NLRP3 inflammasome pathway is involved in the pathogenesis of DLEAD.Research design and methods The serum levels of interleukin-1β (IL-1β) and IL-18 in the control group (n=39), diabetes without lower extremity artery diseases group (n=39) and DLEAD group (n=85) were measured. H&E and Von Kossa staining were used to observe the vasculature of amputated feet from patients with diabetic foot. Furthermore, immunohistochemical staining, immunofluorescence and western blot were used to detect the expression of NEK7 and the NLRP3 inflammasome.Results The serum IL-1β level in the DLEAD group was significantly increased compared with that in the control group and diabetes without lower extremity artery disease group. The serum IL-18 level was significantly higher in the DLEAD group and diabetes without lower extremity artery disease group than in the control group. H&E staining showed that the subintimal tissue of the arteries of patients with diabetic foot were highly thickened and exhibited irregular atherosclerotic plaques, and the arterial lumen was nearly occluded. Von Kossa staining showed dense brown-black calcium salt deposits in the vascular mesangium. Moreover, the expression of NEK7 and the NLRP3 inflammasome was significantly increased in the vascular cells of patients with diabetic foot, especially in vascular smooth muscle cells.Conclusion The NEK7/NLRP3 inflammasome pathway might be involved in the pathogenesis of DLEAD.

Introduction Generally, complete resection with cancer cell negative (R0) margin has been accepted as the most effective treatment of gastric cancer and positive resection (R1/R2) margin has been associated with decreased survival to varied degrees. However, the independent impact of microscopical positive (R1) margin on long-term survival may be confounded. No meta-analysis has worked at the association between R1 margin and outcomes of gastric cancer and the available evidence are scant. Therefore, we plan to conduct a systematic review and meta-analysis to quantitatively explore the role of R1 margin on gastric (including oesophagogastric junction) cancer survival after curative intent resection.Methods and analysis The protocol was conducted according to Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guideline. A systematic search of PubMed, Embase and the Cochrane Central Register of Controlled Trials databases will be performed from their inceptions to 30 April 2020 to identify randomised controlled trials (RCTs), cohort studies and case–control studies focusing on the impact of R1 margin on survival of gastric cancer after curative intent resection. The primary outcome will be the overall survival (OS) and disease-free survival (DFS) and the secondary outcomes will be 5-year OS rate and 5-year DFS rate. The Cochrane tool for bias assessment in randomised trials and Risk Of Bias In Non-randomised Studies-I for the assessment of bias in non-randomised studies (NRS) will be used. Statistical heterogeneity will be assessed by visual inspection of forest plots and measured using the I2 statistics. A fixed-effect model will be used when heterogeneity is low, otherwise, a random-effect model will be chosen. Publication bias will be assessed by funnel plots, subgroup analysis and sensitivity analysis will be performed in the right context. For each outcome, we will perform data synthesis separately for RCTs and NRS using Rev Man V.5.3 software and compile ‘summary of findings’ tables separately for RCTs and NRS using GRADEpro software. Grading of Recommendations, Assessment, Development and Evaluations considerations will also be used to make an overall assessment of the quality of evidence.Ethics and dissemination There is no requirement for ethics approval because no patient data will be collected at an individual level in this systematic review and meta-analysis.The results of this systematic review will be published in a peer-reviewed journal and presented at relevant conferences, any deviations from the protocol will be clearly documented and explained in its final report.PROSPERO registration number CRD42020165110.

Objectives To explore the characteristics of the low-income elderly who underwent free cataract surgery and to determine the degree of patient satisfaction with the free cataract surgery programme in urban China.Methods A free cataract surgery management workflow was designed as a poverty relief project in Guangzhou. In this study, participants who underwent free cataract surgery between January and August 2014 received a telephone interview based on a structured questionnaire. Data were collected on patient demographics, resources, health conditions, reasons for undergoing the free surgery and overall evaluation of the free cataract surgery programme.Results Among the 833 participants, the mean surgical age was 76.85±7.46 years (95% CI 76.34 to 77.36), and the male to female ratio was 385:448. The majority (94.31%, 746/791) of patients resided in the main urban districts. Patients underwent surgery 61.08±60.15 months (95% CI 56.17 to 66.00) after becoming aware of the cataract, although 66.83% of them reported that their daily lives were influenced by cataracts. Only 21.5% of the respondents underwent physical examinations that included regular eye screening, and only 6.30% were highly educated patients. Financial problems were the primary reason cited by patients for participating in the free surgery programme. Those patients with a monthly family income of 1000–2999¥ (US$161–482) per capita constituted the largest patient population. The free clinics in the parks and the free cataract surgery were highly rated (9.46 and 9.11 of 10 points) by the beneficiaries.Conclusions The telephone survey revealed a high level of patient satisfaction regarding the free cataract surgery programme. Most of the patients who participated in the programme resided in major urban districts and had poor health awareness and a low level of education. The information provided by this study is crucial for improving and expanding the management of free cataract surgery programmes.Trial registration number NCT02633865; Post-results.

