Objective:To explore the cooperation and clinical significance of HIF-1α,ALDH1 and Hedgehog signaling pathway in the activation of cancer stem cell(CSC) in triple negative breast cancer(TNBC).Methods: ALDH1+(Aldehyde dehydrogenase1)breast cancer stem cells and ALDH1-breast cancer cells were selected from MDA-MB-231 cells by magnetic activated cell sorting system(MACS),qRT-PCR method was employed to analyze the expression differences of HIF-1α and Hedgehog signaling molecules Sonic hedgehog(SHH),patched1(PTCH1),Smoothened(SMO) and Glioma-associated oncogene homoglog1(GLI1) in ALDH1+ breast cancer stem cells and ALDH1-breast cancer cells.Immunohistochemical method was applied to study the expressions of HIF-1α and ALDH1 and the relationships among HIF-1α,ALDH1 and Hedgehog signaling molecules in TNBC.Results: The expressions of HIF-1α mRNA,SMO mRNA and GLI1 mRNA in ALDH1+ breast cancer stem cell were higher than those in ALDH1-breast cancer cell(P all<0.05).The positive expression rates of HIF-1α were 90.0% and 70.0%,and the positive rates of ALDH1 were 93.3 % and 66.7 % in TNBC and non-TNBC,respectively(P all<0.05).Spearman rank correlation analysis showed that the expression of HIF-1α was positively related with that of ALDH1 in TNBC(r=0.53,P<0.01).HIF-1α expression was correlated with lymph node metastasis and TNM stage(P all<0.05),ALDH1 expression was correlated with histological grade and TNM stage(P all<0.05).In addition,the expression of HIF-1α was positively related with that of Hedgehog signaling molecules SHH(r=0.584,P<0.01),SMO(r=0.467,P<0.01) and GLI1(r=0.439,P<0.05),the expression of ALDH1 was positively related with that of SHH(r=0.426,P<0.05) and GLI1(r=0.394,P<0.05).Conclusion: HIF-1α and Hedgehog signaling pathway were activated in ALDH1+ breast cancer stem cell.HIF-1α,ALDH1 and Hedgehog molecules may cooperate with each other to activate breast CSC to promote the malignant progression of TNBC.

H1 gene inactivation.Demethylation agent inhibits human pancreatic cancer cell line growth in association with ARH1 re-expression and reduced p-stat3 expression.

Objective To investigate the expression level and clinical significance of melanoma antigen gene A (MAGEA) in osteosarcoma patients. Methods Compare gene expression profiles in osteosarcoma cell lines and osteoblasts with gene microarrays. Validation of differentially expressed genes was carried out by real-time polymerase chain reaction analysis. Corresponding protein levels were measures by Western blot analysis in osteosarcoma cell lines and by immunohistochemistry in osteosarcoma tissues. The staining intensity of immuno-histochemistry was correlated with clinical outcome , and its prognostic significance was analyzed. Results Sev-eral genes belonging to MAGEA increased significantly in all osteosarcoma cell lines and tumor tissue , but not in normal osteoblast cell. Patients with MAGEA expression has higher risk of lung metastasis (relative risk 2.79, 95% confidence interval, 1.12-6.93; P = 0.028) and lower five-year survival rates (39.6% ± 8.4% vs. 80% ± 8.9%, P = 0.01) compared with patients without MAGEA expression. Conclusions The expression of MAGEA increased in osteosarcoma , which inversely correlating with outcome of osteosarcoma patients.

OBJECTIVETo investigate the mitochondrial DNA (mtDNA) five coding region sequence polymorphisms encompassing positions nt3954-4506, nt5218-5974, nt7942-8711, nt10296-10653, and nt14496-14867 in Chinese Han population of Yanbian area, Jilin province.

METHODSPolymerase chain reaction (PCR) and direct sequencing method were used to detect the haplotype distribution of mtDNA coding region in 200 unrelated Chinese Han individuals.

RESULTSOne hundred and ten haplotypes were observed in the 200 individuals. The gene diversity was 0.9879 and the random match probability was 0.0171. Compared with the Anderson's sequence,81 nucleotide variants were obtained,of which 66 were previously registered in MITOMAP,and 15 were novel.

CONCLUSIONThe obtained data suggest that these sequence polymorphisms are valuable genetic markers for personal identification when added to mtDAN control region investigation, and thus could be used as basic data for the forensic application in Chinese Han population.

