Publications by authors named "Jun-Cheng Wang"

25 Publications

  • Page 1 of 1

A Deep Learning Based Framework for Diagnosing Multiple Skin Diseases in a Clinical Environment.

Front Med (Lausanne) 2021 16;8:626369. Epub 2021 Apr 16.

Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Numerous studies have attempted to apply artificial intelligence (AI) in the dermatological field, mainly on the classification and segmentation of various dermatoses. However, researches under real clinical settings are scarce. This study was aimed to construct a novel framework based on deep learning trained by a dataset that represented the real clinical environment in a tertiary class hospital in China, for better adaptation of the AI application in clinical practice among Asian patients. Our dataset was composed of 13,603 dermatologist-labeled dermoscopic images, containing 14 categories of diseases, namely lichen planus (LP), rosacea (Rosa), viral warts (VW), acne vulgaris (AV), keloid and hypertrophic scar (KAHS), eczema and dermatitis (EAD), dermatofibroma (DF), seborrheic dermatitis (SD), seborrheic keratosis (SK), melanocytic nevus (MN), hemangioma (Hem), psoriasis (Pso), port wine stain (PWS), and basal cell carcinoma (BCC). In this study, we applied Google's EfficientNet-b4 with pre-trained weights on ImageNet as the backbone of our CNN architecture. The final fully-connected classification layer was replaced with 14 output neurons. We added seven auxiliary classifiers to each of the intermediate layer groups. The modified model was retrained with our dataset and implemented using Pytorch. We constructed saliency maps to visualize our network's attention area of input images for its prediction. To explore the visual characteristics of different clinical classes, we also examined the internal image features learned by the proposed framework using t-SNE (t-distributed Stochastic Neighbor Embedding). Test results showed that the proposed framework achieved a high level of classification performance with an overall accuracy of 0.948, a sensitivity of 0.934 and a specificity of 0.950. We also compared the performance of our algorithm with three most widely used CNN models which showed our model outperformed existing models with the highest area under curve (AUC) of 0.985. We further compared this model with 280 board-certificated dermatologists, and results showed a comparable performance level in an 8-class diagnostic task. The proposed framework retrained by the dataset that represented the real clinical environment in our department could accurately classify most common dermatoses that we encountered during outpatient practice including infectious and inflammatory dermatoses, benign and malignant cutaneous tumors.
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http://dx.doi.org/10.3389/fmed.2021.626369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085301PMC
April 2021

Stereotactic Body Radiotherapy vs. Radiofrequency Ablation in the Treatment of Hepatocellular Carcinoma: A Meta-Analysis.

Front Oncol 2020 29;10:1639. Epub 2020 Oct 29.

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Both stereotactic body radiotherapy (SBRT) and radiofrequency ablation (RFA) are effective local treatments for hepatocellular carcinoma (HCC), but whether RFA is superior to SBRT is still controversial. Therefore, we performed a meta-analysis to compare the treatment outcomes of SBRT with RFA as curable or bridge intention. We searched online databases for studies that compared treatment outcomes for SBRT and RFA. Eligibility criteria included evaluation of local control, overall survival (OS), transplant rate, and post-transplant pathological necrosis. As no randomized clinical trials met the criteria, 10 retrospective studies with a total of 2,732 patients were included. Two studies were in favor of SBRT in local control, two studies preferred RFA in OS, and others reported comparable outcomes for both. SBRT demonstrated significantly higher 1- and 3-year local control than RFA [odds ratio (OR) 0.42, 95% CI 0.24-0.74, = 0.003; and OR 0.54, 95% CI 0.37-0.80, = 0.002, respectively]. However, SBRT reported significantly shorter 1- and 2-year OS (OR 1.52, 95% CI 1.21-1.90, = 0.0003; and OR 1.66, 95% CI 1.38-2.01, < 0.00001, respectively). As bridge treatment, no significant difference was shown in transplant rate and post-transplant pathological necrosis rate (OR 0.57, 95% CI 0.32-1.03, = 0.060; and OR 0.49, 95% CI 0.13-1.82, = 0.290, respectively). This study demonstrates SBRT is able to complete a better local control for HCC than RFA, though the OS is inferior to RFA because of tumor burden or liver profiles of the enrolled studies. Well-designed, randomized, multicenter trials will be required to further investigate the conclusion.
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http://dx.doi.org/10.3389/fonc.2020.01639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658324PMC
October 2020

Tescalcin is an unfavorable prognosis factor that regulats cell proliferation and survival in hepatocellular carcinoma patients.

Cancer Commun (Lond) 2020 08 1;40(8):355-369. Epub 2020 Jul 1.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China.

Background: Hepatocellular carcinoma (HCC) is a major health problem and a primary cause of cancer-related death worldwide. Although great advances have achieved recently by large-scale high-throughput analysis, the precise molecular mechanism underlying HCC progression remains to be clearly elucidated. We investigated the relationship between Tescalcin (TESC), a candidate oncogene, and clinicopathological features of HCC patients and explored the role of TECS in HCC development.

Methods: To identify new genes involved in HCC development, we analyzed The Cancer Genome Atlas liver cancer database, and TESC was selected for further investigation. HCC tissue microarray analysis for TESC and its association with clinicopathological features were performed to investigate its clinical significance. TESC was knocked down by using short-hairpin RNAs. Cell proliferation was analyzed by WST-1 assay and cell counting. Cell apoptosis was tested by fluorescence-activated cell sorting. A subcutaneous xenograft tumor model in nude mice was established to determine the in vivo function of TESC. Affymetrix microarray was used to identify its molecular mechanism.

Results: TESC was significantly increased in HCC tissues compared with the adjacent normal liver tissues. High expression of TESC was detected in 61 of 172 HCC patients by tissue microarray. Large tumor (> 5 cm) and elevated total bilirubin were associated with high TESC expression (both P < 0.050). In multivariate analysis, TESC was identified as an independent prognostic factor for short overall survival of HCC patients. TESC knockdown impaired HCC cell growth in vitro and in vivo. TESC knockdown significantly increased cell apoptosis in HCC cell lines. Furthermore, Affymetrix microarray analysis revealed that TESC knockdown inhibited tumor proliferation-related pathways while activated cell death-related pathways.

