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Background and purpose: The prognosis of malignant melanoma (MM) in China and Asia is significantly worse than that of European and American populations, mainly because acral melanoma (AM) is inferior to cutaneous melanoma (CM) in terms of biological behavior, clinical features, prognosis, and efficacy of drugs (mainly immunotherapy). Certain changes have occurred in the last 5 years in the choice of surgical and drug-adjuvant treatment for MM. This study retrospectively analyzed the survival outcomes of Chinese CM and AM patients after surgical treatment in a single cancer center for the past five years. Methods:Data of melanoma patients undergoing surgical treatment were retrospectively collected from 2017 to 2021 in Fudan University Shanghai Cancer Center. The basic clinical characteristics, pathological features, lymph node tumor burden and survival information were carefully collected from medical document. Patients with mucosal subtype, unknown primary sites, or follow-up less than 6 months were excluded. Survival analysis and multivariable Cox regression analysis were performed to explore prognosis and associated risk factors. Results:Totally 585 patients were enrolled, including 397 AM and 188 CM patients. The median age was 59 (19-89) years, and 54% were female. AM and CM patients differed in gender, age, primary tumor location, gene mutation distribution and adjuvant therapy, but not in tumor burden associated factors including the Breslow thickness, ulceration and lymph node involvment. The median follow-up time was 24 months, and the median relapse-free survival (mRFS) was 36 months, with 1-year and 2-year RFS of 75.6% and 61.2%, respectively. However, there was no statistically significant difference in prognosis between the two subtypes. Primary ulceration (HR=2.265, 95% CI: 1.257-4.080), NRAS mutation (HR=1.816, 95% CI: 1.211-2.725) and advanced N stage (HR of N1, N2 and N3 versus N0 were 1.850, 4.085 and 4.191, respectively) were independent prognostic risk factors for RFS in AM; while the protective factors were female (HR=0.636, 95% CI: 0.433-0.933) and upper extremity primary lesions (HR=0.259, 95% CI: 0.105-0.639). Independent risk factors for RFS in CM included primary ulceration (HR=4.073, 95% CI: 1.718-9.654), and later N stage (HR=5.482, 95% CI: 2.385-12.601 for N3 stage). Conclusion: High tumor burden of primay lesion still deteriorates overall outcomes for both AM and CM, while harboring NRAS mutation might suggest even worse outcome for AM.

Background and purpose: For cutaneous and acral malignant melanoma, sentinel lymph node biopsy (SLNB) is an effective tool to evaluate the situation of regional lymph node metastasis and to determine the pathological stage. As an important part of the standard procedure for surgical diagnosis and treatment, SLNB has been recommended in major guidelines and already has a ten-year clinical application. Since the introduction of targeted therapy and immune therapy for malignant melanoma in 2017, the prognosis of patients has been significantly improved. This study aimed to collect the clinical data of Chinese malignant melanoma cases in recent five years so as to discover, in the era of new drug treatment, the significance of sentinel lymph node (SLN) status in clinical application and its influence on survival outcome. Methods: Data of 381 patients with histologically diagnosed malignant melanoma were retrospectively collected from 2017 to 2021 in Fudan University Shanghai Cancer Center. SLNB was performed with wide resection of the primary lesion for each case, and follow-ups of at least 6 months were taken afterwards. Lymphoscintigraphy or methylene blue dye was applied for identification of SLN. Results: A total of 381 patients were included. The mean Breslow thickness was 3.10 mm, among the 381 patients, 69.8% with acral lesion, 59.7% with ulceration, 34.6% with positive SLN, and the median relapse-free survival (RFS) was 17 months. Patient’s survival was significantly influenced by SLN status. Patients with more than 2 biopsied SLN had significantly better RFS in subgroups of N1a stage and T4 stage. There was no significant difference in RFS between patients who received complete lymph node dissection (CLND) and those who did no, and the latter even showed better RFS in subgroups of SLN biopsied number >2 and SLN micrometastasis diameter

