Unravelling the genetic causality of immunoglobulin G N-glycans in ischemic stroke.

BACKGROUND: Evidence suggests that immunoglobulin G (IgG) N-glycosylation is associated with ischemic stroke (IS). However, the causality of IgG N-glycosylation for IS remains unknown. METHODS: Two-sample Mendelian randomization (MR) analyses were performed to investigate the potential causal effects of genetically determined IgG N-glycans on IS using publicly available summarized genetic data from East Asian and European populations. Genetic instruments were used as proxies for IgG N-glycan traits. IgG N-glycans were analysed using ultra-performance liquid chromatography. Four complementary MR methods were performed, including the inverse variance weighted method (IVW), MR‒Egger, weighted median and penalized weighted median. Furthermore, to further test the robustness of the results, MR based on Bayesian model averaging (MR-BMA) was then applied to select and prioritize IgG N-glycan traits as risk factors for IS. RESULTS: After correcting for multiple testing, in two-sample MR analyses, genetically predicted IgG N-glycans were unrelated to IS in both East Asian and European populations, and the results remained consistent and robust in the sensitivity analysis. Moreover, MR-BMA also showed consistent results in both East Asian and European populations. CONCLUSIONS: Contrary to observational studies, the study did not provide enough genetic evidence to support the causal associations of genetically predicted IgG N-glycan traits and IS, suggesting that N-glycosylation of IgG might not directly involve in the pathogenesis of IS.

Immunoglobulin G N-glycan, inflammation and type 2 diabetes in East Asian and European populations: a Mendelian randomization study.

BACKGROUND: Immunoglobulin G (IgG) N-glycans have been shown to be associated with the risk of type 2 diabetes (T2D) and its risk factors. However, whether these associations reflect causal effects remain unclear. Furthermore, the associations of IgG N-glycans and inflammation are not fully understood. METHODS: We examined the causal associations of IgG N-glycans with inflammation (C-reactive protein (CRP) and fibrinogen) and T2D using two-sample Mendelian randomization (MR) analysis in East Asian and European populations. Genetic variants from IgG N-glycan quantitative trait loci (QTL) data were used as instrumental variables. Two-sample MR was conducted for IgG N-glycans with inflammation (75,391 and 18,348 participants of CRP and fibrinogen in the East Asian population, 204,402 participants of CRP in the European population) and T2D risk (77,418 cases and 356,122 controls of East Asian ancestry, 81,412 cases and 370,832 controls of European ancestry). RESULTS: After correcting for multiple testing, in the East Asian population, genetically determined IgG N-glycans were associated with a higher risk of T2D, the odds ratios (ORs) were 1.009 for T2D per 1- standard deviation (SD) higher GP5, 95% CI = 1.003-1.015; P = 0.0019; and 1.013 for T2D per 1-SD higher GP13, 95% CI = 1.006-1.021; P = 0.0005. In the European population, genetically determined decreased GP9 was associated with T2D (OR = 0.899 per 1-SD lower GP9, 95% CI: 0.845-0.957). In addition, there was suggestive evidence that genetically determined IgG N-glycans were associated with CRP in both East Asian and European populations after correcting for multiple testing, but no associations were found between IgG N-glycans and fibrinogen. There was limited evidence of heterogeneity and pleiotropy bias. CONCLUSIONS: Our results provided novel genetic evidence that IgG N-glycans are causally associated with T2D.

Moderate physical activity may not decrease the risk of cardiovascular disease in persistently overweight and obesity adults.