Conclusion: TESC was identified as an independent prognostic factor for short overall survival of HCC patients, and was critical for HCC cell proliferation and survival.
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http://dx.doi.org/10.1002/cac2.12069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427307PMC
August 2020

Preventive effect of celecoxib in sorafenib-related hand-foot syndrome in hepatocellular carcinoma patients, a single-center, open-label, randomized, controlled clinical phase III trial.

Am J Cancer Res 2020 1;10(5):1467-1476. Epub 2020 May 1.

Department of Liver Surgery, Sun Yat-sen University Cancer Center Guangzhou, P. R. China.

Skin toxicity, especially hand-foot syndrome (HFS), is one of the most common sorafenib-induced adverse events (AEs) in hepatocellular carcinoma (HCC) patients, leading to treatment interruption and failure. Mucocutaneous inflammation may cause HFS; therefore, we investigated whether celecoxib can alleviate HFS, improve patients' quality of life and increase survival when administered in conjunction with active therapy. Our randomized, open-label study prospectively enrolled 116 advanced HCC patients receiving sorafenib as targeted therapy from July 2015 to July 2016. All patients were randomly assigned (1:1) via a computer-generated sequence to receive sorafenib with or without celecoxib. Sorafenib-related AEs were recorded, Survival was compared between the two groups. Compared to the Sorafenib group, the SoraCele group had lower incidence rates of ≥ grade 2 and grade 3 HFS (63.8% vs 29.3%, < 0.001; 19.0% vs 3.4%, = 0.008, respectively), hair loss, rash and abdominal pain. Kaplan-Meier analysis revealed a lower risk of ≥ grade 2 HFS (HR, 0.384; = 0.002) and a lower dose reduction/interruption rate (46.6% to 15.5%, < 0.001) in the SoraCele group. Cox proportional hazards regression analysis demonstrated that celecoxib was the only independent predictive factor of developing ≥ grade 2 HFS (HR, 0.414; = 0.004). Longer progression-free survival (PFS) was also observed in the SoraCele group ( = 0.039), although overall survival was not prolonged ( = 0.305). These results suggest that sorafenib + Celecoxib administration alleviated sorafenib-related skin toxicity. Longer PFS was achieved in clinical practice, although overall survival was not prolonged (ClinicalTrials.gov: NCT02961998).
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269790PMC
May 2020

Impact of overweightness and critical weight loss on overall survival in patients with hepatocellular carcinoma initially treated with chemoembolization.

Gastroenterol Rep (Oxf) 2020 Apr 28;8(2):125-133. Epub 2019 Aug 28.

Department of Hepatobiliary and Pancreatic Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, P. R. China.

Background: The effects of overweightness and weight loss on the development and prognosis of hepatocellular carcinoma (HCC) remain unclear. In this study, we aimed to evaluate the impact of overweightness and weight loss on the survival of patients with intermediate/advanced HCC receiving chemoembolization as initial treatment.

Methods: We examined 1,170 patients who underwent chemoembolization as initial treatment for Barcelona-Clínic Liver Cancer stages B and C HCC at Sun Yat-sen University Cancer Center (Guangzhou, China) between December 2009 and May 2015. A baseline body mass index (BMI) of ≥23 kg/m was defined as overweight, and body-weight loss of ≥5.0% from baseline was defined as critical weight loss (CWL). Cox regression analysis was used to determine the association between overweightness or CWL and overall survival (OS).

Results: The median survival time was 16.8 (95% confidence interval, 13.9-19.7) months and 11.1 (95% confidence interval, 10.0-12.2) months in the overweight and non-overweight groups (log-rank test, <0.001), respectively. Cox multivariate analysis identified overweightness as an independent protective prognostic factor for OS (<0.001). Subgroup stratification analysis revealed a significant association between overweightness and survival among patients receiving further treatment (=0.005), but not in those not receiving further treatment (=0.683). Multivariate analysis showed that both overweightness and CWL were independent prognostic factors for OS among patients receiving further treatment.

Conclusion: Among patients with intermediate- or advanced-stage HCC initially treated with chemoembolization, overweightness was associated with longer OS. Furthermore, CWL was an independent adverse prognostic factor for OS in patients receiving additional treatment.
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http://dx.doi.org/10.1093/gastro/goz040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136712PMC
April 2020

Intention to control low central venous pressure reduced blood loss during laparoscopic hepatectomy: A double-blind randomized clinical trial.

Surgery 2020 06 23;167(6):933-941. Epub 2020 Mar 23.

Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, P.R. China; Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, P.R. China. Electronic address:

Background: Excessive intraoperative hemorrhage is a critical factor of poor prognoses after hepatectomy. Low central venous pressure during parenchymal transection is recognized to effectively reduce intraoperative hemorrhage in open procedures. However, the role of controlled low central venous pressure in laparoscopic hepatectomy is still controversial.

Methods: In the present randomized clinical trial, we set up a standard boundary of low central venous pressure according to our Pilot Study, then enrolled patients scheduled for elective laparoscopic hepatectomy and allocated them randomly to a group undergoing central venous pressure reduction by anesthesiologic interventions or a control group. The primary efficacy endpoint was total intraoperative blood loss and perioperative adverse events. Analyses were performed following the intention-to-treat principle, and patients and surgeons were blinded (ClinicalTrials.gov, Number: NCT03422913).

