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OBJECTIVE: To explore the value of artificial intelligence (AI) in improving the detection rate of traumatic rib fractures by radiologist residents and the consistency among different readers. METHODS: Chest CT images of 393 patients with acute trauma from China-Japan Union Hospital of Jilin University (hospital 02) and Shanghai Ninth People' s Hospital (hospital 03) were collected in this research. The consensus achieved by three radiology experts was regarded as the reference standard. All the images assigned to three hospitals: Peking University First Hospital (hospital 01), hospital 02 and hospital 03, and were then randomly divided into two groups (group A and group B: group A included 197 patients, and group B included 196 patients). Each group was read by one radiologist resident from each hospital for rib fracture detection. Each case was read twice by the same radiologist, with and without the assistance of the AI ["radiologist-only" reading and "radiologist + AI" reading]. The detection rates of different types of rib fractures (displaced fractures and occult fractures) were compared between "radiologist-only" reading and "radiologist + AI" reading. The consistencies of different radiologists with different reading methods were evaluated. RESULTS: The detection rates of displaced rib fractures and occult rib fractures by "radiologist + AI" reading were significantly higher than those read by "radiologist-only" reading (94.56% vs. 78.40%, 76.60% vs. 49.42%, P < 0.001). For "radiologist-only reading", the Kappa coefficients of the radiologists between hospital 01 and hospital 03 were slightly greater than 0.4 (indicating moderate consistency), the coefficients of the radiologists between hospital 01/hospital 02 and hospital 02/hospital 03 were less than 0.4 (indicating poor consistency). The Phi coefficients of the radiologists among different hospitals were all less than 0.6 (indicating moderate correlation). With "radiologist + AI" reading, the Kappa and Phi coefficient among the radiologists in dif-ferent hospitals were greater than or equal to 0.6 (indicating good consistency and correlation). CONCLUSION: AI software can be used to automatically detect suspected rib fracture lesions, which helps to improve the detection rate of fracture lesions and the consistency among different readers.
Subject(s)
Radiology , Rib Fractures , Humans , Rib Fractures/diagnostic imaging , Artificial Intelligence , China , Radiography , Retrospective StudiesABSTRACT
Scarring, naturally induced by fibroblasts(Fb) during wound healing, is an essential process in response to repair damaged tissue. Excessive Fb proliferation which produces the excessive collagen deposition, including increased extracellular matrix synthesis or insufficient decomposition, typically contributes to hypertrophic scar(HS) formation. Although exact mechanisms of HS are not yet fully understood, it is generally believed that dysfunction of Fb and regulation of signal pathways play an important role in HS formation. Biologically, Fb function is affected by various factors such as cytokines, extracellular matrix and itself. In addition, modifications of miRNA, ceRNA, lncRNA, peptides and histones participate in HS formation by affecting the biological function of Fb. Despite the clinical importance, very few therapeutic modalities are available to prevent HS. To achieve this, a deeper characterization of Fb is required to identify mechanisms of HS. To the aspect of HS prevention and treatment, we review recent findings, concentrating on Fb function and collagen secretion. The objective of this article is to frame the current understanding, gain the deeper insights into Fb function, and provide the more comprehensive cognition and perspective for prevention and treatment of HS.