BACKGROUND: Body mass index (BMI) and physical activity (PA) has been documented to be associated with cardiovascular disease (CVD). However, the evidences regarding joint phenotypes of BMI and PA trajectories with risk for CVD and all-cause mortality are still limited. METHODS: Participants from the Kailuan Study, followed up during 2006-2019 were included, with primary outcomes of CVDs (myocardial infarction or stroke) and all-cause mortality. BMI and PA were repeatedly measured at least three times, and thus joint phenotypes trajectory groups were identified by group-based trajectory modeling. Cox proportional hazards models were used to examine the associations between trajectory groups and CVDs and all-cause mortality. RESULTS: Totally 88,141 (6 trajectories) and 89,736 participants (5 trajectories) were included in the final analyses relating trajectories to CVDs and all-cause mortality, respectively. Compared with persistent normal-weight with moderate PA group, participants were associated with increased risk of CVD in persistent overweight with moderate PA trajectory group (adjusted hazard ratio [aHR]: 1.31, 95% confidence interval [CI]: 1.22-1.41) and persistent obesity with moderate PA trajectory group (aHR: 1.55, 95% CI: 1.41-1.69). While the rising to overweight with moderate PA in normal-weight status with active PA (aHR: 0.72, 95% CI: 0.65-0.79), persistent overweight with moderate PA (aHR: 0.92, 95% CI: 0.87-0.97) and decline to normal-weight in overweight status with moderate PA (aHR: 0.73, 95% CI: 0.67-0.80) trajectories group were significantly associated with decreased all-cause mortality risk. The associations remained robust among stratifying by age and sex individuals and sensitive analysis. CONCLUSIONS: The long-term trajectories analysis showed that moderate PA may not decrease the risk of CVD in persistently overweight and obesity adults.

Vascular endothelial growth factor and the risk of venous thromboembolism: a genetic correlation and two-sample Mendelian randomization study.

BACKGROUND: The relationship between vascular endothelial growth factor (VEGF) and the risk of venous thromboembolism (VTE) has always been one of the concerns in the medical field. However, the causal inferences from published observational studies on this issue may be affected by confounders or reverse causality. We performed a two-sample bidirectional Mendelian randomization (MR) to infer the associations between VEGF and VTE. METHODS: Summary statistics from genome-wide association studies (GWAS) for VEGF and VTE were obtained from published meta-analysis studies and the FinnGen consortium, respectively. Independent genetic variables significantly associated with exposure were selected as instrumental variables. Linkage disequilibrium score regression (LDSC) and five robust MR analytical approaches were conducted to estimate the genetic correlations and causal inference. The MR-Egger intercept, Cochran's Q, and MR pleiotropy residual sum and outlier (MR-PRESSO) were performed to evaluate the horizontal pleiotropy, heterogeneities, and stability of these genetic variants on outcomes. Notably, replication analyses were performed using different subgroups of VTE. RESULTS: LDSC failed to identify genetic correlations between VEGF and VTE. Based on 9 SNPs, the circulating VEGF level was positively related to the risk of VTE using inverse variance weighting (IVW) method (odds ratio (OR) = 1.064, 95% confidence interval (CI), 1.009-1.122). Reverse MR analyses showed that genetic liability for VTE was not associated with increased VEGF level (ß = -0.021, 95% CI, -0.087-0.045). Pleiotropy-robust methods indicated no bias in any estimates. CONCLUSIONS: Our findings failed to detect coheritability between VEGF and VTE. The suggestive positive effect of the higher VEGF level on the VTE risk may have clinical implications, suggesting that VEGF as a possible predictor and therapeutic target for VTE prevention need to be further warranted.

Causal associations between COVID-19 and atrial fibrillation: A bidirectional Mendelian randomization study.

BACKGROUND AND AIMS: Observational studies showed that coronavirus disease (2019) (COVID-19) attacks universally and its most menacing progression uniquely endangers the elderly with cardiovascular disease (CVD). The causal association between COVID-19 infection or its severity and susceptibility of atrial fibrillation (AF) remains unknown. METHODS AND RESULTS: The bidirectional causal relationship between COVID-19 (including COVID-19, hospitalized COVID-19 compared with not hospitalized COVID-19, hospitalized COVID-19 compared with the general population, and severe COVID-19) and AF are determined by using two-sample Mendelian randomization (MR) analysis. Genetically predicted severe COVID-19 was not significantly associated with the risk of AF [odds ratio (OR), 1.037; 95% confidence interval (CI), 1.005-1.071; P = 0.023, q = 0.115]. In addition, genetically predicted AF was also not causally associated with severe COVID-19 (OR, 0.993; 95% CI, 0.888-1.111; P = 0.905, q = 0.905). There was no evidence to support the association between genetically determined COVID-19 and the risk of AF (OR, 1.111; 95% CI, 0.971-1.272; P = 0.127, q = 0.318), and vice versa (OR, 1.016; 95% CI, 0.976-1.058; P = 0.430, q = 0.851). Besides, no significant association was observed for hospitalized COVID-19 with AF. MR-Egger analysis indicated no evidence of directional pleiotropy. CONCLUSION: Overall, this MR study provides no clear evidence that COVID-19 is causally associated with the risk of AF.

