Comparative transcriptomic analysis reveals candidate genes for seasonal breeding in the male Lion-Head goose.

1. Due to seasonal breeding, geese breeds from Southern China have low egg yield. The genetic makeup underlying performance of local breeds is largely unknown, and few studies have investigated this problem. This study integrated 21 newly generated and 50 publicly existing RNA-seq libraries, representing the hypothalamus, pituitary and testis, to identify candidate genes and importantly related pathways associated with seasonal breeding in male Lion-Head geese.2. In total, 19, 119 and 302 differentially expressed genes (DEGs) were detected in the hypothalamus, pituitary and testis, respectively, of male Lion-Head geese between non-breeding and breeding periods. These genes were significantly involved in the neuropeptide signalling pathway, gland development, neuroactive ligand-receptor interaction, JAK-STAT signalling pathway, cAMP signalling pathway, PI3K-Akt signalling pathway and Foxo signalling pathway.3. By integrating another 50 RNA-seq samples 4, 18 and 40 promising DEGs were confirmed in hypothalamus, pituitary and testis, respectively.4. HOX genes were identified as having important roles in the development of testis between non-breeding and breeding periods of male Lion-Head geese.

[Epidemiological characteristics of pulmonary tuberculosis in Motuo County, Tibet Autonomous Region from 2012 to 2021].

To analyze the epidemiological characteristics of pulmonary tuberculosis (PTB) in Motuo County from 2012 to 2021 and provide evidence for the prevention and control of PTB. A total of 223 cases of PTB were reported from 2012 to 2021 in Motuo County, with an average annual reported incidence rate of 171.39/100 000. Joinpoint regression model analysis showed that the average decline rate was 9.2% (P<0.001) from 2012 to 2021. Among the various types of PTB patients reported from 2012 to 2021, there were 69 cases of etiologic-positive cases which increased from 28.57% to 52.63%. Results from the circular distribution methods showed that there was no obvious peak time of PTB in Motuo County. There was no statistical difference in the average annual incidence of PTB between different genders (χ2=0.108, P=0.743). Among all age groups, the 20-29 years group had the highest proportion (26.91%, 60/223). The Monpa ethnic group (153 cases, 68.61%) had the largest number of cases, followed by the Lhoba people (44 cases, 19.73%) and the Tibetan (22 cases, 9.87%). Farmers (168 cases, 75.34%) had the highest occupational composition ratio, followed by students (40 cases, 17.94%). The main detection methods of PTB were clinical consultation and transferring consultation. Overall, the incidence rate of PTB decreased from 2012 to 2021. The majority of PTB patients were young adults with high transmission risk. It is necessary to pay more attention to the key populations and strengthen the comprehensive prevention and control for reducing the risk of PTB.

[Clinical application of bipolar tweezers-clamp for hepatic parenchymal transection].

Objective: To investigate the clinical value of the bipolar tweezers-clamp for the hepatic parenchymal transection in the resection of hepatocellular carcinoma. Methods: From January 2020 to January 2021,63 patients with the hepatocellular carcinoma for hepatectomy at Department of Hepatopancreatobiliary Surgery,Yuebei People's Hospital Affiliated to Shantou University Medical College were analyzed retrospectively.According to the different instruments used in the hepatic parenchymal transection,the patients were divided into bipolar tweezers-clamp group and ultrasonic scalpel group.There were 32 patients in bipolar tweezers-clamp group,with age of (55.5±10.5)years(range:37 to 78 years),including 22 males and 10 females,tumor size was (6.0±3.4)cm(range:2.4 to 13.4 cm). There were 6 patients with portal vein tumor thrombus and 5 patients with portal hypertension. There were 31 patients in ultrasonic scalpel group,with aged(57.8±10.1)years(range:37 to 79 years),including 27males and 4 females,tumor size was(7.9±5.1)cm(range: 2.4 to 21.3 cm),3 patients with portal vein tumor thrombus and 2 patients with portal hypertension. The preoperative baseline data,operation time,blood loss,postoperative liver function and the complications were compared between two groups using t test,χ2 test and Fisher exact probabilityrespectively. Results: The operation was successfully completed in both groups.Compared with the ultrasonic scalpel group,the operation time was significantly shorter((219.3±76.4)minutes vs.(294.0±100.8)minutes,t=-3.322,P=0.002),the blood loss was less((250(475)ml vs. 500(1 050)ml,t=-2.307,P=0.026),the concentrate red blood cells transfusion volume was less(0.92(0.88)U vs. 2.32(4.00)U,Z=-1.987,P=0.047) in the bipolar tweezers-clamp group.The postoperative serum ALB level was higher in the bipolar tweezers-clamp group than that in the ultrasonic scalpel group((33.5±6.1)g/L vs. (29.5±4.2)g/L,t=3.226,P=0.020) on postoperative day 1;((35.7±4.5)g/L vs.(30.1±3.2)g/L,t=5.575,P<0.01) on postoperative day 3;((33.2±3.7)g/L vs. (31.0±4.4)g/L,t=3.020,P=0.004) on postoperative day 7. There was no significant difference in serum ALT,TBIL and PT level between the two groups(all P>0.05).No postoperative bile leakage occurred in both groups.The postoperative complications occurred in 8 cases(25.0%)in the bipolar tweezers-clamp group,including liver failure in one,and in 11 cases(35.5%)in the ultrasonic scalpel group,including liver failure in two(P>0.05). Conclusion: The bipolar tweezers-clamp is a safe and reliable method for the hepatic parenchymal transaction,which is quick and less bleeding during the hepatic resection.

