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1.  Primary gliosarcoma with long-survival: report of two cases and review of literature 
Background: Gliosarcoma (GS) is a rare high-grade malignant tumor with poor prognosis. The survival period of GS ranges from 4 to 18.5 months. Rarely would it be over 40 months. Survival of intraventricular GS is less than 8 months. Methods: There were 2 cases of primary gliosarcoma in our hospital with long-term survival after resection, with one of pure intraventricular origin. We confirmed that our diagnosis was correct by light microscopy, GFAP immunohistochemistry and histochemistry of reticular fiber staining. Results: In the first case, a 47-year-old man with intraventricular gliosarcoma survived for 130 months after surgery. In another case, a 63-year-old woman survived for 4 years after resection. Both cases of GS exhibited biphasic glioblastoma and fibrosarcoma with necrosis. According to the review of surgical records, complete tumor resections, including extended resections were carried out in both cases. The two patients received postoperative radiation therapy and chemotherapy without any further recurrence and metastasis. Conclusions: We reported two cases of GS with long survival. The presented cases demonstrate that, in rare instances, gliosarcoma may show prolonged survival with after surgical excision combined with radiotherapy and chemotherapy.
PMCID: PMC4203257  PMID: 25337286
Primary gliosarcoma; intraventricular gliosarcoma; long survival
2.  The Relationship between Extent of Thyroid Cancer Surgery and Use of Radioactive Iodine 
Annals of surgery  2013;258(2):354-358.
Objective
To determine the relationships between surgeon recommendations for extent of resection and radioactive iodine use in low-risk thyroid cancer.
Background
There has been an increase in thyroid cancer treatment intensity; the relationship between extent of resection and medical treatment with radioactive iodine remains unknown.
Methods
We randomly surveyed thyroid surgeons affiliated with 368 hospitals with Commission on Cancer accredited cancer programs. Survey responses were linked to the National Cancer Database. The relationship between extent of resection and the proportion of AJCC Stage I well-differentiated thyroid cancer patients treated with radioactive iodine after total thyroidectomy was assessed with multivariable weighted regression controlling for hospital and surgeon characteristics.
Results
The survey response rate was 70% (560/804). Surgeons who recommend total thyroidectomy over lobectomy for subcentimeter unifocal thyroid cancer were significantly more likely to recommend prophylactic central lymph node dissection for thyroid cancer regardless of tumor size (P<0.001). They were also more likely to favor radioactive iodine in patients with intrathyroidal unifocal cancer ≤ 1 cm (P=0.001), 1.1 – 2 cm (P=0.004), as well as intrathyroidal multifocal cancer ≤ 1 cm (P=0.004). In multivariable analysis, high hospital case volume, fewer surgeon years of experience, general surgery specialty, and preference for more extensive resection were independently associated with greater hospital-level use of radioactive iodine for Stage I disease.
Conclusion
In addition to surgeon experience and specialty, surgeons’ tendency to perform more extensive thyroid resection is associated with greater use of radioactive iodine for Stage I thyroid cancer.
doi:10.1097/SLA.0b013e31826c8915
PMCID: PMC3708979  PMID: 23567930
3.  Referral Patterns for Patients with High-Risk Thyroid Cancer 
Objective
Knowledge of referral patterns for specialty cancer care is sparse. Information on both need and reasons for referral of high-risk well-differentiated thyroid cancer patients should provide the foundation needed for eliminating obstacles to appropriate patient referrals and for improving patient care.
Methods
We surveyed 370 endocrinologists involved in thyroid cancer management. From information in a clinical vignette, respondents were asked to identify the reasons they would need to refer a high-risk patient to a more specialized facility for care. We performed multivariable analysis controlling for hospital and physician characteristics.
Results
Thirty-two percent of respondents reported never referring thyroid cancer patients to another facility. Of those that would refer a high-risk patient to another facility, the opportunity for a patient to enter a clinical trial was the most common reason reported (44%), followed by high dose radioactive iodine with or without dosimetry (33%), lateral neck dissection (24%) and external beam radiation (15%). In multivariable analysis, endocrinologists with a higher percentage of their practice devoted to thyroid cancer care were significantly less likely to refer patients to another facility (P=0.003).
Conclusion
The majority of endocrinologists treating thyroid cancer patients report referring a high-risk patient to another facility for some or all of their care. Knowledge of the patterns of physician referrals and the likelihood of need for referral are the foundation for understanding discrepancies in referral rates and obstacles in the referral process.
doi:10.4158/EP12288.OR
PMCID: PMC3747229  PMID: 23512381
thyroid cancer; referral; radioactive iodine; lateral neck dissection; clinical trial
4.  Tumor necrosis factor-α induces interleukin-34 expression through nuclear factor-κB activation in MC3T3-E1 osteoblastic cells 
Molecular Medicine Reports  2014;10(3):1371-1376.
