Humans ; Waldenstrom Macroglobulinemia ; Prospective Studies

Diabetic nephropathy is a microvascular complication of diabetes. Its etiology involves metabolic disorder-induced endothelial dysfunction. Endothelium-derived nitric oxide (NO) plays an important role in a number of physiological processes, including glomerular filtration and endothelial protection. NO dysregulation is an important pathogenic basis of diabetic nephropathy. Hyperglycemia and dyslipidemia can lead to oxidative stress, chronic inflammation and insulin resistance, thus affecting NO homeostasis regulated by endothelial nitric oxide synthase (eNOS) and a conglomerate of related proteins and factors. The reaction of NO and superoxide (O₂^.-) to form peroxynitrite (ONOO^-) is the most important pathological NO pathway in diabetic nephropathy. ONOO^- is a hyper-reactive oxidant and nitrating agent in vivo which can cause the uncoupling of eNOS. The uncoupled eNOS does not produce NO but produces superoxide. Thus, eNOS uncoupling is a critical contributor of NO dysregulation. Understanding the regulatory mechanism of NO and the effects of various pathological conditions on it could reveal the pathophysiology of diabetic nephropathy, potential drug targets and mechanisms of action. We believe that increasing the stability and activity of eNOS dimers, promoting NO synthesis and increasing NO/ONOO^- ratio could guide the development of drugs to treat diabetic nephropathy. We will illustrate these actions with some clinically used drugs as examples in the present review.
Diabetes Mellitus ; Diabetic Nephropathies/drug therapy* ; Endothelium, Vascular ; Humans ; Nitric Oxide/metabolism* ; Nitric Oxide Synthase Type III/therapeutic use* ; Oxidative Stress ; Peroxynitrous Acid/therapeutic use*

Objective To investigate the genetic polymorphisms of Plasmodium falciparum multidrug resistance protein 1 (PfMDR1), chloroquine resistance transporter (PfCRT) and Kelch 13 (PfK13) genes in Bioko Island, Equatorial Guinea, so as to provide insights into the development of the malaria control strategy in local areas. Methods A total of 85 peripheral blood samples were collected from patients with Plasmodium falciparum infections in Bioko Island, Equatorial Guinea in 2018 and 2019, and genomic DNA was extracted. The PfMDR1, PfCRT and PfK13 genes were amplified using a nested PCR assay. The amplification products were sequenced, and the gene sequences were aligned. Results There were no mutations associated with artemisinin resistance in PfK13 gene in Bioko Island, Equatorial Guinea, while drug-resistant mutations were detected in PfMDR1 and PfCRT genes, and the proportions of PfMDR1_N86Y, PfMDR1_Y184F and PfCRT_K76T mutations were 35.29% (30/85), 72.94% (62/85) and 24.71% (21/85), respectively. Conclusion There are mutations in PfMDR1, PfCRT and PfK13 genes in P. falciparum isolates from Bioko Island, Equatorial Guinea.

Here, we developed a prostate cancer (PCa) risk nomogram including lymphocyte-to-monocyte ratio (LMR) for initial prostate biopsy, and internal and external validation were further conducted. A prediction model was developed on a training set. Significant risk factors with P < 0.10 in multivariate logistic regression models were used to generate a nomogram. Discrimination, calibration, and clinical usefulness of the model were assessed using C-index, calibration plot, and decision curve analysis (DCA). The nomogram was re-examined with the internal and external validation set. A nomogram predicting PCa risk in patients with prostate-specific antigen (PSA) 4-10 ng ml