[MRI associated biomarker analysis for diagnosis of lymph node metastasis in T1-2 stage rectal cancer].

Objective: To explore the diagnostic accuracy improved by magnetic resonance imaging (MRI) biomarkers for lymph node metastasis in T1-2 stage rectal cancer before treatment. Methods: Medical records of 327 patients with T1-2 rectal cancer who underwent pretreatment MRI and rectal tumor resection between January 2015 and November 2019 were retrospectively analyzed. Fifty-seven cases were divided into the lymph node metastasis group (N+ group) while other 270 cases in the non-lymph node metastasis group (N-group) according to the pathologic diagnosis. Two radiologist evaluated the tumor characteristics of MRI images. The relationship of the clinical and imaging characteristics of lymph node metastasis was assessed by using univariate analysis and multivariable logistic regression analysis. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic abilities for the differentiation of N- from N+ tumors. Results: Among the 327 patients, MR-N evaluation was positive in 67 cases, which was statistically different from the pathological diagnosis (P<0.001). The sensitivity, specificity and accuracy of MRI for lymph node metastasis were 45.6%, 84.8% and 78.0%, respectively. Multivariate regression analysis showed that tumor morphology (P=0.002), including mucus or not (P<0.001), and MR-N evaluation (P<0.001) were independent influencing factors for stage T1-2 rectal cancer with lymph node metastasis. The area under the ROC curve of rectal cancer with lymph node metastasis analyzed by the logistic regression model was 0.786 (95%CI: 0.720~0.852). Conclusions: Tumor morphology, including mucus or not, and MR-N evaluation can serve as independent biomarkers for differentiation of N- and N+ tumors. The model combined with these biomarkers facilitates to improve the diagnostic accuracy of lymph node metastasis in T1-2 rectal cancers by using MRI.

Dual roles of misshapen/NIK-related kinase (MINK1) in osteoarthritis subtypes through the activation of TGFß signaling.

OBJECTIVE: To identify the role of misshapen/NIK-related kinase (MINK1) in age-related Osteoarthritis (OA) and injury-induced OA, and the effects of enhanced TGFß signaling in these progresses. DESIGN: The effect of MINK1 was analyzed with MINK1 knock out (Mink1-/-) mice and C57BL/6J mice. OA progress was studied in age-related OA and instability-associated OA (destabilization of the medial meniscus, DMM) models. The murine knee joint was evaluated through histological staining, Osteoarthritis Research Society International (OARSI) scores, immunohistochemistry, and µCT analysis. Primary chondrocytes were isolated from wild type and Mink1-/- mice and subjected to osteogenic induction and Western blot analysis. RESULTS: MINK1 is highly expressed during cartilage development and in normal cartilage. Mink1-/- mice displayed markedly lower OARSI scores, aggrecan degradation neoepitope positive cells and increased Safranin O and pSMAD2 staining in aging-related OA model. However, in injury-induced OA, loss of MINK1 accelerates extracellular matrix (ECM) destruction, osteophyte formation, and subchondral bone sclerosis. Accelerated subchondral bone remodeling in Mink1-/- mice was accompanied with increased numbers of nestin-positive mesenchymal stem cells (MSCs) and osterix-positive osteoprogenitors. pSMAD2 staining was increased in the subchondral bone marrow of Mink1-/- mice and overexpression of MINK1 inhibited SMAD2 phosphorylation in vitro. CONCLUSIONS: This study shows for the first time that activation of TGFß/SMAD2 by MINK1 deficiency plays opposite roles in aging-related and injury-induced OA. MINK1 deficiency protects cartilage from degeneration in aging joints through increased SMAD2 activation in chondrocytes, while accelerating OA progress in injury-induced model through enhanced osteogenesis of MSCs in the subchondral bone. These findings provide insights for developing precision OA therapeutics targeting TGFß/SMAD2 signaling.

The impact of stroke on bone properties and muscle-bone relationship: a systematic review and meta-analysis.

