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Background: On the basis of immunohistochemistry PD-L1 testing results, patients with advanced non-small cell lung cancer (NSCLC) are treated differently. Theoretically, patients with high PD-L1 expression (50% or 1%) should receive PD-1 monotherapy for fewer adverse reactions and cost savings from avoiding chemotherapy; however, there is controversy surrounding the cut-off criteria (1% or 50%) for immunohistochemistry testing and threshold for PD-1 monotherapy. Objective: This study aims to predict the effectiveness and cost-effectiveness of different immunotherapy strategies for patients with NSCLC in China from the healthcare system perspective. Patients and Methods: A microsimulation model was developed to evaluate the effectiveness and cost-effectiveness of three treatment strategies: PD-L1 testing (1%) (PD-1 monotherapy for those with PD-L1 expression at 1% threshold, and combination with chemotherapy for others with immunohistochemistry testing), PD-L1 testing (50%) (PD-1 monotherapy for those with PD-L1 expression at 50% threshold, and combination with chemotherapy for others with immunohistochemistry testing), and No PD-L1 testing (PD-1 combined with chemotherapy without immunohistochemistry testing). The model assumed 1000 patients per strategy, with each patient entering a unique clinical path prior to receiving treatment on the basis of PD-L1 test results. Clinical inputs were derived from clinical trials. Cost and utility parameters were obtained from the database and literature. One-way probabilistic sensitivity analyses (PSA) and six scenario analyses were used to test the model's robustness. Results: The study revealed a hierarchy of survival benefits across three strategies, with No PD-L1 testing demonstrating the most survival advantage, followed by PD-L1 testing (50%), and finally, PD-L1 testing (1%). The comparative analysis demonstrated that No PD-L1 testing significantly enhanced overall survival (OS) (HR 0.85, 95% CI 0.78–0.93), progression-free survival (HR 0.82, 95% CI 0.75–0.90), and progression-free2 survival (PFS2) (HR 0.91, 95% CI 0.83–0.99) when juxtaposed against PD-L1 testing (1%). However, these improvements were not as pronounced when compared with PD-L1 testing (50%), particularly in relation to PFS, PFS2, and OS. The cost-effectiveness analysis further unveiled incremental cost-utility ratios (ICUR), with No PD-L1 testing versus PD-L1 testing (50%) at $34,003 per quality-adjusted life year (QALY) and No PD-L1 testing versus PD-L1 testing (1%) at $34,804 per QALY. In parallel, the ICUR for PD-L1 testing (50%) versus PD-L1 testing (1%) stood at $35,713 per QALY. Remarkably, the PSA result under a willingness-to-pay (WTP) threshold of $10,144 per QALY, with a 100% probability, demonstrated PD-L1 testing (1%) as the most cost-effective option. Conclusions: The survival benefits of PD-1 monotherapy for high expression with PD-L1 immunohistochemistry testing are inferior to those of PD-1 combined with chemotherapy without testing, but it is found to be more cost-effective at the WTP thresholds in China and holds great potential in increasing affordability and reducing the economic burden. [ABSTRACT FROM AUTHOR]

On the Qinghai-Tibet Plateau, the restoration of natural grasslands is an urgent task, but finding the appropriate green restoration approach still faces many challenges. In this study, experimental plots were set up in a degraded alpine meadow with different fertilization treatments, i.e., chemical fertilizer (F), microbial fertilizer (M) (i.e., Rhizobium indicum strain JKLM 13E), and unfertilized (CK). Grass yields, soil properties, and the rhizospheric and bulk soil microbial communities (including both prokaryotes and eukaryotes) were measured to evaluate grassland productivity and soil sustainability. Both microbial and chemical fertilizers could significantly increase grassland biomass, as well as the biotic interactions of the inorganic nitrogen-related prokaryotic communities. We evaluated the biomass and productivity of the aboveground vegetation in response to the fertilization treatments. Our results demonstrated that both chemical and microbial fertilizers significantly increased the yield of grassland vegetation, with the effect of chemical fertilizer treatment being the most prominent (P <0.05). Moreover, chemical fertilizer mainly increased the concentration of NO3--N by reshaping the bulk soil microbial community, while microbial fertilizer mainly increased the concentration of NH4+-N by reshaping the rhizospheric microbial community. Both the chemical and microbial fertilizers could significantly increase the predation of Cercozoa to the inorganic nitrogen-related prokaryotic community, thus improving the soil resistance to pathogenic bacteria. In conclusion, our results suggest that microbial fertilizer treatment shows potential as an alternative or complementary approach to chemical fertilizer, potentially reducing the environmental impact associated with chemical fertilizers. While the chemical fertilizer treatment demonstrated higher biomass production in our experiment, further investigations combining the two types of fertilization may provide insights into the synergistic effects and potential for optimizing grassland restoration strategies. [ABSTRACT FROM AUTHOR]

