Fibrolipomatous hamartoma of the median nerve: a case report and literature review / Hamartoma fibrolipomatoso del nervio mediano: reporte de un caso y revisión de la literatura

Abstract Fibrolipomatous hamartoma (FLH) of the nerve, also known as lipomatosis of the nerve, neurofibrillary lipomatous lesion, or intraneural lipoma, is a rare benign soft tissue tumor which mainly occurs in the nerves of the upper limb, especially in the median nerve. In April 2021, a 30-year-old male patient was secondly admitted to our hospital and underwent his third surgery, due to the recurrence of a mass and pain in the right palm, noticeable swelling and numbness of the right index and ring fingers, and limited flexion and extension activities of the right ring finger. He first visited our hospital in December 2017 due to a mass and pain in the right palm and swelling and numbness of the right index and ring fingers. When the clinician asked for the patient medical history, his parents stated that his right middle finger was swollen after birth. When the patient was ten years old; he was diagnosed with "macrodactyly" at the local county hospital, not in our hospital, and subsequently, the middle finger was amputated at the metacarpophalangeal joint level at the local county hospital. The postoperative pathological examination was not performed at that time, which was the first surgery the patient received. FLH is clinically rare, and its exact epidemiology and etiology are poorly understood. FLH is highly suspected in cases where a painless mass is present in the wrist, combined with macrodactyly. Magnetic resonance imaging and pathological examination are helpful in clarifying the diagnosis. Although FLH is a benign tumor, an individual treatment plan is the best choice according to the severity of the patient's symptoms. Therefore, further exploration and understanding of this disease by clinicians radiologists, and pathologists is necessary.

Resumen El hamartoma fibrolipomatoso (FLH) del nervio, también conocido como lipomatosis del nervio, lesión neurofibrilar lipomatosa, o lipointraneural, es un tumor benigno de tejido blando poco frecuente, que se presenta principalmente en los nervios del miembro superior, especialmente en el nervio mediano. En abril de 2021, un paciente masculino de 30 años fue ingresado por segunda vez en nuestro hospital y sometido a su tercera cirugía debido a la recurrencia de una masa y dolor en la palma derecha, evidente hinchazón y entumecimiento de los dedos índice y anular derecho y limitadas actividades de flexión y extensión del dedo anular derecho. En diciembre de 2017, visitó por primera vez nuestro hospital debido a una masa y dolor en la palma derecha, y a la hinchazón y entumecimiento de los dedos índice y anular derecho. Cuando el clínico preguntó la historia clínica del paciente, sus padres declararon que su dedo medio derecho estaba hinchado después del nacimiento, y cuando el paciente tenía 10 años, fue diagnosticado con "macrodactilia" en el hospital local del condado, no en nuestro hospital Posteriormente, el dedo medio fue amputado a nivel de la articulación metacarpofalángica en el hospital comarcal local, pero no se realizó la patología postoperatoria en ese momento, siendo ésta la primera cirugía a la cual se sometió el paciente. La FLH es clínicamente rara, y su epidemiología y etiología exactas no se entienden bien. En los casos que presentan una masa indolora en la muñeca, combinada con macrodactilia, se sospecha de FLH. La resonancia magnética y la patología son útiles para aclarar el diagnóstico. Aunque la FLH es un tumor benigno, el plan de tratamiento individual es la mejor opción de acuerdo con la gravedad de los síntomas del paciente. Por lo tanto, es necesaria una mayor exploración y comprensión de esta enfermedad por parte de médicos, radiólogos y patólogos.

Activation of PGRN/MAPK axis stimulated by the hypoxia-conditioned mesenchymal stem cell-derived HIF-1α facilitates osteosarcoma progression.

