Multiple myeloma identified within the same site of the mandible with medication-related osteonecrosis of jaw: An unusual case report.

RATIONALE: Multiple myeloma (MM) is a malignant disease characterized by abnormal proliferation of plasma cells, which usually occurs in middle-aged and elderly male patients. Bisphosphonates (BP) are commonly used for the treatment of MM bone disease. Long-time use of BP may cause medication-related osteonecrosis of the jaw (MRONJ). MRONJ occurs in jaw exclusively, and Multiple myeloma can also invade the jaw. The 2 diseases have similar clinical manifestations and imaging findings. This report present a case of MM identified in surgical specimen at the site that had been previously pathologically diagnosed as MRONJ in a patient with MM. PATIENT CONCERNS: A 57-years-old male patient visited our clinic on October 16, 2020 because of gingival swelling and pain in the right mandible for 1 month after extraction of the lower right premolar. The patient had a long-time illness history of multiple myeloma, and received intravenous zoledronic acid treatment. DIAGNOSES: Based on the clinical characteristics, imaging, and pathological findings of sequestrum formation and high inflammatory cell infiltration, the patient was diagnosed with MRONJ. After 1 year, a mandibular osteotomy was performed and pathological analysis showed the presence of necrotic bone and a large number of abnormal plasma cell infiltration, suggesting the presence of MM in the mandible. INTERVENTIONS: The patient was treated with a series of conservative treatments including antibiotic treatment, saline irrigation and laser irradiation, as well as superficial sequestration was. One year later, a mandibular osteotomy was performed. OUTCOMES: For the patient, the symptoms of gingival swelling, pain and discharge disappeared after surgery. LESSONS: These findings suggested MRONJ and MM could occur simultaneously at same site, so patients with MM presenting with symptoms of MRONJ should be screened for concurrent or disease relapse of multiple myeloma to prevent misdiagnosis or inadequate management. Meanwhile, this also suggests long-term inflammatory may lead to invasion of multiple myeloma.

SLC27A5 promotes sorafenib-induced ferroptosis in hepatocellular carcinoma by downregulating glutathione reductase.

Sorafenib, a first-line drug for advanced hepatocellular carcinoma (HCC), shows a favorable anti-tumor effect while resistance is a barrier impeding patients from benefiting from it. Thus, more efforts are needed to lift this restriction. Herein, we first find that solute carrier family 27 member 5 (SLC27A5/FATP5), an enzyme involved in the metabolism of fatty acid and bile acid, is downregulated in sorafenib-resistant HCC. SLC27A5 deficiency facilitates the resistance towards sorafenib in HCC cells, which is mediated by suppressing ferroptosis. Further mechanism studies reveal that the loss of SLC27A5 enhances the glutathione reductase (GSR) expression in a nuclear factor erythroid 2-related factor 2 (NRF2)-dependent manner, which maintains glutathione (GSH) homeostasis and renders insensitive to sorafenib-induced ferroptosis. Notably, SLC27A5 negatively correlates with GSR, and genetic or pharmacological inhibition of GSR strengthens the efficacy of sorafenib through GSH depletion and the accumulation of lipid peroxide products in SLC27A5-knockout and sorafenib-resistant HCC cells. Based on our results, the combination of sorafenib and carmustine (BCNU), a selective inhibitor of GSR, remarkably hamper tumor growth by enhancing ferroptotic cell death in vivo. In conclusion, we describe that SLC27A5 serves as a suppressor in sorafenib resistance and promotes sorafenib-triggered ferroptosis via restraining the NRF2/GSR pathway in HCC, providing a potential therapeutic strategy for overcoming sorafenib resistance.

Immunoglobulin G4-related disease: case report and literature review.

