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Objectives To develop a sustained release 5-fluorouracil (5-FU) implant by three-dimensional (3D) printing to effectively prevent conjunctival fibrosis after glaucoma surgery. Methods 3D-printed implants composed of polycaprolactone (PCL) and chitosan (CS) were fabricated by heat extrusion technology and loaded with 1% 5-FU. Light microscopy and scanning electron microscopy were used to study the surface morphology. The 5-FU concentration released over 8 weeks was measured by ultraviolet visible spectroscopy. The effects on cell viability, fibroblast contractility and the expression of key fibrotic genes were assessed in human conjunctival fibroblasts. Key findings The PCL–CS-5-FU implant sustainably released 5-FU over 8 weeks and the peak concentration was over 6.1 μg/ml during weeks 1 and 2. The implant had a smooth surface and its total weight decreased by 3.5% after 8 weeks. The PCL–CS–5-FU implant did not affect cell viability in conjunctival fibroblasts and sustainably suppressed fibroblast contractility and key fibrotic genes for 8 weeks. Conclusions The PCL–CS–5-FU implant was biocompatible and degradable with a significant effect in suppressing fibroblast contractility. The PCL–CS–5-FU implant could be used as a sustained release drug implant, replacing the need for repeated 5-FU injections in clinic, to prevent conjunctival fibrosis after glaucoma surgery.

Loss of idiopathic retinal ganglion cells (RGCs) leads to irreversible vision defects and is considered the primary characteristic of glaucoma. However, effective treatment strategies in terms of RGC neuroprotection remain elusive. In the present study, the protective effects of resveratrol on RGC apoptosis, and the mechanisms underlying its effects were investigated, with a particular emphasis on the function of optic atrophy 1 (Opa1). In an ischemia/reperfusion (I/R) injury model, the notable thinning of the retina, significant apoptosis of RGCs, reduction in Opa1 expression and long Opa1 isoform to short Opa1 isoform ratios (L‑Opa1/S‑Opa1 ratio) were observed, all of which were reversed by resveratrol administration. Serum deprivation resulted in reductions in R28 cell viability, superoxide dismutase (SOD) activity, Opa1 expression and induced apoptosis, which were also partially reversed by resveratrol treatment. To conclude, results from the present study suggest that resveratrol treatment significantly reduced retinal damage and RGC apoptosis in I/R injury and serum deprivation models. In addition, resveratrol reversed the downregulated expression of Opa1 and reduced SOD activity. Mechanistically, resveratrol influenced mitochondrial dynamics by regulating the L‑Opa1/S‑Opa1 ratio. Therefore, these observations suggest that resveratrol may exhibit potential as a therapeutic agent for RGC damage in the future.

Excessive fibrosis is the major factor in the failure of glaucoma filtration surgery. So far, the dominant approach for inhibiting fibrosis is the use of an antimetabolite drug, but the complications it causes, such as filtering bleb leakage, bacterial endophthalmitis and ocular hypotony, are also inevitable. Herein, a multifunctional anti-scarring platform (PVA@rGO-Ag/5-Fu) integrated with outstanding photothermal, antibacterial and drug delivery abilities is developed. PVA@rGO-Ag shows favorable biocompatibility as well as an accurate regional photothermal killing ability on both conjunctival fibroblasts and bacteria under 808 nm near-infrared (NIR) irradiation. Furthermore, PVA@rGO-Ag/5-Fu improves bleb survival rates and results in the satisfactory reduction of intraocular pressure (IOP) by decreasing the fibrous reaction