Results: Between January 2017 and October 2018, 146 out of 469 patients were randomized and eligible for inclusion in the final analyses. Based on the retrospective training cohort, we set a central venous pressure of 5 cm HO as a cutoff value (standard low central venous pressure). Compared with patients in the control group, those in the controlled low central venous pressure group had a significantly lower central venous pressure during resection (4.83 ± 3.41 cm HO vs 9.26 ± 3.38 cm HO; P < .001) and significantly reduced total intraoperative blood loss (188.00 ± 162.00 mL vs 346.00 ± 336.00 mL; P < .001). The perioperative adverse events were comparable in both study groups (P = .313).

Conclusion: The safety and efficacy of controlled low central venous pressure were demonstrated in complex laparoscopic hepatectomy for the first time by our study, and this technique is recommended to be applied routinely in laparoscopic hepatectomy.
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http://dx.doi.org/10.1016/j.surg.2020.02.004DOI Listing
June 2020

Single versus multiple port laparoscopic left lateral sectionectomy for hepatocellular carcinoma: A retrospective comparative study.

Int J Surg 2020 May 13;77:15-21. Epub 2020 Mar 13.

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, PR China; Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, PR China. Electronic address:

Background: Single port laparoscopic hepatectomy has been applied in some surgeries. We aimed to describe our experience with single port laparoscopic left lateral sectionectomy (SPLS) and to compare the safety and feasibility of this technique with those of conventional multi-port laparoscopic left lateral sectionectomy (MPLS) in the treatment of hepatocellular carcinoma (HCC).

Methods: A total of 72 consecutive patients who underwent SPLS (n = 33) and MPLS (n = 39) for HCC were enrolled. The peri-operative parameters of safety and feasibility, as well as the short-term oncological outcomes were compared.

Results: The length of postoperative hospital stay (LOS) was significantly shorter in the SPLS group than in the MPLS group (4.12 vs. 4.59 days, P = 0.043). No significant difference between the two groups was found in the operation time (104.58 vs. 95.69 min in the SPLS group and MPLS group respectively, P = 0.353) or the amount of blood loss (62.73 vs. 68.46 ml, P = 0.595). The 1-year recurrence-free survival rate was 77.9% in the SPLS group and 70.7% in the MPLS group (P = 0.82). Subgroup analysis showed that for patients without cirrhosis, the LOS was shorter in the SPLS group than in the MPLS group (P = 0.033), while for patients with cirrhosis, the LOS was not significantly different between the two groups (P = 0.201), although it was shorter in the SPLS group.

Conclusions: SPLS was a feasible and safe surgical approach for the treatment of HCC on left lateral section.
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http://dx.doi.org/10.1016/j.ijsu.2020.03.003DOI Listing
May 2020

A case of clonal seborrheic keratosis with characteristic dermoscopic features.

Chin Med J (Engl) 2020 Feb;133(4):499-500

Department of Dermatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.

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http://dx.doi.org/10.1097/CM9.0000000000000630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046253PMC
February 2020

Carpesium abrotanoides (L.) Root as a Potential Source of Natural Anticancer Compounds: Targeting Glucose Metabolism and PKM2/HIF-1α Axis of Breast Cancer Cells.

J Food Sci 2019 Dec 21;84(12):3825-3832. Epub 2019 Nov 21.

College of Life Science, Zhejiang Chinese Medical Univ., Hangzhou, China.

Carpesium abrotanoides L. (CA) is widely used as a medicinal plant in Asia. The biological activities of the extract from the roots of Carpesium abrotanoides L. (PCA) and its major components were analyzed in this study. PCA was separated and identified with mass spectrometry. Furthermore, we sought to elucidate the anticancer activity of PCA and its mechanisms. PCA exerted its anti-breast cancer activity through inhibiting the expression of glycolysis-related genes, such as glucose transporter 1, lactate dehydrogenase A, and hexokinase 2. Moreover, PCA downregulated the expression of pyruvate kinase M2 and altered its cellular translocation. We also demonstrated PCA is an inhibitor of the PKM2/hypoxia-inducible factor-1α axis, indicating that PCA is potentially useful as an anti-breast cancer agent. PRACTICAL APPLICATION: In this study, the extract from roots of Carpesium abrotanoides Linn. (PCA) was shown to have a noticeable anticancer effect against breast cancer in vitro, and PCA exerts the anticancer activity by regulating glucose metabolism and PKM2 expression. These findings indicate that PCA is a promising agent with practical applications in the development of functional food containing Carpesium abrotanoides L. root extracts.
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http://dx.doi.org/10.1111/1750-3841.14953DOI Listing
December 2019

A nomogram predicting the recurrence of hepatocellular carcinoma in patients after laparoscopic hepatectomy.

Cancer Commun (Lond) 2019 10 11;39(1):55. Epub 2019 Oct 11.

State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.

Background: Patients with hepatocellular carcinoma (HCC) undergoing surgical resection still have a high 5-year recurrence rate (~ 60%). With the development of laparoscopic hepatectomy (LH), few studies have compared the efficacy between LH and traditional surgical approach on HCC. The objective of this study was to establish a nomogram to evaluate the risk of recurrence in HCC patients who underwent LH.

Methods: The clinical data of 432 patients, pathologically diagnosed with HCC, underwent LH as initial treatment and had surgical margin > 1 cm were collected. The significance of their clinicopathological features to recurrence-free survival (RFS) was assessed, based on which a nomogram was constructed using a training cohort (n = 324) and was internally validated using a temporal validation cohort (n = 108).

Results: Hepatitis B surface antigen (hazard ratio [HR], 1.838; P = 0.044), tumor number (HR, 1.774; P = 0.003), tumor thrombus (HR, 2.356; P = 0.003), cancer cell differentiation (HR, 0.745; P = 0.080), and microvascular tumor invasion (HR, 1.673; P  =0.007) were found to be independent risk factors for RFS in the training cohort, and were used for constructing the nomogram. The C-index for RFS prediction in the training cohort using the nomogram was 0.786, which was higher than that of the 8th edition of the American Joint Committee on Cancer TNM classification (C-index, 0.698) and the Barcelona Clinic Liver Cancer staging system (C-index, 0.632). A high consistency between the nomogram prediction and actual observation was also demonstrated by a calibration curve. An improved predictive benefit in RFS and higher threshold probability of the nomogram were determined by receiver operating characteristic curve analysis, which was also confirmed in the validation cohort compared to other systems.

