RANKL/RANK signaling recruits Tregs via the CCL20-CCR6 pathway and promotes stemness and metastasis in colorectal cancer.

TNF receptor superfamily member 11a (TNFRSF11a, RANK) and its ligand TNF superfamily member 11 (TNFRSF11, RANKL) are overexpressed in many malignancies. However, the clinical importance of RANKL/RANK in colorectal cancer (CRC) is mainly unknown. We examined CRC samples and found that RANKL/RANK was elevated in CRC tissues compared with nearby normal tissues. A higher RANKL/RANK expression was associated with a worse survival rate. Furthermore, RANKL was mostly produced by regulatory T cells (Tregs), which were able to promote CRC advancement. Overexpression of RANK or addition of RANKL significantly increased the stemness and migration of CRC cells. Furthermore, RANKL/RANK signaling stimulated C-C motif chemokine ligand 20 (CCL20) production by CRC cells, leading to Treg recruitment and boosting tumor stemness and malignant progression. This recruitment process was accomplished by CCL20-CCR6 interaction, demonstrating a connection between CRC cells and immune cells. These findings suggest an important role of RANKL/RANK in CRC progression, offering a potential target for CRC prevention and therapy.

Double base mismatches mediated catalytic hairpin assembly for enzyme-free single-base mutation detection: integrating signal recognition and amplification in one.

Single nucleotide polymorphism (SNP) biosensors are emerging rapidly for their promising applications in human disease prevention diagnosis, treatment, and prognosis. However, it remains a bottleneck in equipping simple and stable biosensors with the traits of high sensitivity, non-enzyme, and low cost. Double base mismatches mediated chain displacement reactions have attracted fascinating advantages of tailorable thermodynamics stability, non-enzyme, and excellent assembly compliance to involvement in SNP identification. As the base mismatch position and amount in DNA sequence can be artificially adjusted, it provides plenty of selectivity and specificity for exploring perfect biosensors. Herein, a biosensor with double base mismatches mediated catalytic hairpin assembly (CHA) is designed via one base mismatch in the toehold domain and the other base mismatch in the stem sequence of hairpin 1 (H1) by triggering CHA reaction to achieve selective amplification of the mutation target (MT) and fluorescence resonance energy transfer (FRET) effect that is composed of Cy3 and Cy5 terminally attached H1 and hairpin 2 (H2). Depending on the rationally designed base mismatch position and toehold length, the fabricated biosensors show superior SNP detection performance, exhibiting a good linearity with high sensitivity of 6.6 fM detection limit and a broad detection abundance of 1%. The proposed biosensor can be used to detect the KRAS mutation gene in real samples and obtain good recoveries between 106 and 116.99%. Remarkably, these extendible designs of base mismatches can be used for more types of SNP detection, providing flexible adjustment based on base mismatch position and toehold length variations, especially for their thermodynamic model for DNA-strand displacement reactions.

Solvent-promoted photochemical carbonylation of benzylic C-H bonds under iron catalysis.

This paper describes the iron-catalyzed photochemical carbonylation of benzylic C-H bonds resulting in the synthesis of various aryl ketones. Using 5 W blue LED irradiation, the reactions proceed smoothly in the presence of 2 mol% of FeBr3 in MeOH at 35 °C. The catalytic system could be extended for the oxidation of silane, thioether, and phosphine into silenol, sulphoxide, and phosphoxide, respectively. A mechanistic study suggests that a hydrogen bond-stabilized iron-hydroperoxo species is the reactive intermediate. It is shown that the reaction proceeds via a four-electron-transfer pathway, and a benzylic cation seems to be the crucial reactive species. The method is applied for the synthesis of pomalyst, haloperidol, melperone, and lenperone.

RANK promotes colorectal cancer migration and invasion by activating the Ca2+-calcineurin/NFATC1-ACP5 axis.