Osteoblasts produce various types of cytokines under pathological conditions and control osteoclast differentiation. Tumor necrosis factor-α (TNF-α) has been demonstrated to exert complex effects in osteoblasts under local inflammatory conditions, including in periodontal and periapical diseases. Interleukin-34 (IL-34) has been recently identified as a novel regulatory factor for the differentiation and function of osteoclasts. The present study provides the first evidence, to the best of our knowledge, that the expression of IL-34 is induced by TNF-α through nuclear factor-κB (NF-κB) activation in MC3T3-E1 osteoblastic cells. TNF-α induced IL-34 expression in a dose- and time-dependent manner. Immunocytochemistry with an NF-κB antibody demonstrated that NF-κB was mainly localized in the cytoplasm of the untreated MC3T3-E1 cells. Rapid translocation of NF-κB from the cytoplasm to the nucleus was observed in the cells treated with TNF-α for 15 min. Translocation and transcriptional activity of NF-κB were also determined by western blotting and a luciferase reporter assay, respectively. Pretreatment with 100 μM CAPE, an inhibitor of NF-κB, significantly inhibited TNF-α-induced IL-34 expression. These results indicate that TNF-α induces IL-34 expression via NF-κB in osteoblasts.
doi:10.3892/mmr.2014.2353
PMCID: PMC4121411  PMID: 24970360
tumor necrosis factor-α; interleukin-34; nuclear factor-κB; osteoblast
5.  Cardiac troponin I is abnormally expressed in non-small cell lung cancer tissues and human cancer cells 
Cardiac troponin I (cTnI) is the only sarcomeric protein identified to date that is expressed exclusively in cardiac muscle. Its expression in cancer tissues has not been reported. Herein, we examined cTnI expression in non-small cell lung cancer (NSCLC) tissues, human adenocarcinoma cells SPCA-1 (lung) and BGC 823 (gastric) by immunohistochemistry, western blot analysis and real-time PCR. Immunopositivity for cTnI was demonstrated in 69.4% (34/49) NSCLC tissues evaluated, and was strong intensity in 35.3% (6/17) lung squamous cell carcinoma cases. The non-cancer-bearing lung tissues except tuberculosis (9/9, 100%) showed negative staining for cTnI. Seven monoclonal antibodies (mAbs) against human cTnI were applied in immunofluorescence. The result showed that the staining pattern within SPCA-1 and BGC 823 was dependent on the epitope of the cTnI mAbs. The membrane and nucleus of cancer cells were stained by mAbs against N-terminal peptides of cTnI, and cytoplasm was stained by mAbs against the middle and C-terminal peptides of cTnI. A ~25 kD band was identified by anti-cTnI mAb in SPCA-1 and BGC 823 extracts by western blot, as well as in cardiomyocyte extracts. The cTnI mRNA expressions in SPCA-1 and BGC 823 cells were about ten thousand times less than that in cardiomyocytes. Our study shows for the first time that cTnI protein and mRNA were abnormally expressed in NSCLC tissues, SPCA-1 and BGC 823 cells. These findings challenge the conventional view of cTnI as a cardiac-specific protein, enabling the potential use of cTnI as a diagnostic marker or targeted therapy for cancer.
PMCID: PMC4014212  PMID: 24817928
Cardiac troponin I; non-small cell lung cancer; human lung adenocarcinoma cell line SPCA-1; human gastric adenocarcinoma cell line BGC 823
6.  Surgeon Training and Use of Radioactive Iodine in Stage I Thyroid Cancer Patients 
Annals of surgical oncology  2012;20(3):733-738.
BACKGROUND
The majority of thyroid cancer diagnoses in the United States are Stage I well-differentiated cancer. The use of radioactive iodine (RAI) in these low-risk patients has increased over time. The role of surgeon training in decision making regarding treatment with RAI is unknown.
METHODS
Thyroid surgeons affiliated with 368 hospitals associated with the US National Cancer Database (NCDB) were surveyed. Survey data were linked to the NCDB data. A multivariable weighted analysis controlling for surgeon and hospital characteristics was conducted to examine the relationship between surgeon training, continuing education and hospital-level RAI use for Stage I well-differentiated thyroid cancer.
RESULTS
The response rate was 70% (560/804). In both univariate and multivariable analysis controlling for hospital case volume, practice setting and surgeon specialty, training with a thyroid surgeon was associated with less RAI use for Stage I thyroid cancer (P= 0.022 and 0.028 respectively). Attending one or more professional society meetings a year was associated with a lower rate of hospital-level RAI use in univariate analysis (P= 0.044) but not multivariable analysis.
CONCLUSIONS
Training with a surgeon or group of surgeons who focus on thyroid surgery was associated with a lower proportion of Stage I thyroid cancer patients receiving RAI post total thyroidectomy. This study emphasizes the importance of surgeon training in hospital practice patterns.
doi:10.1245/s10434-012-2745-0
PMCID: PMC3667416  PMID: 23224826
7.  Diagnostic and prognostic value of minor elevated cardiac troponin levels for percutaneous coronary intervention-related myocardial injury: a prospective, single-center and double-blind study 
Journal of Biomedical Research  2014;28(2):98-107.