Subject(s)
Cicatrix, Hypertrophic , Humans , Cicatrix, Hypertrophic/prevention & control , Cicatrix, Hypertrophic/drug therapy , Cicatrix, Hypertrophic/metabolism , Collagen/metabolism , Collagen/therapeutic use , Fibroblasts , Signal Transduction , Extracellular Matrix/metabolismABSTRACT
Objective: To explore the clinical significance of hepatitis B pregenomic RNA (pgRNA) for deciding antiviral therapy discontinuation in patients with chronic hepatitis B (CHB). Methods: Data of patients with CHB who were treated with long-term antiviral therapy in the Center for Infectious Diseases, West China Hospital of Sichuan University from January 2019 to December 2019 were collected. Drug discontinuity after evaluation of high-sensitivity HBV DNA and HBV pgRNA (HBV DNA ≤20 IU/ml and HBV pgRNA<150 copies/ml) was observed. The prospective observational study on 91 patients with HBeAg-negative CHB was conducted. The clinical conditions were followed up 3, 6 and 12 months after the drug discontinuation. The relationship between HBV pgRNA and relapse after drug discontinuation was analyzed. Results: From observation to 12 months after drug discontinuation, a total of 34 patients (37.4%) had developed recurrence and resumed antiviral therapy, and the cumulative recurrence rate within 12 months of drug discontinuation was 46.8%. Among the relapsed patients, 14 (41.2%) had biochemical breakthroughs, and all achieved good biochemical and virological responses after the resumption of antiviral therapy. The Cox multivariate proportional hazards regression analysis showed that the level of HBV pgRNA before drug discontinuation and the type of antiviral drugs taken were associated with recurrence after drug discontinuation. The risk of recurrence after drug withdrawal in the HBV pgRNA ≤50 copies/ml group was 2.316 times higher than that in the HBV pgRNA negative group (HR=2.316, 95%CI: 1.047-5.126, P=0.038). The risk of recurrence after drug withdrawal in the HBV pgRNA >50 copies/ml group was 3.45 times higher than that in the HBV pgRNA negative group (HR=3.450, 95%CI: 1.338-8.892, P=0.010). Conclusion: HBV pgRNA can be used to predict the risk of recurrence after antiviral therapy discontinuation in patients with CHB. Patients with negative serum HBV pgRNA before drug discontinuation have a relatively low risk of relapse after drug discontinuation, and drug discontinuation is not recommended for patients with HBV pgRNA >50 copies/ml.
Subject(s)
Hepatitis B virus , Hepatitis B, Chronic , Humans , Hepatitis B virus/genetics , Hepatitis B e Antigens , Hepatitis B, Chronic/drug therapy , DNA, Viral , RNA , Antiviral Agents/therapeutic use , Recurrence , Hepatitis B Surface AntigensABSTRACT
Curvatures in mode shapes and operating deflection shapes have been extensively studied for vibration-based structural damage identification in recent decades. Curvatures of mode shapes and operating deflection shapes have proved capable of localizing and manifesting local effects of damage on mode shapes and operating deflection shapes in forms of local anomalies. The damage can be inversely identified in the neighborhoods of the anomalies that exist in the curvatures. Meanwhile, propagating flexural waves have also been extensively studied for structural damage identification and proved to be effective, thanks to their high damage-sensitivity and long range of propagation. In this work, a baseline-free structural damage identification method is developed for beam-like structures using curvature waveforms of propagating flexural waves. A multi-resolution local-regression temporal-spatial curvature damage index (TSCDI) is defined in a pointwise manner. A two-dimensional auxiliary TSCDI and a one-dimensional auxiliary damage index are developed to further assist the identification. Two major advantages of the proposed method are: (1) curvature waveforms of propagating flexural waves have relatively high signal-to-noise ratios due to the use of a multi-resolution central finite difference scheme, so that the local effects of the damage can be manifested, and (2) the proposed method does not require quantitative knowledge of a pristine structure associated with a structure to be examined, such as its material properties, waveforms of propagating flexural waves and boundary conditions. Numerical and experimental investigations of the proposed method are conducted on damaged beam-like structures, and the effectiveness of the proposed method is verified by the results of the investigations.
