DPYD gene polymorphisms are associated with risk and chemotherapy prognosis in pediatric patients with acute lymphoblastic leukemia.

We aimed to investigate the association between dihydropyrimidine dehydrogenase (DPYD) gene polymorphisms and the risk of pediatric acute lymphoblastic leukemia (ALL) and its prognosis after chemotherapy. A total of 147 pediatric ALL patients diagnosed by our hospital between January 2011 and December 2014 were included in the case group, and 102 healthy people who received a physical examination during the same time frame in our hospital were included in the control group. DNA sequencing was applied for site determination and genotyping of the DPYD 85T > C, 2194G > A, 1156G > T, and IVS14 + 1G > A polymorphisms. The genotype and allele frequencies of the two groups were compared. A significant difference was found in the comparison of the mutant gene and allele frequencies of the 85T > C polymorphism between the case and control groups (P < 0.05). The CT and CC genotypes in the 85T > C polymorphism were associated with the risk of the disease (OR = 1.592, 95 % CI = 1.010-2.509), suggesting that the recessive gene (85C) was more likely to lead to the occurrence of ALL compared with the dominant gene (85T) (P < 0.05). Patients carrying the C allele of the 85T > C polymorphism presented higher damage of their liver functions and higher infection rates compared with patients carrying the non-C allele (P < 0.05). A higher proportion of liver function damage and a higher infection rate were found in patients with the GA genotype in the IVS14 + 1G > A polymorphism compared with the GG genotype (P < 0.05). The complete remission (CR) rate in patients with the GG genotype in the IVS14 + 1G > A polymorphism was higher than in patients with the GA genotype (P = 0.020). After 5-fluorouracil/calcium folinate (5-FU/CF)-based chemotherapy, the event-free survival (EFS) rate of patients with the TT genotype was higher than patients with the CT and CC genotypes (P < 0.05). Our results revealed that the C allele of the 85T > C polymorphism might be associated with susceptibility to pediatric ALL. Patients carrying the C allele may have an increased risk of ALL. Thus, the 85T > C polymorphism may be a predictor of CR for pediatric ALL patients.

Cucurbit[8]uril-Based Supramolecular Probe for the Detection of 3-Nitrotyrosine in Human Serum and Plasma.

The biomarker 3-nitrotyrosine (3-NT) is widely recognized as an indicator of renal oxidative stress injury, making its detection crucial for the early identification of renal insufficiency. This study presents the design and synthesis of a tetraphenylstyrene imidazole derivative (TIPE-MI), which is utilized to create a supramolecular probe in conjunction with cucurbit[8]uril (Q[8]) through host-guest interactions. The resulting supramolecular self-assembly exhibits excellent optical properties and has been employed for the specific detection of 3-NT through fluorescence quenching. The introduction of 3-NT resulted in a decreased fluorescence intensity of the yellow fluorescent probe, which gradually transitioned from bright yellow to light yellow and then became colorless as the 3-NT concentration was increased. A portable detection platform was devised to augment the efficiency of detection. In order to facilitate biological applications, we have substantiated the probe's exceptional precision in detecting 3-NT in biological samples, encompassing human serum and plasma. The probe also exhibited negligible cytotoxicity. The accumulation of the probe in renal cells elicited a fluorescence signal, thereby indicating the prospective viability of this system for visual detection with renal cytocompatibility.

Long-term outcomes and predictive factors of achieving low disease activity status in childhood systemic lupus erythematosus: a Chinese bicentric retrospective registered study.