Immunoglobulin (Ig) G4-related disease (IgG4-RD) is a rare and chronic progressive clinical entity, characterized by elevated serum IgG4 along with tissue infiltration by IgG4 + plasma cells. It is an immune-mediated fibro-inflammatory condition that can affect virtually any organ and tissue. IgG4-related lung disease (IgG4-RLD) occupies 14% of all IgG4-RD, with nonspecific symptoms and various abnormal radiographic patterns. Published data on IgG4-related hypertrophic pachymeningitis (IgG4-RHP), an increasingly recognized central nervous system manifestation of IgG4-RD, is also limited. Both lung and cranial dura involvement have not yet been reported until now. We further entail a review of the literature on the clinicopathologic features and differential diagnosis of this uncommon disease. We herein report an interesting case of a 70-year-old male patient admitted due to headache and fever. A magnetic resonance imaging (MRI) of the brain revealed extensive dural thickening with marked enhancement. Chest computed tomography (CT) scan showed nodular or mass-like consolidation and focal interstitial change. Thoracoscopic lung biopsy and lumbar puncture were conducted. After careful histopathological observation and consideration of alternative differential diagnoses, he was diagnosed with IgG4-related disease with lung and cranial dural involvement based upon significant elevation of serum and cerebrospinal fluid (CSF) IgG4 concentration. The patient was started on oral prednisolone 60 mg/day (1.0 mg/kg/day) for 14 days, and a tapering dose of 5 mg every 2 weeks followed by maintenance therapy at low dose for 3 months. His clinical manifestations, and serologic and imaging findings improved with steroid treatment. Currently, the patient remains well without disease progression. IgG4-RD should be considered as a differential when diagnosing other similar multisystemic lesions. Clinical examination, careful histological observation, and immunostaining for appropriate markers are essential in establishing the diagnosis. Clinicians should become familiar with this alternative differential diagnosis.

Management of Sonographically Suspicious Thyroid Nodules 1 cm or Smaller and Candidacy for Active Surveillance: Experience of a Tertiary Center in China.

OBJECTIVE: Our objective was to investigate the management of patients with asymptomatic suspicious thyroid nodules ≤1 cm. METHODS: We retrospectively reviewed medical records of patients with sonographically suspicious thyroid nodules ≤1 cm and without distant metastases, suspicious lymph node metastasis (LNM), or extrathyroidal extension (ETE). RESULTS: Of the 386 enrolled patients, 174 (45.1%) had immediate surgery (IS), while 212 (54.9%) underwent active surveillance (AS). In the IS group, 166 (95.4%) patients were confirmed as having papillary thyroid microcarcinoma. LNM and ETE were observed in 24.7% and 2.4% cases, respectively. In the AS group, nodule size increased by ≥3 mm in 11 (5.2%) patients and 39 (18.4%) had a >50% increase in nodule volume after a median follow-up of 12 months. Nodules with smaller volume at diagnosis were more likely to increase in volume later. Newly suspicious LNM was detected in 23 (10.8%) patients. Delayed surgery (DS) was performed in 101 patients, with 27 showing disease progression. ETE and LNM were detected in 3% and 36%, respectively, of patients with papillary thyroid microcarcinoma. Compared with IS, tumors in the DS group more frequently showed lateral LNM and capsular invasion (P < .05). No patient had recurrence or died of thyroid cancer during postoperative follow-up (median 26 [4-60] months). CONCLUSIONS: IS or DS of patients with asymptomatic suspicious thyroid nodules ≤1 cm was relatively high in China. The inertia of low-risk nodules and the effectiveness of DS for those that progressed make AS a feasible strategy.

Heparin versus 0.9% saline solution to maintain patency of totally implanted venous access ports in cancer patients: A systematic review and meta-analysis.

AIM: The use of heparin and 0.9% saline solution is always controversial for central venous catheters. However, there is no systematic review or guideline about whether saline solution can replace heparin solution in adult cancer patients with totally implantable venous access ports (TIVAPs). The purpose of this review is to evaluate whether saline solution can replace heparin saline to lock TIVAPs. METHODS: The following databases were searched: PubMed, the Cochrane Library, Web of Science, Embase, CINAHL and Ovid (January 1, 1982, and February 21, 2020). All statistical analyses of the meta-analysis were completed using the Review Manager 5.3. RESULTS: A total of 201 studies were identified from these databases after initial review, and four studies met inclusion criteria, including 2652 cases. There was little heterogeneity among the included studies (I2 < 30%), and all analyses were conducted by the fixed-effects model. The total complications, catheter occlusions, catheter-related bloodstream infections and other complication rates in the heparin solution group were higher than in the saline solution group. In the subgroup analysis of heparin concentration, total complication rates in the saline solution group were higher than with 50 U of heparin and lower than with 100 U of heparin. However, the differences in these complications were small, and no significant difference was observed (all P > 0.05). CONCLUSIONS: Based on existing clinical studies, we recommend that saline solution can replace 50 or 100 U/ml of heparin as a safe and effective flush solution for TIVAPs.

Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial.

BACKGROUND: This is the first randomised controlled trial for assessment of the immunogenicity and safety of a candidate non-replicating adenovirus type-5 (Ad5)-vectored COVID-19 vaccine, aiming to determine an appropriate dose of the candidate vaccine for an efficacy study. METHODS: This randomised, double-blind, placebo-controlled, phase 2 trial of the Ad5-vectored COVID-19 vaccine was done in a single centre in Wuhan, China. Healthy adults aged 18 years or older, who were HIV-negative and previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-free, were eligible to participate and were randomly assigned to receive the vaccine at a dose of 1 × 1011 viral particles per mL or 5 × 1010 viral particles per mL, or placebo. Investigators allocated participants at a ratio of 2:1:1 to receive a single injection intramuscularly in the arm. The randomisation list (block size 4) was generated by an independent statistician. Participants, investigators, and staff undertaking laboratory analyses were masked to group allocation. The primary endpoints for immunogenicity were the geometric mean titres (GMTs) of specific ELISA antibody responses to the receptor binding domain (RBD) and neutralising antibody responses at day 28. The primary endpoint for safety evaluation was the incidence of adverse reactions within 14 days. All recruited participants who received at least one dose were included in the primary and safety analyses. This study is registered with ClinicalTrials.gov, NCT04341389. FINDINGS: 603 volunteers were recruited and screened for eligibility between April 11 and 16, 2020. 508 eligible participants (50% male; mean age 39·7 years, SD 12·5) consented to participate in the trial and were randomly assigned to receive the vaccine (1 × 1011 viral particles n=253; 5 × 1010 viral particles n=129) or placebo (n=126). In the 1 × 1011 and 5 × 1010 viral particles dose groups, the RBD-specific ELISA antibodies peaked at 656·5 (95% CI 575·2-749·2) and 571·0 (467·6-697·3), with seroconversion rates at 96% (95% CI 93-98) and 97% (92-99), respectively, at day 28. Both doses of the vaccine induced significant neutralising antibody responses to live SARS-CoV-2, with GMTs of 19·5 (95% CI 16·8-22·7) and 18·3 (14·4-23·3) in participants receiving 1 × 1011 and 5 × 1010 viral particles, respectively. Specific interferon γ enzyme-linked immunospot assay responses post vaccination were observed in 227 (90%, 95% CI 85-93) of 253 and 113 (88%, 81-92) of 129 participants in the 1 × 1011 and 5 × 1010 viral particles dose groups, respectively. Solicited adverse reactions were reported by 183 (72%) of 253 and 96 (74%) of 129 participants in the 1 × 1011 and 5 × 1010 viral particles dose groups, respectively. Severe adverse reactions were reported by 24 (9%) participants in the 1 × 1011 viral particles dose group and one (1%) participant in the 5 × 1010 viral particles dose group. No serious adverse reactions were documented. INTERPRETATION: The Ad5-vectored COVID-19 vaccine at 5 × 1010 viral particles is safe, and induced significant immune responses in the majority of recipients after a single immunisation. FUNDING: National Key R&D Programme of China, National Science and Technology Major Project, and CanSino Biologics.

CD5+MYC+ predicts worse prognosis in diffuse large B-cell lymphoma.

The dual expression of CD5 and MYC protein (DECM) on B-lymphocytes may arise at a specific stage of de novo diffuse large B-cell lymphoma (DLBCL). This study retrospectively reviewed 210 patients with de novo DLBCL at the Affiliated Hospital of Jiangnan University between 2006 and 2017. DECM was significantly correlated with a worse prognosis than that in either the CD5+ or MYC+ or CD5-MYC- patients. Furthermore, patients with DECM showed a similar outcome to MYC+BCL2+ lymphoma patients who have extremely poor survival rates. Multivariate analysis demonstrated that DECM was a significant independent predictor for overall survival (P < .0001) and progression-free survival (P < .0001) in DLBCL. DLBCL patients with DECM showed significantly inferior clinical outcomes compared to the CD5+, MYC+ or CD5-MYC- patients. Combinational therapeutic modalities might be a candidate approach to improve the prognosis of these patients.

