scEWE: high-order element-wise weighted ensemble clustering for heterogeneity analysis of single-cell RNA-sequencing data.

With the emergence of large amount of single-cell RNA sequencing (scRNA-seq) data, the exploration of computational methods has become critical in revealing biological mechanisms. Clustering is a representative for deciphering cellular heterogeneity embedded in scRNA-seq data. However, due to the diversity of datasets, none of the existing single-cell clustering methods shows overwhelming performance on all datasets. Weighted ensemble methods are proposed to integrate multiple results to improve heterogeneity analysis performance. These methods are usually weighted by considering the reliability of the base clustering results, ignoring the performance difference of the same base clustering on different cells. In this paper, we propose a high-order element-wise weighting strategy based self-representative ensemble learning framework: scEWE. By assigning different base clustering weights to individual cells, we construct and optimize the consensus matrix in a careful and exquisite way. In addition, we extracted the high-order information between cells, which enhanced the ability to represent the similarity relationship between cells. scEWE is experimentally shown to significantly outperform the state-of-the-art methods, which strongly demonstrates the effectiveness of the method and supports the potential applications in complex single-cell data analytical problems.

Investigation the mechanism of iron overload-induced colonic inflammation following ferric citrate exposure.

Iron overload occurs due to excessive iron intake compared to the body's demand, leading to iron deposition and impairment of multiple organ functions. Our previous study demonstrated that chronic oral administration of ferric citrate (FC) caused colonic inflammatory injury. However, the precise mechanism underlying this inflammatory response remains unclear. The current study aims to investigate the mechanism by which iron overload induced by FC exposure leads to colonic inflammation. To accomplish this, mice were orally exposed to three different concentrations of FC (71 mg/kg/bw (L), 143 mg/kg/bw (M) and 286 mg/kg/bw (H)) for continuous 16 weeks, with the control group receiving ultrapure water (C). Exposure to FC caused disturbances in the excretory system, altered colonic flora alpha diversity, and enriched pathogenic bacteria, such as Mucispirillum, Helicobacter, Desulfovibrio, and Shigella. These changes led to structural disorders of the colonic flora and an inflammatory response phenotype characterized by inflammatory cells infiltration, atrophy of intestinal glands, and irregular thickening of the intestinal wall. Mechanistic studies revealed that FC-exposure activated the NF-κB signaling pathway by up-regulating TLR4, MyD88, and NF-κB mRNA levels and protein expression. This activation resulted in increased production of pro-inflammatory cytokines, further contributing to the colonic inflammation. Additionally, in vitro experiments in SW480 cells confirmed the activation of NF-κB signaling pathway by FC exposure, consistent with the in vivo findings. The significance of this study lies in its elucidation of the mechanism by which iron overload caused by FC exposure leads to colonic inflammation. By identifying the role of pathogenic bacteria and the NF-κB signaling pathway, this study could potentially offer a crucial theoretical foundation for the research on iron overload, as well as provide valuable insights for clinical iron supplementation.

Non-invasive assessment of periodontal inflammation by continuum-removal hemodynamic spectral indices.

