Skeletal muscle-secreted myokine interleukin-6 induces white adipose tissue conversion into beige adipose tissue in myostatin gene knockout pigs.

Myostatin (MSTN) is primarily expressed in skeletal muscle and plays an important role in the regulation of muscle growth and development as well as fat deposition; however, little is known about the molecular mechanism through which MSTN regulates body fat deposition. Therefore, in this study, we sought to identify the signaling pathways through which MSTN regulates fat accumulation in pigs. MSTN knockout (MSTN-/-) pigs showed increased muscle mass, decreased fat mass, and a leaner body composition. In this study, we found that the adipose tissue of MSTN-/- pigs exhibits the characteristics of beige adipose tissue, and the mRNA expression levels of beige adipose marker genes, including UCP3, Cidea, and CD137, were significantly increased. Remarkably, the observed beige phenotype was not adipocyte autonomous but rather caused by muscle-secreted myokine interleukin (IL)-6. This occurrence results in increased AMP-activated protein kinase (AMPK) phosphorylation in adipose tissue, which subsequently activates peroxisome proliferator-activated receptor gamma coactivator 1α and the conversion of white adipocytes to beige in pigs. Therefore, we concluded that MSTN deficiency leads to increased IL-6 secretion in skeletal muscle and activates AMPK in adipocytes, thereby increasing the beige adipose tissue in MSTN-/- pigs.

Simultaneous multi-slice accelerated diffusion-weighted imaging with higher spatial resolution for patients with liver metastases from neuroendocrine tumours.

AIM: To evaluate the imaging characteristics of simultaneous multi-slice (SMS) accelerated diffusion-weighted imaging (DWI) with decreased section thickness, with and without motion correction, in comparison to conventional DWI (cDWI) for the detection of lesions in patients with neuroendocrine tumour (NET) liver metastases. MATERIALS AND METHODS: Fifteen patients with NET liver metastases underwent cDWI (section thickness [SL]=4 mm) and SMS-DWI (SL=2 mm). Non-linear motion-corrected (Moco)-SMS-DWI was generated in addition to the original series. Qualitative imaging characteristics (five-point Likert scale), the number of high signal lesions, and the detectability and delineation of lesions were evaluated and compared using the Friedman and the Dunn-Bonferroni tests. The test-retest variability (TRV) of the cDWI and SMS-DWI techniques was investigated among 11 healthy volunteers who underwent cDWI (SL=4 mm) and SMS-DWI (SL=4 mm) twice. The Friedman and the Dunn-Bonferroni post-hoc tests were used to compare the mean apparent diffusion coefficient (ADC) and the TRV in different liver regions between the three series. RESULTS: Moco-SMS-DWI demonstrated significantly superior overall image quality (p<0.001) with significantly fewer artefacts (p=0.003) than cDWI. The number of lesions detected by cDWI, SMS-DWI, and Moco-SMS-DWI were 348, 504, and 523, respectively. The detectability and delineation of the lesions and the ADC values were significantly higher on the SMS-DWI and Moco-SMS-DWI images than on the cDWI images (all p<0.001). Moco-SMS-DWI showed significantly higher TRV than cDWI in regions near the liver edge (p=0.018). CONCLUSIONS: SMS-DWI achieves higher spatial resolution than cDWI within the same acquisition time, detects more lesions, and provides better lesion delineation. By applying motion correction, the TRV of DWI could be enhanced in regions near the liver edge.

[Diagnostic value of 4-dimensional computed tomography in preoperative localization in patients with primary hyperparathyroidism].