Aims To investigate myopic maculopathy in Chinese children with high myopia and its association with choroidal and retinal changes. Methods This cross-sectional study included Chinese children aged 4-18 years with high myopia. Myopic maculopathy was classified by fundus photography and retinal thickness (RT) and choroidal thickness (ChT) in the posterior pole were measured by swept-source optical coherence tomography. A receiver operation curve was used to determine the efficacy of fundus factors in classifying myopic maculopathy Results In total, 579 children aged 12.8±3.2 years with a mean spherical equivalent of -8.44±2.20 D were included. The proportions of tessellated fundus and diffuse chorioretinal atrophy were 43.52% (N=252) and 8.64% (N=50), respectively. Tessellated fundus was associated with a thinner macular ChT (OR=0.968, 95% CI: 0.961 to 0.975, p<0.001) and RT (OR=0.977, 95% CI: 0.959 to 0.996, p=0.016), longer axial length (OR=1.545, 95% CI: 1.198 to 1.991, p=0.001) and older age (OR=1.134, 95% CI: 1.047 to 1.228, p=0.002) and less associated with male children (OR=0.564, 95% CI: 0.348 to 0.914, p=0.020). Only a thinner macular ChT (OR=0.942, 95% CI: 0.926 to 0.959, p<0.001) was independently associated with diffuse chorioretinal atrophy. When using nasal macular ChT for classifying myopic maculopathy, the optimal cut-off value was 129.00 μm (area under the curve (AUC)=0.801) and 83.85 μm (AUC=0.910) for tessellated fundus and diffuse chorioretinal atrophy, respectively. Conclusion A large proportion of highly myopic Chinese children suffer from myopic maculopathy. Nasal macular ChT may serve as a useful index for classifying and assessing paediatric myopic maculopathy. [ABSTRACT FROM AUTHOR]

Aim To assess the role of the corneal radius of curvature (CR) in the identification of fundus tessellation in children with low myopia. Methods In the cross-sectional study, students aged 9–12 years from 24 primary schools in Shanghai were enrolled by cluster sampling. Participants underwent measurements including cycloplegic refraction and axial length. Fundus images and choroidal thickness were obtained by swept-source optical coherence tomography. Fundus tessellation was classified into four grades according to fundus photographs. Results A total of 1127 children with low myopia (spherical equivalence (SE) >−3.00 dioptre (D) but ≤−0.50 D) were included, with a mean age of 10.29±0.60 years and a mean SE of −1.44±0.69 D. Fundus tessellation was found in 591 (52.4%) cases (grade 1: 428, 38.0%; grade 2: 128, 11.4%; grade 3: 35, 3.1%). Choroidal thickness decreased as fundus tessellation grade increased (p trend <0.001). According to regression analysis, higher fundus tessellation grade was independently associated with larger CR (OR, 7.499; 95%CI 2.279 to 24.675, p=0.001). For those with CR >7.9mm, along with CR, degree and proportion of fundus tessellation increased sharply. Conclusion Fundus tessellation existed in more than half of children with low myopia. Preliminary fundus photography conducted in children with low myopia with large CR would be necessary and beneficial to the early management of myopic fundus changes. [ABSTRACT FROM AUTHOR]

