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The selection of a correct level in lumbar spinal stenosis (LSS) remains a common problem and is critically important to the effectiveness of this surgical treatment. Surgery is invasive, and extended laminectomy may lead to secondary surgical complications. The application of diffuse tensor imagining (DTI) and paraspinal mapping (PM) in addition to conventional magnetic resonance imaging (cMRI) may be helpful in this respect. However, the superiority of cMRI + DTI over cMRI+ (DTI or PM) in reducing decompression has not yet been established. We compared the surgical levels, determined by cMRI + DTI and cMRI+ (DTI or PM) (self-control). Treatment outcome measurements were performed at two weeks, three months, six months, and twelve months postoperatively. The surgical levels determined by cMRI ± DTI showed less than that determined by cMRI± (DTI or PM) with statistically significant differences (p value = 0.0199) and cMRI ± PM with no statistically significant differences (p value = 0.5503). The effectiveness of cMRI ± DTI in the reduction of the surgical levels in degenerative lumbar spinal stenosis is superior than that of cMRI± (DTI or PM). [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the relationships among participation, peer support, self-regulated learning (SRL), course discipline and academic performance in small private open course (SPOC) environments. The study sample comprised of 309 undergraduates who completed SPOCs within the past year and consisted of 53% males (N = 164) and 47% females (N = 145). Multilevel modeling showed that participation, self-regulated learning, and peer support significantly predicted academic performance. Furthermore, findings revealed that emotional support did not have a significant impact on students' academic performance in contrast to informational support. In addition, students within science courses or social and humanity courses accomplish significantly higher academic performance than students within art courses. The findings also highlighted that, compared to students within art courses, the positive effect of participation and informational support on academic performance increased among students within science courses and social and humanity courses. [ABSTRACT FROM AUTHOR]

This study aims to explore tooth growth variation by regions and ethnicity in China, and to validate the modified Tibetan so as to assist in proposing a better approach. A total of 1320 orthopantomograms of Han children aged 4–14.99 were retrospectively collected from eastern and western regions of China. The Demirjian method and modified Tibetan method were applied. Results showed that dental maturity scores (DMS) in eastern children were significantly greater than western children. Age was overestimated by both methods in eastern children. MAE was 0.88 and 1.3 years by Demirjian method, 1.01 and 1.21 years by modified Tibetan method in eastern girls and boys respectively. In western children, age was significantly underestimated in girls and slightly overestimated by Demirjian method; by modified method, age was generally overestimated. MAE was 0.79 and 0.84 years by Demirjian method, 0.51 and 0.69 years by modified Tibetan method in girls and boys respectively. The current study reveals that tooth growth was significantly advanced in Eastern Han children compared with Western Han children. Ethnic variation between Eastern Han and Tibetan Chinese was substantial. Neither method was sufficiently accurate in Eastern Han children. The modified Tibetan method was reliable in Western Han children. [ABSTRACT FROM AUTHOR]

As a result of the rapid advancement in information and communication technologies, learning cyberspace has become a channel for teachers to share learning resources. This study explored the influencing factors of learning resource sharing in teacher learning cyberspace. The study sample consisted of 363 high-quality teacher learning cyberspaces that had received platform awards from 2015 to 2019, among which 41% of cyberspace owners were male (N = 149) and 59% were female (N = 214). The number of space-associated friends, space follows, space followers, space messages, resources spread, space visits, community contributions, external rewards, the proportion of original resources and uploaded resources, which were collected by the web crawler technology were taken as measurement dimensions. The results of structural equation model indicated that trust positively correlated with learning resource sharing, while self-efficacy and reciprocity were not significantly related to learning resource sharing. In addition, it was shown that trust affected self-efficacy and reciprocity dramatically. Based on this, the trust level of teachers in learning cyberspace can be improved by adding the function of friend circle, setting up effective incentives, and copyright protection mechanisms to facilitate teachers’ learning resource sharing. [ABSTRACT FROM AUTHOR]

