Decision model for durable clinical benefit from front- or late-line immunotherapy alone or with chemotherapy in non-small cell lung cancer.

BACKGROUND: Predictive biomarkers and models of immune checkpoint inhibitors (ICIs) have been extensively studied in non-small cell lung cancer (NSCLC). However, evidence for many biomarkers remains inconclusive, and the opaqueness of machine learning models hinders practicality. We aimed to provide compelling evidence for biomarkers and develop a transparent decision tree model. METHODS: We consolidated data from 3,288 ICI-treated patients with NSCLC across real-world multicenter, public cohorts and the Choice-01 trial (ClinicalTrials.gov: NCT03856411). Over 50 features were examined for predicting durable clinical benefits (DCBs) from ICIs. Noteworthy biomarkers were identified to establish a decision tree model. Additionally, we explored the tumor microenvironment and peripheral CD8+ programmed death-1 (PD-1)+ T cell receptor (TCR) profiles. FINDINGS: Multivariate logistic regression analysis identified tumor histology, PD-ligand 1 (PD-L1) expression, tumor mutational burden, line, and regimen of ICI treatment as significant factors. Mutation subtypes of EGFR, KRAS, KEAP1, STK11, and disruptive TP53 mutations were associated with DCB. The decision tree (DT10) model, using the ten clinicopathological and genomic markers, showed superior performance in predicting DCB in the training set (area under the curve [AUC] = 0.82) and consistently outperformed other models in test sets. DT10-predicted-DCB patients manifested longer survival, an enriched inflamed tumor immune phenotype (67%), and higher peripheral TCR diversity, whereas the DT10-predicted-NDB (non-durable benefit) group showed an enriched desert immune phenotype (86%) and higher peripheral TCR clonality. CONCLUSIONS: The model effectively predicted DCB after front-/subsequent-line ICI treatment, with or without chemotherapy, for squamous and non-squamous lung cancer, offering clinicians valuable insights into efficacy prediction using cost-effective variables. FUNDING: This study was supported by the National Key R&D Program of China.

[A study of cognitive impairment quantitative assessment method based on gait characteristics].

Alzheimer's disease (AD) is a common and serious form of elderly dementia, but early detection and treatment of mild cognitive impairment can help slow down the progression of dementia. Recent studies have shown that there is a relationship between overall cognitive function and motor function and gait abnormalities. We recruited 302 cases from the Rehabilitation Hospital Affiliated to National Rehabilitation Aids Research Center and included 193 of them according to the screening criteria, including 137 patients with MCI and 56 healthy controls (HC). The gait parameters of the participants were collected during performing single-task (free walking) and dual-task (counting backwards from 100) using a wearable device. By taking gait parameters such as gait cycle, kinematics parameters, time-space parameters as the focus of the study, using recursive feature elimination (RFE) to select important features, and taking the subject's MoCA score as the response variable, a machine learning model based on quantitative evaluation of cognitive level of gait features was established. The results showed that temporal and spatial parameters of toe-off and heel strike had important clinical significance as markers to evaluate cognitive level, indicating important clinical application value in preventing or delaying the occurrence of AD in the future.

Assessment of human leukocyte antigen-based neoantigen presentation to determine pan-cancer response to immunotherapy.

Despite the central role of human leukocyte antigen class I (HLA-I) in tumor neoantigen presentation, quantitative determination of presentation capacity remains elusive. Based on a pooled pan-cancer genomic dataset of 885 patients treated with immune checkpoint inhibitors (ICIs), we developed a score integrating the binding affinity of neoantigens to HLA-I, as well as HLA-I allele divergence, termed the HLA tumor-Antigen Presentation Score (HAPS). Patients with a high HAPS were more likely to experience survival benefit following ICI treatment. Analysis of the tumor microenvironment indicated that the antigen presentation pathway was enriched in patients with a high HAPS. Finally, we built a neural network incorporating factors associated with neoantigen production, presentation, and recognition, which exhibited potential for differentiating cancer patients likely to benefit from ICIs. Our findings highlight the clinical utility of evaluating HLA-I tumor antigen presentation capacity and describe how ICI response may depend on HLA-mediated immunity.

Early-life exposure to ambient air pollution with cardiovascular risk factors in adolescents: Findings from the "Children of 1997" Hong Kong birth cohort.

