Publications by authors named "Ding Sun"

37 Publications

Expression of nuclear factor erythroid-2-related factor 2, broad complex-tramtrack-bric a brac and Cap'n'collar homology 1 and γ-glutamic acid cysteine synthase in peripheral blood of patients with chronic obstructive pulmonary disease and its clinical significance.

Exp Ther Med 2021 May 22;21(5):516. Epub 2021 Mar 22.

Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.

The purpose of the present study was to explore the relationship between nuclear factor erythroid 2-related factor 2 (Nrf2)/BTB-CNC allogeneic 1 (Bach1)/γ-glutamic acid cysteine synthase (γ-GCS) and chronic obstructive pulmonary disease (COPD). The expression of Nrf2, Bach1, γ-GCS mRNA and protein in the peripheral blood mononuclear cells (PBMCs) of 80 COPD patients and 40 healthy volunteers were studied. Then, the correlation between Nrf2, Bach1, γ-GCS and lung function, inflammation and oxidative stress indicators was analyzed. Compared with healthy controls, Nrf2, Bach1 mRNA and protein levels were significantly increased in the PBMCs of COPD patients, while γ-GCS mRNA and protein levels were significantly decreased. Nrf2 and Bach1 protein levels in the nucleus were significantly elevated in acute exacerbation COPD patients compared with patients with a stable stage of COPD, while γ-GCS mRNA levels were significantly reduced. In addition, it was found that Nrf2 nuclear protein levels were significantly reduced in COPD patients compared with the control group, while Bach1 nuclear protein levels were significantly increased. Correlation analysis in COPD group demonstrated that γ-GCS mRNA was positively correlated with Nrf2 nuclear protein level, but negatively correlated with Bach1 nuclear protein level. Further analysis demonstrated that γ-GCS mRNA and Nrf2 protein in the nucleus was positively correlated with forced expiratory volume in one second (FEV)/forced vital capacity (FVC)% and FEV% predicted, and Bach1 protein in the nucleus was negatively correlated with FEV/FVC% and FEV% predicted. Additionally, the expression levels of Nrf2, Bach1 and γ-GCS were also associated with smoking. The expression of Nrf2, Bach1 and γ-GCS in peripheral blood mononuclear cells of patients with COPD was dysregulated and related to lung function, which provides a new basis for exploring further the pathogenesis of COPD.
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http://dx.doi.org/10.3892/etm.2021.9947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014872PMC
May 2021

[Clinical Analysis of Allogeneic Hematopoietic Stem Cell Transplantation for Treatment of 12 Patients with Acute Leukemia in Tropical Area].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2020 Jun;28(3):742-747

Department of Hematology, Chinese PLA General Hospital, Beijing 100853, China,E-mail:

Objective: To analyze the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treatment of acute leukemia in the tropical area.

Methods: Twelve acute leukemia patients who were underwent allo-HSCT from April 2013 to November 2018 in Hainan Hospital of Chinese PLA General Hospital were selected, including 5 cases of acute lymphoblastic leukemia (ALL) and 7 case of acute myeloid leukemia (AML). Three cases received HLA matched sibling hematopoietic stem cell transplantation, 8 cases received haploidentical hematopoietic stem cell transplantation, 1 cases received partially mismatched unrelated hematopoietic stem cell transplantation. Pretreatment regimen: 9 cases received modified BU/CY+ATG pretreatment regimen, 3 cases received BU/CY pretreatment regimen. Graft-versus-host disease (GVHD) prevention regimen: all patients received cyclosporine A, mycophenolate mofetil combined with short-term methotrexate regimen. The clinical efficacy of allo-HSCT in treatment of acute leukemia in the tropical area was analyzed by detecting hematopoietic reconstitution, GVHD, infection, relapse and survival after transplantation.

Results: All the 12 patients achieved granulocyte reconstruction and megakaryocyte reconstruction. The median time of granulocyte reconstruction was 11.5 (6-14) days, and the median time of megakaryocytic reconstruction was 12.5 (10-22) days. Within 100 days after transplantation, the acute GVHD occurved in 8 cases, including 6 cases of Ⅱ-Ⅳ degree acute GVHD and 2 cases of Ⅲ-Ⅳ degree acute GVHD, 11 cases survived more than 100 days after transplantation, and the chronic GVHD occurred in 1 case, which was mildly limited. Pulmonary infection occurred in 7 cases, cytomegaloviremia occurred in 6 cases, EB viremia occurred in 6 cases, and hemorrhagic cystitis occurred in 5 cases. 2 cases relapsed and eventually died, and the remaining 10 patients survived without disease until the date of follow-up. The median follow-up time was 4 (1-68) months, 83.3% (10/12) survived without disease, and 16.7% (2/12) relapsed.

Conclusion: Allo-HSCT is an effective method for the treatment of acute leukemia in adults. Leukemia patients should be transplanted as soon as possible after remission. The incidence of pulmonary fungal infection in transplanted patients in tropics is high, therefore the prevention and treatment of fungal infection should be strengthened.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2020.03.005DOI Listing
June 2020

HANR Enhances Autophagy-Associated Sorafenib Resistance Through miR-29b/ATG9A Axis in Hepatocellular Carcinoma.

Onco Targets Ther 2020 9;13:2127-2137. Epub 2020 Mar 9.

Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.

Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and chemoresistance is the main obstacle for effective treatments of HCC. Accumulating studies indicated that long non-coding RNAs (lncRNAs) contribute to the chemoresistance of human carcinoma. However, the functional role of HANR in autophagy-mediated chemoresistance of HCC is unknown.

Methods: The expressions of HANR, miR-29b and ATG9A in tissues and cell lines were detected by real-time quantitative PCR (RT-qPCR). The expression of autophagy-related protein LC3-I and LC3-II was evaluated by Western blotting. The cell viability and apoptosis were examined by CCK-8 and flow cytometry, respectively. Bioinformatics analysis and luciferase activity assay were applied to determine the downstream target gene of HANR or miR-29b. Xenograft experiment was used to detect the effect of HANR on tumor growth.

