[Changes in Plasma Amyloid-ß Level and Their Relationship With White Matter Microstructure in Patients With Mild Cognitive Impairment].

Objective To investigate the changes in plasma amyloid-ß (Aß) level and their relationship with white matter microstructure in the patients with amnesic mild cognitive impairment(aMCI) and vascular mild cognitive impairment (vMCI).Methods A total of 36 aMCI patients,20 vMCI patients,and 34 sex and age matched healthy controls (HC) in the outpatient and inpatient departments of the First Affiliated Hospital of Anhui Medical University were enrolled in this study.Neuropsychological scales,including the Mini-Mental State Examination,the Montreal Cognitive Assessment,and the Activity of Daily Living Scale,were employed to assess the participants.Plasma samples of all the participants were collected for the measurement of Aß42 and Aß40 levels.All the participants underwent magnetic resonance scanning to obtain diffusion tensor imaging (DTI) data.The DTI indexes of 48 white matter regions of each individual were measured (based on the ICBM-DTI-81 white-matter labels atlas developed by Johns Hopkins University),including fractional anisotropy (FA) and mean diffusivity (MD).The cognitive function,plasma Aß42,Aß40,and Aß42/40 levels,and DTI index were compared among the three groups.The correlations between the plasma Aß42/40 levels and DTI index of aMCI and vMCI patients were analyzed.Results The Mini-Mental State Examination and the Montreal Cognitive Assessment scores of aMCI and vMCI groups were lower than those of the HC group (all P<0.001).There was no significant difference in the Activity of Daily Living Scale score among the three groups (P=0.654).The plasma Aß42 level showed no significant difference among the three groups (P=0.227).The plasma Aß40 level in the vMCI group was higher than that in the HC group (P=0.014),while it showed no significant difference between aMCI and HC groups (P=1.000).The plasma Aß42/40 levels in aMCI and vMCI groups showed no significant differences from that in the HC group (P=1.000,P=0.105),while the plasma Aß42/40 level was lower in the vMCI group than in the aMCI group (P=0.016).The FA value of the left anterior limb of internal capsule in the vMCI group was lower than those in HC and aMCI groups (all P=0.001).The MD values of the left superior corona radiata,left external capsule,left cingulum (cingulate gyrus),and left superior fronto-occipital fasciculus in the vMCI group were higher than those in HC (P=0.024,P=0.001,P=0.003,P<0.001) and aMCI (P=0.015,P=0.004,P=0.019,P=0.001) groups,while the MD values of the right posterior limb of internal capsule (P=0.005,P=0.001) and left cingulum (hippocampus) (P=0.017,P=0.031) in the aMCI and vMCI groups were higher than those in the HC group.In the aMCI group,plasma Aß42/40 level was positively correlated with FA of left posterior limb of internal capsule (r=0.403,P=0.015) and negatively correlated with MD of the right fonix (r=-0.395,P=0.017).In the vMCI group,plasma Aß42/40 level was positively correlated with FA of the right superior cerebellar peduncle and the right anterior limb of internal capsule (r=0.575,P=0.008;r=0.639,P=0.002),while it was negatively correlated with MD of the right superior cerebellar peduncle and the right anterior limb of internal capsule (r=-0.558,P=0.011;r=-0.626,P=0.003).Conclusions Plasma Aß levels vary differently in the patients with aMCI and vMCI.The white matter regions of impaired microstructural integrity differ in the patients with different dementia types in the early stage.The plasma Aß levels in the patients with aMCI and vMCI are associated with the structural integrity of white matter,and there is regional specificity between them.

Integrated Chinese and Western medicine in the treatment of a patient with podocyte infolding glomerulopathy: A case report.

BACKGROUND: Podocyte infolding glomerulopathy (PIG) is a newly described and rare glomerular disease. To date, only approximately 40 cases have been reported globally. CASE SUMMARY: A 26-year-old female patient presented to our hospital with a complaint of intermittent edema of both lower limbs over the past 2 years. The patient was diagnosed with PIG. She was prescribed corticosteroid therapy in other hospitals during the initial stage, to which she had responded poorly and had developed femoral head necrosis. Therefore, we administered immunosuppressants, renin-angiotensin system inhibitors, combined with traditional Chinese medicine. The patient was followed for 1 year, during which her clinical condition improved. CONCLUSION: Integrated Chinese and Western medicine may be effective for PIG treatment, which requires active intervention to improve prognosis.

