Stem cell quiescence and its clinical relevance.

Quiescent state has been observed in stem cells (SCs), including in adult SCs and in cancer SCs (CSCs). Quiescent status of SCs contributes to SC self-renewal and conduces to averting SC death from harsh external stimuli. In this review, we provide an overview of intrinsic mechanisms and extrinsic factors that regulate adult SC quiescence. The intrinsic mechanisms discussed here include the cell cycle, mitogenic signaling, Notch signaling, epigenetic modification, and metabolism and transcriptional regulation, while the extrinsic factors summarized here include microenvironment cells, extracellular factors, and immune response and inflammation in microenvironment. Quiescent state of CSCs has been known to contribute immensely to therapeutic resistance in multiple cancers. The characteristics and the regulation mechanisms of quiescent CSCs are discussed in detail. Importantly, we also outline the recent advances and controversies in therapeutic strategies targeting CSC quiescence.

Thyroid paraganglioma accompanied by lymph node metastasis or trachea invasion: A case report.

Thyroid paraganglioma (TP) is an uncommon neuroendocrine tumor with potential for misdiagnosis. Case 1 (male; 44 years old) presented with hoarseness for 3 months. A 2.5-cm gray nodule in the left thyroid was diagnosed as TP by immunohistochemistry. Lymph node metastasis was confirmed by H&E staining and immunohistochemistry. The patient was followed-up for 3 years without any signs of recurrence or metastasis. Case 2 (female; 39 years old) presented with an asymptomatic but rapidly growing thyroid nodule. The patient underwent thyroidectomy 8 years ago (2008) and was diagnosed with TP postoperatively. The patient was diagnosed with recurrence and exhibited trachea invasion. Thyroidectomy and partial trachea resection were performed. A literature review revealed that 62 other cases of TP have been reported, and most of them exhibited low malignant potential. However, the two cases presented in the current case report exhibited a high malignant potential, accompanied by lymph node metastasis or trachea invasion, and these features imply that the choice of treatment for patients should be based on their different degrees of malignancy.

Multi-Omics Analysis of Acute Lymphoblastic Leukemia Identified the Methylation and Expression Differences Between BCP-ALL and T-ALL.

Acute lymphoblastic leukemia (ALL) as a common cancer is a heterogeneous disease which is mainly divided into BCP-ALL and T-ALL, accounting for 80-85% and 15-20%, respectively. There are many differences between BCP-ALL and T-ALL, including prognosis, treatment, drug screening, gene research and so on. In this study, starting with methylation and gene expression data, we analyzed the molecular differences between BCP-ALL and T-ALL and identified the multi-omics signatures using Boruta and Monte Carlo feature selection methods. There were 7 expression signature genes (CD3D, VPREB3, HLA-DRA, PAX5, BLNK, GALNT6, SLC4A8) and 168 methylation sites corresponding to 175 methylation signature genes. The overall accuracy, accuracy of BCP-ALL, accuracy of T-ALL of the RIPPER (Repeated Incremental Pruning to Produce Error Reduction) classifier using these signatures evaluated with 10-fold cross validation repeated 3 times were 0.973, 0.990, and 0.933, respectively. Two overlapped genes between 175 methylation signature genes and 7 expression signature genes were CD3D and VPREB3. The network analysis of the methylation and expression signature genes suggested that their common gene, CD3D, was not only different on both methylation and expression levels, but also played a key regulatory role as hub on the network. Our results provided insights of understanding the underlying molecular mechanisms of ALL and facilitated more precision diagnosis and treatment of ALL.

Clinical Analysis of 122 Cases with Mycoplasma Pneumonia Complicated with Atelectasis: A Retrospective Study.