Abstract
Cardiac troponin-I (cTnI) and -T (cTnT) are sensitive and specific markers of myocardial injury. However, the role of increased cTnI and cTnT in percutaneous coronary intervention (PCI)-related myocardial injury remains controversial. In this prospective, single-center and double-blind study, we aimed to determine the diagnostic and prognostic value of cTnI as well as cTnT (cTns) in PCI-related myocardial injury in a Chinese population. A total of 1,008 patients with stable angina pectoris and non-ST-segment elevation acute coronary syndrome were recruited. The levels of cTnI and cTnT were examined before and after PCI. All patients were followed up for 26±9 months to observe the incidence of major adverse cardiac events (MACEs). Our results showed that post-PCI cTnI and/or cTnT levels were increased to more than the 99th percentile upper reference limit (URL) in 133 (13.2%) patients, among which 22 (2.2%) were more than 5 × 99th percentile URL. By univariate analysis, an elevation in cTns after PCI was not an independent predictor of increased MACEs, HR 1.35 (P  =  0.33, 95%CI: 0.74–2.46). In conclusion, our data demonstrate that the incidence of PCI-related myocardial injury is not common in a Chinese population and minor elevated cTns levels may not be a sensitive prognostic marker for MACEs.
doi:10.7555/JBR.28.20130124
PMCID: PMC3968280  PMID: 24683407
percutaneous coronary intervention (PCI); troponins; PCI-related myocardial injury; major adverse cardiac events; diagnosis; prognosis
8.  Impaired dopamine D1 receptor-mediated vasorelaxation of mesenteric arteries in obese Zucker rats 
Background
Obesity plays an important role in the pathogenesis of hypertension. Renal dopamine D1-like receptor-mediated diuresis and natriuresis are impaired in the obese Zucker rat, an obesity-related hypertensive rat model. The role of arterial D1 receptors in the hypertension of obese Zucker rats is not clear.
Methods
Plasma glucose and insulin concentrations and blood pressure were measured. The vasodilatory response of isolated mesenteric arteries was evaluated using a small vessel myograph. The expression and phosphorylation of D1 receptors were quantified by co-immunoprecipitation and immunoblotting To determine the effect of hyperinsulinemia and hyperglycemia on the function of the arterial D1 receptor, we studied obese Zucker rats (six to eight-weeks old) fed (6 weeks) vehicle or rosiglitazone, an insulin sensitizer (10 mg/kg per day) and lean Zucker rats (eight to ten-weeks old), fed high-fat diet to induce hyperinsulinemia or injected intraperitoneally with streptomycin (STZ) to induce hyperglycemia.
Results
In obese Zucker rats, the vasorelaxant effect of D1-like receptors was impaired that could be ascribed to decreased arterial D1 receptor expression and increased D1 receptor phosphorylation. In these obese rats, rosiglitazone normalized the arterial D1 receptor expression and phosphorylation and improved the D1-like receptor-mediated vasorelaxation. We also found that D1 receptor-dependent vasorelaxation was decreased in lean Zucker rats with hyperinsulinemia or hyperglycemia but the D1 receptor dysfunction was greater in the former than in the latter group. The ability of insulin and glucose to decrease D1 receptor expression and increase its phosphorylation were confirmed in studies of rat aortic smooth muscle cells.
Conclusions
Both hyperinsulinemia and hyperglycemia caused D1 receptor dysfunction by decreasing arterial D1 receptor expression and increasing D1 receptor phosphorylation. Impaired D1 receptor-mediated vasorelaxation is involved in the pathogenesis of obesity-related hypertension.
doi:10.1186/1475-2840-13-50
PMCID: PMC3938077  PMID: 24559270
Dopamine D1 receptor; Vasorelaxation; Hyperinsulinemia; Hyperglycemia; Obesity-related hypertension; Obese Zucker rats
9.  Factors That Influence Radioactive Iodine Use for Thyroid Cancer 
Thyroid  2013;23(2):219-224.
Background
There is variation in the use of radioactive iodine (RAI) as treatment for well-differentiated thyroid cancer. The factors involved in physician decision-making for RAI remain unknown.
Methods
We surveyed physicians involved in postsurgical management of patients with thyroid cancer from 251 hospitals. Respondents were asked to rate the factors important in influencing whether a thyroid cancer patient receives RAI. Multivariable analyses controlling for physician age, gender, specialty, case volume, and whether they personally administer RAI, were performed to determine correlates of importance placed on patients' and physicians' worry about death from cancer and differences between low– versus higher–case-volume physicians.
Results
The survey response rate was 63% (534/853). Extent of disease, adequacy of surgical resection, patients' willingness to receive RAI, and patients' age were the factors physicians were most likely to report as quite or very important in influencing recommendations for RAI to patients with thyroid cancer. Interestingly, both physicians' and patients' worry about death from thyroid cancer were also important in determining RAI use. Physicians with less thyroid cancer cases per year were more likely than higher-volume physicians to report patients' (p<0.001) and physicians' worry about death (p=0.016) as quite or very important in decision-making. Other factors more likely to be of greater importance in determining RAI use for physicians with lower thyroid cancer patient volume versus higher include the accepted standard at the affiliated hospital (p=0.020), beliefs about RAI expressed by colleagues comanaging patients (p=0.003), and patient distance from the nearest facility administering RAI (p=0.012).