Value of High-Frequency Ultrasound for Differentiating Invasive Basal Cell Carcinoma from Non-invasive Types.

The purpose of the study was to evaluate the value of high-frequency ultrasound (HFUS) for differentiating invasive basal cell carcinomas (BCCs) from non-invasive BCCs. We established a prediction model based on ultrasound features and validated it further. One hundred patients in the pilot cohort and another 43 in the validation cohort were evaluated. All patients underwent HFUS examinations by the same radiologist, and then were divided on the basis of pathology into invasive and non-invasive types. With respect to growth pattern, 60.5% of invasive BCCs had an irregular pattern, whereas 89.5% of non-invasive BCCs had a nodular or crawling pattern (p < 0.001). As for the layers involved, the more invasive BCCs broke through the dermis compared with non-invasive BCCs (23.3% vs. 1.8%) (p < 0.001). With respect to intralesional hyperechoic spot distribution, invasive and non-invasive BCCs tended to be clustered and absent/scattered-like, respectively (55.8% vs. 91.2%) (p < 0.001). On the basis of the aforementioned features, a prediction model was established with accuracies of 84.0% and 76.7%, respectively, in the pilot and validation cohorts. HFUS holds promise for the differentiation of the invasiveness of BCCs and is helpful in its clinical management.

High-frequency ultrasound in the diagnosis of the spectrum of cutaneous squamous cell carcinoma: Noninvasively distinguishing actinic keratosis, Bowen's Disease, and invasive squamous cell carcinoma.

OBJECTIVE: To evaluate high-frequency ultrasound (HFUS) features for diagnosing cutaneous squamous cell carcinoma (cSCC) as a spectrum of progressively advanced malignancies, including precursor actinic keratosis (AK), Bowen's disease (BD), and invasive squamous cell carcinoma (iSCC). METHOD: In this retrospective study, 160 skin lesions diagnosed histopathologically (54 AK, 54 BD, and 52 iSCC) in 160 patients were included. The HFUS features of AK, BD, and iSCC were analyzed. The obtained data were evaluated using univariate and forward multivariate logistic regression analyses. RESULTS: The most significant HFUS features in AK were regular surface (odds ratio [OR], 8.42) and irregular basal border (OR, 6.36). The most significant HFUS features in BD were crumpled surface (OR, 19.62) and layer involvement confined to the epidermis (OR, 3.96). The most significant HFUS features in iSCC were concave surface (OR, 27.06), stratum corneum (SC) detachment (OR, 14.41), irregular basal border (OR, 4.01), and convex surface (OR, 3.73). The characteristics of surface features, basal border, and layer involvement could be valuable HFUS clues in the discrimination of AK, BD, and iSCC. CONCLUSION: High-frequency ultrasound is valuable for the differentiation of AK, BD, and iSCC, which may allow dynamic and noninvasive monitoring in the spectrum of cSCC.

The lncRNA ALMS1-IT1 may promote malignant progression of lung adenocarcinoma via AVL9-mediated activation of the cyclin-dependent kinase pathway.

Lung adenocarcinoma (LUAD) is the primary epithelial tumor of the lung. The lack of clinical symptoms and specific molecular diagnostic indicators during the early stages of LUAD mean that the disease may not be detected until late stages, and the 5-year survival rate is only approximately 15%. Long non-coding RNA ALMS1 intronic script 1 (ALMS1-IT1) was previously reported to be correlated with the poor prognosis of head and neck squamous cell carcinoma patients. Here, we investigated whether ALMS1-IT1 has prognostic potential for LUAD. Bioinformatics analyses were performed to examine the expression and prognostic value of ALMS1 and AVL9 (for which gene expression is positively correlated with ALMS1-IT1 expression in LUAD) in LUAD based on TCGA and Oncomine databases. We report that ALMS1-IT1 and AVL9 were both highly expressed in LUAD and correlated with poor outcomes in LUAD patients. Of note, the prognosis of LUAD patients with low expression of both ALMS1-IT1 and AVL9 was superior to that of other patients. Furthermore, the proliferation, migration and invasion of LUAD cells were decreased in cells lacking ALMS1-IT1, and this decrease could be almost completely reversed through overexpression of AVL9. Gene set enrichment analysis revealed that expression of genes related to the cell cycle pathway is closely related to both the high expression of ALMS1-IT1 and AVL9 in LUAD. Finally, up-regulation of ALMS1-IT1 can activate the cyclin-dependent kinase pathway, whereas absence of AVL9 can reverse this activation, as shown by western blotting. In summary, ALMS1-IT1/AVL9 may promote the malignant progression of LUAD, at least in part by regulating the cyclin-dependent kinase pathway.