OBJECTIVE: To summarize and compare the clinical baseline characteristics of patients with monoclonal gammopathy of undetermined significance (MGUS), primary light chain amyloidosis (pAL), multiple myeloma (MM), or MM with concurrent amyloidosis, especially the differences in cytogenetic abnormalities. METHODS: The clinical data of 15 cases of MGUS, 34 cases of pAL, 842 cases of MM and 23 cases of MM with concurrent amyloidosis were analyzed and compared retrospectively. RESULTS: Cytogenetic statistics showed that the incidence of t (11; 14) in the four groups (MGUS vs pAL vs MM vs MM with concurrent amyloidosis) was 0%, 33.3%, 16.4%, and 15.8%, respectively (P=0.037); that of 13q deletion was 20.0%, 14.7%, 45.8% and 56.5%, respectively (P<0.001); gain of 1q21 was 50.0%, 12.5%, 47.4% and 40.9%, respectively (P=0.001). Proportion of pAL patients with 0, 1 and≥2 cytogenetic abnormalities (including 13q deletion, 17p deletion, 1q21 amplification and IgH translocation) accounted for 41.9%, 41.9% and 16.1%, respectively; while the proportion of the same category in MM was 17.6%, 27.3%, and 55.2% respectively; this ratio of MM with concurrent amyloidosis was more similar to MM. Subgroup analysis showed that genetic abnormalities (including 13q deletion, 17p deletion and 1q21 amplification) were comparable within t (11; 14) negative and positive groups. Compared with positive cases, t(11; 14) negative patients with MM or MGUS were more likely to have 13q deletions and multiple genetic abnormalities. CONCLUSION Clinical characteristics of pAL, especially cytogenetic abnormalities, are significantly different from MM with concurrent amyloidosis. It suggests that although the onset characteristics are similar, actually the two diseases belong to different disease subtypes which should be carefully predicted and identified.
Amyloidosis ; Humans ; In Situ Hybridization, Fluorescence ; Monoclonal Gammopathy of Undetermined Significance/complications* ; Multiple Myeloma ; Retrospective Studies

Aim To study the therapeutic effect of 35% and 70% ethanol elution sites of Gardeniae Fructus extract on 2,4,6-trinitrobenzene sulfonic acid (TNBS)/ethanol induced ulcerative colitis (UC) in rats, and to identify the chemical composition of the active elution site using mass spectrometry. Methods The UC model induced by TNBS was used in rats, and the different eluted parts were administered by gavage at a dose of 2. lg/kg for 7 days. Body weight measurement , disease activity index (DAI) score, and pathological score of colon tissues were compared. Myeloperoxidase (MPO) , superoxide dismutase (SOD), malondialdehyde ( MDA ) , nitric oxide ( NO ) , tumor necrosis factor-a (TNF-a) , interleukin in mouse colon tissue -6 (IL-6), interleukin-1 (3 (IL-ip) levels were compared among groups. Liquid-mass spectrometry was used to identify the chemical components of the parts with better efficacy. Results Compared with model group, the weight loss in 35% elution site group was significantly improved, the DAI and histopathology scores were markedly reduced, and the contents of MPO, NO, MDA, TNF-a, IL-6 and IL-1(3 in tissues were apparently reduced. SOD content increased significantly (P <0. 01). A total of 19 chemical components were identified by LC-MS, 11 of which were iri- doids. Conclusions The 35% elution site of Gardeni- a has obvious therapeutic effect on UC rats, and the iridoid component may be the material basis for its function.

Objective To explore the prognostic factors of central venous catheter-related bloodstream infection(CR-BSI)and provide reference for clinical practice. Methods The clinical data of 346 CR-BSI patients from February 2014 to July 2019 were retrospectively reviewed,and the prognostic factors were analyzed. Results Of the 346 CR-BSI patients,62 died,yielding a case-fatality rate of 17.92%.Univariate analysis showed that 18 factors including age(
Anti-Bacterial Agents ; Carbapenem-Resistant Enterobacteriaceae ; Central Venous Catheters/adverse effects* ; Humans ; Hyperglycemia ; Hypoproteinemia ; Klebsiella Infections ; Klebsiella pneumoniae ; Methicillin-Resistant Staphylococcus aureus ; Mycoses ; Prognosis ; Pseudomonas Infections ; Retrospective Studies ; Risk Factors ; Sepsis/mortality*