BACKGROUND: Progranulin (PGRN) is an important survival factor in the progression of multiple cancers. PURPOSE: To explore the effects and mechanisms of PGRN on malignant biological behavior of osteosarcoma (OS) cells and the effects of mesenchymal stem cells (MSCs) and the hypoxic microenvironment on PGRN alteration. MATERIAL AND METHODS: The expression pattern of PGRN in OS were evaluated in OS tissues and cell lines. Next, a loss-of-function assay investigated the function of PGRN on the proliferation, migration and cell death of OS cells. The activation of MAPK signaling in the process was examined by western blot and functional experiments accompanied by skatole. Additionally, we internally silenced hypoxia-inducible factor-1α (HIF-1α) in MSCs along with exogenously added HIF-1α (exo-HIF-1α) to explore how MSCs affect PGRN alteration and the malignant behavior of OS cells. RESULTS: An aberrantly high expression of PGRN was observed in OS and associated with the poor prognosis of OS patients. PGRN knockdown repressed the proliferation, migration and induced cell death of OS cells, and activating MAPK pathway reversed these effects. Further evidence showed that MSCs regulated PGRN to mediate the malignant biological behavior of OS cells. Hypoxia enhanced HIF-1α expression in MSCs. HIF-1α silencing in MSCs under hypoxia suppressed the oncogenic effects of MSCs and reduced PGRN expression in OS cells, while the treatment of exo-HIF-1α reversed the depressive effects of HIF1α silencing on OS progression. CONCLUSION: Overall, we concluded that PGRN, which was activated by the increase of hypoxic-MSCs-derived HIF-1α, promoted OS progression through the activation of MAPK signaling.

lncRNA AC007207.2 Promotes Malignant Properties of Osteosarcoma via the miR-1306-5p/SIRT7 Axis.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been implicated in initiation and development of numerous cancers. In the present study, we explored the role of lncRNAs AC007207.2 in osteosarcoma (OS). METHODS: Gene expression data of OS tissues was downloaded from the TARGET database. All the experiments were repeated at least three times. Data were analyzed using Perl, R, SPSS v12.0 and GraphPad Prism 8 software. RESULTS: We found lncRNA AC007207.2 was over-expressed in OS tissues and cell lines, and this phenomenon was associated with the worse prognosis of OS. Moreover, we found that AC007207.2 promotes proliferation and metastasis of OS cells via the miR-1306-5p/SIRT7 axis. Meanwhile, we found miR-1306-5p remarkably inhibits the malignant behavior of OS cells. CONCLUSION: lncRNA AC007207.2 promotes progression of OS by upregulating SIRT7 expression through miR-1306-5p sponging. Thus, lncRNA AC007207.2/miR-1306-5p/SIRT7 axis is a promising therapeutic target for OS treatment.

Effect of Deep-Level Defects on the Performance of CdZnTe Photon Counting Detectors.

The effect of deep-level defects is a key issue for the applications of CdZnTe high-flux photon counting devices of X-ray irradiations. However, the major trap energy levels and their quantitive relationship with the device's performance are not yet clearly understood. In this study, a 16-pixel CdZnTe X-ray photon counting detector with a non-uniform counting performance is investigated. The deep-level defect characteristics of each pixel region are analyzed by the current-voltage curves (I-V), infrared (IR) optical microscope photography, photoluminescence (PL) and thermally stimulated current (TSC) measurements, which indicate that the difference in counting performance is caused by the non-uniformly distributed deep-level defects in the CdZnTe crystals. Based on these results, we conclude that the CdZnTe detectors with a good photon counting performance should have a larger Te cd 2 + and Cd vacancy-related defect concentration and a lower A-center and Tei concentration. We consider the deep hole trap Tei, with the activation energy of 0.638-0.642 eV, to be the key deep-level trap affecting the photon counting performance. In addition, a theoretical model of the native defect reaction is proposed to understand the underlying relationships of resistivity, deep-level defect characteristics and photon counting performance.

miR-421 promotes apoptosis and suppresses metastasis of osteosarcoma cells via targeting LTBP2.

