Xinming Chen

IgA nephropathy (IgAN) represents the main cause of renal failure, while the precise pathogenetic mechanisms have not been fully determined. Herein, we conducted a cross-species single-cell survey on human IgAN and mouse and rat IgAN models to explore the pathogenic programs. Cross-species single-cell RNA sequencing (scRNA-Seq) revealed that the IgAN mesangial cells (MCs) expressed high levels of inflammatory signatures CXCL12, CCL2, CSF1, and IL-34 and specifically interacted with IgAN macrophages via the CXCL12/CXCR4, CSF1/IL-34/CSF1 receptor, and integrin subunit alpha X/integrin subunit alpha M/complement C3 (C3) axes. IgAN macrophages expressed high levels of CXCR4, PDGFB, triggering receptor expressed on myeloid cells 2, TNF, and C3, and the trajectory analysis suggested that these cells derived from the differentiation of infiltrating blood monocytes. Additionally, protein profiling of 21 progression and 28 nonprogression IgAN samples revealed that proteins CXCL12, C3, mannose receptor C-type 1, and CD163 were negatively correlated with estimated glomerular filtration rate (eGFR) value and poor prognosis (30% eGFR as composite end point). Last, a functional experiment revealed that specific blockade of the Cxcl12/Cxcr4 pathway substantially attenuated the glomerulus and tubule inflammatory injury, fibrosis, and renal function decline in the mouse IgAN model. This study provides insights into IgAN progression and may aid in the refinement of IgAN diagnosis and the optimization of treatment strategies.

Dear Editor, This letter is concerned with the distributed localization issue for wireless sensor networks subject to deception attacks. It is assumed that malicious nodes randomly launch attacks to tamper the ranging information between sensors. In order to accommodate the effects of deception attacks, a trust assessment-based distributed localization algorithm is proposed. Combined with data fusion of barycentric coordinates, our algorithm can achieve accurate localization. Finally, numerical simulations are given to validate the effectiveness of the proposed localization algorithm.

X-box-binding protein 1 (XBP1) contributes to various types of cancer including breast, bladder cancer and esophageal squamous cell carcinoma. The aim of the study was to examine the metastatic role of XBP1 in oral squamous cell carcinoma (OSCC), and identify possible downstream molecules. Immunohistochemical staining was conducted on tissue microarrays comprising 96 OSCC cases to determine the expression level of XBP1 and analyze its association with metastasis, clinicopathological characteristics and survival prognosis. Compared with the adjacent normal tissues of OSCC, the expression of XBP1 was significantly increased in the tumor center and front area, and lymph nodes metastases (P<0.05). A relatively high XBP1 expression was associated with histological grades (P<0.05), advanced clinical stages (P<0.05), unfavorable 5-year survival (P=0.027). Suppressed XBP1 expression caused a significant reduction of cell invasion capability (P<0.05). AXL and the downstream molecules, such as PI3K, MMP1, MMP3, and uPA were significantly suppressed when XBP1 expression was inhibited in OSCC cells. Once XBP1 was activated by Thapsigargin, AXL expression was restored. Moreover, aberrant AXL expression was associated with XBP1 overexpression in OSCC tissues (P<0.05). In conclusion, XBP1 is a potential target that is relevant to suppressing cell invasion and is associated with patient prognosis in OSCC.