Objective: To compare the results obtained from the computer-aided sperm analysis (CASA) systems of the two fully-automated commercial sperm quality analyzers, Hamilton-Thorn IVOS Ⅱ (IVOS Ⅱ) and Spanish Sperm Class Analyzer (SCA). METHODS: A total of 99 semen samples were collected in the Center of Reproduction of Shenzhen Zhongshan Urology Hospital from September 2018 to October 2018 and, according to the sperm concentration, divided into groups A (<15 ×10⁶/ml), B (15－50 ×10⁶/ml) and C (>50 ×10⁶/ml). IVOS Ⅱ, SCA and manual microscopy were used for the examination of each sample, followed by comparison of the sperm concentration, sperm motility and percentage of progressively motile sperm (PMS) obtained from IVOS Ⅱ and SCA. RESULTS: The sperm concentrations derived from IVOS Ⅱ and SCA were significantly higher than that from manual microscopy in group A (［10.24 ± 4.60］ and ［10.20 ± 5.11］ vs ［8.45 ± 4.15］ ×10⁶/ml, P < 0.05), but showed no statistically significant difference in group B (［30.95 ± 11.84］ and ［31.81 ± 12.90］ vs ［29.14 ± 10.65］ ×10⁶/ml, P > 0.05) or C (［102.14 ± 45.97］ and ［109.48 ± 46.32］ vs ［104.74 ± 41.87］ ×10⁶/ml, P > 0.05). Significant differences were not observed between IVOS Ⅱ and SCA in the percentage of PMS (［24.21 ± 14.62］% vs ［23.92 ± 15.42］%, P > 0.05) or sperm motility (［37.48 ± 19.34］% vs ［37.69 ± 16.61］%, P > 0.05) in group B, nor in group C (PMS: ［30.80 ± 12.06］% vs ［32.98 ± 16.10］%, P > 0.05; sperm motility: ［44.50 ± 15.62］% vs ［47.26 ± 17.46］%, P > 0.05). Both the percentage of PMS and sperm motility obtained from IVOS Ⅱ were remarkably lower than those derived from SCA in group A (PMS: ［18.54 ± 12.96］% vs ［22.90 ± 12.88］%, P < 0.05; sperm motility: ［26.97 ± 14.05］% vs ［34.90 ± 15.18］%, P < 0.05). IVOS Ⅱ and SCA both showed a high repeatability (CV <15%), and the former exhibited an even higher one than the latter, in detection of sperm concentration, sperm motility and the percentage of PMS. CONCLUSIONS IVOS Ⅱ and SCA both had a good consistency in the results of sperm concentration, motility and progressive motility, but showed a poor comparability with low-concentration semen samples.

Background: Malignant pleural effusion (MPE) is a complicated condition of patients with advanced tumors. Further dissecting the microenvironment of infiltrated immune cells and malignant cells are warranted to understand the immune-evasion mechanisms of tumor development and progression. Methods: The possible involvement of microRNAs (miRNAs) in malignant pleural fluid was investigated using small RNA sequencing. Regulatory T cell (Treg) markers (CD4, CD25, forkhead box P3), and Helios (also known as IKAROS Family Zinc Finger 2 [IKZF2]) were detected using flow cytometry. The expression levels of IKZF2 and miR-4772-3p were measured using quantitative real-time reverse transcription polymerase chain reaction. The interaction between miR-4772-3p and Helios was determined using dual-luciferase reporter assays. The effects of miR-4772-3p on Helios expression were evaluated using an in vitro system. Correlation assays between miR-4772-3p and functional molecules of Tregs were performed. Results: Compared with non-malignant controls, patients with non-small cell lung cancer had an increased Tregs frequency with Helios expression in the MPE and peripheral blood mononuclear cells. The verified downregulation of miR-4772-3p was inversely related to the Helios⁺ Tregs frequency and Helios expression in the MPE. Overexpression of miR-4772-3p could inhibit Helios expression in in vitro experiments. However, ectopic expression of Helios in induced Tregs reversed the effects induced by miR-4772-3p overexpression. Additionally, miR-4772-3p could regulate Helios expression by directly targeting IKZF2 mRNA. Conclusion Downregulation of miR-4772-3p, by targeting Helios, contributes to enhanced Tregs activities in the MPE microenvironment.