To systematically review available evidence related to the characteristics of bone changes post-stroke and the relationship between various aspects of muscle function (e.g., strength, spasticity) and bone properties after stroke onset. An extensive online database search was undertaken (last search in January 2019). Articles that examined the bone properties in stroke patients were included. The quality of the studies was evaluated with the National Institutes of Health (NIH) Study Quality Assessment Tools. Publication bias of meta-analyses was assessed using the Egger's regression asymmetry test. The selection and evaluation of the articles were conducted by two independent researchers. Fifty-nine studies were identified. In subacute and chronic stroke studies, the skeletal sites in the paretic limbs sustained a more pronounced decline in bone quality than did their counterparts in the non-paretic limbs. The rate of changes showed a decelerating trend as post-stroke duration increased, but the timing of achieving the steady rate differed across skeletal sites. The magnitude of bone changes in the paretic upper limb was more pronounced than the paretic lower limb. There was a strong relationship between muscle strength/mass and bone density/strength index. Muscle spasticity seemed to have a negative impact on bone integrity in the paretic upper limb, but its influence on bone properties in the paretic lower limb was uncertain. Substantial bone changes in the paretic limbs occurred particularly in the first few months after stroke onset. Early intervention, muscle strength training, and long-term management strategies may be important to enhance bone health post-stroke. This review has also revealed the knowledge gaps which should be addressed in future research.

[Comparison of Imaging and Pathologic Findings of Retroperitoneal Dedifferentiated Liposarcoma].

Objective: To investigate the imaging appearance of CT and MRI in retroperitoneal dedifferentiated liposarcoma (DDL) based on pathological findings. Methods: Twelve patients with retroperitoneal DDL (13 lesions) who were surgically and pathologically confirmed were retrospectively collected in the Cancer Hospital of Chinese Academy of Medical Sciences. The correlation of CT and MRI features with histopathologic findings was analyzed. Results: The CT and MRI images of retroperitoneal DDLs were large, heterogeneous soft-tissue masses, mostly lobulated (30.8%, 4/13) or multinodular (46.2%, 6/13), invading adjacent anatomic structures (46.2%, 6/13). The lesions contained different proportions of fatty and non-fatty components, and usually with clear boundaries. The CT images of dedifferentiated components showed non-fatty masses of soft tissue density or mixed density, among which ground-glass nodules may be related to mucinous components. Occasionally calcification or ossification was seen (45.5%, 5/11). The contrast-enhanced CT and MRI images of non-fatty components commonly showed intense heterogeneous enhancement (84.6%, 11/13), central cystic changes and necrosis (61.5%, 8/13), pathologically corresponding to multiple types of soft tissue sarcomas without significant specificity. The well-differentiated components were fatty masses with irregular fibrous septa or soft tissue nodules, which is pathologically corresponding to well differentiated liposarcoma. Lymph node or distant metastasis was rare. Conclusions: The imaging manifestations of retroperitoneal DDLs are diverse and closely related to the proportion and distribution of different components. CT, MRI and contrast-enhanced imaging has a certain diagnostic value for retroperitoneal DDLs.

Analysis of angiogenesis biomarkers for ramucirumab efficacy in patients with metastatic colorectal cancer from RAISE, a global, randomized, double-blind, phase III study.

Background: The phase III RAISE trial (NCT01183780) demonstrated that the vascular endothelial growth factor (VEGF) receptor (VEGFR)-2 binding monoclonal antibody ramucirumab plus 5-fluororuracil, leucovorin, and irinotecan (FOLFIRI) significantly improved overall survival (OS) and progression-free survival (PFS) compared with placebo + FOLFIRI as second-line metastatic colorectal cancer (mCRC) treatment. To identify patients who benefit the most from VEGFR-2 blockade, the RAISE trial design included a prospective and comprehensive biomarker program that assessed the association of biomarkers with ramucirumab efficacy outcomes. Patients and methods: Plasma and tumor tissue collection was mandatory. Overall, 1072 patients were randomized 1 : 1 to the addition of ramucirumab or placebo to FOLFIRI chemotherapy. Patients were then randomized 1 : 2, for the biomarker program, to marker exploratory (ME) and marker confirmatory (MC) groups. Analyses were carried out using exploratory assays to assess the correlations of baseline marker levels [VEGF-C, VEGF-D, sVEGFR-1, sVEGFR-2, sVEGFR-3 (plasma), and VEGFR-2 (tumor tissue)] with clinical outcomes. Cox regression analyses were carried out for each candidate biomarker with stratification factor adjustment. Results: Biomarker results were available from >80% (n = 894) of patients. Analysis of the ME subset determined a VEGF-D level of 115 pg/ml was appropriate for high/low subgroup analyses. Evaluation of the combined ME + MC populations found that the median OS in the ramucirumab + FOLFIRI arm compared with placebo + FOLFIRI showed an improvement of 2.4 months in the high VEGF-D subgroup [13.9 months (95% CI 12.5-15.6) versus 11.5 months (95% CI 10.1-12.4), respectively], and a decrease of 0.5 month in the low VEGF-D subgroup [12.6 months (95% CI 10.7-14.0) versus 13.1 months (95% CI 11.8-17.0), respectively]. PFS results were consistent with OS. No trends were evident with the other antiangiogenic candidate biomarkers. Conclusions: The RAISE biomarker program identified VEGF-D as a potential predictive biomarker for ramucirumab efficacy in second-line mCRC. Development of an assay appropriate for testing in clinical practice is currently ongoing. Clinical trials registration: NCT01183780.