BACKGROUND: Hyperspectral techniques have aroused great interest in non-invasively measuring periodontal tissue hemodynamics. However, current studies mainly focused on three typical inflammation stages (healthy, gingivitis and periodontitis) and practical approaches for using optical spectroscopy for early and precisely detection of periodontal inflammation at finer disease stages have not been well studied. METHODS: This study provided novel spectroscopic insights into periodontitis at different stages of disease, and developed six simple but physically meaning hemodynamic spectral indices (HSIs) including four spectral absorption depths of oxyhemoglobin ( D HbO 2 ), deoxyhemoglobin ( D Hb ), total hemoglobin ( t Hb ) and tissue water ( D water ), and two normalized difference indices of oxyhemoglobin( N D HbO 2 I ) and deoxyhemoglobin ( N D Hb I ) from continuum-removal spectra (400-1700 nm) of periodontal tissue collected from 47 systemically healthy subjects over different severities from healthy, gingivitis, slight, moderate to severe periodontitis for early and precision diagnostics of periodontitis. Typical statistical analyses were conducted to explore the effectiveness of the proposed HSIs. RESULTS: D Hb and t Hb exerted significant increasing trends as inflammation progressed, whereas D HbO 2 exhibited significant difference (P < 0.05) from the healthy sites only at moderate and severe periodontitis and D water presented unstable sensitives to disease severity. By contrast, N D HbO 2 I and N D Hb I showed more steadily downward trends as severity increased, and demonstrated the highest correlations with clinical gold standard parameters. Particularly, the proposed normalized HSIs ( N D HbO 2 I and N D Hb I ) yielded high correlations of - 0.49 and - 0.44 with probing depth, respectively, far outperforming results achieved by previous studies. The performances of the HSIs were also confirmed using the periodontal therapy group. CONCLUSIONS: These results indicated great potentials of combination optical spectroscopy and smart devices to non-invasively probe periodontitis at earlier stages using the simple and practical HSIs. Trial registration This study was retrospectively registered in the Chinese Clinical Trial Registry on October 24, 2021, and the clinical registration number is ChiCTR2100052306.

Association of glycemic control with hypertension in patients with diabetes: a population-based longitudinal study.

BACKGROUND: Diabetes increases the risk of hypertension morbidity, but whether this association is varied with glycemic control remains unknown. We aimed to examine the association of glycemic control with hypertension among individuals with diabetes. METHODS: Data was from the China Health and Retirement Longitudinal Study (CHARLS) between 2011 and 2018. Participants were categorized as having adequate glycemic control (HbA1c < 7%) and inadequate glycemic uncontrol (HbA1c ≥ 7%) by combining blood glucose tests and physician's diagnoses in 2011. Incident hypertension was ascertained through self-reported physician diagnoses from 2011 to 2018. Cox proportional hazards regression models were used to examine the effect of glycemic control on hypertension. RESULTS: Among 436 participants with diabetes in this study, 102 met the glycemic control standard, and 334 were insufficient glycemic control. During 7 years of follow-up, 141 individuals developed hypertension. Compared with adequate glycemic control, the hazard ratio of inadequate glycemic control on hypertension was 1.54 (95% CI, 1.07-2.21) in the multivariate model. Additionally, the influence of glycemic control on hypertension varied based on educational attainment and the presence of depressive symptoms (P for interaction < 0.05). CONCLUSIONS: Insufficient glycemic control was associated with a higher risk of hypertension among individuals with diabetes. Notably, the effect of glycemic control on hypertension was more pronounced among those with lower educational attainment and those exhibiting depressive symptoms. These findings underscore the significance of vigilant glycemic monitoring, educational background considerations, and mental health assessments in managing diabetic individuals.

Predictors of referral behaviour and intention amongst physicians in a medical consortium based on the theory of planned behaviour: a cross-sectional study in China.

Introduction: To promote patients' referral across healthcare institutions and integrated care delivery, we identified predictors of physicians' behaviour and intention to refer patients in a county medical consortium in China on the basis of the theory of planned behaviour (TPB). Methods: This census-based cross-sectional study was conducted in Yangxi Hospital Group (YHG). All physicians in county hospitals and township health centres were invited to participate. Structural equation modelling was employed to analyse the relationships between referral intention and behaviour and other TPB variables in the group of whole participants and in sub-groups. Results: In total, 330 physicians participated in this study. One-third of participants were general practitioners, and half of them were from county hospitals. Referral behaviour of females (χ2 = 20.372, p < 0.001), who had lower education levels (χ2 = 17.859, p = 0.001), lower professional title (χ2 = 14.963, p = 0.005), and lower monthly salary (χ2 = 33.753, p < 0.001) were less frequent than the others. Among them, 116 (35.2%), 108 (32.7%), and 106 (32.1%) respondents reported that they had never referred patients, had referred patients 1-9 times, and had referred patients over 10 times during the past 3 months, respectively. The mean score of referral intention was 4.23/5 (SD = 0.71). In the model with all participants, a stronger referral intention (ß = 0.218, 95% CI = 0.080-0.356) was associated with more frequent referral behaviour. The subjective norm (ß = 0.703, 95% CI = 0.590-0.817) was the strongest predictor of physicians' referral intention, followed by perceived behavioural control (ß = 0.234, 95% CI = 0.090-0.378). Mediated by referral intention, subjective norms (ß = 0.153, p < 0.01) and perceived behavioural control (ß = 0.190, p < 0.01) had significant indirect effects on physicians' referral behaviour. The model with participants in county hospitals showed similar results to the model with all participants. Meanwhile, in the model with participants in township health centres, there were no significant associations between referral behaviour and other TPB constructs. Conclusion: Physicians' referral behaviour was influenced by intention, subjective norms, and perceived behavioural control in Chinese county hospitals.