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Objective: To study the value of chromosome microarray analysis (CMA) application in children with developmental delay (DD), intellectual disability (ID), autistic spectrum disorder (ASD) and multiple congenital anomalies (MCA). Methods: Genomic DNA was extracted from peripheral blood samples. Array-based comparative genomic hybridization (array-CGH) analysis and single nucleotide polymorphism array (SNP-array) were performed in 1 320 children with DD/ID, ASD, with or without epilepsy and MCA who were admitted to Peking University First Hospital from 2014 to 2019. The results of genetic etiology test of CMA in children with mental retardation or global DD was summarized. Results: Of 1 320 samples, there were 10 cases of aneuploid abnormality, 6 cases of uniparental disomy and one case of mosaicism, respectively. Pathogenic copy number variations (CNVs) were found in 320 cases and pathogenic CNVs were detected in 23 cases, with a combined detection rate of 26% (343/1 320). CNVs of uncertain clinical significance occurred in 107 cases, accounting for 8.1% (107/1 320). There were 25 cases of possible benign CNVs, accounting for 2% (25/1 320), while benign CNVs were reported in 20 cases, accounting for 1.5% (20/1 320). The detection rate of MCA with DD/ID was 39.8% (130/327). Conclusions: CMA has the advantages of high resolution and covering the whole genome. It can detect the chromosomal abnormalities, microdeletions and duplications seen under the microscope, thus the genetic etiology of children with mental retardation or global DD can be diagnosed.
Subject(s)
Intellectual Disability , Child , Chromosome Aberrations , Chromosomes , Comparative Genomic Hybridization , DNA Copy Number Variations , Developmental Disabilities/genetics , Humans , Intellectual Disability/genetics , Microarray AnalysisABSTRACT
Birth defects and rare diseases have become major public health problems, and early prevention and control are the most effective interventions. In recent years, with the rapid development of genomic techniques such as high-throughput sequencing, the level of screening and diagnosis of genetic birth defects and rare diseases has been greatly improved. This article reviews the application of genomic technologies in the pre-pregnancy, preimplantation, prenatal and neonatal stages, as well as the trend of clinical transformation, highlighting the broad prospects of constructing an early and precise prevention and control system in the era of genomic medicine.
Subject(s)
Genomics , Rare Diseases , Female , High-Throughput Nucleotide Sequencing , Humans , Pregnancy , Rare Diseases/genetics , Rare Diseases/prevention & controlABSTRACT
Hepatitis B virus RNA plays an important role in the process of hepatitis B virus replication, especially pregenomic RNA (pgRNA), which serves as a template for the viral capsids, so its particularity is increasing day by day. This article analyzes the recent clinical studies, and further discusses the guiding significance of HBV RNA as a new clinical serological marker for hepatitis B patients.
Subject(s)
Hepatitis B virus , Hepatitis B , Hepatitis B virus/genetics , Humans , RNA, Viral/genetics , Virus ReplicationABSTRACT
Hepatitis E is an important zoonosis that is prevalent in China. Hepatitis E virus (HEV) is a pathogen that affects humans and animals and endangers public health in China. In this study, the detection of HEV epidemics in swine in Sichuan Province, China, was carried out by nested real-time PCR. A total of 174 stool samples and 160 bile samples from swine in Sichuan Province were examined. In addition, software was used to analyse the biological evolution of HEV. The results showed that within 2 years of swine HEV (SHEV) infection in China, SHEV was first detected in Sichuan Province. HEV was endemic in Sichuan; the positive rate for pig farms was 11.1%, and the total positive sample rate was 10.5%. The age of swine with the highest positive rate (17.9%) was 5-9 weeks. The examined swine species in order of highest to lowest HEV infection rates were Chenghua pig, Large White, Duroc, Pietrain, Landrace and Hampshire. Nucleotide and amino acid sequence analysis showed that the HEV epidemic in swine in Sichuan Province was related to genotype IV, which had the highest homology to HEV in Beijing. Sichuan strains have greater variation than Chinese representative strains, which may indicate the presence of new HEV strains.