Results: In the present study, we demonstrated that HANR was notably overexpressed in sorafenib-resistant HepG2 (HepG2/sora) and sorafenib-resistant Huh7 (Huh7/sora) cells, and HANR enhanced sorafenib resistance by facilitating autophagy in HepG2/sora and Huh7/sora cells. Furthermore, we demonstrated that miR‑29b could directly interact with HANR and abolished HANR-induced sorafenib resistance by suppressing autophagy in HepG2/sora and Huh7/sora cells. Moreover, ATG9A was validated as a target of miR-29b and its overexpression obviously reversed the inhibitory effect of miR-29b on sorafenib resistance and autophagy. In addition, HANR could act as a competing endogenous RNA (ceRNA) to upregulate ATG9A expression by sponging miR-29b. Hence, HANR increased autophagy-related sorafenib resistance via inhibiting the miR-29b/ATG9A axis in HepG2/sora and Huh7/sora cells, indicating that it may be a potential target to prevent chemoresistance of HCC.

Conclusion: Our study revealed HANR enhanced sorafenib resistance by acting as an autophagy promoter by regulating miR-29b/ATG9A axis in sorafenib‑resistant HCC cells and might provide potential therapeutic strategies for HCC treatment.
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http://dx.doi.org/10.2147/OTT.S229913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069583PMC
March 2020

HANR promotes lymphangiogenesis of hepatocellular carcinoma via secreting miR-296 exosome and regulating EAG1/VEGFA signaling in HDLEC cells.

J Cell Biochem 2019 10 24;120(10):17699-17708. Epub 2019 May 24.

Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, P.R. China.

The long noncoding RNA HANR has been shown to be involved in the progression of hepatocellular carcinoma (HCC). However, the underlying mechanism of HCC-associated long noncoding RNA (HANR)-regulated HCC metastasis and lymphangiogenesis has not been elucidated. RT-qPCR and Western blot methods were utilized to detect the gene expressions. Interaction of HANR with miR-296 was predicted by a bioinformatic program and validated by a dual-luciferase reporter assay. For the functional experiment, a transwell invasion assay was utilized to examine the invasion abilities of HepG2 and Huh-7 cells. The lymphatic vessel formation assay was used to show the HCC-associated lymphatic vessel formation ability of human dermal lymphatic endothelial cells (HDLEC). HANR was shown to directly bind to miR-296, and miR-296 downregulated HANR expression in HepG2 cells. Then, we observed that miR-296 inhibitor transfection in shHANR HCC cells could promote lymphatic vessel formation and invasion of HDLEC cells compared with shHANR HCC cells. EAG1 or VEGFA overexpression in HDLEC cells rescued lymphatic vessel formation and invasion in HDLEC cells coincubated with the medium of HepG2 cells expressing shHANR or miR-296 mimic. Ultimately, HANR knockdown and miR-296 mimic led to a significant decrease in the EAG1 and VEGFA expression levels in HepG2 cells. Here, we reveal a novel molecular mechanism in which the HANR/miR-296/EAG1/VEGF axis is responsible for the lymphangiogenesis of HCC cells. Our findings provide more insights into developing therapeutical or diagnostic methods by targeting HANR.
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http://dx.doi.org/10.1002/jcb.29036DOI Listing
October 2019

HANR promotes hepatocellular carcinoma progression via miR-214/EZH2/TGF-β axis.

Biochem Biophys Res Commun 2018 11 19;506(1):189-193. Epub 2018 Oct 19.

Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, PR China. Electronic address:

Background: LncRNA has been shown to associates with the initiation and progression of hepatocellular carcinoma (HCC). Recently, some studies showed that HANR function as an oncogene in HCC; however, the detailed mechanism of HANR-regulated HCC tumorigenesis and progression needs to be elucidated.

Methods: We used RT-qPCR method to probe genes expression. MTT assay, wound healing assay and transwell invasion assay were utilized to examine proliferation and migration and invasion abilities of HepG2 cells. Xenograft tumor experiment was used to show the growth of tumors in vivo.

Results: HANR was evidently upregulated in HCC tumors and cells compared to normal tissues and cells. Besides, HANR knockdown induces attenuated cell proliferation, migration, invasion of HCC cells. By bioinformatic analysis and dual luciferase reporter assay, we found that miR-214 was the downstream target of HANR. Furthermore, miR-214 inhibitor largely enhanced tumor phenotypes of HCC cells regulated by HANR knockdown. HANR and miR-214 regulated the EZH2, then affecting TGFBR2 level. Finally, we demonstrated that EZH2 overexpression could greatly rescue HANR knockdown or miR-214 mimic-induced HCC tumorigenesis and progression.

Conclusions: In this study, we report a newly identified regulatory mechanism HANR/miR-214/EZH2/TGF-β axis, which is implicated in tumorigenesis and progression of HCC. Our findings suggest that HANR facilitates the development of therapeutical strategies or diagnostic markers by targeting HANR.
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http://dx.doi.org/10.1016/j.bbrc.2018.10.038DOI Listing
November 2018

Perforation caused by gastric mucosa associated lymphoid tissue lymphoma: A case report and literature review.

Medicine (Baltimore) 2018 Aug;97(33):e11713

The First Affiliated Hospital of Soochow University Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.

Rationale: Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is the most common and best-studied extranodal marginal zone lymphoma of the MALT. It is characterized by an indolent clinical course and excellent survival compared with other malignant tumor. Complications such as obstruction, perforation or bleeding are rarely observed. The treatment strategy is still controversial.

Patient Concerns: A 59-year-old man, who had been diagnosed with MALT lymphoma by gastroscopy and biopsy one month before, came to the hospital for a sudden onset of abdominal pain after breakfast.

Diagnoses: MALT lymphoma; gastric perforation.

Interventions: Emergency surgery.

Outcomes: Gastric perforation repair and jejunostomy was performed. The patient recovered well and is preparing for combined chemotherapy.