Has_circ_0000069 expression in breast cancer and its influences on prognosis and cellular activities.

Circular RNA (circRNA), as a newly discovered non-coding RNA with important regulatory potential, is closely related to the occurrence and progression of various tumors. This study aimed to investigate has_circ_0000069 expression in breast cancer and its influence on cellular activities. Using real-time quantitative polymerase chain reaction, has_circ_0000069 levels were measured in 137 pairs of tissue specimens, as well as cancer cell lines. The cellular activities of cell lines were determined by cell counting kit-8 (CCK-8) and Transwell assays. The potential targeting miRNAs were predicted and verified using an online database and dual-luciferase reporter assay. Has_circ_0000069 was highly expressed in breast cancer tissues and cells. The expression of has_circ_0000069 was associated with the five-year overall survival of patients. After silencing has_circ_0000069 in breast cancer cells, its expression reduced, and the ability of cell proliferation, migration, and invasion decreased. MiR-432 was verified as a targeting miRNA of has_circ_0000069. Has_circ_0000069 expression increased in breast cancer and was negatively related to patient's prognosis. Has_circ_0000069 may facilitate breast cancer tumor progression by sponging miR-432. These findings revealed that has_circ_0000069 may be a biomarker for predicting prognosis and a therapeutic target for treating patients with breast cancer.

Identification of circRNA-miRNA-mRNA network in luminal breast cancers by integrated analysis of microarray datasets.

Introduction: Circular RNAs (circRNAs) regulatory network is important in human cancer. We, therefore, mapped the regulatory networks driven by circRNA in luminal-subtype breast cancer. Methods: Breast cancer-related microarray datasets from GEO database were analyzed for the differentially expressed circRNAs, miRNAs, and mRNAs. The potential downstream RNAs were collected using Circular RNA Interactome or Targetscan database. Protein-protein interaction (PPI) analysis was performed for the filtered genes to identify hub genes. The functions were annotated by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. CircRNA-miRNA-mRNA networks were mapped using Cytoscape software. Hsa_circ_0086735-miR-1296-5p-STAT1 axis was used for verification. The expression levels of hsa_circ_0086735, miR-1296-5p, and STAT1 mRNA were confirmed by qRT-PCR in luminal-subtype tissues and cell lines. The interactions among them were verified by Luciferase reporter assay and RNA pull-down assay. Cell proliferation and apoptosis were assayed. Overall and distant metastasis-free survival was analyzed. Results: A total of 70 genes were finally targeted and enriched in multi-process and multi-pathway. Networks containing 96 circRNA-miRNA-mRNA axes were constructed. Hsa_circ_0086735 and STAT1 mRNA was upregulated in luminal breast cancer, while miR-1296-5p was downregulated. Hsa_circ_0086735-miR-1296-5p-STAT1 axis promotes breast cancer progression and contributes to tamoxifen resistance. High hsa_circ_0086735 was associated with poor overall and distant metastasis-free survival. Discussion: This study identified the hsa_circ_0086735-miR-1296-5p-STAT1 as an important regulatory axis in luminal-subtype breast cancer, aiding to determine potential therapeutic targets.

Effects of processing procedures on the formation of aroma intensity and odor characteristic of Benshan tea (Oolong tea, Camellia sentences).