Background: This study aims to explore the clinical value of low disease activity state (LDAS) in the treat-to-target strategy of pediatric systemic lupus erythematosus (pSLE) and find the risk factors for never reaching LDAS. Methods: A total of 272 children with SLE who were diagnosed and followed up in two tertiary hospitals in China during the period from January 2012 to December 2019 were involved in this study, and the clinical presentation, pathology, and treatment were retrospectively studied. Results: The male-to-female ratio was 1:5.2, the age at diagnosis was 11.1 years (IQR, 9.8-13.1 years), the disease duration was 1.0 month (IQR, 0.5-2.0 months), and follow-up was 36.5 months (IQR, 25.7-50.9 months). During follow-up, 230 children achieved LDAS, and 42 were never been in. Male (P = 0.018), mucosal ulcer (P = 0.048), liver function damage (P = 0.026), cardiac effusion (P = 0.034), anemia (P = 0.048), urine red blood cells (P = 0.017), urinary leukocytes (P = 0.032), and endothelial cell proliferation in renal biopsy (P = 0.004)-these indexes have statistical differences between the two groups in the baseline. At baseline, endothelial cell proliferation (P = 0.02) is an independent risk factor for never achieving LDAS by multivariate logistic analysis. During follow-up, non-compliance was a risk factor for never achieving LDAS by comparing between groups. Children with biologics achieved LDAS at a higher rate than children without biologics (P = 0.038). The proportion of organ damage in patients never been in LDAS was significantly higher than that in patients who achieved LDAS (P < 0.001). Conclusion: Endothelial cell proliferation in renal biopsy and non-compliance during follow-up were independent risk factors for never achieving LDAS. At the end of the follow-up, the organ damage in the remission group was similar to that in the LDAS group, indicating that LDAS can be used as a target for pSLE treatment.

Expression profile of circular RNAs in patients with unstable angina.

BACKGROUND: Circular RNAs (circRNAs) are a new class of noncoding RNAs, which interfere with gene transcription by absorbing microRNAs (miRNAs). OBJECTIVE: The expression profile and roles of circRNAs in unstable angina (UA) patients remains unclear. METHODS: An initial screening of circRNA expression by microarray analysis was performed using blood samples from three pairs of UA patients and matched healthy individuals. The differential expression of the chosen six circRNAs from the results of the microarray analysis was validated by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: The microarray results demonstrated that some circRNAs were markedly different in UA patients, when compared with matched healthy individuals. In these UA patients, 22 circRNAs were upregulated and six circRNAs were downregulated when a P-value of < 0.05 was considered as a cut-off level and the fold change was > 1.5. Among the six circRNAs chosen for further analysis, qRT-PCR identified that five of these were upregulated, and the remaining circRNA was downregulated. By comparing the outcome of the six candidate circRNAs between the circRNAs microarray assay and RT-PCR validation, it was found that four circRNAs (hsa_circ_0002229, hsa_circ_0005580, hsa_circ_0046667, and hsa_circ_0001451) had the same variation trend. CONCLUSION: The present study provided the expression profile of circRNAs in UA patients. Moreover, some circRNAs have the potential to be biomarkers for the detection of UA patients. Further studies with a larger population will focus on hsa_circ_0002229, hsa_circ_0005580, hsa_circ_0046667 and hsa_circ_0001451.

Supramolecular Room-Temperature Phosphorescent Hydrogel Based on Hexamethyl Cucurbit[5]uril for Cell Imaging.

The host-guest interaction between hexamethyl cucurbit[5]uril (HmeQ[5]) and 1,4-diaminobenzene (DB) was investigated, and a new low-molecular-weight supramolecular gel was prepared by a simple heating/mixing cooling method. The structure and properties of the supramolecular gel were characterized. Results revealed that DB molecules did not enter the cavity of HmeQ[5] and that hydrogen bonding between the carbonyl group at the HmeQ[5] port and the DB amino groups, together with dipole-dipole interactions and outer wall interactions, were the main driving forces for the formation of the supramolecular gel. The HmeQ[5]/DB gel system exhibits temperature sensitivity. The phosphor 6-bromo-2-naphthol (BrNp) was embedded in the gel to give the gel fluorescent phosphorescence double emission. The double emission ability at room temperature can be attributed to the ordered microstructure of the supramolecular gel, which effectively avoids the nonradiative transition of BrNp. Meanwhile, HmeQ[5]/DB-BrNp has good biocompatibility and low biotoxicity, which is compatible with HeLa cells to achieve cytoplasmic staining of HeLa in the red channel. The supramolecular gels constructed by this supramolecular assembly strategy not only have good temperature sensitivity but also extend the application of Q[n]s in biomedical fields.

