A urine extracellular vesicle lncRNA classifier for high-grade prostate cancer and increased risk of progression: A multi-center study.

To construct a urine extracellular vesicle long non-coding RNA (lncRNA) classifier that can detect high-grade prostate cancer (PCa) of grade group 2 or greater and estimate the risk of progression during active surveillance, we identify high-grade PCa-specific lncRNAs by combined analyses of cohorts from TAHSY, TCGA, and the GEO database. We develop and validate a 3-lncRNA diagnostic model (Clnc, being made of AC015987.1, CTD-2589M5.4, RP11-363E6.3) that can detect high-grade PCa. Clnc shows higher accuracy than prostate cancer antigen 3 (PCA3), multiparametric magnetic resonance imaging (mpMRI), and two risk calculators (Prostate Cancer Prevention Trial [PCPT]-RC 2.0 and European Randomized Study of Screening for Prostate Cancer [ERSPC]-RC) in the training cohort (n = 350), two independent cohorts (n = 232; n = 251), and TCGA cohort (n = 499). In the prospective active surveillance cohort (n = 182), Clnc at diagnosis remains a powerful independent predictor for overall active surveillance progression. Thus, Clnc is a potential biomarker for high-grade PCa and can also serve as a biomarker for improved selection of candidates for active surveillance.

Detailed analysis of the association between urate deposition and bone erosion in gout: a dual-energy computed tomography study.

Objective: This study aimed to analyze the effect of urate deposition (UD) on bone erosion and examine the association between the volume of monosodium urate (MSU) crystals and an improved bone erosion score method, as measured in the metatarsophalangeal (MTP) joints of patients with gout. Materials and methods: Fifty-six patients diagnosed with gout using the 2015 European League Against Rheumatism and American College of Rheumatology criteria were enrolled. MSU crystals volume at each MTP joint was measured using dual-energy computed tomography (DECT) images. The degree of bone erosion was evaluated with the modified Sharp/van der Heijde (SvdH) erosion scoring system based on CT images. Differences in clinical features between patients with (UD group) and without (non-UD group) UD were assessed, and the correlation between erosion scores and urate crystal volume was analyzed. Results: The UD and non-UD groups comprised 30 and 26 patients, respectively. Among the 560 MTP joints assessed, 80 showed MSU crystal deposition, and 108 showed bone erosion. Bone erosion occurred in both groups but was significantly less severe in the non-UD group (p <0.001). Both groups had equivalent levels of serum uric acid (p=0.200). Symptom duration was significantly longer in the UD group (p=0.009). The UD group also had a higher rate of kidney stones (p=0.023). The volume of MSU crystals was strongly and positively associated with the degree of bone erosion (r=0.714, p <0.001). Conclusion: This study found that patients with UD show significant increased bone erosion than those without UD. The volume of MSU crystals is associated with the improved SvdH erosion score based on CT images, regardless of serum uric acid level, demonstrating the potential of combining DECT and serum uric acid measurements in helping optimize the management of patients with gout.

Plasma extracellular vesicle circRNA signature and resistance to abiraterone in metastatic castration-resistant prostate cancer.

BACKGROUND: We aimed to develop and validate a plasma extracellular vesicle circular RNA (circRNA)-based signature that can predict overall survival (OS) in first-line abiraterone therapy for metastatic castration-resistant prostate cancer (mCRPC) patients. METHODS: In total, 582 mCRPC patients undergoing first-line abiraterone therapy from four institutions were sorted by three phases. In the discovery phase, 30 plasma samples from 30 case-matched patients with or without early progression were obtained to generate circRNA expression profiles using RNA sequencing. In the training phase, differentially expressed circRNAs were examined using digital droplet PCR in a training cohort (n = 203). The circRNA signature was constructed using a least absolute shrinkage and selection operator Cox regression to predict OS. In the validation phase, the prognostic ability of this signature was prospectively validated in two external cohorts (Cohort I, n = 183; Cohort II, n = 166). RESULTS: We developed a five-circRNA signature, based on circCEP112, circFAM13A, circBRWD1, circVPS13C and circMACROD2, which successfully stratified patients into high-risk and low-risk groups. The prognostic ability of this signature was prospectively validated in two external cohorts (P < 0.0001, P < 0.0001). Patients with high-risk scores had shorter OS than patients with low-risk scores. CONCLUSION: This five-circRNA signature is a reliable predictor of OS for mCRPC patients undergoing abiraterone.

[Impacts of biochar and phosphorus application on soil phosphorus availability and soybean phosphorus uptake]. / ä¸åŒç£·æ°´å¹³é æ–½ç”Ÿç‰©ç‚­å¯¹åœŸå£¤ç£·æœ‰æ•ˆæ€§.