Benshan tea is a kind of oolong tea, and Benshan (Camellia sinensis) tea tree originates from Anxi County of Fujian Province in China, which is a national tea tree breed. Tea processing is the key to the formation of its odor characteristics. It is extremely important to step by step analyze effects of tea processing on aroma intensity and the formation of odor characteristics for optimizing tea processing process and improving tea quality. The results of this study showed that processing resulted in a significant increase in the content of volatile compounds in tea leaves, i.e., from 25.213 µg/kg to 111.223 µg/kg, in which the volatile compounds were mainly terpenoids. Secondly, the analysis found that 20 kinds of key compounds constituted to odor characteristics of Benshan tea leaves, among which geraniol, trans-ß-ionone, gerol, citronellol, benzeneacetaldehyde, and trans-nerolidol were the most key six. Floral and fruity aromas, especially floral aroma, mainly formed odor characteristics of Benshan tea after processing, while floral aroma mainly came from the contribution of geraniol, which was the foremost compound in the formation of floral aroma of Benshan tea.

Patients' and Care Professionals' Evaluation of the Effect of a Hospital Group on Integrated Care in Chinese Urban Health Systems: A Propensity Score Matching and Difference-in-differences Regression Approach.

BACKGROUND: A hospital group is an organizational integration strategy that has recently been widely implemented in Chinese urban health systems to promote integrated care. This study aims to evaluate the effect of hospital group on integrated care from the perspectives of both patients and care professionals. METHODS: Two cross-sectional surveys were conducted in Shenzhen city of China, in June 2018 and July 2021. All thirty Community Health Stations (CHSs) in the hospital group were included in the intervention group, with 30 CHSs in the same district selected as the control group by simple random sampling. All care professionals within both the intervention and the control groups were invited to participate in the surveys. Twelve CHSs were selected from 30 CHSs in the intervention and the control groups by simple random sampling, and 20 patients with type 2 diabetes mellitus (T2DM) were selected from each of these selected CHSs to participate in the survey by systematic sampling. The Rainbow Model of Integrated Care-Measurement Tool (Chinese version) was used to assess integrated care. Propensity score matching and difference-in-differences regression (PSM-DID) were used to evaluate the effect of the hospital group on integrated care. RESULTS: After matching, 528 patients and 1896 care professionals were included in the DID analysis. Results from care professionals indicated that the hospital group significantly increased technical competence of the health system by 0.771 points, and cultural competence by 1.423 points. Results from patients indicated that the hospital group significantly decreased organizational integration of the health system by 0.649 points. CONCLUSION: The results suggests that the effect of the hospital group on integrated care over and above routine strategies for integrated care is limited. Therefore, it is necessary to pay attention to implementing professional, clinical and other integration strategies beyond establishing hospital groups, in urban Chinese health systems.

Relationships between job satisfaction, organizational commitment, burnout and job performance of healthcare professionals in a district-level health care system of Shenzhen, China.

Background: Existing research indicates that job satisfaction has effects on job performance, but little evidence exists about the mechanism through which the satisfaction-performance association operates. This study aims to examine the effect of job satisfaction on job performance in a district-level health care system of China and to explore the effect mechanism mediated by organizational commitment and burnout. Methods: Cluster sampling was used in this study. All healthcare professionals in the Nanshan Medical Group, who were at work in the last 3 months and able to complete online questionnaire independently were invited to participate the anonymous online survey. Job satisfaction, organizational commitment, burnout and job performance were measured by tools, which have been validated in China. Descriptive statistics were used for the socio-demographic variables and the four job psychological variables. Pearson correlation coefficients was used to determine associations among each of the psychological variables. Linear regression was used to examine association between job performance and other three psychological variables. PROCESS macro was used to examine the mediation effects of organizational commitment and burnout on the association between job satisfaction and performance. Results: In total, 1,200 healthcare professionals completed the anonymous online survey. Job satisfaction, organizational commitment, and job performance were positively correlated with one another, with burnout negatively correlated with them. Linear regression revealed that demographic characteristics, job satisfaction, organizational commitment, and burnout explained 5, 6, 2, and 9% of the variance in job performance. Path analysis showed that the coefficient of the direct effect of job satisfaction on job performance was 0.18, the coefficients of the indirect effects of job satisfaction on job performance through organizational commitment and burnout were 0.17 and 0.37, respectively. The coefficients of the indirect effects of organizational commitment on job performance through burnout was -0.04, but it was not significant. Conclusion: It is promising to improve job performance of providers in Chinese healthcare systems by improving job satisfaction and reducing burnout. Tailored support policies for female healthcare professionals, appropriate incentive mechanisms and improving multidisciplinary healthcare delivery are potential to improve job performance of healthcare professionals in integrated healthcare systems.