The tumor necrosis factor (TNF) receptor superfamily member 11a (TNFRSF11a, also known as RANK) was demonstrated to play an important role in tumor metastasis. However, the specific function of RANK in colorectal cancer (CRC) metastasis and the underlying mechanism are unknown. In this study, we found that RANK expression was markedly upregulated in CRC tissues compared with that in matched noncancerous tissues. Increased RANK expression correlated positively with metastasis, higher TNM stage, and worse prognosis in patients with CRC. Overexpression of RANK promoted CRC cell metastasis in vitro and in vivo, while knockdown of RANK decreased cell migration and invasion. Mechanistically, RANK overexpression significantly upregulated the expression of tartrate-resistant acid phosphatase 5 (TRAP/ACP5) in CRC cells. Silencing of ACP5 in RANK-overexpressing CRC cells attenuated RANK-induced migration and invasion, whereas overexpression of ACP5 increased the migration and invasion of RANK-silencing cells. The ACP5 expression was transcriptionally regulated by calcineurin/nuclear factor of activated T cells c1 (NFATC1) axis. The inhibition of calcineurin/NFATC1 significantly decreased ACP5 expression, and attenuated RANK-induced cell migration and invasion. Furthermore, RANK induced phospholipase C-gamma (PLCγ)-mediated inositol-1,4,5-trisphosphate receptor (IP3R) axis and stromal interaction molecule 1 (STIM1) to evoke calcium (Ca2+) oscillation. The RANK-mediated intracellular Ca2+ mobilization stimulated calcineurin to dephosphorylate NFATC1 and induce NFATC1 nuclear translocation. Both blockage of PLCγ-IP3R axis and STIM1 rescued RANK-induced NFATC1 nuclear translocation, ACP5 expression, and cell metastasis. Our study revealed the functional expression of RANK in human CRC cells and demonstrated that RANK induced the Ca2+-calcineurin/NFATC1-ACP5 axis in the regulation of CRC metastasis, that might be amenable to therapeutic targeting.

AHA1 upregulates IDH1 and metabolic activity to promote growth and metastasis and predicts prognosis in osteosarcoma.

Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents. Although activator of HSP90 ATPase activity 1 (AHA1) is reported to be a potential oncogene, its role in osteosarcoma progression remains largely unclear. Since metabolism reprogramming is involved in tumorigenesis and cancer metastasis, the relationship between AHA1 and cancer metabolism is unknown. In this study, we found that AHA1 is significantly overexpressed in osteosarcoma and related to the prognosis of osteosarcoma patients. AHA1 promotes the growth and metastasis of osteosarcoma both in vitro and in vivo. Mechanistically, AHA1 upregulates the metabolic activity to meet cellular bioenergetic needs in osteosarcoma. Notably, we identified that isocitrate dehydrogenase 1 (IDH1) is a novel client protein of Hsp90-AHA1. Furthermore, the IDH1 protein level was positively correlated with AHA1 in osteosarcoma. And IDH1 overexpression could partially reverse the effect of AHA1 knockdown on cell growth and migration of osteosarcoma. Moreover, high IDH1 level was also associated with poor prognosis of osteosarcoma patients. This study demonstrates that AHA1 positively regulates IDH1 and metabolic activity to promote osteosarcoma growth and metastasis, which provides novel prognostic biomarkers and promising therapeutic targets for osteosarcoma patients.

ALK-positive pulmonary adenocarcinoma with signet ring features (PASRF) and polygonal cell morphology simultaneously co-expressing TTF-1/p63/P40: a case report.

