The role of Pleistocene dispersal in shaping species richness of sky island wintergreens from the Himalaya-Hengduan Mountains.

In addition to topography and climate, biogeographic dispersal has been considered to influence plant diversity in the Himalaya-Hengduan Mountains (HHM), yet, the mode and tempo of sky island dispersal and its influence on species richness has been little explored. Through phylogenetic analysis of Gaultheria ser. Trichophyllae, a sky island alpine clade within the HHM, we test the hypothesis that dispersal has affected current local species richness. We inferred the dynamics of biogeographic dispersal with correlation tests on direction, distance, occurrence time, and regional species richness. We found that G. ser. Trichophyllae originated at the end of the Miocene and mostly dispersed toward higher longitudes (eastward). In particular, shorter intra-regional eastward dispersals and longer inter-regional westward dispersals were most frequently observed. We detected a prevalence of eastward intra-region dispersals in both glacial periods and interglacials. These dispersals may have been facilitated by the reorganization of paleo-drainages and monsoon intensification through time. We suggest that the timing of dispersal corresponding to glacial periods and the prevalence of intra-region dispersal, rather than dispersal frequency, most influenced the pattern of species richness of G. ser. Trichophyllae. This study facilitates a more comprehensive understanding of biodiversity in the sky islands within the HHM.

[Research Progress of Ubiquitin Proteasome Inhibitors in Acute Myeloid Leukemia].

Ubiquitin-proteasome system (UPS) plays an essential role in eukaryotic protein cycle,the dysregulation of which can lead to tumorigenesis.Increased activities of UPS have been observed in the patients with cancers including leukemia.UPS inhibitors can kill cancer cells by affecting ubiquitin-ligating enzyme E3,deubiquitinase,and protein degradation active sites of UPS.Therefore,UPS inhibitors have emerged as an important therapy for treating hematological malignancies,while they are rarely applied in the treatment of acute myeloid leukemia.This paper summarizes the research progress in the inhibitors affecting the protein ubiquitination at different stages of acute myeloid leukemia,aiming to provide new clues for the clinical treatment of acute myeloid leukemia.

Case report: Safety and efficacy of adalimumab in treating difficult-to-treat rheumatoid arthritis in a human immunodeficiency virus-positive patient, one year follow-up.

Rheumatoid arthritis (RA) is a joint-disabling inflammatory disease associated with the pathology of synovitis. Some patients with RA are difficult to treat, using disease-modifying anti-rheumatic drugs (DMARDs). Biology and targeted synthetic DMARDs (b/tsDMARDs) are options for patients with RA. Acquired immunodeficiency syndrome (AIDS) is an infectious disease caused by the human immunodeficiency virus (HIV). Adalimumab is an anti-tumor necrosis factor therapy commonly used in patients with RA. However, there are no reports or related data on patients with RA-HIV/AIDS treated with adalimumab are available. In this report, we described the first successful case of a 60-year-old HIV-positive woman with difficult-to-treat RA treated with ADA after being screened for hepatitis virus, latent tuberculosis (LTBI), and other infections. She contracted HIV from sexual exposure while on adalimumab therapy. As the patient was resistant to first-line DMARDs, she continued adalimumab along with the initiation of highly active antiretroviral therapy (HAART). The patient was treated with adalimumab therapy for a year; her CD4+ lymphocyte count was normal, HIV-1 RNA decreased, and no new infections were triggered. The patient achieved clinical remission of RA. In conclusion, adalimumab is a safe option for patients with RA-HIV and may slow the progression of HIV infection. Furthermore, HAART has the potential to reduce joint pain and fatigue in patients with difficult-to-treat RA. Conclusions: Adalimumab is a safe option for patients with RA-HIV, and may slow down the progression of HIV infection. The HAART therapy has the potential to reduce joint pain and fatigue in patients with difficult-to-treat RA.

Association of neutrophil-to-lymphocyte ratio with renal impairment among patients with acute gouty arthritis.

OBJECTIVE: Gouty arthritis (GA) is an inflammatory disease, and renal impairment may occur to varying degrees with the progress of disease. The neutrophil-to-lymphocyte ratio (NLR) is an inflammatory marker. In this study, we aimed to explore the association between NLR and renal impairment in GA. MATERIALS AND METHODS: The subjects comprised 499 patients with gouty arthritis (GA) (473 men, 26 women; age range, 39-61 years old) from our hospital. They were divided into a chronic kidney disease (CKD) group (n = 206) and non-CKD group (n = 293) according to the glomerular filtration rate. Blood samples were collected during the gout flares. The differences in NLR, general data, and laboratory indexes of patients with GA between the two groups were compared, such as serum uric acid (SUA), serum creatinine (SCREA), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), high-density lipoprotein (HDL), and low-density lipoprotein (LDL). RESULTS: NLR (3.38 vs. 2.38 (p < 0.001)) was higher in the CKD group, compared to the non-CKD group. Similarly, both SUA (527 vs. 507 (p < 0.05)) and SCREA (122 vs. 87 (p < 0.001)) were higher in the CKD group than in the non-CKD group. Multivariate logistic regression analysis showed that NLR (OR = 1.122, p < 0.05), age, hypertension, and SUA were risk factors for CKD in patients with GA, although HDL and HGB were protective factors. The receiver operating characteristic (ROC) curve analysis indicated that the area under the curve of NLR for predicting CKD in patients with GA was 0.646 (95% CI 0.597-0.694). CONCLUSION: Our data showed that NLR might be an important potential factor for evaluating renal impairment in GA during flares.