The Economic Burden Associated with Depressive Symptoms among Middle-Aged and Elderly People with Chronic Diseases in China.

Coexisting physical diseases and depressive symptoms exacerbate morbidity and disability, but their incremental economic burden remains unclear. We used cross-sectional data from the China Health and Retirement Longitudinal Study (CHARLS) survey in 2018 to estimate the economic burden associated with depressive symptoms among middle-aged and elderly people with chronic diseases. A multivariable regression model was used to assess the annual health care utilization, expenditures, and productivity loss of depressive symptoms among people with 12 common chronic diseases. We found that depressive symptoms were associated with higher incremental economic burdens, as the total health care costs increased by 3.1% to 85.0% and annual productivity loss increased by 1.6% to 90.1%. Those with cancer or malignant tumors had the largest economic burden associated with depressive symptoms, with CNY 17,273.7 additional annual health care costs and a loss of CNY 2196.2 due to additional annual productivity loss. The effect of depressive symptoms on the economic burden of patients with chronic conditions did not increase by the number of chronic conditions. Considering the high economic burden associated with depressive symptoms among patients with chronic conditions, it is important to consider the mental health of patients in chronic disease treatment and management.

[Spatial Distribution and Sources of Heavy Metals in Soil of a Typical Lead-Zinc Mining Area, Yangshuo].

Taking a typical lead-zinc mining area in Yangshuo county, Guangxi as the research object, the contents of 10 metal elements (Cr, Mn, Ni, Cu, Zn, As, Cd, Sb, Hg, and Pb) in the surface soil of Sidihe River basin in Yangshuo were analyzed and determined. Pearson correlation analysis, principal component analysis (PCA), positive definite matrix factorization (PMF), and other methods were comprehensively used to quantitatively analyze their contributions and identify pollution sources. In total, 168 surface soil samples were collected across the study area. The mean concentrations of Zn, Cd, Hg, and Pb in the soils were higher than the National Environmental Quality Standards for Soils in China. The mean contents of Sb, Cd, Cu, Pb, and Zn were higher than their corresponding local background values by approximately 1.01, 5.50, 3.29, 9.11, and 10.67 times, respectively, indicating that heavy metals have been enriched in topsoil. The Igeo showed that the major pollutant element in the soils was Hg, followed by Pb, Zn, and Mn. Correlation analysis and principal component analysis showed that the sources of metal pollution in surface soil in the study area were complex and mainly from human activities. Cu, Zn, Cd, Sb, As, and Pb were mainly derived from mining activities; Hg, Cr, and Ni were controlled by soil parent material sources; and Mn and Cd were mainly derived from mining activities and agricultural activities. PMF model analysis results showed that the metal pollution sources in the surface soil were jointly affected by these three sources. Mining activities, natural sources, and a mixed source of mining activities and agricultural activities were the main sources of heavy metal pollution in the soils, accounting for 58.0%, 13.5%, and 28.6% of the total heavy metal accumulation, respectively. Ni, Cu, Zn, As, Sb, Hg, and Pb were derived mainly from mining activities. Cr, Ni, and Hg were mainly attributed to natural sources, such as soil parent materials and rainfall erosion (44.6%, 23.2%, and 21.0%, respectively), and Mn and Cd were associated with a mixed source of mining activities and agricultural activities (75.4% and 70.4%).

