Identification and validation of immunity- and disulfidptosis-related genes signature for predicting prognosis in ovarian cancer.

Background: Ovarian cancer (OC) ranks as the fifth most prevalent neoplasm in women and exhibits an unfavorable prognosis. To improve the OC patient's prognosis, a pioneering risk signature was formulated by amalgamating disulfidptosis-related genes. Methods: A comparative analysis of OC tissues and normal tissues was carried out, and differentially expressed disulfidptosis-related genes (DRGs) were found using the criteria of |log2 (fold change) | > 0.585 and adjusted P-value <0.05. Subsequently, the TCGA training set was utilized to create a prognostic risk signature, which was validated by employing both the TCGA testing set and the GEO dataset. Moreover, the immune cell infiltration, mutational load, response to chemotherapy, and response to immunotherapy were analyzed. To further validate these findings, QRT-PCR analysis was conducted on ovarian tumor cell lines. Results: A risk signature was created using fourteen differentially expressed genes (DEGs) associated with disulfidptosis, enabling the classification of ovarian cancer (OC) patients into high-risk group (HRG) and low-risk group (LRG). The HRG exhibited a lower overall survival (OS) compared to the LRG. In addition, the risk score remained an independent predictor even after incorporating clinical factors. Furthermore, the LRG displayed lower stromal, immune, and estimated scores compared to the HRG, suggesting a possible connection between the risk signature, immune cell infiltration, and mutational load. Finally, the QRT-PCR experiments revealed that eight genes were upregulated in the human OC cell line SKOV3 compared with the human normal OC line IOSE80, while six genes were down-regulated. Conclusions: A fourteen-biomarker signature composed of disulfidptosis-related genes could serve as a valuable risk stratification tool in OC, facilitating the identification of patients who may benefit from individualized treatment and follow-up management.

Regulating neuronal excitability: The role of S-palmitoylation in NaV1.7 activity and voltage sensitivity.

S-palmitoylation, a reversible lipid post-translational modification, regulates the functions of numerous proteins. Voltage-gated sodium channels (NaVs), pivotal in action potential generation and propagation within cardiac cells and sensory neurons, can be directly or indirectly modulated by S-palmitoylation, impacting channel trafficking and function. However, the role of S-palmitoylation in modulating NaV1.7, a significant contributor to pain pathophysiology, has remained unexplored. Here, we addressed this knowledge gap by investigating if S-palmitoylation influences NaV1.7 channel function. Acyl-biotin exchange assays demonstrated that heterologously expressed NaV1.7 channels are modified by S-palmitoylation. Blocking S-palmitoylation with 2-bromopalmitate resulted in reduced NaV1.7 current density and hyperpolarized steady-state inactivation. We identified two S-palmitoylation sites within NaV1.7, both located in the second intracellular loop, which regulated different properties of the channel. Specifically, S-palmitoylation of cysteine 1126 enhanced NaV1.7 current density, while S-palmitoylation of cysteine 1152 modulated voltage-dependent inactivation. Blocking S-palmitoylation altered excitability of rat dorsal root ganglion neurons. Lastly, in human sensory neurons, NaV1.7 undergoes S-palmitoylation, and the attenuation of this post-translational modification results in alterations in the voltage-dependence of activation, leading to decreased neuronal excitability. Our data show, for the first time, that S-palmitoylation affects NaV1.7 channels, exerting regulatory control over their activity and, consequently, impacting rodent and human sensory neuron excitability. These findings provide a foundation for future pharmacological studies, potentially uncovering novel therapeutic avenues in the modulation of S-palmitoylation for NaV1.7 channels.

Microplastic pollution interaction with disinfectant resistance genes: research progress, environmental impacts, and potential threats.

The consumption of disposable plastic products and disinfectants has surged during the global COVID-19 pandemic, as they play a vital role in effectively preventing and controlling the spread of the virus. However, microplastic pollution and the excessive or improper use of disinfectants contribute to the increased environmental tolerance of microorganisms. Microplastics play a crucial role as vectors for microorganisms and plankton, facilitating energy transfer and horizontal gene exchange. The increase in the use of disinfectants has become a driving force for the growth of disinfectant resistant bacteria (DRB). A large number of microorganisms can have intense gene exchange, such as plasmid loss and capture, phage transduction, and cell fusion. The reproduction and diffusion rate of DRB in the environment is significantly higher than that of ordinary microorganisms, which will greatly increase the environmental tolerance of DRB. Unfortunately, there is still a huge knowledge gap in the interaction between microplastics and disinfectant resistance genes (DRGs). Accordingly, it is critical to comprehensively summarize the formation and transmission routes of DRGs on microplastics to address the problem. This paper systematically analyzed the process and mechanisms of DRGs formed by microbes. The interaction between microplastics and DRGs and the contribution of microplastic on the diffusion and spread of DRGs were expounded. The potential threats to the ecological environment and human health were also discussed. Additionally, some challenges and future priorities were also proposed with a view to providing useful basis for further research.