Typical reinforcement learning (RL) requires a huge amount of data before achieving an acceptable result, and its performance can be rather poor during initial interacting process. Sample inefficiency and cold-start phenomenon of RL limits its feasibility in a range of real-world applications such as traffic signal control (TSC). On the other hand, a large amount of data on TSC can be accumulated by various model-based controllers (MBCs) rooted in traffic engineering. In this context, we propose a new RL approach which can avoid the appearance of cold starts by taking advantage of MBC experiences. First, three frameworks of joint utilization of RL and MBC are summarized for TSC, and staged framework is considered to have the edge over the other two. Then, a staged noisy-net prioritized dueling double deep Q-network (NPDD-DQN) is described in detail for TSC, where MBC experiences are used in both pre-training and online training processes. Experimental evaluation demonstrates that staged NPDD-DQN can achieve a boost in initial performance as compared to pure NPDD-DQN that does not utilize any control experiences, and learn to improve final performance beyond the underlying MBC. The effectiveness of the proposed method opens up the possibility of real implementation of RL in TSC. [ABSTRACT FROM AUTHOR]

Biological soil crust is an important feature of desert ecosystem composition and surface landscape. Determining the role of biological soil crust in the energy flow and logistics cycle in the desert ecosystem is one of the frontier areas of ecological restoration in arid and semi-arid areas. Obtaining biological soil crust information from drone images is an efficient, fast, and low-cost method. However, due to the scattered and uneven growth of biological soil crusts and the complexity of the field environment, it is difficult to accurately extract biological soil crusts. In view of this, this study used the improved UNet++ model to extract biological soil crusts based on UAV image data. Firstly, the optimal Epoch, Backbone, and Loss function are selected and trained based on the network structure of UNet++ model. Then, the improved UNet++ model proposed in this paper, which takes ResNeXt as the Backbone and Soft Cross-Entropy Loss+Dice Loss as the Loss Function, is obtained. Finally, the test results of UNet++, U-Net, LinkNet, FPN, and PSPNet are compared with the improved UNet++ model in this paper. The results showed that the improved UNet++ model had the best segmentation effect, and the precision, recall, F1-Score, and IoU were 0.9788, 0.9501, 0.9495, and 0.9309, respectively. UAV image biological soil crust recognition based on the improved UNet++ model in this paper can obtain high-precision extraction results, provide good data support for studying the development of biological soil crusts in arid areas, and provide a new method for precise segmentation of different features in arid areas. In particular, it is of great significance to evaluate the governance effect of ecological restoration projects. [ABSTRACT FROM AUTHOR]

Recent years have witnessed the increasing collaboration between science and visual art/design projects. Kuang-Yi Ku, a Taiwanese artist based in the Netherlands whose artistic practice that converges art, design, and biotechnology is a case in point. Ku's works often deal with the human body, sexuality, interspecies interactions, and medical technology that aim to investigate the relationships among technology, individuals, and the environment. Based on Ku's practices in and observations on the expanded field of "Art and Science Collaboration", he converses with Liang-Kai Yu, PhD researcher in radical museology and queer studies. Firstly, they begin with Ku's speculative approach in bio-art/design that mobilizes not only visual languages in arts but also biomedical technology. Of interest here is whether the future orientation of a speculative approach in art/design could not only stimulate imaginations but also trouble the linear notion towards the future. Secondly, Ku and Yu reflect on the increasing demand for social and ecological goals requested by science-based artist residencies and open calls in Europe. This institutional phenomenon concerns the functionality of art and remains a debated subject. Thirdly, they discuss the shared concerns between bio-art/design and STS studies and consider how both fields could benefit from each other. Finally, the conversation moves back to Ku's bio-artistic projects with a focus on reproductive technology as well as the cross-species future. They address Ku's recent projects such as "Grandma Mom" (2021) that questions the patriarchal regime within the medical field and the ongoing "Queer Termite Project" that speculates an inter-species architecture in which humans and termites reciprocate one another. [ABSTRACT FROM AUTHOR]