BackgroundIn 2019, there are more than 290 million people who have ever migrated from rural to urban areas in China. These rural-to-urban internal migrants account for more than one-fifth of China’s population and is the largest internal migrant group globally. We present the first systematic review that examines whether internal migrants are more likely to exhibit non-communicable diseases (NCDs) risk factors and have worse NCD management outcomes than non-migrant counterparts in China.MethodsA systematic review was conducted via medical, public health, and economic databases including Scopus, MEDLINE, JSTOR, WHO Library Database and World Bank e-Library from 2000 to 2020. Study quality was assessed using the National Institute of Health Quality Assessment tool. We conducted a narrative review and synthesised differences for all studies included, stratified by different types of outcomes. We also conducted random-effects meta-analysis where we had a minimum of two studies with 95% CIs reported. The study protocol has been registered with PROSPERO: CRD42019139407.ResultsFor most NCD risk factors and care cascade management, comparisons between internal migrants and other populations were either statistically insignificant or inconclusive. While most studies found migrants have a higher prevalence of tobacco use than urban residents, these differences were not statistically significant in the meta-analysis. Although three out four studies suggested that migrants may have worse access to NCD treatment and both studies suggested migrants have lower blood pressure control rates than non-migrants, these findings were not statistically significant.ConclusionFindings from this systematic review demonstrate that there is currently insufficient evidence on migrant and non-migrant differences in NCD risk factors and management in China. Further research is expected to investigate access to healthcare among internal and its effect on both their NCD outcomes and long-term healthcare costs in China.

Objectives This study aims to examine: (1) temporal trends in the percentage of cost-sharing and amount of out-of-pocket expenditure (OOPE) from 2011 to 2015; (2) factors associated with cost-sharing and OOPE; and (3) the relationships between province-level economic development and cost-sharing and OOPE in China. Setting A total of 10,316 adults aged ≥45 years from China followed-up from 2011 to 2015 were included in the analysis. We measured two main outcome variables: (1) patient cost sharing, measured by the percentage of OOPE as total healthcare expenditure, and (2) absolute amount of OOPE. Results Based on self-reported data, we did not find substantial differences in the percentage of cost sharing, but a significant increase in the absolute amount of OOPE among the middle-aged and older Chinese between 2011 and 2015. The percentage of cost-sharing was considerably higher for outpatient than inpatient care, and the majority paid more than 80% of the total cost for prescription drugs. Provinces with higher GDP per capita tend to have lower cost-sharing and a higher OOPE than their counterparts, but the relationship for OOPE became insignificant after adjusting for individual factors. Conclusion Reducing out-of-pocket expenditure and patient cost sharing is required to improve financial protection from illness, especially for those with those with chronic conditions and reside in less developed regions in China. Ongoing monitoring of financial protection using data from various sources is warranted.

Physical non-communicable diseases (NCDs) and mental health disorders are a rapidly increasing health burden in low-and middle-income countries. This study aims to examine the relationships between mental health disorders and cascade of care in managing four common physical NCDs (hypertension, diabetes, dyslipidemia, chronic kidney disease) in China. We utilized two waves of nationally-representative China Health and Retirement Longitudinal Study (CHARLS 2011, 2015) of older adult population aged 45 and above. A series of unadjusted and adjusted mixed-effect logistic regression was applied to evaluate the association between presence of mental health disorder and physical chronic disease awareness, treatment, and control. We found that the odds of dyslipidemia (AOR 1.81, 95% CI 1.36–2.39) and kidney disease awareness (AOR 2.88, 95% CI 2.12–3.92) were higher for individuals with mental chronic conditions, compared to those without mental chronic conditions. The odds of having hypertension treatment was higher for subjects with mental health disorder, compared to those without (AOR 1.32, 95% CI 1.02–1.70). The odds of having physical chronic conditions controlled was not significantly associated with having mental chronic conditions (P > 0.05). These results indicated that adults with mental health disorder have a greater likelihood of awareness of having dyslipidemia and kidney disease, and receiving treatment for hypertension. Strategies to address the growing burden of physical-mental NCDs in China should include efforts to improve management of patients with comorbid health condition and improve access to continual high-quality treatment after the first diagnosis.