Conclusions: We constructed and validated a nomogram able to quantify the risk of recurrence after initial LH for HCC patients, which can be clinically implemented in assisting the planification of individual postoperative surveillance protocols.
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http://dx.doi.org/10.1186/s40880-019-0404-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788088PMC
October 2019

Stereotactic Body Radiotherapy as a Salvage Therapy after Incomplete Radiofrequency Ablation for Hepatocellular Carcinoma: A Retrospective Propensity Score Matching Study.

Cancers (Basel) 2019 Aug 5;11(8). Epub 2019 Aug 5.

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.

(1) : To investigate the clinical outcomes between radiofrequency ablation (RFA) and stereotactic body radiotherapy (SBRT) for residual hepatocellular carcinoma (RHCC). (2) : 139 patients were diagnosed with the RHCC after post-operative checkup, among whom 39 and 33 patients underwent RFA or SBRT as salvage treatments, respectively. We applied the propensity score matching (PSM) to adjust for imbalances in treatment assignment. Local disease progression, progression-free survival (PFS), overall survival (OS), and treatment-related side effects were the study endpoints. (3) : Before PSM, the SBRT group demonstrated significantly lower local disease progression rate (6/33 vs. 23/39; = 0.002), better PFS (the 1- and 3-year PFS were 63.3% and 49.3% vs. 41.5% and 22.3%, respectively, = 0.036), and comparable OS (the 1- and 3-year OS were 85.4% and 71.1% vs. 97.3% and 57.6%, respectively, = 0.680). After PSM of 23 matched cases, the SBRT group demonstrated significantly lower local disease progression rate, better PFS and comparable OS. Centrally located tumor predicted the worse OS. No acute grade 3+ toxicity was observed in both groups. (4) : SBRT might be the preferred treatment for RHCC, especially for patients with larger tumors or tumors abutting major vessels, rather than repeated RFA.
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http://dx.doi.org/10.3390/cancers11081116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721575PMC
August 2019

Clinical conditions and treatment requirements for long-term survival among hepatitis B-related hepatocellular carcinoma initially treated with chemoembolization.

Cancer Med 2019 Sep 17;8(11):5097-5107. Epub 2019 Jul 17.

Department of Hepatobiliary and Pancreatic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.

Objective: Transarterial chemoembolization (TACE) is recommended to treat intermediate/advanced stage of hepatocellular carcinoma (HCC). However, the overall survival among initially TACE-treated patients varies significantly. The clinical characterization of long-term survival following TACE remains uncertain. We sought to identify clinical parameters and treatment requirements for long-term survival among patients with hepatitis B-related HCC who were initially treated with TACE.

Materials And Methods: The included patients with HCC were admitted to our cancer center between December 2009 and May 2015. Patients who survived for >3 years were compared with those who died within 3 years. The clinical and laboratory findings that were associated with the survival were also analyzed.

Results: One in six (17.9%) patients with HCC in this cohort survived for > 3 years after TACE. Body mass index (BMI) ≥ 23kg/m , aspartate aminotransferase levels ≤ 40 U/L, an activated partial thromboplastin time ≤ 34 seconds, α-fetoprotein (AFP) levels ≤ 25 ng/mL, antiviral therapy, tumor size ≤ 8 cm, solitary nodule, and the absence of vascular invasion were independently favorably associated with a 3-year survival. An absence of vascular invasion was the only independent factor associated with 3-year survival in patients who received resection and/or ablation after TACE.

Conclusion: In this cohort, a 3-year survival was associated with BMI, antivirus treatment, tumor status, hepatic function, and AFP level. Distant metastasis did not negatively impact the long-term survival among patients with hepatitis B-related HCC initially treated with TACE. Vascular invasion was the single impediment to long-term survival in patients who received add-on resection and/or ablation after TACE.
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http://dx.doi.org/10.1002/cam4.2380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6718579PMC
September 2019

[Finite element analysis of anterior ring injuries in unstable pelvic fractures treated by different methods].

Zhongguo Gu Shang 2019 Feb;32(2):156-160

Department of Orthopaedics, the Third Affiliated Hospital of Wenzhou Medical University, Wenzhou 325200, Zhejiang, China;

Objective: To compare the biomechanical stability of different fixation methods for anterior ring injury of unstable pelvic fractures, and to provide reference for clinical treatment.

Methods: An unstable pelvic fracture model (Tile C) with one side of the sacroiliac joint dislocation and the pubic rami fracture was constructed via three-dimensional finite element analysis. Five different fixation methods were used in the front, and the rear was fixed with sacroiliac screws. The von Mises stress and strain distributions of different combinations of fixation methods were analyzed under mimicking standing conditions.

Results: After being loaded with 500 N vertically, the maximum stress in the anterior fracture was 3.56 MPa in anterior pelvic external fixation (AEF) group, the total displacement and the vertical displacement of the Y axis at the sacroiliac joint and the fracture were not more than 1.5 mm. The maximum stress at fixation, the front of the fracture and sacroiliac joints in the anterior pelvic subcutaneous approach(APA) group and AEF, was significantly higher than anterior modified Stoppa approach(ASA) group, anterior pelvic Ilioinguinal approach (AIA) group, and canulated screw fixation(CSF) group. The total displacement and the vertical displacement of the Y axis at the sacroiliac joint and the fracture in APA group and AEF group were also greater than the other three groups.

Conclusions: Anterior ring injury of unstable pelvic fractures can be significantly improved after the fixation of the implants in the five combined methods. However, overall biomechanical properties of ASA, AIA and CSF group are superior to APA and AEF group.
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http://dx.doi.org/10.3969/j.issn.1003-0034.2019.02.012DOI Listing
February 2019

Effect of Nucleos(t)ide Analogs on Patients with Intermediate and Advanced Hepatitis B Virus-Related Hepatocellular Carcinoma.