Immunoglobulin A nephropathy (IgAN), the most common primary renal disease, is characterized by abnormal IgA1 deposition. IgAN is caused by NOD-like receptor pyrin domain-containing-3 (NLRP3), which regulates innate immunity. Gubentongluo (GB) decoction, a traditional Chinese medicine, is an effective clinical treatment for IgAN in China. However, little is known about the underlying mechanisms. In this study, IgA1, which is separated from patients with IgAN, together with GB decoction was applied to treat human mesangial cells (HMCs). CCK-8 and the enzyme-linked immunosorbent assay were used to assess cell proliferation and the production of interleukin-1β (IL-1β), respectively. qPCR and Western blot were applied to detect the expression levels of NLRP3, IL-1β, and caspase-1. Our results showed that GB decoction inhibited IgA1-induced cell proliferation and IL-1β production. Furthermore, IgA1-induced upregulation of IL-1β, NLRP3, and caspase-1 was reduced after treatment with GB. Interestingly, MCC950, an NLRP3 inhibitor, showed similar effect as GB decoction. Additionally, NLRP3 overexpression stimulated cell proliferation, IL-1β secretion, and the expressions of IL-1β and caspase-1 in HMCs. But these effects could be alleviated by GB decoction. In conclusion, GB may play a protective role in IgAN cell model by inhibiting NLRP3. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has spread rapidly and significantly impacted most countries in the world. Providing an accurate forecast of COVID-19 at multiple scales would help inform public health decisions, but recent forecasting models are typically used at the state or country level. Furthermore, traditional mathematical models are limited by simplifying assumptions, while machine learning algorithms struggle to generalize to unseen trends. This motivates the need for hybrid machine learning models that integrate domain knowledge for accurate long-term prediction. We propose a three-layer, geographically informed ensemble, an extensive peer-learning framework, for predicting COVID-19 trends at the country, continent, and global levels. As the base layer, we develop a country-level predictor using a hybrid Graph Attention Network that incorporates a modified SIR model, adaptive loss function, and edge weights informed by mobility data. We aggregated 163 country GATs to train the continent and world MLP layers of the ensemble. Our results indicate that incorporating quantitatively accurate equations and real-world data to model inter-community interactions improves the performance of spatio-temporal machine learning algorithms. Additionally, we demonstrate that integrating geographic information (continent composition) improves the performance of the world predictor in our layered architecture. [ABSTRACT FROM AUTHOR]

With the outbreak of coronavirus disease 2019 (COVID-19), there has been an increasing focus on exploring the relationship between SARS-CoV-2 infection and tumors. However, there is no consensus on the association between COVID-19 and lymphoma. In this study, genome-wide association study (GWAS) summary data sets for COVID-19 and lymphoma were obtained from the OPEN GWAS website. Single nucleotide polymorphisms (SNPs) were selected as genetic instrument variants for fulling P < 5 × 10−8 and linkage disequilibrium [LD] r2 < 0.001. Both palindromic and outlier SNPs were removed. Cochran's Q test, the MR‒Egger intercept test, and leave-one-out analysis were employed to assess the sensitivity of the effect of COVID-19 on lymphoma. The results showed that COVID-19 patients with very severe respiratory symptoms have an increased risk of developing diffuse large B-cell lymphoma (IVW, OR = 1.765, 95% CI 1.174–2.651, P = 0.006). There was no association between COVID-19 with very severe respiratory symptoms and Hodgkin's lymphoma or other types of non-Hodgkin's lymphoma. No horizontal or directional pleiotropy was observed in the Mendelian randomization analysis. In conclusion, SARS-CoV-2 infection with very severe respiratory symptoms may be a potential risk factor for diffuse large B-cell lymphoma (DLBCL), and follow-up studies with larger samples are needed. [ABSTRACT FROM AUTHOR]

