Endoscopic ultrasound features of rectal melanoma: A case report and review of literature.

BACKGROUND: Rectal mucosal melanoma is a rare and highly aggressive disease. Common symptoms include anal pain, an anal mass, or bleeding. As such, the disease is usually detected on rectal examination of patients with other suspected anorectal diseases. However, due to its rarity and nonspecific symptoms, melanoma of the rectal mucosa is easily misdiagnosed. CASE SUMMARY: This report describes the case of a 58-year-old female patient who presented with a history of blood in her stool for the prior one or two months, without any identifiable cause. During colonoscopy, a bulge of approximately 2.2 cm × 2.0 cm was identified. Subsequently, the patient underwent endoscopic ultrasound (EUS) to characterize the depth of invasion of the lesions. EUS suggested a hypoechoic mucosal mass with involvement of the submucosal layer and heterogeneity of the internal echoes. Following surgical intervention, the excised tissue samples were examined and confirmed to be rectal malignant melanoma. The patient recovered well with no evidence of recurrence during follow-up. CONCLUSION: This case shows that colonoscopy with EUS and pathological examination can accurately diagnose rare cases of rectal mucosal melanoma.

Association between gestational cardiovascular health in the first trimester and pregnancy outcomes in the China birth cohort.

OBJECTIVES: To determine whether gestational cardiovascular health (CVH) during the first trimester is associated with a risk of adverse pregnancy outcomes. STUDY DESIGN: A multicentre prospective cohort; part of the China birth cohort study. METHODS: Pregnant women were recruited at 6-13+6 gestation weeks and followed to delivery to identify pregnancy outcomes. Gestational CVH in the first trimester was assessed using five CVH metrics: body mass index, smoking, blood pressure, glucose, and lipids. Multilevel modified Poisson regression models calculated the relative risks (RRs) and 95% confidence intervals (95% CIs) of gestational CVH for adverse pregnancy outcomes. RESULTS: Among 56,852 pregnant women, the mean score for gestational CVH during the first trimester was 9.1. Adjusting for confounding factors, each 1-point decrease in the total gestational CVH score significantly increased the risk of hypertensive disorders of pregnancy (RR = 1.682, 95% CI: 1.624-1.743), gestational diabetes mellitus (RR = 1.405, 95% CI: 1.384-1.426), preterm birth (RR = 1.184, 95% CI: 1.174-1.195), large for gestational age (RR = 1.224, 95% CI: 1.199-1.250), caesarean delivery (RR = 1.073, 95% CI: 1.049-1.097), and low Apgar score (RR = 1.131, 95% CI: 1.003-1.277) significantly increased. Meanwhile, the risk of small for gestational age decreased (SGA; RR = 0.922, 95% CI: 0.898-0.946). Worsened CVH categories significantly increased the risk of adverse pregnancy outcomes, excluding SGA. CONCLUSIONS: Poor gestational CVH in the first trimester significantly increases the risk of adverse pregnancy outcomes, emphasising the need for early improvement in gestational CVH.

Resistomycin Inhibits Wnt/ß-Catenin Signaling to Induce the Apoptotic Death of Human Colorectal Cancer Cells.

Resistomycin is a natural antibiotic related to quinone that has been shown to exhibit robust antitumor activity. To further characterize the mechanistic basis for such activity, human colorectal cancer (CRC) cells were selected as a model to explore the role of Wnt/ß-catenin signaling in the ability of resistomycin to induce apoptotic cell death. These analyses revealed that resistomycin was able to suppress ß-catenin, TCF4, and GSK-3ß expression, together with that of the downstream targets c-Myc and survivin. This coincided with elevated cleaved caspase-3 and Bax protein levels and a decline in Bcl-2 content. When ß-catenin was silenced, this further enhanced the ability of resistomycin to induce apoptotic CRC cell death, whereas this apoptotic process was partially ablated when cells were treated using lithium chloride to activate Wnt/ß-catenin signaling. Overall, these results support a model wherein resistomycin inhibits Wnt/ß-catenin signaling within CRC cells, thereby inducing apoptotic death. Further research may be warranted to better clarify the potential utility of this compound as a candidate drug for use in the treatment of patients suffering from this form of cancer.

Targeted Degradation of XIAP is Sufficient and Specific to Induce Apoptosis in MYCN-overexpressing High-risk Neuroblastoma.

