New-onset glucose disorders in peritoneal dialysis patients: a meta-analysis and systematic review.

BACKGROUND: Peritoneal dialysis (PD) patients are at high risk of developing glucose metabolism disturbance (GMD). The incidence and prevalence of new-onset GMD, including diabetes mellitus (DM), impaired glucose tolerance (IGT) and impaired fast glucose (IFG), after initiation of PD, as well as their correlated influence factors, varies among studies in different areas and of different sample sizes. Also, the difference compared with hemodialysis (HD) remained unclear. Thus we designed this meta-analysis and systematic review to provide a full landscape of the occurrence of glucose disorders in PD patients. METHODS: We searched the MEDLINE, Embase, Web of Science and Cochrane Library databases for relevant studies through September 2018. Meta-analysis was performed on outcomes using random effects models with subgroup analysis and sensitivity analysis. RESULTS: We identified 1124 records and included 9 studies involving 13 879 PD patients. The pooled incidence of new-onset DM (NODM) was 8% [95% confidence interval (CI) 4-12; I2 = 98%] adjusted by sample sizes in PD patients. Pooled incidence rates of new-onset IGT and IFG were 15% (95% CI 3-31; I2 = 97%) and 32% (95% CI 27-37), respectively. There was no significant difference in NODM risk between PD and HD [risk ratio 0.99 (95% CI 0.69-1.40); P = 0.94; I2 = 92%]. PD patients with NODM were associated with an increased risk of mortality [hazard ratio 1.06 (95% CI 1.01-1.44); P < 0.001; I2 = 92.5%] compared with non-DM PD patients. CONCLUSIONS: Around half of PD patients may develop a glucose disorder, which can affect the prognosis by significantly increasing mortality. The incidence did not differ among different ethnicities or between PD and HD. The risk factor analysis did not draw a definitive conclusion. The glucose tolerance test should be routinely performed in PD patients.

[Preparation and identification of a monoclonal antibody against human PD-L1].

OBJECTIVE: To prepare mouse anti-human PD-L1 monoclonal antibodies (mAbs) and identify their biological characteristics. METHODS: BALB/c mice were immunized with recombinant GST-PDL1 protein,and the strain of hybridoma cell secreting anti-PD-L1 mAb was obtained. The specificity of anti-PD-L1 mAb was checked and evaluated with ELISA and Western blot. Its titer, immunoglobulin subtype were also measured. The combining capacity of anti-PD-L1 mAb with PD-L1 on MDA-MB-231 cells, which had been induced with IFN-gamma for 72 hours, was identified through immunohistochemistry and flow cytometry. The peripheral blood mononuclear cell was labeled with CFSE, and the effect of anti-PD-L1 mAb on the activation and proliferation of the lymphocyte induced with antigens was evaluated by flow cytometry analysis. RESULTS: A strain of hybridoma cell secreting anti-PD-L1 mAb was successfully obtained and identified belong to IgG1 subtype. Its titers in cultural supernatant and ascetic fluid were 1:6400 and 1:102400, respectively, by ELISA. The purified mAbs showed good affinity and specificity against GST-PDL1 protein in Western blot, also could block the PD-1/PD-L1 pathway and promote the proliferation of lymphocyte induced with antigens. CONCLUSION: Hyperactivity mouse anti-human PD-L1 hybridoma cell lines and their secreted monoclonal antibodies have been successfully obtained and identified.

[Effect of astragalus membranaceus on the proliferation, osteogenic capacity and structure of periodontal ligament cells in vitro].

OBJECTIVE: To investigate the effect of Astragalus membranaceus (APS) on the proliferation, osteogenic capacity and structure of periodontal ligament cells (PDLCs) in vitro. METHODS: PDLCs were cultured in vitro with APS of 0.08, 0.1, 0.2, 0.4 mg x mL(-1). Methyl thiazolyl tetrazolium (MTr), alkaline phosphatase (ALP) and cell structure were detected to determine the proliferation and differentiation of PDLCs proliferation and differentiation. RESULTS: When the APS was 0.2 mg x mL(-1), the absorbance of MTT and ALP exhibit significantly increased as compared to the control (P < 0.05). The cells cultured in vitro with APS of 0.2 mg x mL(-1) had the normal structure. CONCLUSION: APS with proper concentration in short-term culture may promote the proliferation and differentiation of PDLCs.

Hypoxia inducible factor 1α and hypoxia inducible factor 2α play distinct and functionally overlapping roles in oral squamous cell carcinoma.