Dig Dis Sci 2019 08 28;64(8):2187-2198. Epub 2019 Feb 28.

Department of Hepatobiliary and Pancreatic Surgery, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, People's Republic of China.

Background: The role of nucleos(t)ide analogs (NAs) therapy in intermediate and advanced hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remains unclear.

Aims: The aim was to evaluate the effect of NAs therapy on survival of intermediate- and advanced-stage HBV-related HCC patients initially treated with chemoembolization.

Methods: A total of 1016 Barcelona Clinic Liver Cancer (BCLC) stage B/C HBV-related HCC patients initially treated with chemoembolization were included. Propensity score matching (PSM) was performed to decrease heterogeneity between the antiviral and non-antiviral groups. Kaplan-Meier and Cox regression analysis were performed to evaluate the effects of NAs therapy on overall survival (OS).

Results: Antiviral group (n = 394) significantly prolonged OS compared with non-antiviral group (n = 622) (p = 0.003). NAs therapy (p < 0.001) along with tumor size (p = 0.002), tumor number (p = 0.001), gross vascular invasion (p < 0.001), metastasis (p < 0.001), α-fetoprotein (p < 0.001), Child-Pugh score (p = 0.008), aspartate aminotransferase (p < 0.001), and HBV DNA (p = 0.018) were identified as independent prognostic factors for OS. After PSM processing, deducting the influence of subsequent treatments for HCC, NAs therapy was still identified as an independent protective factor (p = 0.009) for OS in patients who survived ≥ 7 months, regardless of BCLC stage B or C HCC.

Conclusion: NAs therapy prolongs OS in intermediate- and advanced-stage HBV-related HCC patients initially treated with chemoembolization. After PSM processing, patients who survived ≥ 7 months still benefited from NAs therapy.
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http://dx.doi.org/10.1007/s10620-019-05543-4DOI Listing
August 2019

Robot-assisted laparoscopic partial hepatic caudate lobectomy.

Minim Invasive Ther Allied Technol 2019 Oct 27;28(5):292-297. Epub 2018 Sep 27.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.

Hepatic caudate lobectomy is considered to be a technically difficult surgery because of the unique anatomy and deep location of the hepatic caudate lobe. Here, we assessed the technical feasibility and safety of robotic partial caudate lobectomy using the da Vinci Surgical System and compared it with traditional open/laparoscopic surgery. Six patients diagnosed with liver cancer (primary liver cancer, 5; metastasis of breast cancer, 1) who underwent caudate lobectomy were prospectively enrolled. Two patients underwent robotic surgery, one underwent laparoscopic surgery, and three underwent traditional/open surgery. Surgical procedure, recovery, and characteristics of robotic surgery were noted and compared with other approaches. All surgeries were successfully completed, and no serious postsurgical complications were observed. In the robotic group, the time taken to complete the surgery and the estimated intraoperative bleeding were 150 and 90 min and 50 and 100 ml in patient 1 and patient 2, respectively. The patients were able to tolerate fluid diet on the following postsurgical day. These two patients had no postsurgical complications and were discharged from the hospital on days 5 and 6 after recovery, respectively. Pathologically, the margins of specimens obtained from these two patients were tumor-free (R0 resection). Tumor size in the traditional/open group was larger than that in the robotic and laparoscopic groups. Blood loss in the laparoscopic case was 50 ml and was less than that in the traditional/open surgery cases (300, 2100, and 1500 ml). Robot-assisted partial hepatic caudate lobectomy is a technically feasible surgery. Our study illustrated an advantage of robotic hepatic caudate lobectomy over laparoscopic or traditional/open surgery and suggested that da Vinci minimally invasive hepatectomy is applicable in even more technically challenging anatomic locations.
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http://dx.doi.org/10.1080/13645706.2018.1521434DOI Listing
October 2019

Juniperus Communis Extract Exerts Antitumor Effects in Human Glioblastomas Through Blood-Brain Barrier.

Cell Physiol Biochem 2018 27;49(6):2443-2462. Epub 2018 Sep 27.

Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan.

Background/aims: Herbal materials derived from Juniperus communis (JCo) possess anticancer activity. In this study, we evaluated the efficacy of a JCo berry extract in suppressing glioblastoma growth.

Methods: The effects of JCo extract on the viability of normal and glioma cell lines was analyzed using a modified 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The synergistic therapeutic effect of JCo extract and temozolomide (TMZ) on glioma cells was examined by MTT analysis. Flow cytometry analysis, the terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) test, and western blotting were performed to identify the apoptotic pathway. To determine the in vivo efficacy of the JCo extract, rats were injected with 5 × 104 rat glioma RG2 cells in the back skin and brain hemisphere and then received a subcutaneous injection in the back skin that contained either JCo extract or vehicle. Finally, blood and histologic examinations were performed to evaluate JCo toxicity.

Results: The IC50 values of JCo extract were 57-69 µg/mL and 49-67 µg/mL in the glioblastoma cell lines after 24 and 48 h, respectively. However, in non-tumor cell lines, the respective IC50 values of JCo extract were 76-105 µg/mL and 77-108 µg/mL. The JCo extract had a stronger cytotoxicity and a larger range of IC50 values in glioma than in normal cells as compared to those effects caused by temozolomide (TMZ). In addition, the results of flow cytometry analysis, TUNEL test, and western blotting revealed that the JCo extract induced glioma cell cycle arrest through intrinsic and extrinsic apoptotic pathways. In the in vivo studies, a significant reduction of tumor size in JCo-treated rats, as measured by animal MRI, demonstrated that the JCo extract effectively inhibited glioma cell growth and successfully penetrated the blood-brain barrier. The immunohistochemical (IHC) staining detected positive signals of PCNA, VEGFR-1, and VEGFR -2 in 44.49%, 5.88%, and 5.85% of JCo-treated glioma cells, respectively. However, positive signals of PCNA, VEGFR-1, and VEGFR-2 were detected in 73.08%, 9.67%, and 11.70% of vehicle-treated glioma cells, respectively. The IHC examination of PCNA and VEGFR-1 and -2 indicated that JCo extract significantly decreased the degree of neovascularization. However, no significant differences in serum levels of blood cell count and hepatic enzymes, renal function index, and the histologic appearance of vital organs were detected between the JCo and vehicle-treated rats.

