Sporoderm-broken spores of Ganoderma lucidum modulate hepatoblastoma malignancy by regulating RACK1-mediated autophagy and tumour immunity.

Hepatoblastoma (HB), a primary liver tumour, is notorious for its high metastatic potential and poor prognosis. Ganoderma lucidum, an edible mushroom species utilized in traditional Chinese medicine for addressing various tumour types, presents an intriguing avenue for HB treatment. However, the effectiveness of G. lucidum in managing HB and its underlying molecular mechanism necessitates further exploration. Standard in vitro assays were conducted to evaluate the impact of sporoderm-broken spores of G. lucidum (SBSGL) on the malignant characteristics of HB cells. The mechanism of SBSGL in treating HB and its tumour immunomodulatory effects were explored and validated by various experiments, including immunoprecipitation, Western blotting, mRFP-GFP-LC3 adenovirus transfection and co-localization analysis, as well as verified with in vivo experiments in this regard. The results showed that SBSGL effectively inhibited the malignant traits of HB cells and suppressed the O-GlcNAcylation of RACK1, thereby reducing its expression. In addition, SBSGL inhibited immune checkpoints and regulated cytokines. In conclusion, SBSGL had immunomodulatory effects and regulated the malignancy and autophagy of HB by regulating the O-GlcNAcylation of RACK1. These findings suggest that SBSGL holds promise as a potential anticancer drug for HB treatment.

Reply to "Matters arising: cost-effectiveness of first-line immunotherapy combinations with or without chemotherapy for advanced non-small cell lung cancer: a modelling approach".

In this article, we read with great attention the correspondence by Bullement et al., regarding our published study on cost-effectiveness of first-line immunotherapy combinations with or without chemotherapy for advanced non-small cell lung cancer. We referred to a few the most important comments from Bullement et al. in our opinion, including proportional hazard (PH) assumption, accelerated failure time (AFT) model, and health utility, and made some explanations.

Time-dependent efficacy analysis of first-line immunotherapies for advanced non-small cell lung cancer.

BACKGROUND: Many randomized controlled trials (RCTs) and network meta-analyses have demonstrated that the progression-free survival (PFS) and overall survival (OS) of advanced non-small cell lung cancer (NSCLC) patients can be improved through combination immunotherapy or monotherapies. However, time-dependent analysis of the treatment effect is currently lacking. Thus, we aimed to evaluate the efficacy of first-line immunotherapy, and establish a hazard ratio function to reflect the time-varying progression or mortality risk of patients with NSCLC. METHODS: Seventeen clinical trials were selected based on search strategy. Baseline characteristics, including the age, sex, smoking status, geographical region, and Eastern Cooperative Oncology Group (ECOG) performance status of patients, were balanced, resulting in ten immunotherapies from nine appropriate clinical trials to conduct treatment effect comparison. RESULTS: We found that nivolumab plus ipilimumab (nivo + ipi) improved the PFS and OS over time. The hazard ratio of nivo + ipi, relative to that of pembrolizumab, decreased from 1.11 to 0.36 for PFS, and from 0.93 to 0.49 for OS over a 10-year period. In terms of the response to immunotherapy in patients with different PD-L1 expression levels, patients with PD-L1 > = 50% experienced lower rates of progression and a reduced mortality risk over time. The hazard ratio of patients with PD-L1 > = 50% relative to all of the patients decreased from 0.73 to 0.69 for PFS, and from 0.78 to 0.67 for OS. CONCLUSIONS: Based on the fact that time-dependent progression and mortality risk existed during the treatment duration, physicians should select a suitable treatment regimen for patients based on the hazard ratio.

Preoperative prediction of rectal Cancer staging combining MRI deep transfer learning, radiomics features, and clinical factors: accurate differentiation from stage T2 to T3.

