Tislelizumab plus neoadjuvant chemotherapy and concurrent chemoradiotherapy versus neoadjuvant chemotherapy and concurrent chemoradiotherapy for locally advanced nasopharyngeal carcinoma: A retrospective study.

BACKGROUND: The efficacy of immunotherapy plus neoadjuvant chemotherapy and concurrent chemoradiotherapy (CCRT) for locally advanced nasopharyngeal carcinoma (LA-NPC) has not been reported. This study retrospectively compared the efficacy of tislelizumab plus neoadjuvant chemotherapy and CCRT with neoadjuvant chemotherapy followed by CCRT. METHODS: Ninety patients with stages III-IVa NPC were identified between January 2020 and March 2021 at the Affiliate Hospital of Guangdong Medical University. Forty-three patients in the observation group (OG) received tislelizumab plus nano albumin-paclitaxel and cisplatin (nab-TP) regimen, followed by CCRT, while forty-seven patients in the control group (CG) received nab-TP regimen followed by CCRT. RESULTS: The complete response rate after neoadjuvant therapy was significantly higher in the OG compared to the CG (37.2% vs. 12.8 %). The objective response rates were 88.4 % in the OG and 70.2 % in the CG. The 3-year progression-free survival (PFS) rates for OG and CG patients were 93.0 % and 78.7 %, respectively (P = 0.04, HR = 0.31). The overall survival (OS) rates for the OG and the CG were 95.3 % and 87.2 %, respectively (P = 0.15, HR = 0.36). Locoregional relapse-free survival (LRFS) rates were 90.7 % for the OG and 72.3 % for the CG (P = 0.04, HR = 0.38), and distant metastasis-free survival (DMFS) rates were 95.3 % for the OG, and 80.9 % for the CG (P = 0.04, HR = 0.30). For PD-L1 high-expression and low-expression rates, the 3-year PFS rates were 89.2 % and 85.7 % (P = 0.77, HR = 1.21), and the OS rates were 90.2 % and 89.2 % (P = 0.65, HR = 1.36), respectively. CONCLUSION: Tislelizumab combined with neoadjuvant chemotherapy and CCRT showed encouraging therapeutic effects and good tolerability in patients with LA-NPC compared to the standard treatment.

Mitochondrial quality control in human health and disease.

Mitochondria, the most crucial energy-generating organelles in eukaryotic cells, play a pivotal role in regulating energy metabolism. However, their significance extends beyond this, as they are also indispensable in vital life processes such as cell proliferation, differentiation, immune responses, and redox balance. In response to various physiological signals or external stimuli, a sophisticated mitochondrial quality control (MQC) mechanism has evolved, encompassing key processes like mitochondrial biogenesis, mitochondrial dynamics, and mitophagy, which have garnered increasing attention from researchers to unveil their specific molecular mechanisms. In this review, we present a comprehensive summary of the primary mechanisms and functions of key regulators involved in major components of MQC. Furthermore, the critical physiological functions regulated by MQC and its diverse roles in the progression of various systemic diseases have been described in detail. We also discuss agonists or antagonists targeting MQC, aiming to explore potential therapeutic and research prospects by enhancing MQC to stabilize mitochondrial function.

[Health Risk Assessment of Heavy Metals in Soils of a City in Guangdong Province Based on Source Oriented and Monte Carlo Models].