Prevalence of hypertension, diabetes, and dyslipidemia, and their additive effects on myocardial infarction and stroke: a cross-sectional study in Nanjing, China.

BACKGROUND: This study aimed to investigate the prevalence and risk factors for hypertension, diabetes, and dyslipidemia, and to evaluate their additive effects on myocardial infarction (MI) and stroke in Nanjing in East China. METHODS: A multistage, stratified random cluster sampling method was used to select representative participants. All eligible participants completed questionnaires, physical measurements, and blood tests. Multivariable and univariable logistic regression analyses were used to identify associated risk factors and evaluate additive effects on cardiovascular events, respectively. RESULTS: Hypertension was the most prevalent chronic disease among 11,036 participants enrolled (18.5%), followed by dyslipidemia (8.3%) and diabetes (6.0%). The prevalence of hypertension was higher in men than in women while no sex-related difference was observed in the prevalence of diabetes and dyslipidemia. Older age and higher body mass index were risk factors for all three diseases. Sex, central obesity, smoking, number of family members, salt intake, and family history of hypertension were associated with hypertension; central obesity, smoking, alcohol assumption, and family history of diabetes correlated with diabetes; and female sex, higher education, and alcohol assumption were risk factors for dyslipidemia. Hypertension complicated with dyslipidemia conferred more risk of MI and stroke than independent effects. Diabetes also contributed to risk based on hypertension or dyslipidemia. CONCLUSIONS: The burden of hypertension and diabetes has stopped increasing. However, total cholesterol (TC) concentration in the population has not been well controlled. A more comprehensive approach to managing dyslipidemia, hypertension, and diabetes needs to be developed, especially for individuals with multiple cardiovascular risk factors.

Prognostic significance of serum aspartic transaminase in diffuse large B-cell lymphoma.

BACKGROUND: Liver function is routinely assessed in clinical practice as liver function tests provide sensitive indicators of hepatocellular injury. However, the prognostic value of enzymes that indicate hepatic injury has never been systematically investigated in lymphoma, including diffuse large B-cell lymphoma (DLBCL). METHODS: This study examined the prognostic value of baseline aspartic transaminase (AST) in DLBCL patients. The association between AST and clinical features was analyzed in 179 DLBCL patients treated from 2006 to 2016. All enrolled patients were treated with R-CHOP or R-CHOP-like chemotherapy. Log-rank test, univariable analysis, and subgroup analysis were performed to evaluate the impact of AST on survival. RESULTS: AST 33.3 U/L was considered to be the optimal threshold value for predicting prognosis. A higher AST level was associated with advanced stage (P = 0.001), poorer performance status (P = 0.014), elevated lactate dehydrogenase level (P <  0.0001), presence of B symptoms (P = 0.001), high-risk International Prognostic Index (IPI, IPI 3-5) (P = 0.002), non-germinal center B-cell subtypes (P = 0.038), hepatitis B virus surface antigen positivity (P = 0.045) and more extra nodal involvement (ENI, ENI ≥ 2) (P = 0.027). Patients with a higher AST level had a shorter overall survival (OS) (2-year OS rate, 53.6% vs. 83.6%, P <  0.001). Subgroup analysis indicated that higher AST levels have poorer prognostic values in patients without B symptoms and LDH positive groups. CONCLUSION: A pretreatment AST level is associated with OS in DLBCL patients treated with R-CHOP or similar chemotherapy regimens. A high pretreatment AST level might be a reliable prognostic factor for predicting a dismal outcome in DLBCL patients. Serum AST levels may be investigated for use as an easily determinable, inexpensive biomarker for risk assessment in patients with DLBCL.

Validation and comparison of three newly-released Thyroid Imaging Reporting and Data Systems for cancer risk determination.