Cost-effectiveness of using protons for breast irradiation aiming at minimizing cardiotoxicity: A risk-stratification analysis.

Background: Incidental exposure of the heart to ionizing irradiation is associated with an increased risk of ischemic heart disease and subsequent fatality in patients with breast cancer after radiotherapy. Proton beam therapy can limit the heart dose in breast irradiation to a negligible level. However, compared with conventional photon modality, proton breast irradiation is more expensive. In this study, we performed cost-effectiveness analyses to identify the type of patients who would be more suitable for protons. Methods: A Markov decision model was designed to evaluate the cost-effectiveness of protons vs. photons in reducing the risk of irradiation-related ischemic heart disease. A baseline evaluation was performed on a 50-year-old woman patient without the preexisting cardiac risk factor. Furthermore, risk-stratification analyses for photon mean heart dose and preexisting cardiac risk were conducted on 40-, 50-, and 60-year-old women patients under different proton cost and willingness-to-pay (WTP) settings. Results: Using the baseline settings, the incremental effectiveness (protons vs. photons) increased from 0.043 quality-adjusted life-year (QALY) to 0.964 QALY when preexisting cardiac risk increased to 10 times its baseline level. At a proton cost of 50,000 US dollars ($), protons could be cost-effective for ≤ 60-year-old patients with diabetes and ≤50-year-old patients with grade II-III hypertension at the WTP of China ($37,653/QALY); for ≤ 60-year-old patients with diabetes and ≤ 50-year-old patients with grade II-III hypertension or ≥ 2 major cardiac risk factors at a WTP of $50,000/QALY; and for ≤ 60-year-old patients with diabetes, grade II-III hypertension or ≥ 2 major cardiac risk factors and ≤ 50-year-old patients with total cholesterol ≥ 240 mg/dL at a WTP of $100,000/QALY. Conclusion: Patients' preexisting cardiac risk status was a key factor affecting the cardiac benefits gained from protons and should therefore be a major consideration for the clinical decision of using protons; cost-effective scenarios of protons exist in those patients with high risk of developing cardiac diseases.

Better preservation of erectile function in localized prostate cancer patients with modern proton therapy: Is it cost-effective?

BACKGROUND: Stereotactic body radiation therapy (SBRT) has gradually been recognized as favorable curative treatment for localized prostate cancer (PC). However, the high rate of erectile dysfunction (ED) after traditional photon-based SBRT remains an ongoing challenge that greatly impacts the quality of life of PC survivors. Modern proton therapy allows higher conformal SBRT delivery and has the potential to reduce ED occurrence but its cost-effectiveness remains uninvestigated. METHODS: A Markov decision model was designed to evaluate the cost-effectiveness of proton SBRT versus photon SBRT in reducing irradiation-related ED. Base-case evaluation was performed on a 66-year-old (median age of PC) localized PC patient with normal pretreatment erectile function. Further, stratified analyses were performed for different age groups (50, 55, 60, 65, 70, and 75 years) and threshold analyses were conducted to estimate cost-effective scenarios. A Chinese societal willingness-to-pay (WTP) threshold (37,653 US dollars [$])/quality-adjusted life-year [QALY]) was adopted. RESULTS: For the base case, protons provided an additional 0.152 QALY at an additional cost of $7233.4, and the incremental cost-effectiveness ratio was $47,456.5/QALY. Protons was cost-effective for patients ≤62-year-old at the WTP of China (≤66-year-old at a WTP of $50,000/QALY; ≤73-year-old at a WTP of $100,000/QALY). For patients at median age, once the current proton cost ($18,000) was reduced to ≤$16,505.7 or the patient had a life expectancy ≥88 years, protons were cost-effective at the WTP of China. CONCLUSIONS: Upon assumption-based modeling, the results of current study support the use of proton SBRT in younger localized PC patients who are previously potent, for better preservation of erectile function. The findings await further validation using data from future comparative clinical trials.