Asian Continental Ancestry Group ; ethnology ; genetics ; Base Sequence ; China ; DNA, Mitochondrial ; genetics ; Genetics, Population ; Humans ; Molecular Sequence Data ; Open Reading Frames ; Polymorphism, Genetic ; Sequence Analysis, DNA

Acu-moxibustion oncology is an emerging subject which needs further exploration in many aspects. We tried to describe the origin and application of acu-moxibustion oncology in this paper. It is a novel therapy based on the combination of traditional meridian theory, classical traditional Chinese and Western medicine knowledge and new theories and viewpoints on tumors. Acupuncture surrounding tumors can change tumor microenvironment. Surrounding acupuncture alone can inhibit the growth of tumors, if combining with chemotherapy, it increases the tumor targeting of chemotherapy drugs, and may reduce the risk of drug-resistance. Surrounding acupuncture will probably become a breakthrough of tumor inhibition by acu-moxibustion. We hope that this novel therapy of traditional Chinese medicine will play a bigger role in tumors treatment.

OBJECTIVETo detect the expression of SCUBE3 in human osteosarcoma cell lines and surgical specimens of osteosarcomas and investigate its association with the patients' prognosis.

METHODSThe expression of SCUBE3 protein was detected in 5 osteosarcoma cell lines using Western blotting. CCK8 assay was used to assess the effect of SCUBE3 suppression mediated by two specific small interfering RNAs (siRNAs) on the proliferation of U2OS osteosarcoma cells, and the cell cycle changes were detected using flow cytometry. Immunohistochemistry was performed to detect the expression of SCUBE3 in 60 osteosarcoma tissues, and Kaplan-Meier method was performed for survival analysis of the patients.

RESULTSCompared with osteoblast hFOB1.19 cells, the osteosarcoma cell lines all showed significantly higher expressions of SCUBE3. In U2OS cells, suppression of SCUBE3 expression by siRNA significantly inhibited the cell proliferation (P<0.05). Kaplan-Meier survival analysis indicated that patients with high SCUBE3 expression had worse prognosis than those with low SCUBE3 expression (P=0.036).

CONCLUSIONSCUBE3 is up-regulated in the 5 osteosarcoma cell lines and in primary osteosarcoma tissues to promote the proliferation of osteosarcoma cells. A high SCUBE3 expression in osteosarcoma tissues is associated with a poor prognosis of the patients, suggesting that SCUBE3 can serve as a potential therapeutic target for osteosarcoma.

Bone Neoplasms ; metabolism ; pathology ; Calcium-Binding Proteins ; metabolism ; Cell Cycle ; Cell Line, Tumor ; Cell Proliferation ; Flow Cytometry ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Osteosarcoma ; metabolism ; pathology ; Prognosis ; RNA, Small Interfering ; Up-Regulation

Objective To investigate the effects of the multidisciplinary cooperative management intervention model on the self‐management efficacy of patients with ileostomy irritant dermatitis. Methods Among the patients with irritative dermatitis in the ileostomy section of the Anorectal Surgery and Ostomy Clinic of Hwamei Hospital, the Chinese Academy of Sciences, 72 patients, who visited the clinic from August 2016 to August 2018, met the inclusion criteria and were finally included in the study. According to the random number table method, 36 patients each were assigned to the control and observation groups respectively. There were no significant differences in age, sex and education between the two cohorts. The control groups were compared. The control group was treated with routine nursing methods. The observation group underwent multidisciplinary nursing intervention that was based on the routine measures of the control group. The Chinese version of the cancer self‐management efficacy was used as the questionnaire survey that was administered before and after treatment. The results were compared and analyzed between the patient groups. The independent sample t‐test was used to compare the results between the groups, and the paired sample t‐test was used for intra‐group comparisons. Results After intervention, the total scores of self‐management efficacy and positive attitude, self‐decompression and self‐decision scores were higher in the observation group than in the control group (t=4.192, 3.095, 4.123, 2.267, P<0.05). The scores of self‐administration efficacy and each dimension of the two groups were higher than those before intervention, and the difference was statistically significant (P<0.01). After the intervention, 3 patients (10.0%) in the observation group with recurrent dermatitis and 13 patients (43.3%) in the control group. The recurrence rate of the observation group was significantly lower than that of the control group (χ2= 8.357, P<0.05). Conclusion Multidisciplinary cooperative management can improve the self‐management efficacy of patients with irritating dermatitis and reduce the incidence of this condition.