PURPOSE: To validate and compare diagnostic value of three newly-released Thyroid Imaging Reporting and Data Systems (TIRADS) for cancer risk determination. METHODS: Total 2031 patients with 2465 thyroid nodules were recruited for this study. Ultrasound (US) images were categorized based on three TIRADS editions established by Korean Society of Thyroid Radiology (KSThR), European Thyroid Association (ETA) and American College of Radiology (ACR). ROC curves were established to compare diagnostic value. RESULTS: Total 1460 benign and 1005 malignant nodules were enrolled. The malignancy rates of each category in KSThR-TIRADS were 2.8%, 5.1%, 33.7% and 79.6%, respectively. For European-TIRADS, 0, 3.1, 22.8, and 73.5% of nodules categorized as 2 to 5 were malignant. Distribution of carcinomas among ACR-TIRADS categories was 0%, 2.3%, 7.5%, 40.1% and 81.4%, respectively. In terms of diagnostic value, KSThR-TIRADS had highest AUC (0.855) and specificity (87.4%), while lowest (71.4%) sensitivity. ACR-TIRADS showed best sensitivity (96.6%) with lowest specificity (52.9%) and the AUC (0.846) was slightly lower than KSThR-TIRADS. Total 56.1, 45.4, and 37.4% fine-needle aspiration biopsy (FNAB) were recommended by KSThR, ETA and ACR, revealing 42.8%, 44.5% and 53.6% malignant lesions, respectively. The rate of unnecessary FNAB was lowest with the ACR (17.3%), followed by ETA (25.2%) and KSThR (32.1%). CONCLUSION: All these US models showed great value in predicting thyroid malignancy. Among them, KSThR-TIRADS showed the most effective diagnostic performance in specificity, while ACR-TIRADS yielded best sensitivity. As for FNAB criteria, ACR-TIRADS showed the lowest rate of unnecessary FNAB and highest rate of malignancy in FNAB.

Inflammation marker ESR is effective in predicting outcome of diffuse large B-cell lymphoma.

BACKGROUND: Systemic inflammation has been implicated in cancer development and progression. This study examined the best cutoff value of erythrocyte sedimentation rate (ESR) in diffuse large B-cell lymphoma (DLBCL) patients. METHODS: The relationship between ESR and clinical characteristics was analyzed in 182 DLBCL patients from 2006 to 2017. The log-rank test, univariate analysis, and Cox regression analysis were applied to evaluate the relationship between ESR and survival. An ESR of more than 37.5 mm/hour was found to be the optimal threshold value for predicting prognosis. RESULTS: ESR was associated with more frequent advanced Ann Arbor stage, poorer performance status, elevated lactate dehydrogenase level, the presence of B symptoms, high-risk International Prognostic Index (IPI 3-5), more extranodal involvement (ENI ≥2), non-germinal-center B-cell (non-GCB) subtypes, and more frequent Myc protein positivity. Shorter overall survival (OS) and progression-free survival (PFS) were found for patients with higher ESRs. Multivariate analysis demonstrated that ESR level is an independent prognostic factor of both OS and PFS. In addition, dynamic changes in ESR are valuable in assessing curative effect and predicting disease recurrence. CONCLUSION: High ESR in DLBCL patients indicated unfavorable prognosis that may require alternative treatment regimens.

[Effects of inhibitory concentration minocycline on the proliferation, differentiation, and mineralization of osteoblasts].

OBJECTIVE: To study the effect of the inhibitory concentration minocycline on the proliferation, differentiation, and expression of Runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and osteopontin (OPN) mRNA of osteoblasts. METHODS: Primary osteoblasts were cultured in osteogenic induction medium containing 0, 0.1, 0.5, 1, 10 µg·mL⁻¹ minocycline. Cell counting kit-8 was used to observe cell proliferation. ALP activity assay, alizarin red S staining, and real-time quantitative polymerase chain reaction (PCR) were used to determine cell differentiation and mineralization. RESULTS: The groups with 0.1, 0.5, 1 µg·mL⁻¹ minocycline promoted cell proliferation. The mRNA expression levels of ALP and Runx2 were up-regulated. Osteoblast-mediated mineralization was increased. The group with 1 µg·mL⁻¹ showed maximal promotion effect (P<0.05). When the concentration increased to 10 µg·mL⁻¹, the promoting effect began to decline, and the ALP activity and OPN expression were significantly inhibited (P<0.01). CONCLUSIONS: Appropriate concentration of minocycline can promote osteoblasts proliferation, up-regulate the expression levels of Runx2, ALP and OPN, and increase the differentiation and mineralization of osteoblasts.