[Comparison of parameters for diffusion-weighted intravoxel incoherent motion imaging in lung cancer patients with different histopathological subtypes].

Objective: To explore the intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) model in lung cancer patients with different histopathological subtypes. Methods: A total of 105 patients were recruited, including 68 cases of adenocarcinoma, 22 cases of squamous carcinoma and 15 cases of small cell carcinoma. All patients underwent magnetic resonance examination consisting of axial IVIM-DWI sequence on a 3.0 T whole body scanner, then the standard ADC (sADC), diffusion coefficient (D), pseudo-diffusion coefficient(D(*)), perfusion fraction (f), distributed diffusion coefficient (DDC) and water diffusion heterogeneity index (α) were calculated for each lesion within the IVIM-DWI model. Results: Mean sADC values were (1.45±0.26) ×10(-3)mm(2)/s, (1.36±0.48) ×10(-3)mm(2)/s and (1.35±0.40) ×10(-3)mm(2)/s for adenocarcinoma, squamous carcinoma and small cell carcinoma, respectively. Mean f values were (59.75±16.37) %, (47.41±18.69) % and (48.96±19.88) % for adenocarcinoma, squamous carcinoma and small cell carcinoma, respectively. Mean α values were 0.72±0.13 for adenocarcinoma, 0.62±0.12 for squamous carcinoma, and 0.63±0.11 for small cell carcinoma, respectively. Statistical analyses indicated that the sADC, f and α values among different histopathological subtypes were significantly different (P<0.05), while there was no significant difference in D, D(*) and DDC values (P>0.05). Furthermore, the comparison showed that the sADC, f and α values of patients with adenocarcinoma were significantly higher than those with squamous carcinoma or small cell carcinoma (P<0.05), whereas there was no significant difference between squamous carcinoma group and small cell carcinoma group (P>0.05). Conclusions: The sADC, f and α values derived from the IVIM-DWI model can be used for comprehensive non-invasive evaluation of diffusion, perfusion and heterogeneity of microenvironment in lung cancer patients. And the IVIM-DWI model may be a promising tool for predicting histopathological subtypes of lung cancer.

[Combined T2-weighted and diffusion-weighted MR imaging for staging of rectal cancers].

Objective: To compare the diagnostic value of T2 weighted imaging (T2WI), diffusion-weighted imaging (DWI), and T2WI+ DWI magnetic resonance imaging (MRI) for staging of rectal cancers for improving the accuracy of tumor staging. Methods: From January 2011 to December 2013, 120 cases of rectal cancers proved by colonoscopy without receiving any anti-tumor treatment were enrolled retrospectively. The MRI data for these patients were divided into three groups, ie., T2WI, DWI and T2WI+ DWI, for evaluating the tumor stages. The results were compared with histopathologic findings. The sensitivity and specificity were calculated and compared with chi-square test. The nodal staging was predicted by using T2WI+ DWI. Results: The accuracy for prediction of tumor staging was 83.3%, 65.0% and 92.5% for T2WI, DWI, and T2WI+ DWI respectively. The specificity for evaluating T1 and T2 stage, and the sensitivity for evaluating T3 by DWI was significantly lower than those using T2WI and T2WI+ DWI in rectal cancers. The sensitivity for evaluation of T2 by DWI was lower than that using T2WI+ DWI (63.0% vs. 88.9%). The sensitivity for evaluation T2 and specificity for T3 by T2WI+ DWI was higher than thouse using T2WI only (88.9% vs. 51.9%, 94.0% vs. 72.0%). The accuracy for prediction of nodal staging by using T2WI+ DWI was 62.1% (72/116). Conclusions: T2WI is the key sequence for staging of rectal cancers. Although the diagnostic accuracy was not good by using DWI alone, the combination of T2WI and DWI can improve the accuracy significantly for tumor staging in rectal cancers, whereas the nodal staging was still a hard task for radiologists.

[Texture analysis based on contrast-enhanced MRI can predict treatment response to neoadjuvant chemotherapy of breast cancer].