BACKGROUND: This study evaluates the efficacy of integrating MRI deep transfer learning, radiomic signatures, and clinical variables to accurately preoperatively differentiate between stage T2 and T3 rectal cancer. METHODS: We included 361 patients with pathologically confirmed stage T2 or T3 rectal cancer, divided into a training set (252 patients) and a test set (109 patients) at a 7:3 ratio. The study utilized features derived from deep transfer learning and radiomics, with Spearman rank correlation and the Least Absolute Shrinkage and Selection Operator (LASSO) regression techniques to reduce feature redundancy. Predictive models were developed using Logistic Regression (LR), Random Forest (RF), Decision Tree (DT), and Support Vector Machine (SVM), selecting the best-performing model for a comprehensive predictive framework incorporating clinical data. RESULTS: After removing redundant features, 24 key features were identified. In the training set, the area under the curve (AUC)values for LR, RF, DT, and SVM were 0.867, 0.834, 0.900, and 0.944, respectively; in the test set, they were 0.847, 0.803, 0.842, and 0.910, respectively. The combined model, using SVM and clinical variables, achieved AUCs of 0.946 in the trainingset and 0.920 in the test set. CONCLUSION: The study confirms the utility of a combined model of MRI deep transfer learning, radiomic features, and clinical factors for preoperative classification of stage T2 vs. T3 rectal cancer, offering significant technological support for precise diagnosis and potential clinical application.

Safety and Pharmacokinetic Assessment of the FIC CLDN18.2/4-1BB Bispecific Antibody in Rhesus Monkeys.

Gastric cancer is one of the most common cancers worldwide, particularly in China, with over half a million new cases and over 400 thousand deaths in 2022. Zolbetuximab, a first-in-class investigational monoclonal antibody (mAb) targeting tumor-associated antigen CLDN18.2 which is highly expressed on gastric cancer cells, was recently reported to meet the primary endpoint in Phase III trial as first-line treatment in CLDN18.2 positive and HER2-negative gastric cancers. In the present study, we developed a humanized bispecific antibody (bsAb) CLDN18.2/4-1BB named PM1032. PM1032 activates immune cells via CLDN18.2 mediated crosslinking of 4-1BB, a potent stimulator of T/NK cells. It induced strong immunological memory in multiple tumor-bearing animal models, indicating significant potential as an effective treatment for CLDN18.2 positive cancers such as gastric cancer. Since liver and gastrointestinal (GI) related toxicities were reported in 4-1BB and CLDN18.2 targeting programs during the clinical development, respectively, extensive pharmacokinetics (PK) and safety profile characterization of PM1032 was performed in rhesus monkeys. PM1032 had a half-life comparable to a conventional IgG1 mAb, and serum drug concentration increased in a dose-dependent pattern. Furthermore, PM1032 was generally well tolerated, with no significant abnormalities observed in toxicity studies, including the liver and stomach. In summary, PM1032 demonstrated good PK and an exceptional safety profile in rhesus monkeys supporting further investigation in clinical studies.

Cost-effectiveness of first-line immunotherapy combinations with or without chemotherapy for advanced non-small cell lung cancer: a modelling approach.

BACKGROUND: Many studies have explored the cost-effectiveness of immunotherapy versus chemotherapy alone. However, there is paucity of evidence on direct pharmacoeconomic studies related to immunotherapy combinations. Thus, we aimed at assessing the economic outcomes of first-line immunotherapy combinations in the treatment of advanced non-small cell lung cancer (NSCLC) from the Chinese health care perspective. METHODS: The mutual hazard ratios (HRs) of ten immunotherapy combinations and one chemotherapy regimen for the overall survival (OS) and progression-free survival (PFS) were obtained from a network meta-analysis. Based on proportional hazard (PH) assumption, adjusted OS and PFS curves were established to make the effects comparable. With the parameters of cost and utility, and of scale and shape from the fit of adjusted OS and PFS curves obtained from previous studies, a partitioned survival model was designed to estimate the cost-effectiveness of immunotherapy combinations versus chemotherapy alone. Parameter uncertainty in model inputs was assessed using one-way deterministic and probabilistic sensitivity analyses. RESULTS: The incremental cost of camrelizumab plus chemotherapy versus chemotherapy alone was $13,180.65, the lowest among all the other immunotherapy combinations. Furthermore, sintilimab plus chemotherapy (sint-chemo) provided the highest quality-adjusted life-year (QALY) benefit versus chemotherapy alone (incremental QALYs = 0.45). Sint-chemo yielded the best incremental cost-effectiveness ratio (ICER) versus chemotherapy alone (ICER = $34,912.09/QALY), at the current price. The cost-effectiveness probabilities were 32.01% and 93.91% for pembrolizumab plus chemotherapy, and atezolizumab plus bevacizumab plus chemotherapy, respectively (if the original price of the pembrolizumab, atezolizumab, and bevacizumab were decreased by 90%). CONCLUSIONS: Based on the fact that there is fierce competition in the PD-1/PD-L1 market, pharmaceutical enterprises should strive for greater efficacy, and optimal pricing strategy for therapies.