Combination of Multiple Hemodialysis Modes: Better Treatment Options for Patients Under Maintenance Hemodialysis.

PURPOSE: Chronic renal failure has become a major public health concern and treatment strategies are urgently needed. We aimed to investigate whether combination of hemodialysis modes was superior to regular hemodialysis for patients under maintenance hemodialysis. PATIENTS AND METHODS: A total of 144 patients with end-stage renal failure (ESRF) were enrolled in this single-center retrospective study. Patients received regular hemodialysis (HD) were included in HD group (n=52), patients received regular HD plus hemodiafiltration (HDF) in HD/HDF group (n=47), patients received the combination of regular HD, HDF and hemoperfusion (HP) in HD/HDF/HP group (n=45). After 1-month and 24-months treatment, therapeutic effects were assessed in terms of nutritional status, control of complications, dialysis adequacy, mean arterial pressure (MAP), infection rate and living quality. RESULTS: When patients received 1-month treatment, there were no statistically significant differences among three groups. After 24-months treatment, patients in HD/HDF and HD/HDF/HP group presented with better dialysis adequacy, lower MAP and infection rate, higher serum albumin, hemoglobin and calcium levels, lower serum phosphorus and intact parathyroid hormone levels, lower incidence of malnutrition and the Hamilton Depression Scale score, higher the Barthel Index score than HD group (P<0.05). The levels of calcium, phosphorus and intact parathyroid hormone in HD/HDF/HP group were lower than those in HD/HDF group (P<0.05). CONCLUSION: Our finding highly indicated that combination of hemodialysis modes was superior to regular HD for patients with ESRF in nutritional status, control of complications, dialysis adequacy, and living quality.

Contribution of Inflammation and Hypoperfusion to White Matter Hyperintensities-Related Cognitive Impairment.

White matter hyperintensities (WMHs) of presumed vascular origin are one of the most important neuroimaging markers of cerebral small vessel disease (CSVD), which are closely associated with cognitive impairment. The aim of this study was to elucidate the pathogenesis of WMHs from the perspective of inflammation and hypoperfusion mechanisms. A total of 65 patients with WMHs and 65 healthy controls were enrolled in this study. Inflammatory markers measurements [hypersensitive C-reactive protein (hsCRP) and lipoprotein-associated phospholipase A2 (Lp-PLA2)], cognitive evaluation, and pseudocontinuous arterial spin labeling (PCASL) MRI scanning were performed in all the subjects. The multivariate logistic regression analysis showed that Lp-PLA2 was an independent risk factor for WMHs. Cerebral blood flow (CBF) in the whole brain, gray matter (GM), white matter (WM), left orbital medial frontal gyrus [MFG.L (orbital part)], left middle temporal gyrus (MTG.L), and right thalamus (Tha.R) in the patients was lower than those in the controls and CBF in the left triangular inferior frontal gyrus [IFG.L (triangular part)] was higher in the patients than in the controls. There was a significant correlation between Lp-PLA2 levels and CBF in the whole brain (R = -0.417, p < 0.001) and GM (R = -0.278, p = 0.025), but not in the WM in the patients. Moreover, CBF in the MFG.L (orbital part) and the Tha.R was, respectively, negatively associated with the trail making test (TMT) and the Stroop color word test (SCWT), suggesting the higher CBF, the better executive function. The CBF in the IFG.L (triangular part) was negatively correlated with attention scores in the Cambridge Cognitive Examination-Chinese Version (CAMCOG-C) subitems (R = -0.288, p = 0.020). Our results revealed the vascular inflammation roles in WMHs, which may through the regulation of CBF in the whole brain and GM. Additionally, CBF changes in different brain regions may imply a potential role in the modulation of cognitive function in different domains.

