Single-arm study of camrelizumab plus apatinib for patients with advanced mucosal melanoma.

BACKGROUND: Previous studies have suggested the potential synergistic antitumor activity when combining immune checkpoint inhibitors with anti-angiogenic agents in various solid tumors. We aimed to assess the efficacy and safety of camrelizumab (a humanized programmed cell death-1 antibody) plus apatinib (a vascular endothelial growth factor receptor tyrosine kinase inhibitor) for patients with advanced mucosal melanoma (MM), and explore-related biomarkers. METHODS: We conducted a single-center, open-label, single-arm, phase II study. Patients with unresectable or recurrent/metastatic MM received camrelizumab and apatinib. The primary endpoint was the confirmed objective response rate (ORR). RESULTS: Between April 2019 and June 2022, 32 patients were enrolled, with 50.0% previously received systemic therapy. Among 28 patients with evaluable response, the confirmed ORR was 42.9%, the disease control rate was 82.1%, and the median progression-free survival (PFS) was 8.05 months. The confirmed ORR was 42.9% (6/14) in both treatment-naïve and previously treated patients. Notably, treatment-naïve patients had a median PFS of 11.89 months, and those with prior treatment had a median PFS of 6.47 months. Grade 3 treatment-related adverse events were transaminase elevation, rash, hyperbilirubinemia, proteinuria, hypertension, thrombocytopenia, hand-foot syndrome and diarrhea. No treatment-related deaths were observed. Higher tumor mutation burden (TMB), increased T-cell receptor (TCR) diversity, and altered receptor tyrosine kinase (RTK)/RAS pathway correlated with better tumor response. CONCLUSION: Camrelizumab plus apatinib provided promising antitumor activity with acceptable toxicity in patients with advanced MM. TMB, TCR diversity and RTK/RAS pathway genes were identified as potential predictive biomarkers and warrant further validation. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry, ChiCTR1900023277.

Correlation analysis between HLA-DQA1*0102/DQB1*0602 genotypes and narcolepsy patients in China.

Background and objective: At present, the etiology of narcolepsy is not fully understood, and it is generally believed to be an autoimmune reaction caused by interactions between environmental and genetic factors. Human leukocyte antigen (HLA) class II genes are strongly associated with this gene, especially HLA-DQB1*0602/DQA1*0102. In this study, we mainly analyzed the correlation between different genotypes of HLA-DQB1*0602/DQA1*0102 and clinical manifestations in Chinese patients with narcolepsy. Experimental method: Narcolepsy patients who were treated at the Department of Neurology, The First Affiliated Hospital of Shandong First Medical University from January 2021 to September 2023 were selected. General information, sleep monitoring data, cerebrospinal fluid (CSF) orexin levels, and human leukocyte antigen gene typing data were collected. The statistical analysis was performed using SPSS 26.0, and the graphs were drawn using GraphPad Prism 9.5. Main results: A total of 78 patients were included in this study. The DQA1 and DQB1 gene loci were detected in 54 patients, and only the DQB1 gene locus was detected in 24 narcoleptic patients. The most common allele at the HLA-DQB1 locus was *0602 (89.7%), and the most common genotype at this locus was *0602*0301 (19.2%), followed by *0602*0602 (17.9%). The most common phenotype of the HLA-DQA1 locus is *0102 (92.6%), and the most common genotype of this locus is *0102*0102 (27.8%), followed by *0102*0505 (14.8%). There were significant differences (p < 0.05) between HLA-DQB1*0602-positive and HLA-DQB1*0602-negative patients in terms of orexin-A levels, presence or absence of cataplexy, UNS, PSG sleep latency, REM sleep latency, N1 sleep percentage, oxygen depletion index, and average REM latency on the MSLT. The HLA-DQA1*0102-positive and HLA-DQA1*0102-negative patients showed significant differences (p < 0.05) in disease course, presence or absence of sudden onset, PSG REM sleep latency, N1 sleep percentage, and average REM latency on the MSLT. There were significant differences in the average REM latency of the MSLT between HLA-DQB1*0602/DQA1*0102 homozygous and heterozygous patients p < 0.05, and no differences were found in the baseline data, orexin-A levels, scale scores, or other sleep parameters. Conclusion: Different genotypes of HLA-DQA1*0102/DQB1*0602 are associated with symptoms of cataplexy in Chinese narcoleptic patients. Homozygous individuals have a shorter mean REM latency in the MSLT, greater genetic susceptibility, and relatively more severe sleepiness.

The mechanism of solid acid-catalyzed bamboo sawdust liquefaction under polyol systems.