Cucurbit [8] uril-based supramolecular fluorescent biomaterials for cytotoxicity and imaging studies of kidney cells.

An accurate diagnosis of acute kidney injury (AKI) at the early stage is critical to not only allow preventative treatments in time but also forecast probable medication toxicity for preventing AKI from starting and progressing to severe kidney damage and death. Therefore, supramolecular fluorescent biomaterials based on Q [8] and PEG-APTS have been prepared herein. This study has found that the unique properties of outer surface methine and the positive density of Q [8] can form a stable assembly with PEG-APTS, and has provided the possibility for the faster crossing of the glomerular filtration barrier to enter into the resident cells of the kidney. In addition to the excellent fluorescence properties, the as-synthesized biomaterial Q [8]@PEG-APTS has possessed significantly low biological toxicity. Most importantly, the accumulation of Q [8]@PEG-APTS in large amounts in cytoplasm and nucleus of HK2 and HMCs cells, respectively, within 24 h enabled distinguishing kidney cells when diagnosing and providing some foundation for early AKI.

Complete mitochondrial genome sequence of Acer miaotaiense (Aceraceae).

Acer miaotaiense P. C. Tsoong is a rare and endangered tree endemic to the Qinling Mountains of China and is listed as a national third-class protected plant. In this study, we sequenced the complete mitochondrial genome of Acer miaotaiense using the Illumina Novaseq 6000 and Nanopore platforms. The total mitochondrial genome length is 819,227 bp and has 69 genes, including 41 protein-coding, 25 tRNA, and 3 rRNA genes. The genome nucleotide composition was asymmetric, with an overall G + C content of 45.7%. Phylogenetic analysis indicated that Acer miaotaiense is closely related to the congeneric Acer yangbiense.

Association between HLA alleles and sub-phenotype of childhood steroid-sensitive nephrotic syndrome.

BACKGROUND: Few studies have addressed the effects of human leukocyte antigen (HLA) alleles on different clinical sub-phenotypes in childhood steroid-sensitive nephrotic syndrome (SSNS), including SSNS without recurrence (SSNSWR) and steroid-dependent nephrotic syndrome/frequently relapse nephrotic syndrome (SDNS/FRNS). In this study, we investigated the relationship between HLA system and children with SSNSWR and SDNS/FRNS and clarified the value of HLA allele detection for precise typing of childhood SSNS. METHODS: A total of 241 Chinese Han individuals with SSNS were genotyped using GenCap-WES Capture Kit, and four-digit resolution HLA alleles were imputed from available Genome Wide Association data. The distribution and carrying frequency of HLA alleles in SSNSWR and SDNS/FRNS were investigated. Additionally, logistic regression and mediating effects were used to examine the relationship between risk factors for disease process and HLA system. RESULTS: Compared with SSNSWR, significantly decreased serum levels of complement 3 (C3) and complement 4 (C4) at onset were detected in SDNS/FRNS (C3, P < 0.001; C4, P = 0.018). The average time to remission after sufficient initial steroid treatment in SDNS/FRNS was significantly longer than that in SSNSWR (P = 0.0001). Low level of C4 was further identified as an independent risk factor for SDNS/FRNS (P = 0.008, odds ratio = 0.174, 95% confidence interval 0.048-0.630). The HLA-A*11:01 allele was independently associated with SSNSWR and SDNS/FRNS (P = 0.0012 and P = 0.0006, respectively). No significant HLA alleles were detected between SSNSWR and SDNS/FRNS. In addition, a mediating effect among HLA-I alleles (HLA-B*15:11, HLA-B*44:03 and HLA-C*07:06), C4 level and SDNS/FRNS was identified. CONCLUSIONS: HLA-I alleles provide novel genetic markers for SSNSWR and SDNS/FRNS. HLA-I antigens may be involved in steroid dependent or frequent relapse in children with SSNS as mediators of immunoregulation.

[Effects of TGF-ß1 on gene expression of connective tissue growth factor in lung fibroblasts].