Expression and localization of Copine-3-enhanced green fluorescent protein fusion protein / 解剖学报

Objective To construct the eukaryotic expression vector plasmid enhanced green fluorescent protein (pEGFP)-N1-CPNE3, and identify the expression and localization of Copine-3 protein in cells. Methods The Copine-3 coding sequences (CPNE3) was amplified by RT-PCR from human bronchial epithelial (HBE) cells and inserted into eukaryotic expression vector pEGFP-Nl. The recombinant plasmid pEGFP-Nl-CPNE3 was confirmed by endonuclease digestion and sequencing before it was transfected into 293T and H1299 cells. Cellular localization of Copine-3-EGFP fusion protein was detected by con-focal laser scanning. Expression of Copine-3 in 293T and H1299 cells was detected by Western blotting analysis. Localization of Copine-3 in clinical samples of the lung adenocarcinoma patients was detected by immunohistochemistry. Results CPNE3 was successfully constructed into the eukaryotic expression vector pEGFP-Nl and expressed in 293T and H1299 cells. Furthermore, the location of Copine-3 protein in cytoplasm and nucleus was determined by immunofluorescence staining, immuno Western blotting and immunohistochemistry in those cells and clinical samples. Conclusion The eukaryotic expression vector pEGFP-Nl-CPNE3 is constructed successfully, and Copine-3 protein is localized in cytoplasm and nucleus.

Ultrasound validation of predictive model for central cervical lymph node metastasis in papillary thyroid cancer on BRAF.

Aim: To compare the value of predictive power of the models for central cervical lymph node metastasis (CLNM) in papillary thyroid carcinomas (PTCs). Patients & methods: 220 PTCs were prospectively enrolled into the study with pathological examination. We established a new risk model with univariate and multivariate analyses and receiver-operating characteristic curves were plotted. Z-test was performed to compare the area under two curves and validated the predictive model for central CLNM in PTCs. The comparison of previous and new predictive model was analyzed. Results: Microcalcification, capsule contact or involvement, internal flow and BRAFV600E mutation were four independent risk factors for PTCs with central CLNMs. The area under the curves for the new and the previous model were 0.948 and 0.934 (p = 0.572), respectively. Conclusion: Two predictive models showed strong consistency in predicting central CLNM in PTCs. The predictive model may be helpful in selecting appropriate treatment method in PTCs.

Conventional ultrasound characteristics, TI-RADS category and shear wave speed measurement between follicular adenoma and follicular thyroid carcinoma.

The purpose of the study was to explore the differences of conventional ultrasound characteristics, thyroid imaging reporting and data system (TI-RADS) category and shear wave speed (SWS) measurement between follicular adenoma (FA) and follicular thyroid carcinoma (FTC). Twenty-eight FTCs and 67 FAs proven by surgery were retrospectively included for analysis. Conventional ultrasound and point-shear wave elastography (p-SWE) were performed in all of the included patients. The ultrasound features, American Thyroid Association (ATA) TI-RADS category and American College of Radiology (ACR) TI-RADS category, SWS measurement were compared between the two groups. Receiver operating characteristic (ROC) curve was performed and area under ROC curve (AUC) was obtained for significant features. There were no statistical differences in mean age (46.9±15.7years vs. 48.6±13.6years, P = 0.639), gender (9 males, 32.1% vs. 18 males, 29.0%, P = 0.766) and mean diameter (28.3±16.2 mm vs. 33.8±11.9 mm, P = 0.077) between FTCs and FAs. Hypoechogenicity, lobulated or irregular margin, macrocalcification were more common in FTCs than FAs (all P < 0.05). Mean SWS of FTCs (2.29±0.64 m/s) was slightly higher than that of FAs (1.94±0.68 m/s) (P = 0.023). The AUCs were 0.655, 0.744, and 0.744 with the cut-off SWS≥1.89 m/s, ACR TI-RADS category 4 and intermediate suspicion of ATA TI-RADS category. The sensitivity and AUC were 82.1% and 0.812 with combined ultrasound features of hypoechogenicity, lobulated or irregular margin and macrocalcification. In Conclusion, SWS measurement and TI-RADS categories were useful for the identification of FTCs from FAs.

Imaging findings of Bowen's disease: A comparison between ultrasound biomicroscopy and conventional high-frequency ultrasound.