INTRODUCTION: This study aims to explore the clinical characteristics, treatment, and prognosis of mycoplasma pneumonia complicated with atelectasis. METHODS: A retrospective analysis was performed on 122 children with mycoplasma pneumonia complicated with atelectasis. These children were hospitalized in the Xiamen Campus of the Pediatric Hospital of Fudan University and the Children's Hospital of Xiamen between December 2015 and December 2018. A diagnosis was made for each case on the basis of the clinical symptoms and signs, Mycoplasma pneumoniae-specific IgM antibody, and imaging results. RESULTS: Among the 122 cases with mycoplasma pneumonia complicated with atelectasis, all cases had retractable M. pneumoniae infection, 102 cases underwent fibrobronchoscopic lavage treatment, and all cases were treated with macrolide antibiotics after a definite diagnosis was made. Furthermore, 107 cases improved and were discharged. Follow-up was performed for 3-4 weeks for all patients, and all patients, including the five cases with retractable disease, recovered well. CONCLUSION: The major clinical manifestations for M. pneumoniae pneumonia are fever and stimulatory dry cough. Macrolide antibiotics remain the treatment of choice.

Primary thoracic neuroblastoma in an adult: A rare case report.

RATIONALE: Neuroblastoma is one of the most common malignant tumors in childhood, which mainly occurs in adrenal glands and peripheral sympathetic nerve system. Neuroblastoma occurring in adulthood is rare, and adults with neuroblastoma arising from thorax are exceedingly rare. A case of neuroblastoma that originated from thorax was reported, and was treated by resection operation. PATIENT CONCERNS: A 46-year-old woman was admitted to our hospital with left side chest pain for 5 days. Laboratory examinations were all normal. Chest computerized tomogram (CT) showed a lesion with clear boundary that was located at the left dorsal pleura. The nature of the mass was heterogeneous, showing slight heterogeneous enhancement after contrast and there was no obvious necrosis. DIAGNOSES: Based on the morphologic and immunohistochemical features, the tumor diagnosis was favorable for neuroblastoma. INTERVENTIONS: A resection operation was carried out. OUTCOMES: Three years postoperative, no sign of recurrence or metastasis has been observed. LESSONS: Primary neuroblastoma in adulthood is rare and has poor prognosis. Resection can be an important treatment option, and combining with other methods like chemotherapy, stem cell transplantation, the survival rate may be improved.

Angiosarcoma originating in the anterior mediastinum: A case report.

RATIONALE: Angiosarcomas are malignant vascular tumors, and angiosarcoma occurring in the anterior mediastinum is rare. Here we report a case of angiosarcoma that originated in the anterior mediastinum treated with surgery, followed by radiotherapy and synchronous chemotherapy. PATIENT CONCERNS: A 56-year-old female was admitted to our hospital with chest pain for 3 days. Chest computerized tomogram (CT) examination showed a heterogeneous mass in the anterior superior mediastinum, and after injection of contrast agent, the mass showed obvious heterogeneous enhancement. Magnetic resonance imaging (MRI) with T1 weighted image (T1WI) showed isointensity and T2 weighted image (T2WI) showed heterogeneous signal intensity, the mass showed an obvious heterogeneously enhancement after intravenous administration of contrast material. DIAGNOSIS AND INTERVENTIONS: Surgical resection operation was carried out. According to its morphologic and immunohistochemic feature of tumor cells which expressing CD31, CD34, and ERG, the tumor was categorized as an angiosarcoma. After operation, the patient received radiotherapy and synchronous chemotherapy. OUTCOMES: At present, 8 months postoperatively, no signs of recurrence have been observed. LESSONS: Although angiosarcoma in anterior mediastinum is rare, when a mass located in this area, a more careful immunohistological analysis should be performed to avoid overlooking the presence of angiosarcoma.

Directly obtaining pristine magnetic silk fibers from silkworm.

By feeding the silkworms with the nano Fe3O4 powder together with mulberry leaves, we directly obtained silkworm spun pristine magnetic silk fiber, MSF. To compare with the normal SF found that this MSF not only has expected magnetic properties, but also has enhanced thermal stability and mechanical properties, e.g. stress and strain.

[Study on activation of AKT/mTOR pathway in anaplastic large cell lymphoma].

