Integrating genomics and transcriptomics to identify candidate genes for high-altitude adaptation and egg production in Nixi chicken.

1. This study combined genome-wide selection signal analysis with RNA-sequencing to identify candidate genes associated with high altitude adaptation and egg production performance in Nixi chickens (NXC).2. Based on the whole-genome data from 20 NXC (♂:10; ♀:10), the population selection signal was analysed by sliding window analysis. The selected genes were screened by combination with the population differentiation statistic (FST). The sequence diversity statistic (θπ). RNA-seq was performed on the ovarian tissues of NXC (n = 6) and Lohmann laying hens (n = 6) to analyse the differentially expressed genes (DEGs) between the two groups. The functional enrichment analysis of the selected genes and differentially expressed genes was performed.3. There were 742 genes under strong positive selection and 509 differentially expressed genes screened in NXC. Integrated analysis of the genome and transcriptome revealing 26 overlapping genes. The candidate genes for adaptation to a high-altitude environment, as well as for egg production, disease resistance, vision and pigmentation in NXC were preliminarily screened.4. The results provided theoretical guidance for further research on the genetic resource protection and utilisation of NXC.

[A multicenter cross-sectional study of quality of life and nonsurgical treatment in patients with knee osteoarthritis].

Objective: To explore the influencing factors of health-related quality of life (HRQoL) in patients with knee osteoarthritis, and to analyze the non-surgical treatment of knee osteoarthritis. Methods: Demographic variables, treatment modalities, imaging data, and 12-item short form health survey (SF-12) scores of patients with knee osteoarthritis in orthopedic outpatient departments of five hospitals in Beijing from December 2017 to November 2018 were collected to analyze influencing factors of HRQoL and non-surgical treatment. Results: A total of 2 034 patients were included. There were 530 males (26.1%) and 1 504 females (73.9%), with a mean age of (59.17±10.22) years. In terms of physical quality of life, female patients with knee osteoarthritis had lower physical components summary (PCS) compared with male patients (ß=-0.521, P=0.036); patients aged ≥64 years had lower PCS than those aged<55 years (ß=-0.636, P=0.026). Patients with an education of more than 12 years had higher PCS than those with less than 10 years (ß=1.063, P<0.001). Compared to patients with mild clinical symptoms, the PCS of patients with moderate clinical symptoms was lower (ß=-0.860, P=0.002), while the PCS of those with severe clinical symptoms was much lower (ß=-1.126, P<0.001). Patients treated with combination therapy had higher PCS than untreated patients (ß=0.731, P=0.005). In terms of mental quality of life, compared to patients engaged in sedentary work, the mental components summary (MCS) of patients engaged in mild manual labor jobs was lower (ß=-0.712, P=0.015); Compared to patients with a Charson comorbidity index of 0, patients with a Charlson comorbidity index ≥ 2 had lower MCS (ß=-1.183, P=0.007). In the past 12 months, 648 (31.9%), 143 (7.0%), 406 (20.0%), 680 (33.4%), 343 (16.9%), 681 (33.5%), 170 (8.4%) patients had used non-steroid anti-inflammatory drugs (NSAIDs), acetaminophen, glucosamine/chondroitin formulations, physical therapy, articular cavity puncture injection, traditional Chinese medicine treatment and exercise therapy, respectively. Total of 451 patients (22.2%) received monotherapy and 889 patients (43.7%) received combination therapy. Conclusions: The major non-surgical treatment methods for patients with knee osteoarthritis in Beijing are NSAIDs, physiotherapy and traditional Chinese medicine. Combination therapy is used more frequently than monotherapy. Physical quality of life is related to gender, age, education, severity of symptoms and treatment, while mental quality of life is related to occupational labor and comorbidities.

Whole-genome resequencing of Dulong Chicken reveal signatures of selection.

1. Dulong Chickens (DLCs) live at high altitude (~3000 m) and humidity (~90%), are endemic to the Yunnan province, and have gradually developed unique physiological characteristics, but their genetic basis is still unclear. Using the fixation index (FST ) approach, based on whole-genome resequencing, DLCs were analysed to uncover the genomic architecture of the population and candidate genes involved in selection during domestication. 2. A total of 469 candidate genes were obtained to be putatively under selection in DLCs. Further investigations revealed the genic footprint for local adaptation (high-altitude and high-humidity) as the genic signatures that are involved in economic traits (related to egg production). 3. Candidate genes were identified that may be associated with disease resistance, aggressiveness, small body size and positive selection of vision in DLCs. 4. These data revealed loci of selective signals that operate during selection for production at high altitude and humidity.