BACKGROUND: Long-term exposure to ambient air pollution is associated with cardiovascular disease (CVD) risk. Little is known about the impact of early-life exposure to air pollutants on CVD risk factors in late adolescence, which may track into adulthood. To clarify, we examined this question in a unique setting with high air pollution and a high level of economic development. METHODS: This study leveraged the "Children of 1997" Hong Kong birth cohort (N = 8327), including here 3350 participants. We estimated ambient air pollutant exposure including inhalable particulate matter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2) and nitrogen monoxide (NO) by growth phase (in utero, infancy, childhood) and overall based on residential address. Generalized linear regression was used to assess the associations of air pollutants exposure by growth phase and sex with CVD risk factors (fasting blood glucose, glycosylated hemoglobin, lipid profile, blood pressure, and body mass index) at 17.6 years. We also assessed whether associations varied by sex. RESULTS: Early life exposed had little association with glucose metabolism, blood pressure or body mass index, but after considering multiple comparisons early exposure to PM10 was associated with low density lipoprotein (LDL) in boys, with ß and 95 % confidence intervals (95 % CI) of 0.184 (0.069 to 0.298) mmol/l, 0.151 (0.056 to 0.248) mmol/l, and 0.157 (0.063 to 0.252) mmol/l by per interquartile range (IQR) increment of PM10 for in utero, infancy, and overall, respectively. No such associations were evident for girls, differences by sex were evident. CONCLUSIONS: Our study suggested sex-specific associations of early-life PM10 exposure with elevated LDL in adolescence, especially exposure in utero and infancy.

The association between dual sensory loss and healthcare expenditure: Mediating effect of depression.

BACKGROUND: Previous studies have suggested the dual sensory loss (DSL) is linked to depression, and that they are associated with higher healthcare expenditures, respectively. However, the association between DSL, depression and healthcare expenditures remains ambiguous. OBJECTIVES: The current study aims to examine the association between DSL, depression and healthcare expenditures as well as catastrophic health expenditures (CHE) among Chinese people aged 45 and above. METHODS: We first utilized the China Health and Retirement Longitudinal Survey (CHARLS) 2018 to obtain data from a total of 13,412 Chinese individuals aged 45 and above to conduct a cross-sectional study. DSL was defined as a combined variable of self-reported vision loss and hearing loss. Depression was measured using The Center for Epidemiologic Studies Depression Scale (CESD-10). The healthcare expenditures, including outpatient out-of-pocket cost and inpatient out-of-pocket cost, were obtained from the Harmonized CHARLS section. CHE were defined as out-of-pocket (OOP) health spending equal to or higher than 40 % of a household's capacity to pay. A Tobit linear regression with three models and a path analysis were conducted to estimate the association between DSL, depression and healthcare expenditures and CHE. Then we utilized 2011CHARLS and 2018CHARLS to present a longitudinal analysis. A path analysis was conducted to estimate the association between 2011DSL, 2018depression and 2018healthcare expenditures and CHE. RESULTS: Depression has a significant mediating effect between DSL and healthcare expenditures. (For outpatient OOP cost: a = 0.453, b = 23.559, c = 25.257, the proportion of mediating effect in total effect = 29.71 %; for inpatient OOP cost: a = 0.453, b = 13.606, c = 15.463, the proportion of mediating effect in total effect = 28.50 %; all P < 0.05). The mediating effect of depression also exists in the association between DSL and CHE (a = 0.453, b = 0.018, c = 0.043, the proportion of mediating effect in total effect = 15.90 %; P < 0.05). The mediation effect of depression on healthcare expenditures and CHE also exists in the longitudinal analysis using CHARLS 2011 and CHARLS 2018 (all P < 0.05). LIMITATIONS: The DSL status were based on self-report and we used 2018CHARLS to conduct the study, which may cause some bias. CONCLUSION: Significant mediating effect of depression exists between DSL and higher healthcare expenditures and CHE. The mental health of elder people with DSL should be focused on, and we should have an overall viewpoint on the topic of healthcare expenditures and CHE.

Epidemiological and clinical features, treatment status, and economic burden of traumatic spinal cord injury in China: a hospital-based retrospective study.

Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death. China has the largest population of patients with traumatic spinal cord injury. Previous studies of traumatic spinal cord injury in China have mostly been regional in scope; national-level studies have been rare. To the best of our knowledge, no national-level study of treatment status and economic burden has been performed. This retrospective study aimed to examine the epidemiological and clinical features, treatment status, and economic burden of traumatic spinal cord injury in China at the national level. We included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of China. Patient epidemiological and clinical features, treatment status, and total and daily costs were recorded. Trends in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression Program. The percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall (annual percentage change, -0.5% and 2.1%, respectively). A total of 10,053 (74.7%) patients underwent surgery. Only 2.8% of patients who underwent surgery did so within 24 hours of injury. A total of 2005 (14.9%) patients were treated with high-dose (≥ 500 mg) methylprednisolone sodium succinate/methylprednisolone (MPSS/MP); 615 (4.6%) received it within 8 hours. The total cost for acute traumatic spinal cord injury decreased over the study period (-4.7%), while daily cost did not significantly change (1.0% increase). Our findings indicate that public health initiatives should aim at improving hospitals' ability to complete early surgery within 24 hours, which is associated with improved sensorimotor recovery, increasing the awareness rate of clinical guidelines related to high-dose MPSS/MP to reduce the use of the treatment with insufficient evidence.

Cost-effectiveness analysis of dinutuximab ß for the treatment of high-risk neuroblastoma in China.

BACKGROUND: Dinutuximab ß can be used to treat children with high-risk neuroblastoma (NB). Due to its high price, whether dinutuximab ß is cost-effective for the treatment of high-risk NB remains uncertain. Therefore, assessing the cost-effectiveness of dinutuximab ß in children with high-risk NB is of high importance. METHODS: The health utilities and economic outcomes in children with high-risk NB were projected using a partitioned survival model. The individual patient data (IPD) of add-on treatment with dinutuximab ß (GD2 group) were derived from the literature, while the IPD of traditional therapy (TT group) were obtained from retrospective data of Shanghai Children's Medical Center. Treatment costs included drugs, adverse event-related expenses, and medical resource use. Utility values were obtained from the literature. Costs and quality-adjusted life-years (QALYs) were measured over a 10-year time horizon. Deterministic sensitivity analyses (DSA) and probabilistic sensitivity analyses (PSA) were also conducted. RESULTS: Compared with the TT group, QALY increased in the GD2 group by 0.72 with an increased cost of $171,269.70, leading to an incremental cost-effectiveness ratio of 236,462.75$/QALY. DSA showed that the price of dinutuximab ß was the main factor on the results than other parameters. Compared with the TT group, the GD2 group could not be cost-effective in the PSA at the $37,920/QALY threshold. CONCLUSION: Results found that dinutuximab ß is not a cost-effective treatment option for children with high-risk NB unless its price is significantly reduced.

Low-Cost Preparation of High-Performance Na-B-H-S Electrolyte for All-Solid-State Sodium-Ion Batteries.

All-solid-state sodium-ion batteries have the potential to improve safety and mitigate the cost bottlenecks of the current lithium-ion battery system if a high-performance electrolyte with cost advantages can be easily synthesized. In this study, a one-step dehydrogenation-assisted strategy to synthesize the novel thio-borohydride (Na-B-H-S) electrolyte is proposed, in which both raw material cost and preparation temperature are significantly reduced. By using sodium borohydride (NaBH4 ) instead of B as a starting material, B atoms can be readily released from NaBH4 with much less energy and thus became more available to generate thio-borohydride. The synthesized Na-B-H-S (NaBH4 /Na-B-S) electrolyte exhibits excellent compatibility with current cathode materials, including FeF3 (1.0-4.5 V), Na3 V2 (PO4 )3 (2.0-4.0 V), and S (1.2-2.8 V). This novel Na-B-H-S electrolyte will take a place in mainstream electrolytes because of its advantages in preparation, cost, and compatibility with various cathode materials.

Factorial structure and measurement invariance of the Chinese version of the Oral Health Impact Profile-14 among clinical populations and non-clinical populations: an evidence for public oral investigations.