This study aimed to explore cellular localisation of CD38 in the retina and evaluate the role and potential mechanism of CD38 deficiency in retinal ischaemia/reperfusion (I/R) injury.Six-to eight-week-old male CD38 knockout (KO) and wild-type mice in C57BL/6 background were used. Immunostaining was performed to determine the cellular localisation of CD38 in the retina. Haematoxylin and eosin staining and immunostaining of Brn3a were used to evaluate the retinal I/R injury. Western blotting was performed to detect toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), p-p65, ionised calcium-binding adapter molecule 1, Sirtuin1 (Sirt1), Ac-p65, and pro-inflammatory cytokines protein expression.CD38 was highly expressed in mouse retinal microglia and astrocytes/Müller cells. CD38 deficiency reduced I/R-induced retinal damage and retinal ganglion cell death. Following retinal I/R injury, TLR4, MyD88, nuclear factor-κB p-p65 (NF-κB p-p65), pro-inflammatory cytokines and CD38 protein levels were also upregulated. After I/R injury, retinal inflammation factors IL-1β, IL-6, and TNF-α mRNA and protein levels were increased. IL-1β, IL-6, and TNF-α were reduced in CD38 KO mice after I/R injury. Retinal I/R injury induced the activation of microglia, but this effect was also suppressed by KO of CD38. Additionally, retinal I/R induced a significant increase in Ac-p65 protein levels and decrease in Sirt1 protein levels, while this effect was greatly attenuated by KO of CD38.CD38 deficiency protects the retina from I/R injury by suppressing microglial activation partly via activating Sirt1-mediated suppression of TLR4/MyD88/NF-κB signalling.

Physical non-communicable diseases (NCDs) and mental disorder are a rapidly increasing health burden in low-and middle-income countries. This study aims to examine the relationships between mental disorder and cascade of care in managing four common physical NCDs (hypertension, diabetes, dyslipidemia, chronic kidney disease) in China. We utilized two waves of nationally-representative China Health and Retirement Longitudinal Study (CHARLS 2011, 2015) of older adult population aged 45 and above. A series of multivariate mixed-effect logistic regression was applied to evaluate the association between presence of mental disorder and physical chronic disease awareness, treatment, and control. We found that the odds of dyslipidemia (AOR=2.88, 95% CI=2.21-3.74) and kidney disease awareness (AOR=4.14, 95% CI=2.95-5.81) were higher for individuals with mental chronic conditions, compared to those without mental chronic conditions. The odds of having hypertension treatment was higher for subjects with mental disorder, compared to those without (AOR=1.57, 95% CI=1.23-2.01). The odds of having physical chronic conditions controlled was not significantly associated with having mental chronic conditions. These results indicated that adults with mental disorder have a greater likelihood of awareness of having dyslipidemia and kidney disease, and receiving treatment for hypertension. Strategies to address growing burden of physical-mental NCDs in China should include efforts to improve management of patients with comorbid health condition and improve access to continual high-quality treatment after the first diagnosis.

ObjectivesUnderstanding the variation in user fees is essential for the design of targeted health financing strategies and monitoring progress towards universal health coverage. This study examines user fees in terms of: (1) temporal trends in cost sharing and out-of-pocket payment (OOPs); (2) factors associated with cost sharing and OOPs; and (3) the relationships between province-level economic development and cost sharing and OOPs in China.Setting28 provinces of ChinaParticipantsA total of 10316 elderly aged ≥45 years were included in the analysis.ResultsOverall, there were no substantial changes in cost sharing, but the OOPs continued to rise among the middle-aged and older Chinese. Cost sharing was substantially higher for outpatient than inpatient care (84.0% vs 69.2% in 2011; 80.8% vs 62.2% in 2015), and the majority paid more than 80% of the total cost for prescription drugs when visiting outpatient or inpatient care. Provinces with higher GDP per capita tend to have lower cost sharing and a higher OOPs than their counterparts, but the relationship for OOPs became insignificant after adjusting for individual factors. Respondents with health insurance and older age were associated with lower cost sharing. The respondents with higher socioeconomic status and a higher number of chronic conditions incurred higher OOPs for outpatient and inpatient utilisation.ConclusionCost sharing and OOPs remain very high despite near-universal insurance coverage. Health financing reforms should prioritise improving health services coverage and reducing cost sharing to improve financial protection and reduce health inequalities. Although such improvement will likely have the greatest benefits for financial protection for populations from less developed regions, developed provinces with a higher OOPs will benefit as well.STRENGTHS AND LIMITATIONS OF THIS STUDYThis is the first longitudinal study to measure the trend of and variation in patient cost sharing and OOPs in China.User fees was self-reported by the respondents, which may be subject to recall bias.User fees in this study only reflected the general cost burden from formal healthcare services, therefore, user fees from informal care services were not captured.KEY FINDINGThere were no substantial changes in patient cost sharing for outpatient and inpatient services, but the amount of out-of-pocket payment (OOPs) continued to rise during 2011-2015, especially for outpatient services from 371 Yuan in 2011 to 1031 Yuan in 2015.Despite universal health insurance coverage, patient cost sharing was still high among the middle-aged and older Chinese: 84.0% for outpatient care and 69.2% for inpatient care in 2011; and 80.8% vs 62.2% in 2015. The majority of patients paid more than 80% of the total cost for prescription drugs when visiting outpatient or inpatient care.Several patient-level characteristics affected cost-sharing and OOPs, including insurance status, age, education, household economic status and number of chronic conditions. Cost sharing was lower for those with insurance compared to those without insurance.Provinces with higher GDP per capita had lower cost sharing than provinces with lower GDP per capita, but no significant difference was found in the amount of OOPs after controlling for individual-level factors.

