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Immune checkpoint inhibitors (ICI) have emerged as a promising therapeutic option for melanoma, which demonstrating improved clinical outcomes in melanoma patients regardless of specific genetic mutations. However, the identification of reliable biomarkers for predicting immunotherapy response and prognosis remains a challenge. In this study, we performed genetic profiling of the melanoma patients with different subtypes and evaluated the efficacy of ICI treatment. A total of 221 melanoma patients were included in our cohort, consisting primarily of acral lentiginous melanoma (ALM), cutaneous malignant melanoma (CMM), and mucosal malignant melanoma (MMM). Genetic analysis revealed BRAF mutations was predominant in CMM and NRAS mutations was prevalent in ALM. Copy number variants (CNVs) and structural variants (SV) were also detected, with CCND1 and CDK4 being the most affected genes in CNV and BRAF, ALK and RAF1 being the druggable targets in SV. Furthermore, NRAS mutations were associated with a poor prognosis in ALM, while TERT mutations were linked to unfavorable outcomes in CMM after receiving PD-1 therapy. Additionally, ALK expression exhibited improved outcomes in both ALM and CMM subtypes. Our study provides a comprehensive genomic and pathological profiling of Chinese melanoma patients, shedding light on the molecular landscape of the disease. Furthermore, numbers of gene mutations and ALK expression were identified as prognostic indicators. These findings contribute to the understanding of melanoma genetics in the Chinese population and have implications for personalized treatment approaches. [ABSTRACT FROM AUTHOR]

Background/Aim: Depression is associated with metabolic disorders, including non-alcoholic fatty liver disease (NAFLD). However, the mechanisms underlying the interaction between them are still poorly known. Materials and Methods: In this study, mice on a choline deficiency, L-amino acid-defined, high-fat diet (CDAHFD) developing steatosis were challenged with chronic restraint stress (CRS), a protocol widely used to induce depression. The development of depression and steatosis was evaluated using histopathology analysis, ELISA, q-PCR and Western Blot. Results: The contribution of the activated HPA axis to hepatic steatosis progress was fully established, which was validated using a hepatocyte model. Histopathological and biochemical analysis indicated that steatosis was exacerbated by CRS challenge, and behavioral tests indicated that the mice developed depression. Among the screened endocrinal pathways, the hypothalamic-pituitary-adrenal (HPA) axis was significantly activated and the synergistic effect of CDAHFD and CRS in activating the HPA axis was observed. In the hypothalamus, expression of corticotropin-releasing hormone (CRH) was increased by 86% and the protein levels of hypothalamic CRH were upregulated by 25% to 33% by CRS treatment. Plasma CRH levels were elevated by 45-56% and plasma adrenocorticotropic hormone (ACTH) levels were elevated by 29-58% by CRS treatment. In the liver, target genes of the HPA axis were activated, accompanied by disruption of the lipid metabolism and progression of steatohepatitis. The lipid metabolism in the Hepa1-6 cell line treated with endogenous corticosterone (CORT) was in accordance with the aforementioned in vivo responses. Conclusion: Depression aggravated hepatic steatosis in CDAHFD-fed mice by activating the HPA axis. The risk of NAFLD development should be fully considered in depressive patients and improvement of psychotic disorders could be an etiological treatment strategy for them. [ABSTRACT FROM AUTHOR]

The Yinggehai Basin is situated at the junction of Indochina and the northern South China Sea (SCS). The origin of the Yinggehai Basin is generally believed to be controlled by the rotation of the Indochina block along the Red River shear zone (RRSZ), which was formed by the collision of India with Asia during the Oligocene. However, the Eocene structural mechanisms of this basin remain debatable. Some studies suggest that the Eocene reactivation of the palaeo‐suture zone (which serves as a precursor to the RRSZ) has influenced the region. In contrast, others propose that the NNW–SSE extension of the northern SCS caused by the subduction of the palaeo‐SCS towards Borneo in the Eocene has played a significant role. To address these controversies, our study takes into account these two crucial factors using physical analogue modelling. The experimental results, including slow sinistral strike‐slip along the palaeo‐suture zone and the adjacent NNW–SSE extension, successfully explain the observed fault pattern during the Eocene period. It is noteworthy that the former primarily controlled the Eocene structure in the northern region of the Yinggehai Basin, whereas the latter played a pivotal role in shaping the ENE–WSW Eocene structures on the eastern slope of the basin. The westward propagating faults of the Qiongdongnan basin are cut off by the Yinggehai Basin structures at later large‐scale rotation stage. The experiment indicates that the basin evolution exhibits diachronous characteristics, with subsidence in the south occurring later than in the north. Our modelling results provide valuable insights into the key controlling factors that shaped the evolution of the basin during each stage. Furthermore, our findings offer evidence of the interaction between two significant tectonic processes: Indochina extrusion and the opening of the SCS. [ABSTRACT FROM AUTHOR]

Background Fractional flow reserve is widely used in coronary disease management, with a threshold of 0.80. However, similar thresholds are unclear in functional assessment of intracranial atherosclerotic stenosis (ICAS). Objective To investigate the potential threshold values in functional assessment of ICAS by studying the relation between pressure-derived indexes and perfusion parameters derived from arterial spin labeling (ASL). Methods Patients were consecutively screened between June 2019 and December 2020. The translesional gradient indices were measured by pressure guidewire under resting-state conditions and recorded as mean distal/proximal pressure ratios (Pd/Pa) and translesional pressure difference (Pa-Pd). Preoperative and postoperative cerebral blood flow (CBF) bilaterally and the relative cerebral blood flow ratio (rCBF) were measured and recorded by ASL imaging. Patients were defined as having reversible hemodynamic insufficiency only if the preoperative rCBF was <0.9 and the postoperative rCBF≥0.9. Preoperative and postoperative Pd/Pa or Pa-Pd values of those patients were used to calculate the threshold. Results Twenty-five patients (19 men, 6 women) with a mean age of 56.7±9.4 years were analyzed. Seventeen patients (68%) had lesions at the M1 segment of the middle cerebral artery, eight patients (32%) had lesions in the intracranial internal carotid artery. In 14 of the 25 patients, the preoperative rCBF was <0.9 and the postoperative rCBF≥0.9. Cut-off values of Pd/ Pa=0.81 and Pa-Pd=8 mm Hg were suggested to be associated with hemodynamic insufficiency. Conclusions In a highly selected subgroup with ICAS, cut-off values of translesional pressure gradients (Pd/Pa=0.81 or Pa-Pd=8 mm Hg) were preliminarily established, which may facilitate clinical decision-making in the management of ICAS. [ABSTRACT FROM AUTHOR]