Lessons: This case report illustrates the challenges in diagnosis and treatment of MALT lymphoma. We discussed the particularity of its clinical characteristics, treatment strategies and prognosis combined with literature review, and we think that early diagnosis and timely appropriate chemotherapy is of great importance.
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http://dx.doi.org/10.1097/MD.0000000000011713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6112864PMC
August 2018

Increased expression of epidermal growth factor-like domain-containing protein 7 is predictive of poor prognosis in patients with hepatocellular carcinoma.

J Cancer Res Ther 2018 ;14(4):867-872

Department of Interventional Radiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.

Objective: Epidermal growth factor-like domain-containing protein 7 (EGFL7) is an endothelial cell-derived secreted factor that regulates vascular tube formation. In human cancer, the specificity of expression is lost as EGFL7 has been detected in tumor cells, in addition to endothelial cells. This study evaluated the intricate relationship between hypoxia-inducible factor 1-alpha (HIF-1α) and EGFL7 under both hyperoxia and hypoxia states.

Materials And Methods: In the present study, immunohistochemical staining and ELISA were applied to examine the relative level of EGFL7 in 182 cases of hepatocellular carcinoma (HCC) formalin-fixed and paraffin-embedded tissues and 110 cases of HCC serum samples. Quantitative polymerase chain reaction and Western blotting were applied to verify the correlation between serum EGFL7 level and anoxic microenvironment. Immunohistochemical staining was performed to determine the correlation between EGFL7 and HIF1-α.

Results: The correlations between EGFL7 expression and patients' age, tumor size, gender, N-stage, history of cirrhosis, M-stage, history of hepatitis C, and history of hepatitis B were statistically insignificant (P = 0.28, 0.34, 0.71, 0.15, 0.8, 0.2, 0.052, and 0.14, respectively). High level of EGFL7 was significantly correlated with overall survival as well as disease-free survival in 182 HCC patients (P = 0.0016 and P < 0.001, respectively). The correlations between serum EGFL7 and vascular invasion and extrahepatic metastasis were statistically significant (P < 0.0001). Among the 35 HIF1-α-positive HCC patients, 69% were medium positive and 31% were strong positive. EGFL7 protein expression level was oxygen dependent in HCC line (P < 0.05).

Conclusions: EGFL7 was found to be a potential predictor for HCC survival and metastasis state; EGFL7 may be a promising biomarker and therapeutic target in human HCC.
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http://dx.doi.org/10.4103/jcrt.JCRT_745_17DOI Listing
October 2018

Characteristics of Long-term Nonprogressors and Viremia Controllers Infected with HIV-1 via Contaminated Blood Donations or Transfusions Conducted 20 Years Earlier.

Biomed Environ Sci 2017 Dec;30(12):907-912

Institute for Prevention and Control of AIDS and STD, Henan Center for Disease Control and Prevention, Zhengzhou 450016, Henan, China.

To characterize long-term nonprogressors (LTNPs) and viremia controllers (VCs), infected with HIV-1 through contaminated blood donation or transfusion between 1992 and 1996 in Henan, China. LTNPs and VCs were defined by CD4+T lymphocyte (CD4) count and viral load (VL). Of 29,294 patients infected with HIV-1 via contaminated blood donation or transfusion that had conducted for more than 20 years, 92 were LTNPs/VCs. There were 70 LTNPs (0.24%), 43 VCs (0.15%), and 48 LTNPs+VCs- (0.16%). VCs had a significantly lower CD4 nadir, compared to LTNPs and LTNPs+VCs-, and no significant differences for the highest VL and HIV-1 DNA. Cases P4 and P5 were LTNPs, while their VL reached approximately 4.3 log copies/mL. P6 was a VC, but with CD4 < 500 cells/μL constantly. Data from the LTNPs/VCs cohort provided valuable information, future research is needed.
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http://dx.doi.org/10.3967/bes2017.121DOI Listing
December 2017

Evaluation on the thyroid disrupting mechanism of malathion in Fischer rat thyroid follicular cell line FRTL-5.

Drug Chem Toxicol 2018 Oct 16;41(4):501-508. Epub 2017 Nov 16.

c Department of Environmental and Occupational Medicine , West China School of Public Health, Sichuan University , Chengdu , China.

Thyroid hormones are involved in many important physiological activities including regulation of energy metabolism, development of nervous system, maintenance of cerebral functions, and so on. Endocrine-disrupting chemicals (EDCs) that interfere with thyroid functions raise serious concerns due to their frequent misuse in areas where regulations are poorly implemented. In addition, chemicals that are originally regarded safe may now be considered as toxic with the development of life sciences. Malathion is an organophosphate insecticide that is widely applied and distributed in agricultural and residential settings. Due to the low acute toxicity and rapid degradation, malathion is not listed as a primary thyroid disrupting chemical. However, emerging evidences reported that malathion affected thyroperoxidase catalyzed iodide oxidation which in turn influenced thyroid hormone transportation, and enhanced parathyroid hyperplasia prevalence. Nevertheless, direct effect of malathion on thyroid hormone biosynthesis remains to be elucidated. This study investigated the effects of thyroid disruption of malathion in Fischer rat thyroid follicular cell line, FRTL-5. Transcriptional and translational analyses on thyroglobulin demonstrated that both mRNA and protein expression levels were significantly inhibited by malathion. Cellular cAMP level and TSH receptor expression were distinctly reduced by malathion (6.0 µg/ml). These results suggested that malathion directly disrupted the biosynthesis of thyroid hormone and the mechanism involved down-regulation of TSH receptor and cellular cAMP. This subsequently led to the suppression of TSH dependent signal transduction, TG transcription inhibition, and obstruction of thyroid hormone biosynthesis.
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http://dx.doi.org/10.1080/01480545.2017.1397162DOI Listing
October 2018

Zymosan-a Protects the Hematopoietic System from Radiation-Induced Damage by Targeting TLR2 Signaling Pathway.

Cell Physiol Biochem 2017 1;43(2):457-464. Epub 2017 Sep 1.

Background/aims: The hematopoietic system is vulnerable to ionizing radiation and is often severely damaged by radiation. Molecules affecting radioresistance include Toll-like receptor 2. We investigated whether Zymosan-A, a novel TLR2 agonist, can protect the hematopoietic system from radiation-induced damage after total body irradiation.