LINC02381 aggravates breast cancer through the miR-1271-5p/FN1 axis to activate PI3K/AKT pathway.

Emerging investigations have demonstrated that lncRNAs are key crucial modulators in cancer. In this study, we investigated the role of LINC02381 in breast cancer (BC). Reverse transcriptase quantitative polymerase chain reaction measured the LINC02381 level in BC tissues and cells. Colony formation, EdU staining, wound healing and Transwell experiments examined the impact of LINC02381 depletion on BC cell phenotypes. Relationship among miR-1271-5p, LINC02381, and FN1 was tested through applying RIP, luciferase reporter, and RNA pull-down assays. We found that LINC02381 expression was elevated in BC. Functionally, LINC02381 knockdown hampered BC cell proliferation, migration, and invasion. LINC02381 overexpression accelerated tumor formation in vivo. Mechanistically, LINC02381 acted as a ceRNA to increase FN1 via decoying miR-1271-5p. Additionally, LINC02381 activated PI3K/AKT pathway by upregulating FN1. Rescue assays indicated that FN1 upregulation or PI3K/AKT activation rescued the LINC02381 knockdown-mediated inhibition on malignant phenotypes of BC cells. Overall, LINC02381 exerts carcinogenic effects in BC by the miR-1271-5p/FN1 axis to activate PI3K/AKT pathway.

TRERNA1 upregulation mediated by HBx promotes sorafenib resistance and cell proliferation in HCC via targeting NRAS by sponging miR-22-3p.

Hepatocellular carcinoma (HCC) is among the most common malignancies and has an unfavorable prognosis. The hepatitis B virus-encoded X (HBx) protein is closely associated with hepatocarcinogenesis. Sorafenib is a unique targeted oral kinase inhibitor for advanced HCC. Long noncoding RNAs (lncRNAs) mediate HCC progression and therapeutic resistance by acting as competing endogenous RNAs (ceRNAs). However, the ceRNA regulatory mechanisms underlying sorafenib resistance in HBx-associated HCC remain largely unknown. In this study, we found that translation regulatory lncRNA 1 (TRERNA1) upregulation by HBx not only promoted HCC cell proliferation by regulating the cell cycle in vitro and in vivo but also correlated positively with poor prognosis in HCC. Importantly, TRERNA1 enhanced sorafenib resistance in HCC cells. RNA sequencing (RNA-seq) analysis indicated that NRAS proto-oncogene (NRAS) is a potential target of TRERNA1 that mediates aspects of hepatocellular carcinogenesis. TRERNA1 acts as a ceRNA to regulate NRAS expression by sponging microRNA (miR)-22-3p. In summary, we show that increased TRERNA1 expression induced by HBx reduces HCC cell sensitivity to sorafenib by activating the RAS/Raf/MEK/ERK signaling pathway. We reveal a novel regulatory mode by which the TRERNA1/miR-22-3p/NRAS axis mediates HCC progression and indicates that TRERNA1 might constitute a powerful tumor biomarker and therapeutic target in HCC.

Associations of Chinese diagnosis-related group systems with inpatient expenditures for older people with hip fracture.