Summary: Background: Multimorbidity, the presence of two or more mental or physical chronic non-communicable diseases, is a major challenge for the health system in China, which faces unprecedented ageing of its population. Here we examined the distribution of physical multimorbidity in relation to socioeconomic status; the association between physical multimorbidity, health-care service use, and catastrophic health expenditures; and whether these associations varied by socioeconomic group and social health insurance schemes. Methods: In this population-based, panel data analysis, we used data from three waves of the nationally representative China Health and Retirement Longitudinal Study (CHARLS) for 2011, 2013, and 2015. We included participants aged 50 years and older in 2015, who had complete follow-up for the three waves. We used 11 physical non-communicable diseases to measure physical multimorbidity and annual per-capita household consumption spending as a proxy for socioeconomic status. Findings: Of 17 708 participants in CHARLS, 11 817 were eligible for inclusion in our analysis. The median age of participants was 62 years (IQR 56–69) in 2015, and 5766 (48·8%) participants were male. 7320 (61·9%) eligible participants had physical multimorbidity in China in 2015. The prevalence of physical multimorbidity was increased with older age (odds ratio 2·93, 95% CI 2·71–3·15), among women (2·70, 2·04–3·57), within a higher socioeconomic group (for quartile 4 [highest group] 1·50, 1·24–1·82), and higher educational level (5·17, 3·02–8·83); however, physical multimorbidity was more common in poorer regions than in the more affluent regions. An additional chronic non-communicable disease was associated with an increase in the number of outpatient visits (incidence rate ratio 1·29, 95% CI 1·27–1·31), and number of days spent in hospital as an inpatient (1·38, 1·35–1·41). We saw similar effects in health service use of an additional chronic non-communicable disease in different socioeconomic groups and among those covered by different social health insurance programmes. Overall, physical multimorbidity was associated with a significantly increased likelihood of catastrophic health expenditure (for the overall population: odds ratio 1·29, 95% CI 1·26–1·32, adjusted for sociodemographic variables). The effect of physical multimorbidity on catastrophic health expenditures persisted even among the higher socioeconomic groups and across all health insurance programmes. Interpretation: Concerted efforts are needed to reduce health inequalities that are due to physical multimorbidity, and its adverse economic effect in population groups in China. Social health insurance reforms must place emphasis on reducing out-of-pocket spending for patients with multimorbidity to provide greater financial risk protection. Funding: None.

Background: Multimorbidity, which is the presence of two or more chronic non-communicable diseases (NCDs), is a growing challenge for the health system in China, which faces unprecedented ageing of its population. This study examined: (1) the distribution of multimorbidity in relation to economic status; (2) the relationships between multimorbidity, healthcare service use, and catastrophic health expenditures (CHE); and (3), whether these relationships varied by economic groups and social health insurance schemes in China. Methods: We used data from the three waves of the nationally-representative China Health and Retirement Longitudinal Study (CHARLS 2011-15), including 11 718 participants aged ≥50 years, and applied random-effects logistic regression to examine the socio-demographic correlates of multimorbidity. Random-effects negative binomial models were used to assess the relationship between the number of NCDs and health service use. Random-effects logistic regression models were used to estimate the impact of multimorbidity on CHE. Findings: Overall, 62% of participants had multimorbidity in China in 2015. The onset of multimorbidity occurred 5 to 10 years earlier in people belonging to the wealthiest socio-economic quartile group compared with the lowest. A higher number of chronic diseases was associated with more frequent health service use for both outpatient visits (Coefficient=0·25, 95% CI=0·24, 0·27) and days of hospitalisation (Coefficient=0·32, 95% CI=0·30, 0·34). There were similar effects from different socioeconomic groups and among those covered by different social health insurance programmes. Overall, multimorbidity was associated with a substantially higher likelihood of experiencing CHE (Adjusted OR=1·29 for the overall population, 95% CI=1·26, 1·32). The effect of multimorbidity on CHE persisted even among the most affluent population and those with the more generous health insurance coverage. Interpretation: Concerted efforts are needed to reduce health inequalities due to multimorbidity, and its adverse economic impact in population groups in China. Multimorbidity is associated with higher levels of health service use and a greater financial burden in China. Social health insurance reforms must place greater emphasis on reducing out-of-pocket spending for patients with multiple chronic conditions to provide greater financial risk protection to those at risk of high out-of-pocket spending due to multimorbidity. Funding: None. Declaration of Interests: We declare no competing interests. Ethical Approval Statement: The Biomedical Ethics Review Committee of Peking University approved the CHARLS study, and all interviewees were required to provide informed consent. The ethical approval number was IRB00001052–11015.