Methods: Mice were exposed to total body radiation after treatment with Zymosan-A or normal saline, and their survival was recorded. Tissue damage was evaluated by hematoxylin-eosin staining. The number of nucleated cells in bone marrow was determined by flow cytometry. Cell viability and apoptosis assay were determined by CCK-8 assay and flow cytometry assay. Enzyme-linked immunosorbent assay was used to detect the level of cytokines.

Results: Zymosan-A protected mice from radiation-induced death and prevented radiation-induced hematopoietic system damage. Zymosan-A also promoted cell viability and inhibited cell apoptosis caused by radiation, induced radioprotective effects via TLR2, upregulated IL-6, IL-11, IL-12, and TNF-α in vivo.

Conclusion: Zymosan-A can provide protection against radiation-induced hematopoietic system damage by targeting the TLR2 signaling pathway. Thus, Zymosan-A can be potentially effective radioprotectant.
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http://dx.doi.org/10.1159/000480472DOI Listing
October 2017

Down regulation of miR-143 promotes radiation - Induced thymic lymphoma by targeting B7H1.

Toxicol Lett 2017 Oct 20;280:116-124. Epub 2017 Jul 20.

Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, PR China. Electronic address:

MicroRNA-143 has been implicated in tumor metastasis by directly targeting Bcl-2, and microRNA-143 expression is decreased in several human tumors. However, the expression and targets of miR-143 in radiation carcinogenesis remain unclear. We found that the expression of miR-143 is down-regulated and the expression of B7H1 (Pdcd1) is up-regulated in radiation-induced thymic lymphoma model in BALB/c mice. Additionally, overexpression of miR-143 strongly inhibited cell proliferation and increased cell apoptosis and its down-regulation promoted cell proliferation and reduced cell apoptosis. We also determined that there is an inverse correlation between miR-143 expression and B7H1 protein expression in radiation-induced thymic lymphoma samples, and miR-143 targets B7H1 in a 3'UTR-dependent manner. In addition, we found that adenovirus over-expression of pre-miR-143 reduced tumorigenesis in vivo. Finally, we conclude that down-regulated expression of miR-143 and up-regulation of its direct target B7H1 may indicate a novel therapeutic method for radiation-induced thymic lymphoma by increased expression of miR-143 or inhibition of B7H1.
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http://dx.doi.org/10.1016/j.toxlet.2017.07.891DOI Listing
October 2017

Polymyxin B Attenuates LPS-Induced Death but Aggravates Radiation-Induced Death via TLR4-Myd88-IL-6 Pathway.

Cell Physiol Biochem 2017 29;42(3):1120-1126. Epub 2017 Jun 29.

Department of Radiation Medicine, Faculty of Naval Medicine, Shanghai, China.

Background/aims: Polymyxin B (PMB) is a cyclic cationic polypeptide antibiotic widely used to counteract the effects of endotoxin contamination, both in vitro and in vivo. Lipopolysaccharide (LPS) is an endotoxin that acts as a radiation protection factor. In this study, we focus on the role of PMB in LPS-induced and radiation-induced mortality in mice.

Methods: Mice received total-body radiation or were pretreated by LPS or PMB, and the survival of mice was recorded. Elisa were used to detect the cytokines levels.

Results: PMB decreased LPS-induced, but increased radiation-induced mortality in mice. Moreover, PMB could block the LPS-induced radioprotective effect. The ELISA and gene knock-out experiments indicated that PMB reduces TNF-α level to block LPS-induced mortality in mice, and inhibits IL-6, G-CSF and IL-10 to increase radiation-induced mortality via the TLR4-Myd88-IL-6 pathway.

Conclusions: Our study revealed a role of PMB in LPS-induced endotoxemia and radiation exposure. We infer that the TLR4-Myd88-IL-6 pathway may play a crucial role in the process.
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http://dx.doi.org/10.1159/000478767DOI Listing
November 2017

[Prognostic factors of lymph node-negative metastasis gastric cancer].

Zhonghua Wei Chang Wai Ke Za Zhi 2017 Feb;20(2):190-194

Department of Surgical Oncology, The First Hospital of China Medical University, Shenyang 110001,China.

Objective: To investigate the prognostic factors of patients with lymph node-negative metastasis gastric cancer (pN0).

Methods: Clinicopathological data of patients with pN0 gastric cancer who underwent radical operation at the Department of Surgical Oncology, The First Hospital of China Medical University from May 1980 to August 2012 were collected and analyzed retrospectively.

Inclusion Criteria: (1) Patients were diagnosed as gastric adenocarcinoma; (2) Postoperative pathology confirmed T1a to 4bN0M0 gastric cancer; (3) Total number of harvested lymph node was more than 15. The patients, who died within 1 month after the operation, died of other diseases, had remnant gastric cancer, or had incomplete follow-up data, were excluded. Univariate analysis was used to analyze the clinical factors that may influence the prognosis of patients with stage pN0 gastric cancer, then, those significant variables were entered into the Cox's proportional hazards regression model for multivariate analysis to obtain the independent prognostic factors for patients with pN0 gastric cancer finally. Furthermore, the prognosis of patients with pN0 advanced gastric cancer (invasive depth ≥ T2) were analyzed using the same method.