XIAP, the most potent mammalian inhibitor of apoptosis protein (IAP), critically restricts developmental culling of sympathetic neuronal progenitors, and is correspondingly overexpressed in most MYCN-amplified neuroblastoma tumors. Because apoptosis-related protein in the TGFß signaling pathway (ARTS) is the only XIAP antagonist that directly binds and degrades XIAP, we evaluated the preclinical effectiveness and tolerability of XIAP antagonism as a novel targeting strategy for neuroblastoma. We found that antagonism of XIAP, but not other IAPs, triggered apoptotic death in neuroblastoma cells. XIAP silencing induced apoptosis while overexpression conferred protection from drug-induced apoptosis. From a screen of IAP inhibitors, first-in-class ARTS mimetic A4 was most effective against high-risk and high XIAP-expressing neuroblastoma cells, and least toxic toward normal liver- and bone marrow-derived cells, compared with pan-IAP antagonists. On target engagement assays and nuclear magnetic resonance spectroscopy, A4 was observed to degrade rather than inhibit XIAP, catalyzing rapid degradation of XIAP through the ubiquitin-proteasome pathway. In MYCN-amplified neuroblastoma patient-derived xenografts, A4 significantly prolonged survival as a single agent, and demonstrated synergism with standard-of-care agents to reduce their effective required doses 3- to 6-fold. Engagement and degradation of XIAP by ARTS mimetics is a novel targeting strategy for neuroblastoma that may be especially effective against MYCN-amplified disease with intrinsically high XIAP expression. First-in-class ARTS mimetic A4 demonstrates preclinical efficacy and warrants further development and study. SIGNIFICANCE: XIAP degradation is sufficient to kill MYCN-amplified neuroblastoma which overexpresses and relies on XIAP as a brake against cell death, without affecting normal cells.

Saponins from Panax japonicus improve neuronal mitochondrial injury of aging rats.

CONTEXT: Panax japonicus is the dried rhizome of Panax japonicus C.A. Mey. (Araliaceae). Saponins from Panax japonicus (SPJ) exhibit anti-oxidative and anti-aging effects. OBJECTIVE: We evaluated the neuroprotective effects of SPJ on aging rats. MATERIALS AND METHODS: Sprague-Dawley rats (18-months-old) were randomly divided into aging and SPJ groups (n = 8). Five-month-old rats were taken as the adult control (n = 8). The rats were fed a normal chow diet or the SPJ-containing diet (10 or 30 mg/kg) for 4 months. An in vitro model was established by d-galactose (d-Gal) in the SH-SY5Y cell line and pretreated with SPJ (25 and 50 µg/mL). The neuroprotection of SPJ was evaluated via Nissl staining, flow cytometry, transmission electron microscopy and Western blotting in vivo and in vitro. RESULTS: SPJ improved the neuronal degeneration and mitochondrial morphology that are associated with aging. Meanwhile, SPJ up-regulated the protein levels of mitofusin 2 (Mfn2) and optic atrophy 1 (Opa1) and down-regulated the protein level of dynamin-like protein 1 (Drp1) in the hippocampus of aging rats (p < 0.05 or p < 0.01 vs. 22 M). The in vitro studies also demonstrated that SPJ attenuated d-Gal-induced cell senescence concomitant with the improvement in mitochondrial function; SPJ, also up-regulated the Mfn2 and Opa1 protein levels, whereas the Drp1 protein level (p < 0.05 or p < 0.01 vs. d-Gal group) was down-regulated. DISCUSSION AND CONCLUSIONS: Further research on the elderly population will contribute to the development and utilization of SPJ for the treatment of neurodegenerative disorders.

A chronicle review of new techniques that facilitate the understanding and development of optimal individualized therapeutic strategies for chordoma.