Objective: To provide more options for preoperative localization diagnosis in patients with primary hyperparathyroidism (PHPT), the diagnostic efficacy of parathyroid 4-dimensional computed tomography (4D-CT) in patients with PHPT was evaluated. Methods: This was a single-center retrospective study including 57 patients with surgical proved PHPT. All of the patients underwent 4D-CT, 99Tcm -sestamibi parathyroid imaging (MIBI), and ultrasonography (US) preoperatively. The reference standard for correct localization was based on operation reports and pathology confirmation. The patients were grouped according to the preoperative serum calcium levels, tumor diameter, or ectopic lesions (yes/no), respectively. The sensitivity, specificity, positive predictive value, negative predictive value and area under the curve (AUC) of 4D-CT, MIBI and US, alone or in combination, were analyzed in total and each subgroup patients. Results: Fifty-seven patients (39 women, 18 men; mean age of 56.5 years) were evaluated, including four cases with multi-gland disease and thirteen cases with ectopic parathyroid lesions. In all the patients, similar diagnostic efficacy was found in 4D-CT (AUC: 0.943) and MIBI (AUC: 0.927), both of which were higher than that of US (AUC: 0.847) (P = 0.01 for 4D-CT vs. US; P = 0.04 for MIBI vs. US). In a subset analysis for ectopic quadrants, the diagnostic efficacy of 4D-CT was significantly higher than that of MIBI (P = 0.04) or US (P = 0.01), with the sensitivity of 100%, 69.2%, and 61.5%, and AUC of 0.989, 0.846, and 0.808 for 4D-CT, MIBI and US, respectively. Conclusions: 4D-CT has similar diagnostic efficacy for preoperative localization to MIBI in patients with PHPT, and it is superior to MIBI and US in identifying the ectopic parathyroid gland. 4D-CT can be recommended as an alternative preoperative localization method, especially when parathyroid lesions could not be precisely located by US and MIBI.

[Factor analysis of diagnosis and surgical treatment of local regional recurrence in breast cancer patients].

Objective: To analyze the association between clinicopathological factors and clinical diagnosis, treatment and surgery of local regional recurrence (LRR) in breast cancer. Methods: A retrospective study was done to evaluate consecutive 7 823 breast cancer LRR cases between January 2009 and August 2018 at Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine. A total of 108 LRR patients were enrolled: 35 cases (32.4%) with ipsilateral breast tumor recurrence (IBTR) after breast conserving surgery, 40 cases (37.0%) of chest wall recurrence (CR), and 33 cases (30.6%) with regional lymph node recurrence (LNR). All patients were female, aged from 26 to 83 years with a mean of 49 years. Clinicopathological factor and its relationship with different sites of LRR and following surgical choice were analyzed by χ(2) test, rank-sum test and Logistic regression. Survival analysis were performed between different LRR patterns and whether undergoing second surgery. Kaplan-Meier survival curves and Log-rank tests demonstrated the distribution of overall survival. Results: Both univariate analysis and multivariate analysis found that axillary lymph nodes (ALN) status (OR=7.27, 95% CI: 1.30 to 40.53, P=0.042) and disease-free interval (OR=0.18, 95% CI: 0.06 to 0.60, P=0.013) were related to different site of LRR. Compared with patients with IBTR, LNR and CR patients had a higher rate of ALN metastasis and a shorter disease-free interval. A total of 36 LRR patients underwent following surgery. In univariate analysis, initial ALN surgery (χ(2)=16.705, P=0.001), pathological type (χ(2)=7.047, P=0.03), ALN status (χ(2)=10.812, P=0.002), disease-free interval (χ(2)=6.118, P=0.023) and LRR site(χ(2)=19.328, P=0.000) were associated with surgical treatment for LRR patients. Multivariate analysis demonstrated that only site of LRR was independently associated with surgery (OR=0.17, 95% CI: 0.05 to 0.65, P=0.024). The 5-year overall survival was 100% and 60.1% (P=0.018) for LRR patients treated with surgery or not. Furthermore, CR patients had significantly worse overall survival than LNR and IBTR patients, with 5-year overall survival 53.1%, 73.5%, and 100% respectively (P=0.021). Conclusions: Initial lymph nodes metastasis and disease-free interval are associated with different site of LRR. LRR site significantly influenced following surgery choice after LRR, which are both related with overall survival after LRR.

Can quantitative CT texture analysis be used to differentiate subtypes of renal cell carcinoma?