Designing a model for implementing diagnosis-related groups in Iran: An action plan approach.

Background and Aims: Implementing diagnosis-related groups (DRGs) in different countries increases the efficiency of healthcare services, improves treatment quality, and reduces treatment costs. Due to the lack of a coherent model for its implementation, the present study aimed to develop a DRGs-based implementation action plan Model for Iran. Methods: The present study was an applied, descriptive cross-sectional study conducted in three stages. In the first stage, a review of studies conducted in different countries was carried out. In the second stage, a model was designed for an action plan to implement the DRGs in Iran. In the third stage, the model was validated based on the Delphi technique. Results: The DRGs-based implementation action plan model in Iran was designed in three primary axes, including the strategic approach of the DRGs-based implementation action plan, technical dimensions, and executive institutions involved in the DRGs-based implementation action plan. Validation of the designed model showed the agreement of experts (94%) for the mentioned axes. Conclusion: The significance of tailoring a DRGs-based implementation action plan to each country's unique context is well-established. Given the intricacies of the Iranian healthcare system, we recommend an initial pilot implementation of DRGs at the hospital level, followed by a gradual national rollout.

[Electrical dorsal root ganglion stimulation (DRGS) for the treatment of refractory postherpetic neuralgia]. / Elektricheskaya stimulyatsiya gangliya zadnikh koreshkov spinnogo mozga (DRGS) dlya lecheniya refrakternoi postgerpeticheskoi nevralgii.

Postherpetic neuralgia (PHN) is a rare complication of herpes zoster characterized by prolonged and excruciating pain. Traditional treatments for PHN, such as analgesics, anticonvulsants and antidepressants, do not always bring the desired result. One promising alternative that is attracting the attention of the scientific community is dorsal root ganglion stimulation (DRGS). This method focuses on targeted and precise targeting of the source of pain, providing a new level of effectiveness in the treatment of PHN. OBJECTIVE: A retrospective analysis of the technique and results of implantation of a permanent device for stimulating the spinal ganglia in patients with refractory PHN at the Burdenko Neurosurgical Center. MATERIAL AND METHODS: The study was conducted in 7 patients (5 men, 2 women) with refractory PHN in the period from 2018 to 2020. The age of the patients ranged from 57 to 84 years (average age 74±8.4). All patients were implanted with Boston systems (Precision or Spectra versions). Stimulation parameters: pulse width - 120-210 µs, frequency - 30-130 Hz, amplitude at the lower limit of the appearance of paresthesia with the possibility of increasing with increased pain up to 5 mA. The position of the electrode depended on the location of the pain. All systems were implanted under X-ray guidance. RESULTS: The duration of follow-up observation was more than 2.5 years. The average pain intensity one year after treatment was 3.42±2.45 points on the visual analogue scale (VAS) (a 62.3% decrease in intensity compared to baseline). In 3 (42.8%) patients, the result was characterized by us as «excellent¼ (intensity according to VAS decreased by 75% or more), in 1 (14.2%) - as «good¼ (intensity according to VAS decreased by 50-74%), in 1 (14.2%) - as «moderate¼ (VAS intensity decreased by 25-49% and in 2 (28.5%) as «unsatisfactory¼ (VAS intensity decreased by less than 25%, or postoperative complications occurred). CONCLUSION: Given the complicated nature of PHN, the use of dorsal ganglion stimulation appears to be a promising and innovative treatment approach. Further research is needed to introduce this technique into clinical practice for the treatment of patients suffering from PHN.

How do hospitals respond to payment unbundling for diagnostic imaging of suspected cancer patients?

Payments for some diagnostic scans undertaken in outpatient settings were unbundled from Diagnosis Related Group based payments in England in April 2013 to address under-provision. Unbundled scans attracted additional payments of between £45 and £748 directly following the reform. We examined the effect on utilization of these scans for patients with suspected cancer. We also explored whether any detected effects represented real increases in use of scans or better coding of activity. We applied difference-in-differences regression to patient-level data from Hospital Episodes Statistics for 180 NHS hospital Trusts in England, between April 2010 and March 2018. We also explored heterogeneity in recorded use of scans before and after the unbundling at hospital Trust-level. Use of scans increased by 0.137 scans per patient following unbundling, a 134% relative increase. This increased annual national provider payments by £79.2 million. Over 15% of scans recorded after the unbundling were at providers that previously recorded no scans, suggesting some of the observed increase in activity reflected previous under-coding. Hospitals recorded substantial increases in diagnostic imaging for suspected cancer in response to payment unbundling. Results suggest that the reform also encouraged improvements in recording, so the real increase in testing is likely lower than detected.