DRR1 promotes glioblastoma cell invasion and epithelial-mesenchymal transition via regulating AKT activation.

Metastatic invasion is the primary cause of treatment failure for GBM. EMT is one of the most important events in the invasion of GBM; therefore, understanding the molecular mechanisms of EMT is crucial for the treatment of GBM. In this study, high expression of DRR1 was identified to correlate with a shorter median overall and relapse-free survival. Loss-of-function assays using shDRR1 weakened the invasive potential of the GBM cell lines through regulation of EMT-markers. The expressions of p-AKT were significantly decreased after DRR-depletion in SHG44 and U373 cells. Moreover, the invasion was inhibited by the AKT inhibitor, MK-2206. The expression of Vimentin, N-cadherin, MMP-7, snail and slug was significantly inhibited by MK-2206, while the expression of E-cadherin was upregulated. Our results provide the first evidence that DRR1 is involved in GBM invasion and progression possibly through the induction of EMT activation by phosphorylation of AKT.

Thyroid nodule sizes influence the diagnostic performance of TIRADS and ultrasound patterns of 2015 ATA guidelines: a multicenter retrospective study.

To evaluate the impact of thyroid nodule sizes on the diagnostic performance of thyroid imaging reporting and data system (TIRADS) and ultrasound patterns of 2015 American Thyroid Association (ATA) guidelines. Total 734 patients with 962 thyroid nodules were recruited in this retrospective study. All nodules were divided into three groups according to the maximal diameter (d < 10 mm, d = 10-20 mm and d > 20 mm). The ultrasound images were categorized based on TIRADS and ATA ultrasound patterns, respectively. A total of 931 (96.8%) and 906 (94.2%) patterns met the criteria for TIRADS and ATA ultrasound patterns. The AUC (0.849) and sensitivity (85.3%) of TIRADS were highest in d = 10-20 mm group. However, ATA had highest AUC (0.839) and specificity (89.8%) in d > 20 mm group. ATA ultrasound patterns had higher specificity (P = 0.04), while TI-RADS had higher sensitivity (P = 0.02). In nodules d > 20 mm, the specificity of ATA patterns was higher than TIRADS (P = 0.003). Our results indicated that nodule sizes may influence the diagnostic performance of TIRADS and ATA ultrasound patterns. The ATA patterns may yield higher specificity than TIRADS, especially in nodules larger than 20 mm.

Application of high-resolution ultrasound, real-time elastography, and contrast-enhanced ultrasound in differentiating solid thyroid nodules.

High-resolution ultrasound (HRUS) is a sensitive tool for identifying thyroid nodules. Real-time elastography (RTE) and contrast-enhanced ultrasound (CEUS) are newly developed methods which could measure tissue elasticity and perfusion features. The aim of the present study was to evaluate and compare the diagnostic efficiency of HRUS, RTE, CEUS and their combined use in the differentiation of benign and malignant solid thyroid nodules.In total, 111 consecutive patients with 145 thyroid nodules who were scheduled for surgery were included in the study. All of them underwent HRUS, RTE, and CEUS examination. The independent ultrasound (US) predictors for malignancy were determined and quantified using logistic regression analysis, based on which a risk-scoring model was established for each method. The diagnostic efficiency of each method was assessed by receiver operating characteristic (ROC) curve analysis.HRUS showed the best diagnostic efficiency among the 3 US methods, with 74.6% sensitivity and 87.8% specificity. CEUS had higher sensitivity (85.7%), whereas RTE alone did not show much advantage. Combined use of RTE and HRUS increased the sensitivity (92.1%). The HRUS-RTE-CEUS combination could increase both the sensitivity and specificity (87.3%, 91.5%), with the best AUC (0.935) among all the methods.The overall diagnostic value of HRUS in predicting malignancy is the best among the 3 US methods. Combined use of RTE and CEUS and HRUS could improve the diagnostic efficiency for solid thyroid nodules.

Cullin-1 promotes cell proliferation in human breast cancer and is related to diabetes.

