BACKGROUND:The use of three-dimensional cel culture techniques can better simulate the cel ular microenvironment, providing new tools for tissue engineering research.
OBJECTIVE:To analyze the biomaterial selection and application characteristics in three-dimensional cel culture as wel as applications in tumor tissue engineering.
METHODS:We searched Wanfang database and PubMed database 1998-2015 years for relevant literature using keywords of“three-dimensional cultures;scaffold;cel growth;cel differentiation;tumor tissue engineering”in Chinese and English, respectively.
RESULTS AND CONCLUSION:The selection and application of three-dimensional scaffold materials is one of the keys. So far, scaffold materials, such as col agen gels, gelatin sponge, agarose, chitosan, demineralized bone matrix, cannot provide the extracel ular matrix similar to the micro-environment in which seed cel growth and proliferation are not affected, and the ability to secrete type II col agen and glycosaminoglycan is decreased, although they can provide three-dimensional space for seed cel s. Biomimetic scaffold characterized as little trauma and strong plasticity gradual y shows its unique advantages. Three-dimensional culture conditions raise pro-angiogenic growth factor secretion from tumor cel s, and this feature is positively correlated with the occurrence of in vivo tumor angiogenesis.

Objective:To summarize the clinical features and experience in diagnosis and treatment of subglottic cysts in children.Methods:The clinical data of 5 children with subglottic cysts admitted in Qilu Children′s Hospital of Shandong University from April 2018 to June 2019 were retrospectively analyzed.Results:Among the 5 patients, 2 cases were premature infants and 3 cases were full term infants.All patients had an endotracheal intubation history.One patient was asymptomatic.Four patients had laryngeal stridor, 2 cases of whom were accompanied by hoarseness and dyspnea.These 2 patients were used to be misdiagnosed with laryngomalacia, laryngitis, etc.Bronchoscopy revealed subglottic gray-white cyst-like lesions, and enhanced CT showed low density without enhancement.All patients were treated with laser and forceps, and bronchoscope was applied in the follow up period for 5-12 weeks.There was no recurrence or subglottic stenosis.Conclusions:Laryngeal stridor in children with a history of endotracheal intubation must be examined by bronchoscopy in time to find out whether there is subglottic cysts.Laser therapy is an effective treatment for subglottic cysts.

OBJECTIVETo investigate the effects of benzene poisoning on the expression of multidrug resistance 1 (MDR1) gene and P-glycoprotein (P-gp) in the bone marrow mononuclear cells (BMMNCs) of C57BL/6 mice.

METHODSC57BL/6 mice were randomly divided into control group (n = 24), low-dose group (n = 24), medium-dose group (n = 24), and high-dose group (n = 24) to receive corn oil, 25 mg/kg benzene, 50 mg/kg benzene, or 100 mg/kg benzene by gavage, once daily, 5 days/weeks, for 4 weeks. The mice were sacrificed on day 12, 26, or 29 of poisoning. Peripheral blood routine test was performed; real-time quantitative PCR was used to measure the MDR1 gene expression in BMMNCs; Western blot was used to measure the P-gp expression in BMMNCs.

RESULTSOn day 12, the red blood cell count and hemoglobin level in the high-dose group were significantly lower than those in the control group, low-dose group, and medium-dose group (P < 0.01 or P < 0.05). On day 26, the white blood cell count in the high-dose group was significantly lower than those in the control group, low-dose group, and medium-dose group (P < 0.01 or P < 0.05). At each time point, the mRNA expression of MDR1 gene in the low-dose group, medium-dose group, and high-dose group was significantly lower than that in the control group (P < 0.01). On day 26, the P-gp expression in the high-dose group was significantly lower than those in the control group, low-dose group, and medium-dose group, and the P-gp expression in the medium-dose group was significantly lower than that in the low-dose group (P < 0.01 or P < 0.05). On day 29, the P-gp expression in the low-dose group, medium-dose group, and high-dose group was significantly lower than that in the control group (P < 0.05).

CONCLUSIONBenzene poisoning can affect the expression of MDR1 gene and P-gp, which may be one of the mechanisms of benzene hematotoxicity.

ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; metabolism ; Animals ; Benzene ; toxicity ; Bone Marrow Cells ; cytology ; drug effects ; metabolism ; Drug Resistance, Multiple ; genetics ; Male ; Mice ; Mice, Inbred C57BL ; Monocytes ; cytology ; drug effects ; metabolism

OBJECTIVETo study the potential aging effect on workers exposed to acrylonitrile (ACN).

METHODSThe deletion rates of mitochondrial DNA (mtDNA) in peripheral blood nucleate cells of 47 exposed workers and 47 non-exposed workers (as control), as well as 12 old people and 12 young people were measured with polymerase chain reaction (PCR).

RESULTSThe positive rates of mtDNA deletion in peripheral blood nucleate cells were 17.02% in the workers exposed to ACN and 25.00% in group of old people. However, the mtDNA deletion was not detected in the control group and young people.

CONCLUSIONSACN could induce mtDNA deletion in peripheral blood nucleate cells of the exposed workers. There may be a potential molecular effect of occupational ACN exposure on workers' aging.