Recent studies have shown that by using channel-correlation and cosparsity in a centralized framework, the accuracy of reconstructing multichannel EEG signals can be improved. A single-channel electroencephalogram (EEG) signal is intrinsically non-sparse in both the converted and raw time domains, which presents a number of important issues. However, this is ignored by contemporary compressive sensing (CS) algorithms, resulting in less recovery quality than is ideal. To address these constraints, we provide a novel CS method that takes advantage of Nonlocal Low-Rank and Cosparse priors (NLRC). By utilizing low-rank approximations and block operations, our method aims to improve the CS recovery process and take advantage of channel correlations. The Alternating Direction Method of Multipliers (ADMM) are also used to efficiently solve the resulting non-convex optimization problem. The outcomes of the experiments unequivocally demonstrate that by using NLRC, the quality of signal reconstruction is significantly enhanced. [ABSTRACT FROM AUTHOR]

Introduction Persistent antigen stimulation causes [CD8.sup.+] T cells to become functionally exhausted, with upregulation of programmed death-1 (PD-1) and other inhibitory receptors, perturbed proliferation and cytokine secretion, impaired immune memory, [...], [CD8.sup.+] exhausted T cells ([T.sub.ex]) are heterogeneous. PD-1 inhibitors reinvigorate progenitor [T.sub.ex], which subsequently differentiate into irresponsive terminal [T.sub.ex]. The ability to maintain a capacity for durable proliferation of progenitor [T.sub.ex] is important, but the mechanism remains unclear. Here, we showed [CD8.sup.+] progenitor [T.sub.ex] pretreated with decitabine, a low-dose DNA demethylating agent, had enhanced proliferation and effector function against tumors after anti-PD-1 treatment in vitro. Treatment with decitabine plus anti-PD-1 promoted the activation and expansion of tumor-infiltrated [CD8.sup.+] progenitor T and efficiently suppressed tumor growth in multiple tumor models. Transcriptional and epigenetic profiling of tumor-infiltrated T cells demonstrated that the combination of decitabine plus anti-PD-1 markedly elevated the clonal expansion and cytolytic activity of progenitor [T.sub.ex] compared with anti-PD-1 monotherapy and restrained [CD8.sup.+] T cell terminal differentiation. Strikingly, decitabine plus anti-PD-1 sustained the expression and activity of the AP-1 transcription factor JunD, which was reduced following PD-1 blockade therapy. Downregulation of JunD repressed T cell proliferation, and activation of JNK/AP-1 signaling in [CD8.sup.+] T cells enhanced the antitumor capacity of PD-1 inhibitors. Together, epigenetic agents remodel [CD8.sup.+] progenitor [T.sub.ex] populations and improve responsiveness to anti-PD-1 therapy.

Esophageal cancer is one of the most lethal digestive system cancers, and its pathogenic factors have always been the focus of research. Recently, it has been found that microorganisms and their metabolites in the esophagus may also represent one of the pathogenic factors. Because of their continuity in anatomical structure, the oral cavity and esophagus have a certain correlation in terms of the composition of flora. In recent years, many scholars have studied the relationship between oral microorganisms and esophageal cancer to monitor changes in oral microorganisms as well as to diagnose and treat esophageal cancer more effectively. In this paper, the research status of oral microorganisms and esophageal cancer was reviewed. The Results of the literature review show that the diversity of bacteria in the esophagus is affected by oral flora in terms of the occurrence and development of esophageal cancer. Among these bacteria, the periodontal red complex, which includes Porphyromonas gingivalis, forsythia and Treponema dentata, as well as common oral microorganisms, such as Streptococcus viridis and Fusobacterium nucleatum, are all related to the occurrence and development of esophageal cancer to a certain extent. At present, there are few studies on the mechanism of microorganisms and esophageal cancer, but scholars have found that lipopolysaccharides and endotoxins, the products of Gram-negative bacteria in the esophagus, may participate in the innate immune response of the host, and the relevant mechanism of action needs further study in order to find new targets for monitoring and treatment.