Pulmonary adenocarcinoma with signet ring features (PASRF) is relatively rare and often harbors anaplastic large cell kinase gene (ALK) rearrangements. As patients with ALK+ lung adenocarcinoma typically present at advanced stages, it is important to detect ALK+ PASRF at metastatic sites to ensure ALK-targeted therapy can be best applied. In this study, we report a case of PASRF with polygonal cell morphology in an 85-year-old female who had metastasized to the supraclavicular lymph node and was treated with Alectinib, a novel small molecule tyrosine kinase inhibitor targeting ALK. Biopsy of the node revealed numerous microscopic neoplastic cells which had formed nests or cords, in addition to signet ring cells (60%), and another morphology of polygonal cells (40%) which contained eosinophilic cytoplasm. Mitotic images were common, and necrosis was observed. Immunohistochemically, both morphology tumor cells were diffusely positive for TTF1, CK7, and Napsin A, and most of the two were positive for P40, P63, and CK5/6 and negative for CK20 and CDX2. Co-expression of TTF-1, CK7, Napsin A, and P40, P63, and CK5/6 were overtly present, and Alcian blue-periodic acid-Schiff (AB-PAS) staining showed intracytoplasmic mucin in the two cells. In addition, ALK rearrangements were detected by ALK (clone D5F3) immunohistochemical assay and fluorescence in situ hybridization (FISH), A final diagnosis of metastatic ALK-positive PASRF with polygonal cell morphology to the supraclavicular lymph node was made, and the patient was treated with Alectinib, which brought a reduction in tumor size and good results.

The PPRD score stratifies patients with hepatocellular carcinoma and portal vein tumor thrombus treated with sorafenib plus transarterial chemoembolization.

OBJECTIVES: To identify clinical prognostic and predictive factors in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) undergoing sorafenib plus transarterial chemoembolization (TACE) and establish a prognostic score for these patients. METHODS: Between January 2012 and December 2017, 184 consecutive patients with HCC and PVTT were concurrently treated with sorafenib and TACE. Univariate and multivariate analyses were performed to explore the clinical factors independently correlated with overall survival (OS). A prognostic score was then developed to identify different prognoses in an initial cohort and validated in an external cohort (n = 72). RESULTS: In the multivariate analysis, performance status, extension of PVTT, initial radiological response, and sorafenib-related dermatologic toxicity were identified as predictors associated with OS. These factors were used to develop a prognostic score (PPRD score, range from 0 to 11). The median survival was found to decrease as the PPRD score increased, and patients were stratified into a favorable group (0 points), intermediate group (1-4 points), and dismal group (> 4 points). The median survival of patients in the three groups was 34.0 months, 20.0 months, and 7.0 months, respectively (p < 0.001). Additionally, the time to progression (TTP) (p < 0.001) was stratified along the same prognostic groups. The external validation cohort confirmed the prognostic scores. CONCLUSIONS: The proposed score system can accurately stratify the outcomes of patients with HCC and PVTT treated with sorafenib plus TACE to help identify which group of patients may benefit from treatment. KEY POINTS: • The survival benefits of patients with advanced HCC treated with sorafenib plus TACE remains controversial. • The independent factors associated with survival were identified to develop a prognostic score, called the PPRD score (standing for performance status, PVTT grade, radiological response, and sorafenib-related dermatologic toxicity); the median survival decreases as the score increases. • The scoring system can accurately stratify the survival benefits of patients with HCC and PVTT treated with combination therapy and help to identify which group of patients may benefit from the treatment. Graphical abstract.

Tripartite motif containing 24 regulates cell proliferation in colorectal cancer through YAP signaling.

The protein, tripartite motif containing 24 (TRIM24) is a member of the TRIM protein family, and acts as a critical co-regulator of multiple nuclear receptors. TRIM24 is dysregulated in many cancers, including colorectal carcinoma. However, its biological functions and molecular mechanisms with respect to colorectal carcinoma are still largely unknown. In the current study, we found that TRIM24 promotes YAP signaling for driving cell proliferation in colorectal cancer. TRIM24 was significantly upregulated in colorectal carcinoma, and its expression was negatively correlated with the survival of patients. Depletion of TRIM24 impaired the ability of the cancer cells to proliferate and form colonies. Furthermore, this study also revealed the mechanism underlying the recruitment of TRIM24 by the DANCR/KAT6A complex, which is bound to acetylated lysine 23 of histone H3 (H3K23), resulting in binding to the YAP promoter and activation of YAP transcription that ultimately enhances the proliferation of colorectal cancer cells. Our results revealed a novel mechanism involving TRIM24-YAP signaling for the regulation of colorectal cancer. We also identified TRIM24 as a potential therapeutic molecule for targeting colorectal cancer.

