Ferredoxin 1: a gatekeeper in halting lung adenocarcinoma progression through activation of the GPRIN2 signaling pathway.

BACKGROUND: Lung adenocarcinoma (LUAD) is a highly lethal form of lung cancer. Despite advancements in treatments, managing LUAD is still challenging due to its aggressive behavior. Recent studies indicate that various molecular pathways, including the dysregulation of ferredoxin 1 (FDX1), play roles in LUAD progression. FDX1, a crucial protein in cellular redox reactions and energy metabolism, has been linked to several cancers. However, its exact role in the development of LUAD is not yet fully understood. METHODS: We investigated the role of ferredoxin 1 (FDX1) in LUAD progression through analysis of its expression in LUAD tissues and its impact on patient survival. Functional assays were performed to assess the effects of FDX1 overexpression on LUAD cell proliferation, migration, and invasion. A xenograft model was employed to evaluate the tumorigenesis potential of LUAD cells with FDX1 overexpression. Mechanistic insights into FDX1 regulation were gained through depletion experiments targeting the G protein-regulated inducer of neurite outgrowth 2 (GPRIN2)/PI3K signaling pathway. RESULTS: FDX1 expression was down-regulated in LUAD tissues, correlating with shorter patient survival. Overexpression of FDX1 suppressed LUAD cell proliferation, migration, and invasion in vitro, and inhibited tumorigenesis in vivo. Mechanistically, the GPRIN2/PI3K signaling pathway was implicated in FDX1 regulation, as depletion of GPRIN2 reversed the effects of FDX1 overexpression on cellular functions. CONCLUSIONS: Our findings highlight FDX1 as a potential tumor suppressor in LUAD, acting through modulation of the GPRIN2/PI3K signaling pathway. These results suggest FDX1 as a promising therapeutic target for LUAD treatment, warranting further investigation into its clinical relevance.

Predicting future vaccination habits: The link between influenza vaccination patterns and future vaccination decisions among old aged adults in China.

BACKGROUND: Annual influenza vaccination is crucially recommended for the elderly to maintain humoral immunity. Insufficient coverage requires us to understand the determinants of their influenza behaviors and how these patterns impact vaccination choices. METHODS: Data from 540 Beijing residents aged over 65 were collected through interviews, capturing vaccination history and sociodemographic details. Individual influenza vaccination records from 2016 to 2020 were obtained from China's Immunization Information Systems. A latent class model identified three vaccination patterns. Multinomial logistic regression assessed relative risk ratios (RRRs) for vaccination based on sociodemographic factors. Vaccination patterns were used to predict future vaccination likelihood. RESULTS: The analysis revealed three groups: sporadically vaccinated (63.33%), occasionally vaccinated (18.71%), and frequently vaccinated (17.96%). Factors associated with frequent vaccination included age over 70 (RRR = 2.81), lower income (RRR = 0.39), higher vaccine hesitancy (RRR = 3.10), multiple chronic conditions (RRR = 2.72), and rural residence (RRR = 2.48). The frequently vaccinated group was more likely to sustain regular vaccination habits in subsequent years compared to the occasionally vaccinated group. CONCLUSIONS: Only 17.96% of Beijing's older population exhibited a consistent influenza vaccination pattern. Older age, rural residency, and chronic diseases correlated with repeated influenza vaccination. Segmenting the population based on past vaccination behavior can aid in designing targeted interventions to improve vaccination rates.

Microwave ablation combined with PD-L1 blockade synergistically promotes Cxcl9-mediated antitumor immunity.