Background Vision-dependent mechanisms play a role in myopia progression in childhood. Thus, we investigated the distribution of ocular and corneal higher-order aberrations (HOAs) in highly myopic Chinese children and adolescents and the relationship between HOA components and 1-year axial eye growth. Methods Baseline cycloplegic ocular and corneal HOAs, axial length (AL), spherical equivalent (SE), astigmatism and interpupillary distance (IPD) were determined for the right eyes of 458 highly myopic (SE =-5.0D) subjects. HOAs were compared among baseline age groups (=12 years, 13-15 years and 16-18 years). Ninety-nine subjects completed the 1-year follow-up. Linear mixed model analyses were applied to determine the association between HOA components, other known confounding variables (age, gender, SE, astigmatism and IPD) and axial growth. A comparison with data from an early study of moderate myopia were conducted. Results Almost all ocular HOAs and few corneal HOAs exhibited significant differences between different age groups (all p<0.05). After 1 year, only ocular HOA components was significantly negative associated with a longer AL, including secondary horizontal comatic aberration (p=0.019), primary spherical aberration (p<0.001) and spherical HOA (p=0.026). Comparing with the moderate myopia data, the association of comatic aberration with AL growth was only found in high myopia. Conclusion In highly myopic children and adolescents, lower levels of annual ocular secondary horizontal comatic aberration changes, besides spherical aberrations, were associated with axial elongation. This suggests that ocular HOA plays a potential role in refractive development in high myopia. [ABSTRACT FROM AUTHOR]

Objective: Tricuspid regurgitation (TR) is a common valvular heart disease with unsatisfactory medical therapeutics and high surgical mortality. The present study aims to evaluate the safety and effectiveness of transcatheter tricuspid valve replacement (TTVR) in high-risk patients with severe TR.Methods: This was a compassionate multicentre study. Between September 2018 and November 2019, 46 patients with TR who were not suitable for surgery received compassionate TTVR under general anaesthesia and the guidance of trans-oesophageal echocardiography and fluoroscopy in four institutions. Access to the tricuspid valve was obtained via a minimally invasive thoracotomy and transatrial approach. Patients' data at baseline, before discharge, 30 days and 6 months after the procedure were collected.Results: All patients had severe TR with vena contracta width of 12.6 (11.0, 14.5) mm. Procedural success (97.8%) was achieved in all but one case with right ventricle perforation. The procedural time was 150.0 (118.8, 180.0) min. Intensive care unit time was 2.0 (1.0, 4.0) days. 6-month mortality was 17.4%. Device migration occurred in one patient (2.4%) during follow-up. Transthoracic echocardiography at 6 months after operation showed TR was significantly reduced (none/trivial in 33, mild in 4 and moderate in 1) and the primary safety end point was achieved in 38 cases (82.6%). Patients suffered from peripheral oedema and ascites decreased from 100.0% and 47.8% at baseline to 2.6% and 0.0% at 6 months.Conclusions: The present study showed TTVR was feasible, safe and with low complication rates in patients with severe TR. [ABSTRACT FROM AUTHOR]

Objectives: Autoreactive B cells play a crucial role in the pathogenesis of rheumatoid arthritis (RA), and B cell-depleting therapies using an antibodies, such as rituximab, have been suggested to be effective in RA treatment. However, transient B cell depletion with rituximab is associated with significant safety challenges related to global suppression of the immune system and thus increases the risks of infection and cancer development. To address selective and persistent issues associated with RA therapy, we developed a customised therapeutic strategy employing universal antifluorescein isothiocyanate (FITC) chimeric antigen receptor T cells (CAR-T cells) combined with FITC-labelled antigenic peptide epitopes to eliminate autoreactive B cell subsets recognising these antigens in RA.Methods: For a proof-of-concept study, four citrullinated peptide epitopes derived from citrullinated autoantigens, namely, citrullinated vimentin, citrullinated type II collagen, citrullinated fibrinogen and tenascin-C, and a cyclocitrulline peptide-1 were selected as ligands for targeting autoreactive B cells; Engineered T cells expressing a fixed anti-FITC CAR were constructed and applied as a universal CAR-T cell system to specifically eliminate these protein-specific autoreactive B cells via recognition of the aforementioned FITC-labelled autoantigenic peptide epitopes.Results: We demonstrated that anti-FITC CAR-T cells could be specifically redirected and kill hybridoma cells generated by immunisation with antigenic peptides, and autoreactive B cell subsets from RA patients via recognition of corresponding FITC-labelled citrullinated peptide epitopes. Additionally, the cytotoxicity of the CAR-T cells was dependent on the presence of the peptides and occurred in a dose-dependent manner.Conclusions: The approach described here provides a direction for precise, customised approaches to treat RA and can likely be applied to other systemic autoimmune diseases. [ABSTRACT FROM AUTHOR]