AIM: To investigate whether computed tomography (CT) texture analysis (TA) can be used to differentiate non-clear-cell renal cell carcinoma (non-ccRCC) from clear-cell RCC (ccRCC) and classify non-ccRCC subtypes. MATERIALS AND METHODS: One hundred ccRCC and 27 non-ccRCC (12 papillary and 15 chromophobe) were analysed. Texture parameters quantified from multiphasic CT images were compared for the objectives. Receiver operating characteristic (ROC) analysis was performed and the area under the ROC curve (AUC) was calculated. The optimal discriminative texture parameters were used to produce support vector machine (SVM) classifiers. Diagnostic accuracy and 10-fold cross-validation was performed. RESULTS: Compared to ccRCC, non-ccRCC had significantly lower mean grey-level intensity (mean), standard deviation (SD), entropy, mean of positive pixels (MPP), and higher kurtosis (p<0.001). A model incorporating SD, entropy, MPP, and kurtosis produced an AUC of 0.94±0.03 with an accuracy of 87% (sensitivity=89%, specificity=92%) to identify non-ccRCC from ccRCC. Compared to chromophobe RCC, papillary RCC had significantly lower mean and MPP (p=0.002). A model incorporating SD, MPP, and skewness resulted in an AUC of 0.96±0.04 with an accuracy of 78% (sensitivity=87%, specificity=92%) to differentiate between papillary and chromophobe RCC. CONCLUSION: CT TA could potentially be used as a less invasive tool to classify histological subtypes of RCC.

Visualising the boundary sharpness of uterine zonal structures using high-resolution T2-weighted images during the menstrual cycle.

AIM: To investigate whether there is an optimal time in the menstrual cycle to obtain the best image quality of uterine zonal structures with high-field magnetic resonance imaging (MRI). MATERIALS AND METHODS: Thirty-eight normal volunteers with regular menstrual cycles underwent pelvic 3 T high-resolution T2-weighted three-dimensional (3D) turbo spin echo (TSE) with variable flip angle MRI examinations during the menstrual phase (MP), follicular phase (FP), peri-ovulatory phase (OP), and luteal phase (LP). Two radiologists blinded evaluated the boundary sharpness of the three zonal structures of the uterine corpus and cervix on mid-sagittal images using a three-point Likert-scale. The signal intensity (SI) on T2-weighted sequences of each zonal structure was measured and the ratio between the SI of adjacent structures was calculated. Paired Wilcoxon's test and repeated measurement analysis of variance were used to investigate the differences among the four phases. RESULTS: No variation during the menstrual cycle was found in 10.5% (4/38) of volunteers and their boundaries were all well-defined. The OP exhibited the clearest boundaries of the corpus zonal structures. For the endometrium to junctional zone, mean scores of boundary sharpness from high to low were 3 (OP), 2.97 (FP), 2.76 (LP), 2.74 (MP); that for the junctional zone to myometrium were 2.76 (OP), 2.42 (FP), 2.32 (LP), 2.11 (MP); which were consistent with the SI ratio results. The results for the cervix showed no statistical difference during the menstrual cycle (p>0.05), and was well-defined throughout. CONCLUSIONS: The OP is recommended as the best phase to investigate zonal-related uterine corpus diseases due to the best contrast. For cervical diseases, imaging could be performed when necessary at any time point, due to the limited influence of menstrual phases on cervical zone delineation.

[The occurrence and clinical significance of contrast agent spillover on immediate enhanced CT reexamination after radiofrequency ablation of liver cancer].