Although microwave ablation (MWA) is an important curative therapy in colorectal cancer liver metastasis, recurrence still occurs clinically. Our previous studies have shown that the expression of programmed cell death 1 ligand 1 (PD-L1) is upregulated following MWA, suggesting that MWA combined with anti-PD-L1 treatment can serve as a promising clinical therapeutic strategy against cancer. Using MWA-treated preclinical mice models, MWA combined with αPD-L1 treatment decreased tumor growth and prolonged overall survival (OS). Furthermore, through flow cytometry and single-cell RNA sequencing analysis, we determined that the MWA plus αPD-L1 therapy significantly suppressed CD8+ T cell exhaustion and enhanced their effector function. A significant increase in γ-interferon (IFN-γ) stimulated transcription factors, specifically Irf8, was observed. This enhancement facilitated the polarization of tumor-associated macrophages (TAM1s and TAM2s) through the nuclear factor-κB/JAK-STAT1 signaling pathway. Furthermore, the combination therapy stimulated the production of CXC motif chemokine ligand (CXCL9) by TAM1s and tumor cells, potentially increasing the chemotaxis of CD8 T cells and Th1 cells. Knocking out Cxcl9 in MC38 tumor cells or using CXCL9 blockade enhanced tumor growth of untreated tumors and shortened OS. Taken together, our study showed that blocking the IFN-γ-Cxcl9-CD8+ T axis promoted tumor progression and discovered a potential involvement of IRF8-regulated TAMs in preventing T cell exhaustion. Collectively, we identified that the combination of MWA with anti-PD-L1 treatment holds promise as a therapeutic strategy to rejuvenate the immune response against tumors. This merits further exploration in clinical studies.

Primary care providers' preferences for pay-for-performance programs: a discrete choice experiment study in Shandong China.

BACKGROUND: Pay-for-performance (P4P) schemes are commonly used to incentivize primary healthcare (PHC) providers to improve the quality of care they deliver. However, the effectiveness of P4P schemes can vary depending on their design. In this study, we aimed to investigate the preferences of PHC providers for participating in P4P programs in a city in Shandong province, China. METHOD: We conducted a discrete choice experiment (DCE) with 882 PHC providers, using six attributes: type of incentive, whom to incentivize, frequency of incentive, size of incentive, the domain of performance measurement, and release of performance results. Mixed logit models and latent class models were used for the statistical analyses. RESULTS: Our results showed that PHC providers had a strong negative preference for fines compared to bonuses (- 1.91; 95%CI - 2.13 to - 1.69) and for annual incentive payments compared to monthly (- 1.37; 95%CI - 1.59 to - 1.14). Providers also showed negative preferences for incentive size of 60% of monthly income, group incentives, and non-release of performance results. On the other hand, an incentive size of 20% of monthly income and including quality of care in performance measures were preferred. We identified four distinct classes of providers with different preferences for P4P schemes. Class 2 and Class 3 valued most of the attributes differently, while Class 1 and Class 4 had a relatively small influence from most attributes. CONCLUSION: P4P schemes that offer bonuses rather than fines, monthly rather than annual payments, incentive size of 20% of monthly income, paid to individuals, including quality of care in performance measures, and release of performance results are likely to be more effective in improving PHC performance. Our findings also highlight the importance of considering preference heterogeneity when designing P4P schemes.

TIGIT Blockade Reshapes the Tumor Microenvironment Based on the Single-cell RNA-Sequencing Analysis.

SUMMARY: Immune checkpoint blockade therapy is a pivotal approach in treating malignant tumors. TIGIT has emerged as a focal point of interest among the diverse targets for tumor immunotherapy. Nonetheless, there is still a lack of comprehensive understanding regarding the immune microenvironment alterations following TIGIT blockade treatment. To bridge this knowledge gap, we performed single-cell sequencing on mice both before and after the administration of anti-TIGIT therapy. Our analysis revealed that TIGIT was predominantly expressed on T cells and natural killer (NK) cells. The blockade of TIGIT exhibited inhibitory effects on Treg cells by downregulating the expression of Foxp3 and reducing the secretion of immunosuppressive cytokines. In addition, TIGIT blockade facilitated the activation of NK cells, leading to an increase in cell numbers, and promoted cDC1 maturation through the secretion of XCL1 and Flt3L. This activation, in turn, stimulated the TCR signaling of CD8 + T cells, thereby enhancing their antitumor effect. Consequently, anti-TIGIT therapy demonstrated substantial potential for cancer immunotherapy. Our research provided novel insights into future therapeutic strategies targeting TIGIT for patients with cancer.

Effectiveness of financial incentives on influenza vaccination among older adults in China: a randomized clinical trial.

