Toward the Scalable, Rapid, Reproducible, and Cost-Effective Synthesis of Personalized Nanomedicines at the Point of Care.

Organic nanoparticles are used in nanomedicine, including for cancer treatment and some types of COVID-19 vaccines. Here, we demonstrate the scalable, rapid, reproducible, and cost-effective synthesis of three model organic nanoparticle formulations relevant to nanomedicine applications. We employed a custom-made, low-cost fluid mixer device constructed from a commercially available three-dimensional printer. We investigated how systematically changing aqueous and organic volumetric flow rate ratios determined liposome, polymer nanoparticle, and solid lipid nanoparticle sizes, size distributions, and payload encapsulation efficiencies. By manipulating inlet volumes, we synthesized organic nanoparticles with encapsulation efficiencies approaching 100% for RNA-based payloads. The synthesized organic nanoparticles were safe and effective at the cell culture level, as demonstrated by various assays. Such cost-effective synthesis approaches could potentially increase the accessibility to clinically relevant organic nanoparticle formulations for personalized nanomedicine applications at the point of care, especially in nonhospital and low-resource settings.

Development of a nutritional screening and assessment indicator system for patients with esophageal cancer in China: Findings from the Delphi method.

BACKGROUND: In China, individuals diagnosed with esophageal cancer are confronted with an elevated risk of nutritional inadequacy or malnutrition throughout the course of their disease, a condition that contributes to various adverse clinical outcomes. A vast corpus of data are burgeoning at an unprecedented rate, primarily due to the revolutionary growth of digitalization technologies and artificial intelligence, notably within the domains of health care and medicine. The purpose of this investigation is to initiate the development of a nutritional screening and assessment indicator framework for patients with esophageal cancer within the Chinese context. We seek to furnish an instrumental reference to facilitate preparations for the forthcoming era of advanced, "deep," evidence-based medicine. METHODS: An integrative methodology was employed to forge the preliminary draft of the nutritional screening and assessment indicator system for preoperative patients with esophageal cancer. This encompassed a rigorous literature survey, in-depth clinical practice investigation, and the facilitation of expert panel discussions. Thereafter, two iterative consultation phases were conducted using the Delphi method in China. The analytic hierarchy process was deployed to ascertain the weighting of each index within the definitive evaluation indicator system. RESULTS: The effective response rates for the dual rounds of expert consultation were 91.7% and 86.4%, with commensurate authority coefficients of 0.97 and 0.91. The Kendall harmony coefficients were ascertained to be 0.19 and 0.14 (p < 0.01), respectively. The culminating nutritional screening and assessment indicator system for patients with esophageal cancer comprised 5 primary-level indicators and 38 secondary-level indicators. CONCLUSIONS: The nutritional screening and assessment indicator system contrived for patients with esophageal cancer is underpinned by cogent theoretical principles, leverages an astute research methodology, and manifests dependable outcomes. This system may be appositely utilized as a meaningful reference for the nutritional screening and assessment process in patients afflicted with esophageal cancer.

Evaluation and prediction of water conservation of the Yellow river basin in Sichuan Province, China, based on Google Earth Engine and CA-Markov.

The Yellow River Basin in China has the world's most serious soil erosion problem. The Yellow River Basin in Sichuan Province (YRS), as the upper reaches of the Yellow River, and its water conservation (WC) capacity greatly affects the ecological environment of the downstream basin. In recent years, YRS has received more and more attention, and numerous policies have been developed to improve local WC. However, there is a vacancy in the long-term research of WC in the YRS due to the lack of in-situ data. This study quantitatively evaluated the WC of YRS from 2001 to 2020 through Google Earth Engine (GEE) and analyzed the spatio-temporal variations of WC and land cover (LC). CA-Markov predicted the LC and WC in 2025 under three scenarios to assess the contribution of different scenarios to WC. The WC in YRS fluctuated from 1.93 to 6.77 billion m3. The climate is the dominant factor of WC change, but the effect of LC on WC is also evident. The WC capacity increases with vegetation coverage and height. The WC capacity of forests per km2 exceeds 600 mm, while that of grasslands is about 250 mm, and barren can cause around 300 mm of WC loss. In 2025, the WC in YRS may exceed 7.5 billion m3, but the past ecological management mode should be transformed. Improving the quality of land use and converting grasslands to forests is better than reducing cropland to improve WC.

In-patient Expenditure Between 2012 and 2020 Concerning Patients With Liver Cirrhosis in Chongqing: A Hospital-Based Multicenter Retrospective Study.