OBJECTIVE: To study the effects of transforming growth factor-ß1 (TGF-ß1) on the gene expression of connective tissue growth factor (CTGF) in cultured lung fibroblasts of embryonic rats in vitro. METHODS: Wistar rats of embryonic 19 days were used for primary culture of lung fibroblasts (LFs). The cells in the experimental group were treated by different concentrations (1, 5 or 10 ng/mL) and different durations (12, 24 or 48 hrs) of TGF-ß1 to stimulate the LFs. The cells in the control group were cultured in serum-free medium. RT-PCR method was applied to detect CTGF mRNA expression in LFs. RESULTS: Compared with the control group, the levels of CTGF mRNA in LFs in the experimental group increased significantly (P<0.05). CTGF mRNA expression gradually increased with increasing concentration and duration of TGF-ß1 treatment (P<0.05). CONCLUSIONS: TGF-ß1 can stimulate CTGF gene expression in LFs and increase CTGF gene expression in a dose-and time-dependent manner.

[Effect of DR4 Demethylation to the Proliferation and Apoptosis of Myeloid Leukemia K562 Cells].

OBJECTIVE: To investigate the effect of tumor necrosis factor death receptor (DR) 4 demethylation to the proliferation and apoptosis of myeloid leukemia K562 cells. METHODS: The logarithmic phase of K562 cells were treated by desitabine (DCA) at 0, 0.8, 1.6 and 3.2 µmol/L, and the cells were divided into control group, DCA low dose group, DCA medium dose group and DCA high dose group respectively. The cells in control group were treated by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) 0.5 µg/ml for 24 h, and the cells were divided into TRAIL group. The cells in DCA high dose group were treated by TRAIL 0.5 µg/ml for 24 h, and were divided into DCA high dose + TRAIL group. Methylation-specific polymerase chain reaction (MS-PCR) was used to measure the methylation status of the DR4 gene promoter in the control group and DCA low, medium and high dose groups. Real-time fluorescent quantitative polymerase chain reaction (qRT-PCR) and Western blot were used to determine the relative expression of DR4 mRNA and protein in the control group and DCA low, medium and high dose groups. Dime- thylthiazole (MTT) method was used to determine the inhibition rate of cell proliferation of the cells in control group, DCA high dose group, TRAIL group, DCA high dose + TRAIL group. Flow cytometry was used to determine the apoptotic rate of the cells in control group, DCA high dose group, TRAIL group, DCA high dose + TRAIL group. RESULTS: The cells in the control group were methylation-positive, the brightness of the methylation bands of the cells in the DCA low, medium, and high dose groups was gradually decreased to disappear, and the DCA high dose group showed negative for methylation. The relative expression of DR4 mRNA and protein in the control group, DCA low, medium and high dose groups was increased sequentially (r=0.624, 0.704). The inhibition rate of cell proliferation of the cells in the control group, DCA high dose group, TRAIL group, DCA high dose + TRAIL group was increased sequentially (r=0.653, 0.754, 0.709, 0.725) at 24, 48 and 72 h. CONCLUSION: DCA can reverse the methylation level of DR4 gene promoter in ML K562 cells and up-regulate the expression of DR4, which may enhance the proliferation inhibition and apoptosis promotion effects of TRAIL on K562 cells.

[CLAG Regimen Composed of Continuous Intravenous Infusion of Cladribine in the Treatment of Refractory/Relapsed Acute Myeloid Leukemia].