Results: A total of 610 patients with pN0 gastric cancer were enrolled in the study, including 441 males and 169 females with age ranging from 19 to 83 (mean 56.4±11.0) years, D1 lymph node dissection in 45 cases, D2 lymph node dissection in 543 cases, D3 lymph node dissection in 22 cases, and 384 cases of advanced gastric cancer. The overall followed-up was 1 to 372 (median 32) months. Ninety cases (14.8%) were dead during the follow-up. The median survival was 277.7(95%CI: 257.6 to 297.8) months, and the 1-, 3-, 5-year survival rates were 96.5%, 87%, 83.2%. Univariate analysis showed that tumor diameter, depth of invasion, gross type, lymph node dissection and lymph vessel cancer embolus were related to the prognosis (all P<0.05). The 5-year survival rate of patients with tumor diameter >4 cm was significantly lower than those with tumor diameter ≤4 cm (75.6% vs. 87.8%, P=0.000). The 5-year survival rates of T1a, T1b, T2, T3 and T4 were 98.4%, 92.8%, 84.2%, 61.0% and 31.4% respectively, and the difference was statistically significant (P=0.000). In gross type, 5-year survival rate of early gastric cancer was 96.0%, and of Borrmann I( to IIII( type gastric cancer was 100%, 83.4%, 73.7% and 68.9% respectively, whose difference was statistically significant(P=0.000). The 5-year survival rates in patients undergoing lymph node dissection D1, D2 and D3 were 100%, 83.3% and 58.7%, and the difference was significant (P=0.005). The 5-year survival rate of patients with positive lymphatic cancer embolus was lower than those with negative ones (69.4% vs. 86.9%, P=0.000). Multivariate analysis showed that the gross type [Borrmann II(/early gastric cancer: HR(95% CI)=15.129(3.284 to 69.699), Borrmann III(/early gastric cancer: HR(95% CI)=14.613 (3.292 to 64.875), Borrmann IIII(/early gastric cancer: HR (95% CI)=15.430 (2.778 to 85.718),Borrmann IIIII(/early gastric cancer: HR(95%CI)=12.604 (1.055 to 150.642), P=0.025] and the positive lymphatic cancer embolus [HR(95% CI)=3.241 (2.056 to 5.108), P=0.000] were the independent prognostic factors of patients with pN0 gastric cancer. For pN0 patients with advanced gastric cancer, multivariate analysis showed that the depth of invasion [stage T3/stage T2: HR(95%CI)=1.520 (0.888 to 2.601), stage T4/stage T2: HR(95%CI)=2.235(1.227 to 4.070); P=0.031] and the positive lymphatic cancer embolus [HR(95%CI)=3.065 (1.930 to 4.868); P=0.000] were the independent risk factors influencing the prognosis.

Conclusions: Positive lymphatic cancer embolus and worse gross pattern indicate poorer prognosis of patients with pN0 gastric cancer, which may be used as effective markers in evaluating the prognosis. As for pN0 advanced gastric cancer, invasion depth and positive lymphatic cancer embolus can play a more important role in the prediction.
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February 2017

Gelsolin Inhibits the Inflammatory Process Induced by LPS.

Cell Physiol Biochem 2017 20;41(1):205-212. Epub 2017 Jan 20.

Background/aims: Endotoxemia is a life-threatening situation that signifies a key challenge in the field of intensive care medicine. Proinflammatory mediators produced by macrophages play a key role in endotoxemia. Gelsolin (GSN) is involved in the process of inflammation.

Methods: IL-6 and TNF-α in the supernatant were measured with an ELISA kit. NO production was assessed by measurement of nitrite concentration with the Griess assay. si-RNA directed against GSN (si-GSN) was transfected by Lipofectamine.

Results: LPS decreased the levels of GSN. Recombinant GSN inhibited the cytokines induced by LPS and rescued mice from LPS-induced death, and si-GSN increased death in the LPS-pretreated mice.

Conclusion: GSN exhibited a protective role in endotoxemia.
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http://dx.doi.org/10.1159/000456043DOI Listing
June 2017

A single-step lithography system based on an enhanced robotic adhesive dispenser.

Rev Sci Instrum 2016 Sep;87(9):095005

State Key Laboratory of Robotics and Systems, Harbin Institute of Technology, 2 Yikuang, C1 HIT Science Park, 150080 Harbin, People's Republic of China.

In the paper, we present a single-step lithography system whereby the robotically controlled micro-extrusion of resist adhesive onto a substrate surface to directly create resist adhesive patterns of interest. This system is modified from a robotic adhesive dispenser by shrinking the aperture of the nozzle to a few micrometers aiming to realize patterns at microscale. From experimental investigation, it is found that working factors including writing speed, working time, and applied pressure can be adopted to conveniently regulate the feature size (the width of the line features and the diameter of the dot features). To test its functionality, the system was used to pattern line features on silicon dioxide (SiO) and generate an array of square-like silicon microstructure by combining with wet etching. It provides a simple and flexible alternative tool to facilitate the development of microfabrication.
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http://dx.doi.org/10.1063/1.4963357DOI Listing
September 2016

Extrusion printing for fabrication of spherical and cylindrical microlens arrays.

Appl Opt 2016 Sep;55(25):6947-52

In this paper, we present an extrusion printing technique for producing spherical and cylindrical plano-convex microlens arrays with controllable feature dimensions. This technique employs a robotic adhesive dispenser for robotically controlled microextrusion of ultraviolet (UV) curable polymer onto a glass substrate surface to directly deposit the microlens arrays. It provides a simple and flexible alternative to fabricate both spherical and cylindrical microlens arrays.
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http://dx.doi.org/10.1364/AO.55.006947DOI Listing
September 2016

Radioprotective Effect of Grape Seed Proanthocyanidins In Vitro and In Vivo.

Oxid Med Cell Longev 2016 26;2016:5706751. Epub 2016 Jun 26.

Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.

We have demonstrated that grape seed proanthocyanidins (GSPs) could effectively scavenge hydroxyl radical (•OH) in a dose-dependent manner. Since most of the ionizing radiation- (IR-) induced injuries were caused by •OH, this study was to investigate whether GSPs would mitigate IR-induced injuries in vitro and in vivo. We demonstrated that GSPs could significantly reduce IR-induced DNA strand breaks (DSBs) and apoptosis of human lymphocyte AHH-1 cells. This study also showed that GSPs could protect white blood cells (WBC) from IR-induced injuries, speed up the weight of mice back, and decrease plasma malondialdehyde (MDA), thus improving the survival rates of mice after ionizing radiation. It is suggested that GSPs have a potential as an effective and safe radioprotective agent.
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http://dx.doi.org/10.1155/2016/5706751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4939198PMC
March 2017

A polymeric nanoparticle formulation of curcumin in combination with sorafenib synergistically inhibits tumor growth and metastasis in an orthotopic model of human hepatocellular carcinoma.