Conclusion: The JCo extract penetrated the blood-brain barrier and significantly induced glioma cell apoptosis by reducing neovascularization via suppression of the PI3K/AKT/mTOR pathway. Furthermore, JCo extract was less cytotoxic to non-neoplastic vital organs than TMZ.
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http://dx.doi.org/10.1159/000493842DOI Listing
October 2018

Clinicopathological characteristics and prognostic factors of gastrointestinal stromal tumors in Chinese patients.

Oncol Lett 2018 Oct 17;16(4):4905-4914. Epub 2018 Aug 17.

Department of Internal Medicine, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms in the gastrointestinal tract, exhibiting wide variability in their biological behavior. The aim of the present study was to investigate the clinicopathological characteristics and prognostic factors of GISTs in Chinese patients. All GIST cases (n=182) retrieved from the pathology database and the archived files in Shanghai Changzheng Hospital between January 2011 and December 2014 were reviewed. The clinical symptoms, preoperative investigations, treatments, pathological characteristics and follow-up data of these patients were reviewed, and univariate and multivariate survival analyses were performed. A total of 73.1% of the GISTs were located in the stomach, and the most common three symptoms included abdominal pain (30.2%), dyspepsia (23.1%) and gastrointestinal bleeding (21.4%). Univariate analysis revealed that larger tumor size (P<0.001), higher mitotic rate (P<0.001), aggressive behavior (P<0.001), negative smooth muscle actin expression (P=0.009) and palliative resection (P<0.001) contributed toward poor overall survival (OS). In addition, non-gastric disease location (P<0.001), larger tumor size (P<0.001), higher mitotic rate (P=0.004), aggressive behavior (P<0.001) and palliative resection (P<0.001) were associated with poor relapse-free survival (RFS). Multivariate analysis indicated that mitotic rate [hazard ratio (HR=3.761, P=0.015)] and aggressive behavior (HR=3.916, P=0.010) were independent risk factors for OS, while non-gastric location (HR=4.740, P=0.002) and aggressive behavior (HR=4.009, P=0.004) were independent risk factors for RFS. The present study provided information on the clinicopathological characteristics and epidemiology of GISTs in the Chinese population. Non-gastric disease location, higher mitotic rate and tumor metastasis or local invasion prior to treatment were identified as predictors of a poor prognosis.
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http://dx.doi.org/10.3892/ol.2018.9320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6144732PMC
October 2018

Peritumoral monocytes induce cancer cell autophagy to facilitate the progression of human hepatocellular carcinoma.

Autophagy 2018 28;14(8):1335-1346. Epub 2018 Jul 28.

a MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences , Sun Yat-sen University , Guangzhou , P. R. China.

Macroautophagy/autophagy is an important catabolic process mediating cellular homeostasis and plays critical roles in cancer development. Whereas autophagy has been widely studied in various pathological models, little is known about the distribution, clinical significance and regulatory mechanism of this process in human hepatocellular carcinoma (HCC). In the present study, we found that tumor tissues exhibited significantly increased levels of autophagy compared with non-tumor tissues, and cancer cells with higher levels of autophagy were predominantly enriched in the invading edge regions of human HCC. Increased MAP1LC3B/LC3B expression in the invading edge regions was significantly correlated with a higher density of closely located monocytes, and TNF and IL1B derived from tumor-activated monocytes synergistically induced cancer cell autophagy in the invading edge regions of HCC. Monocyte-elicited autophagy induced the epithelial-mesenchymal transition (EMT) of cancer cells and promoted tumor metastasis by activating the NFKB-SNAI1 signaling pathway. Moreover, the increase of LC3B cancer cells in the invading edge areas was associated with high mortality and reduced survival of patients with HCC. These findings indicated that cancer cell autophagy is regulated by a collaborative interaction between tumor and immune cell components in distinct HCC microenvironments, thus allowing the inflammatory monocytes to be rerouted in a tumor-promoting direction.
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http://dx.doi.org/10.1080/15548627.2018.1474994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6103724PMC
October 2019

Hepatocellular carcinoma with en bloc diaphragmatic resection: A single-center experience over 14 years.

Int J Surg 2018 May 16;53:93-97. Epub 2018 Mar 16.

Department of Hepatobiliary & Pancreatic Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, No. 651 Dongfeng Road East, Guangzhou 510060, China. Electronic address:

Background: Diaphragmatic resection is not common in patients undergoing hepatectomy for hepatocellular carcinoma (HCC). This study aims to evaluate retrospectively the clinical characteristics and surgical results of HCC patients undergoing hepatectomy plus diaphragmatic resection.

Methods: Between January 2000 and December 2013, 52 HCC patients underwent curative resections combined with diaphragmatic resection, with 11 patients had pathological diaphragmatic invasion (DI), 41 patients had diaphragmatic fibrous adhesion (DFA). The clinicopathological features and results were compared between the two groups.

Results: 86.5% of the patients had HBV infection. Diameter of tumors was 8.6 ± 3.4 cm, and 34.6% had multiple tumors. In addition, 28.8% had microvascular invasion, 3.8% had macrovascular invasion, but none of the patients had lymph node metastasis or distant metastasis. Moreover, 21.2% had tumor rupture before surgical resection. The DI group exhibited similar clinicopathological features with the DFA group. There were no treatment-related deaths, and major complication was postoperative pleural effusion (46.2%). Other clinical pulmonary issues, such as pneumothorax (5.8%) and pneumonia (3.8%), were also detected. OS at 1, 3 and 5 years was 82.0%, 41.2% and 35.7%, respectively. There was no significant difference in OS and DFS between the DI and DFA groups (P = 0.499 and P = 0.956, respectively).