OBJECTIVE: To study the expression of anaplastic lymphoma kinase (ALK) and the phosphorylation status of AKT, mammalian target of rapamycin (mTOR), 4E-binding protein 1 (4E-BP1) and ribosomal protein S6 kinase (p70S6K) and their interrelationships and clinical pathological significance in anaplastic large cell lymphoma (ALCL) patients. METHODS: Immunohistochemical and EnVision methods were used to detect the expression of ALK, p-AKT, p-mTOR, p-4E-BP1 and p-p70S6K. RESULTS: Among the 81 ALCL patients, 51 (63.0%) expressed ALK, whereas the other 30 (37.0%) did not. Patients with ALK(+) ALCL had a better prognosis than those with ALK-ALCL (P < 0.05). Out of the 71 ALCL samples studied, p-AKT was detected in 54 (76.1%) samples and its phosphorylation was correlated with ALK expression (P < 0.05); p-mTOR was detected in 57 (80.3%) samples and its expression was correlated with both ALK and p-AKT (P < 0.05); p-4E-BP1 and p-p70S6K were detected in 64 (90.1%) and 66 (93.0%) samples respectively, and their expressions were related with p-mTOR (P < 0.05), but not with ALK or p-AKT (P > 0.05). COX Proportional Hazard Model analysis showed that both the expression of ALK and the B symptoms affected the prognosis (P < 0.05), moreover, the former had greater impact than the later. CONCLUSION: Expressions of p-AKT, p-mTOR, p-4E-BP1 and p-p70S6K are detected in ALCL, while ALK(+) cases have higher incidence than those with ALK(-) cases. Phosphorylation of AKT and mTOR is correlated with ALK expression, suggesting that there is an activated pathway of AKT/mTOR in patients with ALK(+) ALCL, but the activation have no obvious prognostic significance.

[Blockage of mTOR signaling pathway by rapamycin contributes to inhibition of tumor cell proliferation in ALK-positive lymphoid cell strains].

OBJECTIVE: To investigate the relationship between mTOR signaling pathway and ALK-positive lymphoid cell lines. METHODS: The expression of the downstream effector proteins of mTOR were analyzed by Western blot before and after Karpas299, BaF3/NPM-ALK and BaF3 cell lines treated with rapamycin. Effect of rapamycin on cell proliferation was detected by MTT assay. FACS was used to analyze apoptosis and cell cycles. RESULTS: mTOR signaling phosphoproteins, p-p70S6K and p-4E-BP1 were highly expressed in ALK(+) Karpas299, BaF3/NPM-ALK and parental BaF3 cell lines, and they were dephosphorylated after 1 h withdrawal of IL-3 in BaF3 cells. After 48 h exposure to 10 nmol/L rapamycin, p-p70S6K and p-4E-BP1 proteins expression were decreased, and mainly for the former. The relative inhibitory rate to its control cells was 24.4% in Karpas299, 37.8% in BaF3/NPM-ALK and 61.6% in BaF3. The apoptotic ratio was increased from (11.97 +/- 0.11)% to (15.87 +/- 0.62)% in Karpas299 (P < 0.05), from (3.23 +/- 0.11)% to (7.67 +/- 0.49)% in BaF3 (P < 0.05) and from (1.90 +/- 0.47)% to (2.80 +/- 0.27)% in BaF3/NPM-ALK (P > 0.05). The fraction of G(1) phase cells increased from (37.63 +/- 1.91)% to (69.77 +/- 5.44)% in BaF3/NPM-ALK, from (31.13 +/- 2.51)% to (40.70 +/- 1.47)% in Karpas299 and (53.57 +/- 2.22)% to (63.70 +/- 1.20)% in BaF3 (P < 0.05). CONCLUSION: NPM-ALK kinase can activate mTOR signaling pathway. Rapamycin can inhibit the proliferation of ALK(+) lymphoid cells by blocking mTOR signaling pathway and inducing cell cycling arrest at G(1) phase.

[Expression of anaplastic lymphoma kinase and survivin proteins in anaplastic large cell lymphoma and its significance].