BACKGROUND: Hip fracture is frequent in older people and represents a major public health issue worldwide. The increasing incidence of hip fracture and the associated hospitalization costs place a significant economic burden on older patients and their families. On January 1, 2018, the Chinese diagnosis-related group (C-DRG) payment system, which aims to reduce financial barriers, was implemented in Sanming City, southern China. This study aimed to evaluate the associations of C-DRG system with inpatient expenditures for older people with hip fracture. METHODS: An uncontrolled before-and-after study employed data of all the patients with hip fracture aged 60 years or older from all the public hospitals enrolled in the Sanming Basic Health Insurance Scheme from January 1, 2016 to December 31, 2018. The 'pre C-DRG sample' included patients from January 1, 2016 to December 31, 2017. The 'post C-DRG sample' included patients from January 1, 2018 to December 31, 2018. A propensity score matching analysis was used to adjust the difference in baseline characteristic parameters between the pre and post samples. Data were analyzed using generalized linear models adjusted for the demographic, clinical, and institutional factors. Robust tests were performed by accounting for time trend, the fixed effects of the year and hospitals, and clustering effect within hospitals. RESULTS: After propensity score matching, we obtained two homogeneous groups of 1123 patients each, and the characteristic variables of the two matched groups were similar. We found that C-DRG reform was associated with a 19.51% decrease in out-of-pocket (OOP) payments (p < 0.001) and a 99.93% decrease in OOP payments as a share of total inpatient expenditure (p < 0.001); whereas total inpatient expenditure was not significantly associated with the C-DRG reform. All the sensitivity analyses did not change the results significantly. CONCLUSION: The implementation of C-DRG payment system reduced both the absolute amount of OOP payments and OOP payments as a share of total inpatient expenditure for older patients with hip fracture, without affecting total inpatient expenditure. These results may provide significant insights for policymakers in reducing the financial burden on older patients with hip fracture in other countries.

Complementary protective effects of autophagy and oxidative response against graphene oxide toxicity in Caenorhabditis elegans.

Graphene oxide (GO) exposure may cause damage to C. elegans. However, the role of autophagy and its interactive effect with oxidative response in GO toxicity still remain largely unclear. In the present study, we investigated the protective role of autophagy against GO and its association with oxidative response using C. elegans as an in vivo system. Results indicated that GO exposure induced autophagy in a dose dependent manner in C. elegans. Autophagy inhibitor 3-methyladenine (3-MA) and silencing autophagy genes lgg-1, bec-1 and unc-51 exacerbated the toxicity of GO whereas autophagy activator rapamycin alleviated it. In addition, the antioxidant N-Acetyl-L-cysteine (NAC) effectively suppressed the toxicity of GO with increased resistance to oxidative stress. Worms with RNAi-induced antioxidative genes sod-1, sod-2, sod-3 and sod-4 knockdown were more sensitive to GO. 3-MA increased the expression of superoxide dismutase SOD-3 under GO exposure conditions and exacerbated the toxicity of GO under the anti-oxidation inaction condition by sod-3 RNAi. In contrast, NAC reduced autophagy levels in GO exposed nematodes and increased tolerance to GO in autophagy-defective worms. These results suggested that autophagy and antioxidative response provide complementary protection against GO in C. elegans.

Sublethal toxicity of graphene oxide in Caenorhabditis elegans under multi-generational exposure.

Nanomaterials have received increasing attentions owing to their potential hazards to the environment and human health; however, the multi-generational toxicity of graphene oxide under consecutive multi-generational exposure scenario still remains unclear. In the present study, Caenorhabditis elegans as an in vivo model organism was employed to explore the multi-generational toxicity effects of graphene oxide and the underlying mechanisms. Endpoints including development and lifespan, locomotion behaviors, defecation cycle, brood sizes, and oxidative response were evaluated in the parental generation and subsequent five filial generations. After continuous exposure for several generations, worms grew smaller and lived shorter. The locomotion behaviors were reduced across the filial generations and these reduced trends were following the impairments of locomotion-related neurons. In addition, the extended defecation cycles from the third filial generation were in consistency with the relative size reduction of the defecation related neuron. Simultaneously, the fertility function of the nematode was impaired under consecutive exposure as reduced brood sizes and oocytes numbers, increased apoptosis of germline, and aberrant expression of reproductive related genes ced-3, ced-4, ced-9, egl-1 and ced-13 were detected in exposed worms. Furthermore, the antioxidant enzyme, SOD-3 was significantly increased in the parent and filial generations. Thus, continuous multi-generational exposure to graphene oxide caused damage to the neuron development and the reproductive system in nematodes. These toxic effects could be reflected by indicators such as growth inhibition, shortened lifespan, and locomotion behavior impairment and induced oxidative response.

Associations between academic burnout, resilience and life satisfaction among medical students: a three-wave longitudinal study.