Objective: To investigate the relationship between radiofrequency ablation immediately after enhanced CT scanning and the occurrence of contrast agent spillover and postoperative severe bleeding, and analyze the risk factors for hepatocellular carcinoma (HCC). Methods: A retrospective analysis of 199 patients with hepatocellular carcinoma who underwent radiofrequency ablation of liver cancer in our hospital from January 2016 to January 2017 was reviewed. A total of 232 cases were treated with ablation. The agent spillovers were divided into two groups, one for the contrast agent spill group and the other for the non-contrast agent spill group. Its basic clinical data, laboratory data related to the risk of bleeding, and imaging data were analyzed to explore their clinical treatment effects and the risk factors for their occurrence. According to different data, t-test, χ2 test or logistic regression test was used for statistical analysis. Results: In 199 patients, a total of 232 cases were treated with ablation, including 138 males and 61 females. The average age was (57.56 ± 12.09) years and the average diameter of lesions was (3.42 ± 2.30) cm. A total of 30 cases (12.93%) of contrast agent spillover occurred immediately after the ablation of CT scanning needle. There were no severe bleeding and no special clinical intervention after the operation. The other 202 cases were non- contrast agent spill group, but 2 cases had severe bleeding and had corresponding clinical interventions. Univariate analysis showed that there were statistically significant differences in thoracentesis (P = 0.019), complications of cirrhosis (P < 0.001), and histological types of liver cancer (P = 0.013), and other clinical data [age, lesion size]. There were no significant differences in Child-Pugh classification, preoperative hemoglobin (HGB), platelet count, prothrombin time, APTT, international standardized ratio, number of puncture needles, and puncture length. There was also no significant difference in postoperative HGB (P = 0.160), preoperative-postoperative HGB change (P = 0.999), and length of hospital stay (P = 0.730) between the two groups. Logistic regression analysis showed that with cirrhosis (OR = 5.59, P < 0.001), transthoracic puncture (OR = 2.67, P = 0.021) may be a risk factor for contrast agent spillover after CT-enhanced CT scan in patients with hepatocellular carcinoma. Conclusion: Contrast agent spillover is not uncommon in the evaluation of curative effect of CT immediately after ablation (12.93%). It is not predictive for the occurrence of postoperative severe bleeding and does not require excessive clinical intervention. Liver cirrhosis and transthoracic cavity puncture may be the risk factors for its occurrence. The risk of severe postoperative bleeding should not be ignored for patients who have no contrast agent spills after surgery.

[Value of MRI in the pre-operative diagnosis and classification of oblique vaginal septum syndrome].

Objective: To explore the role of MRI in the pre-operative diagnosis and classification of oblique vaginal septum syndrome (OVSS) . Methods: A retrospective analysis of the clinical records and pre-operative MRI images of 19 patients with surgery proved OVSS was carried out. Two experienced radiologists reviewed the pre-operative pelvic MRI of the 19 patients in consensus blind to the surgery results. Characteristics including malformations of the uterus, cervix and vagina, the diagnosis of the disorder and classification were evaluated. Pre-operative MRI diagnosis and classification were correlated with surgical findings. Results: Mean age of onset of symptoms for the 19 patients was 15 years (ranged 9-25 years) , and mean age of menarche was 12 years. Ten patients suffered from dysmenorrhea or lower abdominal pain, 5 patients complained of vaginal discharge, 3 patients had a history of irregular menstruation, 1 patient suffered from primary infertility. All 19 patients showed uteri didelphys. Eighteen patients showed vaginal oblique septum.One patient showed cervical atresia.MRI was completely correlated with the surgery in the pre-operative diagnosis of OVSS. MRI classification was in line with surgery in 17 patients, including 9 patients with imperforate septum (typeⅠ) , 6 patients with perforate septum (type Ⅱ) , 1 patient with imperforate septum and cervical fistula (type Ⅲ) , and another one with cervical agenesis (type Ⅳ) . One case of type Ⅱ was misdiagnosed as type Ⅰ, another one of type Ⅰ was misdiagnosed as type Ⅲ. Pre-operative MRI classification was correlated with surgery in 17 out of 19 patients. Conclusion: Pre-operative MRI allows excellent manifestation and accurate diagnosis of OVSS, and could also facilitate the evaluation of the classification.

[A cohort study of HIV incidence among injecting drug users in Dehong Prefecture, Yunnan Province].