OBJECTIVES: To compare the imaging findings of Bowen's disease (BD) between ultrasound biomicroscopy (UBM) and conventional high-frequency ultrasound (HFUS). METHODS: A total of 29 pathologically proven BD lesions in 28 patients were retrospectively enrolled in the study, and all were after surgery. All the lesions were imaged with both UBM and HFUS. The imaging features on HFUS and UBM were analyzed and compared. The diagnostic results of ultrasound for BD were referenced with pathology results. RESULTS: All the 29 (100%) BD lesions appeared hypoechogenicity, solid component, and superficial hyperechoic layer (ie, keratinization) on both UBM and HFUS. The typical imaging feature of BD lesions, that was, infiltration depth confined to the epidermis, was visualized in 25 (86.2%, 25/29) lesions on UBM whereas 15 (51.7%, 15/29) on HFUS (P = .002). A "wave sign," which corresponds to the surface keratinization of BD lesion, was visualized in 17 (58.6%, 17/29) of BD lesions on UBM whereas 6 (20.7%, 6/29) on HFUS (P = .001). UBM and HFUS correctly diagnosed 25 (86.2%, 25/29) and 15 (51.7%, 15/29) BD lesions, respectively (P = .002). CONCLUSIONS: Bowen's disease has some typical imaging features on US. The "wave sign" of the superficial hyperechoic layer and the clear borderline between the tumor in epidermis and the slightly hyperechoic dermis layer are better depicted by UBM in comparison with HFUS, which leads to a more accurate diagnosis of BD. UBM has potential to be used as a diagnostic tool for characterization of BD on account of its high resolution.

Ultrasound Biomicroscopy and High-Frequency Ultrasound for Evaluating Extramammary Paget Disease With Pathologic Correlation.

OBJECTIVES: The purpose of this study was to investigate the performance of ultrasound biomicroscopy (UBM) and high-frequency ultrasound (HFUS) in the assessment of extramammary Paget disease (EMPD) and to correlate the imaging features with pathologic findings. METHODS: In this retrospective study, we described the imaging features from UBM and HFUS based on 17 pathologically proven EMPD cases. The performance for visualizing layer involvement by UBM and HFUS was compared. Additionally, we checked the consistency between layer involvement of the lesions on UBM images and the pathologic results. Additionally, blood flow and the status of lymph nodes were investigated with HFUS. RESULTS: Ultrasound biomicroscopy revealed that all 17 lesions (100%) were hypoechoic and grew in a creeping form. The feature of layer involvement was shown in 10 lesions (58.8%) limited to the epidermis and 6 lesions (35.3%) involving the dermis, and the remaining lesion (5.9%) involved the full skin layers. Layer involvement was clearly displayed by UBM for all lesions (100%) but for only 5 lesions (29.4%) by HFUS (P < .001). Additionally, the layer involvement of 15 lesions (88.2%) on UBM was consistent with the pathologic results (κ = 0.746). High-frequency ultrasound revealed profuse blood flow in most lesions (64.7% [11 of 17]), and 1 case showed inguinal lymph node metastasis. CONCLUSIONS: Combined use of UBM and HFUS can provide key information on EMPD based on ultrasound features. Comparatively, UBM provides clearer morphologic information, whereas HFUS provides information on lymph node metastasis and blood flow.

Isolation and genetic analysis of a nidovirus from crucian carp (Carassius auratus).

A nidovirus was isolated from crucian carp (Carassius auratus). The complete genome of the crucian carp nidovirus (CCNV) is 25,971 nt long and has five open reading frames, encoding the polyprotein 1ab (pp1ab), spike glycoprotein (S), membrane protein (M), and nucleocapsid protein (N). CCNV has the highest similarity to Chinook salmon nidovirus (CSNV). However, the CCNV HB93 pp1ab protein sequence has three long fragment deletions compared with the CSNV. Phylogenetic analysis based on the complete genome sequence showed that CCNV HB93 clusters with CSNV, indicating that CCNV represents a second species in the new genus Oncotshavirus within the new family Tobaniviridae in the order Nidovirales.

