[Objective] The study was conducted to investigate the effect of micronized fenofibrate on acute insulin response in the subjects with impaired glucose metabolism and hypertriglyceridemia. [Methods] Fifty-three subjects were randomly (2:1 ratio) allocated to fenofibrate group (n=36, including IFG 3 cases, IGT 19 cases, IFG/IGT 6 cases, T2DM 8 cases) or control group (n = 17, including IFG 1 case, IGT 9 cases, IFG/IGT 4 cases, T2DM 3 cases) without any intervention for 3 months. Fasting blood samples were collected for measuring fasting plasma glucose (FPG), free fatty acids (FFA), and lipid profile. IVGTTs were carried out with measurement of plasma insulin before and after treatment. Acute insulin response (AIR), the maximum insulin concentrations (C_(INS,MAX)) to fasting insulin (FINS) ratio (C_(INS,MAX)/FINS) and values of the maximum insulin concentrations increment (△C_(INS)) during IVGTT were calculated as indexes of first-phase insulin secretion. HOMA insulin resistance index (HOMA IR) was used for assessing insulin resistance. [Results] After 3-month treatment, the lipid profile was evidently improved in fenofibrate group. Levels of trigiyceridemia (TG), low-density lipoprotein cholesterol and FFA were significantly reduced and high-density lipoprotein cholesterol increased significantly. Waist circumference was also significantly declined. No change of above indicators was found in control group. In fenofibrate group, C_(INS,MAX)/FINS and △C_(INS) were significantly increased (median 8.4 pmol/L vs. 5.3 pmol/L, 808±473 pmol/L vs. 660±472 pmol/L, both P<0.0001), along with great improvement of AIR (5 585±3 441 pmol·L~(-1)·min~(-1) vs. 4 444±3 642 pmol·L~(-1)·min~(-1), P<0.0001). The level of FINS and HOMA IR was also markedly reduced (108±65 pmol/L vs. 166±115 pmol/L, P = 0.002; 3.8±2.3 vs. 6.0±4.2, P = 0.001). In contrast, there were modest declining in acute insulin response (AIR: 4 313～1 943 pmol·L~(-1)·min~(-1) vs. 5 362±2 861 pmol·L~(-1).min~(-1); C_(INS,MAX)/FINS: median 4.6 vs. 7.0, P= 0.01; △C_(INS): 641±286 pmol/L, vs. 720±321 pmol/L, P= 0.003 9) and increasing HOMA IR (7.8±4.2 vs. 5.6±3.2, P<0.000 1) in control group after 3-month follow-up. The improvement of AIR was correlated with the decreasing of plasma FFA and TG (r=0.41, 0.36, P = 0.002, 0.014), but no correlation with the changing of FPG and HOMA IR. [Conclusions] These results indicated that sbort-term lipid-lowering treatment with fenofibrate evidently improved acute insulin response and alleviated insulin resistance in subjects with impaired glucose metabolism and hypertriglyceridemia. Moreover, the improvement of insulin secretion capacity may be mainly due to the relieving of iipotoxity resulting from finofibrate.

Thirty six patients with hypertriglyceridemia and impaired glucose regulation or newly diagnosed type 2 diabetes, whose fasting plasma glucose was ≤8.0 mmol/L, were treated by fenofibrate for 3 months. Lipid profile, insulin during intravenous glucose tolerance test and oral glucose tolerance test ( including glucose) were measured before and after treatment After treatment, lipid profile was significantly improved. Insulinogenic index (△I30/△G30) and acute insulin response were significantly increased (98. 9vs. 129. 2, 3558.9 vs. 4783. 3 pmol · L - 1 · min - 1, respectively, P ＜ 0. 05 ). Fasting insulin and insulin resistant index in homeostasis model assessment ( HOMA IR) decreased ( 128. 6 vs. 84. 8 pmol/L, 4. 8 vs.3.0, respectively, P ＜0. 05 ). The improvement of insulin secretory function was more significant in patients with higher triglyceride (TG ＞ 3. 3 mmol/L). These results indicate that short-term lipid-lowering treatment with fenofibrate can improve β-cell function and insulin resistance. Patients with higher triglyceride are likely to achieve more benefit from lipid-lowering treatment.