Objective: To investigate the incidence rates of HIV among injection drug users (IDU) in Dehong Prefecture, Yunnan Province. Methods: We recruited 1 413 HIV-negative IDU attending drug rehabilitation centers and identified a further 1 830 potential participants from a historical database from 2004-2009 using the same criteria. Fingerprint recognition technology was used to confirm the identity of all participants. A total of 3 243 HIV-negative IDU were recruited by the end of 2015, of which 2 546 (78.5%) had been followed up at least once since the initial data collection and 697 (21.5%) were lost to follow-up. Epidemiological data were collected through structured face-to-face interviews which included items on knowledge of AIDS, drug use, sexual activity and history of HIV testing. We collected 3-5 ml of venous blood from each subject for HIV testing. The Chi-squared test was used to compare the characteristics of those IDUs successfully followed up and those lost to follow-up. Results: We identified 226 new HIV cases among the 2 546 respondents-representing 13 907.1 person-years of follow-up and implying an average HIV incidence rate of 1.6 per 100 person-years over the entire study period (95%CI: 1.4-1.9). The incidence rate (per 100 person-years) was 2.6 (95%CI: 2.2-3.1) for the period 2004-2009 and 1.6 (95%CI: 1.0-2.3), 1.7 (95%CI: 1.1-2.4), 1.2 (95%CI: 0.8-1.9), 0.6 (95%CI: 0.3-1.1), 0.2 (95%CI:0.0-0.7), 0.5 (95%CI: 0.1-1.4) for each year from 2010 to 2015 respectively. Conclusion: Although the incidence rate of HIV remains high among IDUs in Dehong, there was a declining trend over the period studied.

Image quality of mean temporal arterial and mean temporal portal venous phase images calculated from low dose dynamic volume perfusion CT datasets in patients with hepatocellular carcinoma and pancreatic cancer.

PURPOSE: Dynamic volume perfusion CT (dVPCT) provides valuable information on tissue perfusion in patients with hepatocellular carcinoma (HCC) and pancreatic cancer. However, currently dVPCT is often performed in addition to conventional CT acquisitions due to the limited morphologic image quality of dose optimized dVPCT protocols. The aim of this study was to prospectively compare objective and subjective image quality, lesion detectability and radiation dose between mean temporal arterial (mTA) and mean temporal portal venous (mTPV) images calculated from low dose dynamic volume perfusion CT (dVPCT) datasets with linearly blended 120-kVp arterial and portal venous datasets in patients with HCC and pancreatic cancer. MATERIALS AND METHODS: All patients gave written informed consent for this institutional review board-approved HIPAA compliant study. 27 consecutive patients (18 men, 9 women, mean age, 69.1 years±9.4) with histologically proven HCC or suspected pancreatic cancer were prospectively enrolled. The study CT protocol included a dVPCT protocol performed with 70 or 80kVp tube voltage (18 spiral acquisitions, 71.2s total acquisition times) and standard dual-energy (90/150kVpSn) arterial and portal venous acquisition performed 25min after the dVPCT. The mTA and mTPV images were manually reconstructed from the 3 to 5 best visually selected single arterial and 3 to 5 best single portal venous phases dVPCT dataset. The linearly blended 120-kVp images were calculated from dual-energy CT (DECT) raw data. Image noise, SNR, and CNR of the liver, abdominal aorta (AA) and main portal vein (PV) were compared between the mTA/mTPV and the linearly blended 120-kVp dual-energy arterial and portal venous datasets, respectively. Subjective image quality was evaluated by two radiologists regarding subjective image noise, sharpness and overall diagnostic image quality using a 5-point Likert Scale. In addition, liver lesion detectability was performed for each liver segment by the two radiologists using the linearly blended120-kVp arterial and portal venous datasets as the reference standard. RESULTS: Image noise, SNR and CNR values of the mTA and mTPV were significantly higher when compared to the corresponding linearly blended arterial and portal venous 120-kVp datasets (all p<0.001) except for image noise within the PV in the portal venous phases (p=0.136). OBJECTIVE: image quality of mTA and mTPV were rated significantly better when compared to the linearly blended 120-kVp arterial and portal venous datasets. Both readers were able to detect all liver lesions found on the linearly blended 120-kVp arterial and portal venous datasets using the mTA and mTPV datasets. The effective radiation dose of the dVPCT was 27.6mSv for the 80kVp protocol and 14.5mSv for the 70kVp protocol. The mean effective radiation dose for the linearly blended 120-kVp arterial and portal venous CT protocol together of the upper abdomen was 5.60mSv±1.48mSv. CONCLUSION: Our preliminary data suggest that subjective and objective image quality of mTA and mTPV datasets calculated from low-kVp dVPCT datasets is non-inferior when compared to linearly blended 120-kVp arterial and portal venous acquisitions in patients with HCC and pancreatic cancer. Thus, dVPCT could be used as a stand-alone imaging technique without additionally performed conventional arterial and portal venous CT acquisitions.