Chordoma is a rare malignant bone tumor that mainly occurs in the sacrum and the clivus/skull base. Surgical resection is the treatment of choice for chordoma, but the local recurrence rate is high with unsatisfactory prognosis. Compared with other common tumors, there is not much research and individualized treatment for chordoma, partly due to the rarity of the disease and the lack of appropriate disease models, which delay the discovery of therapeutic strategies. Recent advances in modern techniques have enabled gaining a better understanding of a number of rare diseases, including chordoma. Since the beginning of the 21st century, various chordoma cell lines and animal models have been reported, which have partially revealed the intrinsic mechanisms of tumor initiation and progression with the use of next-generation sequencing (NGS) techniques. In this study, we performed a systematic overview of the chordoma models and related sequencing studies in a chronological manner, from the first patient-derived chordoma cell line (U-CH1) to diverse preclinical models such as the patient-derived organoid-based xenograft (PDX) and patient-derived organoid (PDO) models. The use of modern sequencing techniques has discovered mutations and expression signatures that are considered potential treatment targets, such as the expression of Brachyury and overactivated receptor tyrosine kinases (RTKs). Moreover, computational and bioinformatics techniques have made drug repositioning/repurposing and individualized high-throughput drug screening available. These advantages facilitate the research and development of comprehensive and personalized treatment strategies for indicated patients and will dramatically improve their prognoses in the near feature.

Saquayamycin B1 Suppresses Proliferation, Invasion, and Migration by Inhibiting PI3K/AKT Signaling Pathway in Human Colorectal Cancer Cells.

Moromycin B (Mor B), saquayamycin B1 (Saq B1), saquayamycin B (Saq B), and landomycin N (Lan N), four angucyclines produced by the marine-derived actinomycete Streptomyces sp., are a class of polyketone compounds containing benzanthracene. Here, the structure-activity relationship of these four compounds was analyzed in human colorectal cancer (CRC) cells. Saq B1, which showed the strongest cytotoxicity with an IC50 of 0.18-0.84 µM for CRC cells in MTT assays, was employed to test underlying mechanisms of action in SW480 and SW620 cells (two invasive CRC cell lines). Our results showed that Saq B1 inhibited CRC cell proliferation in a dose- and time-dependent manner. Notably, lower cytotoxicity was measured in normal human hepatocyte cells (QSG-7701). Furthermore, we observed proapoptosis, antimigration, and anti-invasion activities of Saq B1 in CRC cells. At the same time, the protein and mRNA expression of important markers related to the epithelial-mesenchymal transition (EMT) and apoptosis changed, including N-cadherin, E-cadherin, and Bcl-2, in Saq B1-treated CRC cells. Surprisingly, the PI3K/AKT signaling pathway was shown to be involved in Saq B1-induced apoptosis, and in inhibiting invasion and migration. Computer docking models also suggested that Saq B1 might bind to PI3Kα. Collectively, these results indicate that Saq B1 effectively inhibited growth and decreased the motor ability of CRC cells by regulating the PI3K/AKT signaling pathway, which provides more possibilities for the development of drugs in the treatment of CRC.

The Mechanism of Volatile Oil of Rhodiola tangutica against Hypoxia-Induced Pulmonary Hypertension in Rats Based on RAS Pathway.

Materials and Methods: Seventy-five male Sprague-Dawley (SD) rats were separated into control (Ctr), hypoxia (Hyp), and Hyp+VORA treatment (100 mg/kg/d, 80 mg/kg/d, and 40 mg/kg/d) groups in random. To achieve the chronic hypoxia condition, rats were kept inside the hypobaric chamber with automatically adjusted inner pressure as well as oxygen content equal to those of 4500 m in altitude for 4 continuous weeks. After 4 weeks, the rats' physiological parameters were determined (mean pulmonary artery pressure (mPAP); right ventricular hypertrophy index (RVHI)). Based on hematoxylin and eosin (HE) staining and transmission electron microscope (TEM), morphological features of their lung tissues were also analyzed. Proliferation of pulmonary arterial smooth muscle cells (PASMCs) was detected by MTS Cell Proliferation Colorimetric assay. The levels of glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD) in PASMCs were detected through corresponding kits, respectively. The protein levels in PASMCs and HPH rats were evaluated by Western blot (WB). Chemical components of VORA were detected through gas chromatography-mass spectrometer (GC-MS). Results: After induced by hypoxia for 4 weeks, the mPAP and RVHI levels were increased significantly in hypoxia group in contrast to the Ctr group, indicating the establishment of HPH rat model. The subsequent administration of VORA decreased the mPAP and RVHI level. The vascular wall thickness and lumen size were also decreased after treated by VORA compared with Hyp group. Meanwhile, VORA suppressed the proliferation and oxidant stress in PASMCs. Therefore, the effect of VORA on decreasing vascular wall thickening and lumen size could be related to its antiproliferation effect on PASMCs. In addition, compared to the Hyp group, VORA downregulated the ACE, AngII, and AT1R protein expressions but increased ACE2 and MAS protein expressions (P < 0.05). A total of 48 constituents in VORA were identified by GC-MS in comparison with reference standards as well as the reference pieces of literatures. Conclusions: HPH rat model as established based on the significant increased mPAP and RVHI. VORA presented a significant antihypoxia function plus an inhibiting effect on PASMC proliferation induced by hypoxia. Moreover, VORA treatment inhibited oxidative stress among PASMCs. With regard to the mechanism, VORA reduced ACE, AngII, and AT1R protein expressions but increased ACE2 and MAS protein expressions. There were 48 constituents in VORA identified by GC-MS.