EFEMP1 as a Potential Biomarker for Diagnosis and Prognosis of Osteosarcoma.

Osteosarcoma (OS) is the most common primary bone malignancy. Our previous study revealed an association between the level of epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) and the invasion, metastasis, and poor prognosis of OS. However, the exact correlation between the serum EFEMP1 level and OS diagnosis and progression was unclear. This study is aimed at determining the value of the serum EFEMP1 level in the diagnosis and prognosis of OS. Fifty-one consecutive OS patients were prospectively registered in this study. The serum EFEMP1 levels were measured using ELISA at diagnosis, after neoadjuvant chemotherapy, and before and after surgical treatment. Sixty-nine healthy subjects in the control group, nine patients with chondrosarcoma, and 12 patients with giant cell tumor of the bone were also enrolled in this study. Surgical orthotopic implantation was used to generate a mouse OS model, and the correlation between the circulating EFEMP1 levels and tumor progression was examined. Then, OS patients had significantly higher mean serum EFEMP1 levels (7.61 ng/ml) than the control subjects (1.47 ng/ml). The serum EFEMP1 levels were correlated with the Enneking staging system (r = 0.32, P = 0.021) and lung metastasis (r = 0.50, P < 0.001). There was also a correlation between the serum EFEMP1 level and EFEMP1 expression in the respective OS samples (r = 0.49, P < 0.001). Additionally, patients with either chondrosarcoma or giant cell tumor of the bone had significantly higher serum EFEMP1 levels than OS patients. Surgical and chemotherapeutic treatment led to an increase in the serum EFEMP1 levels. Then, the destruction of bone tissues might be one of the factors about the EFEMP1 levels. In the mouse OS model, the serum EFEMP1 level was correlated with tumor progression. Our results suggested that serum EFEMP1 levels might be used to distinguish OS patients from healthy controls and as an indicator for OS lung metastasis. Serum EFEMP1 levels could serve as a new and assisted biomarker for the auxiliary diagnosis and prognosis of OS.

Long non-coding RNA DANCR promotes colorectal tumor growth by binding to lysine acetyltransferase 6A.

Recent studies have demonstrated that long non-coding RNAs (lncRNAs) play critical roles in cancer development and progression. However, the mechanism by which lncRNAs contribute to colorectal cancer remains unclear. In this study, we identified the lncRNA, DANCR, which was upregulated in colorectal cancer. The upregulation of DANCR expression was associated with shorter patient survival time. DANCR depletion decreased cell proliferation, cell cycle progression, and tumorigenesis in a subcutaneous mouse xenograft model system. We further demonstrated that DANCR bound with lysine acetyltransferase 6A. This binding was essential for KAT6A acetyltransferase activity and thus, it influenced the expression of KAT6A target genes. Our data indicated that DANCR functions as an oncogenic lncRNA that promotes tumor development and progression. Therefore, DANCR may be a target molecule for colorectal cancer treatment.

Glutaminyl cyclase inhibitor contributes to the regulation of HSP70, HSP90, actin, and ribosome on gene and protein levels in vitro.