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Objective: To evaluate the safety and efficacy of diagnosis and treatment of pleuroperitoneal communication in patients on peritoneal dialysis by computerized tomography (CT) peritoneography and thoracoscopic surgery. Methods: The records of 8 pleuroperitoneal communication patients treated by thoracoscopic surgery in Peking University First Hospital from January 2012 to March 2017 were retrospectively reviewed.CT peritoneography was performed before surgical treatment. Iopamiro (50 mlâ¶15 g) was mixed with 2 L of peritoneal dialysate solution, and then was instilled into the peritoneal cavity through the Tenckhoff catheter. After dwelling for 1 hour, CT scan was taken from thorax to upper abdomen.The thoracic cavity was filled with sterile saline, and then carbon dioxide was inflated to the peritoneal cavity via Tenckhoff catheter.Air bubbles leaking from the diaphragmatic defect were identified during thoracoscopic operation.Then defect was repaired and pleurodesis was performed. Results: The CT value of pleural effusion increased to (155±57) HU.Pleuroperitoneal communication was clearly diagnosed.The diaphragmatic defects in 5 cases were detected and repaired.However, defects in the other 3 cases were not found.The mean operative time was (152±50) minutes. All patients had uneventful recovery and reinstated normal peritoneal dialysis 3 weeks after the operation.The median follow-up time was 14.5 months (1-68 months) and no recurrence occurred. Conclusions: CT peritoneography could identify pleuroperitoneal communication clearly. Thoracoscopic surgery is a safe and reliable method for pleuroperitoneal communication and could restore patients to peritoneal dialysis.
Subject(s)
Peritoneal Dialysis , Humans , Hydrothorax , Peritoneal Dialysis, Continuous Ambulatory , Pleural Diseases , Retrospective StudiesABSTRACT
This study further evaluated the in vitro and in vivo anti-Helicobacter pylori activities and potential underlying mechanism of patchouli alcohol (PA), a tricyclic sesquiterpene. In the in vitro assay, the capacities of PA to inhibit and kill H. pylori were tested on three standard strains at different pH values and on 12 clinical isolates. The effects of PA on H. pylori adhesion (and its alpA, alpB, and babA genes), motility (and its flaA and flaB genes), ultrastructure, and flagellation were investigated. Moreover, the H. pylori resistance to and postantibiotic effect (PAE) of PA were determined. Furthermore, the in vivo effects of PA on H. pylori eradication and gastritis were examined. Results showed that MICs of PA against three standard strains (pH 5.3 to 9) and 12 clinical isolates were 25 to 75 and 12.5 to 50 µg/ml, respectively. The killing kinetics of PA were time and concentration dependent, and its minimal bactericidal concentrations (MBCs) were 25 to 75 µg/ml. In addition, H. pylori adhesion, motility, ultrastructure, and flagellation were significantly suppressed. PA also remarkably inhibited the expression of adhesion genes (alpA and alpB) and motility genes (flaA and flaB). Furthermore, PA treatment caused a longer PAE and less bacterial resistance than clarithromycin and metronidazole. The in vivo study showed that PA can effectively eradicate H. pylori, inhibit gastritis, and suppress the expression of inflammatory mediators (COX-2, interleukin 1ß, tumor necrosis factor alpha, and inducible nitric oxide synthase [iNOS]). In conclusion, PA can efficiently kill H. pylori, interfere with its infection process, and attenuate gastritis with less bacterial resistance, making it a potential candidate for new drug development.
Subject(s)
Anti-Bacterial Agents/pharmacology , Gastritis/drug therapy , Helicobacter Infections/drug therapy , Helicobacter pylori/drug effects , Sesquiterpenes/pharmacology , Adhesins, Bacterial/biosynthesis , Adhesins, Bacterial/genetics , Animals , Bacterial Adhesion/drug effects , Bacterial Outer Membrane Proteins/biosynthesis , Bacterial Outer Membrane Proteins/genetics , Bacterial Proteins/biosynthesis , Bacterial Proteins/genetics , Clarithromycin/pharmacology , Female , Flagellin/biosynthesis , Flagellin/genetics , Gastritis/microbiology , Gene Expression/drug effects , Helicobacter Infections/microbiology , Helicobacter pylori/isolation & purification , Humans , Hydro-Lyases/biosynthesis , Hydro-Lyases/genetics , Inflammation/drug therapy , Inflammation/microbiology , Male , Metronidazole/pharmacology , Mice , Mice, Inbred C57BL , Microbial Sensitivity Tests , Oxidoreductases/biosynthesis , Oxidoreductases/geneticsABSTRACT
Objective: To investigate the prognosis of osteosarcoma patients with lung metastases and its correlated factors. Methods: The clinical data of 104 osteosarcoma patients with lung metastasis from April 2007 to September 2015 were retrospectively analyzed. Univariate analysis was performed using Kaplan-Meier and Log rank test. Multivariate Cox regression was applied to analyze independent prognostic factor for patient survival. Results: The one-year, two-year and five-year survival rates of the 104 osteosarcoma patients with lung pulmonary metastasis were 93.3%, 61.5% and 11.5%, respectively, and the median survival time was 33 months. The univariate analysis revealed that number of lung metastases, objective response of first-line chemotherapy and therapeutic methods for lung metastases were significant prognostic factors for patient survival, whereas gender, age, time to lung metastasis and time to other metastasis were not (P>0.05). The multivariate analysis indicated that number of lung metastases, objective response of first-line chemotherapy and therapeutic methods for lung metastases were independent significant prognostic factors for patient survival. Conclusions: The prognosis of osteosarcoma patients with advanced lung metastases and active treatment is better. Surgery and adjuvant chemotherapy could effectively prolong survival time for osteosarcoma patients with pulmonary metastasis.