OBJECTIVES: To investigate the short-term and long-term effectiveness of different levels of financial incentives on increasing the willingness to vaccinate and vaccine uptake. METHODS: A randomized controlled trial was conducted to investigate the effectiveness of financial incentives of three groups with monetary incentives (CNY 20, CNY 40, and CNY 60; 1 CNY = 0.13 EUR) vs. a control group-CNY 0-on influenza vaccine uptake among 720 older adults (≥60 years) in Beijing, China. The primary outcome was vaccine uptake, and the secondary outcomes were intention to vaccinate and length of time to immunization. RESULTS: Financial incentive significantly promoted higher intention to influenza vaccination (120/178 [67.42%] vs. 442/542 [81.55%]; Relative Risk [RR], 1.21; 95% CI, 1.02-1.42) and higher vaccination participation (74/178 [41.57%] vs. 316/542 [58.30%]; RR, 1.39; 95% CI, 1.10-1.75). CNY 60 had the largest impact on the intention to vaccinate (15.00% vs. 13.48% and 13.90%) and vaccination uptake (19.42% vs. 14.05% and 16.67%) compared with CNY 20 and CNY 40. Time to vaccination was significantly lower among participants receiving incentives than those without ([37.21 days; 95% CI, 34.33-39.99] vs. [48.27 days; 95% CI, 43.47-53.07]; Hazard Ratio [HR] 1.57, 95% CI 1.22-2.03). We found no long-term influence of financial incentives on vaccination decisions in the following year (217/542, 40.04% vs. 65/178, 36.52%; RR 1.08, 95% CI 0.82-1.42). DISCUSSION: Our study suggests that modest financial incentives will boost short-term influenza vaccination rates and shorten the length of time to immunization in China. No one single-time financial incentive had a long-term effect on future vaccination behaviours or helped establish regular vaccination behaviours.

Health insurance as a moderator in the relationship between financial toxicity and medical cost-coping behaviors: Evidence from patients with lung cancer in China.

OBJECTIVE: This study investigates the relationship between financial toxicity and medical cost-coping behaviors (MCCB) in Chinese patients with lung cancer, with a particular focus on the moderating role of health insurance. METHODS: We surveyed 218 patients with lung cancer and assessed their Comprehensive Score for Financial Toxicity (COST) and self-reported MCCB. Patients were categorized into Urban Employee's Basic Medical Insurance (UEBMI) group and Urban-Rural Resident Basic Medical Insurance Scheme (URRBMI) groups by their medical insurance, and matched for socioeconomic, demographic, and disease characteristics via propensity score. RESULTS: Significant different characteristics were noted between UEBMI patients and URRBMI patients. Patients with UEBMI had higher COST scores but lower levels of MCCB compared to URRBMI patients in the original dataset. After data matching, multivariate logit regression analysis showed that better financial toxicity was associated with lower levels of MCCB (OR = 0.95, 95% CI: 0.92-0.99). Health insurance type did not have a direct association with cost-coping behaviors, but an interaction was observed between health insurance type and financial toxicity. Among patients with URRBMI, better financial toxicity was associated with lower levels of cost-coping behaviors (OR = 0.89, 95% CI: 0.83-0.95). Patients with UEBMI had a lower probability of engaging in any cost-coping behaviors in situations of worse financial toxicity compared to patients with URRBMI. CONCLUSION: The findings suggest that financial toxicity is correlated with MCCB in Chinese patients with lung cancer. The type of health insurance, specifically UEBMI and URRBMI, plays a moderating role in this relationship. Understanding these dynamics is essential for developing targeted interventions and policies to mitigate financial toxicity and improve patients' management of medical costs.

Fibrinogen as a potential diagnostic marker for prediction and evaluation of postpartum hemorrhage: a retrospective study.