County Hospital Responses to Funding Reforms in Zhejiang, China: An Interrupted Time-Series Analysis.

This study aimed to assess the effects of a two-stage funding reform, involving DRGs-based (Diagnostic Related Groups) payments for inpatient care and capitation funding for outpatient care, respectively, on services volume and care expenditure of county hospitals in Zhejiang province, China. A quasi-experimental design was adopted, involving 6 hospitals from 2 counties in the intervention group and 12 hospitals from 5 counties in the control group. The DRGs-based payments for inpatient care and capitation funding for outpatient care were introduced in January 2018 and January 2019, respectively. Controlled interrupted time-series analyses were performed to determine the effects of the funding reforms using monthly data over the period from January 2017 to December 2019. The volume of inpatient care decreased after the introduction of the first-stage DRGs-based payments, which was accompanied by an increase in the volume of outpatient visits. The DRGs-based payments led to a reduction of on average 1390 Yuan total expenditure per episode of inpatient care and 1116 Yuan out-of-pocket (OOP) payment per episode of inpatient care. However, the average outpatient expenditure per visit increased. So did the corresponding OOP payment per outpatient visit. The introduction of the second-stage capitation funding for outpatient care reversed the increasing trend of outpatient care. The average expenditure and OOP payment per outpatient visit decreased. The funding reforms create a significant effect on service volumes and expenditures in county hospitals. A coordinated approach to both inpatient and outpatient funding mechanisms is needed to minimize cost-shifting between inpatient and outpatient care and to achieve the intended policy outcomes.

A Bibliometric Analysis of Diagnosis Related Groups from 2013 to 2022.

Purpose: As an important management method of the global healthcare system, diagnosis related groups (DRGs) classify patients into different cost groups and pay more attention to the equitable distribution of medical resources and the quality of medical services. At present, most countries have used DRGs to help medical institutions and doctors to treat patients more accurately, avoid the waste of medical resources, and improve treatment efficiency. Methods: The Web of Science database was searched to collect all relevant literature on DRGs from 2013 to 2022. The literature information was imported into CiteSpace, Vosviewer, and Histcite for data analysis and visualization of the results. Analyze the cooperative relationship among the countries, institutions, journals, and authors. The usage trend of keywords; Highlight the content of the cited articles. Results: The number of articles published in this decade was stable, and the number of citations in 2014 was the highest. The United States and Germany, as the first countries to use the DRGs system, are ahead of other countries in terms of the number and quality of articles. We have carried out content research on the articles with high citations, and summarized the application range of DRGs; classification method; advantages and disadvantages of the application. In general, the development trend of DRGs in foreign countries is to continuously optimize the classification method, expand the scope of application, and improve the application effect. These provide support and reference for the improvement of medical services and the perfection of the medical insurance system. Conclusion: The application of DRGs can improve the quality and efficiency of medical services, and reduce the waste of medical expenses. It can also promote the rational allocation of medical resources and the equity of medical services. In the future, DRGs will pay more attention to the personalized diagnosis and treatment and fine management of patients, and the sharing and standardization of medical data, to promote the development of medical informatization.

Transcriptomic and Functional Evidence That miRNA193a-3p Inhibits Lymphatic Endothelial Cell (LEC) and LEC + MCF-7 Spheroid Growth Directly and by Altering MCF-7 Secretome.

MicroRNA 193a-3p (miR193a-3p) is a short non-coding RNA with tumor suppressor properties. Breast cancer (BC) progression is governed by active interaction between breast cancer cells, vascular (V)/lymphatic (L) endothelial cells (ECs), and BC secretome. We have recently shown that miR193a-3p, a tumor suppressor miRNA, inhibits MCF-7 BC cell-driven growth of VECs via direct antimitogenic actions and alters MCF-7 secretome. Since LEC-BC cross-talk plays a key role in BC progression, we investigated the effects of miR193a-3p on MCF-7 secretome and estradiol-mediated growth effects in LECs and LEC + MCF-7 spheroids, and delineated the underlying mechanisms. Transfection of LECs with miR193a-3p, as well as secretome from MCF-7 transfected cells, inhibited LEC growth, and these effects were mimicked in LEC + MCF-7 spheroids. Moreover, miR193a-3p inhibited ERK1/2 and Akt phosphorylation in LECs and LEC + MCF-7 spheroids, which are importantly involved in promoting cancer development and metastasis. Treatment of LECs and LEC + MCF-7 spheroids with estradiol (E2)-induced growth, as well as ERK1/2 and Akt phosphorylation, and was abrogated by miR193a-3p and secretome from MCF-7 transfected cells. Gene expression analysis (GEA) in LEC + MCF-7 spheroids transfected with miR193a-3p showed significant upregulation of 54 genes and downregulation of 73 genes. Pathway enrichment analysis of regulated genes showed significant modulation of several pathways, including interferon, interleukin/cytokine-mediated signaling, innate immune system, ERK1/2 cascade, apoptosis, and estrogen receptor signaling. Transcriptomic analysis showed downregulation in interferon and anti-apoptotic and pro-growth molecules, such as IFI6, IFIT1, OSA1/2, IFITM1, HLA-A/B, PSMB8/9, and PARP9, which are known to regulate BC progression. The cytokine proteome array of miR193a-3p transfected MCF secretome and confirmed the upregulation of several growth inhibitory cytokines, including IFNγ, Il-1a, IL-1ra, IL-32, IL-33, IL-24, IL-27, cystatin, C-reactive protein, Fas ligand, MIG, and sTIM3. Moreover, miR193a-3p alters factors in MCF-7 secretome, which represses ERK1/2 and Akt phosphorylation, induces pro-apoptotic protein and apoptosis in LECs, and downregulates interferon-associated proteins known to promote cancer growth and metastasis. In conclusion, miR193a-3p can potentially modify the tumor microenvironment by altering pro-growth BC secretome and inhibiting LEC growth, and may represent a therapeutic molecule to target breast tumors/cancer.