PURPOSE: This study aimed to investigate the functional difference between hypoxia inducible factor (HIF)-1α and HIF-2α in oral squamous cell carcinomas (OSCC). EXPERIMENTAL DESIGN: We evaluated the correlations between HIF-1α and HIF-2α expression and the clinical-pathologic characteristics of 97 patients with OSCC by immunohistochemical staining. OSCC cell lines transfected with lentivirus encoding short hairpin RNA against HIF-1α/2α were used to investigate the HIF-1α/2α-dependent target genes. Xenograft tumors in nude mice were established using cells affected by lentivirus, and tumor growth, angiogenesis, proliferation, and apoptosis were measured. RESULTS: HIF-1α expression was significantly associated with T stage (P = 0.004), lymph node involvement (P = 0.006), histologic differentiation (P = 0.013), and microvessel density (P = 0.014), whereas that of HIF-2α was associated with T stage (P = 0.011) and microvessel density (P = 0.005). Patients with positive HIF-1α nuclear staining had a significantly worse overall survival (P < 0.001) and disease-free survival (P < 0.001) than those with negative HIF-1α staining. When OSCC cells were cultured at 5% O(2), only HIF-2α contributed to the expression of vascular endothelial growth factor. At 1% O(2), vascular endothelial growth factor was regulated by both HIF-1α and HIF-2α, but glucose transporter 1, carbonic anhydrase 9, and urokinase-type plasminogen activator receptor were regulated by HIF-1α rather than by HIF-2α. Knocking down HIF-1α or HIF-2α individually inhibited the xenograft tumor angiogenesis and growth, and knocking them down simultaneously revealed a better inhibitory effect than knocking down either unit alone. CONCLUSIONS: HIF-1α and HIF-2α correlated with different clinical-pathologic parameters, stabilized at different oxygen levels, and regulated different genes in OSCC. However, both HIF-1α and HIF-2α showed promoting roles in tumor angiogenesis and growth, and therapeutic outcome may benefit from combined targeting of HIF-1α and HIF-2α.

[The expression of vascular endothelial growth factor-C in oral squamous cell carcinoma and its associations with angiogenesis, lymphangiogenesis and lymph node metastasis].

OBJECTIVE: To study the expression of vascular endothelial growth factor-C (VEGF-C) in oral squamous cell carcinoma (OSCC) and its relation to angiogenesis, lymphangiogenesis, as well as lymph node metastasis. METHODS: Sixty-seven archival specimens from patients with oral squamous cell carcinoma were investigated, whose clinicopathologic data were completely conserved. Immunohistochemical staining was performed to detect the expression of VEGF-C, microvessel density (MVD), lymphatic vessel density (LVD). The correlations between VEGF-C expression and MVD, LVD, as well as other clinicopathological features were measured. RESULTS: Although no correlation between VEGF-C expression and tumor location, histological grade, or gender of the patients was observed (P > 0.05), OSCC patients with more advanced clinical stages and lymph node metastasis were prone to have high expression of VEGF-C (P = 0.015 and P < 0.001, respectively). Cases with high-expression of VEGF-C also showed significantly more often higher LVD (P = 0.001) but not MVD (P = 0.125). In addition, cases with lymph node involvement presented higher LVD than other cases (P = 0.026). CONCLUSION: VEGF-C may promote lymph node metastasis by inducing lymphangiogenesis in OSCC.

[The effect of ginkgolic acids on multidrug resistance in oral squamous cell carcinoma].