OBJECTIVE: To study the efficacy and safety of continuous intravenous infusion of 2-Chlorodeoxyadenosine (2-CdA) combined with high-dose cytarabine (Ara-C) and granulocyte colony-stimulating factor (G-CSF) (CLAG regiem) in the treatment of relapsed/refractory acute myeloid leukemia (AML). METHODS: Fifteen patients with refractory/relapsed AML hospitalized in 5 medical units such as Department of Hematology, the Affiliated Tumor Hospital of Zhengzhou University and received one course of CLAG regimen from June 2014 to August 2019 were analyzed retrospectively (specifically: cladribine 5 mg/M2, day 1 to day 5, continuous 24-hour intravenous infusion; Ara-C 2 g/M2, 1 time/day, day 1 to day 5, intravenous infusion; G-CSF 300 mg, 1 time/day, day 0 to day 5, subcutaneous injection). RESULTS: Among the 15 patients with refractory/relapsed AML, 9 males and 6 females, the median age was 35 (13-63) years old. FAB classification: 1 case of M1, 3 cases of M2a, 4 cases of M2b (including 1 case with extramedullary invasion), 1 case of M4 with extramedullary invasion, 5 cases of M5, 1 case of HAL; NCCN classification: 6 cases in intermediate risk group, 9 cases in high risk group; 8 cases refractory, 7 cases relapsed. The median time of pre-chemotherapy was 4 (2-8) (of which NO.15 had received 8 cycles of chemotherapy and received CLL1-CAR-T), and the median white blood cell count before chemotherapy was 12.27 (from 0.78 to 5.29)×109/L. After 1 course of treatment with CLAG regimen, 12 patients achieved complete remission (12/15, 80%), and the median duration of CR was 65 days (0-528) days. IV grade leukopenia and thrombocytopenia was found in all the patients after chemotherapy. The median duration of granulocytosis was 20 (14 to 33) days, and 1 patient died. Seven patients received allogeneic hematopoietic stem cell transplantation. The median EFS and OS time of 15 patients was 85 (19-558) days and 117 (19-558) days, respectively. CONCLUSION: The CLAG regimen consisting of continuous intravenous infusion of cladribine shows high CR in the treatment of AML patients, but the duration of CR is short, myelosuppression is sever, so that infection control is the key. Allogeneic hematopoietic stem cells transplantation should be performed as soon as possible after CR.

Chloroplast genome features and phylogenomic placement of Sorbus hupehensis var. paucijuga (Rosaceae).

The complete chloroplast genome of Sorbus hupehensis var. paucijuga was sequenced with Illumina HiSeq 2000 platform. It was a typical quadruple structure as other plants of Sorbus with 160,050 bp in length, including a large single-copy (LSC: 87,905 bp) region and a small single-copy (SSC: 19,325 bp) which were separated by a pair of inverted repeats (IRa, b: 26,410 bp) region. The overall GC content is 36.5%. A total of 130 genes was annotated which contained 85 protein-coding genes including the Trans splicing gene of rps12, 37 tRNA genes, and 8 rRNA genes. ML phylogenetic analysis compared with 7 expressed chloroplast genomes of Rosaceae revealed that S. hupehensis var. paucijuga was a sister to other Sorbus species. Six species of Sorbus were divided into two groups, the species of group one is distributed in Asia and the species of group two distributed in Europe. Among group one, S. hupehensis var. paucijuga had the closest genetic relationship with S. ulleungensis which is a New Endemic Species on Ulleung Island of Korea, and followed by S. setschwanensis which is only distributed in Sichuan and Guizhou of China. Sorbus hupehensis var. paucijuga has a relatively close relationship with the other three species of Sorbus in the group two. And, it has a relatively distant from other genera of Prunus mongolica and Rosa rugosa.

[Synergistic Mechanism of Interferon alpha-1b, Interleukin-2 and Thalidomide for Immune Regulation in Patients with Acute Myeloid Leukemia].