AIM: Breast carcinoma (BCA) and diabetes mellitus (DM) are two major health problems in women and the general population. Cullin-1 is reported to be an important tumor-related protein involved in cell-cycle progression, signal transduction and transcription. The aim of this work is to investigate the role of Cullin-1 in the development of BCA and to find potential relationships between Cullin-1 and diabetes in BCA patients. METHODS: To evaluate the function of Cullin-1, we entered 168 patients with primary invasive BCA in this study. Pairs of BCA tissues and adjacent noncancerous tissues from these patients were collected between 2006 and 2008. We used immunohistochemistry to analyze the correlation between Cullin-1 expression and clinicopathological variables and patient survival. In addition, we investigated the role of Cullin-1 in BCA cell proliferation. RESULTS: Cullin-1 expression was upregulated in BCA tissues. Enhanced immunoreactivity for Cullin-1 in BCA tissues was inversely correlated with overall survival and disease-free survival, which suggested a poor prognosis in BCA patients. Strong expression of Cullin-1 was more frequently observed in patients with estrogen receptor negativity and HER2 positivity. We also found that Cullin-1 expression was increased in BCA patients with a previous diagnosis of diabetes. CONCLUSIONS: Our results demonstrate that increased Cullin-1 expression is significantly correlated with poor prognosis in patients with BCA. Cullin-1 might regulate BCA cell proliferation through the ubiquitin-proteasome system. Thus, Cullin-1 might be an important marker and a therapeutic target in BCA.

Downregulation of SATB1 increases the invasiveness of Jurkat cell via activation of the WNT/ß-catenin signaling pathway in vitro.

Special AT-rich sequence-binding protein-1 (SATB1) is critical for genome organizer that reprograms chromatin organization and transcription profiles, and associated with tumor growth and metastasis in several cancer types. Many studies suggest that SATB1 overexpression is an indicator of poor prognosis in various cancers, such as breast cancer, malignant cutaneous melanoma, and liver cancer. However, their expression patterns and function values for adult T cell leukemia (ATL) are still largely unknown. The aim of this study is to examine the levels of SATB1 in ATL and to explore its function and mechanisms in Jurkat cell line. Here, we reported that SATB1 expressions were decreased in ATL cells (p < 0.001) compared with normal controls. Knockdown of SATB1 expression significantly enhanced invasion of Jurkat cell in vitro. Furthermore, knockdown of SATB1 gene enhances ß-catenin nuclear accumulation and transcriptional activity and thus may increase the invasiveness of Jurkat cell through the activation of Wnt/ß-catenin signaling pathway in vitro.

Elevation of serum uric acid and incidence of type 2 diabetes: A systematic review and meta-analysis.

OBJECTIVE: Recently, several cohort studies suggested a positive relationship between serum uric acid (SUA) and type 2 diabetes mellitus (T2DM), which is inconsistent with the results of functional research. Our aim was to further evaluate this correlation by conducting a systematic review. METHODS: Computerized literature searches of the Medline database, EMBASE database, and PubMed were used to evaluate the relationship between SUA and T2DM in cohort studies. Cochran's Q and I2 statistics were used to evaluate heterogeneity among studies, and pooled relative risk (RR) and odds ratio (OR) with 95% confidence intervals (CIs) were calculated using random-effects and fixed-effects models. The summary RR and OR of per 1 mg/ml-SUA increase were calculated separately because of their different epidemiological implications and calculation methods. Additionally, sensitivity analysis, stratified analysis, meta-regression, and multiple meta-regression were applied to investigate the heterogeneity among studies. RESULTS: A total of 970 articles were retrieved from the searches. Sixteen publications of cohort studies containing 61,714 participants were included. The pooled RR was 1.131 (95% CI: 1.084-1.179) with significant heterogeneity among studies (I2  = 51.9%, P = 0.018). Adjusted RR to evaluate the stability of the relationship between SUA and T2DM in the sensitivity analysis was similar (RR = 1.140, 95% CI: 1.087-1.197), with statistically significant heterogeneity (I2  = 54.5%, P = 0.015). Stratified analysis and meta-regression showed that the positive relationship remained irrespective of age, sex, region, and adjustment for confounding factors including body mass index, fasting blood glucose, systolic blood pressure, diastolic blood pressure, alcohol consumption, smoking, blood cholesterol, waist circumference, fatty liver, and drugs affecting SUA. CONCLUSION: Although SUA is independently associated with development of T2DM, insulin resistance increased as the baseline SUA concentration increased; thus, the correlation between SUA and T2DM requires further evaluation and the baseline insulin resistance status should also be considered.