[Application value of diffusion-weighted imaging signal pattern in the qualitative diagnosis of renal lesions with T(2)WI hypointensity].

Objective: To analyze the diagnostic value of diffusion-weighted imaging (DWI) signal pattern in renal lesions with T(2)WI hypointensity. Methods: Retrospective analysis was performed on DWI imaging datasets of 135 renal lesions with hypointentsity on T(2)WI confirmed by surgery, biopsy, or follow-up in the First Medical Center of Chinese PLA General Hospital from February 2016 to February 2017.One hundred and thirty-five renal lesions,43 benign lesions(age from 28 to 70 years,mean age was 43.5 years, male 18 lesions and female 25 lesions) and 92 malignant lesions (age from 17 to 86 years, mean age was 54.1 years, male 62 lesions and female 30 lesions). DWI signal pattern was classified into six categories: homogeneously high signal, homogeneously low signal, heterogeneously high signal, high halo signal, high halo and nodular signal, and high nodular signal. The agreement between two observers were tested using kappa statistic. The statistical difference between DWI signal characteristics in benign and malignant lesions was analyzed with Chi-Square test. Diagnostic efficacy in differentiation of benign and malignant renal lesions using DWI signal pattern were calculated. Results: One hundred and thirty-five lesions were detected in 135 cases with T(2)WI hypointensity. There were 43 benign lesions and 92 malignant lesions. The agreement between two observers was very good (kappa value=0.878 6). In renal T(2)WI hypointensity lesions, the proportion of DWI homogeneous high signal, homogeneous low signal, heterogeneous high signal, high halo signal, high halo and nodular signal, high nodular signal was 4.7% (2/43), 25.6% (11/43), 30.2% (13/43), 18.6% (8/43), 11.6% (5/43), 9.3% (4/43), respectively. The proportion of malignant lesions was 10.9% (10/92), 0 (0/92), 17.4% (16/92), 13.0% (12/92), 56.5% (52/92) and 2.2% (2/92), respectively. The difference of high halo and nodules signal and homogeneous low signal was statistically significant (all P<0.01). The sensitivity, specificity, positive prediction value (PPV) and negative prediction value (NPV) of high halo and nodular signal for malignancy were 56.5% (52/92), 88.4%(38/43), 91.2% (52/57) and 48.7%(38/78), respectively and homogeneous low signal for benign lesions were 25.6% (11/43), 100.0% (92/92), 100.0% (11/11) and 74.2% (92/124), respectively. Conclusions: DWI signal features may facilitated the accurate diagnosis of renal lesions with T(2)WI hypointensity. Malignant lesions exhibit a higher propensity with high halo and nodular signal on DWI while benign lesions with homogeneous low signal.

[Application of multimode MRI in prediction of nuclear grade of clear cell renal cell carcinoma].

Objective: To investigate the predictive value of multimode MRI features for nuclear grade of clear cell renal cell carcinoma (ccRCC). Methods: From January 2016 to October 2017, 381 patients (387 tumors) with ccRCC proven by pathology in Chinese PLA General Hospital First Medical Center were enrolled (male 293, female 88, age 24-87 years old). The clinical and imaging data of these patients were retrospectively analyzed, including clinical information (gender, age, BMI, smoke, hypertension) and preoperative renal MRI. Pre-and post-contrast MRI features were subjectively scored. The largest diameter of each lesion was measured. Two-sample t-test,Chi-squared test and binuary Logistic regression analysis were used to evaluate the predictive efficacy of clinical and MRI data. Results: According to WHO/ISUP nuclear grade system,all ccRCCs (n=387) were divided into low grade (n=322) and high grade group (n=65). Between two groups, there were significant differences in age and diameter((54±12) vs (59±10) years old, P=0.001; (4.1±2.2) vs (6.2±3.0) cm, P<0.01). In MRI scores,there were significant differences in scores of pseudocapsule, shape and margin,hemorrhage,enhancement degree,cystic-solid,intratumoral vessel,peritumoral vessel, renal sinus invasion, vein thrombosis, lymphadenopathy, necrosis, perinephric invasion and metastasis, DWI signal intensity between high grade group and low grade group (all P<0.01). Binuary Logistic regression analysis showed that shape and margin, enhancement degree and DWI signal intensity were independent predictors for high grade ccRCC (OR=0.181, 95%CI 0.049-0.666; OR=0.393, 95%CI 0.182-0.846; OR=0.336, 95%CI 0.155-0.728). A nomogram model for predicting the risk of high grade ccRCC was constructed. Conclusions: Multimode MRI features can differentiate low grade and high grade ccRCC. The nomogram developed in this study might aid urologist in the pre-operative prediction of nuclear grade of ccRCC,which might contribute to developing treatment strategy.