Objective: To investigate whether texture analysis based on contrast-enhanced MRI can predict pathological complete response of locally advanced breast cancer undergoing neoadjuvant chemotherapy(NAC). Methods: Forty-seven patients with breast cancer undergone neoadjuvant chemotherapy from January 2015 to February 2016 were divided into pathological complete response (pCR) group or non-pathological complete response (non-pCR) group based on surgical pathology. Their parameters of texture analysis based on MRI before neoadjuvant chemotherapy and after 2 cycles of treatment were analyzed. Parameters(Energy, Entropy, Inertia, Correlation, Inverse Difference Moment)before and after 2 cycles of NAC between pCR and non-pCR groups were compared using Student t or Wilcoxon rank sum test. The diagnostic performance of different parameters was judged by the receiver-operating characteristic (ROC) curve analysis. Results: The post-NAC value was significantly different from that of pre-NAC (all P<0.05). Pre-treatment parameters (Energy, Entropy, Inertia, Correlation, Inverse Difference Moment) were 78.58×10(-5)(55.64×10(-5), 135.23×10(-5)), 10.06 ± 1.02, 7 993.91±2 428.10, (4.76±0.99) ×10(-5) and (18.10±4.13) ×10(-3) in pCR group, and 76.84×10(-5) (48.68×10(-5), 154.15×10(-5)), 10.28±1.26, 7 184.77 (4 938.03, 9 974.04), (5.21±2.01) ×10(-5) and (17.68±5.87) ×10(-3) in non-pCR group. No significant difference was found between both groups. (P>0.05 for all). At the end of the second cycle of NAC, parameters(Energy, Entropy, Inertia, Correlation, Inverse Difference Moment) were (542.11±361.04) ×10(-5,) 7.95±1.28, 16 765.08±97 06.56, (0.43±0.07) ×10(-5,) and (12.18±9.82) ×10(-3) in pCR group, and 133.00×10(-5) (79.80×10(-5,) 239.00×10(-5)), 9.29±1.46, 7 916.64(6 418.89, 10 934.40), (0.38±0.08) ×10(-5) and (14.80±5.06) ×10(-3) in non-pCR group. At the end of the second cycle of NAC, there was significant difference in the parameters (Energy, Entropy, Inertia, Correlation) and Δparameters (ΔEnergy, ΔEntropy, ΔInertia, ΔInverse Difference Moment) between both groups (P<0.05 for all). The area under curve (AUC) of post-treatment ΔEntropy was 0.81, which was the largest one among parameters. Sensitivity of ΔEntropy for predicting pCR was 75.0% and specificity was 85.7%, respectively. Conclusion: Texture analysis based on dynamic contrast-enhanced MRI can predict early treatment response in primary breast cancer.

[The quantitative analysis of MR dynamic contrast-enhangced imaging on efficacy and prognosis of transcatheter arterial chemoembolization on hepatocellular carcinoma].

Objective: To investigate the prognostic value of quantitative parameters of dynamic contrast-enhangced MR (DCE-MR) on short-term efficacy of transcatheter arterial chemoembolization (TACE) on hepatocellular carcinoma(HCC). Methods: 79 patients with HCC underwent non-enhanced MR imaging and DCE on a 3.0T MR scanner before and one month after TACE. The quantitative parameters were measured on the maximal tumor region, including maximal tumor diameter(MTD), ADC, K(trans,) K(ep) and V(e) value before and after TACE. All patients were divided into stable group (36 patients) and progressive group (43 patients) based on follow-up. The quantitative data of the two groups before and after TACE was collected for analysis. Results: Among the 79 lesions in 79 patients, 21 were located in the left lobe of the liver, 53 in the right lobe of the liver and 5 in the junction area of the hepatic lobe. The maximum tumor diameter (MTD) was 2.2-9.9 cm, the median MTD was 5.1 cm. There were significant differences between progressive group and the stable group in MTD, K(trans,) K(ep) values of the tumor before TACE (P<0.05). One month after TACE, the MTD, K(trans,) K(ep,)ΔMTD, ΔK(trans) and ΔK(ep) values of the tumor in progressive group were statistically different with the stable group (P<0.05, respectively). For all the patients, the pre-TACE MTD, AFP, K(trans) and K(ep) values of tumors were statistically different with the post-TACE values (P<0.05). Conclusion: The quantitative parameters (K(trans,) K(ep,)ΔK(trans) and ΔK(ep) values) of the DCE-MR could predict and evaluate the short-term efficacy of TACE on HCC.

[Measurement reproducibility of parameters derived from introvoxel incoherent motion diffusion-weighted MRI imaging of rectal cancer].