Aim: To explore the impact of puberty on refractive development and its interaction with outdoor time in children and adolescents. Methods: In this 2-year observational study, students aged 7-13 years were selected with cluster sampling. All participants underwent cycloplegic refraction and axial length measurements once every year. Information of related factors was acquired through proper questionnaire or inquiry. The level of testosterone/estradiol was detected from the saliva of the subjects using the ELISA kit. Multiple linear regression and generalised estimating equation (GEE) were used to analyse the relationship among puberty, outdoor activities and refractive indicators. Results: A total of 776 children and adolescents were included, with an average baseline age of 9.64±1.54 years and 53.6% boys. There were 350 myopes (55.2% of the 634 cyclopleged subjects) at baseline. There was a significant difference in the mean axial length changes and outdoor time among different puberty groups (for axial length: p=0.017, for outdoor time: p=0.015). Myopic parents, less outdoor time and more changes in estradiol were associated with greater changes in axial length and spherical equivalent (SE) (axial length changes: parental myopia β=0.230, outdoor time β=-0.250, changes in estradiol β=0.261; SE changes: parental myopia β=-0.267, outdoor time β=0.256, changes in estradiol β=-0.297). In the GEE model, the interaction between outdoor time and puberty was significantly associated with axial length (p=0.024, β=1.199). Conclusions: This study implies puberty may play a regulating role on the relationship between outdoor time and refractive development among Chinese children and adolescents, which provides clues for in-depth mechanism interpretation and efficient intervention strategies. [ABSTRACT FROM AUTHOR]

Objectives The presence of a bystander witness is a crucial predictor of patient survival after out-of-hospital cardiac arrest (OHCA). However, the differences in survival and neurological outcomes among different types of citizen bystanders are not well understood. Design We analysed data from the All-Japan Utstein Registry, a prospective, nationwide, population-based, observational study that was started in January 2005. Setting The registry includes all patients with OHCA who were transported to the hospital by emergency medical service (EMS) in Japan. The type of citizen bystander was classified as family member, friend, colleague, passerby or other. Participants We analysed 210 642 patients in the registry who were 18 years or older and experienced OHCA of cardiac origin witnessed by a citizen bystander between 2005 and 2014. Primary and secondary outcome measures The main outcomes were 1 month survival and 1 month survival with minimal neurological impairment. Results Of the citizen bystander-witnessed cases, 65.1% (137 147/210 642) were witnessed by a family member. However, among patients who survived to 1 month and who had a favourable 1 month neurological outcome, much lower proportions (53.9% (10 907/20 239) and 48.9% (5722/11 696)) were witnessed by a family member. Witness by a friend, colleague or passerby was associated with good 1 month neurological function, after controlling for the patient's age, first recorded rhythm, gender, bystander cardiopulmonary resuscitation (CPR), use of a public-access automated external defibrillator, dispatcher instructions, collapse-call time and response time compared with witness by a family member (friend: OR 1.35, 95% CI 1.24 to 1.46, colleague: OR 1.63, 95% CI 1.33 to 1.98, passerby: OR 1.60, 95% CI 1.39 to 1.84). Conclusions One-month survival and favourable1 month neurological outcome of patients with OHCA of cardiac origin witnessed by a family member were worse than those in cases witnessed by a friend, colleague or passerby, independent of the patient characteristics and the response of EMS. [ABSTRACT FROM AUTHOR]