[Microbiology analysis of periprothetic joint infection post total hip and knee arthroplasty of 9 centers in Beijing between 2014 and 2016].

Objective: To investigate the microbiological test, antibiotic sensitivity and surgical treatment of periprosthetic joint infection(PJI) cases in post total hip arthroplasty (THA) and total knee arthroplasty (TKA) patients. Methods: A retrospective cross-sectional survey was conducted on 318 patients who underwent THA or TKA in 9 clinical centers in Beijing from January 2014 to December 2016.The data of microbiology, antibiotic sensitivity and surgical treatment were collected.The average age of patients was (62.3±13.1) years old (range: 21-86 years old), including 145 males and 173 females.The body mass index was (25.6±3.8) kg/m (2) (range: 15.6-38.1 kg/m(2)). Results: In total, 318 patients had microorganisms detected by periprosthetic tissue culture or synovial fluid culture, 209 cases (65.7%) had Gram-positive bacteria, 29 cases (9.1%) had Gram-negative bacteria, 10 cases (3.1%) had fungi, 3 cases (0.9%) had non-tuberculous mycobacteria, 72 cases (22.6%) were negative, 69 cases (21.7%) had methicillin-resistant bacteria. The antibiotic sensitivity results showed that the overall resistance rate of penicillin, cefuroxime, amoxicillin+clavulanic acid was 79.9%, 69.9%, and 68.1%, respectively; meropenem, vancomycin, and linezolid resistance rate was 0. For the treatment methods of hip and knee PJI, two-stage revision surgery acounted for 72.9% (108/148) and 64.1% (109/170), respectively. One-stage revision surgery accounted for 21.6% (32/148) and 7.6% (13/170), and open debridement surgery accounted for 4.7%(7/148) and 26.4% (45/170). Conclusions: Gram-positive bacteria was still the main pathogen of PJI.The methicillin-resistant bacteria and rare bacteria should be payed attention to. The Majority of hip and knee PJI cases were treated by two-stage revision surgery.

Chronic sun exposure is associated with distinct histone acetylation changes in human skin.

BACKGROUND: Photoageing is attributed to continuous sunlight or artificial ultraviolet exposure and manifests as clinical and histological changes in skin. Epigenetic changes have been found to be involved in the pathogenesis of photoageing. However, the underlying mechanisms are unclear. OBJECTIVES: To analyse histone modification patterns in sun-exposed and nonexposed skin, and to identify the abnormally histone-modified genes related to photoageing. METHODS: Skin biopsies were collected from both the outer forearm (sun-exposed area) and the buttock (sun-protected area) in 20 healthy middle-aged female volunteers. Global histone H3/H4 acetylation and H3K4/H3K9 methylation statuses were assessed by enzyme-linked immunosorbent assay. Expression levels of histone acetyltransferases and histone deacetylases were measured by reverse-transcriptase quantitative polymerase chain reaction (qPCR) and Western blot. Chromatin immunoprecipitation combined with DNA microarray (ChIP-chip) assay with anti-acetyl-histone H3 antibody in a sun-exposed pool (combining six sun-exposed skin samples) and a nonexposed pool (combining six nonexposed skin samples) was conducted to explore the abnormally acetylated histone H3 genes related to photoageing; ChIP-qPCR was then used to verify the results of ChIP-chip. RESULTS: We observed higher global histone H3 acetylation levels increased EP300 and decreased HDAC1 and SIRT1 expression in sun-exposed skin compared with matched nonexposed skin. Furthermore, the ChIP-chip assay showed that 227 genes displayed significant hyperacetylation of histone H3, and 81 genes displayed significant hypoacetylation of histone H3 between the two groups. Histone H3 acetylation levels on the promoters of PDCD5, ITIH5, MMP1 and AHR were positively correlated with the mRNA expression of the corresponding gene. CONCLUSIONS: Chronic sun exposure-induced histone H3 hyperacetylation may play a critical role in the pathogenesis of skin photoageing.