Challenges of implementing diagnostic-related groups and healthcare promotion in Iran: A strategic applied research.

Background and Aim: Implementing the diagnostic-related groups (DRGs) promotes the efficiency of healthcare. Therefore, the present study aimed to identify the challenges facing implementing the DRGs in Iran. Methods: The present study is a strategic applied research conducted in two phases. In the first phase, the challenges facing DRGs were extracted through a literature review. Then the collected data is entered into a checklist consisting of five sections including technological, cultural, organizational, strategic, and natural challenges. In the second phase, data were collected by purposive sampling and semistructured interviews with 10 managers of the Medical Services Organization of Tehran, Iran. Data analysis was performed by conventional content analysis using MAXQDA software and descriptive using SPSS software version 19. Results: The challenges facing the implementing DGRs from the experts' perspective included technological, organizational, nature, strategic, and cultural in order of priority. The three main fundamental challenges were reported; lack of integrating the DGRs with health information system (70%), frequent changes of management (70%), reducing the quality of care following early patient discharge (60%). Conclusion: The results of the present study showed that the DRG system faced with challenges and healthcare officials should apply policies and guidelines to reform the system before changing the reimbursement system in Iran. By considering the leading countries experiences in the nationalizing the DRG system field, the problems and solutions of the system can be identified and aid in the more successful implementation of these systems.

Insights on DRGs, guideline compliance and economic sustainability. The case of mastectomy with immediate breast reconstruction.

Background: Immediate breast reconstruction is recommended for eligible patients undergoing mastectomy, raising the issue of economic sustainability of both mastectomy and breast reconstruction performed within the same hospitalization, as opposed to two surgical procedures in two different hospitalizations. Study design: A retrospective analysis was conducted to compare economic sustainability of mastectomies with or without immediate breast reconstruction. Methods: Economic data on hospitalizations for mastectomy in a Teaching Hospital between 1 January 2019 and 31 March 2021 were analyzed to assess their sustainability. Results: 338 admissions were selected (63.9% with immediate breast reconstruction (CI 99%: 57.2% to 70.6%). Compared to mastectomy alone, mastectomy with immediate breast reconstruction had higher cost of € 2,245 (p < 0.001), with operating rooms and devices as main cost drivers. Current reimbursements rates (which are the same for mastectomy alone and for mastectomy with immediate breast reconstruction) led to an average loss of € 1,719 for each mastectomy with immediate breast reconstruction. Conclusion: Current DRGs reimbursement rates for hospital admissions for breast cancer surgery do not guarantee immediate breast reconstruction's economic sustainability. DRGs system should be revised, or other solutions as bundled payment should be implemented in the light of the costs of innovation in healthcare, considering mastectomy and breast reconstruction steps in a path of linked actions aimed at improving patients' health.

Micro-RNA193a-3p Inhibits Breast Cancer Cell Driven Growth of Vascular Endothelial Cells by Altering Secretome and Inhibiting Mitogenesis: Transcriptomic and Functional Evidence.