Optimal post-remission treatment for individual favorable and intermediate risk acute myeloid leukemia (AML) patients has not yet been established. Human leukocyte antigen (HLA)-mismatched stem cell microtransplantation (MST), may improve outcomes and avoid graft-versus-host disease in patients with first complete remission of AML. We retrospectively analyzed the efficacy, safety, and survival of 63 patients with favorable- or intermediate-risk AML who received MST, autologous stem cell transplantation (ASCT), or cytarabine single agent (CSA) as post-remission treatment from January 2014 to August 2021. The neutrophil recovery time was shorter in the MST group than in the CSA group. The 2-year cumulative incidences of relapse in the MST, ASCT, and CSA groups were 27.27%, 29.41%, and 41.67%, respectively. During follow-up, 21 patients (33.30%) died of relapse, including six (9.52%), five (7.94%), and 10 (15.84%) in the MST, ASCT, and CSA groups, respectively. The estimated 2-year overall survival (OS) and relapse-free survival (RFS) were 62.20% vs. 50.00% (P = 0.101) and 57.10% vs. 50.00% (P = 0.136), in the >60 years MST and CSA groups (P = 0.101). The estimated 2-year OS was 100%, 66.20%, and 69.10% in the MST, ASCT, and CSA groups (MST vs CSA, P = 0.044), meanwhile, the estimated 2-year RFS was 100%, 65.40%, and 59.80% in patients ≤60 years. MST, ASCT, and CSA are acceptable post-remission treatments for patients with favorable- and intermediate-risk AML and may not only improve the prognosis of the elderly but also prolong the OS and RFS of favorable- or intermediate-risk patients ≤60 years. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the incidence and prognostic significance of common cytogenetic and molecular abnormalities in patients with TP53-mutated and non-TP53-mutated acute myeloid leukemia (AML). We retrospectively analyzed the clinical data of 326 patients with newly diagnosed AML hospitalized in our institution between October 2015 and June 2021. Classification variables were reported as percentages and compared by χ2 tests. Survival rates were evaluated by the Kaplan-Meier method. The incidence of TP53 mutations in AML patients in this clinic was 9.8%, of whom 87.5% patients were over 50 years old. The common concurrent mutations of TP53 were DNMT3A, IDH2, NRAS and TET2. Patients with a TP53 variant allele frequency (VAF) ≤ 40% had better overall survival (OS) than patients with a VAF >40%. Compared with non-TP53-mutated patients, significantly more TP53-mutated patients were gene-fusion negative, +mar, – 7/del (7q), – 5/del (5q), – 17/17p-, – 12/12p-, incomplete (inc) karyotype, or complex karyotype (CK), and had FLT3-ITD or IDH2 mutations, as well as a lower complete remission (CR) rate (31.3%) and higher recurrence rate (80.0%). The 2-year OS rates of TP53-mutated and non-TP53-mutated patients were 18.8% and 47.3%, respectively (P < 0.001). Univariate analysis showed that non-TP53-mutated patients with MLL family gene fusion, +mar or – 17/17p – karyotype, and FLT3-ITD mutations had a poor prognosis, while t(8; 21) karyotype was associated with a better prognosis. TP53-mutated patients with – 7/del (7q) or – 5/del (5q) karyotype had a poor prognosis. The cytogenetic and molecular landscapes differed between TP53-mutated and non-TP53-mutated patients, and some abnormalities had different values between them. [ABSTRACT FROM AUTHOR]