Targeted Therapy for Inflammatory Diseases with Mesenchymal Stem Cells and Their Derived Exosomes: From Basic to Clinics.

Inflammation is a beneficial and physiological process, but there are a number of inflammatory diseases which have detrimental effects on the body. In addition, the drugs used to treat inflammation have toxic side effects when used over a long period of time. Mesenchymal stem cells (MSCs) are pluripotent stem cells that can be isolated from a variety of tissues and can be differentiate into diverse cell types under appropriate conditions. They also exhibit noteworthy anti-inflammatory properties, providing new options for the treatment of inflammatory diseases. The therapeutic potential of MSCs is currently being investigated for various inflammatory diseases, such as kidney injury, lung injury, osteoarthritis (OA), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD). MSCs can perform multiple functions, including immunomodulation, homing, and differentiation, to enable damaged tissues to form a balanced inflammatory and regenerative microenvironment under severe inflammatory conditions. In addition, accumulated evidence indicates that exosomes from extracellular vesicles of MSCs (MSC-Exos) play an extraordinary role, mainly by transferring their components to recipient cells. In this review, we summarize the mechanism and clinical trials of MSCs and MSC-Exos in various inflammatory diseases in detail, with a view to contributing to the treatment of MSCs and MSC-Exos in inflammatory diseases.

The Emerging Roles of Pellino Family in Pattern Recognition Receptor Signaling.

The Pellino family is a novel and well-conserved E3 ubiquitin ligase family and consists of Pellino1, Pellino2, and Pellino3. Each family member exhibits a highly conserved structure providing ubiquitin ligase activity without abrogating cell and structure-specific function. In this review, we mainly summarized the crucial roles of the Pellino family in pattern recognition receptor-related signaling pathways: IL-1R signaling, Toll-like signaling, NOD-like signaling, T-cell and B-cell signaling, and cell death-related TNFR signaling. We also summarized the current information of the Pellino family in tumorigenesis, microRNAs, and other phenotypes. Finally, we discussed the outstanding questions of the Pellino family in immunity.

Comprehensive Analysis of LPCATs Highlights the Prognostic and Immunological Values of LPCAT1/4 in Hepatocellular Carcinoma.

BACKGROUND: The prognosis of patients with advanced hepatocellular carcinoma (HCC) remains poor. Lipid remodeling modulators are considered promising therapeutic targets of cancers, owing to their functions of facilitating cancer cells' adaption to the limited environment. Lysophosphatidylcholine acyltransferases (LPCATs) are enzymes regulating bio-membrane remodeling, whose roles in HCC have not been fully illuminated. METHODS: Multiple bioinformatic tools were applied to comprehensively evaluate the expression, genetic alterations, clinical relevance, prognostic values, DNA methylation, biological functions, and correlations with immune infiltration of LPCATs in HCC. RESULTS: We found LPCAT1 was significantly overexpressed and the most frequently altered in HCC. The high-expression of LPCAT1/4 indicated clinicopathological advancements and poor prognoses of HCC patients. Even though the global DNA methylation of LPCATs in HCC showed no significant difference with that in normal liver, the hypermethylation of numerous CpG sites of them implied worse survivals of HCC patients. Thirty LPCATs' interactive genes were identified, which were generally membrane components and partook in phospholipid metabolism pathways. Finally, we found the expression of LPCATs was extensively positively correlated with the infiltration of various stimulatory and suppressive tumor-infiltrating immune cells (TIICs) in the tumor microenvironment. CONCLUSION: This study addressed LPCAT1/4 were potential prognostic and immunotherapeutic biomarkers of HCC targeting bio-membrane lipid remodeling.