Because of the crucial roles of upregulated glutaminyl cyclase (QC) in the initiation and development of Alzheimer's disease (AD), QC inhibitors are supposed as disease-modifying agents for the treatment of AD. And reported compounds encourage this hypothesis greatly based on the remarkable anti-AD effects in vivo. To illustrate the mechanism in detail, the actions of a selected QC inhibitor (23) were assessed firstly in a cell system here. It was demonstrated that QC activities and the generation of pyroglutamate-modified ß-amyloids in PC12 cells were both inhibited obviously after the treatment of 23. A total of 13 and 15 genes were up- and downregulated significantly in treated cells by RNA-sequencing analysis. Quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, WB, and immunofluorescence analysis supported the effects of 23 on the transcriptome of PC12 cells consequently. The expressions of chaperones, heat shock proteins (HSP) 70, and 90, were upreglutated, while gene expression of actin and the level of encoded protein were reduced significantly in PC12 cells with the treatment. Furthermore, the regulations of ribosome were observed after the treatment. These results indicate the potency of 23 to improve the translation, expression and folding regulation of proteins and affect the multivalent cross-linking of cytoskeletal protein and other proteins subsequently in the cell system and might contribute to the understanding of the mechanism of QC inhibitor as potential anti-AD agents.

Clinical outcomes and associated factors of radioiodine-131 treatment in differentiated thyroid cancer with cervical lymph node metastasis.

Cervical lymph node metastasis (CLNM) is common in differentiated thyroid cancer (DTC). Radioiodine-131 (131I) treatment is recommended for the removal of residual thyroid tissue following thyroidectomy. To date, the effect of 131I therapy on the outcomes of patients with DTC with CLNM is unclear. The aim of the present study was to evaluate the final outcome of patients with DTC with CLNM according to 131I administration, and to analyze the factors that may affect clinical outcomes. A total of 357 patients with DTC with CLNM were recruited and divided into three groups: Those who received 2, 3 or 4 doses of 131I therapy, respectively. Successful ablation was defined as levels of stimulated serum thyroglobulin <2 ng/ml in the absence of CLNM. The rates of successful ablation were 80.35 (229/285), 76.36 (42/55) and 70.59% (12/17) for patients who received 2, 3 and 4 doses, respectively. The patients with DTC with CLNM who were <45 years old, with tumor sizes <2 cm, solitary nodules and TNM stage I-II disease exhibited significantly higher rates of successful ablation compared with the patients who were ≥45 years old, with tumor size ≥2 cm, multiple nodules and stage III-IV disease. Multivariate analyses revealed that tumor size, number of nodules and TNM stage were independent risk factors associated with successful ablation in patients with DTC with CLNM who received 2 doses of 131I therapy. 131I administration is a useful therapy to eradicate cervical lymph node metastasis in patients with DTC, and may be preferentially indicated in patients with DTC with CLNM who are aged <45 years, with tumor sizes <2 cm, solitary nodules and lower TNM stages, in order to control and prevent recurrence and/or metastases.

Design, synthesis and biological evaluations of novel pyridone-thiazole hybrid molecules as antitumor agents.

A hybrid pharmacophore approach was adopted to design and synthesize new series of pyridone-thiazole hybrid compounds. The structures of the compounds were established by IR, 1H NMR, 13C NMR, and HRMS. All the newly prepared compounds (3a-3m) were in vitro evaluated for their antiproliferative activity against three human cancer cell lines, namely Colon cancer (HCT-116), gastric carcinoma (MGC803) and hepatocellular cancer (Huh7). Bioassay results demonstrated that most of the tested compounds showed potent anti-tumor activities against various cancer cells in vitro, and some compounds exhibited stronger effects than positive control 5-Fluorouracil (5-FU). Compound 3b showed the best anti-tumor activity with IC50 values of 8.17 µM and 3.15 µM against HCT116 and MGC803 cell lines, respectively, which was 1.4-8.1 times more potent than 5-Fluorouracil (IC50 = 11.29 µM and 25.54 µM against HCT116 and MGC803 respectively). These findings suggest that compound 3b may have potential to be developed as a promising lead for the design of novel anticancer small-molecule drugs.

Mixed epithelial and stromal tumor of kidney with renal vein extension: an unusual case report and review of literature.