OBJECTIVE: To investigate whether prenatal fibrinogen (FIB) or other related factors could be utilized to evaluate the risk of postpartum hemorrhage (PPH). METHODS: A retrospective study was conducted in a database from January 2015 to December 2019. A total of 128 patients were enrolled and evaluated with FIB, in which 55 patients were assigned to low FIB and 73 in normal FIB. RESULTS: According to the volume of blood loss, the mean of the low FIB group (<4 g/L) was markedly higher than that of the normal FIB group (≥4 g/L). Prenatal FIB was negatively correlated with PPH volume. The receiver operating characteristic (ROC) curve results indicated that the value of prenatal FIB was 0.701 to predict refractory PPH. CONCLUSIONS: Prenatal FIB was significantly related to thrombin time (TT), which may be an independent factor to predict the coagulation state of prenatal pregnancy.

Effects of retirement on inpatient healthcare utilisation: an observational study in China.

OBJECTIVE: Previous studies have presented mixed evidence on retirement and inpatient healthcare utilisation. We aimed to examine the causal effect of retirement on inpatient healthcare utilisation in China and explore the heterogenous effects of sex, disease types and ways of hospital admission. DESIGN: This was a retrospective observational study from the electronic medical record at 376 tertiary hospitals in China between 2013 and 2018. SETTING: Nationwide data from China. PARTICIPANTS: We included the male sample aged between 50 and 70, and the female sample aged between 40 and 60 and with basic medical insurance system or public medical insurance. Observations with total expenditures per visit at the top or bottom 1% were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: Inpatient expenditures per visit and inpatient days per visit. METHODOLOGY: We examined the effects by a non-parametric fuzzy regression discontinuity design, exploiting the mandatory retirement age as a source of exogenous variation in retirement status. RESULTS: Retirement reduced drug expenditures (ß=-467.46, p<0.05) and inpatient days per visit (ß=-0.99, p<0.05). The mitigation effect was concentrated on people admitted into hospital due to chronic diseases (ß=-551.28, p<0.05 for drug expenditures; ß=-1.08, p<0.05 for inpatient days per visit) and people admitted into hospital through outpatient services (ß=-353.75, p<0.001 for drug expenditures). For males, retirement significantly reduced diagnostic tests expenditures (ß=-302.38, p<0.05) and drug expenditures (ß=-728.31, p<0.05). Retirement significantly reduced inpatient days per visit (ß=-1.13, p<0.05) for females. CONCLUSION: The empirical findings suggested that retirement may lead to a reduction in inpatient healthcare utilisation, which underlined the importance for policy-makers to consider the externalities of retirement policies on inpatient healthcare utilisation.

Sulforaphane Attenuates AOM/DSS-Induced Colorectal Tumorigenesis in Mice via Inhibition of Intestinal Inflammation.

Sulforaphane (SFN) is a compound derived from cruciferous plants. It has received considerable attention in recent years due to its effectiveness in cancer prevention and anti-inflammatory properties. The purpose of this study was to evaluate the antitumor potential of sulforaphane on colitis-associated carcinogenesis (CAC) through the establishment of a mouse model with AOM/DSS. First, AOM/DSS and DSS-induced model were established and administered SFN for 10 wk, and then the severity of colitis-associated colon cancer was examined macroscopically and histologically. Subsequently, immune cells and cytokines in the tumor microenvironment (TME) were quantified. Finally, the influence of sulforaphane was also investigated using different colon cell lines. We found that sulforaphane treatment decreased tumor volume, myeloid-derived suppressor cells (MDSC) expansion, the expression of the proinflammatory cytokine IL-1ß, and the level of IL-10 in serum. Also, it enhanced the antitumor activities of CD8+ T cells and significantly reduced tumorigenesis as induced by AOM/DSS. SFN also attenuated intestinal inflammation in DSS-induced chronic colitis by reshaping the inflammatory microenvironment. This work demonstrates that sulforaphane suppresses carcinogenesis-associated intestinal inflammation and prevents AOM/DSS-induced intestinal tumorigenesis and progression.

The role of primary health care in improving health status, financial protection and health equity in the context of China's health system reform.