Biochar is beneficial to soil phosphorus (P) availability and crop growth, but the effects vary greatly across different soil types. We investigated the effects of rice straw biochar (4% of total mass) and P application (0, 30, and 90 kg P·hm-2) on soil P availability, phosphomonoesterase activity, and soybean P uptake by using lateritic red soil (pH 4.91) and cinnamon soil (pH 7.24) as test materials. The results showed that biochar application at different P levels significantly increased available P and total P in both soils. Biochar application with 30 kg P·hm-2 increased soil available P with maxima at 192.6% and 237.1% in lateritic red soil and cinnamon soil, respectively. Biochar application with 30 kg P·hm-2 in lateritic red soil significantly increased the activity of alkaline phosphomonoesterase by 78.9%, decreased the content of active organic P by 39.3%, and subsequently stimulated soybean P absorption and growth. Biochar amendment significantly reduced active organic P content in cinnamon soil, but did not affect soil phosphomonoesterase activity and plant growth. The content of active organic P was significantly negatively correlated with soil available P content. In summary, the effect of biochar on soil P availability varied across different soil types (lateritic red soil > cinnamon soil) and P levels (better at 30 kg P·hm-2). Our results could provide scientific basis for a promising application of biochar in reducing the amount of P fertilizer and increasing soybean P uptake, especially in lateritic red soil.

A urine extracellular vesicle circRNA classifier for detection of high-grade prostate cancer in patients with prostate-specific antigen 2-10 ng/mL at initial biopsy.

The aim of this study was to identify a urine extracellular vesicle circular RNA (circRNA) classifier that could detect high-grade prostate cancer (PCa) of Grade Group (GG) 2 or greater. For this purpose, we used RNA sequencing to identify candidate circRNAs from urinary extracellular vesicles from 11 patients with high-grade PCa and 11 case-matched patients with benign prostatic hyperplasia. Using ddPCR in a training cohort (n = 263), we built a urine extracellular vesicle circRNA classifier (Ccirc, containing circPDLIM5, circSCAF8, circPLXDC2, circSCAMP1, and circCCNT2), which was evaluated in two independent cohorts (n = 497, n = 505). Ccirc showed higher accuracy than two standard of care risk calculators (RCs) (PCPT-RC 2.0 and ERSPC-RC) in both the training cohort and the validation cohorts. In all three cohorts, this novel urine extracellular vesicle circRNA classifier plus RCs was statistically more predictive than RCs alone for predicting ≥ GG2 PCa. This assay, which does not require precollection digital rectal examination nor special handling, is repeatable, noninvasive, and can be easily implemented as part of the basic clinical workflow.

Clinical and MRI response to dose reduction of an etanercept-biosimilar for hip arthritis in patients with ankylosing spondylitis: an observational, retrospective cohort study.

OBJECTIVES: Hip arthritis plays a critical role in the prognosis of ankylosing spondylitis (AS). Dose reduction of tumor necrosis factor inhibitors preserves general improvement of AS, so this study attempted to examine the equivalence between Yisaipu® tapering and conventional therapy for hip arthritis in AS patients, using clinical parameters and magnetic resonance image (MRI). METHODS: AS patients received this etanercept-biosimilar injections (50 mg/week) in the first 12 weeks. Participants in the tapering group were treated with this reagent 50 mg every other week from week 13 to week 24, while the control group kept undergoing full-dose therapy. Clinical and laboratory parameters were assessed at baseline, week 12 and week 24. MRI examination of hip was performed at baseline and week 24. RESULTS: One hundred and thirty-six patients were enrolled, and 80 of them were in the tapering group. Linear mixed model revealed that main effects of tapering group with control group as reference in disease activity parameters were insignificant (p > 0.05). Main effects of baseline with week 24 as reference were significant (p < 0.05), but main effects of week 12 with week 24 as reference were not (p > 0.05). Prevalence of acute inflammatory change in MRI significantly decreased in the tapering group (76.88% vs 20.00%, p < 0.05) and control group (76.79% vs 19.64%, p < 0.05). Influence of both treatments on acute inflammatory change was equivalent (p > 0.05). CONCLUSION: Efficacy of Yisaipu® tapering treatment is comparable to the full-dose therapy for hip arthritis in AS patients. Both treatments maintain remission of hip arthritis after patients achieved low disease activity.

[Early intervention of BK virus replication promotes stabilization of renal graft function].