Prospective prediction of the major component of urinary stone composition with dual-source dual-energy CT in vivo.

AIM: To prospectively evaluate the diagnostic accuracy of dual-source dual-energy computed tomography (DSDECT) for predicting the major component and determining the composition of urinary calculi in patients with urolithiasis, using postoperative in vitro Fourier transform infrared spectroscopy (FT-IR) analysis as the reference standard. MATERIALS AND METHODS: Patients with known urolithiasis underwent preoperative DSDECT evaluation, and subsequently, underwent surgical removal of the stones. All patients were examined using the dual-energy renal stone protocol. Material-specific chromatic images were made using dedicated post-processing software. The final determination of stone composition was made using FT-IR postoperatively. Diagnostic parameters of DSDECT for predicting the major component and detecting the presence of four composition types were calculated. RESULTS: A total of 81 urinary calculi were included in this study. Forty-three were pure stones and 38 were mixed stones according to FT-IR. DSDECT correctly identified the major component of all pure stones and 36 mixed stones. The major component of two mixed stones with uric acid as the major component was falsely interpreted as calcium oxalate. The overall accuracy of DSDECT for predicting the major component of stones was 97.5% (79/81). The accuracy of DSDECT for detecting the presence of four types of composition, uric acid, cysteine, hydroxyapatite, and calcium oxalate, was 97.5% (79/81), 93.8% (76/81), 80.2% (65/81), and 93.8% (76/81), respectively. CONCLUSION: DSDECT could accurately predict the major component of urinary calculi and detect uric acid, cysteine, and calcium oxalate with a satisfactory accuracy.

Predictive role of RRM1 and BRCA1 mRNA expression on the clinical outcome of advanced non-small cell lung cancer.

This study aimed to evaluate the association between RRM1 and BRCA1 expressions and the therapeutic efficacy of platinum-based chemotherapy in non-small cell lung cancer patients in terms of their response and prognosis. In total, 377 patients agreed to participate in our study, and all of them received platinum-based combination chemotherapy between January 2008 and January 2009. The relative cDNA quantitation for RRM1 and BRCA1 was conducted using a fluorescence-based, real-time detection method, using ß-actin as a reference gene. The average age of the 377 patients was 64.6 years (range: 25.5-86.4 years), including 269 men and 108 women. Patients with high RRM1 expression benefited more from a platinum-containing regimen, and patients with high BRCA1 expression showed a high response rate to a platinum-containing regimen and reduced disease progression. Patients with high RRM1 expression were associated with a longer progression-free survival (PFS) and overall survival (OS) than those with low expression, and the hazard ratios (HRs) (95% confidence interval (CI)) were 0.67 (0.32-0.91) and 0.54 (0.30-0.95), respectively. Patients with high BRCA1 expression showed longer PFS and OS compared to those with low expression, and the HRs (95%CI) were 0.54 (0.30-0.95) and 0.62 (0.32-0.93), respectively. These results could be used in personalized chemotherapy decisions and to increase the response rate and prolonged survival, and could encourage exploration of the predictive value of other genes.

Effects of polymorphisms in the XRCC1, XRCC3, and XPG genes on clinical outcomes of platinum-based chemotherapy for treatment of non-small cell lung cancer.