Breast cancer (BC) cell secretome in the tumor microenvironment (TME) facilitates neo-angiogenesis by promoting vascular endothelial cell (VEC) growth. Drugs that block BC cell growth or angiogenesis can restrict tumor growth and are of clinical relevance. Molecules that can target both BC cell and VEC growth as well as BC secretome may be more effective in treating BC. Since small non-coding microRNAs (miRs) regulate cell growth and miR193a-3p has onco-suppressor activity, we investigated whether miR193a-3p inhibits MCF-7-driven growth (proliferation, migration, capillary formation, signal transduction) of VECs. Using BC cells and VECs grown in monolayers or 3D spheroids and gene microarrays, we demonstrate that: pro-growth effects of MCF-7 and MDA-MB231 conditioned medium (CM) are lost in CM collected from MCF-7/MDA-MB231 cells pre-transfected with miR193a-3p (miR193a-CM). Moreover, miR193a-CM inhibited MAPK and Akt phosphorylation in VECs. In microarray gene expression studies, miR193a-CM upregulated 553 genes and downregulated 543 genes in VECs. Transcriptomic and pathway enrichment analysis of differentially regulated genes revealed downregulation of interferon-associated genes and pathways that induce angiogenesis and BC/tumor growth. An angiogenesis proteome array confirmed the downregulation of 20 pro-angiogenesis proteins by miR193a-CM in VECs. Additionally, in MCF-7 cells and VECs, estradiol (E2) downregulated miR193a-3p expression and induced growth. Ectopic expression of miR193a-3p abrogated the growth stimulatory effects of estradiol E2 and serum in MCF-7 cells and VECs, as well as in MCF-7 and MCF-7+VEC 3D spheroids. Immunostaining of MCF-7+VEC spheroid sections with ki67 showed miR193a-3p inhibits cell proliferation. Taken together, our findings provide first evidence that miR193a-3p abrogates MCF-7-driven growth of VECs by altering MCF-7 secretome and downregulating pro-growth interferon signals and proangiogenic proteins. Additionally, miR193a-3p inhibits serum and E2-induced growth of MCF-7, VECs, and MCF-7+VEC spheroids. In conclusion, miRNA193a-3p can potentially target/inhibit BC tumor angiogenesis via a dual mechanism: (1) altering proangiogenic BC secretome/TME and (2) inhibiting VEC growth. It may represent a therapeutic molecule to target breast tumor growth.

The challenge of healthcare big data to China's commercial health insurance industry: evaluation and recommendations.

BACKGROUND: China's social medical insurance system faces challenges in financing, product coverage, patient health responsibility sharing and data security, which commercial health insurance companies can help address. Confronting accelerated population aging, the rapid increase of patients with chronic diseases and the maternal and child healthcare needs created by the three-child policy, the Chinese government has encouraged the development of commercial health insurance. But China's commercial health insurance companies face financial sustainability problems, limited product ranges and high operating costs. At the same time, the informatization level of China's healthcare industry, and the value of healthcare big data, is increasing. We analyze and describe the potential application of healthcare big data in the life cycle of China's commercial health insurance system and provide specific action plans for Chinese commercial health insurance companies; identify the challenges to commercial health insurers; and make recommendations for the application of big health data by commercial health insurers. Our recommendations inform healthcare policy makers on the development of commercial health insurance and the improvement of the healthcare financing system. We not only verify the value of healthcare big data, but also identify specific ways that healthcare big data plays in the development of commercial health insurance. Based on the research results, we recommend new policies for government and new uses of healthcare big data for commercial health insurance institutions. The benign development of commercial health insurance will improve the level of health services in China. METHODS: By interviewing health insurance managers (including actuaries, product managers, business executives, information technology medical workers, and commercial health insurance personnel) and by accessing research papers, industry reports, news reports and public information disclosure documents about commercial health insurance, we describe the impact of healthcare big data on the life cycle of commercial health insurance products and processes. RESULTS: We identify the issues and challenges of commercial health insurers in the use of healthcare big data, and advance specific strategies to expand the use of healthcare big data. In the life cycle of commercial health insurance products, healthcare big data can improve premium income, control medical costs and increase operational efficiency. First, healthcare big data can increase premiums, products and services by attenuating moral hazard and adverse selection problems, where high quality clients over-pay and high-risk clients underpay for health insurance. Second, healthcare big data can reduce medical expenses compensation pay-outs by promoting the establishment of a management medical system. Finally, the use of healthcare big data improves operational efficiency by increasing payment speeds, identifying fraud and increasing claim verification processes through automating payments and reducing offline processes. We discuss the obstacles to obtain healthcare big data confronting commercial health insurance companies. The sharing and data mining of healthcare big data brings privacy risks to the insured and there are significant differences in data standards and quality of healthcare big data that limit the application of healthcare big data in commercial health insurance. We recommend that national, regional and local government departments coordinate policies to facilitate the cooperation between commercial health insurance companies and regional healthcare big data platforms. In terms of technology, we recommend the establishment of data sharing platforms and data exchange mechanism across institutions and regions according to nation-wide standards and specifications. Government management departments should establish healthcare big data standards and specification system, promote the construction of healthcare big data and ensure the integrity, authenticity and reliability of health data. We recommend data quality continuous improvement and management mechanisms that combine technology and management. Government regulation should oversee commercial health insurance institutions and establish data security management systems to monitor and supervise the privacy of personal data. CONCLUSIONS: Healthcare big data can play an important role in the development of China's commercial health insurance industry. Healthcare big data can increase commercial health insurers' financial viability while providing improved, and cost-effective, products and services. By providing more and better information to insurers, healthcare big data attenuates the asymmetric information problem, addressing moral hazard and adverse selection problems. By combining hospital and medical organization management information systems with insurers' data management, healthcare big data can help insurers set sustainable premiums, control medical costs and promote operational efficiency. At present, the informatization degree of China's healthcare industry remains limited. To improve the performances, products and services of commercial health insurers, we recommend government reforms in healthcare big data, such as expanding medical industry cooperation; further developing the processes of applying healthcare big data; augmenting data sharing; addressing privacy risks; setting data standards; and improving data quality.