OBJECTIVE: Oral health-related quality of life (OHRQoL) is a multidimensional concept that is commonly used to examine the impact of oral health status on quality of life. The purpose of this study was to examine the optimal factor model of the Chinese version of the Oral Health Impact Profile (OHIP-14) questionnaire in clinical populations, measurement invariance across clinical status and gender cohorts. This would ensure equal validity of the Chinese version of OHIP-14 in different populations and further support public oral investigations. METHODS: The Chinese version of OHIP-14 was used to investigate 490 dental patients and 919 college students. Confirmatory factor analysis (CFA), item analysis and reliability, measurement invariance, and the t-test were used for data analyses. RESULTS: We found that the 7-factor structure had the best-fit index in the sample (CFI = 0.970, TLI = 0.952; SRMR = 0.029, RMSEA = 0.052(0.040,0.063)). The reliability of the scales was satisfactory (Cronbach's α = 0.942). The error variance invariance fitted the data adequately in measurement invariance, indicating that measurement invariance is acceptable both across the clinical and non-clinical populations (∆CFI=-0.017, ∆RMSEA = 0.010) and across genders in the clinical population (∆CFI = 0.000, ∆RMSEA=-0.003). T-test for scores showed that the clinical populations scored significantly higher than the non-clinical populations, as did the overall score (t = 7.046, p < 0.001, d = 0.396), in terms of functional limitation (t = 2.178, p = 0.030, d = 0.125), physical pain (t = 7.880, p < 0.001,d = 0.436), psychological discomfort (t = 8.993, p < 0.001, d = 0.514), physical disability (t = 6.343, p < 0.001, d = 0.358), psychological disability (t = 5.592, p < 0.001, d = 0.315), social disability (t = 5.301, p < 0.001,d = 0.304), social handicap (t = 4.452, p < 0.001, d = 0.253), and that in the non-clinical populations, females scored significantly higher than males, as did in terms of physical pain (t = 3.055, p = 0.002, d = 0.280), psychological discomfort (t = 2.478, p = 0.014, d = 0.222), and psychological disability (t = 2.067, p = 0.039, d = 0.188). CONCLUSION: This study found that the Chinese version of OHIP-14 has measurement invariance between the clinical and non-clinical populations and across genders in the clinical populations, and can be widely used in OHRQoL assessment for public oral investigations.

In five wastewater treatment plants in Xinjiang, China: Removal processes for illicit drugs, their occurrence in receiving river waters, and ecological risk assessment.

Residues of illicit drugs are frequently detected in wastewater, but data on their removal efficiency by wastewater treatment plants (WWTPs) and the ecological risks to the aquatic environment are lacking in this study. The research evaluates the residues, mass load, drug removal efficiency, and risk assessment of illicit drugs in WWTPs and aquatic environments (lakes) in Xinjiang, China. Initially, the concentration (incidence) and mass load of 10 selected illicit drugs were analyzed through wastewater analysis. The detected substances included methamphetamine (METH), morphine (MOR), 3,4-methylenedioxy methamphetamine (MDMA), methadone (MTD), cocaine (COC), benzoylecgonine (BE), ketamine (KET), and codeine (COD), with concentrations ranging from 0.11 ± 0.01 ng/L (methadone) to 48.26 ± 25.05 ng/L (morphine). Notably, morphine (59.74 ± 5.82 g/day) and methamphetamine (41.81 ± 4.91 g/day) contributed significantly to the WWTPs. Next, the drug removal efficiency by different sewage treatment processes was ranked as follows: Anaerobic-Oxic (A/O) combined Membrane Bio-Reactor (MBR) treatment process > Oxidation ditch treatment process > Anaerobic-Anoxic-Oxic (A2/O) treatment process > Anaerobic-Anoxic-Oxic combined Membrane Bio-Reactor treatment process. Finally, the research reviewed the concentration and toxicity assessments of these substances in the aquatic environment (lakes). The results indicated that Lake1 presented a medium risk level concerning the impact of illicit drugs on the aquatic environment, whereas the other lakes exhibited a low risk level. As a result, it is recommended to conduct long-term monitoring and source analysis of illicit drugs, specifically in Lake1, for further investigation. In conclusion, to enhance the understanding of the effects of illicit drugs on the environment, future research should expand the list of target analytes.

Association of Depressive Symptoms With Health Service Use and Catastrophic Health Expenditure Among Middle-Aged and Older Chinese Adults: Analysis of Population-Based Panel Data.

