Associations Between High-Altitude Residence and End-Stage Kidney Disease in Chinese Patients with Type 2 Diabetes.

Zhao, Lijun, Xi Wang, Tingli Wang, Wenxin Fan, Honghong Ren, Rui Zhang, Yutong Zou, Huan Xu, Jie Zhang, Yunhong Wu, and Fang Liu. Associations between high-altitude residence and end-stage kidney disease in Chinese patients with type 2 diabetes. High Alt Med Biol. 21:396-405, 2020. Background: This study investigated whether living at high altitude was associated with progression to end-stage kidney disease (ESKD) in Chinese patients with diabetic nephropathy (DN). Materials and Methods: This retrospective study included 369 patients with type 2 diabetes mellitus (T2DM) and biopsy-confirmed DN. Cox proportional hazards models were used to estimate hazard ratios (HRs) for the influence of living at high altitude on ESKD. Results: Patients living at ≥2,000 m above sea level were more likely to be Tibetan, and they had higher mean body mass indexes, glycosylated hemoglobin, hemoglobin concentrations, and baseline estimated glomerular filtration rates than those living at lower altitudes. During a median follow-up period of 20 months, 141 (38%) patients progressed to ESKD. In multivariable Cox analysis adjusted for age, sex, ethnicity, and clinical and pathological parameters, living at high altitude was independently associated with progression to ESKD in Chinese DN patients [HR 2.83, 95% confidence interval (CI) 1.05-7.58]. Compared with Han Chinese, Tibetans were at a lower risk of progression to ESKD (HR 0.15, 95% CI 0.04-0.59). Conclusions: Living at high altitude was independently associated with renal outcome in Han Chinese patients with T2DM and DN, but not native Tibetans.

G protein-coupled receptor 68 increases the number of B lymphocytes.

G protein-coupled receptor 68 (GPR68) is a proton sensor that is activated upon binding to extracellular protons. We have previously found that GPR68 induces a proapoptotic pathway in bone marrow (BM) cells from the patients with myelodysplastic syndromes (MDS) after treated with lenalidomide. However, the function of GPR68 in normal hematopoietic cells remains unclear. With genetic loss of function approach, we found reduced frequency and number of B lymphocytes in the peripheral blood (PB) of whole body Gpr68-/- mice compared to control littermates upon aging. During hematopoietic regeneration, such as in response to fluorouracil (5-FU), we also found reduced frequency and number of B lymphocytes in Gpr68-/- mice compared to wild type mice. Mechanism studies revealed that Gpr68 expression was upregulated in B lymphocytes of BM during aging and in hematopoietic progenitor cells after treatment with 5-FU. In addition, activation of Gpr68 by its activators increased the frequency and number of B lymphocytes. Our studies indicate that Gpr68 expression is upregulated in hematopoietic cells upon aging and during hematopoietic regeneration that ends up with increased number of B lymphocytes.

Retrospective study of the treatment of port-wine stains with 595-nm pulsed dye laser in 261 Chinese patients.

Pulsed dye laser (PDL) at the wavelength of 595 nm is the common choice for the treatment of port-wine stains (PWSs). In this study, the efficacy of 595-nm PDL in treatment of PWSs in Chinese patients was investigated. A follow-up visit was performed on 261 Fitzpatrick skin type II-III Chinese patients with PWS who received more than two treatments with 595-nm PDL. Based on cosmetic improvement, treatment response was graded as follows: complete, if color blanching was > 90%; significant, if color blanching was 60-90%; moderate, if color blanching was 30-60%; and poor, if color blanching was < 30%. The efficacy of laser treatment on patients of different treatment numbers, ages, lesion locations, lesion colors, extents of hypertrophy, and laser pulse durations was evaluated. All patients improved following an average of almost 4 to 5 laser treatments. The earlier the intervention, the better the efficacy was. Lesions on cheek, neck, and forehead were better than that those on oral, eye periorbital, and nose areas. The purple group had a more excellent clearance, i.e., complete and significant clearance rate (53.6%), than the red group (36.1%). Treatment effect became worse as the extent of lesion hypertrophy increased. PWS lesions treated with short pulse durations of 0.45, 1.5, and 3 ms had better clearance (complete and significant clearance) rate of 56.5% than those treated with pulse durations of 6 ms or longer (34.8%). Pulsed dye laser with 595-nm laser equipped with dynamic cooling device is an effective option for the treatment of PWS in Chinese patients. Younger patients with lateral face position, larger vessel size (deeper color), and lesser hypertrophy received better clinical effect than the others. Treatment with short pulse duration of less than 3 ms for 4 to 5 times was recommended to treat PWS.