Identification of Candidate Genes Related to Synovial Macrophages in Rheumatoid Arthritis by Bioinformatics Analysis.

OBJECTIVE: Rheumatoid arthritis (RA) is one of the most prevalent inflammatory arthritis worldwide. However, the genes and pathways associated with macrophages from synovial fluids in RA patients still remain unclear. This study aims to screen and verify differentially expressed genes (DEGs) related to identifying candidate genes related to synovial macrophages in rheumatoid arthritis by bioinformatics analysis. METHODS: We searched the Gene Expression Omnibus (GEO) database, and GSE97779 and GSE10500 with synovial macrophages expression profiling from multiple RA microarray dataset were selected to conduct a systematic analysis. GSE97779 included nine macrophage samples from synovial fluids of RA patients and five macrophage samples from primary human blood of HC. GSE10500 included five macrophage samples from synovial fluids of RA patients and three macrophage samples from primary human blood of HC. Functional annotation of DEGs was performed, including Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Protein-protein interaction (PPI) network of DEGs was established using the STRING database. CytoHubba was used to identify hub genes. MCODE was used to determine gene clusters in the interactive network. RESULTS: There were 2638 DEGs (1425 upregulated genes and 1213 downregulated ones) and 889 DEGs (438 upregulated genes and 451 downregulated ones) selected from GSE97779 and GSE10500, respectively. Venn diagrams showed that 173 genes were upregulated and 106 downregulated in both two datasets. The top 10 hub genes, including FN1, VEGFA, HGF, SERPINA1, MMP9, PPBP, CD44, FPR2, IGF1, and ITGAM, were identified using the PPI network. CONCLUSION: This study provides new insights for the potential biomarkers and the relevant molecular mechanisms in RA patients. Our findings suggest that the 10 candidate genes might be used in diagnosis, prognosis, and therapy of RA in the future. However, further studies are required to confirm the expression of these genes in synovial macrophages in RA and control specimen.

Plastid phylogenomics and adaptive evolution of Gaultheria series Trichophyllae (Ericaceae), a clade from sky islands of the Himalaya-Hengduan Mountains.

Gaultheria series Trichophyllae Airy Shaw is an angiosperm clade of high-alpine shrublets endemic to the Himalaya-Hengduan Mountains and characterized by recent species divergence and convergent character evolution that has until recently caused much confusion in species circumscription. Although multiple DNA sequence regions have been employed previously, phylogenetic relationships among species in the group have remained largely unresolved. Here we examined the effectiveness of the plastid genome for improving phylogenetic resolution within the G. series Trichophyllae clade. Plastid genomes of 31 samples representing all 19 recognized species of the series and three outgroup species were sequenced with Illumina Sequencing technology. Maximum likelihood (ML), maximum parsimony (MP) and Bayesian inference (BI) phylogenetic analyses were performed with various datasets, i.e., that from the whole plastid genome, coding regions, noncoding regions, large single-copy region (LSC) and inverted-repeat region a (IRa). The partitioned whole plastid genome with inverted-repeat region b (IRb) excluded was also analyzed with ML and BI. Tree topologies based on the whole plastid genome, noncoding regions, and LSC region datasets across all analyses, and that based on the partitioned dataset with ML and BI analyses, are identical and generally strongly supported. Gaultheria series Trichophyllae form a clade with three species and one variety that is sister to a clade of the remaining 16 species; the latter comprises seven main subclades. Interspecific relationships within the series are strongly supported except for those based on the coding-region and IRa-region datasets. Eight divergence hotspot regions, each possessing >5% percent variable sites, were screened across the whole plastid genome of the 28 individuals sampled in the series. Results of morphological character evolution reconstruction diagnose several clades, and a hypothesis of adaptive evolution for plant habit is postulated.

High expression of S100A8 gene is associated with drug resistance to etoposide and poor prognosis in acute myeloid leukemia through influencing the apoptosis pathway.

S100A8 has been increasingly recognized as a biomarker in multiple solid tumors and has played pivotal roles in hematological malignancies. S100A8 is potentially an indicator for poor survival in acute myeloid leukemia (AML) in retrospective studies. However, the mechanisms of S100A8 are diverse in cancers. In this study, we investigated the correlation of S100A8 at the transcription level with clinical parameters in 91 de novo AML patients and explored its mechanisms of chemoresistance to etoposide in vitro. The transcription level of S100A8 was significantly lower at initial and relapse stages of AML samples than at complete remission (P<0.001) and than in the control group (P=0.0078), while no significant difference could be found between initial and relapse stages (P=0.257). Patients with high transcription levels of S100A8 exhibited a shorter overall survival (P=0.0012). HL-60 cells transfected with S100A8 showed resistance to etoposide with a higher level IC50 value and lower apoptosis rate compared with HL-60 cells transfected with empty vector. Thirty-six genes were significantly downregulated and 12 genes were significantly upregulated in S100A8 overexpression group compared with control group in which 360 genes involved in apoptotic genes array were performed by real-time reverse transcriptase polymerase chain reaction. Among them, the caspase-3, Bcl-2, and Bax were verified by Western blot analysis which indicated that the role of S100A8 in resistance to chemotherapy was closely related with antiapoptosis. In conclusion, critical S100A8 provided useful clinical information in predicting the outcome of AML. The main mechanism of S100A8 which promoted chemoresistance was antiapoptosis.