In vitro effects of brominated flame retardants, selected metals and their mixtures on ethoxyresorufin-O-deethylase activity in Mossambica tilapia liver.

The in vitro effects of individual brominated flame retardants (BFRs), selected metals, and their binary mixtures on ethoxyresorufin-O-deethylase (EROD) activity were evaluated using a plate-reader method. The BFRs, 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), decabromodiphenyl oxide (BDE-209), hexabromocyclododecane (HBCD), and tetrabromobisphenol A (TBBPA), were tested at doses ranging from 0.1 ng/L to 100 µg/L. Selected metals (Cu2+, Cd2+, Hg2+, and Zn2+) were screened at doses of 0.1 mg/L to 50 mg/L. The activity of EROD was significantly induced by TBBPA, BDE-209, and Zn2+, while HBCD, Cu2+, Cd2+, and Hg2+ decreased EROD activity. Moreover, following exposure to binary mixtures of metals and BFRs, the EROD activity dose-response curves were similar to those of the metals alone, indicating that EROD activity was governed by the metals.

Technology acceptance model perspective on the intention to participate in medical talents training in China.

Objectives: This study seeks to investigate the willingness of medical professionals to embrace training in sports medicine integrated talents, as well as the factors that influence their decision-making process. By utilizing technology acceptance models, the objective is to gain a comprehensive understanding of this phenomenon and provide valuable recommendations to facilitate the development of proficient integration of sports and medicine (ISM) talents. Methods: The questionnaire was developed through a comprehensive review of relevant literature and consultation with experts in the field. A cluster sampling method was employed to select medical professionals from various medical institutions in Guangxi Zhuang Autonomous Region (Guangxi) who had participated in ISM talent training. The collected data were analyzed using the AMOS structural equation model, ensuring a rigorous and systematic approach to data analysis. Results: A total of 403 questionnaires were collected in this survey, and 8 out of the 9 research hypotheses formulated for the model variables were found to be supported. Perceived usefulness, perceived ease of use, subjective norm and training satisfaction were identified as significant factors influencing the behavioral intention of medical professionals to engage in ISM talent training (P < 0.05). The path coefficients for these factors were 0.17, 0.16, 0.31 and 0.24, respectively. Conclusion: In order to enhance the effectiveness of training for ISM talents, it is imperative for relevant departments to collaborate and focus on improving the perceived usefulness, perceived ease of use, and training satisfaction. By doing so, we can effectively harness the subjective initiative of medical professionals, thereby increasing their willingness to participate in training programs. This, in turn, will contribute to the cultivation of "high-quality, high-level" ISM talents that are essential for the betterment of society.

Low Concentration of Wenyang Tonglin Decoction Promotes Conjugation and Transfer of Drug-Resistant Plasmids among Heterologous Strains.

OBJECTIVE: To investigate the effect of low concentration of Wenyang Tonglin Decoction (WTD) on the binding conditions of R45 plasmid conjugative transfer under liquid phase conjugation and its mechanism. METHODS: Escherichia coli CP9 (R45) and Staphylococcus aureus RN450RF were cultured in medium containing WTD, and their minimum inhibitory concentration (MIC) values were obtained. Using promoter fusion technology, E. coli CP9 (R45) containing a promoter fusion was obtained. ß-Galactosidase activity of TrfAp and TrbBp was tested, and the mRNA expression of regulatory factors (TrbA, KorA, and KorB) was detected by real-time fluorescent quantitative polymerase chain reaction. RESULTS: The MIC of E. coli CP9 (R45) was 400 g/L and that of S. aureus RN450RF was 200 g/L. When the drug concentration in the culture medium was 200 g/L, the highest number of conjugants was (3.47 ±0.20) × 107 CFU/mL At 90 h of conjugation, the maximum number of conjugants was (1.15 ±0.06) × 108 CFU/mL When the initial bacterial concentration was 108 CFU/mL, the maximum number of conjugants was (3.47 ± 0.20) × 107 CFU/mL. When the drug concentration was 200 g/L, the ß-galactosidase activity of TrfAp and TrbBp significantly increased; the relative quantification of TrbA, KorA and KorB were significantly inhibited. CONCLUSION: Low concentration of WTD promoted the development of bacterial resistance by affecting promoters and inhibiting the expression of regulatory factors.