OBJECTIVE Tostudytheeffectofeffectivefractions(EFC)frommodifiedSimiaoWan (MSW)onthelevelofuricacidinhyperuricemicratsandinvestigatethemechanism.METHODS Two types of hyperurice mic models were established.A persistant hyperurice mic model was prepared by giving rats oxonic acid 200 mg·kg -1 and feeding the m with hypoxanthine.The models were ig given with modified Simiaowan (MSW)50 g·kg -1 or EFC 1 2.5,25 and 50 g·kg -1 consecutively for 5 d.The models were treated with MSW or EFC 50 g·kg -1 for 3 d.After the final treatment,the uric acid concen-trations in seru m and urine were determined by an auto matic bioche mistry analyzer.The activity of xan-thine oxidase (XOD )in the serum and liver was determined by enzymic colorimetric method.The activity of purine nucleoside phosphorylase (PNP)and uricase was detected by spectrophotometry. RESULTS Comparedwithnormalcontrolgroup,theserumlevelofuricacidinbothmodelgroupswas remarkably increased(P<0.01 ).Compared to model control group,MSW 50 g·kg -1 and EFC 12.5, 25 and 50 g·kg -1 significantly reduced the serum level of uric acid(P<0.05,P<0.01 ),but increased the activity of erythrocyte PNP(P<0.01 )in the oxonic acid potassium-induced hyperuricemia rats. MSW 50 g·kg -1 and EFC 50 g·kg -1 elevated the activity of liver uricase in the nicotinic acid-induced hyperuricemia rats(P<0.05).EFC 50 g·kg -1 also significantly decreased the serum XOD activity of hyperuricemicrats.CONCLUSION EFCsignificantlyinhibitstheserumlevelofuricacidinhyperurice-mic rats,which might involve down-regulation of protein levels of serum XOD to inhibit the production of uric acid and activation of uricase to pro mote the deco mposition of uric acid.

GATA6 transcription factor belongs to the GATA family and contains 2 conserved zinc ifnger DNA binding domains. GATA6 not only presents in embryonic tissues but also found in heart, lung and pancreas and is essential for the maintenance of their function.The present review focuses on the critical roles of GATA6 in heart development and atrial septal defect to provide theoretical basis for diagnosis and treatment of atrial septal defect.

ObjectiveTo identify mutations ofGATA4 andGATA6 genes in children with isolated congenital atrial septal defect (ASD).Methods From November 2012 to November 2013, 101 patients with ASD (99 unrelated patients and one twin) who were submitted to catheter-based intervention and 100 ethnicity-matched children without congenital heart disease, blood disorders and chromosomal abnormalities were enrolled. The blood was collected. The coding regions and lfanking regions of theGATA4 andGATA6 genes were ampliifed by polymerase chain reaction and sequenced using the dideoxvnucleotide chain termination technique, and then compared with the normal sequence in the Genbank.Results Two novel heterozygous missense GATA6mutations, c. G145A and c. G151A, were identiifed in 2 unrelated ASD patients, which were not present in the controls. These two mutations predicted the conversion of glycine into serine at amino acid residue 49 (G49S) and glutamate into lysine at amino acid residue 52 (K52E). A heterozygous missenseGATA6 mutation c.43 G>C, which caused a conversion from glycine to arginine, was found in 9 ASD patients and 7 controls. A single nucleotide polymorphism c.99G>T, which did not cause amino acid conversion inGATA4 gene, was found.ConclusionsGATA6 gene is an important transcription factor in heart development. The mutation ofGATA6 gene may cause the change of its transcriptional activity, and lead to ASD.

OBJECTIVE: To study the clinical phenotype and gene mutation analysis of a hereditary abnormal fibrinogenemia family and explore its molecular pathogenesis. METHODS: The STA-R automatic hemagglutination analyzer to detect the proband and its family members (3 generations of 5 people) of prothrombin time(PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen activity (Fg: C), D-dimer (D-D), fibrinogen and fibrin degradation products (FDPs), plasminogen activity (PLG: A); The plasma levels of Fg: C and fibrinogen (Fg: Ag) were measured by Clauss method and immunoturbidimetry respectively. All exons and flanking sequences of FGA, FGB and FGG genes of fibrinogen were amplified by PCR, and the PCR products were purified and sequenced for gene analysis. The model was analyzed by Swiss software. RESULTS: The PT and APTT of the proband, her mother and sister were slightly prolonged, TT was significantly extend, Fg: C decreased significantly, Fg: Ag, PLG: A, D-D and FDPs are within the normal range; Her brother and daughter of the results are normal. Genetic analysis showed that g.7476 G>A heterozygous missense mutation in exon 8 of FGG gene resulted in mutations in arginine at position 275 of fibrinogen gamma D domain to histidine (Arg275His). Her mother and sister have the same Arg275His heterozygous mutation, brother and daughter for the normal wild type. CONCLUSION The heterozygous missense mutation of FGG gene Arg275His in patients with hereditary dysfibrinogenemia is associated with a decrease in plasma fibrinogen activity.
Afibrinogenemia ; genetics ; DNA Mutational Analysis ; Female ; Fibrinogen ; genetics ; Fibrinogens, Abnormal ; genetics ; Humans ; Male ; Mutation ; Pedigree

