Objective To evaluate the effect of glucose-insulin-potassium (GIK) on intestinal injury in endotoxemic rats.Methods Sixty male Sprague-Dawley rats, weighing 200-250 g, were equally and randonly divided into endotoxemia group (lipopolysaccharide [LPS] group) and GIK group.LPS 8 mg/kg was injected intraperitoneally once a day for 3 times in total to establish the model of endotoxemia-caused intestinal injury.Starting from 2 h after the initial injection of LPS, normal saline was continuously infused at 4 ml · kg 1 · h-t in group LPS, and GIK 4 ml · kg 1 · h 1was infused intravenously in group GIK.Before establishment of the model, and at 3 and 5 days after establishment of the model, 10 rats in each group were sacrificed, and blood samples were collected from the abdominal aorta for determination of tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) and diamine oxidase (DAO) concentrations in plasma by enzyme-linked immunosorbent assay.TNF-α/IL-10 ratio was calculated.A segment of ileum of 2 cm in length, 20 cm from the ileocecal junction, was removed for microscopic examination.The degree of damage to the intestinal mucous membrane was scored according to Chiu.Results Compared with the values before establishment of the model, the plasma TNF-α/IL-10 ratio, DAO concentration, and Chiu's scores were significantly increased at 3 days after establishment of the model in the two groups, the plasma TNF-α/IL-10 ratio, DAO concentration, and Chiu's scores were increased at 5 days after establishment of the model in group LPS, and the plasma DAO concentration, and Chiu's scores were increased at 5 days after establishment of the model in group GIK (P＜0.05).Compared with the values at 3 days after establishment of the model, the TNF-α/IL-10 ratio and plasma DAO concentration were significantly increased in group LPS, and the TNF-α/IL-10 ratio and plasma DAO concentration were decreased in group GIK at 5 days after establishment of the model in group GIK (P＜0.05).Compared with group LPS, the TNF-α/IL-10 ratio, plasma DAO concentration, and Chiu's scores were significantly decreased at 3 and 5 days after establishment of the model in group G1K (P＜0.05).Conclusion GIK can reduce intestinal injury in endotoxemic rats.

Objective To explore the correlation of PAI-1 and TNF-α and the pathophysiology of the metabolic syndrome (MS) and coronary heart disease,and explore the role of metformin in the MS.Methods Sixty cases of old patients with the MS were chosen.These patients were divided into two groups at random.One group interfered with living style and metformin,the other group only interfered with living style.The activity of PAI-1 was detected by chromogenic substrate method,and the level of TNF-α was detected by ELISA assay.Results (1) The levels of PAI-1 and TNF-α in the MS patients [(0.95 ± 0.05) AU/ml,(24.81 ± 3.87)ng/ml] were significantly higher than in normal old people[(0.66 ± 0.10)AU/ml,(10.76 ±2.00) ng/ml] (P ＜0.001) ;(2)The levels of PAI-1 and TNF-α in the MS patients with CHD [(0.96 ± 0.05) AU/ml,(26.12 ± 2.83) ng/ml] were significantly higher than those in the patients without CHD [(0.94 ± 0.03) AU/ml,(23.71 ± 4.27) ng/ml] (P ＜ 0.05) ;(3)The activity of PAI-1 and the level of TNF-α in the metformin group was decreased significantly [△ was (0.20 ± 0.17)AU/ml,(4.42 ± 0.85ng/ml),P ＜0.01],and metformin can improve the components of the MS.Conclusions The old patients with MS is prone to develop cardiac vascular disease.PAI-1 and TNF-α participate in pathophysiology of the MS and its complication.Metformin can inhibit the expression of PAI-1 and TNF-α to suppress the components of the MS,and block the complication of the MS.

