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Tumor cells can metabolize glucose through glycolysis to intermediates for biomacromolecule synthesis by inhibiting the activity of the pyruvate dehydrogenase complex (PDC) in mitochondria. In this process, pyruvate dehydrogenase kinases (PDKs) play a key role. The inhibition of the activity of PDKs can effectively block this metabolic pathway, activate mitochondrial oxidative metabolism, and induce tumor cell apoptosis. PDK inhibitors have become a research hotspot in medicinal chemistry, and novel structures targeting classical binding sites have been synthesized. In this paper, recent research progress on PDK inhibitors is reviewed to provide information on these latest entities and to explore their clinical applicability.
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Objective:To discuss influence of addition and subtraction therapy of Zhenwutang to residual renal function （RRF）， nutritional status， dialysis adequacy and quality of life of patients with maintenance hemodialysis （MHD）. Method:One hundred and thirty-six patients were randomly divided into control group （68 cases） and observation group （68 cases） by random number table. Patients in two group got MHD， 3 times/week， 4 h/time， levocarnitine injection （1 g dissolved in 5-10 mL water for injection） after the dialysis， 2-3 min/time， recombinant human erythropoietin injection with subcutaneous injection for 4 weeks， 3 000 U， 3 times/day， valsartan capsules for 3 months， 80 mg/time， 1 time/day. The control group took Manshenning mixture， 35 mL / time， 3 times / day.Patients in observation group added addition and subtraction therapy of Zhenwutang for 3 months， 1 dose/day. Before and after treatment， urea nitrogen （BUN）， creatinine （CR） and 24 hours' urine volume were recorded. And RRF， rate of decrease of RRF and rate of decrease in urine volume were also calculated. Levels of hemoglobin （HB）， albumin （ALB）， prealbumin （PA） and transferrin （TRF） were detected. After treatment， standardized protein metabolism rate （nPCR）， urea clearance index （Kt / V） and glomerular filtration rate （EGFR） were discussed. And improved subjective comprehensive nutrition assessment （SGA）， dialysis related quality of life （kdta） and health survey summary （SF-36） were graded. Six months' follow-up， primary end point event （24 h urine volume ≤ 400 mL） and no residual renal function （24 h urine volume ≤ 400 mL） were recorded. Result:Levels of RRF， Kt/V， nPCR， eGFR， Hb， Alb， PA， TRF and total scores of KDTA and SF-36 in observation group were higher than those in control group （P<0.01）. And score of SGA， rate of decrease of RRF and rate of decrease in urine volume were less than those in control group （P<0.01）.Incidence rate of primary end point event was 27.94%（19/68） lower than 47.06%（32/68） in control group （χ2=5.302， P<0.05）， incidence rate of no residual renal functionwas 17.65%（11/68） lower than 36.76%（25/68） in control group （χ2=6.274， P<0.05）. And BUN and Cr were lower than those in control group （P<0.01）， 24 h urine volume was more than that in control group （P<0.01）. Conclusion:Addition and subtraction therapy of Zhenwutang can maintenance of RRF， improvement of nutritional status， improvement of dialysis adequacy and quality of life of patients .
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The aetiology of developmental dyslexia (DD) is complex; although candidate genes have been suggested, the molecular mechanism and risk factors remain unknown. The KIAA0319 gene is functionally related to neuronal migration and axon growth, and several studies have examined associations between KIAA0319 polymorphisms with DD, but the results remain inconsistent. The sample size affects the results of meta-analysis. The aim of this meta-analysis was to clarify the effect of KIAA0319 polymorphisms on dyslexia susceptibility according to the available evidence. All eligible case–control and transmission/disequilibrium test (TDT) studies published until March 2018 were identified by searchingMedline, PubMed, Embase, Web of Science and Chinese Biomedical Database, limited to Chinese and English language papers. Pooled odds ratios and 95% confidence intervals were calculated using STATS package v12.0. A total of 11 related studies, including 3130 cases of dyslexia and 3460 healthy control subjects, as well as four TDT studies with 842 families were included in our meta-analysis. The results indicated that the polymorphisms rs4504469, rs2038137, rs2179515, rs3212236, rs6935076, rs9461045, rs2143340 and rs761100 have no association between the polymorphisms and dyslexia risk. Three subgroup meta-analyseswere performed according to the study design, country and population. The stratified analysis revealed that the KIAA0319 rs4504469 minor allele was a risk allele t in the TDT subgroup, rs3212236 minor allele was a risk allele t in the UK subgroup and rs6935076 minor allele was a risk allele t in the Canada subgroup. Further studies with larger sample sizes that assess gene–gene and gene–environment interactions are required. The sample size of our study is larger than that of the previous studies, and the results are different from those of the previous studies.We have synthesized all the current studies on KIAA0319 and obtained reliable results.