Analysis of optimal dose of thoracic radiotherapy for patients with extensive stage small cell lung cancer / 中华放射肿瘤学杂志

Objective To investigate the optimal dosage of thoracic radiotherapy in patients diagnosed with extensive stage small cell lung cancer (ES-SCLC).Methods Clinical data of ES-SCLC patients admitted to Tianjian Medical University Cancer Institute& Hospital between February 2010 and October 2015 were retrospectively analyzed.All patients received the first-line induction chemotherapy.Subsequently,216 patients without progression after the first-line induction chemotherapy were apportioned to the thoracic radiotherapy (n=180) group and chemotherapy alone group (n=36).According to the distribution characteristics of the biological equivalent dose,all patients were assigned into the A (31.3-40.2 Gy,n=23),B (46.0-46.8 Gy,n=38),C (49.5-53.7 Gy,n=43) and D groups (55.1-60.6 Gy,n=76).For the subgroup analysis,the low (31.3-46.8 Gy,n=61) and high dose groups (49.5-60.6 Gy,n=119) were divided.Kaplan-Meier survival analysis was used for prognostic analysis.Cox's regression model was conducted for multivariate prognostic analysis.Propensity score matching was utilized to control the confounding variables.Results The median overall survival of all patients was 13.2 months,and 8.3,11.0,15.8,17.8 and 8.1 months for patients in the A,B,C,D and chemotherapy alone groups,respectively (all P=0.000).The median overall survival did not significantly differ between A and B/ chemotherapy groups (P=0.172,P=0.495),and similar results were obtained between the C and D groups (P=0.624).The median overall survival in the B group was significantly longer than that in the chemotherapy alone group (P=0.020).Statistical significance was noted between C and D groups,and A and B groups (all P＜0.05).The median progression-free survival for all patients was 8.7 months,and 6.5,7.6,11.8,12.4 and 6.1 months in the A,B,C,D and chemotherapy alone groups,respectively (all P=0.000).The median progression-free survival did not significantly differ between A and B chemotherapy groups (P=0.588,P=0.668).The progression-free survival in the B group was slightly longer than that in the chemotherapy group without statistical significance (P=0.070).No statistical significance was observed between the C and D groups (P=0.627).Statistical significance was noted between C and D groups,and A and B groups (all P＜0.02).Uni-and multi-variate analyses prompted that the number of metastatic lesions and dose of thoracic radiotherapy were the independent predictors of the overall survival and progression-free survival (both P＜0.05).Concurrent chemoradiotherapy was the independent predictor of the overall survival (P=0.018).After the propensity score matching,the median overall survival and progression-free survival significantly differed between the low (n=50) and high dose groups (n=50) (10.9 vs.17.5 months,P=0.045;7.4 vs.10.7 months,P=0.014).Conclusions A relatively high dose ranging from 49.5 to 53.7 Gy is recommended during thoracic radiotherapy for ES-SCLC patients.An excessively low dose (≤ 40.2 Gy) probably fails to prolong the survival time,and an extremely high dose (≥55.1 Gy) cannot enable the patients to obtain survival benefits.

Conventional Ultrasound, Immunohistochemical Factors and BRAFV600E Mutation in Predicting Central Cervical Lymph Node Metastasis of Papillary Thyroid Carcinoma.

The study was aimed at evaluating the correlation between central cervical lymph node metastasis (CLNM) in papillary thyroid carcinoma (PTC) patients and ultrasound (US) features, immunohistochemical factors and BRAFV600E mutation. A total of 225 consecutive patients (225 PTCs) who had undergone surgery were included. All PTCs were pre-operatively analysed by US with respect to size, components, echogenicity, shape, margins, microcalcification, multiple cancers or not, internal vascularity and capsule contact or involvement. The presence of four immunohistochemical factors, including cytokeratin 19, human bone marrow endothelial cell 1, galectin-3 and thyroid peroxidase, and BRAFV600E mutation was also evaluated. Univariate and multivariate analyses were performed to identify the risk factors for central CLNM, and a risk model was established. Pathologically, 44% (99/225) of the PTCs had central CLNMs. Multivariate analysis revealed that size ≤10mm, microcalcification, internal vascularity, capsule contact or involvement and BRAFV600E mutation were independent risk factors for central CLNM. The risk score for central CLNM was calculated as follows: risk score = 1.5 × (if lesion size ≤10 mm) + 1.9 × (if microcalcification) + 0.8 × (if internal flow) + 3.0 × (if capsule contact or involvement) + 1.5 × (if BRAFV600E mutation). The rating result was divided into six stages, and the relevant risk rates of central CLNM were 0% (0/1), 0% (0/22), 7.4% (4/54), 48.6% (34/70), 71.2% (42/59) and 100% (19/19), respectively. In conclusion, PTC ≤10mm, microcalcification, internal vascularity, capsule contact or involvement and BRAFV600E mutation are risk factors for central CLNM. The risk model may be useful in treatment planning and management of patients with PTCs.