The DEMATEL method explores the interdependent relationship structure and weights for diagnosis-related groups system.

Purpose: This study constructs a structure of interaction between dimensions and criteria within the diagnosis-related groups (DRGs) system from a quantitative system and identifies key factors affecting the overall performance of medical services. Method: From September to December 2020, the influence relation structure diagram (IRSD) of the dimensions and corresponding criteria was developed from the practical experience of a group of domain experts, based on the DEMATEL method. Subsequently, all dimensions and criteria construct influential weights from a systems perspective. Finally, the main influential factors were identified based on the analysis results. Results: The IRSD results showed that, in the overall performance of medical services, "Medical service capacity (C 1)" was the main influential dimension, influencing both "Medical service efficiency (C 2)" and "Medical service safety (C 3)." At the criteria level, "Case-mix index (CMI) (C 12)," "Time efficiency index (C21)," and "Inpatient mortality of medium-to-low group (C32)" were the main influential criteria in the corresponding dimensions. The influential weight results showed that "Medical service capacity (C 1)" was also a key dimension. "Case-mix index (CMI) (C 12)," "Cost efficiency index (C 22)," and "Inpatient mortality of medium-to-low group (C 32)" were the key criteria in their respective dimensions. Conclusion: Patients and managers should first focus on the capacity of medical service providers when making a choice or deciding using the results of the DRGs system. Furthermore, they should pay more attention to medical safety even if it is not as weighted as medical efficiency.

Cell Trajectory-Related Genes of Lung Adenocarcinoma Predict Tumor Immune Microenvironment and Prognosis of Patients.

Background: Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer which typically exhibits a diverse progression trajectory. Our study sought to explore the cell differentiation trajectory of LUAD and its clinical relevance. Methods: Utilizing a single-cell RNA-sequencing dataset (GSE117570), we identified LUAD cells of distinct differential status along with differentiation-related genes (DRGs). DRGs were applied to the analysis of bulk-tissue RNA-sequencing dataset (GSE72094) to classify tumors into different subtypes, whose clinical relevance was further analyzed. DRGs were also applied to gene co-expression network analysis (WGCNA) using another bulk-tissue RNA-sequencing dataset (TCGA-LUAD). Genes from modules that demonstrated a significant correlation with clinical traits and were differentially expressed between normal tissue and tumors were identified. Among these, genes with significant prognostic relevance were used for the development of a prognostic nomogram, which was tested on TCGA-LUAD dataset and validated in GSE72094. Finally, CCK-8, EdU, cell apoptosis, cell colony formation, and Transwell assays were used to verify the functions of the identified genes. Results: Four clusters of cells with distinct differentiation status were characterized, whose DRGs were predominantly correlated with pathways of immune regulation. Based on DRGs, tumors could be clustered into four subtypes associated with distinct immune microenvironment and clinical outcomes. DRGs were categorized into four modules. A total of nine DRGs (SFTPB, WFDC2, HLA-DPA1, TIMP1, MS4A7, HLA-DQA1, VCAN, KRT8, and FABP5) with most significant survival-predicting power were integrated to develop a prognostic model, which outperformed the traditional parameters in predicting clinical outcomes. Finally, we verified that knockdown of WFDC2 inhibited proliferation, migration, and invasion but promoted the apoptosis of A549 cells in vitro. Conclusion: The cellular composition and cellular differentiation status of tumor mass can predict the clinical outcomes of LUAD patients. It also plays an important role in shaping the tumor immune microenvironment.

Integrative pharmacogenomics revealed three subtypes with different immune landscapes and specific therapeutic responses in lung adenocarcinoma.