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BACKGROUND: Blood hemoperfusion with resin adsorption can clean larger molecules that exceed the molecular weight cutoff of combined continuous veno-venous hemofiltration (CVVH). Hence blood hemoperfusion with resin adsorption combined CVVH (HP+CVVH) has higher ability of mediator clearance, and can improve clinical outcomes in theory. This study aimed to investigate the effect of blood hemoperfusion with resin adsorption combined continuous veno-venous hemofiltration (HP+CVVH) on plasm cytokines like TNF-α, IL-1β, IL-6, cellular immunity and prognosis in patients with multiple organ dysfunction syndrome (MODS). METHODS: This was a prospective, randomized clinical trial. A total of 30 patients who had been diagnosed with MODS were enrolled in this study. Patients were randomly allocated to routine treatment+HP+CVVH group (treatment group) and routine treatment+only CVVH group (control group). In the treatment group, patients received blood hemoperfusion with resin adsorption for 2 hours, and then received CVVH for 10 hours every day. In the control group, patients received CVVH for 12 hours only every day. The patients in the two groups received blood purification therapy for three days. The plasma of patients in the treatment group was obtained at 0, 2, 12, 24, 26, 36, 48, 50, 60 hours, 5th day, 7th day and 10th day, respectively. The plasma of patients in the control group was obtained at 0, 12, 24, 36, 48, 60 hours, 5th day, 7th day and 10th day, respectively. APACHE II score, T-lymphocytes subpopulations, blood lactate acid concentration, heart rate, breathing rate, and oxygenation index were observed. RESULTS: Plasma cytokines like TNF-α, IL-1β, IL-6 decreased markedly after HP (P<0.01);T-lymphocytes subpopulations CD3+, CD4+, CD8+, CD4+/CD8+ increased after HP+CVVH or only CVVH. The plasma concentrations of TNF-α, IL-1β and IL-6 in the two groups were not markedly different at 12, 36, and 50 hours. But on the 5th day, the plasma concentrations of TNF-α, IL-1β and IL-6 in the treatment group were lower than those in the control group (P<0.05). On the 28th day, 5 patients died in the treatment group, and 6 patients in the control group. CONCLUSIONS: Both HP+CVVH and CVVH can clean plasma cytokines like TNF-α, IL-1β, and IL-6, and improve cellular immunity and clinical symptoms and signs of patients. Compared with only CVVH, the plasma concentrations of TNF-α, IL-1β and IL-6 were lower on the 5th day, and patients have an increased survival rate on the 28 day in the HP+CVVH group.
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Objectives: We sought to determine whether the aryl hydrocarbon receptor (AhR) and interleukin (IL)-22 may be involved in the pathogenesis of the peripheral blood mononuclear cells (PBMCs) in allergic asthmatic patients and whether their expression may be related to the severity of the disease. Methods: Blood samples were obtained from each subject with allergic asthma (n =18), controlled asthma (n =17) and healthy controls (n =12) respectively. The PBMCs were collected for AhR mRNA detection by real-time quantitative polymerase chain reaction (PCR). The plasma was collected for IL-22 protein detection by enzyme-linked immunosorbent assay (ELISA).Results: The expression of AhR mRNA in PBMCs and IL-22 protein in plasma of patients with allergic asthma were higher than those in controlled asthma cases and healthy controls. The plasma concentrations of IL-22 had negative correlation with the predicted percentage of forced expiratory volume in the first second (FEV1%) and the percentage of FEV1 and forced vital capacity (FEV1/FVC%) and it was positively correlated with the asthma severity score (ASS) of the asthmatics. Conclusion: Our results suggested that both AhR and IL-22 might be involved in the pathogenesis of allergic asthma in human and the level of IL-22 might have some relationship with the severity of the disease.
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This study compared the efficacy and safety of tiotropium bromide inhalation powder (spiriva) and doxofylline oral tablet (doxofylline) in the treatment of chronic obstructive pulmonary disease (COPD).A multi-center,randomized,double-blind,double-dummy,parallel-controlled study involved 127 eligible stable moderate to severe COPD patients treated with inhaled tiotropium dry powder (18 μg/day) or oral doxofylline tablets (0.2 g/time,2 times a day) for 12 and 24 weeks.Before and after treatment for 12 weeks and 24 weeks,respectively,pulmonary function,6-min walking distance and dyspnea index were recorded.The results showed that in both tiotropium group and doxofylline groups,after 12-week treatment,FEV1,FEV1/FVC％ and 6-min walk distance were significantly higher than those before the medication,while dyspnea index decreased as compared with that before treatment.After 24-week treatment,a slight improvement in the measures was observed as compared with that of 12-weeks treatment,but the difference was not statistically significant.With both 12-week and 24-week treatment,the effect of tiotropium was slightly better than that of doxofylline tablets,with the difference being statistically insignificant.The major adverse events in the tiotropium group and doxofylline group were observed in 9 cases (9.9％) and 12 cases (12.9％),respectively,and no statistically significant difference was found between them.We are led to conclude that both tiotropium at 18 μg a day and doxofylline tablets at 0.2 g/day (two times a day) are effective and safe for the treatment of COPD.