Objectives Patients' stress and satisfaction concerning cancer clinical trials (CCT) may affect study accrual and quality. Our study aimed to evaluate stress and satisfaction in CCT and the influencing factors. Design Cross-sectional analysis done by a questionnaire after informed consent. Setting Cancer Hospital, Chinese Academy of Medical Sciences. Participants 199 CCT participants. Primary and secondary outcome measures self-assessed stress and satisfaction in CCT. Results Among 199 participants, 83.9% would join CCT again; 72.9% had enough time to decide on trial participation; 73.9% claimed complete awareness of CCT; 3.5% doubted CCT's significance and scientific quality; 33.2% deemed CCT time-consuming; 73.9% scored satisfaction =9/10; and 25.6% claimed moderate to severe stress. Positive factors for satisfaction were enough decision time (OR=0.36, p=0.0003), better impressions of doctors (OR=0.41, p=0.047) and less time-consuming trials (OR=0.43, p<0.0001). Individuals with more prior uninsured medical expenses (OR=1.23, p=0.026), less time consumption (OR=2.35, p<0.0001) and more tests in CCT (OR=0.64, p=0.035) were less likely to experience stress. Phase III study participants bore less stress than phase II (OR=0.29, p=0.032) but more than phase I (OR=1.18, p=0.009). Conclusions Our study addressed factors influencing CCT participants' stress and satisfaction. We suggested measures to improve patients' experiences in CCT. [ABSTRACT FROM AUTHOR]

Objectives To synthesise evidence on longer term unmet needs perceived by stroke survivors, and psychometric properties of the tools used to evaluate unmet care needs after stroke. Design Systematic review. Setting Community or patients' home. Participants Stroke survivors. Methods We searched PubMed, PsycINFO, CINAHL, EMBASE from inception to 31 March 2018 to identify survey studies that evaluated unmet needs perceived by stroke survivors after hospital discharge. Reported unmet needs were categorised under three domains: body functioning, activity/participation and environmental factors. Ranges of prevalence rates of unmet needs reported in studies were presented. Results We included 19 eligible studies, with considerable heterogeneity in patients, survey methods and results. Psychometric properties of two stroke-specific tools were formally evaluated, indicating their moderate reliability and content/concurrent validity. The median number of reported unmet needs per stroke survivor was from two to five, and the proportion of stroke survivors with at least one unmet needs was on average 73.8% (range 19.8%-91.7%). Unmet needs perceived by stroke survivors included 55 records of unmet body functioning needs, 47 records of unmet activities/participatory needs and 101 records of unmet environmental needs. Common unmet service needs were unmet information needs (3.1%-65.0%), transport (5.4%-53.0%), home help/personal care (4.7%-39.3%) and therapy (2.0%-35.7%). Conclusions The prevalence of unmet long-term needs is high among stroke survivors, and there is considerable heterogeneity in type and frequency of specific unmet needs. More research is required to link regular assessment of long-term unmet needs of stroke survivors with the provision of cost-effective patient-centred health and social care services. [ABSTRACT FROM AUTHOR]

Objectives: To explore the characteristics of the low-income elderly who underwent free cataract surgery and to determine the degree of patient satisfaction with the free cataract surgery programme in urban China. Methods: A free cataract surgery management workflow was designed as a poverty relief project in Guangzhou. In this study, participants who underwent free cataract surgery between January and August 2014 received a telephone interview based on a structured questionnaire. Data were collected on patient demographics, resources, health conditions, reasons for undergoing the free surgery and overall evaluation of the free cataract surgery programme. Results: Among the 833 participants, the mean surgical age was 76.85±7.46 years (95% CI 76.34 to 77.36), and the male to female ratio was 385:448. The majority (94.31%, 746/791) of patients resided in the main urban districts. Patients underwent surgery 61.08±60.15 months (95% CI 56.17 to 66.00) after becoming aware of the cataract, although 66.83% of them reported that their daily lives were influenced by cataracts. Only 21.5% of the respondents underwent physical examinations that included regular eye screening, and only 6.30% were highly educated patients. Financial problems were the primary reason cited by patients for participating in the free surgery programme. Those patients with a monthly family income of 1000-2999¥ (US$161-482) per capita constituted the largest patient population. The free clinics in the parks and the free cataract surgery were highly rated (9.46 and 9.11 of 10 points) by the beneficiaries. Conclusions: The telephone survey revealed a high level of patient satisfaction regarding the free cataract surgery programme. Most of the patients who participated in the programme resided in major urban districts and had poor health awareness and a low level of education. The information provided by this study is crucial for improving and expanding the management of free cataract surgery programmes. Trial registration number: NCT02633865; Post-results. [ABSTRACT FROM AUTHOR]