Biochem Biophys Res Commun 2015 Dec 19;468(4):525-32. Epub 2015 Oct 19.

Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, PR China. Electronic address:

Curcumin, a yellow polyphenol extracted from the rhizome of turmeric root (Curcuma longa) has potent anti-cancer properties in many types of tumors with ability to reverse multidrug resistance of cancer cells. However, widespread clinical application of this agent in cancer and other diseases has been limited due to its poor aqueous solubility. The recent findings of polymeric nanoparticle formulation of curcumin (NFC) have shown the potential for circumventing the problem of poor solubility, however evidences for NFC's anti-cancer and reverse multidrug resistance properties are lacking. Here we provide models of human hepatocellular carcinoma (HCC), the most common form of primary liver cancer, in vitro and in vivo to evaluate the efficacy of NFC alone and in combination with sorafenib, a kinase inhibitor approved for treatment of HCC. Results showed that NFC not only inhibited the proliferation and invasion of HCC cell lines in vitro, but also drastically suppressed primary tumor growth and lung metastases in vivo. Moreover, in combination with sorafenib, NFC induced HCC cell apoptosis and cell cycle arrest. Mechanistically, NFC and sorafenib synergistically down-regulated the expression of MMP9 via NF-κB/p65 signaling pathway. Furthermore, the combination therapy significantly decreased the population of CD133-positive HCC cells, which have been reported as cancer initiating cells in HCC. Taken together, NanoCurcumin provides an opportunity to expand the clinical repertoire of this agent. Additional studies utilizing a combination of NanoCurcumin and sorafenib in HCC are needed for further clinical development.
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http://dx.doi.org/10.1016/j.bbrc.2015.10.031DOI Listing
December 2015

Spectrally encoded extended source optical coherence tomography.

Opt Lett 2014 Dec;39(24):6803-6

We have developed an extended source optical coherence tomography (SEES-OCT) technique in an attempt to improve signal strength for ophthalmic imaging. A line illumination with a visual angle of 7.9 mrad is produced by introducing a dispersive element in the infinity space of the sample arm. The maximum permissible exposure (MPE) of such an extended source is 3.1 times larger than that of a "standard" point source OCT, which corresponds to sensitivity improvement of 5 dB. The advantage of SEES-OCT in providing superior penetration depth over a point source system is demonstrated using swine eye tissues ex vivo.
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http://dx.doi.org/10.1364/OL.39.006803DOI Listing
December 2014

Dual spectrometer system with spectral compounding for 1-μm optical coherence tomography in vivo.

Opt Lett 2014 Dec;39(23):6727-30

1 μm axial resolution spectral domain optical coherence tomography (OCT) is demonstrated for in vivo cellular resolution imaging. Output of two superluminescent diode sources is combined to provide near infrared illumination from 755 to 1105 nm. The spectral interference is detected using two spectrometers based on a Si camera and an InGaAs camera, respectively. Spectra from the two spectrometers are combined to achieve an axial resolution of 1.27 μm in air. Imaging was conducted on zebra fish larvae to visualize cellular details.
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http://dx.doi.org/10.1364/OL.39.006727DOI Listing
December 2014

Gelsolin: role of a functional protein in mitigating radiation injury.

Cell Biochem Biophys 2015 Jan;71(1):389-96

Division of Radiation Medicine Department of Naval Medicine, Second Military Medical University, Shanghai, China.

The present study was conducted to explore the protective effect of exogenous gelsolin (GSN) in mice exposed to high-dose of radiation. Changes in the levels of GSNs in peripheral blood of mice and cytoplasm of cultured human intestinal epithelial cells (HIECs) were analyzed after their exposure to different doses of (137)Cs γ-rays at a fixed dose rate. The coagulation associated indices, such as prothrombin time (PT) and activated partial thromboplastin time (APTT) were measured. Effect on radiation-mediated oxidative damage was evaluated by estimating the altered glutathione (GSH) and malondialdehyde (MDA) concentrations in the blood. The results showed that radiation induced a pronounced decrease in the pGSN blood levels. However, the cGSN levels of irradiated HIECs were increased in a dose-dependent manner. Administration of recombinant human pGSN to irradiated mice resulted in an ameliorated clotting time as indicated by the PT and the APTT indices. The treatment of mice with hpGSN enhanced the blood levels of GSH while MDA concentrations were decreased indicating an improved antioxidant status. These results suggest that GSNs might play a regulatory role in the suppression of the tissue damage induced by acute radiation exposure.
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http://dx.doi.org/10.1007/s12013-014-0210-3DOI Listing
January 2015

Influence of adriamycin on changes in Nanog, Oct-4, Sox2, ARID1 and Wnt5b expression in liver cancer stem cells.

World J Gastroenterol 2014 Jun;20(22):6974-80

Ding Sun, Lei Qin, Yang Xu, Jian-Xia Liu, Li-Ping Tian, Hai-Xin Qian, Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China.

Aim: To determine the influence of Adriamycin (ADM) on the changes in Nanog, Oct4, Sox2, as well as, in ARID1 and Wnt5b expression in liver cancer stem cells.

Methods: The MHCC97-L and HCCLM3 liver cancer cell lines were selected as the cell models in this study, and were routinely cultured. The 50% lethal dose (LD50) in the cell lines was detected by the MTT assay. Expression changes in liver cancer stem cell related genes (Nanog, Oct-4, Sox2, ARID1, and Wnt5b) were detected by western blot following treatment with ADM (LD50).

Results: The LD50 of ADM in MHCC97-L cells was lower than that in HCCLM3 cells (0.4123 ± 0.0236 μmol/L vs 0.5259 ± 0.0125 μmol/L, P < 0.05). Wnt5b and Nanog were expressed in both MHCC97-L and HCCLM3 cells, while only Sox2 was expressed in HCCLM3 cells. However, neither ARID1A nor Oct4 was detected in these two cell lines. Genes, related to the stem cells, showed different expression in liver cancer cells with different metastatic potential following treatment with ADM (LD50). Wnt5b protein increased gradually within 4 h of ADM (LD50) treatment, while Nanog decreased (P < 0.05). After 12 h, Wnt5b decreased gradually, while Nanog increased steadily (P < 0.05). In addition, only Sox2 was expressed in HCCLM3 cells with high metastatic potential following ADM (LD50) treatment. The expression of Sox2 increased gradually with ADM (LD50) in HCCLM3 cells (P < 0.05).