The challenge of diagnosing seborrheic keratosis by reflectance confocal microscopy.

BACKGROUND: Seborrheic keratosis (SK) is one of the most common skin tumors seen by dermatologists. It should be differentiated with many diseases, especially skin tumors. Reflectance confocal microscopy (RCM) has been applied for evaluation of SK. There are a few studies that describe the RCM of SK. The aim of the study was to find the challenge of diagnosing seborrheic keratosis by reflectance confocal microscopy. METHODS: A total of 390 patients with a clinical suspicious diagnosis of seborrheic keratosis were enrolled in this study, and lesions from each patient were imaged with RCM. Thirty-seven of these patients performed a biopsy in order to be given a histological diagnosis. We retrospectively analyzed the outcomes of RCM diagnosis and histological diagnosis, and then found the RCM characteristics of biopsy-proven lesions. RESULTS: According to RCM images, 258 of 390 (66.2%) patients were diagnosed with SK, 97 of 390 (24.9%) patients could not be diagnosed by the dermatologist according to RCM. Of all 37 biopsied lesions, 23 were SK, 6 were actinic keratosis, 2 were basal cell carcinoma, and 2 were squamous cell carcinoma. CONCLUSION: It is challenge to diagnose seborrheic keratosis by reflectance confocal microscopy. It may due to the variable clinical and RCM appearances of SK, and limited depth of RCM.

[Magnetic resonance imaging findings and differential diagnosis of renal epithelioid angiomyolipoma comparing with renal no-epithelioid angiomyolipoma].

Objective: To investigate whether MRI findings can differentiate renal epithelioid angiomyolipoma (EAML) from renal no-epithelioid (typical) angiomyolipoma. Methods: A total of 44 patients were collected from General Hospital of PLA.These cases were obtained from January 2009 to June 2015.To retrospectively analyze these mainly MRI findings among 12 cases of EAML (age from 27 to 61 years, male 2 cases, female 10 cases, mean age was 46.7 years); 32 cases of renal no-epithelioid AML (age from 34 to 70 years old, male 9 cases, female 23 cases, mean age was 53.4 years old) as case control study. MRI findings included gender, T(2)WI, the signal on gross fat, pseudocapsle, necrosis or cystic degeneration, DWI, hemorrhage and the peak in three phases of dynamic enhancement.All data were analyzed statistically using SPSS version 19.0 (IBM, Armonk, NY, USA). χ(2) test and a single order chart were used to analyze the enumeration data. Results: Comparing with renal no-epithelioid angiomyolipoma, minimal fat, necrosis or cystic degeneration and hemorrhage were statistical significance. P values were 0.002, 0.007, 0.025, respectively.Gender, solid components of tumors on T(2)WI, the signal of DWI, pesudocapsule and the peak of enhancement had no statistical significance. P values were 0.863, 0.053, 0.479, 0.460, respectively. Conclusion: Comparing with renal no-epithelioid AML, necrosis or cystic degeneration and hemorrhage with minimal fat are characteristic MRI findings of EAML.

INSR gene polymorphisms correlate with sensitivity to platinum-based chemotherapy and prognosis in patients with epithelial ovarian cancer.

This study aimed to investigate the correlation between INSR gene polymorphisms on platinum-based chemotherapy sensitivity and prognosis in epithelial ovarian cancer (EOC). A total of 339 EOC patients receiving postoperative chemotherapy were recruited for the study. Tag single-nucleotide polymorphism of INSR gene was screened from HapMap combined with available literature. Frequency distribution of genotypes and alleles in INSR gene was sequenced by ABI3100-Avant. Compared with CC+GC genotype, INSR rs2252673 GG genotype and rs3745546 CC genotype showed less platinum-based chemotherapy sensitivity in EOC patients (odds ratio (OR)=0.269, 95% confidence interval (CI)=0.159~0.456; OR=0.445, 95% CI=0.214~0.926, respectively), as well as serous EOC patients (OR=0.083, 95% CI=0.024~0.278; OR=0.235, 95%CI=0.053~1.041, respectively). The clinical characteristics including age, clinical stage, histological grade and residual lesion size were significantly related with chemosensitivity to platinum drugs and mortality in EOC patients. According to Kaplan-Meier curve, compared with CC+GC genotype, rs2252673 GG genotype showed significantly decreased survival rate in EOC patients (P<0.05). Cox regression model indicated that rs2252673, age and clinical stage were independent risk factors for the prognosis in EOC (all P<0.05). These findings indicate that INSR rs2252673 and rs3745546 polymorphisms were associated with sensitivity to platinum-based chemotherapy in EOC patients and rs2252673 polymorphism may be an independent risk factor for EOC prognosis.