Previous studies validated the prognostic significance of lymphocyte to monocyte ratio (LMR) in patients with solid tumors and some hematologic malignancies. However, the correlation between LMR and Myelodysplastic Neoplasms (MDS) was unclear. The study intends to investigate the prognostic impact of LMR on MDS patients. 91 newly diagnosed MDS patients were included in this retrospective study. The cut-off of LMR was 3.2 by X-Tile. All patients were divided into the low LMR group (<3.2) and the high LMR group (≥3.2). Clinical characteristics were compared between the two groups. Patients in the high LMR group (n = 67) had better OS (P = 0.007) from the Kaplan-Meier survival curves. The results of the univariate analysis demonstrated that LMR was a prognostic factor for OS [hazard ratio (HR) = 2.070, 95%CI 1.201-3.571, P = 0.009]. After multivariate cox analysis, low LMR was confirmed to be an independent predictor of poor OS in MDS patients (HR = 1.872, 95%CI 1.084-3.230, P = 0.024). LMR, a representative marker of systematic inflammation and immune response, has potential prognostic significance in MDS patients. [ABSTRACT FROM AUTHOR]

To explore the clinical outcomes and characteristics of TP53-mutated primary myelodysplastic syndromes (MDS). A total of 74 de novo primary MDS patients who were diagnosed and treated in the Department of Hematology of our hospital from January 2018 and September 2021 were analyzed retrospectively. All patients had evaluable blood cell counts, mean corpuscular volume (MCV), lactate dehydrogenase (LDH), bone marrow (BM) morphology, biopsy, and MDS-related 20-gene mutations sequencing. In addition, 69 of 74 patients had complete cytogenetic analysis through conventional chromosome analysis and fluorescence in-situ hybridization. Patients were divided into two cohorts, the TP53-mutated type (TP53Mut) group (n = 19) and TP53 wild type (TP53WT) group (n = 55). Compared with the TP53WT group, patients in the TP53Mut group had higher ratios of cytogenetic abnormalities (82.4% vs. 30.8%, P < 0.001), with 5q- karyotype (64.70% vs. 38.5%, P < 0.001), complex karyotype(CK) (64.70% vs. 38.5%, P < 0.001), HR-MDS (94.7% vs. 61.8%, P = 0.008), and acute myelogenous leukemia (AML) transformation (26.3% vs. 12.7%, P < 0.001). Interestingly, patients in the TP53Mut group had lower median MCV than the TP53WT group (94.40 fl vs. 101.90 fl, P = 0.008). Furthermore, MCV = 100 fl as cutoff, and found that MCV ≤ 100 fl was more common in the TP53Mut group (73.7% vs. 38.2%, P < 0.001). After 1–4 courses of HMA ± chemotherapy, the overall response rate of the TP53Mut group was higher than the TP53WT group (83.3% vs. 71.4%, P = 0.012). With the median follow-up 12.0 months (1–46 months), the results show that the median OS and leukemia-free survival (LFS) of TP53Mut group was significantly shorter than the TP53WT group (P = 0.0018; P = 0.0310). Results of multivariate Cox proportional hazard analyses show TP53 mutation was an independent prognostic factor for the OS (HR 2.724, 95%CI 1.099–6.750, P = 0.030). TP53-mutated primary MDS patients were associated with higher frequency of cytogenetic abnormalities, with 5q- karyotype, CK, AML transformation, higher risk IPSS-R, lower MCV and sensitive to HMA treatment, but worse survival. [ABSTRACT FROM AUTHOR]

Prognostic nutritional index has been found to be related to the clinical outcomes of patients with cancer. However, its role in myelodysplastic syndromes (MDS) patients is unclear. We aimed to assess the value of nutritional status in predicting the prognosis of MDS patients. Totally 121 MDS patients were analyzed retrospectively. The prognostic nutritional index (PNI) was used to assess nutritional status of the patients. The bio-informatics tool X-tile was used to define the threshold, and accordingly patients were divided into PNIlow and PNIhigh groups, the characteristics were compared between two groups. The PNIhigh was associated with better OS (Overall Survival) than PNIlow in MDS patients (Median OS, 28.03 months versus 19.63 months, P = 0.0205). But there were no statistical differences in PFS (Progression-Free-Survival) between the two groups (P = 0.9373). The univariable and multivariable COX proportional hazard analysis adjusted for age, gender, platelet count, HB level and IPSS-R scores, and the results showed that PNI is a useful index in the evaluation of the OS of MDS (HR 0.588, 95%CI 0.374–0.926, P = 0.024). PNI would be a simple and immediately available tool for predicting the prognosis of MDS. [ABSTRACT FROM AUTHOR]