Astrocyte KDM4A mediates chemokines and drives neutrophil infiltration to aggravate cerebral ischemia and reperfusion injury.

Neutrophils plays a crucial role in acute ischemic brain injury and have emerged as potential treatment targets to mitigate such injuries. Lysine-specific demethylase 4 A (KDM4A), a member of the histone lysine demethylase family of enzymes involved in transcriptional regulation of gene expression, is upregulated during hypoxic events. However, the exact role of KDM4A in the pathological process of ischemic stroke remains largely unexplored. Our findings reveal that there was an upregulation of KDM4A levels in reactive astrocytes within both stroke mouse models and in vitro oxygen-glucose deprivation/regeneration (OGD/R) models. Using a conditional knockout mouse, we observed that astrocytic Kdm4a knockout regulates neutrophil infiltration and alleviates brain injury following middle cerebral artery occlusion reperfusion. Furthermore, Kdm4a deficiency astrocytes displayed lower chemokine C-X-C motif ligand 1 (CXCL1) level upon OGD/R and decreased neutrophil infiltration in a transwell system. Mechanistically, KDM4A, in cooperation with nuclear factor-kappa B (NF-κB), activates Cxcl1 gene expression by demethylating histone H3 lysine 9 trimethylation at Cxcl1 gene promoters in astrocytes upon OGD/R injury. Our findings suggest that astrocyte KDM4A-mediated Cxcl1 activation contributes to neutrophil infiltration via cooperation with NF-κB, and KDM4A in astrocytes may serve as a potential therapeutic target to modulate neutrophil infiltration after stroke.

Association of IgG N-glycomics with prevalent and incident type 2 diabetes mellitus from the paradigm of predictive, preventive, and personalized medicine standpoint.

Objectives: Type 2 diabetes mellitus (T2DM), a major metabolic disorder, is expanding at a rapidly rising worldwide prevalence and has emerged as one of the most common chronic diseases. Suboptimal health status (SHS) is considered a reversible intermediate state between health and diagnosable disease. We hypothesized that the time frame between the onset of SHS and the clinical manifestation of T2DM is the operational area for the application of reliable risk assessment tools, such as immunoglobulin G (IgG) N-glycans. From the viewpoint of predictive, preventive, and personalized medicine (PPPM/3PM), the early detection of SHS and dynamic monitoring by glycan biomarkers could provide a window of opportunity for targeted prevention and personalized treatment of T2DM. Methods: Case-control and nested case-control studies were performed and consisted of 138 and 308 participants, respectively. The IgG N-glycan profiles of all plasma samples were detected by an ultra-performance liquid chromatography instrument. Results: After adjustment for confounders, 22, five, and three IgG N-glycan traits were significantly associated with T2DM in the case-control setting, baseline SHS, and baseline optimal health participants from the nested case-control setting, respectively. Adding the IgG N-glycans to the clinical trait models, the average area under the receiver operating characteristic curves (AUCs) of the combined models based on repeated 400 times fivefold cross-validation differentiating T2DM from healthy individuals were 0.807 in the case-control setting and 0.563, 0.645, and 0.604 in the pooled samples, baseline SHS, and baseline optimal health samples of nested case-control setting, respectively, which presented moderate discriminative ability and were generally better than models with either glycans or clinical features alone. Conclusions: This study comprehensively illustrated that the observed altered IgG N-glycosylation, i.e., decreased galactosylation and fucosylation/sialylation without bisecting GlcNAc, as well as increased galactosylation and fucosylation/sialylation with bisecting GlcNAc, reflects a pro-inflammatory state of T2DM. SHS is an important window period of early intervention for individuals at risk for T2DM; glycomic biosignatures as dynamic biomarkers have the ability to identify populations at risk for T2DM early, and the combination of evidence could provide suggestive ideas and valuable insight for the PPPM of T2DM. Supplementary information: The online version contains supplementary material available at 10.1007/s13167-022-00311-3.