Multicentre study of Y chromosome microdeletions in 1,808 Chinese infertile males using multiplex and real-time polymerase chain reaction.

Azoospermia factor (AZF) genes on the long arm of the human Y chromosome are involved in spermatogenesis, and microdeletions in the AZF region have been recognised to be the second major genetic cause of spermatogenetic failure resulting in male infertility. While screening for these microdeletions can avoid unnecessary medical and surgical treatments, current methods are generally time-consuming. Therefore, we established a new method to detect and analyse microdeletions in the AZF region quickly, safely and efficiently. In total, 1,808 patients with spermatogenetic failure were recruited from three hospitals in southern China, of which 600 patients were randomly selected for screening for Y chromosome microdeletions in AZF regions employing real-time polymerase chain reaction with a TaqMan probe. In our study, of 1,808 infertile patients, 150 (8.3%) were found to bear microdeletions in the Y chromosome using multiplex PCR, while no deletions were found in the controls. Among the AZF deletions detected, two were in AZFa, three in AZFb, 35 in AZFc, three in AZFb+c and two in AZFa+b+c. Our method is fast-it permits the scanning of DNA from a patient in one and a half hours-and reliable, minimising the risk of cross-contamination and false-positive and false-negative results.

An assessment of the correlation between early postinfarction pyramidal tract Wallerian degeneration and nerve function recovery using diffusion tensor imaging.

This study aimed to evaluate the clinical significance of diffusion tensor imaging (DTI) in the early diagnosis of pyramidal tract Wallerian degeneration (WD) and assessment of neurological recovery following cerebral infarction. This study included 23 patients with acute cerebral infarction and 10 healthy adult controls. All participants underwent both magnetic resonance imaging (MRI) and DTI scans. DTI images were analyzed using the Functional MRI of the Brain Software Library to determine the regions of interest (ROI) and obtain the mean diffusivity (MD) and fractional anisotropy (FA) value for each ROI. The correlation between FA or MD and postinfarction functional recovery of the nervous system was further analyzed to assess the feasibility of using a DTI scan in the evaluation of functional recovery of the nervous system in patients with cerebral infarction. DTI may be useful in detecting signals of early postinfarction pyramidal tract WD and is useful for the evaluation of postinfarction neurological recovery. Cerebral lesions were detected using MRI in all patients. It was found that in some patients, the FA value of the ipsilateral pyramidal tract on DTI was decreased as early as day 3 after the onset of infarction and in all patients by day 7. Subsequent correlation studies showed that the FA value of the ipsilateral pyramidal tract on day 13 was negatively correlated with the National Institutes of Health Stroke Scale score, but positively correlated with the Barthel Index, motricity index, and modified Rankin Scale scores.

[Clinical and pathologic analysis of 414 cases of renal angiomyolipomain in a single institution].