Shenling Baizhu Powder is a traditional Chinese medicine formula that has been used for thousands of years to invigorate spleen, nourish stomach and regulate immune function. The multi-herbal extracts, an improved formular from Shenling Baizhu Powder, were used in our study to investigate its immune-enhancing effects and underling mechanisms. Based on UPLC-Q-TOF-MS and SPME-GC-MS analysis, 106 chemical compounds were identified from the extracts. In vitro assays indicated that the extracts could promote cell proliferation and NO secretion of RAW264.7 cells. RNA-seq and RT-qPCR showed that RAW264.7 cells treated with extracts increased the expression of pro-inflammatory factors IL-1ß, iNOS, TNF-a, and TGF-ß. Western-Blot revealed that the extracts could significantly enhance ERK phosphorylation level, and slightly increased JNK and p38 phosphorylation levels. These data suggest that multi-herbal extracts have a potential of regulating immune response via the JNK/p38/ERK signalling of MAPK pathways in RAW264.7 cells. [ABSTRACT FROM AUTHOR]

This study investigated the biological activity of essential oils (EOs) and their main components (caryophyllene and cuminol) against Tribolium castaneum larvae and Lasioderma serricorne adults. EOs were extracted from both flowers and leaves of Elsholtzia stauntoni. The results indicated that the EOs derived from both flowers and leaves, as well as their main components (caryophyllene and cuminol), exhibited contact activities with LD50 values of 35.11, 43.66, 15.44, and 26.05 µg/larva, respectively, against T. castaneum larvae. Moreover, they demonstrated obvious contact toxicities with LD50 values of 14.15, 11.18, 17.81, and 13.91 µg/adult, respectively, against L. serricorne adults. Additionally, EOs from both flowers and leaves exhibited fumigant activities against T. castaneum larvae (LC50 = 24.42 and 62.54 mg/L) and L. serricorne adults (LC50 = 15.26 and 24.29 mg/L). Furthermore, the EOs of flowers and leaves and their main components (caryophyllene and cuminol) remained significantly repellency to T. castaneum larvae and L. serricorne adults within the testing concentration range of 78.63-15.83 nL/cm2 after 12 h of exposure. These findings suggested that the EO from E. stauntoni and its two major components could potentially be developed as a natural insecticide for controlling T. castaneum larvae and L. serricorne adults. [ABSTRACT FROM AUTHOR]

Controlling nutritional status (CONUT) score, based on three indexes including serum albumin (ALB), total cholesterol (CHO), and absolute lymphocyte count (ALC), has been closely associated with the prognosis of cancer patients. Multiple studies revealed the significance of CONUT score in hematological malignancies, including diffuse large B-cell lymphoma (DLBCL), peripheral T-cell lymphoma (PTCL), multiple myeloma (MM), and leukemia. This review aimed to explore the prognostic role of CONUT score in hematological malignancies. We conducted this review through Pubmed to summarize the published studies on the CONUT score in hematological malignancies, using the terms: Controlling nutritional status, CONUT score, hematological malignancy, lymphoma, multiple myeloma, and leukemia. CONUT score can reflect not only the nutritional status but also the inflammatory status of patients with hematological malignancies. It can assist in predicting the survival of patients with DLBCL, PTCL, MM, adult T-cell leukemia (ATL), myelodysplastic syndrome (MDS), and acute myeloid leukemia with myelodysplasia related changes (AML-MRC). CONUT score plays an important role in predicting the prognosis of patients with hematological malignancies. [ABSTRACT FROM AUTHOR]