BACKGROUND: Research shows that there are connections among academic burnout, resilience, and life satisfaction in medical students. However, no study has yet examined the temporal relationships between academic burnout, resilience, and life satisfaction among medical students. This longitudinal study aimed to examine the temporal associations between academic burnout, resilience, and life satisfaction and to explore the possible mediating role of resilience in the relationship between academic burnout and life satisfaction among medical students. METHODS: This is a three-wave longitudinal study covering the preclinical education period of 20 months. From October 2018 to June 2020, a total of 190 students majoring in clinical medicine filled out the Chinese College Student Academic Burnout Inventory (CCSABI), the Connor-Davidson Resilience Scale (CD-RISC) and the Satisfaction With Life Scale (SWLS) three times. Cross-lagged models were constructed to examine the temporal relationships between academic burnout, resilience, and life satisfaction and longitudinal mediation models were constructed to explore the possible mediating role of resilience in the association of academic burnout with life satisfaction. RESULTS: Among medical students, resilience uni-directionally and positively predicted life satisfaction, while academic burnout uni-directionally and negatively predicted life satisfaction. However, the temporal association between resilience and academic burnout was negative and somewhat bidirectional. Resilience had a significant mediating effect on the relationship between academic burnout and life satisfaction in medical students. CONCLUSIONS: Medical educators need to identify and take effective measures to combat academic burnout problems which can lead to reduced life satisfaction among medical students. Resilience-based interventions may be promising in buffering the negative impacts of academic burnout and improving life satisfaction. It is recommended that effective resilience-promotion interventions be developed and implemented in medical education to help enhance medical students' psychological well-being.

Economic Implications of Chinese Diagnosis-Related Group-Based Payment Systems for Critically Ill Patients in ICUs.

OBJECTIVES: To evaluate the economic implications of payments based on Chinese diagnosis-related groups for critically ill patients in ICUs in terms of total hospital expenditure, out-of-pocket payments, and length of stay. DESIGN: A pre-post comparison of patient cohorts admitted to ICUs 1 year before and 1 year after Chinese diagnosis-related group reform was undertaken. Demographic characteristics, clinical data, and medical expenditures were collated from a health insurance database. SETTING: Twenty-two public hospitals in Sanming, Southern China. PATIENTS: All patients admitted to ICUs from January 1, 2017, to December 31, 2018. INTERVENTION: The implementation of Chinese diagnosis-related group-based payments on January 1, 2018. MEASUREMENTS AND MAIN RESULTS: Economic variables (total expenditures, out-of-pocket payments, and length of stay) were calculated for each patient from the day of hospital admission to the day of hospital discharge. Adjusted mean out-of-pocket payment estimates were 29.46% (p < 0.001) lower following reform. Adjusted mean out-of-pocket payments fell by 41.32% for patients in neonatal ICU, whereas there were no significant decreases in out-of-pocket payments for patients in PICU and adult ICU. Furthermore, adjusted mean out-of-pocket payments decreased by 55.74% in secondary hospitals, but there was no significant change in tertiary hospitals after Chinese diagnosis-related group reform. No significant changes were found in total expenditures and length of stay. CONCLUSIONS: Chinese diagnosis-related group policy provided an opportunity for critically ill patients in ICUs to achieve at least short-term financial benefits in reducing out-of-pocket payments, without affecting the total expenditures and length of stay. Chinese diagnosis-related group-based payment significantly relieved financial burdens for patients with lower illness severities, such as patients in neonatal ICU. The results of this study can offer significant insights for policymakers in reducing the financial burden on critically ill patients, both in China and in other countries with similar systems.

Cesarean delivery rates, costs and readmission of childbirth in the new cooperative medical scheme after implementation of an episode-based bundled payment (EBP) policy.

BACKGROUND: In the past decade, the rate of cesarean delivery increased dramatically in rural China under the fee-for-service (FFS) system. In September 2011, the New Cooperative Medical Scheme (NCMS) agency in Yong'an county in Fujian province of China adopted a policy of reforming payment for childbirth by transforming the FFS payment into episode-based bundled payment (EBP), which made the cesarean deliveries less profitable. Thus, this study was conducted to determine the effect of EBP policy on reducing cesarean use and controlling delivery costs for rural patients in the NCMS. METHODS: Data from the inpatient information database of the NCMS agency from January 2010 to March 2013 was collected, in which Yong'an county was employed as a reform county and 2 other counties as controls. We investigated the effects of EBP on cesarean delivery rate, costs of childbirth and readmission for rural patients in the NCMS using a natural experiment design and difference in differences (DID) analysis method. RESULTS: The EBP reform was associated with 33.97% (p<0.01) decrease in the probability of cesarean delivery. The EBP reform, on average, reduced the total spending per admission, government reimbursement expenses per admission, and out-of-pocket (OOP) payments per admission by ¥ 649.61, ¥ 575.01, and ¥ 74.59, respectively. The OOP payments had a net decrease of 14.24% (p<0.01); whereas the OOP payments as a share of total spending had a net increase of 8.72% (p<0.01). There was no evidence of increase in readmission rates. CONCLUSIONS: These results indicate that the EBP policy has achieved at least a short-term success in lowering the increase of cesarean delivery rate and costs of childbirth. Considering both the cesarean rate and the OOP payments as a share of total spending after the reform were still high, China still has a long way to go to achieve the ideal level of cesarean rate and improve the benefits of deliveries for rural population.