Objective: To study the measurement reproducibility of parameters derived from introvoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI)-MRI of rectal cancer between- and within- radiologists. Methods: Clinical data of 34 patients with rectal cancer were prospective analyzed. Conventional MRI sequences, IVIM DWI-MRI with sixteen b values and dynamic contrast enhancement (DCE)-MRI sequences of rectum were acquired by GE 3.0-T MRI imager. The IVIM sequence images with b value=1000 sec/mm(2) were selected to measure the maximum axial section of tumor by a radiologist with 15 year-experiences in gastrointestinal cancer imaging.Two radiologists (radiologist 1 and radiologist 2 with 2 and 10 years of experience in gastrointestinal cancer imaging, respectively) independently draw a freehand region of interest (ROI) that contained the largest available tumor area on the selected section. Monoexponential apparent diffusion coefficient (ADC) and biexponential IVIM metrics maps and IVIM parameters were generated automatically by the software. The repeated measurement was performed at an interval of one week. The average values of each measurement were used for statistical analysis. ADC values and IVIM parameters obtained between- and within- radiologists were analyzed by Wilcoxon signed-rank test. Intraclass correlation coefficients (ICC) and Bland-Altaman plots were used to analyze the parameter reproducibility of two measurements between- and within- radiologists. Results: The first and second measured ADC (×10(-3)mm(2)/s), true diffusivity (D, ×10(-3)mm(2)/s), false diffusivity (D(*,) mm(2)/s) and perfusion fraction (f, %) by radiologist 1 were 0.997, 0.692, 0.043, 34.6 and 0.993, 0.691, 0.038, 32.8, respectively. The first and second measured ADC (×10(-3)mm(2)/s), D (×10(-3)mm(2)/s), D(*) (mm(2)/s), f (%) by radiologist 2 were 0.987, 0.651, 0.046, 32.8 and 0.996, 0.689、0.041, 32.7, respectively. No statistically significant differences were observed in ADC and IVIM parameters obtained between- and within- radiologists (P>0.05). The ADC values and the f values of two times were significantly correlated between- and within- radiologists. The D values were significantly correlated within a radiologist, and the correlation of D(*) values within a radiologist was significantly higher than that between radiologists. The 95% limits of agreement (LoA) of ADC values and f values were smaller than those of D values and D(*) values between- and within- radiologists. The 95% LoA of ADC values was the least, while that of D(*) values varied most.The 95% LoA of f values and D values kept steady within a radiologist, and 95% LoA of f values was slightly smaller than that of D values. The 95% LoA of IVIM parameters (ADC, D, f, D(*) values) within radiologists 2 were better than those within radiologist 1. Conclusions: The reproducibilities of ADC and f values are the best, while the reproducibility of D(*) values is relatively poorer in rectal cancer. Measurement reproducibility of parameters derived from IVIM may be improved by increasing radiologists' experiences in drawing ROI.

[Importance of segmental lymph nodes in the pathological staging of non-small cell lung cancer].

Objective: To explore the role of the segmental lymph node dissection in the pathologic staging of non-small cell lung cancer. Methods: A total of 370 consecutive non-small cell lung cancer patients who underwent radical resection between August 2008 and July 2016 were retrospectively reviewed. All the operations were performed by the same group of surgeons. The relationship of the segmental lymph nodes with pathological stages after radical resection was analyzed in order to explore the role of the lymph node dissection in the pathologic staging of non-small cell lung cancer (using the 7th edition of the American Joint Committee on Cancer and Union for International Cancer Control TNM classification for lung cancer ). Results: The detection rates of hilar nodes, interlobar nodes, lobar nodes and segmental nodes were 69.7%, 86.8%, 84.0%, 67.0%, respectively. The metastasis rates of hilar nodes, interlobar nodes, lobar nodes and segmental nodes were 6.5%, 10.8%, 15.7% and 10.3%, respectively. There were 238 cases of N0 disease, 62 cases of N1 disease, 69 cases of N2 disease and 1 case of N3 disease. If the analysis of segmental lymph nodes had been omitted, 16 patients (25.8% of N1 disease) would have been down-staged to N0, and 5 cases of multiple-station N1 disease would have been misdiagnosed as single-station N1 disease, 2 patients would have been misdiagnosed as N2 disease with skip metastases. Conclusion: Segmental nodes play an important role in the accurate staging of non-small cell lung cancer.

[Predictive value of cardiac magnetic resonance-derived parameters on the improvement of left ventricular function in patients with acute viral myocarditis].

Objective: To evaluate the predictive value of cardiac magnetic resonance (CMR)-derived parameters on the improvement of left ventricular function in patients with acute viral myocarditis. Methods: Forty patients, who referred for acute viral myocarditis in our hospital from September 2011 to September 2015, were prospectively enrolled in this study.All patients were examined by CMR during hospitalization for acute viral myocarditis (baseline) and after 12 months.The CMR sequences include: two dimension steady state free precession, 2D SSFP; triple inversion recovery, triple IR; early gadolinium enhancement; phase sensitive inversion recovery turbo field echo, PSIR TFE. Results: Thirty out of 40 patients with susceptive acute viral myocarditis met the CMR criteria of acute viral myocarditis (Lake Louise Criteria) (LL+ ) and the other 10 patients did not meet the diagnostic criteria (LL-). Left ventricular ejection fraction (LVEF) values were significantly lower in LL+ group than in LL- group at baseline and at 12 months after discharge (P<0.01 or 0.05, respectively). The baseline left ventricular end-systolic volume index (LVESVI) was significantly higher in LL+ group than in LL- group (P<0.05) and was similar between the groups at 12 months follow up.Left ventricular end-diastolic volume index (LVEDVI )was similar between the two groups at baseline and at 12 months follow up.LVEF was significantly higher during 12 months follow up compared to baseline in LL+ group and remained unchanged in LL- group during the two time points.LVESVI and LVEDVI remained unchanged at baseline and during 12 months follow up both in LL+ and LL- groups (P>0.05). Results showed that LL+ , edema ratio (ER) positive and global relative enhancement (gRE) positive were associated with significant increase of LVEF at 12 months follow up.However, LL-, ER negative, gRE negative, late gadolinium enhancement(LGE) negative and LGE positive linked with unchanged LVEF at 12 months follow up (P>0.05). Patients were further divided into LVEF increase (ΔLVEF≥5%) group and non LVEF increase group (ΔLVEF<5%), the results of Chi-square test showed that LL+ and ER positive were related to the improvement of LVEF (P<0.05), while gRE and LGE were not associated with improvement of cardiac function (P>0.05). Multiple linear regression analysis, using ER, gRE and LGE as independent variables and LVEF as dependent variables, showed that the presence of myocardial edema was the strongest independent predictor of an increase in LVEF at follow up (full model: non-standardized coefficient 0.445, P=0.043; reduced model: non-standardized coefficient 0.442, P=0.12). Conclusion: Cardiac magnetic resonance imaging monitoring is valuable to observe the cardiac function and morphology changes in patients with acute viral myocarditis, and myocardial edema imaging is the most powerful parameter to predict the improvement of LVEF in this patient cohort.