Objective: To study the different clinicopathological characteristics between classic and epithelioid renal angiomyolipoma, and the relationships between clinicopathological characteristics and biological behaviors as basis for clinical treatment. Methods: The clinicopathological and follow-up data for the patients diagnosed with renal angiomyolipoma between 2004 and 2011 were retrospectively reviewed and analyzed. Results: There were 414 cases of renal angiomyolipoma diagnosed over 8 years ago, accounting for 8.1% (414/5 287) of all renal parenchymal tumors. The patients included 122 male and 292 female (male-to-female ratio of 1.0∶2.4), mean age 44.0 years (range 15-74 years). Of these, 195(47.1%) tumors occurred in the left kidney, 212(51.2%) in the right kidney and seven (1.7%) were bilateral. Clinically, some cases presented with hypochondrial pain, hematuria or palpable masses. Histologically, 394(95.2%) were classic angiomyolipoma, 20(4.8%) were epithelioid angiomyolipoma; 54, 23 and 7 cases had hemorrhage, necrosis and cystic degeneration, respectively; and 5, 30 and 14 cases had perirenal fat invasion, atypical cells and polymorphic/giant tumor cell. There was a positive correlation between atypical cells and epithelioid tumor type, respectively. The other clinicopathological parameters did not correlate with histological type. Follow-up data was available in 360 patients, with follow-up period of 3 to 99 months. One case died from other causes. The remaining patients were free of disease. Conclusions: Angiomyolipoma is a common renal parenchyma tumor. Clinically, it is usually biologically benign. Histologically, it can be either classic or epithelioid types. The epithelioid type should be differentiated from the classic renal cell carcinoma, Mit family translocation renal tumor and renal hemangioblastoma. Atypical cells, more commonly found in the epithelioid angiomyolipoma, do not affect the clinical prognosis of patients.

Novel insights on the relationship between T-tubular defects and contractile dysfunction in a mouse model of hypertrophic cardiomyopathy.

Abnormalities of cardiomyocyte Ca(2+) homeostasis and excitation-contraction (E-C) coupling are early events in the pathogenesis of hypertrophic cardiomyopathy (HCM) and concomitant determinants of the diastolic dysfunction and arrhythmias typical of the disease. T-tubule remodelling has been reported to occur in HCM but little is known about its role in the E-C coupling alterations of HCM. Here, the role of T-tubule remodelling in the electro-mechanical dysfunction associated to HCM is investigated in the Δ160E cTnT mouse model that expresses a clinically-relevant HCM mutation. Contractile function of intact ventricular trabeculae is assessed in Δ160E mice and wild-type siblings. As compared with wild-type, Δ160E trabeculae show prolonged kinetics of force development and relaxation, blunted force-frequency response with reduced active tension at high stimulation frequency, and increased occurrence of spontaneous contractions. Consistently, prolonged Ca(2+) transient in terms of rise and duration are also observed in Δ160E trabeculae and isolated cardiomyocytes. Confocal imaging in cells isolated from Δ160E mice reveals significant, though modest, remodelling of T-tubular architecture. A two-photon random access microscope is employed to dissect the spatio-temporal relationship between T-tubular electrical activity and local Ca(2+) release in isolated cardiomyocytes. In Δ160E cardiomyocytes, a significant number of T-tubules (>20%) fails to propagate action potentials, with consequent delay of local Ca(2+) release. At variance with wild-type, we also observe significantly increased variability of local Ca(2+) transient rise as well as higher Ca(2+)-spark frequency. Although T-tubule structural remodelling in Δ160E myocytes is modest, T-tubule functional defects determine non-homogeneous Ca(2+) release and delayed myofilament activation that significantly contribute to mechanical dysfunction.

Mechanical stimulation enhanced estrogen receptor expression and callus formation in diaphyseal long bone fracture healing in ovariectomy-induced osteoporotic rats.

UNLABELLED: Estrogen receptor (ER) in ovariectomy-induced osteoporotic fracture was reported to exhibit delayed expression. Mechanical stimulation enhanced ER-α expression in osteoporotic fracture callus at the tissue level. ER was also found to be required for the effectiveness of vibrational mechanical stimulation treatment in osteoporotic fracture healing. INTRODUCTION: Estrogen receptor(ER) is involved in mechanical signal transduction in bone metabolism. Its expression was reported to be delayed in osteoporotic fracture healing. The purpose of this study was to investigate the roles played by ER during osteoporotic fracture healing enhanced with mechanical stimulation. METHODS: Ovariectomy-induced osteoporotic SD rats that received closed femoral fractures were divided into five groups, (i) SHAM, (ii) SHAM-VT, (iii) OVX, (iv) OVX-VT, and (v) OVX-VT-ICI, where VT stands for whole-body vibration treatment and ICI for ER antagonization by ICI 182,780. Callus formation and gene expression were assessed at 2, 4, and 8 weeks postfracture. In vitro osteoblastic differentiation, mineralization, and ER-α expression were assessed. RESULTS: The delayed ER expression was found to be enhanced by vibration treatment. Callus formation enhancement was shown by callus morphometry and micro-CT analysis. Enhancement effects by vibration were partially abolished when ER was modulated by ICI 182,780, in terms of callus formation capacity at 2-4 weeks and ER gene and protein expression at all time points. In vitro, ER expression in osteoblasts was not enhanced by VT treatment, but osteoblastic differentiation and mineralization were enhanced under estrogen-deprived condition. When osteoblastic cells were modulated by ICI 182,780, enhancement effects of VT were eliminated. CONCLUSIONS: Vibration was able to enhance ER expression in ovariectomy-induced osteoporotic fracture healing. ER was essential in mechanical signal transduction and enhancement in callus formation effects during osteoporotic fracture healing enhanced by vibration. The enhancement of ER-α expression by mechanical stimulation was not likely to be related to the increased expression in osteoblastic cells but rather to the systemic enhancement in recruitment of ER-expressing progenitor cells through increased blood flow and neo-angiogenesis. This finding might explain the observed difference in mechanical sensitivity of osteoporotic fracture to mechanical stimulation.