Conclusion
In addition to the extent of disease and adequacy of surgical resection, physicians place importance on physician and patient worry about death from thyroid cancer when deciding whether to treat a patient with RAI. The factors important to physician decision-making differ based on physician thyroid-cancer case-volume, with worry about death being more influential for low–case-volume physicians. As the mortality from thyroid cancer is low, the importance placed on death in decision making may be unwarranted.
doi:10.1089/thy.2012.0380
PMCID: PMC3569922  PMID: 23134514
10.  Phosphorylation and Recruitment of BAF60c in Chromatin Remodeling for Lipogenesis in Response to Insulin 
Molecular cell  2012;49(2):283-297.
SUMMARY
Fatty acid and triglyceride synthesis is induced in response to feeding and insulin. This lipogenic induction involves coordinate transcriptional activation of lipogenic enzymes, including fatty acid synthase and glycerol-3-phosphate acyltransferase. We recently reported the importance of USF-1 phosphorylation and subsequent acetylation in insulin-induced lipogenic gene activation. Here, we show that Brg1/Brm-associated factor (BAF) 60c is a specific chromatin remodeling component for lipogenic gene transcription in liver. In response to insulin, BAF60c is phosphorylated at S247 by atypical PKCζ/λ, which causes translocation of BAF60c to the nucleus and allows a direct interaction of BAF60c with USF-1 that is phosphorylated by DNA-PK and acetylated by P/CAF. Thus, BAF60c is recruited to form the lipoBAF complex to remodel chromatin structure and to activate lipogenic genes. Consequently, BAF60c promotes lipogenesis in vivo and increases triglyceride levels, demonstrating its role in metabolic adaption to activate the lipogenic program in response to feeding and insulin.
doi:10.1016/j.molcel.2012.10.028
PMCID: PMC3786575  PMID: 23219531
11.  The Role of Clinicians in Determining Radioactive Iodine Use for Low-Risk Thyroid Cancer 
Cancer  2012;119(2):259-265.
Background
Controversy exists over the optimal management of thyroid cancer. The proportion of patients with low-risk thyroid cancer treated with radioactive iodine (RAI) increased over the last 20 years and little is known about the role of clinicians in hospital-level RAI use for low-risk disease.
Methods
Thyroid surgeons affiliated with 368 hospitals with Commission on Cancer-accredited cancer programs were surveyed. Survey data were linked to data reported to the National Cancer Database (NCDB). A multivariable analysis was used to assess the relationship between the clinician decision maker and hospital-level RAI use after total thyroidectomy in Stage I well-differentiated thyroid cancer.
Results
The survey response rate was 70% (560/804). The surgeon was identified as the primary decision maker by 16% of the surgeons, endocrinologist by 69%, and nuclear medicine, radiologist, or other physician by 15%. In a multivariable analysis controlling for hospital case volume and hospital type, when the primary decision maker was in a specialty other than endocrinology or surgery, there was greater use of RAI at the hospital (P<0.001). A greater number of providers at the hospital administering RAI and access to a tumor board were also associated with increased use of RAI (P<0.001, P=0.006).
Conclusion
The specialty of the primary decision maker, number of providers administering RAI, and access to a tumor board are significantly associated with use of RAI for Stage I thyroid cancer. The findings have implications for addressing non-clinical variation between hospitals, with the marked heterogeneity in decision-making suggesting standardization of care will be challenging.
doi:10.1002/cncr.27721
PMCID: PMC3465617  PMID: 22744940
thyroid cancer; radioactive iodine; physician; decision making
12.  Correction: Spectrums of Opportunistic Infections and Malignancies in HIV-Infected Patients in Tertiary Care Hospital, China 
PLoS ONE  2014;9(1):10.1371/annotation/bbbcd86d-200e-49d6-a3e3-aef3e083fab2.
doi:10.1371/annotation/bbbcd86d-200e-49d6-a3e3-aef3e083fab2
PMCID: PMC3880926
13.  Spectrums of Opportunistic Infections and Malignancies in HIV-Infected Patients in Tertiary Care Hospital, China 
PLoS ONE  2013;8(10):e75915.
Background
HIV-related opportunistic infections (OIs) and malignancies continued to cause morbidity and mortality in Chinese HIV-infected individuals. The objective for this study is to elucidate the prevalence and spectrums of OIs and malignancies in HIV-infected patients in the Beijing Ditan Hospital.
Methods
The evaluation of the prevalence and spectrums of OIs and malignancies was conducted by using the clinical data of 834 HIV-infected patients admitted in the Beijing Ditan hospital from January 1, 2009, to November 30, 2012.
Results
The prevalence and spectrums of OIs and malignancies varied contingent on geographic region, transmission routes, and CD4 levels. We found that tuberculosis was most common OI and prevalence was 32.5%, followed by candidiasis(29.3%), Pneumocystis pneumonia(PCP)(22.4%), cytomegalovirus(CMV) infection(21.7%), other fungal infections(16.2%), mycobacterium avium complex(MAC)(11.3%), cryptococcosis(8.0%), progressive multifocal leukoencephalopathy(PML)(4.4%), Cerebral Toxoplasmosis(3.5%) and Penicillium marneffei infection(1.4%); while Lymphoma(2.9%), Kaposi’s sarcoma(0.8%) and cervix carcinoma(0.3%) were emerged as common AIDS-defining malignancies. Pulmonary OI infections were the most prevalent morbidity and mortality in patients in the AIDS stage including pulmonary tuberculosis (26.6%) and PCP (22.4%). CMV infection(21.7%) was most common viral infection; Fungal OIs were one of most prevalent morbidity in patients in the AIDS stage, including oral candidiasis (29.3%), other fungal infection (16.2%), Cryptococcosis (8.0%) and Penicillium marneffei infection (1.4%). We found the low prevalence of AIDS-defining illnesses in central neural system in this study, including progressive multifocal leukoencephalopathy (4.4%), cerebral toxoplasmosis (3.5%), tuberculosis meningitis (3.2%), cryptococcal meningitis (2.4%) and CMV encephalitis (1.1%). In-hospital mortality rate was 4.3 per 100 person-years due to severe OIs, malignancies, and medical cost constraints.