Glycomic biomarkers are instrumental for suboptimal health status management in the context of predictive, preventive, and personalized medicine.

Objectives: Suboptimal health status (SHS), a reversible borderline condition between optimal health status and disease, has been recognized as a main risk factor for non-communicable diseases (NCDs). From the standpoint of predictive, preventive, and personalized medicine (PPPM/3PM), the early detection of SHS provides a window of opportunity for targeted prevention and personalized treatment of NCDs. Considering that immunoglobulin G (IgG) N-glycosylation levels are associated with NCDs, it can be speculated that IgG N-glycomic alteration might occur at the SHS stage. Methods: A case-control study was performed and it consisted of 124 SHS individuals and 124 age-, gender-, and body mass index-matched healthy controls. The IgG N-glycan profiles of 248 plasma samples were analyzed by ultra-performance liquid chromatography instrument. Results: After adjustment for potential confounders (i.e., age, levels of education, physical activity, family income, depression score, fasting plasma glucose, and low-density lipoprotein cholesterol), SHS was significantly associated with 16 IgG N-glycan traits at 5% false discovery rate, reflecting decreased galactosylation and fucosylation with bisecting GlcNAc, as well as increased agalactosylation and fucosylation without bisecting GlcNAc. Canonical correlation analysis showed that glycan peak (GP) 20, GP9, and GP12 tended to be significantly associated with the 5 domains (fatigue, the cardiovascular system, the digestive system, the immune system, and mental status) of SHS. The logistic regression model including IgG N-glycans was of moderate performance in tenfold cross-validation, achieving an average area under the receiver operating characteristic curves of 0.703 (95% confidence interval: 0.637-0.768). Conclusions: The present findings indicated that SHS-related alteration of IgG N-glycans could be identified at the early onset of SHS, suggesting that IgG N-glycan profiles might be potential biomarker of SHS. The altered SHS-related IgG N-glycans are instrumental for SHS management, which could provide a window opportunity for PPPM in advanced treatment of NCDs and shed light on future studies investigating the pathogenesis of progression from SHS to NCDs. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-022-00278-1.

Causal Relationship Between Lung Function and Atrial Fibrillation: A Two Sample Univariable and Multivariable, Bidirectional Mendelian Randomization Study.

Background: Observational studies have identified impaired lung function accessed by forced expiratory volume in one second (FEV1), forced vital capacity (FVC) or the ratio of FEV1 over FVC (FEV1/FVC) as an independent risk factor for atrial fibrillation (AF). However, the result may be affected by confounders or reverse causality. Methods: We performed univariable MR (uvMR), multivariable MR (mvMR) and bidirectional two-sample MR to jointly estimate the causality of lung function with AF. Apart from the inverse variance weighted (IVW) approach as the main MR analysis, three complementary sensitive analyses approaches including MR-Egger regression, weighted median (WM) MR and Pleiotropy Residual Sum and Outlier (MR-PRESSO) in uvMR as well as mvMR-Egger and mvMR-PRESSO in mvMR were applied to control for pleiotropy. Linkage disequilibrium score (LDSC) regression was applied to estimate genetic correlation between lung function and AF. Results: All forward and reverse uvMR analyses consistently suggested absent causal relations between lung function and AF risk [forward IVW: odds ratio (OR)FEV1 = 1.031, 95% CI = 0.909-1.169, P = 0.630; ORFVC = 1.002, 95% CI = 0.834-1.204, P = 0.982; ORFEV1/FVC = 1.076, 95% CI = 0.966-1.199, P = 0.182; reverse IVW: ORFEV1 = 0.986, 95% CI = 0.966-1.007, P = 0.187; ORFVC = 0.985, 95% CI = 0.965-1.006, P = 0.158; ORFEV1/FVC = 0.994, 95% CI = 0.973-1.015, P = 0.545]. The forward MR-Egger showed that each standard deviation (SD) increase in FEV1/FVC was related to a higher AF risk (OR = 1.502, 95% CI = 1.178-1.915, P = 0.006) without heterogeneity (Q_pval = 0.064), but pleiotropy effect exist (intercept = -0.017, P = 0.012). However, this significant effect disappeared after adjustment of FEV1 and FVC (OR = 1.523, 95% CI = 0.445-5.217, P = 0.503) in mvMR. No evidence was found for independent causal effects of FEV1 and FVC on AF in mvMR analysis by using mvIVW method (ORFEV1 = 0.501, 95% CI = 0.056-4.457, P = 0.496; ORFVC = 1.969, 95% CI = 0.288-13.474, P = 0.490). Notably, the association between lung function and AF were replicated using the FinnGen cohort data. Conclusions: Our findings reported no coheritability between lung function and AF, and failed to find substantial causal relation between decreased lung function and risk of AF. However, lung function and AF were both associated with inflammation, which may be potential pathway, warranting further study.