Background User charges are widely used health financing mechanisms in many health systems in low- and middle-income countries (LMICs) due to insufficient public health spending on health. This study systematically reviews the evidence on the relationship between user charges and health outcomes in LMICs, and explores underlying mechanisms of this relationship. Methods Published studies were identified via electronic medical, public health, health services and economics databases from 1990 to September 2017. We included studies that evaluated the impact of user charges on health in LMICs using randomised control trial (RCT), or quasi-experimental (QE) study designs. Study quality was assessed using Cochrane Risk of Bias (RoB), and Risk of Bias in Non-Randomized Studies- of Intervention (ROBINS-I) for RCT and QE studies respectively. The review was registered with the PROSPERO (registration CRD 42017054737). Results We identified 17 studies from 12 countries (five upper-middle income countries, five lower-middle income countries, and two low-income countries) that met our selection criteria. The findings suggested a modest relationship between reduction in user charges and improvements in health outcomes, but this depended on health outcomes measured, the populations studied, study quality and policy settings. The relationship between reduced user charges and improved health outcomes was more evident in studies focusing on children and lower-income populations. Studies examining infectious-disease related outcomes, chronic disease management, and nutritional outcomes were too few to draw meaningful conclusions. Improved access to healthcare as a result of reduction in out-of-pocket expenditure was identified as the possible causal pathway for improved health. Conclusions Reduced user charges were associated with improved health outcomes, particularly for lower-income groups and children in LMICs. Accelerating progress towards Universal Health Coverage (UHC) through prepayment mechanisms such as taxation and insurance can lead to improved health outcomes and reduced health inequalities in LMICs.

Background User charges are widely used health financing mechanisms in many health systems in low-income and middle-income countries (LMICs) due to insufficient public health spending on health. This study systematically reviews the evidence on the relationship between user charges and health outcomes in LMICs, and explores underlying mechanisms of this relationship. Methods Published studies were identified via electronic medical, public health, health services and economics databases from 1990 to September 2017. We included studies that evaluated the impact of user charges on health in LMICs using randomised control trial (RCT) or quasi-experimental (QE) study designs. Study quality was assessed using Cochrane Risk of Bias and Risk of Bias in Non-Randomized Studies—of Intervention for RCT and QE studies, respectively. Results We identified 17 studies from 12 countries (five upper-middle income countries, five lower-middle income countries and two low-income countries) that met our selection criteria. The findings suggested a modest relationship between reduction in user charges and improvements in health outcomes, but this depended on health outcomes measured, the populations studied, study quality and policy settings. The relationship between reduced user charges and improved health outcomes was more evident in studies focusing on children and lower-income populations. Studies examining infectious disease–related outcomes, chronic disease management and nutritional outcomes were too few to draw meaningful conclusions. Improved access to healthcare as a result of reduction in out-of-pocket expenditure was identified as the possible causal pathway for improved health. Conclusions Reduced user charges were associated with improved health outcomes, particularly for lower-income groups and children in LMICs. Accelerating progress towards universal health coverage through prepayment mechanisms such as taxation and insurance can lead to improved health outcomes and reduced health inequalities in LMICs. Trial registration number CRD 42017054737.