Taking a city in Guangdong Province as the research area, the concentration and spatial distribution characteristics of heavy metals in the surface soil were studied to clarify the situation of soil heavy metal pollution and priority control factors, providing basic data for the prevention and control of soil heavy metal pollution in the city. The content characteristics of heavy metals in 221 soil samples in the city were analyzed, and the potential health risk assessment and source analysis were carried out through the Monte Carlo model, the potential health risk assessment (HRA) model, and the PMF receptor model. It was found that heavy metals ω(As), ω(Hg), ω(Cd), ω(Pb), ω(Cr), ω(Cu), ω(Ni), and ω(Zn) in the soil of the city were 18.16, 0.43, 1.46, 68.57, 98.34, 64.19, 26.53, and 257.32 mg·kg-1, respectively, with a moderate to high degree of variation. Except for Ni concentration, the soil concentrations of other heavy metal elements exceeded the background values of soil in Guangdong Province to a certain extent, and the concentrations of Cd and Zn exceeded the national secondary standards, resulting in severe heavy metal pollution; the main sources of heavy metals were industrial sources, and natural parent materials, lead battery manufacturing, transportation, artificial cultivation, and pesticide and fertilizer inputs also had an undeniable impact on the accumulation of heavy metals in the soil. Heavy metals in the soil had a certain degree of tolerable carcinogenic health risk for both children and adults, whereas non-carcinogenic risks could be ignored. The potential health risk of children was greater than that of adults, and the main exposure route was through oral intake. The input sources of pesticides and fertilizers and As should be the main controlling factors for the health risks of heavy metals in the city's soil, followed by mixed sources and Cr. There were differences in the spatial distribution characteristics and relative pollution levels of heavy metals, and it is necessary to deepen zoning monitoring and control, strengthen soil pollution prevention and control, and reduce human input of heavy metals in soil.

[Pollution Characteristics and Risk Assessment of Polycyclic Aromatic Hydrocarbons in Soils of Guangzhou].

In order to comprehensively study the pollution characteristics of polycyclic aromatic hydrocarbons （PAHs） in soils of Guangzhou， 222 topsoil samples were collected and analyzed. The ecological risk of soil PAHs pollution was evaluated using the effect interval low/median method （ERL/ERM） and the （BaP） toxicity equivalent method， and the health risk of soil PAHs pollution was evaluated using the lifelong cancer risk increment model. The source of PAHs was analyzed using the characteristic compound ratio method and PMF model. The results indicated that： the content of surface soil （∑16PAHs） in Guangzhou was 38-11 115 µg·kg-1， with an average of 526 µg·kg-1， and 16 types of polycyclic aromatic hydrocarbon monomers showed strong variation. There was a certain degree of ecological risk of PAHs in Guangzhou， and there was already a significant ecological risk of PAHs pollution in individual sampling points， which were generally in a state of mild pollution. Based on the results of the health risk assessment， the contribution rates of total cancer risk in both adults and children were presented as follows： skin contact > ingestion of soil > respiratory intake. The health risk of children was greater than that of adults， and the overall health risk was within an acceptable range. Source analysis showed that the main sources of soil PAHs in Guangzhou were coal （37.1%）； diesel （32%）； coking （17.3%）； and mixed sources of traffic emissions， biomass combustion， and petrochemical product volatilization （13.6%）. The overall source of soil PAHs belonged to mixed sources. The research results have enriched our understanding of the pollution status of PAHs in the surface soil of Guangzhou and are helpful in promoting soil pollution prevention and control actions.

The role of fatty acid metabolism in acute lung injury: a special focus on immunometabolism.

Reputable evidence from multiple studies suggests that excessive and uncontrolled inflammation plays an indispensable role in mediating, amplifying, and protracting acute lung injury (ALI). Traditionally, immunity and energy metabolism are regarded as separate functions regulated by distinct mechanisms, but recently, more and more evidence show that immunity and energy metabolism exhibit a strong interaction which has given rise to an emerging field of immunometabolism. Mammalian lungs are organs with active fatty acid metabolism, however, during ALI, inflammation and oxidative stress lead to a series metabolic reprogramming such as impaired fatty acid oxidation, increased expression of proteins involved in fatty acid uptake and transport, enhanced synthesis of fatty acids, and accumulation of lipid droplets. In addition, obesity represents a significant risk factor for ALI/ARDS. Thus, we have further elucidated the mechanisms of obesity exacerbating ALI from the perspective of fatty acid metabolism. To sum up, this paper presents a systematical review of the relationship between extensive fatty acid metabolic pathways and acute lung injury and summarizes recent advances in understanding the involvement of fatty acid metabolism-related pathways in ALI. We hold an optimistic believe that targeting fatty acid metabolism pathway is a promising lung protection strategy, but the specific regulatory mechanisms are way too complex, necessitating further extensive and in-depth investigations in future studies.