OBJECTIVES: To determine the impact of depressive symptoms on health service use and catastrophic health expenditure, and whether it varied by per-capita household consumption, health insurance schemes, and physical comorbidities. DESIGN: Population-based panel data analysis. SETTING AND PARTICIPANTS: Participants were 8585 adults aged 45 years and older in 2011, and had completed a follow-up survey in 2013, 2015, and 2018 from the China Health and Retirement Longitudinal Study (CHARLS). METHODS: Depressive symptoms were assessed using the short form of the Center for Epidemiologic Studies Depression Scale. The number of outpatient visits and inpatient hospital days were used as proxies for health service use. When households' out-of-pocket spending on health was 40% or above its total expenditure, it was defined as a catastrophic health expenditure. With the panel data approach, random-effects negative binomial regression and logistic regression were used to analyze the effect of depressive symptoms on health service use and health care expenditure, respectively. RESULTS: Depressive symptoms were associated with increased number of outpatient visits (incidence rate ratio 1.52; 95% CI 1.44-1.60) and days spent in the hospital as an inpatient (1.52; 1.43-1.62). Depressive symptoms were also associated with a significantly increased likelihood of catastrophic health expenditure (odds ratio 1.54; 95% CI 1.43-1.66). Their effect on outpatient visits, inpatient hospital days, and catastrophic health expenditure persisted in different age, per-capita household consumption, and physical comorbidities groups, and across all health insurance programs. CONCLUSIONS AND IMPLICATIONS: Depressive symptoms were risk indicators that can drive health service use and household financial stress. Given the rapidly aging population in China, there is an urgent need to integrate mental health care into routine physical examinations to alleviate the economic impacts of depressive symptoms on individuals in China. specifically for individuals with physical comorbidities and in poorer socioeconomic conditions.

The Impact of the Scale of Third-Party Logistics Guaranteeing Firms on Bank Credit Willingness in Supply Chain Finance: An ERP Study.

Supply chain financing guaranteed by third-party logistics (3PL) firms is an effective way to solve the financing difficulties of small and medium-sized enterprises (SMEs). Studies have explored factors that affect the willingness of supply chain financial credit providers under guarantee of 3PL firms (e.g., the scale of financing enterprises and credit). However, whether the scale of 3PL firms will affect the bank's credit decision has not been studied, as well as the neural processing of credit decisions. To clarify these issues, this study extracted behavioral and event-related potentials (ERPs) data when participants performed a selection task of judging whether to grant credit to guaranteed financing-seeking enterprises according to the large or small scale of the 3PL guaranteeing firms. The behavioral results showed that under the condition of a large-scale 3PL guaranteeing firm, the willingness to provide credit to SMEs was higher than that under the condition of a small-scale 3PL guaranteeing firm. This finding indicates there was credit scale discrimination against 3PL guaranteeing firms in supply chain finance. The ERP results showed that compared with the condition of a large-scale 3PL guaranteeing firm, a greater N2 amplitude was induced under the condition of a small-scale 3PL guaranteeing firm, which indicated that credit decision makers experienced greater perceived risk and more decision-making conflict. In contrast, a larger LPP amplitude was detected under the condition of a large-scale 3PL guaranteeing firm (as opposed to a small-scale firm), which indicated that large-scale 3PL guaranteeing firms received more positive comments and more positive emotions from credit decision makers than small-scale 3PL guaranteeing firms. Based on these results, this study reveals the cognition process of credit decision makers regarding the impact of the 3PL guaranteeing firm scale on the willingness to provide credit in supply chain finance and explains the theory of credit scale discrimination from the perspective of decision neuroscience.

Cost-Effectiveness Analysis of the Application of a Porcine-Derived Fibrin Sealant for the Treatment of Cerebrospinal Fluid Leak in China.

PURPOSE: This study aimed to evaluate the cost-effectiveness of a porcine-derived fibrin sealant (PFS) for treating cerebrospinal fluid (CSF) leaks in cranial surgery compared with sutures alone from the perspective of public hospital management in China. METHODS: A decision tree model of cranial surgery patients with intraoperative CSF leak was constructed in R 3.6.3. The cost-effectiveness of using PFS with dural sutures was compared versus using sutures alone. Efficacy and safety data were obtained from a randomized controlled, single-blinded clinical trial that enrolled 200 patients (NCT03110783). Effectiveness was measured as the success rate of CSF leak treatment and the rate of postoperative complication. Hospital procurement costs were used to provide cost measurements from the hospital administrator's perspective. FINDINGS: The PFS strategy had a higher success rate of CSF leak treatment (97.81% vs 49.21%) and a lower complication rate (9.49% vs 14.29%), based on results from the clinical trial. Using PFS also resulted in cost savings amounting to $374.97 in additional intraoperative CSF leak repairs ($18.07 vs $393.04) and $66.68 in postoperative complication treatment ($131.90 vs $198.58). Both one-way sensitivity analysis and probabilistic sensitivity analysis confirmed that the model results were stable against input variations. IMPLICATIONS: The decision tree analysis revealed that using PFS in conjunction with sutures was associated with improved clinical performance and lower overall costs. PFS in combination with sutures is the dominant strategy for treating CSF leak from the perspective of hospital decision-makers.