Conclusions: En bloc resection of diaphragm was associated with acceptable morbidity and mortality, and there was no difference in OS and DFS between HCC patients with DI or DFA. Therefore, it would be advisable to perform en bloc diaphragmatic resection when HCC patients present with gross diaphragmatic involvement.
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http://dx.doi.org/10.1016/j.ijsu.2018.03.033DOI Listing
May 2018

Peritumoral stromal neutrophils are essential for c-Met-elicited metastasis in human hepatocellular carcinoma.

Oncoimmunology 2016;5(10):e1219828. Epub 2016 Sep 27.

State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center , Guangzhou, P.R. China.

Inflammation is a component of tumor progression mechanisms. Neutrophils are a common inflammatory infiltrate in many tumors, but their regulation and functions in neoplasia are not understood. Here, we showed, in detailed studies of c-Met molecule in 225 untreated patients with hepatocellular carcinoma (HCC), that high infiltration of neutrophils in HCC tissues determined malignant cell c-Met-associated clinical outcome of patients. High infiltration of neutrophils in HCCs determined malignant cell c-Met-associated clinical outcome of patients. Neutrophils were enriched predominantly in invading tumor edge of HCCs; the accumulated neutrophils were the major source of c-Met ligand HGF in HCCs. Exposure to HCC environments resulted in neutrophil activation and the following HGF production. Inhibiting the activities of Erk1/2, p38, and NF-κB, but not the phosphorylation of AKT or JNK, successfully attenuated the neutrophil HGF production induced by HCC environments. Further investigation revealed that GM-CSF was an important determinant in malignant cell-elicited neutrophil HGF production and . Moreover, we demonstrated that tumor neutrophils, via HGF/c-Met interaction, actively enhanced the metastasis of malignant cells and . These data provide direct evidence supporting the critical role of neutrophils in human tumor progression and reveal a fine-tuned collaborative action between cancer cells and immune cells in tumor milieu, which reroutes the immune activation into a tumor-promoting direction.
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http://dx.doi.org/10.1080/2162402X.2016.1219828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5087290PMC
September 2016

Polarization of Tissue-Resident TFH-Like Cells in Human Hepatoma Bridges Innate Monocyte Inflammation and M2b Macrophage Polarization.

Cancer Discov 2016 10 16;6(10):1182-1195. Epub 2016 Aug 16.

State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.

The existence, regulation, and functions of IL21 immune cells are poorly defined in human cancers. Here, we identified a subset of protumorigenic IL21 T-like cells in human hepatocellular carcinoma. These cells were the major source of IL21 in tumors and represented about 10% of the CD4 T-cell population at levels comparable with the T cells present in lymph nodes. However, these T-like cells displayed a unique CXCR5PD-1BTLACD69 tissue-resident phenotype with substantial IFNγ production, which differed from the phenotype of T cells. Toll-like receptor 4 (TLR4)-elicited innate monocyte inflammation was important for IL21 T-like cell induction in tumors, and activation of STAT1 and STAT3 was critical for T-like cell polarization in this process. Importantly, the T-like cells operated in IL21-IFNγ-dependent pathways to induce plasma cell differentiation and thereby create conditions for protumorigenic M2b macrophage polarization and cancer progression. Thus, induction of T-like cells links innate inflammation to immune privilege in tumors.

Significance: We identified a novel protumorigenic IL21 T-like cell subset with a CXCR5PD-1 BTLACD69 tissue-resident phenotype in hepatoma. TLR4-mediated monocyte inflammation and subsequent T-cell STAT1 and STAT3 activation are critical for T-like cell induction. T-like cells operate via IL21-IFNγ pathways to induce plasma cells and create conditions for M2b macrophage polarization. Cancer Discov; 6(10); 1182-95. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 1069.
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http://dx.doi.org/10.1158/2159-8290.CD-16-0329DOI Listing
October 2016

[Vacuum sealing drainage combined with discontinuous windowing technique for repairing large area exposed wound of Achilles tendon].

Zhongguo Gu Shang 2015 Dec;28(12):1153-5

Objective: To explore clinical effect of vacuum sealing drainage (VSD) combined with discontinuous windowing technique for repairing large area exposed wounds of Achilles tendon.

Methods: From July 2009 to May 2014, 11 patients with large exposed wounds of Achilles tendon were treated, including 5 males and 6 females with an average age of 43 years old (aged from 7 to 65 years old). Among them, 4 cases were skin necrosis caused by heavy objects abrasion and contusion; 3 cases were caused by distal tibiofibula fractures; 3 cases were caused by bicycle-spoke injuries; 1 case was caused by diabetes. Areas of exposed Achilles tendon were from 6 cmx3 cm to 14 cmx5 cm without tendon rupture or bone exposed. After debridement, discontinuous fenestration on Achilles tendon was made by knife blade parallel with longitudinal axis of Achilles tendon, combined with Vacuum Sealing Drainage (VSD) treatment.

Results: After drainage treatment with one VSD cycle (5 to 7 days), abundant fresh granulation tissues were growing on all wounds and survived well after the second phase dermatoplasty. All patients were followed up for 12 to 24 months, the color of skin flap was good, the texture was soft without burst. At 3 to 4 months after operation, subcutaneous fat was appeared under the flap, the skin was sliding, movement of ankle joints was good. No delayed Achilles tendon rupture were occurred.

Conclusion: Vacuum sealing drainage (VSD) combined with discontinuous fenestration is a simple, safe and effective method for repairing large area exposed wounds of Achilles tendon,which could minimize the secondary damage caused by wounds of skin flap grafting.
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December 2015

The effect of calcium phosphate composite scaffolds on the osteogenic differentiation of rabbit dental pulp stem cells.