OBJECTIVE: To investigate the optimal time window for intervention of BK virus (BKV) replication and its effect on the outcomes of kidney transplant recipients (KTRs). METHODS: A retrospective analysis of the clinical data and treatment regimens was conducted among KTRs whose urine BKV load was ≥1.0×104 copies/mL following the operation between April, 2000 and April, 2015. KTRs with urine BKV load <1.0×104 copies/mL matched for transplantation time served as the control group. RESULTS: A total of 54 recipients positive for urine BKV were included in the analysis. According to urine BKV load, the recipients were divided into 3 groups: group A with urine BKV load of 1.0×104-1.0×107 copies/mL (n=22), group B with urine BKV load >1.0×107 copies/mL (n=24), and group C with plasma BKV load ≥1.0×104 copies/mL (n=8); 47 recipients were included in the control group. During the follow-up for 3.2-34.5 months, the urine and plasma BKV load was obviously lowered after intervention in all the 54 BKV-positive recipients (P<0.05). Eighteen (81.82%) of the recipients in group A and 19 (79.17%) in group B showed stable or improved estimated glomerular filtration rate (eGFR) after the intervention; in group C, 4 recipients (50%) showed stable eGFR after the intervention. In the last follow-up, the recipients in groups A and B showed similar eGFR with the control group (P>0.05), but in group C, eGFR was significantly lower than that of the control group (P=0.001). The recipients in group A and the control group had the best allograft outcome with stable or improved eGFR. CONCLUSION: Early intervention of BKV replication (urine BKV load ≥1.0×104 copies/mL) in KTRs with appropriate immunosuppression reduction can be helpful for stabilizing the allograft function and improving the long-term outcomes.

Prospective validation of DACH2 as a novel biomarker for prediction of metastasis and prognosis in muscle-invasive urothelial carcinoma of the bladder.

Metastasis is the main cause of death from muscle-invasive urothelial carcinoma of the bladder (UCB), and the metastatic potential of tumors is often unpredictable. The role of Dachshund homolog 2 gene (DACH2) in tumorigenesis remains unexplored. We aimed to investigate whether DACH2 can be used as a biomarker to predict metastasis and prognosis of muscle-invasive UCB in a sequential training and validation fashion. For the training set (n = 40), compared with UCB patients without lymph node (LN) metastasis, both DACH2 protein and mRNA expression were greatly increased in case-matched patients with LN metastasis. For the independent validation set (n = 243), patients with primary UCB that did not express DACH2 had a longer metastasis-free survival (MFS) and overall survival (OS) than did those with tumors expressing DACH2 (5-year MFS: 88% [95% CI 80-96] versus 19% [95% CI 7-31], p < 0.001; 5-year OS: 93% [95% CI 87-99] versus 37% [95% CI 23-51], p < 0.001). Multivariable analysis of DACH2 status showed hazard ratios of 7.34 (95% CI 3.15-11.87, p < 0.001) for MFS and 3.96 (95% CI 2.04-7.16, p < 0.001) for OS which were much higher than hazard ratios associated with other independent risk factors. Collectively, DACH2 is an independent prognostic marker that can be used at initial diagnosis of UCB to identify patients who have a high potential to develop metastasis.

Influence of sinomenine on protein profiles of peripheral blood mononuclear cells from ankylosing spondylitis patients: a pharmacoproteomics study.

BACKGROUND: Ankylosing spondylitis (AS) is a common inflammatory rheumatic disease which lacks satisfactory treatment so far. Sinomenine (SIN) is an alkaloid and has recently been utilized in treating multiple rheumatic diseases including AS in China, but its exact mechanism remains to be explored. This study investigated the alteration of proteome in peripheral blood mononuclear cells (PBMCs) from AS patients. METHODS: Thirty AS patients were enrolled in this study. PBMCs from each AS patient were cultured in medium with or without SIN respectively. Then PBMCs proteins from both groups were separated by two-dimensional electrophoresis (2-DE) and analyzed by mass spectrometry (MS). Two differentially expressed proteins were then chosen to be verified using Western blotting. RESULTS: Seven proteins, including a-synuclein (SNCA), calmodulin (CALM), acidic leucine-rich nuclear phosphoprotein 32 family member A (ANP32A), chloride intracellular channel protein 1 (CLIC1), guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (GNB1), gelsolin (GSN) and histone H2B type 1-M (HISTH2BM) were over-expressed, while coronin- 1A (CORO1A) was under-expressed in the SIN-treated PBMCs. Further bioinformatics search indicated that the changes of SNCA, ANP32A and CLIC1 pertained to apoptosis, while changes of GSN and CORO1A were associated with both apoptosis and inhibition of immunological function. Subsequently GSN and CORO1A were selected to validate by Western blotting and the results were consistent with those of 2-DE. CONCLUSION: There were 8 differentially expressed proteins in the SIN-treated PBMCs, which might shed some light on the mechanism of SIN in the treatment of AS.