[Resection and free flap repair of recurrent maxillofacial and paranasal sinus skull base malignant tumor: report of 9 cases].

Objective: To investigate the treatment method and effect of surgical resection and free flap repair of recurrent malignant tumors of maxillofacial paranasal sinus and skull base. Methods: The clinical data of 9 patients with recurrent maxillofacial paranasal sinus and skull base malignant tumors who underwent surgical resection and free flap repair in the Department of Otorhinolaryngology Head and Neck Surgery of Shandong Provincial Hospital from August 2009 to May 2019 were analyzed retrospectively, including 5 males and 4 females, aged 32-69 years. There were 4 cases of squamous cell carcinoma, 3 cases of adenoid cystic carcinoma, 1 case of myoepithelial carcinoma and 1 case of malignant fibrous histiocytoma. All patients were repaired with anterolateral femoral flap. The treatment process and postoperative effect were analyzed by descriptive statistics. Results: All patients were followed up from 16 months to 6 years. There were 6 cases of recurrence after operation, including 1 case of local recurrence and 5 cases of skull base and craniocerebral recurrence. The median tumor free survival time of recurrent patients was 35 months. Conclusion: Surgical resection and free flap repair can effectively prolong the life of patients with recurrent maxillofacial paranasal sinus and skull base malignant tumors.

Actinomycin V Induces Apoptosis Associated with Mitochondrial and PI3K/AKT Pathways in Human CRC Cells.

Actinomycin (Act) V, an analogue of Act D, presented stronger antitumor activity and less hepatorenal toxicity than Act D in our previous studies, which is worthy of further investigation. We hereby report that Act V induces apoptosis via mitochondrial and PI3K/AKT pathways in colorectal cancer (CRC) cells. Act V-induced apoptosis was characterized by mitochondrial dysfunction, with loss of mitochondria membrane potential (MMP) and cytochrome c release, which then activated cleaved caspase-9, cleaved caspase-3, and cleaved PARP, revealing that it was related to the mitochondrial pathway, and the apoptotic trendency can be reversed by caspase inhibitor Z-VAD-FMK. Furthermore, we proved that Act V significantly inhibited PI3K/AKT signalling in HCT-116 cells using cell experiments in vitro, and it also presented a potential targeted PI3Kα inhibition using computer docking models. Further elucidation revealed that it exhibited a 28-fold greater potency than the PI3K inhibitor LY294002 on PI3K inhibition efficacy. Taken together, Act V, as a superior potential replacement of Act D, is a potential candidate for inhibiting the PI3K/AKT pathway and is worthy of more pre-clinical studies in the therapy of CRC.

Resistomycin Induced Apoptosis and Cycle Arrest in Human Hepatocellular Carcinoma Cells by Activating p38 MAPK Pathway In Vitro and In Vivo.

Resistomycin, a quinone-related natural antibiotic, has shown strong inhibitory activity against human hepatocellular carcinoma (HCC) in vitro. Here, we investigated the role of p38 MAPK in the pro-apoptotic and G2/M phase arrest action of HCC HepG2 cells upon treatment with resistomycin in vitro and in vivo. Our results showed that resistomycin dose- and time-dependently reduced the viability of HepG2 cells and also showed lower cytotoxicity in normal human kidney cells (293T) and hepatocyte cells (HL-7702). Resistomycin treatment induced apoptosis and cell cycle arrest in HepG2 cells, accompanied by changes in the expression of related proteins, including Bax, Cyclin B1, etc. Surprisingly, resistomycin-mediated apoptotic cell death and cell cycle arrest were impeded by SB203580 (an inhibitor of p38 catalytic activity), suggesting that p38 MAPK signaling may play an important role that impedes eventual cell death. In this connection, data in vitro and in vivo demonstrated that resistomycin increased the phosphorylation of p38 and MAPKAPK-2 in HepG2 cells. Furthermore, we provided evidence that p38 signaling is involved in resistomycin-induced p38 MAPK pathway effects in HCC, using computer docking models. Our study indicated that resistomycin activates the p38 MAPK signaling pathway by which the growth of HepG2 cells is suppressed for apoptosis and G2/M phase arrest in vitro and in vivo, and it is a promising therapeutic leading compound for drug development in HCC treatment.