Background: Liver cirrhosis is a major global health and economic challenge, placing a heavy economic burden on patients, families, and society. This study aimed to investigate medical expenditure trends in patients with liver cirrhosis and assess the drivers for such medical expenditure among patients with liver cirrhosis. Methods: Medical expenditure data concerning patients with liver cirrhosis was collected in six tertiary hospitals in Chongqing, China, from 2012 to 2020. Trends in medical expenses over time and trends according to subgroups were described, and medical expenditure compositions were analyzed. A multiple linear regression model was constructed to evaluate the factors influencing medical expenditure. All expenditure data were reported in Chinese Yuan (CNY), based on the 2020 value, and adjusted using the year-specific health care consumer price index for Chongqing. Results: Medical expenditure for 7,095 patients was assessed. The average medical expenditure per patient was 16,177 CNY. An upward trend in medical expenditure was observed in almost all patient subgroups. Drug expenses were the largest contributor to medical expenditure in 2020. A multiple linear regression model showed that insurance type, sex, age at diagnosis, marital status, length of stay, smoking status, drinking status, number of complications, autoimmune liver disease, and the age-adjusted Charlson comorbidity index score were significantly related to medical expenditure. Conclusion: Conservative estimates suggest that the medical expenditure of patients with liver cirrhosis increased significantly from 2012 to 2020. Therefore, it is necessary to formulate targeted measures to reduce the personal burden on patients with liver cirrhosis.

Predictive model for diabetic retinopathy under limited medical resources: A multicenter diagnostic study.

Background: Comprehensive eye examinations for diabetic retinopathy is poorly implemented in medically underserved areas. There is a critical need for a widely available and economical tool to aid patient selection for priority retinal screening. We investigated the possibility of a predictive model for retinopathy identification using simple parameters. Methods: Clinical data were retrospectively collected from 4, 159 patients with diabetes admitted to five tertiary hospitals. Independent predictors were identified by univariate analysis and least absolute shrinkage and selection operator (LASSO) regression, and a nomogram was developed based on a multivariate logistic regression model. The validity and clinical practicality of this nomogram were assessed using concordance index (C-index), area under the receiver operating characteristic curve (AUROC), calibration curves, decision curve analysis (DCA), and clinical impact curves (CIC). Results: The predictive factors in the multivariate model included the duration of diabetes, history of hypertension, and cardiovascular disease. The three-variable model displayed medium prediction ability with an AUROC of 0.722 (95%CI 0.696-0.748) in the training set, 0.715 (95%CI 0.670-0.754) in the internal set, and 0.703 (95%CI 0.552-0.853) in the external dataset. DCA showed that the threshold probability of DR in diabetic patients was 17-55% according to the nomogram, and CIC also showed that the nomogram could be applied clinically if the risk threshold exceeded 30%. An operation interface on a webpage (https://cqmuxss.shinyapps.io/dr_tjj/) was built to improve the clinical utility of the nomogram. Conclusions: The predictive model developed based on a minimal amount of clinical data available to diabetic patients with restricted medical resources could help primary healthcare practitioners promptly identify potential retinopathy.

Multiphase Assessment of Mitral Annular Dynamics in Consecutive Patients With Significant Mitral Valve Disease.

OBJECTIVES: The aim of this study was to clarify the dynamics of the mitral annulus throughout the cardiac cycle and its relevance to transcatheter mitral valve replacement (TMVR) sizing and case selection. BACKGROUND: Limited data are available regarding the relevance of mitral annular (MA) and neo-left ventricular outflow tract (LVOT) dynamics in the overall population presenting with significant mitral valve disease. METHODS: Patients attending a combined surgical-transcatheter heart valve clinic for severe symptomatic mitral valve disease were assessed using multiphase computed tomography. The relative influence of MA and neo-LVOT dynamics to TMVR case selection was studied. RESULTS: A total of 476 patients with significant mitral valve disease were evaluated. In 99 consecutive patients with severe mitral regurgitation, a 10-phase assessment showed that the mitral annulus was on average largest in late systole. On comparing maximal MA dimension with late systolic dimension, TMVR size assignment changed in 24.2% of patients. If the average MA perimeter was used to determine sizing, 48.5% were excluded because of MA dimension being too large; in a multiphase assessment of the neo-LVOT, an additional 16.2% were excluded on the basis of neo-LVOT dimension. In an expanded series of 312 consecutive patients, selection protocol influenced anatomical exclusion: a manufacturer-proposed early systolic approach excluded 69.2% of patients, whereas a late systolic approach excluded 82.7% of patients, the vast majority because of large mitral annuli. CONCLUSIONS: Contemporary TMVR can treat only a minority of patients with severe mitral regurgitation, principally because of limitations of large MA dimension.

Chinese and global burdens of gastric cancer from 1990 to 2019.