Mixed epithelial and stromal tumor of kidney (MESTK) is a rare but distinct renal complex neoplasm composed of a mixture of mesenchymal and epithelial elements with characteristic ovarian-type stroma. Due to its relative rarity, little is known about the histogenesis and prognostic factors of this tumor. Although most reported cases display bland histological features and benign clinical course, a few cases of malignant MESTK have been described. We report an unusual case of MESTK in a 50-year-old female patient with renal venous involvement. Macroscopically, the tumor was solid and unencapsulated in the central region of left kidney. There was a polypoid mass with slender pedicle found to extend into the renal vein forming an intravenous tumor thrombus. Histologically, both renal and intravenous mass were composed of bland spindle-shaped cells and round dilated tubules lined by epithelium without any cytological atypia. The spindle cells were diffusely positive for smooth muscle actin and desmin, while tubules were positive for pan-cytokeratin (AE1/AE3). A diagnosis of MESTK with renal vein extension was made. The patient received no adjuvant treatment after radical nephrectomy. There was no sign of recurrence or metastasis of tumor found in a period of 16-month regular follow-up. To our knowledge, this is the first case of MESTK with renal vein extension, but lacking malignant histological appearance. Additional studies of MESTK with vein involvement will be needed to determine whether this imparts any adverse behavior, similar to other benign renal tumors with vascular involvement.

EFEMP1 inhibits migration of hepatocellular carcinoma by regulating MMP2 and MMP9 via ERK1/2 activity.

The role of epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) inhibiting migration in hepatocellular carcinoma (HCC) remains unknown. Expression of EFEMP1 in HCC cell lines were quantified by western blotting and real-time PCR. The role of EFEMP1 in HCC cell migration was explored in vitro via siRNA and adding purified EFEMP1 protein. The associated molecule expression was detected by western blotting after downregulation of EFEMP1 and also tested by immunohistochemistry. Eight pairs of HCC non-HCC liver samples and 215 HCC samples were subjected to immunohistochemistry. EFEMP1 was highly expressed in 7,721 and HepG2 HCC cell lines while HuH7 HCC cell line expressed the lowest level of EFEMP1 compared with the others. Downregulating EFEMP1 by siRNA markedly increased the migration ability of HCC cells while adding purified EFEMP1 protein inhibited HCC cell migration. Downregulation of EFEMP1 increased the expression of ERK1/2, MMP2 and MMP9. Furthermore, U0126 (a highly selective and potent inhibitor of pERK1/2) could abrogate the migration ability enhanced by siRNA. Accordingly, MMP2 and MMP9 were inversely expressed with EFEMP1 expression by immunohistochemistry. EFEMP1 downregulated in HCC tissues, and lower EFEMP1 expression was significantly associated with HCC patients with ascites (P=0.050), vascular invasion (P=0.044), poorer differentiation (P=0.002) and higher clinical stage (P=0.003).

Imiquimod Increases Cutaneous VEGF Expression in Imiquimod-induced Psoriatic Mouse Model.

Psoriasis is a chronic skin disease of unknown aetiology but increasing evidence suggests that cutaneous angiogenesis plays an important role. Vascular endothelial growth factor (VEGF) is one of the pro-angiogenic cytokines which is related to the pathogenesis of psoriasis. Our study evaluated the influence of imiquimod (IMQ) on VEGF in IMQ-induced mouse model. Balb/c female mice (n=16) 8-12 weeks of age were randomly divided into an experimental group (5% IMQ cream) and the control group (Vaseline cream). Serum levels of circulating VEGF-A were quantified by enzyme-linked immunosorbent assay. VEGF protein expression in tested skin was measured by western blotting and immunohistochemical staining. The tested skin in the experimental group expressed higher levels of VEGF protein than in the control group (p=0.012); immunohistochemical staining revealed that the cells over-expressing VEGF localized predominantly in the epidermis and vascular endothelium. Circulating VEGF-A levels showed no significant difference between the experimental and control groups (p=0.445). The IMQ-induced mouse psoriatic model showed an upregulation of VEGF in the skin lesions mimicking human psoriasis but the circulating VEGF-A levels showed no difference. This model may be useful to investigate the role of angiogenesis in psoriasis.