Low-magnitude high-frequency vibration enhanced mesenchymal stem cell recruitment in osteoporotic fracture healing through the SDF-1/CXCR4 pathway.

Low-magnitude high-frequency vibration (LMHFV) has been proven to promote osteoporotic fracture healing. Mechanical stimulation was reported to enhance SDF-1/CXCR4 signalling in mesenchymal stem cells (MSCs). We hypothesised that LMHFV promoted osteoporotic fracture healing by enhancing MSC migration through the SDF-1/CXCR4 pathway. 152 ovariectomised SD-rats received closed femoral fracture in groups of vibration+MSC (VMG) (20 min/d, 5 d/week), vibration+MSC+AMD3100 (VMAG; AMD, a CXCR4 inhibitor) (1 mg/kg/d, intraperitoneal), MSC (MG) (1 × 106 MSC, intracardiac) or control (CG) for a treatment duration of 2, 4 or 8 weeks. MSC migration was evaluated by ex-vivo green fluorescent protein signal in the callus; and fracture healing was examined by weekly radiographs, endpoint computed-tomography and mechanical test. At week-2 and week-4, ex-vivo callus GFP intensity of VMG was significantly higher than other groups (p < 0.05). From week-2 to week-3, both callus width and callus area in VMG were significantly larger; and from week-7 to week-8, smaller than other groups (p < 0.05). At week-8, high-density bone volume fraction, bone volume fraction, bone mineral density and stiffness in VMG were significantly higher than other 3 groups (p < 0.05). This study demonstrated that LMHFV promoted MSC migration and fracture healing in osteoporotic rats. This effect was attenuated by CXCR4 inhibitor, providing strong evidence that SDF-1-mediated MSC migration was one of the important mechanisms through which LMHFV enhanced fracture healing.

[MRI findings of renal cell carcinoma associated with Xp11.2 translocations/TFE3 gene fusions].

Objective: To analyze MRI findings of renal cell carcinoma associated with Xp11.2 translocation-TFE gene fusion(Xp11.2 RCC). Methods: MR imaging features of eleven patients with pathologically-proved Xp11.2 RCC were retrospectively analyzed from December 2008 to December 2015. The following MRI features of the lesions were analyzed in the study: location, maximal diameter, signal intensity, hemorrhage, necrosis, cystic change, enhancement features and metastasis. The data was analyzed by using t test. Results: Four men and seven women (mean age, 35.2 years; age range, 15-49 years) were included. Tumors occurred in the right kidney in 5 cases and the left kidney in 6 cases. On T1WI tumors showed heterogeneously hypo-intensity and iso-intensity, hyper-intensity in 10 cases, 1 cases, respectively. On T2WI tumors showed heterogeneously slight hypo-intensity, heterogeneously slight hyper-intensity and hyper-intensity in 6 cases, 4 cases, 1 case, respectively. On DWI tumors showed hyper-intensity and heterogeneously slight hype-intensity in 2 cases, 9 cases, respectively. ADC value of the tumors were statistically significant lower than that of renal cortex(×10-3mm2/s)(1.35±0.20 vs 2.09±0.11, P<0.05). Imaging findings were suggestive of hemorrhage(n=4) or necrosis (n=1) or cystic change (n=6) or lipid(n=1) in the tumors. On dynamic contrast-enhanced imaging, tumors showed lower signal intensity change (96%±93%, 110%±86% and 103%±46%, respectively) than did renal cortex (285%±109%, 254%±97% and 225%±90%, respectively) (P<0.05). Tumor capsule showed in 7 cases. Enlarged lymph node was found in renal hilum in one case. Conclusion: MRI findings may show characteristic features of Xp11.2 RCC combined with patients' age and assist in preoperative correct diagnosis.