Conclusions
The prevalence and spectrums of OIs, malignancies and co-infections were discussed in this study. It would help increase the awareness for physicians to make a diagnosis and empirical treatment sooner and plan good management strategies, especially in resource limited regions.
doi:10.1371/journal.pone.0075915
PMCID: PMC3808390  PMID: 24204583
14.  Liver steatosis in Chinese HIV-infected patients with hypertriglyceridemia: characteristics and independent risk factors 
Virology Journal  2013;10:261.
Background
Since Highly Active Antiretroviral Therapy (HAART) medications were made available in 2002, multiple serious side effects have been observed. However, no study has yet systematically evaluated the prevalence of liver steatosis, a very serious but treatable side effect.
Objectives
This study examined the prevalence of and independent risk factors for liver steatosis in Chinese HIV-infected, HAART-experienced patients who had been diagnosed with hypertriglyceridemia.
Methods
In this cross-sectional observational study, the prevalence of liver steatosis was determined by ultrasound imaging that detected diffusion in hepatic echogenicity. The risk factors associated with steatosis were evaluated with a proportional odds logistic regression model.
Results
Among 163 HIV-infected patients with hypertriglyceridemia and past HAART experience, 75(46%) patients were determined to have liver steatosis. In multivariable logistic regression model, the risk factors associated with liver steatosis were: higher triglyceride level (OR = 1.086, P = 0.026), metabolic syndromes (OR = 2.092, P = 0.024) and exposure to nucleoside reverse transcriptase inhibitor (NRTIs) ((OR = 2.11, P = 0.001) and Stavudine (OR = 3.75, P = 0.01)). Exposure to Nevirapine (OR = 0 .41, P = 0.003) was a favorable factor for lipid metabolism in vivo and was a protective factors for liver steatosis.
Conclusions
Chinese HIV-infected patients with hypertriglyceridemia appear to be prone to liver steatosis, especially those on NRTIs. Routine screening should be considered on their lipid panels.
doi:10.1186/1743-422X-10-261
PMCID: PMC3765514  PMID: 23941464
HIV; HAART; Liver steatosis; Hypertriglyceridemia
15.  The cytotoxicity evaluation of magnetic iron oxide nanoparticles on human aortic endothelial cells 
Nanoscale Research Letters  2013;8(1):215.
One major obstacle for successful application of nanoparticles in medicine is its potential nanotoxicity on the environment and human health. In this study, we evaluated the cytotoxicity effect of dimercaptosuccinic acid-coated iron oxide (DMSA-Fe2O3) using cultured human aortic endothelial cells (HAECs). Our results showed that DMSA-Fe2O3 in the culture medium could be absorbed into HAECs, and dispersed in the cytoplasm. The cytotoxicity effect of DMSA-Fe2O3 on HAECs was dose-dependent, and the concentrations no more than 0.02 mg/ml had little toxic effect which were revealed by tetrazolium dye assay. Meanwhile, the cell injury biomarker, lactate dehydrogenase, was not significantly higher than that from control cells (without DMSA-Fe2O3). However, the endocrine function for endothelin-1 and prostacyclin I-2, as well as the urea transporter function, was altered even without obvious evidence of cell injury in this context. We also showed by real-time PCR analysis that DMSA-Fe2O3 exposure resulted in differential effects on the expressions of pro- and anti-apoptosis genes of HAECs. Meanwhile, it was noted that DMSA-Fe2O3 exposure could activate the expression of genes related to oxidative stress and adhesion molecules, which suggested that inflammatory response might be evoked. Moreover, we demonstrated by in vitro endothelial tube formation that even a small amount of DMSA-Fe2O3 (0.01 and 0.02 mg/ml) could inhibit angiogenesis by the HAECs. Altogether, these results indicate that DMSA-Fe2O3 have some cytotoxicity that may cause side effects on normal endothelial cells.
doi:10.1186/1556-276X-8-215
PMCID: PMC3651330  PMID: 23647620
Magnetic nanoparticles; Iron oxide; Endothelial cells; Cell viability; Angiogenesis
16.  Inhibition of BDNF in Multiple Myeloma Blocks Osteoclastogenesis via Down-Regulated Stroma-Derived RANKL Expression Both In Vitro and In Vivo 
PLoS ONE  2012;7(10):e46287.