OBJECTIVE: To study the expression of anaplastic lymphoma kinase (ALK) and survivin proteins in anaplastic large cell lymphoma (ALCL) and there clinical significance. METHODS: The morphologic characteristics were studied by routine light microscopy. Immunohistochemical staining for ALK and survivin proteins was performed using LSAB method. RESULTS: ALK protein was positive in 51 cases (63%) and negative in 30 cases (37%) of the 81 cases of ALCL studied. The prognosis of patients with ALK protein expression was better than those without ALK expression (P < 0.05). As for survivin protein, there were various degrees of expression in all the 77 ALCL cases studied. High level of survivin protein expression was observed in 33 cases (42.9%), while low level of expression was seen in 44 cases (57.1%). The expression of survivin protein did not correlate with that of ALK protein (P > 0.05). The survival rate was significantly lower in patients with high survivin protein expression (P < 0.05). In cases with ALK protein expression, the prognosis was less favorable if there was also high co-expression of survivin protein (P < 0.05). In ALK protein negative cases, prognosis did not significantly correlate with the expression of survivin protein (P > 0.05). In addition, multivariate analysis confirmed the prognosis value of ALK protein expression, survivin protein expression and constitutional symptoms. CONCLUSION: Survivin protein expression can serve as an independent prognostic predictor of unfavorable clinical outcome in patients with ALCL, especially when ALK protein is positive.

[Clinico-pathological analysis of 188 cases of bone marrow involvement of lymphoma].

OBJECTIVE: To evaluate pathomorphologic and immunohistochemical characteristics of the bone marrow involvement of lymphoma and its significance in the diagnosis and subtype of lymphoma with bone marrow involvement. METHODS: One hundred and eighty eight formalin fixed and paraffin embedded bone marrow biopsy specimens were studied. Immunohistochemical staining was performed. RESULTS: (1) Five patterns of bone marrow involvement of lymphoma were found, including diffuse (44.9%), focal (29.3%), interstitial (11.6%) and nodular (6.1%). (2) There were many subtypes of lymphoma in these cases, the most common type was lymphoplasmacytic lymphoma (21.7%). (3) The lymphomas in bone marrow biopsy had their own special characteristics of morphology and immunophenotype as did in extra-medullar lymphomas. (4) Fibrosis (75.8%) and hematopoietic tissue hypoplasia (71.1%) were found in most cases and necrosis in a few cases. CONCLUSIONS: Most cases of bone marrow involvement of lymphoma could be diagnosed and classified by combination of histopathological and immunohistochemical analysis. Diagnosis of some cases could be made only after the review of pathological changes of lymph node. A few cases were difficult to classify their subtypes of lymphoma.

[A clinicopathological study of 96 cases of lymphoblastic lymphoma].

OBJECTIVE: To investigate the clinicopathological and immunohistochemical features of lymphoblastic lymphoma (LBL). METHODS: A retrospective clinicopathological study of 96 cases LBL was carried out. Immunohistochemical staining was used for the characterization and immunophenotyping. RESULTS: The patients age ranged from 4 to 72 years, with a median of 16 years, 69 patients were male and 27 female. Seventy-three cases had superficial or multi-lymphoadenopathy and 31 of them had mediastinal masses. Bone marrow was involved in 15 cases. Seventy-three cases were in clinical stages III and IV. The median survival of the followed-up patients was 5.5 (2 approximately 120) months. TdT and CD99 positive reactions were 75.0% and 92.7%, respectively. Of the 96 cases, 78 displayed T-cell marker positivity and 18 B-cell markers. 82.1% of the patients younger than 30 years of age had significantly higher incidences of T-LBL (64 patients), and 93.6% of the patients with mediastinal masses expressed T-cell markers. The poor prognostic factors were T-cell tumors, clinical stages III and IV, Ki-67 PI < 80% and no chemotherapy (P < 0.01). CONCLUSION: In children and young males, mediastinal masses with superficial or multi-lymphoadenopathy favors the diagnosis of LBL, but negative TdT reaction can not exclude this diagnosis. T-LBL is more common than B-LBL. Clinical stages, immunophenotypes and the level of Ki-67 expression were closely related with prognosis of LBL.