Effect of a typical systemic hospital reform on inpatient expenditure for rural population: the Sanming model in China.

BACKGROUND: Considering catastrophic health expenses in rural households with hospitalised members were unproportionally high, in 2013, China developed a model of systemic reform in Sanming by adjusting payment method, pharmaceutical system, and medical services price. The reform was expected to control the excessive growth of hospital expenditures by reducing inefficiency and waste in health system or shortening the length of stay. This study analyzed the systemic reform's impact on the financial burden and length of stay for the rural population in Sanming. METHODS: A total of 1,113,615 inpatient records for the rural population were extracted from the rural new cooperative medical scheme (NCMS) database in Sanming from 2007 to 2012 (before the reform) and from 2013 to 2016 (after the reform). We calculated the average growth rate of total inpatient expenditures and costs of different medical service categories (medications, diagnostic testing, physician services and therapeutic services) in these two periods. Generalized linear models (GLM) were employed to examine the effect of reform on out-of-pocket (OOP) expenditures and length of stay, controlling for some covariates. Furthermore, we controlled the fixed effects of the year and hospitals, and included cluster standard errors by hospital to assess the robustness of the findings in the GLM analysis. RESULTS: The typical systemic reform decreased the average growth rate of total inpatient expenditures by 1.34%, compared with the period before the reform. The OOP expenditures as a share of total expenditures showed a downward trend after the reform (42.34% in 2013). Holding all else constant, individuals after the reform spent ¥308.42 less on OOP expenditures (p < 0.001) than they did before the reform. Moreover, length of stay had a decrease of 0.67 days after the reform (p < 0.001). CONCLUSIONS: These results suggested that the typical systemic hospital reform of the Sanming model had some positive effects on cost control and reducing financial burden for the rural population. Considering the OOP expenditures as a share of total expenditures was still high, China still has a long way to go to improve the benefits rural people have enjoyed from the NCMS.

Empathy, burnout, life satisfaction, correlations and associated socio-demographic factors among Chinese undergraduate medical students: an exploratory cross-sectional study.

BACKGROUND: Medical education is widely known to be a demanding process that may cause various mental health problems, such as burnout, which can lead to lowered levels of life satisfaction among medical students. Research shows that empathy is negatively correlated with burnout, but there are few studies on the relationship among empathy, burnout and life satisfaction in medical students. The objective of the present study is to explore the correlations of empathy and burnout with life satisfaction and the associated socio-demographic factors among Chinese undergraduate medical students. METHODS: In this cross-sectional study, 1271 undergraduate medical students (age 19.42 ± 1.34 years, 36% male) from 1st to 4th grades completed questionnaires including the Interpersonal Reactivity Index Chinese version (IRI-C), the Maslach Burnout Inventory Modified Chinese version (MBI-MC), the Satisfaction With Life Scale (SWLS) and socio-demographic characteristics. Statistical analyses included Student's t-test, one-way ANOVA, post hoc Bonferroni tests, hierarchical linear regression analysis and general linear model-univariate full factorial model. RESULTS: Over four academic years, medical students' empathy levels declined, but their burnout levels almost plateaued and their life satisfaction levels witnessed an initial fall before a rebound. Empathy was correlated with students' age and grade, and burnout was associated with students' maternal education. Significant differences in life satisfaction were detected with regard to medical students' age, academic year, the number of children in the family, place of residence and parents' educational levels. CONCLUSIONS: Empathy explained 0.6% of the variance in life satisfaction in contrast to 13.7% of the variance explained by burnout in life satisfaction. Although empathy did not have a main effect on life satisfaction, there was an interaction effect of empathy and burnout on life satisfaction among students of high and low empathy and burnout levels. Students with high levels of empathy and low levels of burnout were most satisfied with life. Medical institutions and related authorities need to find effective measures to enhance students' empathy levels and reduce burnout to improve their life satisfaction.