BACKGROUND: Stronger primary health care (PHC) is critical to achieving the United Nations' Sustainable Development Goals. However, there is scarce evidence on the impact of PHC on health system performance in developing countries. Since 2009, China has implemented an ambitious health system reform, among which PHC has received unprecedented attention. This study investigates the role of PHC resource in improving health status, financial protection and health equity. METHODS: We obtained province-level and individual-level data to conduct a longitudinal study across the period of China's health system reform. The dependent variables included health outcomes and financial protection. The independent variables were the number of PHC physicians and share of PHC physicians in all physicians. Mixed-effect models were used for adjusted associations. RESULTS: From 2003 to 2017, the number of PHC physicians slightly increased by 31.75 per 100,000 persons and the share of PHC physicians in all physicians increased by 3.62 percentage points. At the province level, greater PHC physician density was positively associated with life expectancy, negatively associated with age-standardized excess mortality, infectious disease mortality, perinatal mortality low birth weight, as well as the share of health expenses in total consumption expenses. At the individual and household level, greater PHC physician density was positively associated with self-assessed health, and negatively associated with incidence of catastrophic health expenditures. Compared to other quintiles, the poorest quintile benefited more from PHC physician density. CONCLUSIONS: In China, an increased PHC physician supply was associated with improved health system performance. While China's PHC system has been strengthened in the context of China's health system reforms, further effective incentives should be developed to attract more qualified PHC workers.

Willingness to vaccinate against herpes zoster in Chinese urban population: a mixed-methods study.

OBJECTIVE: Although the herpes zoster vaccine has been available in mainland China since June 2020, residents' knowledge of herpes zoster and the herpes zoster vaccine is poor, and vaccination rates are low, especially among the elderly, who are at high risk for herpes zoster. This study assessed willingness to be vaccinated against herpes zoster and factors associated with vaccination among urban residents in China. METHODS: A mixed-methods study was conducted in community health centres from August 2022 to September 2022. We used convenience sampling to select 2864 residents from 9 Chinese cities for the quantitative study and 67 adults for the qualitative study. A structured questionnaire was used for the quantitative study, and data were collected through face-to-face interviews. Multinomial logistic regression was used to analyse factors associated with willingness to vaccinate. Qualitative data were analysed using thematic analysis of barriers to herpes zoster vaccination. RESULTS: A total of 2864 eligible respondents were included in the study. Of these, 42.67% intended to receive the herpes zoster vaccine, 21.44% refused and 35.89% were hesitant. The results of the quantitative and qualitative analyses showed that the factors associated with respondents' willingness to be vaccinated against herpes zoster included: personal characteristics such as gender, age and income; knowledge and attitudes about herpes zoster and the vaccine; vaccine characteristics such as efficacy, safety and price; and other factors such as pain tolerance and accessibility to vaccination. CONCLUSION: The low willingness to vaccinate, especially among the elderly, is mainly related to their poor knowledge and negative attitude towards the infection and vaccination. Therefore, health education about herpes zoster, immunisation promotion, and improvement of accessibility and affordability would be valuable in China.

Effects of Starch Molecular Structure and Physicochemical Properties on Eating Quality of Indica Rice with Similar Apparent Amylose and Protein Contents.

It is important to clarify the effects of starch fine structure and protein components on the eating quality of indica rice. In this study, seven indica rice varieties with similar apparent amylose content (AAC) and protein content (PC) but different sensory taste values were selected and compared systematically. It was found that except for AAC and PC, these varieties showed significant differences in starch molecular structure and protein components. Compared with rice varieties with a low sensory taste value, varieties with a higher sensory taste value showed significantly lower amylose and higher amylopectin short chains (degree of polymerization 6-12) content; the protein component showed that the varieties with good taste value had higher albumin and lower globulin and glutelin content (p < 0.05). Rice varieties with lower AC, globulin, and glutelin content, as well as a higher content of albumin and amylopectin short chains, resulted in a higher swelling factor, peak viscosity, breakdown value, and ratio of hardness to stickiness, in which condition cooked rice showed a higher sensory taste value. Moreover, this study indicated that rice varieties with a higher content of albumin and amylopectin short chains were conducive to the good appearance of cooked rice. This study lays the foundation for the taste evaluation of good-tasting indica rice.

Asiatic acid protects against pressure overload-induced heart failure in mice by inhibiting mitochondria-dependent apoptosis.