Differentiating the acute phase of gout from the intercritical phase with ultrasound and quantitative shear wave elastography.

OBJECTIVES: To evaluate the value of ultrasound (US) in differentiating the acute phase of gout from the intercritical phase, particularly using shear wave elastography (SWE). METHODS: 57 gout patients were prospectively enrolled and divided into acute phase and intercritical phase groups. The patients underwent US and SWE examinations for the first metatarsophalangeal joints with the same protocol. Maximum synovial thickness was measured. US features were reviewed by two radiologists independently. The maximum (Emax) and mean (Emean) elastic moduli of synovium were calculated. Diagnostic performances of US, SWE and combined US and SWE were evaluated. RESULTS: US findings demonstrated that the colour Doppler flow signal grade in the acute phase was higher than that in the intercritical phase (p = 0.001), whereas no differences were found for B-mode US features between the two groups (all p > 0.05). For SWE, Emax and Emean were significantly higher in the intercritical phase than in the acute phase (both p < 0.001). The areas under the receiver operating characteristic curve (AUROCs) were 0.494-0.553 for B-mode US, 0.735 for colour Doppler US (CDUS), 0.887 for Emax and 0.882 for Emean. The combination of CDUS and SWE increased the AUROC, sensitivity and accuracy significantly in comparison with CDUS alone (all p < 0.001). However, the combined set did not show stronger diagnostic performance in comparison with SWE alone. CONCLUSION: SWE increases the diagnostic performance in differentiating the acute phase of gout from the intercritical phase in comparison with conventional US. KEY POINTS: • Colour Doppler flow signal grade is higher in acute phase of gout than in intercritical phase. • SWE demonstrates that synovium stiffness is higher in intercritical phase of gout than in acute phase. • SWE increases diagnostic performance in differentiating acute phase of gout from intercritical phase in comparison with conventional US.

The deficiency of CX3CL1/CX3CR1 system ameliorates high fructose diet-induced kidney injury by regulating NF-κB pathways in CX3CR1-knock out mice.

Fructose, the most important functional food additive from the last century, has been widely used in industry, agriculture, light industry, food and medicine. With the improvement of people's living standard and economic level, excess intake of fructose results in metabolic symptoms, including hyperleptinemia, insulin resistance and neuroinflammation is causing high risk of chronic kidney disease development in humans and animals. However, the underlying molecular mechanism of renal injury is still not fully understood, and the development of effective drugs and treatments are delayed. Hence, we investigated the role of crosstalk of CX3CL1-CX3CR1 axis and nuclear factor-κB (NF-κB) signaling pathway in the development of renal injury. CX3CL1-knock-out C57BL/6 mice were constructed and used to analyze the influence of CX3CL1-related signaling pathways on kidney injury of wild­type (WT) mice and CXECR1 deficiency mice, which were administrated with 30% fructose water. Western blotting, quantitative RT-PCR (qRT-PCR), immunohistochemistry, ELISA, flow cytometry and biochemical indicator analysis were used to determine the levels of renal injury and key signaling pathway associated with renal damage. The results indicated that administration of high fructose intake can cause typical renal inflammatory responses in serum and tissues. Fructose enhances the CX3CL1-CX3CR1 axis and NF-κB activation, and promotes crosstalk of CX3CL1-CX3CR1 and NF-κB pathways. The phosphorylated AKT could be significantly activated in fructose-induced renal injury via CX3CL1-CX3CR1 axis. CX3CR1 expression between WT and CX3CR1-/- mice were evaluated to establish their relationship with injury. Our results indicated that CX3CR1 may be the central and major indicator in the process of renal injury, which mediate AKT pathway and further enhance the NF-κB activation. These findings demonstrated that crosstalk of CX3CL1-CX3CR1 axis and NF-κB signaling pathway play a direct role in fructose-induced kidney injury. Inhibition of CX3CL1-CX3CR1 pathway may suppress renal-related diseases. It may be a potential treatment choice for the clinical diagnoses and treatment in the future.