Acrylonitrile ; toxicity ; Adolescent ; Aged ; Aged, 80 and over ; Aging ; drug effects ; Blood Cells ; drug effects ; ultrastructure ; DNA Damage ; DNA, Mitochondrial ; drug effects ; Humans ; Occupational Exposure

Objective:To summarize the clinical data of 18 children with primary tracheobronchial tumors, and to investigate the safety and effectiveness of bronchoscopy intervention therapy.Methods:The clinical features, signs, imaging and bronchoscope characteristics, pathology types, endoscopy intervention therapy methods, and outcomes of 18 patients with primary tracheobronchial tumors treated in Qilu Children′s Hospital of Shandong University from January 2013 to August 2019 were retrospectively analyzed.Results:The patients aged from 2 years old to 12 years old, and the ratio of male and female was 1.71∶1.There were 8 cases of mucoepidermoid carcinoma, 7 cases of inflammatory myofibroblastoma, 1 case of infant fibrosarcoma, 1 case of intermediate vascular tumor, and 1 case of acinar cell carcinoma.All 18 patients received the biopsy under general anesthesia to determine the pathological type of tumor and underwent the interventional therapy to relieve airway obstruction.No complications such as massive bleeding, pneumothorax, and mediastinal emphysema were observed during and after operation.The endoscope examination was applied to assess the curative effect 1 week after the surgery, complete response 17 case, inefficiency 1 case, and the overall effective rate was 94%.Conclusions:It is safe and reliable to treat primary tracheobronchial tumor by bronchoscopy intervention therapy, which can be used as a palliative treatment and create conditions for further radical operation.It may even become a radical cure for tracheobronchial tumors.

BACKGROUND: The efficacy of entecavir (ETV) add-on peg-interferon therapy compared with ETV monotherapy in treatment-naïve hepatitis B virus (HBV) patients remains controversial. We investigated whether adding peg-interferon to ongoing ETV treatment leads to a better curative effect or not. METHODS: All patients have been recruited between August 2013 and January 2015 from the Shanghai Public Health Clinical Center and Zhongshan Hospital (China). Eligible HBV patients (n = 144) were randomly divided (1:1) to receive either ETV monotherapy (n = 70) or peg-interferon add-on therapy from week 26 to 52 (n = 74). Patients were followed-up for at least 2 years. Indexes including hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) seroconversion rate, sustained virologic response, transient elastography value, and histological scores were evaluated every 3 months until the end of the study. The rate of patients with HBsAg loss was defined as the primary endpoint criteria. RESULTS: At week 26, no patient achieved HBsAg seroconversion in either group. At week 52, one patient in the monotherapy group was HBsAg-negative but there was none in the combination therapy group. The monotherapy group showed significantly better liver function recovery results than the combination therapy group. At week 78, one patient in the combination group had HBsAg seroconverted. At week 104, only three patients in the combination therapy group were HBsAg-negative compared with one patient in monotherapy. The mean alanine aminotransferase and aspartate aminotransferase levels and transient elastography values decreased significantly compared with baseline. Both groups showed a favorable decrease in alpha-fetoprotein (monotherapy: 4.5 [2.8, 7.1] vs. 2.2 [1.8, 3.1] ng/mL, P < 0.001; combination therapy: 5.7 [3.0, 18.8] vs. 3.2 [2.0, 4.3] ng/mL, P < 0.001) and an improved result of liver biopsy examination scores. The combination group showed a better improvement in histology compared with the monotherapy group (mean transient elastography value 6.6 [4.9, 9.8] vs. 7.8 [5.4, 11.1] kPa, P = 0.028). But there was no significant difference in HBsAg conversion rate (1.8% [1/56] vs. 4.1% [3/73], P = 0.809) and HBeAg conversion rate (12.5% [7/56] vs. 11.0% [8/73], P = 0.787), as well as HBV-DNA, sustained virologic response (93.2% vs. 98.5%, P = 0.150) between the two groups. CONCLUSIONS: Both therapies supported liver function recovery and histology improvement. Combination therapy did not show better anti-viral efficacy in HBsAg or HBeAg seroconversion compared with monotherapy. However, combination therapy played a more positive role in reversing hepatic fibrosis compared with monotherapy. TRIAL REGISTRATION ClinicalTrials.gov: NCT02849132; https://clinicaltrials.gov/ct2/show/NCT02849132.

Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment. Oral squamous cell carcinoma (OSCC), a representative hypoxic tumor, has a heterogeneous internal metabolic environment. To clarify the relationship between different metabolic regions and the tumor immune microenvironment (TME) in OSCC, Single cell (SC) and spatial transcriptomics (ST) sequencing of OSCC tissues were performed. The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data. The metabolic activity of each spot was calculated using scMetabolism, and k-means clustering was used to classify all spots into hyper-, normal-, or hypometabolic regions. CD4T cell infiltration and TGF-β expression is higher in the hypermetabolic regions than in the others. Through CellPhoneDB and NicheNet cell-cell communication analysis, it was found that in the hypermetabolic region, fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts (iCAFs), and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12. The secretion of CXCL12 recruits regulatory T cells (Tregs), leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment. This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC, ST and TCGA bulk data, and highlights potential targets for therapy.
Humans ; Carcinoma, Squamous Cell/metabolism* ; Squamous Cell Carcinoma of Head and Neck ; Mouth Neoplasms/metabolism* ; Immunosuppression Therapy ; Transforming Growth Factor beta ; Head and Neck Neoplasms ; Gene Expression Profiling ; Tumor Microenvironment