BACKGROUND: Mitochondrial dysfunction and subsequent cardiomyocyte apoptosis significantly contribute to pressure overload-induced heart failure (HF). A highly oxidative environment leads to mitochondrial damage, further exacerbating this condition. Asiatic acid (AA), a proven antioxidant and anti-hypertrophic agent, might provide a solution, but its role and mechanisms in chronic pressure overload-induced HF remain largely unexplored. METHODS: We induced pressure overload in mice using transverse aortic constriction (TAC) and treated them with AA (100 mg/kg/day) or vehicle daily by oral gavage for 8 weeks. The effects of AA on mitochondrial dysfunction, oxidative stress-associated signaling pathways, and overall survival were evaluated. Additionally, an in vitro model using hydrogen peroxide-exposed neonatal rat cardiomyocytes was established to further investigate the role of AA in oxidative stress-induced mitochondrial apoptosis. RESULTS: AA treatment significantly improved survival and alleviated cardiac dysfunction in TAC-induced HF mice. It preserved mitochondrial structure, reduced the LVW/BW ratio by 20.24%, mitigated TAC-induced mitochondrial-dependent apoptosis by significantly lowering the Bax/Bcl-2 ratio and cleaved caspase-9/3 levels, and attenuated oxidative stress. AA treatment protected cardiomyocytes from hydrogen peroxide-induced apoptosis, with concurrent modulation of mitochondrial-dependent apoptosis pathway-related proteins and the JNK pathway. CONCLUSIONS: Our findings suggest that AA effectively combats chronic TAC-induced and hydrogen peroxide-induced cardiomyocyte apoptosis through a mitochondria-dependent mechanism. AA reduces cellular levels of oxidative stress and inhibits the activation of the JNK pathway, highlighting its potential therapeutic value in the treatment of HF.

Community-based integrated care for patients with diabetes and depression (CIC-PDD): study protocol for a cluster randomized controlled trial.

BACKGROUND: Managing the multimorbidity of diabetes and depression remains a clinical challenge for patients and healthcare professionals due to the fragmented healthcare delivery system. To effectively cope with multimorbidity, there is an urgent need for the health system to transform into people-centered integrated care (PCIC) system globally. Therefore, this paper describes the protocol of community-based integrated care for patients with diabetes and depression (CIC-PDD) project, an integrated and shared-care intervention project. METHODS/DESIGN: CIC-PDD project is conducted in two phases, namely "care model development" and "implementation and evaluation." In the first phase, CIC-PDD model was designed and developed based on the four criteria of collaborative care model (CCM) and was subsequently adjusted to align with the context of China. The second phase entails a pragmatic, two-arm, cluster randomized controlled implementation trial, accompanied by parallel mixed-methods process evaluation and cost-effectiveness analysis. DISCUSSION: We anticipate CIC-PDD project will facilitate the development and innovation of PCIC model and related theories worldwide, particularly in low- and middle-income countries (LMICs). In addition, CIC-PDD project will contribute to the exploration of primary health care (PHC) in addressing the multimorbidity of physical and mental health issues. TRIAL REGISTRATION: ClinicalTrials.gov registration ChiCTR2200065608 (China Clinical Trials Registry https://www.chictr.org.cn ). Registered on November 9, 2022.

The Effects of Genotype × Environment on Physicochemical and Sensory Properties and Differences of Volatile Organic Compounds of Three Rice Types (Oryza sativa L.).