Using local multiplicity to improve effect estimation from a hypothesis-generating pharmacogenetics study.

We propose a multiple estimation adjustment (MEA) method to correct effect overestimation due to selection bias from a hypothesis-generating study (HGS) in pharmacogenetics. MEA uses a hierarchical Bayesian approach to model individual effect estimates from maximal likelihood estimation (MLE) in a region jointly and shrinks them toward the regional effect. Unlike many methods that model a fixed selection scheme, MEA capitalizes on local multiplicity independent of selection. We compared mean square errors (MSEs) in simulated HGSs from naive MLE, MEA and a conditional likelihood adjustment (CLA) method that model threshold selection bias. We observed that MEA effectively reduced MSE from MLE on null effects with or without selection, and had a clear advantage over CLA on extreme MLE estimates from null effects under lenient threshold selection in small samples, which are common among 'top' associations from a pharmacogenetics HGS.

Rapid and sensitive LC-MS/MS method for the determination of auraptene in rat plasma and its application in a pharmacokinetic and bioavailability study in rats.

A simple, sensitive and specific liquid chromatography-tandem mass spectrometry method was developed and validated for the determination of auraptene, a constituent isolated from Fructus aurantii with potential to combat Alzheimer's disease, in rat plasma. Rat plasma samples were pretreated by protein precipitation with methanol. The analytes were separated by a Waters Sun Fire C18 column (50 mm x 2 mm, 5 µm) and eluted with 1:1000 methanol and formic acid/water (v/v) mobile phase with a flow rate of 0.5 mL/min. Multiple reaction monitoring was used to monitor the transition of the deprotonated auraptene molecule with an m/z of 299.3 [M+H](+), to the product ion with an m/z of 162.9 [M+H](+). Progesterone, with an m/z of 315.2→ 96.9 was used as an internal standard. The limits of detection and of quantification of auraptene in the rat plasma were 1 and 5 ng/mL, respectively. The method was linear in the concentration range of 20- 2000 ng/mL with coefficient correlation of 0.9956. After auraptene (100 mg/kg, p.o.) administration, the maximum plasma concentration and the time taken to reach maximum concentration were 1719.5 ± 384.3 g/mL and 108.0 ± 25.3 min, respectively. The elimination half-life was 108.0 ± 25.3 for auraptene (100 mg/kg, p.o.) and 3.0 ± 0 min for auraptene (2 mg/kg, i.v.). The oral bioavailability was about 8.5%.

Cinnamon effectively inhibits the activity of leukemia stem cells.

Cinnamon is the main component of Sanyangxuedai, which is one of the effective traditional Chinese medicines for treating malignancies. Leukemia is a prevalent malignant disease that Sanyangxuedai has been used to treat. Although successful in several studies, there is a lack of solid evidence as to why Sanyangxuedai has an effect on leukemia, and little is known about the underlying mechanisms. In this study, the active ingredients of cinnamon were isolated, purified, and identified. The transwell transport pool formed with the Caco-2 cell model was used to filter the active ingredients of cinnamon by simulating the gastrointestinal barrier in vitro. Moreover, the cell morphology, cell cycle status, apoptosis status, and antigenic variation of the cell surface antigens were observed and measured in K562 cells after treatment with the active ingredients of cinnamon. Our results showed that 50-75 µM was a safe concentration of cinnamon extract for treatment of K562 cells for 72 h. The cinnamon extract caused growth inhibition of K562 cells. Cinnamon extract seemed to arrest the cells at the G1 stage and increased the apoptosis rate significantly. Interestingly, cinnamon extract treatment upregulated the expression of erythroid and myeloid differentiation antigens and downregulated that of the megakaryocytic differentiation antigens in a dose-dependent manner. Our findings indicate that cinnamon extract from Sanyangxuedai may be effective for treating leukemia.