Solid acid catalysts are widely used in the field of biomass catalytic conversion owing to their advantages of low environmental pollution, easy separation and reusability. Nevertheless, there are relatively few studies on the mechanism of solid acid liquefaction for biomass. In this study, the effect of acid strength and acid amount of various solid acids on the liquefaction efficiency has been investigated using waste bamboo sawdust generated from the pulp and paper industry as the raw material. In addition, the physicochemical changes of cellulose, hemicellulose and lignin during the reaction process of bamboo sawdust have been studied, and the liquefaction mechanism of bamboo sawdust under the action of various solid acids has been concluded. As a result, the liquefaction efficiency of bamboo sawdust under the polyol system of PEG400/propanetriol is mainly related to the acid strength of the solid acid, and the greater the acid strength of the solid acid, the better the catalytic effect on the bamboo sawdust, in which the residual amount of bamboo sawdust liquefaction catalyzed by the SPA catalyst is only 17.72%. Noteworthy, the most difficult component to liquefy is the crystallization of natural cellulose I into cellulose II during the reaction process, which is the primary obstacle to the complete liquefaction of bamboo sawdust by solid acid. Overall, these findings are valuable for the high value utilization of waste bamboo sawdust in the pulp and paper industry, as well as the application of solid acid catalytic technology for biomass.

Trauma plays an important role in acral melanoma: A retrospective study of 303 patients.

INTRODUCTION: Acral melanoma (AM) is the most common subtype of malignant melanoma in China, with a very poor prognosis. Despite the frequent reporting of trauma events in AM cases, the precise etiology of AM remains elusive. METHODS: A retrospective analysis was conducted on a cohort of 303 AM patients at Nanjing Drum Tower Hospital. The patients were categorized into four distinct groups based on different patterns of disease onset: trauma type (Type 1), pigmented nevus type (Type 2), pigmented nevi with trauma (Type 3), and pigmented nevi with natural ulceration (Type 4). Differences in clinicopathological features, genetic alterations, and tumor immune microenvironment (TIME) were analyzed. RESULTS: Traumatic events accounted for a large proportion of AM cases. Among these categories, Type 1 patients displayed the least favorable pathological traits and an immunosuppressive TIME. Common copy number variations (CNVs) were observed in CCND1, RB1, FGF19, and IL7R, while CNVs in CDK4 and TERT occurred less frequently in patients with a history of trauma (Type 1 and Type 3). Type 2 patients exhibited the most favorable pathological characteristics and genetic profiles, and demonstrated the lowest incidence of CCDN1 and RB1 CNVs but had the highest CDK4 CNVs. In contrast, the pathological behavior of Type 3 and Type 4 patients was in between Type 1 and Type 2. And patients in Type 3 and Type 4 displayed a more favorable overall microenvironment. CONCLUSION: This study provides a clinical classification of Chinese AM based on diverse clinical onset characteristics and highlights the important role of trauma in AM. These findings may help to guide the diagnosis, treatment, and prognosis of AM patients. Further investigations are imperative to elucidate the underlying mechanisms governing the association between trauma and AM.

The value of circadian heart rate variability for the estimation of obstructive sleep apnea severity in adult males.

OBJECTIVES: Heart rate variability (HRV) is becoming more prevalent as a measurable parameter in wearable sleep-monitoring devices, which are simple and effective instruments for illness evaluation. Currently, most studies on investigating OSA severity and HRV have measured heart rates during wakefulness or sleep. Therefore, the objective of this study was to investigate the circadian rhythm of HRV in male patients with OSA and its value for the estimation of OSA severity using group-based trajectory modeling. METHODS: Patients with complaints of snoring were enrolled from the Sleep Center of Shandong Qianfoshan Hospital. Patients were divided into 3 groups according to apnea hypopnea index (AHI in events/h), as follows: (<15, 15≤AHI<30, and ≥30). HRV parameters were calculated using 24 h Holter monitoring, which included time-domain and frequency-domain indices. Circadian differences in the standard deviation of normal to normal (SDNN) were evaluated for OSA severity using analysis of variance, trajectory analysis, and multinomial logistic regression. RESULTS: A total of 228 patients were enrolled, 47 with mild OSA, 48 moderate, and 133 severe. Patients with severe OSA exhibited reduced triangular index and higher very low frequency than those in the other groups. Circadian HRV showed that nocturnal SDNN was considerably higher than daytime SDNN in patients with severe OSA. The difference among the OSA groups was significant at 23, 24, 2, and 3 o'clock sharp between the severe and moderate OSA groups (all P<0.05). The heterogeneity of circadian HRV trajectories in OSA was strongly associated with OSA severity, including sleep structure and hypoxia-related parameters. Among the low-to-low, low-to-high, high-to-low, and high-to-high groups, OSA severity in the low-to-high group was the most severe, especially compared with the low-to-low and high-to-low SDNN groups, respectively. CONCLUSIONS: Circadian HRV in patients with OSA emerged as low daytime and high nocturnal in SDNN, particularly in men with severe OSA. The heterogeneity of circadian HRV revealed that trajectories with low daytime and significantly high nighttime were more strongly associated with severe OSA. Thus, circadian HRV trajectories may be useful to identify the severity of OSA.