Background: Pharmacogenomics is crucial for individualized drug therapy and plays an increasingly vital role in precision medicine decision-making. However, pharmacogenomics-based molecular subtypes and their potential clinical significance remain primarily unexplored in lung adenocarcinoma (LUAD). Methods: A total of 2065 samples were recruited from eight independent cohorts. Pharmacogenomics data were generated from the profiling of relative inhibition simultaneously in mixtures (PRISM) and the genomics of drug sensitivity in cancer (GDSC) databases. Multiple bioinformatics approaches were performed to identify pharmacogenomics-based subtypes and find subtype-specific properties. Results: Three reproducible molecular subtypes were found, which were independent prognostic factors and highly associated with stage, survival status, and accepted molecular subtypes. Pharmacogenomics-based subtypes had distinct molecular characteristics: S-Ⅰ was inflammatory, proliferative, and immune-evasion; S-Ⅱ was proliferative and genetics-driven; S-III was metabolic and methylation-driven. Finally, our study provided subtype-guided personalized treatment strategies: Immune checkpoint blockers (ICBs), doxorubicin, tipifarnib, AZ628, and AZD6244 were for S-Ⅰ; Cisplatin, camptothecin, roscovitine, and A.443654 were for S-Ⅱ; Docetaxel, paclitaxel, vinorelbine, and BIBW2992 were for S-III. Conclusion: We provided a novel molecular classification strategy and revealed three pharmacogenomics-based subtypes for LUAD patients, which uncovered potential subtype-related and patient-specific therapeutic strategies.

Relationship Between Price and Diagnosis-Related Group Tariff for Medical Devices Assessed by a Regional Health Technology Assessment Committee.

Introduction Medical devices (MDs) make up an important share of total in-hospital expenditure. At the level of individual patients, this share is represented by the ratio of the cost of MD incurred by the patient vs. the total cost of in-hospital care for the same patient. If tariffs rather than costs are considered, the denominator of this ratio is given by the diagnosis-related group (DRG) and the ratio is the cost of MD over DRG tariff. The objective of this paper is to present a retrospective analysis comparing the ratio of price vs. DRG tariff for a group of devices belonging to risk class III or active implantable. These devices are those assessed in the years 2020 and 2021 by two committees of the Tuscany region in Italy. Materials and methods The information on price and DRG was taken from the health technology assessment (HTA) reports concerning MDs evaluated by the two above-mentioned regional committees in the years 2020 and 2021. In these reports, the information on the cost-effectiveness ratio was reported for a subset of MDs. In all cases, a preliminary qualitative assessment was carried out to determine the presence or absence of a healthcare impact in the post-discharge phase. In these preliminary analyses, the perspective of NHS was adopted. Results Our analysis was focused on 24 devices of either class III or active implantable. According to our results, a wide variability was found in the ratios between device price and DRG associated with its use. This ratio ranged from a minimum of about 3% in the case of the Hyalobarrier gel (Nordic Pharma GmbH, Zürich, Switzerland) for post-surgical adhesion to a maximum of 132% in the case of the Neovasc Reducer (EPS Vascular AB, Viken, Sweden), a device indicated in the narrowed coronary sinus. Three devices, i.e., PuraStat (3-D Matrix, Ltd., Tokyo, Japan), Ascyrus Medical Dissection Stent (AMDS, CryoLife, Inc., Kennesaw, GA), and Tendyne (Abbott Cardiovascular, Plymouth, MN), were found to be priced more than the reimbursement tariff (i.e., ratio > 100%). Ratios between 50% and 100% were found in about half of the devices. From our preliminary assessment on the presence of a post-discharge impact, 15 devices out of 24 (62%) were found to determine a substantial impact, while the remaining nine (38%) did not. In general, when costs and benefits of a device do not extend beyond the patients' discharge, the presence of a ratio > 100% reliably suggests the conclusion that the device price needs to be reduced and/or the tariff needs to be increased. On the other hand, in cases where the device extends its impact beyond the patient's hospital stay, the decision of reducing price or increasing tariff becomes more complex, and so these adjustments cannot be determined unless more information on some critical aspects is made available. Conclusions Until the above-mentioned improvements do not take place, rational interventions on DRG are virtually unfeasible owing to this lack of critical information. On the other hand, it is also difficult to intervene on device prices, again owing to the lack of critical information.

Improving the clinical ability and quality of endocrinology department with diagnosis-related groups tool.

Background: To evaluate the use of the diagnosis-related groups (DRGs) tool to promote the diagnosis/treatment ability and quality of the endocrinology department under the new policy of grouping payment-related to disease diagnosis. Methods: We compared the income structure of the endocrinology department in a 3a general hospital between the first half of 2019 and the same period in 2021. We also observed the changes in cost efficiency indexes (CEIs), time efficiency indexes (TEIs), case-mix index (CMI), number of DRGs, risk weight (RW) proportion, and surgery number in the inpatient department. Furthermore, the distribution of inpatients with diabetes of the whole hospital and the improvement of treatment efficiency indexes of the sub-specialty department were analyzed. Results: In the first half of 2021, compared with the same period of 2019, the total revenue of the endocrinology department decreased by 20.05%, the average hospitalization cost decreased by 11.72%, the CEI decreased from 1.31 to 1.06, and the TEI decreased from 0.74 to 0.64. Additionally, the number of DRGs increased from 162 to 176, the average CMI value increased from 0.80 to 0.84, and the proportion of RW 1-5 cases increased. Moreover, the number of surgical cases increased by 60.50%, minimally invasive surgery increased by 53.54%, grade 4 surgery increased by 66.67%, and the proportion of entering the clinical pathway increased from 77.76% to 86.64%. From May to August, 2021, the admission rate of endocrinology sub-specialty increased significantly, the number of DRGs showed an increasing trend, and the CEI and TEI decreased significantly. In the first half of 2021, inpatients with diabetes in the departments of rehabilitation, neurology, nephropathy, ophthalmology, and general administration accounted for 21.99-38.54%. Conclusions: The DRGs tool can be used to improve the clinical diagnosis and treatment ability of the endocrinology department, as well as optimize the CEI, TEI, CMI, and RW values. It is an effective way to promote the development of the endocrinology department under the new DRGs payment policy, carry out blood glucose management in the hospital, build endocrinology sub-specialties, and improve surgical and operation capacity.