High pretreatment plasma D-dimer levels predict poor prognosis in gastrointestinal cancers: A meta-analysis.

BACKGROUND: High pretreatment plasma D-dimer levels can predict poor prognosis in various types of gastrointestinal carcinomas. Our meta-analysis explored the correlation between plasma D-dimer levels and prognosis in gastrointestinal malignancies. METHODS: Two independent reviewers conducted a comprehensive search from PubMed, ScienceDirect, Embase, Web of Science and the Cochrane Library. All articles evaluating the correlation between pretreatment plasma D-dimer levels and prognosis in gastrointestinal malignancies were searched. We chose overall survival (OS) as the primary survival outcome measure and progression-free survival (PFS), disease-free survival (DFS) and cancer-specific survival (CSS) as the secondary survival outcome measures. We extracted hazard ratios (HRs) and 95% confidence intervals (CIs) from the eligible publications. RESULTS: We included 30 studies involving 5928 gastrointestinal cancer patients. There was an obvious correlation between high D-dimer levels and poor OS (HR = 2.01, 95% CI = 1.72-2.36, P < .01). High plasma D-dimer levels were correlated with shorter PFS (HR = 1.34, 95% CI = 1.05-1.70, P = .32), DFS (HR =  1.67, 95% CI = 1.12-2.50, P < .01) and CSS rates (HR = 1.93, 95% CI = 1.49-2.49, P = .66). CONCLUSIONS: Elevated pretreatment plasma D-dimer levels might help predict poor prognosis in patients with gastrointestinal malignancies.

Fibulin-3 Has Anti-Tumorigenic Activities in Cutaneous Squamous Cell Carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer. Several previous studies have shown that fibulin-3 participates in the occurrence and development of various tumors; however, its role in cSCC remains unknown. In the present study, we observed that the expression of fibulin-3 was downregulated in cSCC tissues compared with normal skin tissues, which was due to fibulin-3 promoter methylation. In vitro, knockdown of fibulin-3 in cSCC cell lines A431 and SCL-1 cells promoted cell proliferation, protected cells against apoptosis and enhanced migration and invasion abilities. Conversely, overexpression of fibulin-3 inhibited cell proliferation by promoting growth arrest during the G1/S phase transition, induced apoptosis, and reduced migration and invasion abilities. These anticarcinogenic effects of fibulin-3 were associated with inhibition of the AKT signaling pathway. Through a mouse xenograft model, we found that fibulin-3 overexpression inhibited the cSCC tumor growth in vivo. Our results suggest that fibulin-3 has anti-tumorigenic activities in cSCC. Downregulation of fibulin-3 is involved in cSCC development and it may serve as a novel therapeutic target of this disease.

Involvement of inflammation-related miR-155 and miR-146a in diabetic nephropathy: implications for glomerular endothelial injury.

BACKGROUND: MicroRNAs have been demonstrated to play an important role in the pathogenesis of diabetic nephropathy (DN). In this study, we investigated both the repertoire of miRNAs in the kidneys of patients with DN and their potential regulatory role in inflammation-mediated glomerular endothelial injury. METHODS: The miRNA expression profiling of the renal biopsy samples was performed by a microarray analysis; then, in situ hybridization and real-time polymerase chain reaction (PCR) were used to determine the localization and expression of two of the miRNAs significantly up-regulated in human DN kidney samples, miR-155 and miR-146a, in the kidney tissues from type 1 and type 2 DN rat models. Human renal glomerular endothelial cells (HRGECs) cultured under high-glucose conditions were transfected with miR-155 and miR-146a mimics, and the transforming growth factor (TGF)-ß1, tumor necrosis factor (TNF)-α, and nuclear factor (NF)-κB expressions were examined by western blot, real-time PCR, and an electrophoresis mobility shift assay. RESULTS: The expression of both miR-155 and miR-146a was increased more than fivefold in the kidney samples of the DN patients compared with the controls, and the miR-155 expression was closely correlated with the serum creatinine levels (R = 0.95, P = 0.004). During the induction and progression of the disease in type 1 and type 2 DN rat models, miR-155 and miR-146a were demonstrated to increase gradually. In vitro, high glucose induced the over-expression of miR-155 and miR-146a in the HRGECs, which, in turn, increased the TNF-α, TGF-ß1, and NF-κB expression. CONCLUSIONS: Taken together, these findings indicate that the increased expression of miR-155 and miR-146a in the DN patients and in the experimental DN animal models was found to contribute to inflammation-mediated glomerular endothelial injury.