Aim Tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily that preferentially induces apoptosis in cancer cells while exhibiting little or no toxicity in normal cells. In this study, we evaluated the clinicopathological significance of TRAIL signalling members' expression profiles in cervical squamous cell carcinoma (CSCC). Methods TRAIL, DR5, caspase-8 and cellular FLICE-inhibitory protein (c-FLIP) protein expression was investigated in 72 stage IA2-IIIA CSCC patients using immunohistochemistry. Correlation between protein expression and clinicopathological features, radiotherapy response and survival was statistically analysed. Results Positive c-FLIP expression was an independent negative indicator for disease-free survival (DFS) (p=0.015) in multivariate Cox regression analysis. The DR5 nuclear positive group (p=0.069 by log rank test) showed some advantage of radiotherapy for overall survival (OS) compared with the DR5 nuclear negative cohort (p=0.568 by log rank test). In addition, loss of TRAIL expression was associated with worse differentiation (p=0.004), while absence of caspase-8 staining was more frequently observed in cases with lymphovascular invasion ( p=0.035). Conclusions High c-FLIP expression is shown to be an independent prognostic variable, DR5 nuclear expression may serve as a predictive biomarker for radiotherapy, and TRAIL as well as caspase-8 loss may be associated with malignant progression. [ABSTRACT FROM AUTHOR]

Objectives Smoke-free policies not only reduce harm to non-smokers, they may also reduce harm to smokers by decreasing the number of cigarettes smoked and increasing the likelihood of a successful quit attempt. However, little is known about the impact of exposure to smoking on patios on smoking behaviour. Design and participants Smokers from the Ontario Tobacco Survey, a longitudinal population representative cohort of smokers (2005-201 1). There were 3460 current smokers who had completed one to six follow-ups and were asked at each follow-up whether or not they had been exposed to smoking on patios in the month. Main outcome measures Generalised estimating equations and survival analysis were used to examine the association between exposure to patio smoking and smoking behaviour changes (making a quit attempt and time to relapse after a quit attempt), controlling for potential confounders. Results Smokers who were exposed to smoking on patios (adjusted incident rate ratio (aIRR) = 0.89; 95% CI 0.81 to 0.97) or had been to a patio (aIRR = 0.86; 95% CI 0.74 to 0.99) were less likely to have made a quit attempt than smokers who had not visited a patio. Smokers who were exposed to smoking on patios were more likely to relapse (adjusted HR=2.40; 95% CI 1.07 to 5.40)) after making a quit attempt than those who visited a patio but were not exposed to smoking. Conclusions Exposure to smoking on patios of a bar or restaurant is associated with a lower likelihood of success in a quit attempt. Instituting smoke-free patio regulations may help smokers avoid relapse after quitting. [ABSTRACT FROM AUTHOR]

Background Tobacco and non-tobacco-based waterpipe smoking has increased exponentially in many countries in recent decades, particularly among youth and young adults. Although tobacco smoking is banned in many indoor public places, waterpipe smoking, ostensibly non-tobacco, continues in Ontario and other jurisdictions where only tobacco smoking is prohibited. This study assessed air quality and exposure in waterpipe cafes using multiple methods and markers. Methods Indoor (n=12) and outdoor (n=5) air quality was assessed in Toronto, Canada waterpipe cafes from 30 August to 11 October 2012. Real-time measurements of air nicotine, fine particulate matter less than 2.5 microns in diameter (PM2.5) and ambient carbon monoxide (CO) were collected in 2 h sessions. Levels of CO in breath were collected in non-smoking field staff before entering and upon leaving venues. Observations of occupant behaviour, environmental changes and venue characteristics were also recorded. Results In indoor venues, mean values were 1419 mg/m3 for PM2.5, 17.7 ppm for ambient CO, and 3.3 mg/m3 for air nicotine. Levels increased with increasing number of active waterpipes. On outdoor patios, mean values were 80.5 mg/m3 for PM2.5, 0.5 ppm for ambient CO, and 0.6 mg/m3 for air nicotine. Air quality levels in indoor waterpipe cafes are hazardous for human health. Outdoor waterpipe cafes showed less harmful particulate levels than indoors, but mean PM2.5 levels (80.5 mg/m3) were still ‘poor'. Conclusions Staff and patrons of waterpipe cafes are exposed to air quality levels considered hazardous to human health. Results support eliminating waterpipe smoking in hospitality venues indoors and out. [ABSTRACT FROM AUTHOR]