Oxidized linoleic acid metabolites maintain mechanical and thermal hypersensitivity during sub-chronic inflammatory pain.

Inflammatory pain serves as a protective defense mechanism which becomes pathological when it turns into chronic inflammatory pain. This transition is mediated by a variety of peripheral mediators that sensitize nociceptors and increase pain perception in sensory neurons. Besides cytokines, chemokines and growth factors, accumulating evidence shows that oxidized lipids, such as eicosanoids and oxidized linoleic acid metabolites, contribute to this sensitization process. Most notably, the oxidized linoleic acid metabolite and partial TRPV1 agonist 9-HODE (hydroxyoctadecadienoic acid) was shown to be involved in this sensitization process. However, it is still unknown how some of the oxidized linoleic acid metabolites are synthesized in the inflammatory environment and in which phase of inflammation they become relevant. Here we show that the concentrations of oxidized linoleic acid metabolites, especially 9-HODE and 13-HODE, are significantly increased in inflamed paw tissue and the corresponding dorsal root ganglia in the sub-chronic phase of inflammation. Surprisingly, classical inflammatory lipid markers, such as prostaglandins were at basal levels in this phase of inflammation. Moreover, we revealed the cell type specific synthesis pathways of oxidized linoleic acid metabolites in primary macrophages, primary neutrophils and dorsal root ganglia. Finally, we show that blocking the most elevated metabolites 9-HODE and 13-HODE at the site of inflammation in the sub-chronic phase of inflammation, leads to a significant relief of mechanical and thermal hypersensitivity in vivo. In summary, these data offer an approach to specifically target oxidized linoleic acid metabolites in the transition of acute inflammatory pain to chronic inflammatory pain.

A Case Series of Permanent Dorsal Root Ganglion Stimulation.

Introduction  Neuropathic pain commonly causes high levels of pain that impairs multiple facets of the lives of patients. Multiple first-line treatments such as physical therapy and pharmacological intervention exist. Treatment refractory to these interventions may be considered for spinal cord stimulation (SCS). However, modest rates of meaningful relief leave room for improvement. Dorsal root ganglion stimulation (DRGS) has been touted to be a viable alternative solution to SCS with more specific targets and, consequently, fewer side effects. Thus, DRGS has been accepted as a better alternative to spinal cord stimulation. In contrast, we report a series of DRGS patients who had lower rates of meaningful pain relief than what was reported in the literature. Methods We present a series of 11 patients who underwent both DRGS trial and subsequent permanent implantation with negative outcomes (defined by ≥ 50% of pre-surgical pain) in 55% of patients. Patient records were searched for comorbidities that could potentially affect the DRGS implant (diabetes, cancer, smoking, age > 70 years old). Once delineated, the predictive value of each comorbidity for negative outcomes was estimated. Results Eighteen patients had a successful DRGS trial which was defined as a ≥ 50% pain reduction as well as increased ability to perform daily activities. Seven patients elected not to proceed with the permanent DRGS. Of the 11 remaining patients that had the permanent DRGS, four patients reported being completely pain-free ≥ one month following implantation, one reported a significant increase in pain improvement at four months post-operation, and six patients reported pain that was ≥ 50% of their pre-surgical pain 4-12 months following implantation.  Conclusion In our case series, we observed a discrepancy between DRGS trial outcomes and outcomes following permanent implantation. We found that a stronger correlation may exist between worse outcomes and smoking. Older age, the presence of diabetes, and cancer had more modest associations. These comorbidities may have value as tests for predicting negative outcomes of permanent DRGS implantation. Additionally, we hypothesized that this could also be due to the presence of psychological factors which obscure the true result of the DRGS trial. Thus, we suggest that DRGS be prescribed with caution in these patient populations, and use comorbidities to test for the likelihood of negative outcomes. Limitations of this study are those that are intrinsic to a retrospective case series.