Receipt of thoracic radiation therapy and radiotherapy dose are correlated with outcomes in a retrospective study of three hundred and six patients with extensive stage small-cell lung cancer.

BACKGROUND: The importance of the thoracic radiation therapy (TRT) dose has not been clearly defined in extensive stage small-cell lung cancer (ES-SCLC) and it is unclear whether improved TRT dose translates into a survival benefit. METHODS: 306 patients with ES-SCLC were retrospectively reviewed, of which 170 received IMRT/CRT fractionation RT after ChT, and 136 received chemotherapy (ChT) alone. We adopted the time-adjusted BED (tBED) for effective dose fractionation calculation. Due to the nonrandomized nature of this study, we compared the ChT+RT with ChT groups that matched on possible confounding variables. RESULTS: Patients achieved 2-year OS, PFS and LC rates of 19.7%, 10.7% and 28.4%, respectively. After propensity score matching, (113 cases for each group), the rates of OS, PFS and LC at 2 years were 21.4%, 7.7% and 34.5% for ChT+TRT, and 10.3% (p<0.001), 4.6% (p<0.001) and 6.3% for ChT only (p<0.001), respectively. Among propensity score matching patients, 56 cases for each group received the high dose (tBED>50 Gy) TRT and received low dose (tBED≤50 Gy) TRT. Two-year OS, PFS and LC rates were 32.3%, 15.3% and 47.1% for the high dose compared with 17.0% (p<0.001), 12.9% (p=0.097) and 34.7% (p=0.029) for low dose radiotherapy. CONCLUSIONS: TRT added to ChT improved ES-SCLC patient OS. High dose TRT improved OS over lower doses. Our results suggest that high-dose thoracic radiation therapy may be a reasonable consideration in select patients with ES-SCLC.

Therapeutic efficacy of three bispecific antibodies on rheumatoid arthritis mice models / 药学学报

In order to obtain the lead compound for treatment of rheumatoid arthritis (RA), in this study, therapeutic efficacy of three bispecific antibodies (BsAB-1, BsAB-2 and BsAB-3) against both hIL-1beta and hIL-17 were compared on CIA model mice. First, by ELISA method we compared the binding capacity of the three bispecific antibodies to the two antigens. The results showed that all three antibodies could simultaneously bind both antigens, among these antibodies, BsAB-1 was superior over BsAB-2 and BsAB-3. CIA model was established with chicken type II collagen (CII) and developed RA-like symptoms such as ankle swelling, skin tight, hind foot skin hyperemia. The CIA mice were treated with three antibodies once every two days for total of 29 days. Compared with the CIA model mice, the RA-like symptoms of the antibody treated-mice significantly relieved, while the BsAB-1 treated-mice were almost recovered. CII antibody level in the serum and cytokines (IL-2, IL-1beta, IL-17A and TNF-alpha) expression in the spleen were examined. Compared with the CIA model mice, all three antibodies could significantly reduce CII antibody and cytokine expression levels. BsAB-1 antibody was more potent than BsAB-2 and BsAB-3. In summary, BsAB-1 is superior over BsAB-2 and BsAB-3 in amelioration of RA symptoms and regulation of CII antibody production and pro-inflammatory cytokine expression, therefore, BsAB-1 can be chosen as a lead compound for further development of drug candidate for treatment of RA.

Expression of serum cytokines in patients with pneumoconiosis by antibody chip / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the changes in expression of serum cytokines in patients with pneumoconiosis using cytokine antibody chips (CACs).</p><p><b>METHODS</b>The CAC technology was applied to measure the serum levels of 60 cytokines in 12 patients with pneumoconiosis and 3 normal controls.</p><p><b>RESULTS</b>In the patients with pneumoconiosis, the highly expressed serum cytokines included interleukin (IL)-1α, IL-1β, IL-2, ILs 4-16, macrophage colony-stimulating factor, interferon-γ, tumor necrosis factor (TNF)-α, TNF-β, human bone morphogenetic protein-6, fibroblast growth factor-7, neurotrophin-3, and stem cell factor, and the lowly expressed serum cytokines included recombinant human I-309, monocyte chemoattractant protein (MCP)-1, MCP-2, MCP-3, MCP-4, macrophage inflammatory protein (MIP)-1-δ, and MIP-3-α.</p><p><b>CONCLUSION</b>Patients with pneumoconiosis have changes in the expression of most serum cytokines.</p>