The Additional Medical Expenditure Caused by Depressive Symptoms among Middle-Aged and Elderly Patients with Chronic Lung Diseases in China.

Depression is one of the most common comorbidities in patients with chronic lung diseases (CLDs). Depressive symptoms have an obvious influence on the health function, treatment, and management of CLD patients. In order to investigate the additional medical expenditure caused by depressive symptoms among middle-aged and elderly patients with CLDs in China, and to estimate urban-rural differences in additional medical expenditure, our study used data from the 2018 China Health and Retirement Longitudinal Study (CHARLS) investigation. A total of 1834 middle-aged and elderly CLD patients were included in this study. A generalized linear regression model was used to analyze the additional medical expenditure on depressive symptoms in CLD patients. The results show that depressive symptoms were associated with an increase in medical costs in patients with CLDs. Nevertheless, the incremental medical costs differed between urban and rural patients. In urban and rural patients with more severe comorbid CLD and depressive symptoms (co-MCDs), the total additional medical costs reached 4704.00 Chinese Yuan (CNY) (USD 711.60) and CNY 2140.20 (USD 323.80), respectively. Likewise, for patients with lower severity co-MCDs, the total additional medical costs of urban patients were higher than those of rural patients (CNY 4908.10 vs. CNY 1169.90) (USD 742.50 vs. USD 176.90). Depressive symptoms were associated with increased medical utilization and expenditure among CLD patients, which varies between urban and rural areas. This study highlights the importance of mental health care for patients with CLDs.

Projections of the economic burden of care for individuals with dementia in mainland China from 2010 to 2050.

BACKGROUND: China has stepped into an era of aging society, where the impending considerable economic burden attributed to high prevalence of dementia in the elderly appears to be one of the most important health and social issues to deal with for the country. However, population-based quantification and projections for the economic burden of dementia in China are lacking for further health action and policy making. OBJECTIVE: To estimate and predict the costs of managing dementia in the elderly population aged 60 and above from 2010 to 2050 in China. METHODS: Data were collected from a six-province study (n = 7072) and other multiple sources for calculation of the economic burden of dementia. With the convincing data from published studies, we quantified and projected the costs attributed to dementia in China from 2010 to 2050. RESULTS: The national cost of dementia in 2010 was estimated to be US$22.8 billion by the opportunity cost method and US$26.4 billion by the proxy method. In 2050, the costs would increase to US$372.3 billion by the opportunity cost method and US$430.6 billion by the proxy method, consuming 0.53% and 0.61% of China's total GDP, respectively. A series of sensitivity analyses showed that the changes in the proportions of informal caregiving led to the most robust changes in the total burden of care for dementia in China. CONCLUSION: Dementia represents an enormous burden on China's population health and economy. Due to the changes in policies and population structure, policymakers should give priority to dementia care.

Intensity-modulated proton radiation therapy as a radical treatment modality for nasopharyngeal carcinoma in China: Cost-effectiveness analysis.

BACKGROUND: Compared to conventional intensity-modulated photon radiation therapy (IMRT), intensity-modulated proton radiation therapy (IMPT) has potential to reduce irradiation-induced late toxicities while maintaining excellent tumor control in patients with nasopharyngeal carcinoma (NPC). However, the relevant cost-effectiveness remains controversial. METHODS: A Markov decision tree analysis was performed under the assumption that IMPT offered normal tissue complication probability reduction (NTCP reduction) in long-term dysphagia, xerostomia, and hearing loss, compared to IMRT. Base-case evaluation was performed on T2N2M0 NPC of median age (43 years old). A Chinese societal willingness-to-pay threshold (33558 US dollars [$])/quality-adjusted life-year [QALY]) was adopted. RESULTS: For patients at median age and having NTCP reduction of 10%, 20%, 30%, 40%, 50%, and 60%, their incremental cost-effectiveness ratios were $102684.0/QALY, $43161.2/QALY, $24134.7/QALY, $13991.6/QALY, $8259.8/QALY, and $4436.1/QALY, respectively; IMPT should provide an NTCP reduction of ≥24% to be considered cost-effective. CONCLUSIONS: IMPT has potential to be cost-effective for average Chinese NPC patients and should be validated clinically.