OBJECTIVE: To explore the synergistic immunomodulatory mechanism of interferon alpha-1b, interleukin-2 and thalidomide (ITI) regimen on patients with acute myeloid leukemia (AML). METHODS: Sixty eight untreated de novo or relapsed or refractory or maintenance therapy patients with AML admitted in the Affiliated Cancer Hospital of Zhengzhou University and the other 11 medical units from March 2016 to May 2019 were treated with ITI regimen. Peripheral blood specimen per patient was collected into EDTA-K3 anticoagulation vacuum tube before the administration of ITI and 3 months after the treatment; peripheral blood lymphocyte subsets and perforin and Granzyme B expression were analyzed by using flow cytometry; the levels of VEGF, IFN-γ, TNF-α and IL-6 in the plasma were detected by using a cytometric bead array. Thirty-five healthy subjects from the hospital physical examination centre were selected as normal controls. RESULTS: The ratio of CD4+/CD8+ T cells, the percentage of NK cells, the expression of perforin and Granzyme B of NK cells in the peripheral blood of patients with hematological malignancies were lower than those of healthy controls. The level of VEGF, IL-6 and TNF-α in the peripheral plasma were higher than those of the healthy control group, and the difference was statistically significant. The level of IFN-γ was lower, and the difference was not statistically significant. The ratio of CD4+/CD8+ T cells, the percentage of NK cells, the expression of Granzyme B and Perforin of NK cells in peripheral blood were higher after the therapy of thalidomide combined with rhIFNα-1b for 3 months as compared with those before treatment of ITI, the level of the IFN-γ in peripheral plasma was higher while that of VEGF was lower, the difference was statistically significant; after treatment, the ratio of CD3+ CD4+ and CD3+ CD8+ lymphocytes and the level of TNF-α in peripheral blood were higher those that before treatment, IL-6 was lower, while the difference was not statistically significant. CONCLUSION: The ITI regimen can raise the ratio of CD4+/CD8+ T cells and the percentage of natural killer cells, also, can enhance the generation of perforin and granzyme B and the concentration of IFN-γ as well as inhibit the generation of VEGF, suggesting that these activities may enhance the antitumour capacity of patients with AML.

Methionine synthase A2756G polymorphism influences pediatric acute lymphoblastic leukemia risk: a meta-analysis.

Plenty of studies have investigated the effect of methionine synthase (MTR) A2756G polymorphism on risk of developing pediatric acute lymphoblastic leukemia (ALL), but the available results were inconsistent. Therefore, a meta-analysis was conducted to derive a more precise estimation of the association between MTR A2756G polymorphism and genetic susceptibility to pediatric ALL. The PubMed, Embase, Google Scholar, Web of Science, ScienceDirect, Wanfang Databases and China National Knowledge Infrastructure were systematically searched to identify all the previous published studies exploring the relationship between MTR A2756G polymorphism and pediatric ALL risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were applied to evaluate the strength of association. Sensitivity analysis and publication bias were also systematically assessed. This meta-analysis finally included ten available studies with 3224 ALL cases and 4077 matched controls. The results showed that there was significant association between MTR A2756G polymorphism and risk of pediatric ALL in overall population (AG vs. AA: OR = 1.13, 95%CI = 1.02-1.26, P = 0.02; AG+GG vs. AA: OR = 1.13, 95%CI = 1.02-1.25, P = 0.01; G allele vs. A allele: OR = 1.10, 95%CI = 1.01-1.20, P = 0.03). In the stratification analyses by ethnicity, quality score and control source, significant association was found in Caucasians, population-based designed studies and studies assigned as high quality. In conclusion, this meta-analysis suggests that MTR A2756G polymorphism may influence the development risk of pediatric ALL in Caucasians. Future large scale and well-designed studies are required to validate our findings.

[Preparation of MgO Modified Lotus Shell Biochar and Its Phosphorus Adsorption Characteristics].

To study the potential application characteristics of biochar as a phosphate adsorbent, nano-MgO-biochar was prepared by rapid pyrolysis of a mixture of MgO and lotus shells. The physicochemical properties were characterized by XRD, BET, SEM, and TEM, and adsorption experiments were conducted. The results showed that MgO was mainly supported on the surface of carbon in the form of flakes and granules, which increased the adsorption active site, and the adsorption amount of MgO-biochar MBC3 was 14 times higher than that of biochar MBC1 without MgO. The adsorption capacity of MBC9, which was prepared by rapid pyrolysis under 10% CO2 atmosphere, was further increased 16 times higher than that of MBC1. The adsorption kinetics followed a pseudo-second-order model, which indicated the adsorption of phosphate on MgO-biochar was dominated by chemical adsorption. According to the Langmuir equation, the maximum adsorption capacity of MBC3 and MBC9 could reach 283.26 mg·g-1 and 297.96 mg·g-1, respectively. MgO-biochar is a high-efficiency phosphate adsorbent, which can be used to control the eutrophication of water.