Summary: Abiotic stresses have had a substantial impact on fruit crop output and quality. Plants have evolved an efficient immune system to combat abiotic stress, which employs reactive oxygen species (ROS) to activate the downstream defence response signals. Although an aquaporin protein encoded by PbPIP1;4 is identified from transcriptome analysis of Pyrus betulaefolia plants under drought treatments, little attention has been paid to the role of PIP and ROS in responding to abiotic stresses in pear plants. In this study, we discovered that overexpression of PbPIP1;4 in pear callus improved tolerance to oxidative and osmotic stresses by reconstructing redox homeostasis and ABA signal pathways. PbPIP1;4 overexpression enhanced the transport of H2O2 into pear and yeast cells. Overexpression of PbPIP1;4 in Arabidopsis plants mitigates the stress effects caused by adding ABA, including stomatal closure and reduction of seed germination and seedling growth. Overexpression of PbPIP1;4 in Arabidopsis plants decreases drought‐induced leaf withering. The PbPIP1;4 promoter could be bound and activated by TF PbHsfC1a. Overexpression of PbHsfC1a in Arabidopsis plants rescued the leaf from wilting under drought stress. PbHsfC1a could bind to and activate AtNCED4 and PbNCED4 promoters, but the activation could be inhibited by adding ABA. Besides, PbNCED expression was up‐regulated under H2O2 treatment but down‐regulated under ABA treatment. In conclusion, this study revealed that PbHsfC1a is a positive regulator of abiotic stress, by targeting PbPIP1;4 and PbNCED4 promoters and activating their expression to mediate redox homeostasis and ABA biosynthesis. It provides valuable information for breeding drought‐resistant pear cultivars through gene modification. [ABSTRACT FROM AUTHOR]

Dental pulp injury remains a clinical challenge with limited therapeutic approaches. In the present study, we sought to prove that dental pulp stromal cells (DPSCs) mitochondrial transfer could promote dental pulp injury repair and endoplasmic reticulum (ER)‐mitochondrial contacts have a significant regulatory effect on mitochondrial transfer. Healthy DPSCs were co‐cultured directly or indirectly with injured DPSCs in the first molar of 1–2 month SD rats or in vitro. Mitochondrial transfer was observed after 24 h of co‐culture using fluorescence microscopy and live cell workstation. After co‐culture for 1W, 8‐OhdG immunofluorescence, mitochondrial membrane potential and total oxidant status/total antioxidant status were used to detect the mitochondrial function of injured DPSCs before and after mitochondrial transfer. Subsequently, mitochondria‐ER co‐transfer was regulated by modulating mitochondria‐ER binding in healthy DPSCs, and the results of GRP78 and CHOP in DPSCs, and PDI immunofluorescence and haematoxylin and eosin staining of pulp tissue were analysed to clarify the effects of modulating mitochondria‐ER co‐transfer on endoplasmic reticulum stress (ERS), and on pulp injury repair. Fluorescence microscopy and live cell workstation results showed significant mitochondrial transfer between DPSCs. Meanwhile, mitochondrial transfer significantly restored mitochondrial function in injured DPSCs. By modulating mitochondrial‐ER binding, the efficiency of mitochondrial transfer between DPSCs was significantly affected and had an impact on ERS in injured cells. Mitochondrial transfer of DPSCs significantly promotes pulpal injury repair and functional recovery of damaged DPSCs, and mitochondrial transfer of DPSCs is regulated by mitochondria‐ER binding. [ABSTRACT FROM AUTHOR]

Purpose: Metastatic ocular and orbital melanomas are extremely rare. The clinical characteristics and standard treatments for these patients are not fully established. Materials and Methods: We retrospectively analyzed patients with metastatic ocular and orbital melanoma from Fudan University Shanghai Cancer Center and Eye & ENT Hospital of Fudan University between January 2012 and May 2022. Results: Overall, 51 patients with metastatic ocular and orbital melanoma were included. The most common primary sites were uvea (73%), followed by conjunctiva (22%), lacrimal sac (4%), and orbit (2%). Patients with uveal melanoma (UM) had a significantly younger age (48 vs. 68 years, p < 0.001), higher incidence of liver metastases (89% vs. 9%, p<0.001), a lower incidence of lymph nodes metastases (16% vs. 46%, p = 0.043) and a lower incidence of BRAF mutation (0% vs. 55%, p<0.001) compared with patients with conjunctival melanoma (CM). The overall response rate of the first‐line treatment was 18%. Three of the four patients with BRAF‐mutated CM responded to dabrafenib and trametinib treatment. The median progression‐free survival (PFS) and overall survival (OS) of first‐line treatment were 5.1 and 11.9 months, respectively. Among patients with liver metastases, liver‐directed treatment was correlated with better patient PFS (p < 0.001) and OS (p < 0.001) after adjusting for number of metastatic sites and primary sites. Conclusion: CM and UM have different characteristics. Patient with CM had a high incidence of BRAF mutation, and the treatment of BRAF and MEK inhibitors conferred clinical benefit. Liver directed therapies had a potential benefit in disease control in patients with liver metastases. [ABSTRACT FROM AUTHOR]