Understanding the effects of genotype, environment and their interactions on rice quality is of great importance for rice breeding and cultivation. In this study, six rice varieties with two indica, two japonica and two indica-japonica types of rice were selected and planted at ten locations in Zhejiang Province to investigate the genotype (G) × environment (E) on physicochemical and sensory properties and the differences of volatile organic compounds (VOCs) among the three types of rice. Analysis of variances showed that apparent amylose content (AC), total protein content (PC), alkali spreading value (ASV), RVA profiles, and appearance (ACR), palatability (PCR), and sensory evaluation value (SEV) of cooked rice and texture of cooled cooked rice (TCCR) were mainly affected by genotypic variation, whereas the smell of cooked rice (SCR) was mainly affected by environment (p < 0.05). The G × E effect was significant for most parameters. The weather in the middle and late periods of filling had important effects on the formation of rice quality, especially on setback (SB) and pasting temperature (PT) (p < 0.01). They were negatively correlated with the texture of cooked rice (TCR) and SEV (p < 0.05). Peak viscosity (PV) and breakdown (BD) were positively related to the sensory evaluation parameters (p < 0.01) and could be used to predict cooked rice quality. A total of 59 VOCs were detected, and indica, japonica and indica-japonica had 9, 6 and 19 characteristic compounds, respectively. The principal component analysis showed that the physicochemical and sensory properties and VOCs of indica-japonica rice were more stable than those of indica and japonica rice at ten locations in Zhejiang Province. It is helpful for rice breeders to understand how the environment affects the physicochemical, sensory properties and VOCs of the three rice types, and it is also important for food enterprises to provide rice products with stable quality.

Identification of a novel stemness-related signature with appealing implications in discriminating the prognosis and therapy responses for prostate cancer.

PURPOSE: Cancer stemness represents the tumor-initiation and self-renewal potentials of cancer stem cells. It is involved in prostate cancer progression and resistance to therapy. Herein, we aimed to unveil the stemness features, establish a novel prognostic model, and identify potential therapeutic targets. METHODS: 26 stemness-related signatures were obtained from StemChecker. The expression profiles and clinical traits of TCGA-PRAD were obtained from TCGA and cBioPortal, respectively. GSE5446 and GSE70769 cohorts were acquired from GEO. PRAD_MSKCC cohort was also retrieved via the cBioPortal. The consensus clustering method was used for stemness subclusters classification. WGCNA was used to identify hub genes related to the stemness subcluster. The most important feature was explored in vitro. RESULTS: Prostate cancer patients of TCGA-PRAD were divided into two subclusters (C1 and C2) based on the enrichment scores of the 26 stemness-related signatures. C1 was characterized by decreased survival, rich infiltrations of M0 macrophages and regulatory T cells, minimum sensitivity to chemotherapy, and a low response to immunotherapy. Hub genes of the red module with the highest correlation with C1 were subsequently identified by WGCNA and subjected to stemness-related risk model construction based on the machine-learning framework. Prostate cancer patients with high stemness scores had unfavorable prognosis, immunosuppressive tumor microenvironment, minimum sensitivity to chemotherapy, and a low response to immunotherapy. MXD3, the most important factor of the model, can regulate the stemness traits of prostate cancer cells. CONCLUSIONS: Our study depicted the stemness landscapes of prostate cancer and characterized two subclusters with diverse prognoses and tumor immune microenvironments. A stemness-risk signature was developed and demonstrated prospective implications in predicting prognosis and precision medicine.

Data envelopment analysis on the efficiency of vaccination services and its influencing factors in Beijing, China.

OBJECTIVES: Vaccination is an important part of public health services. We aim to assess the efficiency of vaccination services in Beijing, the capital of China, and to further study the influencing factors of efficiency. METHODS: Using the immunization service data of Beijing, China in 2020, we firstly developed a data envelopment analysis (DEA) model to calculate the score of vaccination efficiency. Secondly, we used DEA model scenario simulations with different combinations of input-output factors to derive the magnitude of the effect of each input factor on the efficiency. Finally, combined with the data from the Beijing Regional Statistical Yearbook 2021, we developed the Tobit model to examine the effect of external social environmental factors on efficiency. RESULTS: The average scores of efficiency of POVs (Point of Vaccination) in different areas of Beijing vary greatly. Different input factors had different degrees of positive effects on the efficiency score. In addition, the number of populations served by POV was positively associated with efficiency, the GDP and financial allocation of the POVs' district was also positively associated with efficiency score, while the total dependency ratio of the POVs' district was negatively associated with efficiency score. CONCLUSION: The efficiency of vaccination services varied considerably across POVs. Constrained by limited resources, efficiency scores can be increased by increasing input factors that have a larger impact on efficiency score and reducing those that have a smaller impact on efficiency. In addition, the social environment should be considered in allocating vaccination resources, and more resources should be invested in areas with low levels of economic development, low financial allocation, and high population.