Conclusion: ADM increased the death rate of MHCC97-L and HCCLM3 cells, while the growth suppressive effect of ADM was higher in MHCC97-L cells than in HCCLM3 cells.
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http://dx.doi.org/10.3748/wjg.v20.i22.6974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4051940PMC
June 2014

Heme oxygenase and ocular disease: a review of the literature.

Curr Eye Res 2012 Nov 21;37(11):955-60. Epub 2012 Jun 21.

Department of ophthalmology, Linyi People's Hospital, Linyi City, Shandong Province, China.

Heme oxygenase (HO) catabolizes heme into three products: carbon monoxide (CO), biliverdin/bilirubin and free iron. Two distinct isoforms of HO have been identified: an inducible isozyme HO-1 and a constitutively expressed isozyme HO-2, which participate in a variety of physiological and pathophysiological processes. A growing body of evidence indicates that HO activation plays a variety of roles in several ocular diseases, functioning protectively by reducing oxidative injury, attenuating the inflammatory response, and inhibiting cell apoptosis. This review focuses on the current understanding of the physiological significance of HO and its putative roles in the ocular disease. Possible therapeutic strategies involving HO in the treatment of ocular disease are discussed.
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http://dx.doi.org/10.3109/02713683.2012.700753DOI Listing
November 2012

Hydrogen-rich saline protects immunocytes from radiation-induced apoptosis.

Med Sci Monit 2012 Apr;18(4):BR144-8

Department of Radiation Medicine, Faculty of Naval Medicine, 2nd Military Medical University, Shanghai, PR China.

Background: Radiation often causes depletion of immunocytes in tissues and blood, which results in immunosuppression. Molecular hydrogen (H2) has been shown in recent studies to have potential as a safe and effective radioprotective agent through scavenging free radicals. This study was designed to test the hypothesis that H2 could protect immunocytes from ionizing radiation (IR).

Material/methods: H2 was dissolved in physiological saline or medium using an apparatus produced by our department. A 2-[6-(4'-hydroxy) phenoxy-3H-xanthen-3-on-9-yl] benzoate (HPF) probe was used to detect intracellular hydroxyl radicals (•OH). Cell apoptosis was evaluated by annexin V-FITC and Propidium iodide (PI) staining as well as the caspase 3 activity. Finally, we examined the hematological changes using an automatic Sysmex XE 2100 hematology analyzer.

Results: We demonstrated H2-rich medium pretreatment reduced •OH level in AHH-1 cells. We also showed H2 reduced radiation-induced apoptosis in thymocytes and splenocytes in living mice. Radiation-induced caspase 3 activation was also attenuated by H2 treatment. Finally, we found that H2 rescued the radiation-caused depletion of white blood cells (WBC) and platelets (PLT).

Conclusions: This study suggests that H2 protected the immune system and alleviated the hematological injury induced by IR.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3560832PMC
http://dx.doi.org/10.12659/msm.882616DOI Listing
April 2012

MiR-21 plays an important role in radiation induced carcinogenesis in BALB/c mice by directly targeting the tumor suppressor gene Big-h3.

Int J Biol Sci 2011 Apr 1;7(3):347-63. Epub 2011 Apr 1.

Department of Radiation Medicine, Second Military Medical University, Xiangyin Road, Shanghai 200433, PR China.

Dysregulation of certain microRNAs (miRNAs) in cancer can promote tumorigenesis, metastasis and invasion. However, the functions and targets of only a few mammalian miRNAs are known. In particular, the miRNAs that participates in radiation induced carcinogenesis and the miRNAs that target the tumor suppressor gene Big-h3 remain undefined. Here in this study, using a radiation induced thymic lymphoma model in BALB/c mice, we found that the tumor suppressor gene Big-h3 is down-regulated and miR-21 is up-regulated in radiation induced thymic lymphoma tissue samples. We also found inverse correlations between Big-h3 protein and miR-21 expression level among different tissue samples. Furthermore, our data indicated that miR-21 could directly target Big-h3 in a 3'UTR dependent manner. Finally, we found that miR-21 could be induced by TGFβ, and miR-21 has both positive and negative effects in regulating TGFβ signaling. We conclude that miR-21 participates in radiation induced carcinogenesis and it regulates TGFβ signaling.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3076505PMC
http://dx.doi.org/10.7150/ijbs.7.347DOI Listing
April 2011

A possible prevention strategy of radiation pneumonitis: combine radiotherapy with aerosol inhalation of hydrogen-rich solution.

Med Sci Monit 2011 Apr;17(4):HY1-4

Department of Radiation Medicine, Faculty of Naval Medicine, 2nd Military Medical University, Shanghai, PR China.

Radiotherapy is an important modality of cancer treatment. Radiation pneumonitis is a major obstacle to increasing the radiation dose in radiotherapy, and it is important to prevent this radiation-induced complication. Recent studies show that hydrogen has a potential as an effective and safe radioprotective agent by selectively reducing hydroxyl and peroxynitrite radicals. Since most of the ionizing radiation-induced cellular damage is caused by hydroxyl radicals, we hypothesize that a treatment combining radiotherapy with aerosol inhalation of a hydrogen-rich solution may be an effective and novel prevention strategy for radiation pneumonitis (hydrogen is explosive, while a hydrogen-rich solution such as physiological saline saturated with molecular hydrogen is safer).
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3539519PMC
http://dx.doi.org/10.12659/msm.881698DOI Listing
April 2011

The mechanism for the ameliorative effect of CpG-oligodeoxynucleotides on bone marrow hemopoiesis radiation injury.

Basic Clin Pharmacol Toxicol 2011 Jul 25;109(1):11-6. Epub 2011 Apr 25.

Section of Radiation Medicine, Department of Naval Medicine, Second Military Medical University, Shanghai, China.