Subject(s)
Bone Neoplasms/mortality , Bone Neoplasms/pathology , Lung Neoplasms/mortality , Lung Neoplasms/secondary , Osteosarcoma/mortality , Osteosarcoma/secondary , Analysis of Variance , Bone Neoplasms/therapy , Chemotherapy, Adjuvant , Female , Humans , Kaplan-Meier Estimate , Lung Neoplasms/therapy , Male , Osteosarcoma/therapy , Prognosis , Regression Analysis , Retrospective Studies , Sex Factors , Survival Analysis , Survival Rate , Time FactorsABSTRACT
OBJECTIVE/BACKGROUND: To evaluate the effectiveness of double banding/ligation of hepatic arteries in treating patients with hepatic hereditary hemorrhagic telangiectasia (HHHT). METHODS: From January 2004 to December 2013, 35 patients were diagnosed with HHHT, among whom 11 woman and two men with a mean ± SD age of 44 ± 9 years were treated by double hepatic artery banding/ligation for cardiac insufficiency and/or portal hypertension. The outcomes were evaluated prospectively by measuring clinical manifestations, imaging features, liver and cardiac function, pulmonary arterial systolic pressure, and post-operative complications. Quality of life was evaluated with the Short Form Health Survey questionnaire. RESULTS: For each patient, the common hepatic artery and one branch of the left and/or right hepatic artery were banded, and other significantly dilated hepatic artery branches were ligated. No patient died after surgery. Clinical symptoms were improved in all patients, although ischemic cholangitis was observed in two patients and treated conservatively. Cardiac function, classified per the New York Heart Association (NYHA) cardiac functional grading, improved (NYHA III-IV vs. NYHA I-II); pulmonary arterial systolic pressure significantly decreased in all patients (48 ± 8 mmHg vs. 24 ± 4 mmHg; P < .001) and remained in the normal range (26 ± 3 mmHg) at the end of follow up. The levels of γ-glutamyl transpeptidase and alkaline phosphatase decreased in 11 patients (144 ± 94 U/L vs. 71 ± 34 U/L; P = .003) and 10 patients (207 ± 71 U/L vs. 105 ± 32 U/L; P = .001), respectively. Patients were followed up for 50 ± 28 months (range 6-113 months); one death resulted from causes unrelated to surgery and all dimensions of quality of life improved in all surviving patients. CONCLUSIONS: This study helps to establish double hepatic artery banding/ligation as an effective therapy for selected patients with HHHT.