Brain-derived neurotrophic factor (BDNF) was recently identified as a factor produced by multiple myeloma (MM) cells, which may contribute to bone resorption and disease progression in MM, though the molecular mechanism of this process is not well understood. The purpose of this study was to test the effect of BDNF on bone disease and growth of MM cells both in vitro and in vivo. Co- and triple-culture systems were implemented. The in vitro results demonstrate that BDNF augmented receptor activator of nuclear factor kappa B ligand (RANKL) expression in human bone marrow stromal cells, thus contributing to osteoclast formation. To further clarify the effect of BDNF on myeloma bone disease in vivo, ARH-77 cells were stably transfected with an antisense construct to BDNF (AS-ARH) or empty vector (EV-ARH) to test their capacity to induce MM bone disease in SCID–rab mice. Mice treated with AS-ARH cells were preserved, exhibited no radiologically identifiable lytic lesions and, unlike the controls treated with EV-ARH cells, lived longer and showed reduced tumor burden. Consistently, bones harboring AS-ARH cells showed marked reductions of RANKL expression and osteoclast density compared to the controls harboring EV-ARH cells. These results provide further support for the potential osteoclastogenic effects of BDNF, which may mediate stromal–MM cell interactions to upregulate RANKL secretion, in myeloma bone diseases.
doi:10.1371/journal.pone.0046287
PMCID: PMC3471864  PMID: 23077504
17.  Clinical Analysis of 10 AIDS Patients with Malignant Lymphoma 
Cancer Biology & Medicine  2012;9(2):115-119.
Objective
This work summarizes the clinical features and treatment of 10 AIDS patients with malignant lymphoma.
Methods
A total of 10 AIDS patients with malignant lymphoma seen in Beijing Ditan Hospital since 2009 were enrolled. Clinical manifestations, pathological examinations, immunity levels, Epstein-Barr virus antibody examinations, complications, treatments, and outcomes were retrospectively analyzed.
Results
The main clinical manifestations of these patients included intermittent fever in 2 cases, neck masses and fever in 3 cases, auxiliary lymph node enlargement in 2 cases, and abdominal pain and bloating with fever in 3 cases. Up to 7 patients were pathologically diagnosed with diffuse large B cell lymphoma (DLBCL), and 3 patients were pathologically diagnosed with Burkitt’s lymphoma. Up to 8 patients had CD4 cell counts below 200/µL, and 2 patients had a level of more than 200/µL. Up to 7 patients were negative for EBV-IgM antibodies and 3 patients were not examined. Six patients underwent different chemotherapy and their prognoses were different. One patient with Burkitt’s lymphoma alternatively took CODOXM and IVAC for 3 turns after VP chemotherapy; 1 patient with liver metastasis took R-CHOP 5 times, then changed therapy regimen to R-MINE and MINE. One patient with adrenal DLBCL took CHOP 6 times. Three patients with DLBCL took CHOP 1 or 2 times. Four patients gave up treatment. Various infections and side effects occurred, including bone marrow suppression, gastrointestinal bleeding, and renal dysfunction during chemotherapy. Six patients took HAART, and 4 did not. Six patients died, whereas 3 patients got improved; and 1 patient was discharged.
Conclusions
AIDS patients with malignant lymphoma had various clinical manifestations, were immunocompromised, and had multiple metastases when they were admitted; they were already in the interim or late stage of lymphoma. Chemotherapy was not effective, and additional complications occurred. HAART failed to improve patient prognosis, and the overall prognosis was poor.
doi:10.3969/j.issn.2095-3941.2012.02.006
PMCID: PMC3643651  PMID: 23691465
acquired immunodeficiency syndrome (AIDS); malignant lymphoma; chemotherapy; HAART; prognosis
18.  Lycium barbarum Extracts Protect the Brain from Blood-Brain Barrier Disruption and Cerebral Edema in Experimental Stroke 
PLoS ONE  2012;7(3):e33596.
Background and Purpose
Ischemic stroke is a destructive cerebrovascular disease and a leading cause of death. Yet, no ideal neuroprotective agents are available, leaving prevention an attractive alternative. The extracts from the fruits of Lycium barbarum (LBP), a Chinese anti-aging medicine and food supplement, showed neuroprotective function in the retina when given prophylactically. We aim to evaluate the protective effects of LBP pre-treatment in an experimental stroke model.
Methods
C57BL/6N male mice were first fed with either vehicle (PBS) or LBP (1 or 10 mg/kg) daily for 7 days. Mice were then subjected to 2-hour transient middle cerebral artery occlusion (MCAO) by the intraluminal method followed by 22-hour reperfusion upon filament removal. Mice were evaluated for neurological deficits just before sacrifice. Brains were harvested for infarct size estimation, water content measurement, immunohistochemical analysis, and Western blot experiments. Evans blue (EB) extravasation was determined to assess blood-brain barrier (BBB) disruption after MCAO.
Results
LBP pre-treatment significantly improved neurological deficits as well as decreased infarct size, hemispheric swelling, and water content. Fewer apoptotic cells were identified in LBP-treated brains by TUNEL assay. Reduced EB extravasation, fewer IgG-leaky vessels, and up-regulation of occludin expression were also observed in LBP-treated brains. Moreover, immunoreactivity for aquaporin-4 and glial fibrillary acidic protein were significantly decreased in LBP-treated brains.