Bone marrow is a major site of radiation injury. The extreme sensitivity of bone marrow cells to genotoxic stress largely determines the adverse side effects of radiation. CpG-oligodeoxynucleotide (ODN) is known to be radioprotective in extramedullary hemopoiesis, but its effect on bone marrow hemopoiesis remains unknown. In this study, we investigated whether CpG-ODN ameliorated hemopoiesis radiation injury when administered after total-body irradiation (TBI). Mice were treated with 50 μg of CpG-ODN via intraperitoneal injection (i.p) 30 min., 24 and 48 hr after TBI. Our results show that CpG-ODN was able to mediate the activation of nuclear factor κB (NF-κB) via degradation of inhibitor NF-κB (IκB-α), and some oxidative stress parameters (malondialdehyde, glutathione and superoxide dismutase) showed significant differences between the radiation control group and the radiation and administration of CpG-ODN group. White blood cell count, bone marrow cell count and bone marrow histological examination indicated that CpG-ODN minimized bone marrow damage induced by radiation. Exogenous colony-forming unit-spleen count indicated that CpG-ODN reduced primitive hemopoietic stem cell damage and reconstituted the hemopoietic system after TBI. The survival of mice was also enhanced after various levels of TBI. The calculated dose reduction factor was 1.2. Thus, we conclude that CpG-ODN may contribute to the amelioration of hemopoiesis radiation injury.
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http://dx.doi.org/10.1111/j.1742-7843.2011.00695.xDOI Listing
July 2011

[The disruptive effect of N'N-methylene-bis on the function of FRTL-5 cells].

Sichuan Da Xue Xue Bao Yi Xue Ban 2010 Jan;41(1):73-6

Department of Environmental Health, West China School of Public Health, Sichuan University, Chengdu, China.

Objective: To study the impact of N' N-methylene-bis on thyroglobulin produced by FRTL-5 cells, and to explore the potential of using FRTL-5 cells to screen environmental thyroid hormone disruptors in vitro.

Methods: The FRTL-5 cells were treated with 0.1, 1.0 and 10.0 microg/mL N'N-methylene-bis for 48 hours, respectively. The concentrations of thyroglobulin in the medium of the treated cells were detected by radioimmunoassay. The expression of thyroid peroxidases in the FRTL-5 cells was assessed by enzyme cytochemistry technique. The ultrastructure of the cells was also observed.

Results: The FRTL-5 cells treated with 0.1 and 1.0 microg/mL of N' N-methylene-bis produced less thyroglobulin than the controls (P < 0.05). No thyroglobulin was detected with the cells treated with 10.0 microg/mL of N' N-methylene-bis. No difference in the expression of thyroid peroxidases was found between the treated cells and the controls. The treated cells had expanded rough endoplasmic reticulum.

Conclusion: N' N-methylene-bis disrupts the bio-function of thyroid by damaging the rough endoplasmic reticulum of thyroid follicular cells. FRTL-5 cells can be used for screening thyroid hormone disruptors in vitro.
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January 2010

[Effects of perinatal exposure to sulphamethazine on the thyroid gland function of SD rats].

Wei Sheng Yan Jiu 2010 Jan;39(1):83-5

Department of Environmental Health, West China School of Public Health, China.

Objective: To study the effect of perinatal exposure sulphamethazine on the function of thyroid gland of SD rats.

Methods: Dams were given sulphamethazine 0, 50, 100 and 200 mg/(kg x d) respectively from gestational day (GD) 7 to postpartum day (P) 21. The sections of thyroid gland of pups 20 days after birth were stained by hematoxylin-eosin, and the expression of proliferating cell nuclear antigen (PCNA) were observed by immunohistochemistry staining.

Results: Compare with control, thyroid gland showed proliferation of follicular epithelium in each experimental group, and the numbers of PCNA positive cells in thyroid gland significantly higher than that of control (P < 0.05).

Conclusion: Perinatal exposure to sulphamethazine may affect the function of thyroid gland of offspring.
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January 2010

[Intravitreal injection of Ganciclovir in the treatment of acute retinal necrosis].

Zhonghua Yan Ke Za Zhi 2007 Jul;43(7):631-7

Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Eye Research Center of Chinese Academy of Medical Sciences, Beijing 100730, China.

Objective: To evaluate the indication and clinical effects of intravitreal injection of Ganciclovir in the treatment of acute retinal necrosis (ARN).

Methods: Fourteen cases (14 eyes) of ARN which were consistent with the diagnostic criteria of American Uveitis Society were enrolled. Preoperative visual acuity was: light perception, hand movement and counting fingers (CF), each in 1 eye; 0.08 - 0.1 in 4 eyes; 0.2 - 0.4 in 5 eyes 0.5 in 1 eye and 0.8 in 1 eye. Keratic precipitate and aqueous flare were presented in the anterior segment. Peripheral focal and/or patch retinal necrosis, retinal occlusive arteritis and retinal hemorrhage were observed in the fundus. Acyclovir or Ganciclovir was administrated systematically by intravenous injection. The condition of 14 eyes deteriorated underwent intravitreal injection of Ganciclovir but without retinal detachment. After intravitreal injection 2 eyes became worse and underwent vitrectomy for PVR and retinal detachment. The follow-up time varied from 4 to 74 months (mean 25 months).

Results: The inflammation of anterior segment and vitreoretinopathy of 14 cases disappeared after intravitreal injection of Ganciclovir. The visual acuity markedly increased in 12 eyes without surgical intervention. Visual acuity achieved 1.0 - 1.5 in 5 eyes, 0.5 - 0.9 in 5 eyes and 0.3 in 2 eyes after intravitreal injection of Ganciclovir. The retina of the 2 eyes undergone vitrectomy was reattached and their visual acuity improved from CF to 0.4 and LP to CF, respectively.

Conclusions: In ARN patients whose conditions could not be controlled by systemic antivirus medicine treatment, early intravitreal injection of Ganciclovir can yield satisfactory therapeutic effects and better visual prognoses if applied before the occurrence of PVR or retinal detachment.
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July 2007