Cluster of differentiation (CD)47, which acts as a negative indicator for phagocytic cells, is overexpressed on the surface of multiple human solid tumor cell types. Avoiding phagocytosis by CD47 is required for the progression of solid tumors. The present study investigated the expression of CD47 in oral leukoplakia (OLK) and oral squamous cell carcinoma (OSCC), and preliminarily explored the impact of CD47 on the proliferation of OSCC cells. A total of 56 tissue samples, including 36 cases of OLK, 10 cases of OSCC and 10 cases of normal oral mucosa (NOM) were selected to detect the expression of CD47 by immunohistochemistry. For subgroup analysis, OLK samples were divided into OLK with low‑risk dysplasia (LR‑OLK) and OLK with high‑risk dysplasia (HR‑OLK). The subcellular localization of CD47 was determined by immunofluorescence in three OSCC cell lines (Tca8113, SCC‑9 and Cal‑27). The effect of CD47 antibody on the proliferation of the Cal‑27 cell line was analyzed using the Cell Counting kit‑8 assay. CD47 expression in OLK and OSCC lesions was significantly higher than in NOM (P<0.05). Compared with LR‑OLK, the expression of CD47 in HR‑OLK and OSCC cells was upregulated (P=0.0327 and P=0.0048, respectively). CD47 was highly expressed in OSCC cell lines (Tca8113, Cal‑27 and SCC‑9) and weakly expressed in normal oral keratinocytes. The proliferation of Cal‑27 cells was inhibited by CD47 antibody in a concentration and time‑dependent manner. CD47 may be a reliable biomarker for predicting the progression of oral precancer and cancer, and it may serve as an important molecular target for designing a novel therapy for oral cancer.

MiR-34a suppresses HNSCC growth through modulating cell cycle arrest and senescence

Langerhans cell histiocytosis (LCH) is a rare disorder characterized by the proliferation of pathologic Langerhans cells. Its clinical presentation is highly variable, that range from single-system, limited disease to severe, multi-organ disease with high mortality. LCH usually affects children and young adults. The most frequent sites for LCH are the bone, skin, lung, pituitary gland, and lymph nodes. Salivary gland involvement by LCH is extremely rare, and only a few cases of LHC involving the parotid glands have been reported in the English literature. To our knowledge, the involvement of the sublingual gland as a part of single or multisystem LCH has not been previously described. Herein we reported the first case of primary LCH of the sublingual gland. A 40-year-old woman presented with a 2-month history of a painless mass on the right sublingual area. Excision of the lesion including the right sublingual gland was performed. Histopathological diagnosis of LCH was rendered. The patient remains free of symptoms 17 months after surgery.

Background: Oral squamous cell carcinoma (OSCC) is characterized by a high rate of local recurrence (LR) even when the surgical margins are considered histopathologically ‘normal’. The aim of our study was to determine the relationship between early tumor‐related markers detected in histologically normal margins (HNM) and LR as well as disease‐free survival in OSCC.Methods: The loss of heterozygosity (LOH) of markers on 9p21 (D9s1747, RPS6, D9s162) and 17p13 (TP53) and the immunostaining results of the corresponding mutant P53, P14, P15, and P16 proteins were assessed and correlated with LR and disease‐free survival in 71 OSCC patients who had HNM.Results: Fifteen of 71 patients with HNM developed LR. The presence of the following molecular markers in surgical margins was significantly correlated with the development of LR: LOH on chromosome 9p21 (D9s1747 + RPS6 + D9s162), any LOH, P16, and P53 (chi‐square test, P < 0.05). The presence of TP53 LOH, 9p21 LOH, any LOH, P15, P16, P53, P16 + D9s1747, and P53 + TP53 had a significant effect on LR (Kaplan–Meier analysis, P < 0.05). P16 + D9s1747 was the most predictive factor using multivariate Cox analyses.Conclusions: Detection of tumor‐related markers in histologically ‘normal’ resection margins may be a useful method for assessing LR in OSCC patients.

Basal cell adenocarcinomas (BCACs) of salivary glands are rare malignant neoplasms that mostly affect the major salivary glands. They are generally considered low-grade carcinomas that are locally destructive and tend to recur, but only occasionally metastasize. Currently there are only a few reported cases of distant metastases from BCAC, and metastasis to the liver is not previously described. We report the first case of BCAC with histologically confirmed liver metastases. A 40-year-old man presented with a 2-month history of a painless swelling in the left buccal region. The lesion was completely resected, and the patient underwent postoperative radiotherapy. Permanent histology and immunohistochemical studies revealed a BCAC of the buccal minor salivary gland. After 14 months, two hepatic metastatic nodules were detected. The patient underwent a partial hepatectomy with adjuvant chemotherapy. No evidence of progressive disease or further recurrence was observed for 20 months after the hepatic metastasectomy. BCACs grow indolently and long-term survival can be expected. Surgery should be considered in selected patients as a therapeutic option in metastatic disease.