Downregulated PITX1 Modulated by MiR-19a-3p Promotes Cell Malignancy and Predicts a Poor Prognosis of Gastric Cancer by Affecting Transcriptionally Activated PDCD5.

BACKGROUND/AIMS: PITX1 has been identified as a potential tumor-suppressor gene in several malignant tumors. The molecular mechanism underlying PITX1, particularly its function as a transcription factor regulating gene expression during tumorigenesis, is still poorly understood. METHODS: The expression level and location of PITX1 were determined by quantitative reverse transcription PCR (qRT-PCR) and immunohistochemical staining in gastric cancer (GC). The effect of PITX1 on the GC cell proliferation and tumorigenesis was analyzed in vitro and in vivo. To explore how PITX1 suppresses cell proliferation, we used PITX1-ChIP-sequencing to measure genome-wide binding sites of PITX1 and assessed global function associations based on its putative target genes. ChIP-PCR, electrophoretic mobility shift assay, and promoter reporter assays examined whether PITX1 bound to PDCD5 and regulated its expression. The function of PDCD5 in GC cell apoptosis was further examined in vitro and in vivo. The relationship between the PITX1 protein level and GC patient prognosis was evaluated by the Kaplan-Meier estimator. Meanwhile, the expression level of miR-19a-3p, which is related to PITX1, was also detected by luciferase reporter assay, qRT-PCR, and western blotting. RESULTS: The expression level of PITX1 was decreased in GC tissues and cell lines. Elevated PITX1 expression significantly suppressed the cell proliferation of GC cells and tumorigenesis in vitro and in vivo. PITX1 knockdown blocked its inhibition of GC cell proliferation. PITX1 bound to whole genome-wide sites, with these targets enriched on genes with functions mainly related to cell growth and apoptosis. PITX1 bound to PDCD5, an apoptosis-related gene, during tumorigenesis, and cis-regulated PDCD5 expression. Increased PDCD5 expression in GC cells not only induced GC cell apoptosis, but also suppressed GC cell growth in vitro and in vivo. Moreover, PITX1 expression was regulated by miR-19a-3p. More importantly, a decreased level of PITX1 protein was correlated with poor GC patient prognosis. CONCLUSION: Decreased expression of PITX1 predicts shorter overall survival in GC patients. As a transcriptional activator, PITX1 regulates apoptosis-related genes, including PDCD5, during gastric carcinogenesis. These data indicate PDCD5 to be a novel and feasible therapeutic target for GC.

Validation of Quality of Life Instruments for Cancer Patients - Colorectal Cancer (QLICP-CR) in patients with colorectal cancer in Northeast China.

BACKGROUND: Measuring quality of life is important for cancer patients, but there are regional differences in age-standardized colorectal cancer incidence and mortality rates which may affect measurement. This study aimed to evaluate the reliability, validity and responsiveness of Quality of Life Instruments for Cancer Patients - Colorectal Cancer (QLICP-CR) in colorectal cancer patients in Northeast China, and assess its usefulness for evaluation of quality of life in these patients. METHODS: From November 2016 to January 2017, 152 patients with colorectal cancer from Liaoning Cancer Hospital & Institute were surveyed three times using QLICP-CR and the Functional Assessment of Cancer Therapy - Colorectal (FACT-C) to measure their quality of life (on admission, 2-3 days later and at discharge). Reliability was evaluated by internal consistency and test-retest reliability. Validity was examined by item-domain correlation, criterion-related validity and factor construct validity analysis. Responsiveness was assessed using paired Student's t tests and calculating standardized response mean. RESULTS: Cronbach's α coefficient for QLICP-CR ranged from 0.62 to 0.93. Pearson correlation and intra-class correlation coefficients for QLICP-GM, the five domains and the total scale of QLICP-CR ranged from 0.74 to 0.91 and 0.74 to 0.90. The item-domain correlation analysis showed good convergent validity and discriminant validity. Correlation analysis of domain scores between FACT-C and QLICP-CR showed good criterion-related validity. Exploratory factor analysis revealed that nine and three principal components were extracted from items in the two modules of QLICP-CR, and the contribution rate of cumulative variance was 70.21 and 72.26%. There were significant differences in quality of life between the first and the third measurements, with standardized response mean values ranging from 0.30 to 0.81. CONCLUSIONS: The QLICP-CR was a reliable, valid and sensitive instrument to measure quality of life in colorectal cancer patients in Northeast China.