Preoperative serum lipid profile and outcome in nonmetastatic colorectal cancer.

OBJECTIVE: A large portion of non-metastatic colorectal cancers (non-mCRCs) recur after curative surgery. In addition to the traditional tumor-related factors, host-related factors are also required to accurately predict prognosis. A few studies have shown an association between the serum lipid profile and the survival and treatment response of patients with colorectal cancer. METHODS: We retrospectively evaluated the prognostic significance of the preoperative serum lipid profile [total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)] in patients with non-mCRC treated with curative surgery. The Spearman rank correlation test was used to analyze associations between lipid levels and categorical variables. Lipid levels were modeled as four equal-sized quartiles based on the distribution among the whole cohort. Kaplan-Meier curves were used to estimate survival probabilities, and the log-rank test was used to detect differences between them. Multivariate fractional polynomial (MFP) analysis was used to model any non-linear effects and avoid categorization. To evaluate the added prognostic value of lipids, the predictive power of two models (with and without lipids as covariates) was compared by using Harrell's C-statistic and the Akaike information criterion (AIC). RESULTS: A total of 266 patients with non-mCRC were enrolled in the present study. Spearman rank correlation test showed that TG levels inversely correlated with N stage (r = -0.20, P = 0.00) and Tumor-Node-Metastasis (TNM) stage (r = -0.19, P = 0.00). HDL-C levels positively correlated with perineural invasion (PNI) (r = 0.15, P = 0.02), and LDL-C levels inversely correlated with lymphovascular invasion (LVI) (r = -0.12, P = 0.04). None of the four lipids predicted overall survival (OS) in univariate or multivariate analyses adjusted for age, gender, T stage, N stage, TNM stage, histological grade, tumor deposits, LVI, PNI, and adjuvant treatment (all P > 0.05). In agreement, the Kaplan-Meier curves for OS according to the lipid quartiles were not significantly different, as confirmed by the log-rank test (all P > 0.05). MFP analysis also found no significant associations between lipid levels and OS (all P > 0.05). A prognostic model that included lipids had a higher Harrell's C-statistic and a lower AIC value than did a model that did not include lipids (for Harrell's C-statistic: 0.82 vs. 0.77; for AIC: 398 vs. 432). CONCLUSION: Measuring preoperative serum lipid levels may be a simple and cost-effective way of increasing prognostic accuracy in patients with non-mCRC treated with curative surgery.

Value of TIRADS, BSRTC and FNA-BRAF V600E mutation analysis in differentiating high-risk thyroid nodules.

The thyroid imaging reporting and data system (TIRADS) and Bethesda system for reporting thyroid cytopathology (BSRTC) have been used for interpretation of ultrasound and fine-needle aspiration cytology (FNAC) results of thyroid nodules. BRAF(V600E) mutation analysis is a molecular tool in diagnosing thyroid carcinoma. Our objective was to compare the diagnostic value of these methods in differentiating high-risk thyroid nodules. Total 220 patients with high-risk thyroid nodules were recruited in this prospective study. They all underwent ultrasound, FNAC and BRAF(V600E) mutation analysis. The sensitivity and specificity of TIRADS were 73.1% and 88.4%. BSRTC had higher specificity (97.7%) and similar sensitivity (77.6%) compared with TIRADS. The sensitivity and specificity of BRAF(V600E) mutation (85.1%, 100%) were the highest. The combination of BSRTC and BRAF(V600E) mutation analysis significantly increased the efficiency, with 97.8% sensitivity, 97.7% specificity. In patients with BSRTC I-III, the mutation rate of BRAF(V600E) was 64.5% in nodules with TIRADS 4B compared with 8.4% in nodules with TIRADS 3 or 4A (P < 0.001). Our study indicated that combination of BSRTC and BRAF(V600E) mutation analysis bears a great value in differentiating high-risk thyroid nodules. The TIRADS is useful in selecting high-risk patients for FNAB and patients with BSRTC I-III for BRAF(V600E) mutation analysis.