CA IX is upregulated in CoCl2-induced hypoxia and associated with cell invasive potential and a poor prognosis of breast cancer.

Hypoxia, a common phenomenon during the development of malignant solid tumors including breast cancer, serves to propagate a cascade of molecular pathways triggered by hypoxia-inducible factor-1α (HIF-1α). Carbonic anhydrase IX (CA IX), one of the target genes of HIF-1α, has been reported to be involved in progression of malignant tumors. The objective of this study was to investigate the expression of HIF-1α and CA IX in hypoxia, involvement of CA IX in the regulation of migration and invasion/metastasis and its prognostic significance in breast cancer. We used cobalt chloride (CoCl2) as a hypoxia-mimetic agent and found that the expression of HIF-1α protein, CA IX mRNA and protein, is effectively upregulated, except for HIF-1α mRNA. Data showed that the elevated CA IX expression is closely related to in vitro cell migration and invasion, and the underlying mechanism of this process may be associated with epithelial-mesenchymal transition (EMT). The study of clinical tissue samples also demonstrated that CA IX is an independent prognostic marker that may serve as a useful clinical biomarker for predicting tumor progression and the invasion/metastasis of breast cancer. These results provide further insight into the role of CA IX in tumor progression and put forward further strong evidence as well as new consideration for CA IX target therapy.

Risk Factors Associated with Renal Involvement in Childhood Henoch-Schönlein Purpura: A Meta-Analysis.

BACKGROUND AND OBJECTIVE: Henoch-Schönlein purpura (HSP) is an important cause of chronic kidney disease in children. This meta-analysis identified risk factors associated with renal involvement in childhood HSP. METHODS: PubMed, Embase, and Web of Science were searched. The quality of all eligible studies was assessed using the Newcastle-Ottawa scale criteria. An analysis of possible risk factors was conducted to report the odds ratio (OR) and weighted mean difference (WMD). RESULTS: Thirteen studies (2398 children) revealed 20 possible and 13 significant risk factors associated with renal involvement in HSP, with the following meta-analysis estimates of OR and WMD, with 95% confidence intervals: older age (0.90, 0.61-1.19); age > 10 y (3.13, 1.39-7.07); male gender (1.36, 1.07-1.74); abdominal pain (1.94,1.24-3.04); gastrointestinal bleeding (1.86, 1.30-2.65); severe bowel angina (3.38, 1.17-9.80); persistent purpura (4.02, 1.22-13.25); relapse (4.70, 2.42-9.14); WBC > 15 × 109/L (2.42, 1.39-4.22); platelets > 500 × 109/L (2.98, 1.22-7.25); elevated antistreptolysin O (ASO) (2.17, 1.29-3.64); and decreased complement component 3 (C3) (3.13, 1.62-6.05). Factors not significantly associated with renal involvement were: blood pressure; orchitis; elevated C-reactive protein; elevated erythrocyte sedimentation rate (ESR); and elevated serum IgA/IgE or IgG. Arthritis/arthralgia may be a risk factor according to the criteria of the American College of Rheumatology (1.41, 1.01-1.96). CONCLUSION: The following are associated with renal involvement in pediatric HSP: male gender; > 10 y old; severe gastrointestinal symptoms (abdominal pain, gastrointestinal bleeding, and severe bowel angina); arthritis/arthralgia; persistent purpura or relapse; WBC > 15 × 109/L; platelets > 500 × 109/L; elevated ASO; and low C3. Relevant clinical interventions for these risk factors may exert positive effects on the prevention of kidney disease during the early stages of HSP. However, the results should be interpreted cautiously due to the limitations of the studies.

MicroRNA-320a inhibits breast cancer metastasis by targeting metadherin.