Study on the cost attributable to central venous catheter-related bloodstream infection and its influencing factors in a tertiary hospital in China.

BACKGROUND: Central venous catheters (CVC) have been widely used for patients with severe conditions. However, they increase the risk of catheter-related bloodstream infection (CRBSI), which is associated with high economic burden. Until now, no study has focused on the cost attributable to CRBSI in China, and data on its economic burden are unavailable. The aim of this study was to assess the cost attributable to CRBSI and its influencing factors. METHODS: A retrospective matched case-control study and multivariate analysis were conducted in a tertiary hospital, with 94 patients (age ≥ 18 years old) from January 2011 to November 2015. Patients with CRBSI were matched to those without CRBSI by age, principal diagnosis, and history of surgery. The difference in cost between the case group and control group during the hospitalization was calculated as the cost attributable to CRBSI, which included the total cost and five specific cost categories: drug, diagnostic imaging, laboratory testing, health care technical services, and medical material. The relation between the total cost attributable to CRBSI and its influencing factors such as demographic characteristics, diagnosis and treatment, and pathogenic microorganism, was analysed with a general linear model (GLM). RESULTS: The total cost attributable to CRBSI was $3528.6, and the costs of specific categories including drugs, diagnostic imaging, laboratory testing, health care technical services, and medical material, were $2556.4, $112.1, $321.7, $268.7, $276.5, respectively. GLM analysis indicated that the total cost was associated with the intensive care unit (ICU), pathogenic microorganism, age, and catheter number, according to the sequence of standardized estimate (ß). ICU contributed the most to the model R-square. CONCLUSION: Central venous catheter-related bloodstream infection represents a great economic burden for patients. More attentions should be paid to further prevent and control this infection in China.

Cost-effectiveness of first-line immunotherapy for advanced non-small cell lung cancer with different PD-L1 expression levels: A comprehensive overview.

BACKGROUND: Immunotherapies can substantially improve treatment efficacy, despite their high cost. A comprehensive overview of the cost-effectiveness analysis (CEA) of immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer based on different tumor proportion scores (TPSs) was conducted. METHODS: PubMed, Embase, Cochrane Central Register of Controlled Trials, Health Technology Assessment Database, and NHS Economic Evaluation databases were searched from their inception until August 24, 2022. Data relevant to the CEA results were recorded, and quality assessments conducted based on the Quality of Health Economic Studies (QHES) process. FINDINGS: Fifty-one original studies from seven countries were included. The mean QHES score was 77.0 (range: 53-95). Twenty-seven studies were classified as high-quality, and the rest as fair quality. Pembrolizumab, nivolumab, ipilimumab, atezolizumab, camrelizumab, cemiplimab, sintilimab, tislelizumab, and durvalumab were identified using three TPS categories. While nivolumab plus ipilimumab and pembrolizumab plus chemotherapy were unlikely to be cost-effective in China, the results for the US were uncertain. Atezolizumab combinations were not cost-effective in China or the US, and tislelizumab and sintilimab were cost-effective in China. For TPSs ≥ 50%, the pembrolizumab monotherapy could be cost-effective in some developed countries. Cemiplimab was more cost-effective than chemotherapy, pembrolizumab, and atezolizumab in the US. For TPSs ≥ 1%, the cost-effectiveness of pembrolizumab was controversial due to the different willingness-to-pay thresholds. CONCLUSIONS: None of the atezolizumab combination regimens were found to be cost-effective in any perspective of evaluations. Camrelizumab, tislelizumab, and sintilimab have lower ICERs compared to atezolizumab, pembrolizumab, and nivolumab in China. Cemiplimab may be a more affordable alternative to pembrolizumab or atezolizumab. However, it remains unclear which ICIs are the best choices for each country. Future CEAs are required to select comprehensive regimens alongside randomized trials and real-world studies to help verify the economics of ICIs in specific decision-making settings.