Employing biochemical biomarkers for building decision tree models to predict bipolar disorder from major depressive disorder.

BACKGROUND: Conventional biochemical parameters may have predictive values for use in clinical identification between bipolar disorder (BD) and major depressive disorder (MDD). METHODS: This study enrolled 2470 hospitalized patients with BD (n = 1333) or MDD (n = 1137) at reproductive age from 2009 to 2018 in China. We extracted 8 parameters, uric acid (UA), direct bilirubin (DBIL), indirect bilirubin (IDBIL), lactic dehydrogenase (LDH), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), high-density lipoprotein (HDL) and prealbumin of male, patients and 12 parameters, UA, DBIL, IBIL, LDH, FT3, TSH, glutamic-pyruvic transaminase (GPT), white blood cell (WBC), alkaline phosphatase (ALP), fasting blood glucose (FBG), triglyceride and low-density lipoprotein (LDL) of female patients. Backward stepwise multivariate regression analysis and the Chi-Square Automatic Interaction Detection (CHAID) segmentation analysis via SPSS Decision Tree were implemented to define the discrimination of BD and MDD. RESULTS: DBIL was extracted as the first splitting variable, with LDH and IBIL as the second, TSH and prealbumin as the third in the model of male patients (p-value < .05). For the model of female patients, DBIL was also extracted as the first splitting variable, with UA, LDH, and IBIL as the second, triglyceride and FT3 as the third (p-value < .05). The predictive accuracies of the Decision Tree and multiple logistic regression models were similar (74.9% vs 76.9% in males; 74.4% vs 79.5% in females). CONCLUSIONS: This study suggests the value of the Decision Tree models, which employ biochemical parameters as diagnostic predictors for BD and MDD. The CHAID Decision Tree identified that patients with concomitantly increased LDH, IBIL, and decreased DBIL could be in the group that showed the highest risk of being diagnosed as BD.

Economic Evaluation of First-Line Camrelizumab for Advanced Non-small-cell Lung Cancer in China.

Background: As the first domestic PD-1 antibody approved for lung cancer in China, camrelizumab has exhibited proven effectiveness for non-small-cell lung cancer (NSCLC) patients. However, the cost-effectiveness of this new regimen remains to be investigated. Objective: To evaluate the cost-effectiveness of camrelizumab combination therapy vs. chemotherapy for previously untreated patients with advanced, non-squamous NSCLC without Alk or Egfr genomic aberrations from the perspective of China's healthcare system. Methods: Based on the CameL trial, the study developed a three-health state Markov model to evaluate the cost-effectiveness of adding camrelizumab to chemotherapy compared to chemotherapy alone in NSCLC patients. The analysis models were conducted for patients unselected by PD-L1 tumor expression (the base case) and the patient subgroup with PD-L1-expressing tumors (≥1%). Primary model outcomes included the costs in US dollars and health outcomes in quality-adjusted life-years (QALYs) as well as the incremental cost-effectiveness ratio (ICER) under a willingness-to-pay threshold of $31,500 per QALY. Additionally, a scenario analysis that adjusted within-trial crossover was employed to evaluate camrelizumab combination therapy compared to chemotherapy without subsequent use of PD1/PD-L1 antibodies. Results: Camrelizumab combination therapy was more costly and provided additional 0.11 QALYs over chemotherapy in the base case analysis (0.86 vs. 0.75 QALYs), 0.12 QALYs over chemotherapy in the subgroup analysis (0.99 vs. 0.88 QALYs), and 0.34 QALYs over chemotherapy in the scenario analysis (0.86 vs. 0.52 QALYs). Correspondingly, the ICER was $63,080 per QALY, $46,311 per QALY, and $30,591 per QALY, in the base case, the subgroup, and the scenario analysis, respectively. One-way sensitivity analyses revealed that ICERs of the base case and the subgroup analysis were most sensitive to the cost of camrelizumab, the cost of pemetrexed. Besides, the base case and subgroup analysis were more sensitive to the risk of neutrophil count decreased in the camrelizumab and the utility of stable disease, respectively. Conclusion: Although camrelizumab combination therapy is not cost-effective as first-line therapy for NSCLC patients in China in the base case, adjusting within-trial crossover would move the treatment regimen toward cost-effectiveness in the scenario analysis.