Pituitary metastasis: From pathology to clinical and radiological considerations.

PURPOSE: A review of the literature with respect to pituitary metastases (PM) with clinical and radiological considerations are summarized to facilitate clinical decision making in the management of PM METHODS: A review of literature associated with PM and tumour to tumour metastases in the English literature was reviewed and summarized RESULTS: Pituitary metastases account for 1.0-3.6% of all surgically treated pituitary lesions. Often identified in parallel with extensive disseminated disease, once diagnosed, the prognosis is generally poor, although survival is highly heterogeneous and dependent on the primary tumor histology. Within this anatomical region is also the observation of tumor-to-tumor metastases and collision tumours. Both the tumor macro- and microenvironment play central roles to the progression of disease with distinctive radiological features that may suggest a metastatic sellar lesion as opposed to a primary pituitary lesion. Surgical resection is the first line of therapy followed by adjuvant chemoradiotherapy and endocrinological evaluation for hormonal supplementation CONCLUSION: PMs are relatively rare but important oncological entities representing disseminated disease in the majority of cases. Careful consideration of the relevant clinical history and radiological features can aid the clinician differentiate between a metastatic lesion to the pituitary region and a primary pituitary tumor. While surgical resection is first line therapy, stereotactic radiosurgery in carefully selected patients is emerging as a viable alternative.

Use of dynamic contrast-enhanced MRI for the early assessment of outcome of CyberKnife stereotactic radiosurgery for patients with spinal metastases.

AIM: To explore the value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for evaluating early outcomes of CyberKnife radiosurgery for spinal metastases. MATERIALS AND METHODS: Patients with spinal metastases who were treated with CyberKnife radiosurgery from July 2018 to December 2020 were enrolled. Conventional MRI and DCE-MRI were performed before treatment and at 3 months after treatment. Patients showing disease progression were defined as the progressive disease (PD) group and those showing complete response, partial response, and stable disease were defined as the non-PD group. The haemodynamic parameters (volume transfer constant [Ktrans], rate constant [Kep], and extravascular space [Ve]) before and after treatment between the groups were analysed. Area under the curve (AUC) values were calculated. RESULTS: A total of 27 patients with 39 independent spinal lesions were included. The median follow-up time was 18.6 months (6.2-36.4 months). There were 27 lesions in the non-PD group and 12 lesions in the PD group. Post-treatment Kep, ΔKtrans and ΔKep in the non-PD group (0.959/min, - 32.6% and -41.1%, respectively) were significantly lower than the corresponding values in PD group (1.429/min, 20.4% and -6%; p<0.05). Post-treatment Ve and ΔVe (0.223 and 27.8%, respectively) in the non-PD group were significantly higher than that of the PD group (0.165 and -13.5%, p<0.05). ΔKtrans showed the highest diagnostic efficiency, with an AUC of 0.821. CONCLUSIONS: DCE-MRI parameters change significantly at an early stage after CyberKnife stereotactic radiosurgery for spinal metastases. DCE-MRI may be of value in determining the early treatment response.

[Granulomatosis with polyangiitis with nasal symptoms as the first clinical manifestation: clinical analysis of 18 cases].

Objective: To analyze and summarize the diagnosis, treatment and prognosis of granulomatosis with polyangiitis (GPA) with nasal symptoms as the first clinical manifestation. Methods: The data of 18 patients of GPA with nasal mucosal symptoms as the first clinical manifestation from the Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University between 2005 and 2019 was collected, including 8 males and 10 females, aged from 5 to 68 years. Nasal endoscopy, imaging examination, laboratory examination, immunological and histopathological examination of nasal mucosa were completed. All patients were treated with glucocorticoid combined with cyclophosphamide and were followed up for 2 to 15 years. Descriptive statistical method was used for analysis. Results: All the 18 patients had the nasal mucosal symptoms as the first clinical manifestation, including nasal obstruction, running nose and epistaxis. Nasal endoscopy showed swelling, erosion, scab and bleeding of nasal mucosa, and 6 cases had nasal septal perforation. Nasal sinus CT scan showed high density shadow of sinus, as well as hyperostosis and osteosclerosis. CT imaging features of pulmonary showed nodular lesion or patchy infiltration in 12 patients and cavitation was found in 6 cases. Laboratory results showed that 13 cases were positive for anti-neutrophil cytoplasmic antibodies (ANCA), and 5 cases were negative. During follow-up period, thirteen patients were symptomatic controlled and survived; two patients died of disease progression; one patient gave up treatment and died; two patients were lost to follow-up. Conclusions: Nasal symptoms are the first clinical manifestation of GPA. Early diagnosis and early treatment with glucocorticoid combined with cyclophosphamide can effectively improve the survival rate.