Nucleophosmin 1 (NPM1, also known as B23) is a multifunctional protein involved in a variety of cellular processes, including ribosomal maturation, centrosome replication, maintenance of genomic stability, cell cycle control, and apoptosis. NPM1 is the most commonly mutated gene in adult acute myeloid leukemia (AML) and is present in approximately 40% of all AML cases. The underlying mechanisms of mutant NPM1 (NPM1mut) in leukemogenesis remain unclear. This review summarizes the structure and physiological function of NPM1, mechanisms underlying the pathogenesis of NPM1-mutated AML, and the potential role of NPM1 as a therapeutic target. It is reported that dysfunctional NPM1 might cause AML pathogenesis via its role as a protein chaperone, inhibiting differentiation of leukemia stem cells and regulation of non-coding RNAs. Besides conventional chemotherapies, NPM1 is a promising therapeutic target against AML that warrants further investigation. NPM1-based therapeutic strategies include inducing nucleolar relocalisation of NPM1 mutants, interfering with NPM1 oligomerization, and NPM1 as an immune response target. [ABSTRACT FROM AUTHOR]

Hainanmycin is a polyether antibiotic. Toxicological studies have shown the adverse effects of hainanmycin on animals and humans. At present, no study is available on the detection of hainanmycin in edible tissues of animals. Hence, a fast and accurate detection method for hainanmycin is essential. This study aimed to develop a new analytical method based on ultra-high-performance liquid chromatography-tandem mass spectrometry to detect hainanmycin in 10 matrices, including milk, eggs, fat, kidney, muscles and livers of chicken, beef and sheep. The limit of detection and the limit of quantitation of the 10 matrices were 0.1–0.4 μg/kg and 0.25–1 μg/kg, respectively, and were far below the maximum residue limits of other polyether anticoccidial drugs (1–150 μg/kg). The recoveries of hainanmycin ranged from 79% to 105%, and the relative standard deviation ranged from 2.8% to 12.0%. The research results prove that the proposed method is operational and simple in detecting hainanmycin, and has high precision and accuracy in a variety of matrices. [ABSTRACT FROM AUTHOR]

Abstract Objective: This study aimed to investigate the functions of lncRNA H19 on glomerular endothelial structural damage of diabetic nephropathy (DN). Materials and Methods: Rats were fed a high sugar and fat high feed die, and intraperitoneally administrated with streptozotocin (30 mg/kg) to induce DN model. Meanwile, rat glomerular endothelial cells (rGEnCs) were treated with high a level of glucose （HG, 30 mM glucose）to induce structural damage. Results: Our results showed that H19 level was drastically increased in diabetic glomeruli and high-glucose (HG)-stimulated rat glomerular endothelial cells (rGEnCs). Deficiency of H19 ameliorated microalbumin, creatinine, BUN, and histopathological alterations in diabetic rats. In addition, H19 deficiency significantly attenuated the damage of endothelial structure by upregulating the expression of junction proteins ZO-1 and Occludin, glycolcalyx protein Syndecan-1, and endothelial activation marker sVCAM-1 and sICAM-1 in diabetic rats. The in vitro results also showed that H19-siRNA alleviated glycocalyx shedding, tight junctions damage, and endothelial activation in HG-stimulated rGEnCs. Moreover, H19 deficiency significantly enhanced the expression of p-Akt and p-eNOS and NO concentration in vitro and in vivo. Pre-treatment with Akt inhibitor LY294002 abrogated these favourable effects mediated by H19 deficiency. Discussion and Conclusion: These results indicate that H19 deficiency could mitigate the structural damage of glomerular endothelium in DN via activating Akt/eNOS pathway. [ABSTRACT FROM AUTHOR]