Objective:Clinicopathological characteristics of neuroendocrine neoplasms are highly heterogeneous based on variable origins.Our study aims to explore the clinical features of rectal neuroendocrine neoplasm (RNEN).Methods:Patients with histologically diagnosed rectal neuroendocrine neoplasms were retrospectively analyzed between January 2012 and December 2020. Epidemiological characteristics, clinical manifestations, complete blood count, endoscopy findings, and pathological features were recorded and analyzed. T-test was used for measurement data analysis, Chi-square test was performed for classification data analysis, and Binary logistic regression was applied for analyzing risk factors of metastasis.Results:Among 172 patients, the male to female ratio was 107 to 65 with an average age of (52±12) years (16-77 years). Altered bowel habit was the most common initial symptom (58/172, 33.7%), followed by abdominal pain (36/172, 20.9%) and loss of body weight (27/172, 15.7%). One hundred and sixty-one cases were neuroendocrine tumors, 9 were neuroendocrine carcinomas and 2 were mixed neuroendocrine-non-neuroendocrine neoplasms. Most endoscopic presentations were polypoid lesions (147/172, 85.5%), mainly limited to mucosa (48/172, 27.9%) and submucosa (96/172, 55.8%). Twenty-nine patients developed lymph node invasion or distant metastasis at diagnosis. There were statistical difference of neutrophil-to-lymphocyte ratios (NLR) among groups with different tumor size (<10 mm vs. 10-20 mm vs.>20 mm, mean NLR 1.79±0.55 vs. 2.27±1.23 vs. 2.95±0.66, P<0.01. Compared with non-metastatic group, the metastatic group presented higher NLR(2.61±0.81 vs. 1.89±0.80, P<0.01). Tumor size (<10 mm vs. 10-20 mm vs.>20 mm, OR 1.00 vs. 2.10 vs. 5.25×10 9, P =0.001), invasion to bowel wall (mucosa vs. submucosa vs. muscularis vs. serosa invasion, OR 1.00 vs. 3.26 vs. 14.11 vs. 39.42, P=0.008), and NLR (NLR<2.25 vs. NLR≥2.25, OR 1.00 vs. 5.19, P =0.024) were risk factors for metastasis. Conclusion:Metastasis of RNEN is related with tumor size, degree of bowel invasion and NLR. High NLR is a poor prognostic factor of RNEN.

Immune checkpoint inhibitors (ICIs) have shown significant efficacy in clinical trials and applications of various malignant tumors, and have been approved for clinical application in China. ICIs can cause immune-related adverse events (irAEs), which may affect any organs. Early identification and appropriate treatment can improve patient outcome. 18F-FDG PET/CT is capable of early detection of irAEs and provides effective clinical guidance. This article reviews the clinical application of 18F-FDG PET/CT in detecting irAEs, including typical imaging findings and research progress.

Objective:To investigate the capability of 18F-FDG PET/CT imaging in monitoring combined immunotherapy response and detecting immune related adverse events (irAEs) in patients with advanced hepatobiliary carcinoma. Methods:From August 2018 to July 2019, 21 patients (14 males, 7 females, age (58.5±10.0) years) with advanced hepatobiliary carcinoma routinely underwent 66 18F-FDG PET/CT examinations in Peking Union Medical College Hospital. SUV max, the occurrence time and symptoms of irAEs were obtained and analyzed. Therapy response (complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), progressive metabolic disease (PMD)) was evaluated according to PET response criteria in solid tumors (PERCIST). Results:(1) Clinical results. Twenty-two irAEs occurred in 16 patients, while were not found in 5 patients. Six organs were involved, including thyroiditis(8), colitis(5), pneumonitis(4), rash(2), hepatitis(2), myositis and fasciitis(1). The appearance time of each irAEs were (103.0±58.0), (141.6±103.5), 34.0(6.0, 308.8), 9 and 117, 62 and 67, and 87 d after therapy, respectively. PET/CT detected all pneumonitis and myositis and fasciitis, but no rash and hepatitis were found. For colitis and thyroiditis, PET/CT detected 4 and 6 times respectively. (2) PET/CT signs of irAEs. Except thyroiditis, all irAEs lesions exhibited exudative changes in CT and high-avidity in PET. SUV max of the lesions were 9.0(7.9, 17.6) (colitis), 7.1±3.2 (thyroiditis), 5.3 and 8.6 (pneumonitis), 4.1 (myositis and fasciitis), respectively. (3) Therapy assessment. Among 21 patients, there were 7 for PMR, 9 for SMD, 5 for PMD, which were 7, 8, 1 in patients with irAEs and 0, 1, 4 in patients without irAEs. Conclusions:Patients with advanced hepatobiliary carcinoma can benefit from combined immunotherapy. 18F-FDG PET/CT can be used to evaluate the efficacy of immunotherapy by detecting the changes of tumor lesions and the occurrence of irAEs simultaneously. However, it is necessary to use CT to distinguish tumor progression from irAEs.