CXCL2/10/12/14 are prognostic biomarkers and correlated with immune infiltration in hepatocellular carcinoma.

BACKGROUND: C-x-C motif chemokine ligands (CXCLs) are critical regulators of cancer immunity and angiogenesis, which affect disease progression and treatment responses. The character of each CXCL in the prognosis and immune infiltration of hepatocellular carcinoma (HCC) patients is unclear yet. METHODS: Differentially expressed CXCLs between HCC and normal control were screened by Oncomine and GEPIA2. Genetic alternations of CXCLs in HCC were analyzed by cBioPortal. Clinicopathological relevance of CXCLs in HCC patients was analyzed using UALCAN. The prognostic value of CXCLs was evaluated using univariate and multivariate analyses. Correlations of CXCLs' expression with immune infiltration, chemokines and their receptors were assessed integrating TIMER, TISIDB, and GEPIA2. The co-expressed genes of CXCLs were discovered, and functional enrichment analysis was performed for them. RESULTS: CXCL9/10 was significantly higher expressed while CXCL2/12/14 was lower expressed in HCC than normal tissues, but they didn't show significant clinicopathological relevance in HCC patients. High-expression of CXCL2/10/12/14 indicated favorable outcomes of HCC patients. The expression of CXCL9/10/12/14 was significantly positively correlated with not only the infiltration and biomarkers' expression of various tumor-infiltrating immune cells but also the abundance of chemokines and their receptors. The co-expressed genes of the five CXCLs were extracellular components and regulated immune or inflammatory responses and signaling pathways of chemokine, Toll-like receptor and tumor necrosis factor might be involved. CONCLUSION: The present study proposed CXCL2/10/12/14 might predict outcomes of HCC patients and were extensively related with the immune microenvironment in HCC. It would be a prospective therapeutic strategy for HCC to enhance effective immunity surveillance through intervening in these CXCLs.

Human Gastric Cancer Stem Cell (GCSC) Markers Are Prognostic Factors Correlated With Immune Infiltration of Gastric Cancer.

The prognosis of patients with gastric cancer (GC) is still unsatisfying. Numerous markers of gastric cancer stem cells (GCSCs) have been identified and were thought to be related to cancer aggressiveness. However, the roles of GCSC markers in GC patients' prognosis and immune infiltration remain unknown. Expression of GCSC markers was analyzed using Oncomine and Gene Expression Profiling Interactive Analysis (GEPIA). Their associations with clinicopathological parameters were analyzed using UALCAN and LinkedOmics. Alternations and protein expression of GCSC markers were analyzed by cBioPortal and the Human Protein Atlas databases, respectively. The prognostic significance of GCSC markers was evaluated using Kaplan-Meier plotter. Correlations between the expression of GCSC markers and immune infiltration along with biomarkers of tumor-infiltrating immune cells (TIICs) were assessed combined Tumor Immune Estimation Resource and GEPIA. GeneMANIA was used to discover the interactive genes of GCSC markers, and enrichment analysis was performed using Database for Annotation, Visualization, and Integrated Discovery server. We identified six GCSC markers significantly up-expressed in GC, compared with normal stomach tissues. Among them, the overexpression of ICAM1, THY1, and CXCR4 significantly indicated adverse, while EPCAM indicated beneficial clinicopathological features of GC patients. The up-regulation of CXCR4 showed unfavorable prognostic significance, whereas EPCAM and TFRC showed the opposite. The six GCSC markers were all correlated with the infiltration and activation of distinct TIICs. Especially, ICAM1, THY1, and CXCR4 showed strongly positive correlations with tumor-associated macrophages. Besides, chemokine, Toll-like receptor, NF-kappa B, and HIF-1 signaling pathways might be involved in the regulation of GCSC markers on cancer development. This study proposed that GCSC markers might be promising targets of GC treatment to weaken cancer stem-like properties and strengthen anticancer immunity.