Positive feedback loop of hepatoma-derived growth factor and ß-catenin promotes carcinogenesis of colorectal cancer.

To clarify the role of hepatoma-derived growth factor (HDGF) and ß-catenin in carcinogenesis of colorectal cancer (CRC), our results showed that high HDGF expression was found in CRC cells and tissues and significantly related to histological differentiation (p = 0.035) and lymph node metastasis (p = 0.000). Significant positive correlation between HDGF expression and ß-catenin abnormal expression was found in CRC tissues. High HDGF and lymph node metastasis were the strong independent prognostic indicators for reduced overall survival in CRC patients. HDGF knockdown dramatically inhibited cellular proliferation, migration, invasion, and tumorigenesis, both in vitro and in vivo, but induced G1 phase arrest and apoptosis in CRC cells. HDGF knock-down dramatically suppressed ß-catenin and its down-stream genes expression in CRC cells. Intriguingly, ß-catenin knock-down dramatically suppressed HDGF expression in CRC cells. Human recombinant Wnt3a and DKK1 treatment increased and decreased HDGF, ß-catenin, c-Myc, cyclin D1, MMP9, and phos-GSK-3ß (Ser9) protein expression in nuclear and cytoplasmic fraction of CRC cells upon ß-catenin knock-down, respectively. Three HDGF-binding elements in ß-catenin promoter were found and specific for transcriptional activation of ß-catenin in CRC cells. In conclusion, our results first suggest that HDGF and ß-catenin interacts as a positive feedback loop, which plays an important role in carcinogenesis and progression of CRC.

Hybrid eccrine gland and hair follicle hamartoma: a new entity of adnexal nevus.

Eccrine nevus shows increase in number or size of eccrine glands, whereas hair follicle nevus is composed of densely packed normal vellus hairs, and eccrine-pilar angiomatous nevus reveals increase of eccrine, pilar, and angiomatous structures. No case with increased number of both eccrine glands and hair follicles only in the dermis has been previously reported. A 10-month-old girl presented with cutaneous hamartoma with overlying skin hyperpigmentation on her left hypochondrium since 3 months of age, in whom the lesion was completely excised. Histopathology demonstrated evidently increased number of both eccrine glands and hair follicles in the dermis with reactive hyperplasia of collagen fibers. No recurrence occurred after the tumor was completely excised. A term "hybrid eccrine gland and hair follicle hamartoma" is proposed for this unique lesion.

Value of micro-CT for monitoring spinal microvascular changes after chronic spinal cord compression.

Neurological degeneration can occur after compression of the spinal cord. It is widely accepted that spinal cord compression leads to ischemic lesions and ultimately neurological dysfunction due to a narrowed spinal canal. Therefore, an in-depth understanding of the pathogenesis of spinal cord compression injury is required to help develop effective clinical interventions. In the present study, we propose a new method of quantitative 3D micro-CT to observe microvascular events in a chronic spinal cord compression rat model. A total of 36 rats were divided into two groups: sham control group (n = 12) and compressive spinal cord injury group (n = 24). Rats were scarified at four weeks after surgery. In each group, CD34 micro-vessel immunohistochemical staining was performed in half of the animals, while micro-CT scanning was performed in the other half. Microvessel density (MVD) was measured after immunohistochemical staining, while the vascular index (VI) was measured in 3D micro-CT. In comparison with sham control, abnormal somatosensory evoked potentials (SEP) can be seen in all 24 cases of the compression group, and VI shows the amount of microvessels reduced consistently and significantly (p < 0.01). A significant correlation is also found between MVD and VI (r = 0.95, p < 0.01). These data suggest that quantitative 3D micro-CT is a sensitive and promising tool for investigating microvascular changes during chronic compressive spinal cord injury.