Background: Melanoma frequently harbors BRAF, NRAS, or KIT mutations which influence both tumor development and treatment strategies. For example, it is still controversial whether adjuvant anti‐PD‐1 monotherapy or BRAF/MEK inhibitors may better improve the survival for resected BRAF‐mutant melanoma. Furthermore, outcomes for melanoma with NRAS and KIT mutation receiving adjuvant immunotherapy remain unclear. Methods: One hundred seventy‐four stage III melanoma patients who underwent radical surgery in Fudan University Shanghai Cancer Center (FUSCC) during January 2017 to December 2021 were included in this real‐world study. Patients were followed up until death or May 30th, 2022. Pearson's chi‐squared test or Fisher's exact test was performed for univariable analysis of the different category groups. Log‐rank analysis was used to identify the prognostic factors for disease‐free survival (DFS). Results: There were 41 (23.6%) patients with BRAF mutation, 31 (17.8%) with NRAS mutation, 17 (9.8%) with KIT mutation, and 85 (48.9%) wild‐type patients without either genomic alteration of those three genes. Most (n = 118, 67.8%) of them were acral melanoma, while 45 (25.9%) were cutaneous subtype, and 11 were (6.3%) primary unknown. Among them, 115 (66.1%) patients received pembrolizumab or toripalimab monotherapy as adjuvant therapy; 22 (12.6%) patients received high‐dose interferon (IFN), and 37 (21.3%) patients were just for observation. There was no statistical difference in clinicopathologic factors between anti‐PD‐1 group and IFN/OBS group. Of all the enrolled patients, anti‐PD‐1 group had a better DFS than IFN/OBS group (p = 0.039). In anti‐PD‐1 group, patients with BRAF or NRAS mutations had poorer DFS than wild‐type group. No survival difference was found among patients harboring different gene mutations in IFN/OBS group. In wild‐type patients, anti‐PD‐1 group had a better DFS than IFN/OBS group (p = 0.003), while no survival benefits were found for patients with BRAF, NRAS, or KIT mutations. Conclusion: Although anti‐PD‐1 adjuvant therapy provides a better DFS in the general population and in wild‐type patients, patients with BRAF, KIT or, especially, NRAS mutation may not benefit further from immunotherapy than conventional IFN treatment or observation. [ABSTRACT FROM AUTHOR]

The use of adjuvant therapy has provided survival benefits in patients with advanced melanoma. This study aimed to explore the recurrence and prognosis of the PD-1 inhibitor, conventional interferon (IFN), or observation (OBS) on resected stage III acral and cutaneous melanoma patients through a retrospective analysis. Patients with resected stage III melanoma at Fudan University Shanghai Cancer Center from 2017 to 2021 were enrolled with all of their clinicopathologic characteristics collected. They were divided into three groups: PD-1 inhibitor, IFN, and OBS. Survival analyses were performed to indicate the significance of different adjuvant therapies. A total of 199 patients were enrolled (PD-1 n = 126; IFN n = 31; and OBS n = 42), with their median follow-up times being 21 months, 24 months, and 49 months, respectively. The PD-1 inhibitor significantly improved relapse-free survival (p = 0.027) and overall survival (p = 0.033) compared with conventional treatment (IFN+OBS). The superiority of the PD-1 inhibitor was witnessed in stage IIIC/D (p = 0.000) acral (p = 0.05) melanoma patients with ulceration (p = 0.011) or lymph node macrometastasis (p = 0.010). The PD-1 inhibitor significantly reduced local recurrence and systemic metastasis compared with conventional therapy (p = 0.002). In conclusion, adjuvant anti-PD-1 immunotherapy can achieve better survival outcomes in acral and cutaneous melanoma patients compared with conventional treatment, without considering adverse events. More clinical benefits were seen in later-stage acral melanoma patients with ulceration or lymph node macrometastasis. [ABSTRACT FROM AUTHOR]