[Clinicopathologic characteristics of thyroid-like follicular carcinoma of the kidney: an analysis of five cases and review of literature].

Objective: To study the clinicopathologic features of thyroid-like follicular renal cell carcinoma. Methods: Clinical data were collected in 5 cases of thyroid-like follicular renal cell carcinoma. HE staining and immunohistochemistry were carried out in surgically-removed specimen to analyze the clinical and pathological features with review of the literatures. Results: The patients aged 20-55 years, with one male and four females; the tumor occurred in the left kidney in three cases and right kidney in two cases. One case had a history of thyroid papillary carcinoma 3 years ago, and the patient had left flank pain, macroscopic haematuria for 2 weeks. The rest four cases had no consciousness of clinical symptoms and signs, without history of thyroid gland surgery; the physical examination found a mass in the kidney and normal thyroid glands. Three patients underwent radical nephrectomy, and the other two patients underwent tumor partial nephrectomy. The tumors were 2-4 cm in size. They showed a solitary nodular mass of well circumscribed with taupe and gray on cut surface. Microscopically, most of tumor cells arranged in thyroid follicular pattern in different sizes, with papillary configuration in a small portion, in four cases; the follicular structure was intermixed with the papillary each half in one case. A large amount of thyroid colloid was deposited within follicule-like structure or papillary axis, lined by simple columnar cells or cubic cells, with obvious atypia, ground-glass nuclei, nuclear groove and rare mitosis. Immunohistochemical staining showed tumor cells were positive for PAX8, and negative for thyroid transcription factor 1 (TTF1) and thyroglobulin (Tg). One of five patients presented with lymph node metastases (4/4) of renal hilum the same time in the diagnosis. Five cases were followed up for 5-84 months after operation, and no tumor progression was found. Conclusions: Thyroid-like follicular renal cell carcinoma is primary renal epithelial malignant tumor. The diagnosis mainly depends on its characteristics of histological appearance, namely similar to the histological morphology of well-differentiated thyroid follicular carcinoma and papillary carcinoma, and the metastasis from the thyroid papillary or follicular carcinoma must be excluded. On the premise of clinical history, immunohistochemical markers TTF1 and Tg have certain value in the differential diagnosis.

Endoplasmic reticulum ribosome-binding protein 1, RRBP1, promotes progression of colorectal cancer and predicts an unfavourable prognosis.

BACKGROUND: Ribosome-binding protein 1 (RRBP1) has been implicated in the regulation of unfolded protein response, which is involved in almost every aspect of cancer development. We aimed to explore the significance of RRBP1 in the progression and prognosis of colorectal cancer (CRC). METHODS: The study population consisted of 856 patients with stage I-III CRC from two hospitals. RRBP1 expression was examined by immunohistochemistry (IHC) in colorectal tissues. The correlation of RRBP1 expression and CRC occurrence was assessed in paired cancer-adjacent tissues. Factors contributing to prognosis were evaluated in a training-validation design with univariate and multivariate Cox analysis. Colorectal cancer aggressiveness caused by RRBP1 knockdown or overexpression was evaluated in CRC cells. RESULTS: RRBP1 was aberrantly overexpressed in CRC. Compared with low-RRBP1 patients, high-RRBP1 patients had shorter disease-specific survival in the training (hazard ratio (HR), 2.423; 95% confidence interval (CI), 1.531-3.835) and validation cohorts (HR, 3.749; 95% CI, 2.166-6.448) in multivariate Cox analysis. High-RRBP1 independently predicted a shorter disease-free survival (HR, 4.821; 95% CI, 3.220-7.218) in the validation cohort. RRBP1 knockdown reduced the aggressiveness of CRC cells in vitro and inhibited the growth of CRC xenografts in vivo. CONCLUSIONS: High RRBP1 expression facilitates CRC progression and predicts an unfavourable post-operative prognosis.