Subject(s)
Hepatic Artery/surgery , Telangiectasia, Hereditary Hemorrhagic/surgery , Vascular Surgical Procedures , Adult , Aged , Female , Heart Diseases/diagnosis , Heart Diseases/etiology , Heart Diseases/surgery , Hepatic Artery/abnormalities , Hepatic Artery/diagnostic imaging , Hepatic Artery/physiopathology , Humans , Hypertension, Portal/diagnosis , Hypertension, Portal/etiology , Hypertension, Portal/surgery , Ligation , Male , Middle Aged , Postoperative Complications/etiology , Quality of Life , Retrospective Studies , Risk Factors , Severity of Illness Index , Telangiectasia, Hereditary Hemorrhagic/complications , Telangiectasia, Hereditary Hemorrhagic/diagnosis , Telangiectasia, Hereditary Hemorrhagic/physiopathology , Time Factors , Tomography, X-Ray Computed , Treatment Outcome , Vascular Surgical Procedures/adverse effectsABSTRACT
Cholera is one of a number of infectious diseases that appears to be influenced by climate, geography and other natural environments. This study analysed the environmental factors of the spatial distribution of cholera in China. It shows that temperature, precipitation, elevation, and distance to the coastline have significant impact on the distribution of cholera. It also reveals the oceanic environmental factors associated with cholera in Zhejiang, which is a coastal province of China, using both remote sensing (RS) and geographical information systems (GIS). The analysis has validated the correlation between indirect satellite measurements of sea surface temperature (SST), sea surface height (SSH) and ocean chlorophyll concentration (OCC) and the local number of cholera cases based on 8-year monthly data from 2001 to 2008. The results show the number of cholera cases has been strongly affected by the variables of SST, SSH and OCC. Utilizing this information, a cholera prediction model has been established based on the oceanic and climatic environmental factors. The model indicates that RS and GIS have great potential for designing an early warning system for cholera.
Subject(s)
Cholera/epidemiology , Disease Outbreaks , Environment , Geographic Information Systems , Remote Sensing Technology , China/epidemiology , Cholera/microbiology , Climate , Factor Analysis, Statistical , Geography , Humans , Oceans and Seas , Seawater/chemistryABSTRACT
To understand the potential functions of Wnt7b in different developmental stages and adult tissues of the mussel Mytilus coruscus, the Wnt7b gene was cloned using the rapid amplification of cDNA ends technique. The full-length Wnt7b gene was 1910 bp long, with a 1059-bp open reading frame encoding 352 amino acids. The amino acid sequence of the M. coruscus Wnt7b gene shared high homology with that of Homo sapiens (59%), Mus musculus (61%), Danio rerio (61% similarity), Biomphalaria glabrata (62% similarity), Aplysia californica (66% similarity), and Crassostrea gigas (74%). Wnt7b mRNA expression was detected by reverse transcription PCR in all tissues studied (mantle, adductor muscle, gill, foot, digestive gland, and male and female gonads), with the highest expression found in the gill, and in the male and female gonads. This indicates that Wnt7b may play an important role in gonadal maturation and in the functions of gills in the mussel M. coruscus. Expression of the Wnt7b gene during larval development stages, including the trochophore, D-shaped veliger, umbo veliger, pediveliger, and juvenile stages, was also detected. Wnt7b mRNA was highly expressed in the D-shaped veliger, umbo veliger, and pediveliger larvae stages, suggesting that Wnt7b may participate in larval development and in the process of metamorphosis in the mussel M. coruscus. Taken together, these findings provide new insights into the functions of the Wnt gene family during mussel larval development and settlement and metamorphosis.
Subject(s)
Gene Expression Regulation, Developmental , Mytilus/genetics , Wnt Proteins/genetics , Amino Acid Sequence , Animals , Base Sequence , DNA, Complementary/genetics , Gene Expression Profiling , Mytilus/growth & development , Phylogeny , RNA, Messenger/genetics , RNA, Messenger/metabolism , Sequence Alignment , Wnt Proteins/chemistry , Wnt Proteins/metabolismABSTRACT
The relationship between hepatitis B virus (HBV) gene polymorphism and intrauterine infection has not been completely illuminated. Six pairs of mother and infant from intrauterine infection group and six mothers from nonintrauterine infection group in the previous study were randomly selected and separately divided into group M (Mother group), group N (Neonate group) and group NM (Negative-mother group) in this study. We found that age, gestational weeks, HBsAg titre, HBeAg titre and HBV DNA level of mothers from group M and group NM were not significantly different. Pre-S1/S2 and S regions in HBV genome were amplified, inserted into pUC19 plasmid and sequenced. It was found that all clone sequences clustered into genotype C (AY123041) through the Genotyping tool in NCBI and phylogenetic trees. Compared with AY123041, there were 20 (11 plus 9) mutations significantly different in the three groups. Most of the mutations were synonymous in pre-S1/S2/S region, while mutations of C2990T, T3205A, A167G, C407A, A667T and A680C resulted in amino acid substitution of A90V, S162T, T47A, P127T, L213F and I218L, respectively. In addition, most of the 20 mutations caused amino acid substitution in polymerase region for the tight structure of HBV genome. The occurrence and location of mutations indicated that mutation of C2990T only existing in group NM may serve as an index for nonintrauterine infection. In contrast, the incidence of intrauterine HBV infection from mothers with mutation of T3205A was lower. Then, mutations of G403A, T670G, A673G, A167G, C407A, A667T and A680C may be closely related to intrauterine HBV infection.