Conclusions
Seven-day oral LBP pre-treatment effectively improved neurological deficits, decreased infarct size and cerebral edema as well as protected the brain from BBB disruption, aquaporin-4 up-regulation, and glial activation. The present study suggests that LBP may be used as a prophylactic neuroprotectant in patients at high risk for ischemic stroke.
doi:10.1371/journal.pone.0033596
PMCID: PMC3306421  PMID: 22438957
19.  Global Mapping of H3K4me1 and H3K4me3 Reveals the Chromatin State-Based Cell Type-Specific Gene Regulation in Human Treg Cells 
PLoS ONE  2011;6(11):e27770.
Regulatory T cells (Treg) contribute to the crucial immunological processes of self-tolerance and immune homeostasis. Genomic mechanisms that regulate cell fate decisions leading to Treg or conventional T cells (Tconv) lineages and those underlying Treg function remain to be fully elucidated, especially at the histone modification level. We generated high-resolution genome-wide distribution maps of monomethylated histone H3 lysine 4 (H3K4me1) and trimethylated H3K4 (H3K4me3) in human CD4+CD25+FOXP3+ Tregs and CD4+CD25+FOXP3− activated (a)Tconv cells by DNA sequencing-by-synthesis. 2115 H3K4me3 regions corresponded to proximal promoters; in Tregs, the genes associated with these regions included the master regulator FOXP3 and the chemokine (C-C motif) receptor 7 (CCR7). 41024 Treg-specific H3K4me1 regions were identified. The majority of the H3K4me1 regions differing between Treg and aTconv cells were located at promoter-distal sites, and in vitro reporter gene assays were used to evaluate and identify novel enhancer activity. We provide for the first time a comprehensive genome-wide dataset of lineage-specific H3K4me1 and H3K4me3 patterns in Treg and aTconv cells, which may control cell type-specific gene regulation. This basic principle is likely not restricted to the two closely-related T cell populations, but may apply generally to somatic cell lineages in adult organisms.
doi:10.1371/journal.pone.0027770
PMCID: PMC3223197  PMID: 22132139
20.  Efficacy of Leuprolide Acetate 1-Month Depot for Central Precocious Puberty (CPP): Growth Outcomes During a Prospective, Longitudinal Study 
Introduction
Gonadotropin-releasing hormone analogs (GnRHa) are the treatment of choice for CPP. We investigated growth in GnRHa-naïve subjects, treated with leuprolide acetate 1-month depot for CPP.
Methods
This prospective, open-label study had a long-term, observational, follow-up period. Forty-nine females and 6 males were enrolled. Leuprolide acetate depot was administered intramuscularly every 28 days. Height and growth rate during and after treatment until adulthood were measured.
Results
Among 30 of 49 females having an adult height (AH) measurement, 29 had target heights available (mean = 163.8 cm) and 27 had pretreatment predicted adult heights (PAHs; mean = 157.4 cm). After treatment, the mean AH at mean age 21.8 years [range 13.7-26.7 years] was 162.5 cm, a mean height gain over baseline PAH of 4.0 cm. The mean height standard deviation score was -0.1 at AH.
Conclusions
Treatment of CPP with leuprolide acetate 1-month depot had beneficial effects on growth rate and preservation of AH.
Trial Registration
ClinicalTrials.gov: NCT00660010
doi:10.1186/1687-9856-2011-7
PMCID: PMC3159140  PMID: 21860633
21.  Leuprolide Acetate 1-Month Depot for Central Precocious Puberty: Hormonal Suppression and Recovery 
Methods. This prospective US multicenter trial of leuprolide acetate 1-month depot (7.5–15 mg) for central precocious puberty utilized an open-label treatment period, long-term follow-up, and adult callback. Forty-nine females <9 years old with Tanner breast stage ≥2 before 8 years and 6 males <10 years old with Tanner genital stage ≥2 before 9 years with stimulated LH ≥10 IU/L and bone age advance ≥1 year were enrolled. Results. Subjects were treated for 3.9 ± 2.0 years. Mean peak GnRH-stimulated LH and FSH were prepubertal after the first dose and remained suppressed throughout treatment. During treatment, mean estradiol decreased to the limit of detection and mean testosterone decreased but remained above prepubertal norms. During posttreatment follow-up (3.5 ± 2.2 years), all patients achieved a pubertal hormonal response within 1 year and menses were reported in all females ≥12 years old. No impairment of reproductive function was observed at adulthood (mean age: 24.8 years).
doi:10.1155/2010/398639
PMCID: PMC3062984  PMID: 21437000
22.  Lycium Barbarum Polysaccharides Reduce Neuronal Damage, Blood-Retinal Barrier Disruption and Oxidative Stress in Retinal Ischemia/Reperfusion Injury 
PLoS ONE  2011;6(1):e16380.