OBJECTIVE: Carboplatin (CBP)-resistant cell line (Tca8113/CBP) and pingyangmycin (PYM)-resistant cell line (Tca8113/PYM) were established in vitro. Ginkgolic acids' influence over multidrug resistance (MDR) of drug-resistant cells was discussed by ginkgolic acids coupled with chemotherapy drugs. METHODS: The expression of P-glycoprotein (P-gp) was detected by immunohistochemistry. MTT assay was applied to ascertain the resistance index of drug-resistant cells. The effect of different concentrations of ginkgolic acids on the proliferation of drug-resistant cells and parental cell was measured by MTT assay. Making sure the non-toxic concentration of ginkgolic acids and observing the reversal effect of ginkgolic acids on drug-resistant cells. Resistance index was redetermined by MTT assay after ginkgolic acids coupled with chemotherapy drugs induced the cell lines for some time. RESULTS: Immunohistochemistry showed that P-gp positive expression rate of drug-resistant cells was significantly higher than parental cells. The non-toxic concentration of ginkgolic acids which was determined by MTT assay was 10 microg x mL(-1). The reversal folds of Tca8113/CBP cell line to CBP and Tca8113/PYM cell line to PYM were 2.94 and 2.43 respectively. Before coupled with ginkgolic acids, the resistance indices of Tca8113/CBP and Tca8113/PYM cell lines were 3.24 and 11.9 respectively. When ginkgolic acids was added with chemotherapy drugs for some time, the resistance indices of Tca8113/CBP and Tca8113/PYM cell lines were 2.18 and 4.43 respectively. CONCLUSION: This experiment successfully induced the drug-resistant cell lines of Tca8113/CBP and Tca8113/PYM. The method of chemotherapy drugs coupled with ginkgolic acids further confirmed the effect on proliferation of Tca8113/CBP and Tca8113/PYM cell lines was reducing. Non-toxic concentration of ginkgolic acids can partially reverse the drug resistance of Tca8113/ CBP and Tca8113/PYM cell lines. Furthermore, MDR level of drug-resistant cells decreased somewhat when they were induced by ginkgolic acids coupled with chemotherapy drugs for some time.

Role of NGF in spared DRG following partial dorsal rhizotomy in cats.

Neuroplasticity occurs in the spinal cord in response to lesions, but less is known about the underlying mechanism. This investigation explored the role of intrinsic NGF in axonal sprouting of dorsal root ganglia (DRG) in cats subjected to unilateral removal of L1-L5, L7-S2 DRG, but leaving the L6 DRG (spared DRG) undamaged. The expression of mRNA and protein for NGF and TrkA increased significantly by using in situ hybridization histochemistry and immunohistochemistry. ELISA assay showed that the level of NGF was up-regulated in the spared DRG, compared to the control side. In vitro studies showed that cultured neurons prepared from DRG explants of cats that received partial ganglionectomy had greater neurite growth compared to those prepared from untreated controls, and that such increase in neurite was not observed in explants from cats that received partial ganglionectomy and NGF antibody treatment. Taken together, the present findings provided crucial evidence that NGF in DRG might be involved in axonal sprouting in deafferentated cats.

[Expressional change of nitric oxide synthases in dorsal root ganglia of cats after selective dorsal rhizotomy].

OBJECTIVE: To examine the expressional change of nitric oxide synthase (NOS) in the injured dorsal root ganglia (DRG) and the ipsilateral adjacent uninjured DRG after selective dorsal rhizotomy. METHODS: Immunochemical ABC method was used to detect the distribution of immunoreaction complex of NOS isoforms--nNOS and eNOS, and quantitative analysis was conducted to get the number of nNOS-immunoreactivity (nNOS-IR) neurons in normal DRG, dorsal rhizotomized DRG and spared DRG from adult cats on the 6th day after operation. This operating model was made by rhizotomizing unilateral L1-L5 dorsal roots and leaving L6 as a spared root. RESULTS: nNOS-immunoreactants were mainly distributed in the small-sized neurons in the DRG of cat. The percentage of nNOS-expressing small-sized neurons increased in the deafferentated L5 DRG (29.74%) when compared with the contralateral DRG (19.35%), and it also increased in the spared DRG (24.22%), compared with the contralateral DRG (18.61%). eNOS-IR was not observed in the DRG of adult cats. CONCLUSION: nNOS/NO up-regulated in DRG neurons is involved in a wide variety of biological functions under physiological and lesion-induced pathophysiological conditions in nerve system.

[The neurotrophic effect of endogenous NT-3 from adult cat spared dorsal root ganglion on ganglionic neurons].

OBJECTIVE: To investigate the neurotrophic effect of endogenous NT-3 from adult cat dorsal root ganglion (DRG) on ganglionic neurons. METHODS: Rhizotomy of bilateral L1, L3, L5 and L7 dorsal roots of cats was performed, leaving L2, L4 and L6 DRG as spared DRGs. The separate neurons of normal (control) DRG, spared DRG and anti-NT-3 antibody blocking DRG were cultured in vitro respectively. The number of survival neurons and the length of neurites were measured and used for comparison in the control, spared DRG, and block groups. RESULTS: There were survival neurons and cell clusters in every group. The number of survival neurons and cell clusters of spared DRG group were much larger than those of the control and block groups. The neurite length of neurons, the neurite number and the length of cell clusters of spared DRG group were much greater than those of control and block groups. CONCLUSION: Endogenous NT-3 from spared DRG may act on ganglionic neurons to maintain survival of neuron and stimulate growth of neurite.