BACKGROUND: Gastric cancer is a common cancer in China. This project investigated the disease burden of gastric cancer from 1990 to 2019 in China and globally. METHODS: The global age-standardized rates (ASRs) were extracted from the Global Burden of Disease. Moreover, the estimated annual percentage changes (eAPCs) in the ASRs of incidence (ASIR), mortality (ASMR), and disability-adjusted life-years (DALYs) were calculated to determine the trends by countries and regions. RESULTS: In China, the ASIR declined from 37.56 to 30.64 per 100,000 and the ASMR declined from 37.73 to 21.72 per 100,000. The global ASIR decreased from 22.44 to 15.59 and the ASMR declined from 20.48 to 11.88 per 100,000 persons from 1990 to 2019. The ASIR was the lowest in Malawi (3.28 per 100,000) and the highest in Mongolia (43.7 per 100,000), whereas the ASMR was the lowest in the United States of America (3.40 per 100,000) and the highest in Mongolia (40.04 per 100,000) in 2019. The incidence of early-onset gastric cancer increased in China. The DALYs attributed to gastric cancer presented a slight decrease during the period. China had a higher mortality/incidence ratio (0.845) and 5-year prevalence (27.6/100,000) than most developed countries. CONCLUSION: China presented a steady decline in the incidence and mortality rates for gastric cancer. The global ASIR, ASMR, and DALYs showed a slight rise decrease. Different patterns of gastric cancer rates and temporal trends have been identified in different geographical regions, indicating that specific strategies are needed to prevent the increase in some countries.

True cost of surgical aortic valve replacement and implications for price setting and diagnosis-related groups: evidence from a tertiary hospital in Eastern China.

Background: Surgical aortic valve replacement (SAVR) has long been the standard treatment for patients with severe aortic stenosis in China, but the costs of SAVR from a hospital perspective in China have not been thoroughly researched. Currently, diagnosis-related groups in China are based on historical expenses that are closely related to the unit charges set by the official pricing department and are frequently inaccurate compared with actual resource consumption. Materials & methods: Through a retrospective empirical study on the costs and charges of SAVR cases in a tertiary hospital, this study aimed to compare the costs and charges of service items. We collected clinical information from patients undergoing SAVR (isolated or concomitant procedures) and financial information from the hospital in 2015 and 2016. Top-down full cost accounting and step-allocation were the main methods used in this study. Result: This research selected 203 SAVR cases in 2015 and 214 cases in 2016. The median length of hospital stay was 15.92 days (6.07 days pre surgery and 9.57 days post surgery). The average human resource cost of care per day per bed in the cardiovascular surgery department, including doctors and nurses, was US $62.22 in 2015 and $66.17 in 2016, but the corresponding charge was no more than $24. For operation, the cost of isolated SAVR was $665 in 2015 and $1015 in 2016, while the charge was $820. For anesthesiology, the cost of isolated SAVR was $400 in 2015 and $526 in 2016, while the average charge was $192. For examination service items, some costs did not exceed charges. The average total cost of a case was $19,299 ± 8954, while the average total charge was $18,923 ± 9194. Conclusion: SAVR is associated with significant resource utilization and hospital stay duration. The fees for human resources and services associated with SAVR do not reflect the true costs of SAVR in a Chinese hospital setting. This study may assist in future budget planning and price setting for policy makers in China.

Supra-annular structure assessment for self-expanding transcatheter heart valve size selection in patients with bicuspid aortic valve.

OBJECTIVES: To explore assessment of supra-annular structure for self-expanding transcatheter heart valve (THV) size selection in patients with bicuspid aortic stenosis (AS). BACKGROUND: Annulus-based device selection from CT measurement is the standard sizing strategy for tricuspid aortic valve before transcatheter aortic valve replacement (TAVR). Because of supra-annular deformity, device selection for bicuspid AS has not been systemically studied. METHODS: Twelve patients with bicuspid AS who underwent TAVR with self-expanding THVs were included in this study. To assess supra-annular structure, sequential balloon aortic valvuloplasty was performed in every 2 mm increments until waist sign occurred with less than mild regurgitation. Procedural results and 30 day follow-up outcomes were analyzed. RESULTS: Seven patients (58.3%) with 18 mm; three patients (25%) with sequential 18 mm, 20 mm; and only two patients (16.7%) with sequential 18 mm, 20 mm, and 22 mm balloon sizing were performed, respectively. According to the results of supra-annular assessment, a smaller device size (91.7%) was selected in all but one patient compared with annulus based sizing strategy, and the outcomes were satisfactory with 100% procedural success. No mortality and 1 minor stroke were observed at 30 d follow-up. The percentage of NYHA III/IV decreased from 83.3% (9/12) to 16.7% (2/12). No new permanent pacemaker implantation and no moderate or severe paravalvular leakage were found. CONCLUSIONS: A supra-annular structure based sizing strategy is feasible for TAVR in patients with bicuspid AS.