First-line atezolizumab plus chemotherapy in advanced non-squamous non-small cell lung cancer: a cost-effectiveness analysis from China.

Objective: To assess the cost-effectiveness of atezolizumab in combination with carboplatin plus nab-paclitaxel-based chemotherapy versus chemotherapy alone for first-line treatment of advanced non-squamous non-small cell lung cancer (NSCLC) from the Chinese healthcare system perspective.Methods: A Markov model was developed based on the IMpower130 clinical trial. Drug costs and health state utility were obtained from the literature. Outcomes included life-years (LYs), quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were performed to evaluate the model uncertainty.Results: When compared to chemotherapy alone, atezolizumab plus chemotherapy provides an additional 0.34 LY and 0.19 QALY, and has an ICER of $180,560.15 per additional LY gained and that of $325,328.71 per QALY gained. Sensitivity analysis revealed that the results were most sensitive to changes in atezolizumab cost. Probabilistic sensitivity analysis showed that there was a 0% probability that atezolizumab plus chemotherapy was cost-effective at willingness-to-pay values of $30,828 per QALY. If the WTP threshold increased to $325,000 per QALY, atezolizumab plus chemotherapy has a 50% chance to be cost-effective.Conclusions: From the Chinese healthcare system perspective, atezolizumab combination is not cost-effective for first-line therapy of advanced non-squamous NSCLC.

Clinical immunity and medical cost of COVID-19 patients under grey relational mathematical model.

This study was to explore the performance of immune function and compositions of hospitalization cost for patients with COVID-19 as well as the application of a grey relational mathematical model (GRMM). A total of 100 COVID-19 patients diagnosed by nucleic acid test and chest CT examination in our hospital were collected in this study. They were divided into 2 groups: non-severe group (mild and moderate patients, n = 57 cases), and severe group (severe and critical patients, n = 43 cases) based on the Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7) published by the World Health Organization (WHO). The general clinical data, blood routine indexes, cellular immune and humoral immune function test indexes, and the composition of hospitalization costs of the two groups of patients were collected and analyzed. The results showed that the average age, proportion of males, smoking history, and the number and proportion of patients in the non-severe group were smaller than those in the severe group (P < 0.05); the severe group had significantly more shortness of breath patients than the non-severe group (P < 0.05). Compared with the non-severe group, the number of white blood cells (WBC), the number and proportion of neutrophils, and the count of neutrophils/lymphocytes in the severe group increased obviously (P < 0.05), and the number of lymphocytes and the proportion of monocytes decreased dramatically (P < 0.05); the number and proportion of CD3+, CD4+, CD8+, and CD19+ in the severe group were much lower in contrast to those in the non-severe group (P < 0.05), while the ratio of CD4+/CD8+ was greatly higher in contrast to that of non-severe patients (P < 0.05). Compared with the non-severe group, the bed fee, laboratory test fee, diagnosis fee, and medicine fee of the severe group were increased observably (P < 0.05). The changes in hospitalization cost of patients in the severe group was related to bed fees, laboratory fees, and expenses of proprietary Chinese medicines, while the hospitalization cost of patients in the severe group was related to bed fees, laboratory fees, and examination fees. The results revealed that elderly COVID-19 patients with basic diseases were prone to develop severe disease, immune cell depletion may be one of the reasons for the development of severe patients, and the medical insurance policy greatly reduced the hospitalization costs of COVID-19 patients.

Cost-Effectiveness Analysis of PEG-rhG-CSF as Primary Prophylaxis to Chemotherapy-Induced Neutropenia in Women With Breast Cancer in China: Results Based on Real-World Data.