J Biomed Mater Res A 2015 May 11;103(5):1732-45. Epub 2014 Sep 11.

Institute of Stomatology, Chinese PLA General Hospital, Fuxing Lu 28#, Beijing, 100853, China.

The objective of this study is to compare the effects of the two calcium phosphate composite scaffolds on the attachment, proliferation, and osteogenic differentiation of rabbit dental pulp stem cells (DPSCs). One nano-hydroxyapatite/collagen/poly (l-lactide) (nHAC/PLA), imitating the composition and the micro-structure characteristics of the natural bone, was made by Beijing Allgens Medical Science & Technology Co., Ltd. (China). The other beta-tricalcium phosphate (β-TCP), being fully interoperability globular pore structure, was provided by Shanghai Bio-lu Biomaterials Co, Ltd. (China). We compared the absorption water rate and the protein adsorption rate of two scaffolds and the characterization of DPSCs cultured on the culture plate and both scaffolds under osteogenic differentiation media (ODM) treatment. The constructs were then implanted subcutaneously into the back of severely combined immunodeficient (SCID) mice for 8 and 12 weeks to compare their bone formation capacity. The results showed that the ODM-treated DPSCs expressed osteocalcin (OCN), bone sialoprotein (BSP), type I collagen (COLI) and osteopontin (OPN) by immunofluorescence staining. Positive alkaline phosphatase (ALP) staining, calcium deposition and calcium nodules were also observed on the ODM-treated DPSCs. The absorption water rate and protein adsorption rate of nHAC/PLA was significantly higher than β-TCP. The initial attachment of DPSCs seeded onto nHAC/PLA was significantly higher than that onto β-TCP; and the proliferation rate of the cells was also significantly higher than that of β-TCP on 1, 3, and 7 days of cell culture. The ALP activity, calcium/phosphorus content and mineral formation of DPSCs + β-TCP were significantly higher than DPSCs + nHAC/LA. When implanted into the back of SCID mice, nHAC/PLA alone had no new bone formation, newly formed mature bone and osteoid were only observed in β-TCP alone, DPSCs + nHAC/PLA and DPSCs + β-TCP, and this three groups displayed increased bone formation over the 12-week period. The percentage of total bone formation area had no difference between DPSCs + β-TCP and DPSCs + nHAC/PLA at each time point, but the percentage of mature bone formation area of DPSCs + β-TCP was significantly higher than that of DPSCs + nHAC/PLA. Our results demonstrated that the DPSCs on nHAC/PLA had a better proliferation, and that the DPSCs on β-TCP had a more mineralization in vitro, much more newly formed mature bones in vivo were presented in DPSCs + β-TCP group. These findings have provided a further knowledge that scaffold architecture has different influence on the attachment, proliferation and differentiation of cells. This study may provide insight into the clinical periodontal bone tissue repair with DPSCs + β-TCP construct.
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http://dx.doi.org/10.1002/jbm.a.35303DOI Listing
May 2015

[Effect of insulin on peroxiredoxin-6 in the osteogenic differentiation of rat's mandiular bone marrow stromal cells in high glucose].

Shanghai Kou Qiang Yi Xue 2013 Oct;22(5):523-7

Institute of Stomatology, General Hospital of Chinese PLA. Beijing

Purpose: To explore the effect of insulin on the expression of peroxiredoxin-6 in osteogenic differentiation of rat's mandibular bone marrow stromal cells(rBMSCs) in high glucose.

Methods: Bone marrow stromal cells were obtained from the mandible of Wistar rats and stimulated in three glucose concentrations mineral medium(5.5 mmol/L, 25 mmol/L and 45 mmol/L) with or without insulin(10-5mol/L) for 1, 3, 7, 14, and 21 days. The expression of prohibitin was quantified via enzyme-linked immuno sorbent assays (ELISA). The mineralization nodules were assessed at day 21 by alizarine red staining. Statistical analysis was performed using SPSS 15.0 soft ware package.

Results: High glucose of 45 mmol/L inhibited mineralization of rBMSCs and insulin can improve the mineralization in high glucose. The expression of peroxiredoxin-6 in 45 mmol/L group decreased significantly compared with 5.5 mmol/L group and 25 mmol/L group. The expression of peroxiredoxin-6 in each group achieved maximum at day 21. Insulin (10-5 mol/L) increased the expression of peroxiredoxin-6 in 25 mmol/L group and 45 mmol/L group in osteogenic differentiation of rBMSCs.

Conclusions: High glucose inhibits the expression of peroxiredoxin-6 in osteogenic differentiation of rBMSCs, while insulin upregulates the expression of peroxiredoxin-6 in rBMSCs. Peroxiredoxin-6 may play an important part in later stage in osteogenic differentiation of rBMSCs.
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October 2013

[Two-dimensional morphology of microleakage between dentin and adhesives].

Hua Xi Kou Qiang Yi Xue Za Zhi 2008 Feb;26(1):77-81

Department of Dental Materials, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.

Objective: To observe the two-dimensional morphology of microleakage between dentin and adhesives.

Methods: The occlusal enamel of human third molar was cut out and the dentin exposed, followed by the application of dental adhesive (Prime & Bond NT, Contax and Adper Prompt), then a composite resin crown was built up. After storage in water (37 degrees C) for 24 h, all teeth were vertically serially sectioned into matchstick-shaped specimens through the bond interfaces. Half of the specimens from one tooth were subjected to thermal cycling and another half was stored in water (37 degrees C). All specimens were then immersed in ammoniacal silver nitrate solution, followed by developing solution. At last all specimens were subjected to microtensile test at a cross-head speed of 1.0 mm/min and their fractured surfaces were observed under scanning electron microscope.

Results: The planar contour of all the silver leakage was various branching, treelike shape, spreading from the border of section to the center.

Conclusion: The planar contour of microleakage is treelike shape and its extent is influenced by adhesives and thermal cycling.
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February 2008