[Efficacy of local injection of RhTNFR: Fc in collagen-induced arthritis of rats].

OBJECTIVE: To evaluate the efficacy of recombinant human tumor necrosis factor-α receptor II: IgG fusion protein (RhTNFR:Fc) local injection in collagen-induced arthritis (CIA) of rats. METHODS: Twenty-four CIA rats were randomly divided into 3 groups: single therapy (Group I), multiply therapies (Group II) and control (Group III). Group I received normal saline thrice after a single RhTNFR:Fc local treatment while Groups II and III had 4 times of RhTNFR:Fc or normal saline local injection. The severities of right ankle and systemic inflammation were assessed by arthritis index (AI) at baseline and every week after local injection (visits 1, 2, 3 and 4). Serum C reactive protein (CRP) was measured after the last visit. And right ankles were further examined through radiology and pathology. RESULTS: Local or systemic AI of Group I were significantly lower than that of baseline at visit 1 (P < 0.05), but increased during other visits. And local or systemic AI of Group II gradually decreased at each follow-up, but AI of Group III showed no decline. The radiographic scores (5.70±0.67 and 4.90±0.73), histopathological scores (6.00±0.67 and 3.80±0.91) and serum CRP concentration (7.50±0.87 and 3.09±0.76 µg/ml) of Group I and Group II were lower than those of Group III (6.60±1.26, 7.10±0.7 and 12.15±3.47 µg/ml, P < 0.05). And all these parameters of Group I were higher than those of Group II (P < 0.05). CONCLUSION: Local injection of RhTNFR:Fc can effectively alleviate disease activity of CIA and reduce CRP concentration, radiographic and histopathological scores. Multiple therapies show a better efficacy than single injection.

[Expressions of CD147 in peripheral monocytes and T lymphocytes of patients with ankylosing spondylitis].

OBJECTIVE: To investigate the roles of CD147 in the pathogenesis and development of ankylosing spondylitis (AS). METHODS: Flow cytometry was used to detect the expression levels of CD147 in peripheral monocytes and T lymphocytes of 30 AS patients, 30 rheumatoid arthritis (RA) patients and 30 healthy controls (HC). reverse transcription-polymerase chain reaction (RT-PCR) was used to evaluate the expression levels of CD147 mRNA in peripheral blood mononuclear cells (PBMC). Then the expression levels of CD147 were compared among the groups. And a correlation analysis was conducted between CD147 levels and disease activity indices of AS patients. RESULTS: The mean fluorescence intensities of CD147 in monocytes of AS, RA and HC group were 213.5 ± 37.8, 228.7 ± 49.7 and 163.6 ± 44.8, and in T lymphocytes 36.8 ± 10.1, 40.2 ± 10.5 and 28.3 ± 10.6 respectively. Both the expression levels of CD147 in monocytes and T lymphocytes of AS patients were slightly lower than those of RA patients. But the differences was not statistically significant (P > 0.05). Both the CD147 levels in monocytes and T lymphocytes of AS and RA group were significantly higher than those of HC group (P < 0.05). The expression levels of CD147 mRNA in PBMC of AS and RA group were significantly higher than those of HC group (P < 0.05) while no significant difference was found between AS and RA group (P > 0.05). Both the expression levels of CD147 in monocytes and T lymphocytes of AS patients were positively correlated with the patients' erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). CONCLUSION: The expressions of CD147 in peripheral monocytes and T lymphocytes of AS patients are up-regulated and their levels are positively correlated with patients' ESR and CRP. It implies that CD147 plays critical roles in the pathogenesis and development of AS.

[Study on visual evoked related potentials in young adults of different COMT genotypes by using a numeric working memory task].

AIM: To explore the change of number working memory ability in healthy young adults, a continuous 3-back number working memory task were performed for an hour and 12 Blocks according to different COMT genotypes of young adults. METHODS: 18 different genotype subjects were chosen from 112 healthy young adults, P3 event-related potentials was utilized to observe the relationship between this COMT polymorphism and cortical physiology in a continuous working memory task. RESULTS: Subjects bearing the Val/Val homozygote had significantly higher mean P3 amplitudes than Val/Met heterozygote (P < 0.01), however, no significant differences in comparison to Met/Met homozygote. CONCLUSION: Val/Met Heterozygote subjects are associated with the poorest performance of working memory. There is a relationship between COMT genotype and P3 visual event-related potentials evoked from 3-back task.