Neuronal cell death, glial cell activation, retinal swelling and oxidative injury are complications in retinal ischemia/reperfusion (I/R) injuries. Lycium barbarum polysaccharides (LBP), extracts from the wolfberries, are good for “eye health” according to Chinese medicine. The aim of our present study is to explore the use of LBP in retinal I/R injury. Retinal I/R injury was induced by surgical occlusion of the internal carotid artery. Prior to induction of ischemia, mice were treated orally with either vehicle (PBS) or LBP (1 mg/kg) once a day for 1 week. Paraffin-embedded retinal sections were prepared. Viable cells were counted; apoptosis was assessed using TUNEL assay. Expression levels of glial fibrillary acidic protein (GFAP), aquaporin-4 (AQP4), poly(ADP-ribose) (PAR) and nitrotyrosine (NT) were investigated by immunohistochemistry. The integrity of blood-retinal barrier (BRB) was examined by IgG extravasations. Apoptosis and decreased viable cell count were found in the ganglion cell layer (GCL) and the inner nuclear layer (INL) of the vehicle-treated I/R retina. Additionally, increased retinal thickness, GFAP activation, AQP4 up-regulation, IgG extravasations and PAR expression levels were observed in the vehicle-treated I/R retina. Many of these changes were diminished or abolished in the LBP-treated I/R retina. Pre-treatment with LBP for 1 week effectively protected the retina from neuronal death, apoptosis, glial cell activation, aquaporin water channel up-regulation, disruption of BRB and oxidative stress. The present study suggests that LBP may have a neuroprotective role to play in ocular diseases for which I/R is a feature.
doi:10.1371/journal.pone.0016380
PMCID: PMC3027646  PMID: 21298100
23.  The Effect of Iron Oxide Magnetic Nanoparticles on Smooth Muscle Cells 
Nanoscale Research Letters  2008;4(1):70-77.
Recently, magnetic nanoparticles of iron oxide (Fe3O4, γ-Fe2O3) have shown an increasing number of applications in the field of biomedicine, but some questions have been raised about the potential impact of these nanoparticles on the environment and human health. In this work, the three types of magnetic nanoparticles (DMSA-Fe2O3, APTS-Fe2O3, and GLU-Fe2O3) with the same crystal structure, magnetic properties, and size distribution was designed, prepared, and characterized by transmission electronic microscopy, powder X-ray diffraction, zeta potential analyzer, vibrating sample magnetometer, and Fourier transform Infrared spectroscopy. Then, we have investigated the effect of the three types of magnetic nanoparticles (DMSA-Fe2O3, APTS-Fe2O3, and GLU-Fe2O3) on smooth muscle cells (SMCs). Cellular uptake of nanoparticles by SMC displays the dose, the incubation time and surface property dependent patterns. Through the thin section TEM images, we observe that DMSA-Fe2O3 is incorporated into the lysosome of SMCs. The magnetic nanoparticles have no inflammation impact, but decrease the viability of SMCs. The other questions about metabolism and other impacts will be the next subject of further studies.
doi:10.1007/s11671-008-9204-7
PMCID: PMC2894190
Magnetic nanoparticles; Iron oxide; Smooth muscle cells; Cellular uptake; Viability
24.  The Effect of Iron Oxide Magnetic Nanoparticles on Smooth Muscle Cells 
Nanoscale Research Letters  2008;4(1):70-77.
Recently, magnetic nanoparticles of iron oxide (Fe3O4, γ-Fe2O3) have shown an increasing number of applications in the field of biomedicine, but some questions have been raised about the potential impact of these nanoparticles on the environment and human health. In this work, the three types of magnetic nanoparticles (DMSA-Fe2O3, APTS-Fe2O3, and GLU-Fe2O3) with the same crystal structure, magnetic properties, and size distribution was designed, prepared, and characterized by transmission electronic microscopy, powder X-ray diffraction, zeta potential analyzer, vibrating sample magnetometer, and Fourier transform Infrared spectroscopy. Then, we have investigated the effect of the three types of magnetic nanoparticles (DMSA-Fe2O3, APTS-Fe2O3, and GLU-Fe2O3) on smooth muscle cells (SMCs). Cellular uptake of nanoparticles by SMC displays the dose, the incubation time and surface property dependent patterns. Through the thin section TEM images, we observe that DMSA-Fe2O3is incorporated into the lysosome of SMCs. The magnetic nanoparticles have no inflammation impact, but decrease the viability of SMCs. The other questions about metabolism and other impacts will be the next subject of further studies.
doi:10.1007/s11671-008-9204-7
PMCID: PMC2894190
Magnetic nanoparticles; Iron oxide; Smooth muscle cells; Cellular uptake; Viability
25.  How to Improve the Efficacy of Endoscopic Ultrasound-guided Celiac Plexus Neurolysis in Pain Management in Patients With Pancreatic Cancer: Analysis in a Single Center 
Visceral pain secondary to pancreatic cancer is often difficult to control and poses a challenge to the physician. We retrospectively analyzed the efficacy and safety of endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) in patients with unresectable pancreatic cancer. Forty-one patients with severe pain despite treatment with opioids underwent EUS-CPN with absolute alcohol. Patients scored their pain on a scale of 0 to 10 and were interviewed after the procedure. Of the 41 patients, 33, 37, and 25 patients reported improvement in their pain within 3 days, at 1 week, and at 3 months, respectively, following the procedure. Of all the patients, 19 patients reported substantial improvement and 4 patients showed complete disappearance of pain. Complication appeared in 2 patients with transient hypotension. In our study, EUS-CPN is a safe and effective form of treatment for intractable pain secondary to advanced pancreatic cancer.
doi:10.1097/SLE.0000000000000032
PMCID: PMC4196780  PMID: 24487155
EUS-CPN; pancreatic cancer; pain control

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