In situ analysis of variations of arsenicals, microbiome and transcriptome profiles along murine intestinal tract.

In situ-based studies on microbiome-host interactions after arsenic exposure are few. In this study, the variations in arsenics, microbiota, and host genes along murine intestinal tracts were determined after arsenic exposure for two months. There was a gradual increase in the concentration of total As (CtAs) in feces from ileum to colon, whereas CtAs in the corresponding tissues were relatively stable. Differences in arsenic levels between feces and tissues were significantly different. The proportion of arsenite (iAsⅢ) in feces gradually decreased, however, it gradually increased in tissues. After arsenic exposure, the diversity and abundance of microbial community and networks in each segment were significantly dysregulated. Notably, 328, 579 and 90 differently expressed genes were detected in ileum, cecum, and colon, respectively. In addition, microbiome and transcriptome analyses showed a significant correlation between the abundance of Faecalibaculum and expressions of Plb1, Hspa1b, Areg and Duoxa2 genes. This implies that they may be involved in arsenic biotransformation. In vitro experiments using Biofidobactrium and Lactobacillus showed that probiotics have arsenic transformation abilities. Therefore, gut microbiome may modulate arsenic accumulation, excretion and detoxification along the digestive tract. Moreover, the abundance and diversity of gut microbiome may be related to the changes in host health.

Circular RNA circRPPH1 promotes breast cancer progression via circRPPH1-miR-512-5p-STAT1 axis.

Breast cancer (BC) is one of the most fatal diseases among women all over the world. Non-coding RNAs including circular RNAs (circRNAs) have been reported to be involved in different aspects during tumorigenesis and progression. In this study, we aimed to explore the biological functions and underlying mechanism of circRPPH1 in BC. Candidate circRNAs were screened in dataset GSE101123 from Gene Expression Omnibus (GEO) database and a differentially expressed circRNA, circRPPH1, was discovered in BC. CircRPPH1 expression was higher in the cancerous tissue compared to paired adjacent tissue. Further in vitro and in vivo experiments indicated that circRPPH1 acted as an oncogene in BC. In addition, circRPPH1 was mainly localized in cytoplasm and played the role of miR-512-5p sponge. By sequestering miR-512-5p from the 3'-UTR of STAT1, circRPPH1 inhibited the suppressive role of miR-512-5p, stabilized STAT1 mRNA in BC and finally affected BC progression. In conclusion, these findings indicated that circRPPH1 acted as an oncogene and regulated BC progression via circRPPH1-miR-512-5p-STAT1 axis, which might provide a potential therapeutic target for BC treatment.

Economic Burden of Depressive Symptoms Conditions among Middle-Aged and Elderly People with Hypertension in China.

People with hypertension are more prone to incur depressive symptoms, while depressive symptoms have an obvious influence on the healthy functioning, treatment, and management of hypertensive patients. However, there have been limited studies on the association between depression and the economic burden of hypertension. We used data from the 2018 China Health and Retirement Longitudinal Study (CHARLS) to estimate the additional annual direct and indirect economic burden of depressive symptoms among middle-aged and elderly hypertensive patients with a multivariable regression model. The depressive symptoms were associated with substantial additional direct and indirect economic burden. Compared with non-co-MHDS (non-co-morbid hypertension and depressive symptoms) patients, the direct economic burden of lower co-MHDS (co-morbid hypertension and depressive symptoms) patients and higher co-MHDS patients increased 1887.4 CNY and 5508.4 CNY, respectively. For indirect economic burden, the lower co-MHDS patients increased 331.2 CNY and the higher co-MHDS patients increased 636.8 CNY. Both direct and indirect economic burden were incremental with the aggravation of depressive symptoms. The results showed depressive symptoms increased total healthcare costs by increasing the utilization and expenditure of primary healthcare services. Depressive symptoms also led to economic loss of productivity, especially for agricultural workers. This study highlights the importance of mental healthcare for hypertensive patients.