[Value of diffusion-weighted magnetic resonance imaging in prediction of the response to preoperative chemoradiotherapy in rectal carcinoma].

OBJECTIVE: To investigate the value of diffusion weighted imaging (DWI) in predicting the efficacy of preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer. METHODS: From 2007 to 2012, 86 patients with histopathologicaIly proven rectal cancer who underent pre-CRT were enrolled in this study prospectively. Diffusion-weighted MRl was performed in all patients before pre-CRT, while it was performed in part of the patients during and after pre-CRT as well.ADC values of the tumors were calculated on the workstation. Patients were assigned to the tumor downstaged group or the tumor nondownstaged group on the basis of T staging. The change in ADC following treatment and the difference in ADC between groups were analyzed. RESULTS: Of the 86 patients after surgery, 20 were diagnosed with T0, 2 with T1, 17 with T2, 44 with T3 and 3 with T4. 39 patients were classified as the downstaged group, of which 18 were of pCR. The remaining 47 patients were classified as the nondownstaged group. Of the total of 86 patients, the mean ADC values before, during, and after pre-CRT (pre-ADC, during-ADC, and post-ADC) were (1.03±0.17)×10(-3), (1.39±0.28)×10(-3), and (1.61±0.27)×10(-3) mm(2)/s and there was a significant difference (P<0.001). However, the pre-CRT ADC of the downstaged group did not differ significantly from that of the nondownstaged group (P=0.615). Of the 43 patients who underwent MRI before, during and after pre-CRT, the mean ADC values were (1.05±0.16)×10(-3), (1.39±0.29)×10(-3)and (1.67±0.30)×10(-3) mm(2)/s, respectively, showing a significant difference (P<0.001)as well. CONCLUSIONS: The mean ADC value of rectal cancer is gradually increasing along with the course of chemotherapy. Pre-ADC is not a good parameter to be used to predict the efficacy of pre-CRT for locally advanced rectal cancer.

[Application of diffusion-weighted intravoxel incoherent motion imaging in diagnosis of renal cell carcinoma subtypes].

OBJECTIVE: To evaluate the value of parameters derived from intravoxel incoherent motion diffusion-weighted magnetic resonance imaging in differentiating histopathological subtypes of renal cell carcinoma (RCC). METHODS: Between May 2014 and December 2015, a total of 69 patients who were surgically and pathologically diagnosed as renal cell carcinoma were recruited for the study. We examined 61 clear cell RCC (ccRCC), and 8 non-clear cell carcinoma (non-ccRCC, including 7 chromophobe RCC and 1 papillary RCC). All the ccRCC were divided into well differentiated group (n=46), moderately differentiated group (n=8), and poorly differentiated group (n=7). In addition to routine renal magnetic resonance imaging examination performed on a 3.0-Tesla MR system, all patients were imaged with axial intravoxel incoherent motion diffusion-weighted imaging. Using biexponential model, we calculated the diffusion coefficient (D), pseudodiffusion coefficient (D(*)), and perfusion fraction (f). RESULTS: The D and f values of the ccRCC were higher (each P<0.05) than that for non-ccRCC [D (1.29±0.30)×10(-3)mm(2)/s, D(*) (42.92±20.21)×10(-3)mm(2)/s, and f (35.71±6.61)% versus D (0.78±0.23)×10(-3)mm(2)/s, D(*) (32.60±11.33)×10(-3)mm(2)/s, and f (21.52±8.44)% ]. In the well differentiated group of ccRCC, we found D of (1.36±0.29)×10(-3)mm(2)/s, D(*) (38.39±18.51)×10(-3)mm(2)/s, and f (36.40±6.96)%. The D, D(*,) f values of moderately differentiated lesions were (1.10±0.24)×10(-3)mm(2)/s, (59.90±20.23)×10(-3) mm(2)/s, and (32.88±4.02)%, respectively, those of the poorly differentiated group were (1.03±0.16)×10(-3)mm(2)/s, (53.28±18.74)×10(-3)mm(2)/s, and (34.42±6.21)%. The well differentiated group of ccRCC showed a higher D value than the moderately differentiated and poorly differentiated groups (each P<0.05). D(*) values were significantly lower for the well differentiated group than for the moderately differentiated group (P<0.05). The sensitivity and specificity of D values were 90.2% and 87.5% when focusing on the differentiation of ccRCC. For the diagnosis of ccRCC, the sensitivity and specificity of f values were 98.4% and 75.0%, respectively. CONCLUSIONS: IVIM-DWI can provide certain reliable value in evaluating pathological subtype and differentiation degree of renal cell carcinomas. D and f values are useful to distinguish ccRCC from non-ccRCC. D value is also promising for estimating the differentiation degree of ccRCC, and to indicate the biological behavior of RCC.