Objective To investigate whether 5% strontium-containing brushite bone cements(DCPD) has repair effect on alveolar bone defects in osteoporotic rabbits. Methods Eighteen healthy adult female rabbits were used to establish osteoporosis models and were randomly divided into three groups:the blank control group, DCPD group,doped 5%DCPD group(5%strontium),with 6 rats in each group.In addition to the blank group, rats the other groups were filled with the corresponding bone cements in the bilateral alveolar bone defects. At 4 weeks and 8 weeks after operation,3 rats in each group were killed and given shooting the defect area X-ray.The expression of b-FGF was detected by immunohistochemistry. Results X-ray results showed that the defected of doped 5% DCPD group have been nearly completedat the 8 week,DCPD group partially completed repair,but blank group was not fully repaired. The results of immunohistochemistry showed that the expression of b-FGF was the highest at 4 weeks and decreased at 8 weeks after operation.Expression of b-FGF was significantly different at 4 weeks and 8 weeks among the three groups.Conclusion The 5%strontium-containing brushite bone cements can repair bone defect in osteoporotic rabbits.

Objective:To investigate the feasibility and clinical efficacy of posterior vertebral column resection (PVCR) combined with polymethylmethacrylate-augmented pedicle screw instrumentation and shortening of spinal column for stage Ⅲ Kümmell's disease with very severe collapse of fractured vertebra.Methods:From January 2017 to September 2021, 9 patients with stage Ⅲ Kümmell's disease with very severe collapse of fractured vertebra underwent PVCR combined with polymethylmethacrylate-augmented pedicle screw instrumentation and shortening of spinal column. Their medical records were retrospectively analyzed. There were 1 male and 8 females, aged (66.9±5.8) years. The injured vertebra was located at T 11 in 2 patients, at T 12 in 4, at L 1 in 2 and at L 2 in 1. X-ray, CT and MRI were performed before operation. The posterior intervertebral heights of adjacent vertebral bodies of the fractured vertebra in the median sagittal position were measured on CT or MRI to evaluate the shortening of the spinal column before PVCR. Recorded were intraoperative bleeding volume, operation time, complications, bone graft fusion, and American Spinal Injury Association (ASIA) grading at preoperation and the last follow-up. The visual analogue scale (VAS) pain scores, Oswestry disability index (ODI) scores, and kyphotic cobb angles at preoperation, 1 week and 3 months postoperation, and the last follow-up were compared to evaluate the clinical efficacy of PVCR. Results:All patients underwent surgery successfully, with tight closure of adjacent vertebrae after resection of the injured vertebra and bone grafting. Operation time was (240.6±23.2) min and intraoperative bleeding (505.6±95.0) mL. The 9 patients were followed up for (17.3±5.6) months. No worsening symptoms of nerve injury, cerebrospinal fluid leakage, or other serious complications were found after operation, nor such complications as loosening or breakage of internal fixation or adjacent vertebral fractures. Bone fusion was achieved at the bone graft sites in all patients by the last follow-up. The VAS and ODI scores and cobb angles at 1 week and 3 months postoperation and at the last follow-up were significantly decreased compared with preoperation ( P<0.05). There were no significant differences in VAS scores or cobb angles among postoperative 1 week and 3 months and the last follow-up ( P>0.05), but pairwise comparisons between different time points after operation showed significant differences in ODI, with postoperative 1 week > postoperative 3 months > the last follow-up ( P<0.05). The ASIA grading at the last follow-up was improved from preoperative grade C to grade D in 2 cases, from preoperative grade C to grade E in 1 case and from preoperative grade D to grade E in 5 cases. Conclusion:PVCR combined with polymethylmethacrylate-augmented pedicle screw instrumentation and shortening of spinal column is a feasible and effective surgical treatment for stage Ⅲ Kümmell's disease with very severe collapse of fractured vertebra, leading to good clinical efficacy.

Tumor cells along with a small proportion of cancer stem cells exist in a stromal microenvironment consisting of vasculature, cancer-associated fibroblasts, immune cells and extracellular components. Recent epidemiological and clinical studies strongly support that vitamin D supplementation is associated with reduced cancer risk and favorable prognosis. Experimental results suggest that vitamin D not only suppresses cancer cells, but also regulates tumor microenvironment to facilitate tumor repression. In this review, we have outlined the current knowledge on epidemiological studies and clinical trials of vitamin D. Notably, we summarized and discussed the anticancer action of vitamin D in cancer cells, cancer stem cells and stroma cells in tumor microenvironment, providing a better understanding of the role of vitamin D in cancer. We presently re-propose vitamin D to be a novel and economical anticancer agent.