Subject(s)
Fetal Diseases/virology , Hepatitis B virus/genetics , Hepatitis B virus/isolation & purification , Hepatitis B/virology , Point Mutation , Adult , Cloning, Molecular , Cluster Analysis , Female , Genotype , Hepatitis B Surface Antigens/genetics , Hepatitis B virus/classification , Humans , Infant , Infant, Newborn , Male , Mothers , Mutation, Missense , Random Allocation , Sequence Analysis, DNA , Young AdultABSTRACT
Previous studies have shown that Hh signaling is overexpressed in the development and progression of prostate cancer (PCa), suggesting that Hh pathway inhibitors might be an effective strategy in the treatment of PCa. The combination of chemotherapeutic agents is one of the main approaches in cancer treatment, with the objective of improving efficacy. In the present study, we examined the effect of combing arsenic trioxide (ATO), a useful agent for Hedgehog-driven cancers, and cyclopamine (CYA), a classic Hh pathway inhibitor, on the suppression of PC3 cells (i.e., an androgen-independent PCa cell line). The combination of ATO and CYA more effectively inhibited the proliferation of PC3 cells than either single agent alone. In a xenograft mouse model, the combination of ATO and CYA significantly reduced tumor weight and volume in nude mice that were implanted with PC3 cells. The combination of ATO and CYA in PC3 cells resulted in a more distinct mode of Hh pathway inhibition and strengthened the S phase arrest. The present results indicate that a combination of ATO and CYA may be a rational strategy for treating PCa.
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BACKGROUND: Nin one binding protein (NOB1) was identified as a potential oncogene in human glioma and miR-646 plays an important role in human growth and development. However, the underlying molecular mechanisms of NOB1 in tumorigenicity and its correlation with miR-646 in renal cell carcinoma (RCC) have not been investigated. METHODS: We performed bioinformatic analysis to explore miRNA targeting NOB1. The expression of NOB1 and miR-646 from 100 cases of clear cell RCC (ccRCC) and 30 cases of adjacent non-tumour tissues were detected by quantitative real-time PCR. The expression of miR-646 was correlated with NOB1 expression, tumour features and patient metastasis-free survival. The effect of overexpression of mir-646 on renal cancer cell proliferation was detected by colony formation in soft agar. Using a xenograft tumour model, we observed the in vivo tumorigenesis effect of miR-646 and NOB1. RESULTS: miR-646 negatively regulated NOB1 and inhibited the proliferation and migration of renal cancer cells. There was a significant upregulation of NOB1 in ccRCC and it was further increased in metastatic cases, while miR-646 was downregulated in tumour tissues and further decreased in metastatic ccRCC. Additionally, expression of miR-646 was inversely correlated with the expression of NOB1. The downregulation of miR-646 also indicated a higher probability of developing metastasis. Most importantly, miR-646 expression was an independent predictor of ccRCC metastasis by the univariate analysis and binary logistic regression model (both P<0.05). Colony formation in soft agar and xenograft tumour model suggested that miR-646 and NOB1 are required for tumorigenesis in vitro and in vivo. Furthermore, suppression of NOB1 increased the phosphorylation of several proteins in MAPK pathway. CONCLUSIONS: Downregulated miR-646 in ccRCC was associated with tumour metastasis through MAPK pathway by targeting NOB1. miR-646 and NOB1 may play an important role in the development of ccRCC.