While several studies have demonstrated the negative impacts of environmental pollution on population health, in general, few studies have examined the potential differential effects on the physical health of middle-aged and older populations, i.e., 45 years and older. Given the twin concerns of environmental pollution and population aging in China, this article employed a fixed effects model to infer the impact of environmental pollution on public health with a particular focus on middle-aged and older adults. The analyses were based on data from the 2011 to 2018 waves of the CHARLS and pollutant data from prefecture-level cities. The results showed that both the level and intensity of environmental pollution significantly increased the risk of chronic diseases and negatively impacted the physical health of middle-aged and older adults. Environmental pollution had its greatest negative effect on the physical health of the elderly, urban residents, residents of the Eastern region, and those with lower incomes than their counterparts. We further found that the potential channels of health effect were through reduced physical exercise and sleep duration and an increase in depressive symptoms, and the pollution prevention actions alleviated the health deterioration of environmental pollution for the middle-aged and the elderly. It is imperative for the government to urgently reinforce policy enforcement to decrease air and water pollution and enhance the ability to circumvent pollution for the lower socioeconomic groups. [ABSTRACT FROM AUTHOR]

Developing a mechanistic insight into the specific brain processes that underpin improvement in negative symptoms can help us design novel chemical and physical treatments against these unrelenting symptoms. The aim of the present study is to explore the longitudinal changes in the brain’s regional functional efficiency that accompany improvement in negative symptoms seen in first-episode patients with schizophrenia when treated with antipsychotic for 1 year. Forty-seven first-episode patients with schizophrenia were scanned at a drug-naive baseline state and followed up for 1 year to identify negative symptom responders (Rn) and non-responders (NRn). Fractional amplitude of low-frequency fluctuations (fALFF) and Granger analysis of effective connectivity (EC) were used to examine the different patterns of regional function and connectivity between Rn and NRn during the 1 year follow-up. Increase of fALFF in the left superior temporal gyrus (STG) and increase of EC from the left STG to the dorsolateral prefrontal cortex (DLPFC) was found in Rn compared to NRn. We further validated that the identified changes in fALFF/EC of STG occur specifically in relation to negative symptoms only (i.e., not pseudo-specific in relation to positive, extrapyramidal or depressive symptoms), and occur irrespective of arbitrary clinical categorization of treatment response. An increase in fALFF in the precuneus and the inferior parietal lobule, and a decrease in EC from the left STG to the occipital cortex, were also found at the 1 year follow-up irrespective of improvement in negative symptoms. Interventions that improve the functional efficiency of left STG and its prefrontal connectivity may show efficacy in alleviating negative symptoms in first-episode schizophrenia. [ABSTRACT FROM AUTHOR]

Serotonin plays an important role in mood regulation, but the involvement of serotonin pathway genes in the development of bipolar I disorder (BP-I), a mood disorder, is not clear. We selected 21 singlenucleotide polymorphisms (SNPs) within the HTR2A gene, 8 within the SLC6A4 gene and 23 within the TPH2 gene for genotyping using the GoldenGate genotyping assay. A total of 375 patients with BP-I and 475 normal controls were recruited. Two out of 21 SNPs (rs1475196 and rs9567747) in the HTR2A gene and 1/23 SNPs (rs17110566) in the TPH2 gene were significantly associated with BP-I, both genotype-wise and allele-wise. Furthermore, a specific haplotype in the HTR2A gene showed a significant association with BP-I. Our results indicate that the HTR2A and TPH2 genes in the serotonin pathway play important roles in susceptibility to BP-I. [ABSTRACT FROM AUTHOR]

Soil carbon sequestration is a climate engineering process that could significantly reduce global warming, yet actual estimates of soil organic carbon sequestration in China’s croplands are probably underestimated. Here we estimated soil organic carbon sequestration across China’s croplands from 1980 to 2018 using four different methods. We found that the average sequestration rate in China’s croplands is 298.5 kg ha−1. We present management strategies that could increase the mean soil organic carbon stock by 58.2 Mg ha−1. Insights into the potential for region-specific strategies to enhance soil carbon sequestration are given. [ABSTRACT FROM AUTHOR]