Increasing evidence has confirmed that microRNAs (miRs) are involved in tumor development and progression. A previous study reported that miR-421 could serve as a diagnostic marker in patients with osteosarcoma (OS). The present study explored the potential roles of miR-421 in the regulation of cell proliferation, apoptosis, migration, invasion, and epithelial-mesenchymal transition of OS cells. Our results showed that miR-421 was upregulated in OS tissues and cell lines (MG63, U2OS, HOS, and Saos-2) compared with the corresponding adjacent tissues or human osteoblast cells hFOB1.19, while the latent transforming growth factor ß-binding protein 2 (LTBP2) expression was reduced. In MG63 and U2OS cells, CCK8 assay displayed that cell proliferation was repressed by the miR-421 inhibitor, conversely increased by miR-421 mimics. Inhibition of miR-421 promoted cell apoptosis rate, caspase 3 activity, cleaved-caspase 3 (c-caspase 3) expression, and Bax/Bcl-2 ratio, restoration of miR-421 showed the opposite functions. Suppression of miR-421 blocked migration and invasion, whereas miR-421 overexpression promoted the migration and invasion of MG63 and U2OS cells. In addition, real-time polymerase chain reaction and Western blot analysis revealed that miR-421 negatively regulated E-cadherin expression, and positively regulated the expression of N-cadherin and vimentin. The luciferase reporter assay determined that miR-421 could target LTBP2-3'-UTR, and LTBP2 expression was regulated negatively by miR-421 both in mRNA and protein levels. Depletion of LTBP2 partly abolished the biological functions of miR-421 inhibitor in OS. In conclusion, miR-421 plays an oncogenic role in OS via targeting LTBP2, suggesting that miR-421 may be a potential therapeutic target against OS.

Identification of epigenetically altered genes and potential gene targets in melanoma using bioinformatic methods.

This study aimed to analyze epigenetically and genetically altered genes in melanoma to get a better understanding of the molecular circuitry of melanoma and identify potential gene targets for the treatment of melanoma. The microarray data of GSE31879, including mRNA expression profiles (seven melanoma and four melanocyte samples) and DNA methylation profiles (seven melanoma and five melanocyte samples), were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and differentially methylated positions (DMPs) were screened using the linear models for microarray data (limma) package in melanoma compared with melanocyte samples. Gene ontology (GO) and pathway enrichment analysis of the DEGs were carried out using the Database for Annotation, Visualization, and Integrated Discovery. Moreover, differentially methylated genes (DMGs) were identified, and a transcriptional regulatory network was constructed using the University of California Santa Cruz genome browser database. A total of 1,215 DEGs (199 upregulated and 1,016 downregulated) and 14,094 DMPs (10,450 upregulated and 3,644 downregulated) were identified in melanoma compared with melanocyte samples. Additionally, the upregulated and downregulated DEGs were significantly associated with different GO terms and pathways, such as pigment cell differentiation, biosynthesis, and metabolism. Furthermore, the transcriptional regulatory network showed that DMGs such as Aristaless-related homeobox (ARX), damage-specific DNA binding protein 2 (DDB2), and myelin basic protein (MBP) had higher node degrees. Our results showed that several methylated genes (ARX, DDB2, and MBP) may be involved in melanoma progression.

Enantioselective Michael addition of 3-aryloxindoles to a vinyl bisphosphonate ester catalyzed by a cinchona alkaloid derived thiourea catalyst.

A highly enantioselective Michael addition of 3-aryloxindole to vinyl bisphosphonate ester catalyzed by a cinchonidine derived thiourea catalyst has been investigated. The corresponding adducts, containing a chiral quaternary carbon center and geminal bisphosphonate ester fragment at the 3-position of the oxindole, were obtained in moderate to good yields (65-92%) and moderate to good enantioselectivities (up to 92% ee).

Asymmetric formal [3+2] cycloaddition reaction of α-aryl isocyanoesters with N-aryl maleimides by bifunctional cinchona alkaloids-based squaramide/AgSbF6 cooperative catalysis.

It is better to be cooperative: A highly diastereo- and enantioselective asymmetric [3+2] cycloaddition reaction of α-aryl isocyanoacetates with N-aryl maleimides through cooperative catalysis of cinchona alkaloid-derived squaramide/AgSbF(6) was developed. A wide range of optically active, substituted 1,3a,4,5,6,6a-hexahydropyrrolo[3,4-c] pyrrole derivatives was obtained in high yields (up to 98%), high diastereoselectivities (>20:1 d.r.), and good to excellent enantioselectivities (up to 92% ee) under mild reaction conditions.