Background: Pegylated recombinant human granulocyte colony-stimulating factors (PEG-rhG-CSFs) are more commonly and widely used than recombinant human granulocyte colony-stimulating factors (rhG-CSFs) in preventing chemotherapy-induced neutropenia in patients with stage II-IV breast cancer. To reduce the financial burden on these patients, the corresponding medical insurance directory needs to be revised. Objectives: To evaluate the cost-effectiveness of PEG-rhG-CSF versus rhG-CSF in patients with stage II-IV breast cancer in central China. Methods: Two Markov models, a chemotherapy model and a post-chemotherapy model, were developed to study the effects and costs, with a time horizon of 12 weeks and 35 years, respectively. Cost and probability input data were primarily obtained from a retrospective real-world study conducted in five tertiary hospitals. Propensity score matching was adopted to overcome retrospective bias. Other parameters were extracted from literature as well as advice from clinical experts. Univariate and probabilistic sensitivity analyses were conducted. Results: In the first chemotherapy model, PEG-rhG-CSF was associated with fewer episodes of febrile neutropenia (FN) (N = 19 per 1000 patients treated), infections (N = 24 per 1000 patients treated) and deaths (N = 2 per 1000 patients treated), but higher costs (¥36 more per patient treated). The post-chemotherapy model indicated that PEG-rhG-CSF led to higher gains in quality-adjusted life years (QALYs) (11.695 versus 11.516) in comparison to rhG-CSF. Sensitivity analysis showed that the cost of PEG-rhG-CSF had the greatest impact on the incremental costs, and incremental QALYs were very sensitive to the risk of RDI <85%. The probability of PEG-rhG-CSF being cost-effective compared to rhG-CSF was 66% at the willingness to pay (WTP) thresholds of ¥72,371 per QALY gained. Conclusion: According to this economic evaluation based on real-world data, PEG-rhG-CSF may be considered as a more cost-effective strategy relative to rhG-CSF for stage II-IV breast cancer patients in central China. However, to reflect a national perspective, further evidence is needed using data from larger-scale studies.

Transcription factor NF-κB promotes acute lung injury via microRNA-99b-mediated PRDM1 down-regulation.

Acute lung injury (ALI), is a rapidly progressing heterogenous pulmonary disorder that possesses a high risk of mortality. Accumulating evidence has implicated the activation of the p65 subunit of NF-κB [NF-κB(p65)] activation in the pathological process of ALI. microRNAs (miRNAs), a group of small RNA molecules, have emerged as major governors due to their post-transcriptional regulation of gene expression in a wide array of pathological processes, including ALI. The dysregulation of miRNAs and NF-κB activation has been implicated in human diseases. In the current study, we set out to decipher the convergence of miR-99b and p65 NF-κB activation in ALI pathology. We measured the release of pro-inflammatory cytokines (IL-1ß, IL-6, and TNFα) in bronchoalveolar lavage fluid using ELISA. MH-S cells were cultured and their viability were detected with cell counting kit 8 (CCK8) assays. The results showed that miR-99b was up-regulated, while PRDM1 was down-regulated in a lipopolysaccharide (LPS)-induced murine model of ALI. Mechanistic investigations showed that NF-κB(p65) was enriched at the miR-99b promoter region, and further promoted its transcriptional activity. Furthermore, miR-99b targeted PRDM1 by binding to its 3'UTR, causing its down-regulation. This in-creased lung injury, as evidenced by increased wet/dry ratio of mouse lung, myeloperoxidase activity and pro-inflammatory cytokine secretion, and enhanced infiltration of inflammatory cells in lung tissues. Together, our findings indicate that NF-κB(p65) promotion of miR-99b can aggravate ALI in mice by down-regulating the expression of PRDM1.

Chromatin accessibility and transcriptome landscapes of Monomorium pharaonis brain.

The emergence of social organization (eusociality) is a major event in insect evolution. Although previous studies have investigated the mechanisms underlying caste differentiation and social behavior of eusocial insects including ants and honeybees, the molecular circuits governing sociality in these insects remain obscure. In this study, we profiled the transcriptome and chromatin accessibility of brain tissues in three Monomorium pharaonis ant castes: queens (including mature and un-mated queens), males and workers. We provide a comprehensive dataset including 16 RNA-sequencing and 16 assay for transposase accessible chromatin (ATAC)-sequencing profiles. We also demonstrate strong reproducibility of the datasets and have identified specific genes and open chromatin regions in the genome that may be associated with the social function of these castes. Our data will be a valuable resource for further studies of insect behaviour, particularly the role of brain in the control of eusociality.