The Role of C-Reactive Protein and Fibrinogen in the Development of Intracerebral Hemorrhage: A Mendelian Randomization Study in European Population.

Background: The causal association of C-reactive protein (CRP) and fibrinogen on intracerebral hemorrhage (ICH) remains uncertain. We investigated the causal associations of CRP and fibrinogen with ICH using two-sample Mendelian randomization. Method: We used single-nucleotide polymorphisms associated with CRP and fibrinogen as instrumental variables. The summary data on ICH were obtained from the International Stroke Genetics Consortium (1,545 cases and 1,481 controls). Two-sample Mendelian randomization estimates were performed to assess with inverse-variance weighted and sensitive analyses methods including the weighted median, the penalized weighted median, pleiotropy residual sum and outlier (MR-PRESSO) approaches. MR-Egger regression was used to explore the pleiotropy. Results: The MR analyses indicated that genetically predicted CRP concentration was not associated with ICH, with an odds ratio (OR) of 1.263 (95% CI = 0.935-1.704, p = 0.127). Besides, genetically predicted fibrinogen concentration was not associated with an increased risk of ICH, with an OR of 0.879 (95% CI = 0.060-18.281; p = 0.933). No evidence of pleiotropic bias was detected by MR-Egger. The findings were overall robust in sensitivity analyses. Conclusions: Our findings did not support that CRP and fibrinogen are causally associated with the risk of ICH.

Screening toxicological effects of different contaminants using hepatic homogenates-based ethoxyresorufin-O-deethylase in vitro.

In this paper, we demonstrated the potential of an in vitro method of liver homogenate-based ethoxyresorufin-O-deethylase (EROD) to determine the toxicological effects of multiple kinds of contaminants. We evaluated the in vitro impact of nine pharmaceutically active compounds (PhACs), 13 polycyclic aromatic hydrocarbons (PAHs), and three polychlorinated biphenyls (PCBs). There were different responses of EROD to these contaminants. The response of EROD to PhACs was quite complex, exhibiting both induction and inhibition effects. PAHs and PCBs elicited a strong inhibitory response on EROD activity at high concentrations in a dose-dependent manner. PAHs showed more inhibitory effects as the number of benzene rings increased. Our in vitro bioassay seems to be a potential method for toxicological screening of multiple types of contaminants.

Studying the mixture effects of brominated flame retardants and metal ions by comet assay.

This study was designed to evaluate the sensitivities of diverse cell lines on DNA damage effects and genotoxic effects of three brominated flame retardants (BFRs) and three metal ions (Cu2+, Cd2+, Hg2+) by comet assay. First, THP-1 was identified as the most sensitive cell line in terms of DNA damage among 11 kinds of cells screened. Accordingly, the THP-1 cell line was used as a model in subsequent single/combined genotoxicity tests. Single exposure tests to BFRs or metal ions revealed that the DNA damage effects increased with increasing exposure concentration. In combined exposure tests, BFRs (at concentrations of 1/2 EC50) were deployed in combination with different concentrations of Cu2+, Cd2+, or Hg2+. The results showed that the % tail DNA values were significantly increased by most mixtures. Our findings on combined toxic effects by comet assay provide valuable information for setting valid environmental safety evaluation standards.

Health service security of patients with 8 certain rare diseases: evidence from China's national system for health service utilization of patients with healthcare insurance.