Subject(s)
Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/secondary , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , MicroRNAs/genetics , MicroRNAs/metabolism , Nuclear Proteins/genetics , RNA-Binding Proteins/genetics , Adult , Animals , Apoptosis , Carcinogenesis/genetics , Carcinoma, Renal Cell/chemistry , Cell Line, Tumor , Cell Movement , Cell Proliferation , Computational Biology , Down-Regulation , Female , Gene Expression Regulation, Neoplastic , HEK293 Cells , Humans , Kaplan-Meier Estimate , Kidney Neoplasms/chemistry , MAP Kinase Signaling System , Male , Mice, Nude , Middle Aged , Mitogen-Activated Protein Kinases/metabolism , Nuclear Proteins/analysis , Phosphorylation , Prognosis , RNA-Binding Proteins/analysis , Transfection , Tumor Stem Cell Assay , Up-RegulationABSTRACT
Triptolide (TPL) is a diterpenoid triepoxide derived from the Chinese herb Tripterygium wilfordii and possesses anti-tumor activity against a range of cancer cells. However, the effect of TPL on prostate cancer cells and its potential to overcome multidrug resistance (MDR) have not been explored. Therefore, in this study we used prostate cancer cell line DU145 as the experimental model and established DU145/ADM cell line resistant to adriamycin (ADM). Our results showed that TPL inhibited the proliferation and induced the cell cycle arrest and apoptosis of DU145 cells in a dose and time dependent manner. TPL decreased the levels of Cyclin D1 and anti-apoptotic protein Bcl-2, and increased the levels of pro-apoptotic proteins Fas and Bax. Furthermore, we found that TPL restored the sensitivity DU145/ADM cells to ADM in a dose dependent manner, and this was accompanied by the inhibition of MDR1 expression at both mRNA and protein levels. Taken together, these results provide strong evidence that TPL overcomes MDR in prostate cancer cells by downregulating MDR1 expression, and suggest that TPL is a promising agent for prostate cancer therapy, especially for chemoresistant prostate cancer.
Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Antineoplastic Agents, Alkylating/pharmacology , Diterpenes/pharmacology , Drug Resistance, Multiple/drug effects , Phenanthrenes/pharmacology , Prostatic Neoplasms/pathology , ATP Binding Cassette Transporter, Subfamily B , ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , Apoptosis/drug effects , Blotting, Western , Cell Cycle/drug effects , Cell Proliferation/drug effects , Down-Regulation , Epoxy Compounds/pharmacology , Humans , Male , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/metabolism , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Tumor Cells, CulturedABSTRACT
Data are inconsistent concerning whether the level of the surface electromyographic (SEMG) activity of jaw-closing muscles increases when biting forces elevated during maximal voluntary clenching (MVC). In this study, T-Scan III system and BioEMG III system were used to record bite force, occlusal contacts and SEMG activity of the anterior temporalis (TA) and of the masseter muscles (MM) simultaneously. Recordings were obtained from 16 healthy young adult males during different conditions: (i) a fast MVC from resting position to intercuspal position (ICP); (ii) mandibular movements from ICP to protrusive or lateral edge-to-edge positions with teeth in contact with biting; (iii) a fast MVC in protrusive and lateral edge-to-edge positions. A higher level of SEMG activity was associated with a higher bite force during occluding movements (P < 0.05). However, during fast MVC from rest to ICP, the largest number of occlusal contacts was achieved and distributed more symmetrically, the highest level of biting force was obtained, but the SEMG activity of the jaw elevator muscles was reduced compared with its maximum level (P < 0.05). This phenomenon was not observed during the fast MVC in protrusive or lateral edge-to-edge positions. The present results that a lower SEMG activity was associated with the largest number of occlusal contacts and the highest level of bite force during centric MVC demonstrated a complex integration of jaw-closing muscles when a stable occlusion is present.