Dysregulated microRNAs play important pathological roles in carcinogenesis that are yet to be fully elucidated. This study was performed to investigate the biological functions of microRNA-320a (miR-320a) in breast cancer and the underlying mechanisms. Function analyses for cell proliferation, cell cycle, and cell invasion/migration, were conducted after miR-320a silencing and overexpression. The specific target genes of miR-320a were predicted by TargetScan algorithm and then determined by dual luciferase reporter assay and rescue experiment. The relationship between miR-320a and its target genes was explored in human breast cancer tissues. We found that miR-320a overexpression could inhibit breast cancer invasion and migration abilities in vitro, while miR-320a silencing could enhance that. In addition, miR-320a could suppress activity of 3'-untranslated region luciferase of metadherin (MTDH), a potent oncogene. The rescue experiment revealed that MTDH was a functional target of miR-320a. Moreover, we found that MTDH was negatively correlated with miR-320a expression, and it was related to clinical outcomes of breast cancer. Further xenograft experiment also showed that miR-320a could inhibit breast cancer metastasis in vivo. Our findings clearly demonstrate that miR-320a suppresses breast cancer metastasis by directly inhibiting MTDH expression. The present study provides a new insight into anti-oncogenic roles of miR-320a and suggests that miR-320a/MTDH pathway is a putative therapeutic target in breast cancer.

Meta-analysis of the association of MTHFR polymorphisms with multiple myeloma risk.

The association of methylenetetrahydrofolate reductase (MTHFR) polymorphisms with multiple myeloma (MM) risk has been explored, but the results remain controversial. Thus, a meta-analysis was performed to provide a comprehensively estimate. The case-control studies about MTHFR C677T and A1298C polymorphisms with MM risk were collected by searching PubMed, Elsevier, China National Knowledge Infrastructure and Wanfang Databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were applied to assess the strength of association. Overall, no significant association was found between MTHFR A1298C polymorphism and MM risk under all four genetic models (AC vs. AA, OR = 0.99, 95%CI = 0.82-1.20; CC vs. AA, OR = 1.14, 95%CI = 0.77-1.68; recessive model, OR = 1.10, 95%CI = 0.76-1.59; dominant model, OR = 1.01, 95%CI = 0.84-1.22). The risk was also not significantly altered for C677T polymorphism and MM in overall comparisons (CT vs. CC, OR = 1.04, 95%CI = 0.93-1.17; TT vs. CC, OR = 1.16, 95%CI = 0.98-1.37; recessive model, OR = 1.13, 95%CI = 0.98-1.32; dominant model, OR = 1.07, 95%CI = 0.96-1.20). In subgroup analyses by ethnicity, no significant association was observed in both Caucasians and Asians. This meta-analysis suggested that MTHFR polymorphisms were not associated with MM risk.

Purpurin triggers caspase-independent apoptosis in Candida dubliniensis biofilms.

Candida dubliniensis is an important human fungal pathogen that causes oral infections in patients with AIDS and diabetes mellitus. However, C. Dubliniensis has been frequently reported in bloodstream infections in clinical settings. Like its phylogenetically related virulent species C. albicans, C. Dubliniensis is able to grow and switch between yeast form and filamentous form (hyphae) and develops biofilms on both abiotic and biotic surfaces. Biofilms are recalcitrant to antifungal therapies and C. Dubliniensis readily turns drug resistant upon repeated exposure. More than 80% of infections are associated with biofilms. Suppression of fungal biofilms may therefore represent a viable antifungal strategy with clinical relevance. Here, we report that C. dubliniensis biofilms were inhibited by purpurin, a natural anthraquinone pigment isolated from madder root. Purpurin inhibited C. dubliniensis biofilm formation in a concentration-dependent manner; while mature biofilms were less susceptible to purpurin. Scanning electron microscopy (SEM) analysis revealed scanty structure consisting of yeast cells in purpurin-treated C. dubliniensis biofilms. We sought to delineate the mechanisms of the anti-biofilm activity of purpurin on C. Dubliniensis. Intracellular ROS levels were significantly elevated in fungal biofilms and depolarization of MMP was evident upon purpurin treatment in a concentration-dependent manner. DNA degradation was evident. However, no activated metacaspase could be detected. Together, purpurin triggered metacaspase-independent apoptosis in C. dubliniensis biofilms.