Objectives: Extramedullary multiple myeloma (EMM) is a relatively less frequent subentity of multiple myeloma (MM) and is generally considered to be a poor prognostic factor. Novel agents and hematopoietic stem cell transplantation (HSCT) have led to a significant improvement in the progression-free survival and overall survival of patients with MM, but outcomes of EMM remain dismal. Little is known regarding the role of novel therapies in this setting. This review summarizes the current available data regarding the roles of proteasome inhibitors, immunomodulators, monoclonal antibodies, chimeric antigen receptor (CAR)-T cell therapy and HSCT in EMM. Methods: A systematic literature review through PubMed was conducted to summarize the published evidence on the therapeutic developments of novel agents and HSCT in EMM. Literature sources published in English were searched, using the terms multiple myeloma, extramedullary and treatment. Results: Long-term outcomes of EMM patients remain dismal despite the utilization of novel agents and HSCT. The standard therapy of EMM has not been established. EMM should be managed as high-risk disease and treated accordingly. Discussion and conclusion: This review will provide an insight on the current and emerging treatment strategies as well as their efficacy in EMM. Further subgroup analyses in large prospective trials focusing on EMM is needed to help optimize the therapy. [ABSTRACT FROM AUTHOR]

To explore the relationship between platelet count and bleeding score in immune thrombocytopenia purpura (ITP) and compare the clinical practicability of two bleeding grading systems with adult patients with ITP. A total of 204 patients were retrospectively analyzed with the ITP bleeding scale (IBLS) and the ITP bleeding assessment tool (version 2016) (ITP-2016). The correlation between the two bleeding score systems and the relations among the platelet counts were respectively analyzed. (1) There is a linear relationship between platelet count and bleeding score, no matter which scoring system it is based on (rs = −0.429, p < 0.001; rs = −0.331, p < 0.001, the analysis of the number of sites of Grade 1/2 bleeding were done; and rs = −0.466, p < 0.05, the analysis between platelet count and bleeding score by ITP-2016 respectively). (2) Platelet count and bleeding scores are negatively correlated in those with extremely low platelet counts (< 10*109/L). The number of sites of Grade 2 bleeding and the ITP-2016 scores are negatively correlated with platelet counts (rs = −0.15 and rs = −0.244, p < 0.05, respectively). Significantly, there is no correlation between the platelet count and bleeding scores when the platelet count is more than 10*109/L. (3) It takes less time to score with ITP-2016 than IBLS (z = −3.825, P < 0.001). There is good responsiveness, strong assessment consistency, close correlation between ITP-2016 and IBLS. ITP-2016 takes less time-consuming in clinical application. It can be used as an effective tool of condition judgement, risk assessment and efficacy evaluation of patients with ITP. [ABSTRACT FROM AUTHOR]

Acute myeloid leukaemia (AML) is a haematopoietic malignancy with a dismal outcome. Consequently, risk stratification based on more effective prognostic biomarkers is crucial to make accurate therapy decisions. T cell receptor gamma alternative reading frame protein (TARP) has been reported in prostate and breast cancers, but its correlation with AML remains unclear. Differential expression of TARP mRNA in different AML subtypes was analysed using the UALCAN online platform. Its relationship with baseline clinical attributes, survival and efficacy were analysed based on three GSE1159, GSE425 and GSE6891 microarray datasets downloaded from Gene Expression Omnibus (GEO) and Oncomine databases. Quantitative real-time PCR was performed to determine mRNA levels of TARP in bone marrow mononuclear cells (BMMCs) isolated from AML patients. TARP was significantly overexpressed in AML patients. In AML, relatively low TARP expression was associated with the CBFβ-MYH11 fusion gene. The proportion of FLT3 mutations was significantly higher in non-adolescent and young adult (non-AYA, >39 years of age) AML patients who had high TARP levels but not in AYA (15–39 years) patients. High expression of TARP was related to poor outcome by univariate analysis but not by multivariate analysis and unsatisfactory therapeutic effects, which could be overcome by haematopoietic stem cell transplantation (HSCT). Our findings suggest that TARP might be a potential prognostic marker of AML and serve as a promising immunotherapeutic target. [ABSTRACT FROM AUTHOR]