BACKGROUND: Rare diseases are one of the major challenges in the era of precision medicine and reflect the social security level of minority groups. This study aimed to investigate healthcare service utilization and health security of patients with rare diseases in China. METHODS: From 29 provinces of Mainland China, 7,747 visits with eight common rare diseases who were linked to the national insurance database between 2014 and 2016 were selected as the study population, whose demographic and healthcare service information was collected from China's national monitoring system for health service utilization of patients with healthcare insurance. Univariate analysis was performed to describe the basic statement of healthcare service, such as visit type, institution type, length of stay, healthcare insurance utilization, and the results of disease burden for different groups and its factors were analyzed by multivariate analysis. RESULTS: Medical treatment from general tertiary hospitals was sought by 61.4% of the patients with rare diseases. Of the total treatment cost (TTC) of 40.18 million Chinese Yuan, 63.3% was paid by basic health insurance, and 54.2% of the medical cost resulted from medicine expenditure. Demography, geography and social-economic factors, security level, and health institution situation had an effect on the TTC. The correlations between these factors and TTC were different for outpatients and inpatients. Reimbursement rate had the highest effect on inpatients' TTC. Basic insurance was effective for providing support for patients with rare diseases that involved high costs; however, the coverage was limited. CONCLUSIONS: Healthcare insurance is an effective safeguard for patients with rare diseases; however, affordable and accessible treatment is still lacking for such patients. There remains a need to further improve the diagnostic and treatment technology for rare diseases and expertise among doctors, as well as the security level of healthcare policies.

Evaluation of patient experience in county-level public hospitals in China: a multicentred, cross-sectional study.

OBJECTIVES: Patient experience is being widely considered in the evaluation of healthcare service quality, which is a key target for public hospitals under China's New Healthcare Reform. This study aimed to illustrate patients' experiences in county-level public hospitals, and identify aspects that need to be improved. SETTING AND PARTICIPANTS: Between 2016 and 2018, a cross-sectional study with 500 outpatients and 800 inpatients was conducted in 10 county-level public hospitals from Shandong Province, Hubei Province and Chongqing Municipality. METHOD: A three-part questionnaire was used to evaluate patients' experiences during their visits to hospitals. It comprised a questionnaire for basic information, the Picker Patient Experience (PPE-15) Questionnaire and the overall evaluation (a 3-point Likert scale to express patients' satisfaction and patient loyalty). Patients' experiences were classified according to six dimensions (information transmission and patient education, respect for patient preference, emotional support, physical comfort, involvement of family or friends and continuity of medical service). Both univariate and multivariate analyses were performed to evaluate patient experience. RESULTS: A total of 1241 valid questionnaires were analysed. The mean PPE-15 score was 41.33 (range, 23-56). The better the patient experience and satisfaction, the higher the patient loyalty (p<0.001). Except for hospital disparities, patients' age and occupation status had a significant impact on patient experience (p<0.05). Of the six dimensions, the physical comfort score was the highest, while the respect for patient preference score was the lowest. Additionally, a strong correlation was found between the respect for patient preference dimension and patients' overall satisfaction with their treatment experience. CONCLUSIONS: Hospital managers and staff members should pay close attention to the preferences of patients and their families to improve patient experience.

Is a Mass Prevention and Control Program for Pandemic (H1N1) 2009 Good Value for Money? Evidence from the Chinese Experience.

BACKGROUND: In order to provide guidance on the efficient allocation of health resources when handling public health emergencies in the future, the study evaluated the H1N1 influenza prevention and control program in Hubei Province of China using cost-benefit analysis. METHODS: The costs measured the resources consumed and other expenses incurred in the prevention and control of H1N1. The assumed benefits include resource consumption and economic losses which could be avoided by the measures for the prevention and control of H1N1. The benefit was evaluated by counterfactual thinking, which estimates the resource consumption and economic losses could be happened without any measures for the prevention and control, which have been avoided after measures were taken to prevent and control H1N1 in Hubei Province, these constitutes the benefit of this project. RESULTS: The total costs of this program were 38.81 million U.S. dollars, while the total benefit was assessed as 203.71 million U.S. dollars. The net benefit was 164.9 million U.S. dollars with a cost-effectiveness ratio of 1:5.25. CONCLUSIONS: The joint prevention and control strategy introduced by Hubei for H1N1 influenza is cost-effective.