This study aimed to investigate the effects of single-nucleotide polymorphisms (SNPs) XRCC1 Arg194Trp, XRCC1 Arg280His, XRCC1 Arg399Gln, XRCC3 Thr241Met, XPG His104Asp, and XPG His46His in genes involved in the DNA-repair pathway on the outcomes of platinum-based chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). The study period was from January 2005 to January 2006, and 378 NSCLC patients were enrolled within 1 month after being diagnosed with NSCLC. Genomic DNA was extracted using the Qiagen Blood Kit. Polymerase chain reaction combined with a restriction fragment length polymorphism assay was used for genotyping. Individuals with the XRCC1 399A/A genotype had a higher probability of responding well to platinum-based chemotherapy, indicated by an odds ratio (OR) of 2.27 [95% confidence interval (CI)=1.64-6.97]. Similarly, the XPG T/T genotype was significantly associated with improved responses to chemotherapy, indicated by an OR of 1.90 (95%CI=1.10-3.28). The XRCC1 399A/A genotype was significantly associated with longer disease-free survival and overall survival, indicated by hazard ratios (HRs) of 0.48 (95%CI=0.25-0.88) and 0.51 (95%CI=0.26- 0.98), respectively. Moreover, the XPG 46T/T genotype increased the likelihood of longer disease-free survival and overall survival of NSCLC patients treated with platinum-based chemotherapy (HR=0.47; 95%CI=0.22-0.82 and HR=0.52; 95%CI=0.31- 0.96, respectively). These results indicate that XRCC1 Arg399Gln and XPG His46His might significantly affect the clinical outcomes of platinum-based chemotherapy, highlighting the need for larger studies to confirm the role of these two SNPs in outcomes of NSCLC treatments.

Dual-source dual-energy computed tomography angiography for active gastrointestinal bleeding: a preliminary study.

AIM: To assess the utility of dual-source dual-energy computed tomography angiography (DSDECTA) in the diagnosis of active gastrointestinal bleeding (GIB). MATERIALS AND METHODS: From June 2010 to September 2011, 58 consecutive patients with clinical signs of active GIB underwent DSDECTA. Two radiologists, blinded to clinical data, interpreted images from DSDECTA independently, with discordant interpretation resolved by consensus. The standards of reference included digital subtraction angiography, endoscopy, surgery, or final pathology reports. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, and accuracy of DSDECTA for detection of active GIB were evaluated. Receiver-operating characteristic (ROC) analysis was undertaken and the area under the curve (AUC) calculated. RESULTS: Active GIB source was identified in 39 of 58 patients (67.2%), all of which were confirmed by one or more reference standard. Negative DSDECTA results were obtained in 19 patients (32.8%). Of these, 15 patients did not require any further intervention and were discharged without incident. The overall sensitivity, specificity, PPV, NPV, and accuracy of DSDECTA was 88.6, 100, 100, 73.7, and 91.4%, respectively. The AUC was 0.935 ± 0.063. The dose reduction of a dual-phase DSDECTA protocol was approximately 30%, compared with that of a triple-phase protocol used in a previous study. CONCLUSION: DSDECTA can act as an accurate method for detection and localization of active GIB and has a relatively low radiation dose.

The p53-inducible gene 3 (PIG3) contributes to early cellular response to DNA damage.

The p53-inducible gene 3 (PIG3) is originally isolated as a p53 downstream target gene, but its function remains unknown. Here, we report a role of PIG3 in the activation of DNA damage checkpoints, after UV irradiation or radiomimetic drug neocarzinostatin (NCS). We show that depletion of endogenous PIG3 sensitizes cells to DNA damage agents, and impaired DNA repair. PIG3 depletion also allows for UV- and NCS-resistant DNA synthesis and permits cells to progress into mitosis, indicating that PIG3 knockdown can suppress intra-S phase and G2/M checkpoints. PIG3-depleted cells show reduced Chk1 and Chk2 phosphorylation after DNA damage, which may directly contribute to checkpoint bypass. PIG3 exhibited diffuse nuclear staining in the majority of untreated cells and forms discrete nuclear foci in response to DNA damage. PIG3 colocalizes with gamma-H2AX and 53BP1 to sites of DNA damage after DNA damage, and binds to a gamma-H2AX. Notably, PIG3 depletion decreases the efficient induction and maintenance of H2AX phosphorylation after DNA damage. Moreover, PIG3 contributes to the recruitment of 53BP1, Mre11, Rad50 and Nbs1 to the sites of DNA break lesions in response to DNA damage. Our combined results suggest that PIG3 is a critical component of the DNA damage response pathway and has a direct role in the transmission of the DNA damage signal from damaged DNA to the intra-S and G2/M checkpoint machinery in human cells.