Objective To investigate if glucose-insulin-potassium (GIK)would relieve the liver injury induced by endotoxemia in rats.Methods Sixty SD male rats,weight 200-250g,were randomly divided into three groups (n = 20):control group (group C),lipopolysaccharide group (group LPS,LPS 8 mg/kg)and Glucose-insulin-potassium group(group GIK,8 mg/kg LPS+GIK 4 ml·kg-1 ·h-1 ).All the rats were injected with 20 mg/kg ketamine intraperitonealy before trial. Erythrocin was daubed on the wound to avoid infection.The rats of group LPS and group GIK were injected LPS 8 mg/kg intraperitoneal,then,rats in group LPS and group GIK received saline(4 ml·kg-1 ·h-1 )or GIK(Glucose 200 g/L,Insulin 60 IU/L,KCL 60 mmol/L)infusion continuously. Liver and serum samples were collected on before injection,3 days after injection and 5 days after in-jection.Serum concentrations of ALT and AST were measured.TNF-αlpha of liver homogenate was detected by ELISA.The severity of liver damage was assessed by an approprite histopathological sco-ring system and apoptosis of parenchymal cells were assessed by TUNEL immunofluorescence assay. Results Compared with group control,the level of serum ALT and AST in group LPS and group GIK were significantly higher at 3 days after injection.The level of hepatic TNF-α,the hepatic damage score and the index of hepatic apoptosis in group LPS and group GIK were significantly higher on 3 days after injection and 5 days after injection.(P<0.05).Compared with group LPS,the level of hepatic TNF-αand the hepatocyte apoptosis rates decreased significantly in group GIK on 3 days after injection.The level of serum ALT and AST,hepatic TNF-α,the hepatic damage score and the hepatocyte apoptosis rates decreased significantly in group GIK at 5 days after injection(P <0.05).Conclusion Intraperitoneal injection of endotoxin can cause liver injury in rats,resulting in the liver hepatdysfunction and hepatocyte damage.GIK has protective effects on LPS induced liver injury in rats.

ObjectiveTo investigate the effect of magnesium sulfate combined with monosialoganglioside on the recovery of motor function after spinal cord injury in rats.Methods48 healthy adult rats were randomly divided into groups A, B, C and D, and SCI was made by Allen's mode(10 g×25 mm) on spinal cord T9 extradually, 12 rats in each group. On the 1st d, 3rd d and 7th d after SCI, the recovery of motor function after spinal cord injury in rats was assessed with Basso-Beattie-Bresnahan(BBB)scale and slanting board test. Thiobarbituric acid was used to detect the concentration of malondialdehyde, and was observed the change of free radicals.ResultsAfter spinal cord injury in rats, BBB scores and slanting board test of groups A, B and C were better than group D. BBB scores and slanting board test of group C was better than groups A and B, which had significant difference on the 3rd d and 7th d after injury(P<0.05). After spinal cord injury in rats, concentration of malondialdehyde of groups A, B and C were lower than group D(P<0.05). Concentration of malondialdehyde of group C was lower than groups A and B, which had significant difference after injury(P<0.05).ConclusionMagnesium sulfate combined with GM1 can promote the recovery of motor function early after spinal cord injury in rats, and is superior to magnesium sulfate or GM1.

Objective To observe the effects of electroacupuncture combined with edaravone on the conduction velocity of sciatic nerve and oxidative stress in rats with diabetic peripheral neuropathy. Methods 60 Sprague Dawley (SD) rats were included. 10 of them were selected as normal group. The other rats were modeled as diabetic peripheral neuropathy with streptozotocin. 48 of them were randomly selected and divided into electroacupuncture group (n=12), edaravone group (n=12), electroacupuncture + edaravone group (n=12), and model group (n=12). The threshold temperature for wave tail was tested, the levels of superoxidase dismutase (SOD) and malonaldehyde (MDA) were determined, and the conduction velocity of sciatic nerve were measured, before, and 4 and 8 weeks after modeling. Results 8 weeks after modeling, the conduction velocity and SOD increased in the electroacupuncture group, edaravone group and electroacupuncture+edaravone group compared with the model group (P<0.01), with the MDA decrease (P<0.01), while it was improved more in the electroacupuncture+edaravone group than in the electroacupuncture group or the edaravone group (P<0.01). Conclusion Both electroacupuncture and edaravone can inhibit oxidative stress and improve nerve conduction velocity of the sciatic nerve in rats with diabetic peripheral neuropathy, and it is more effective of combination.

OBJECTIVETo study the chemical constituents of ethyl acetate-soluble fraction from methanolic extract of the roots and rhizomes of Notopterygium incisum .

METHODThe chemical constituents were isolated and purified by various chromatographic methods, and their structures were identified by NMR and MS data analysis.

RESULTFive compounds were obtained and identified as falcarindiol (1), 8-hydroxy-l-methoxy-( Z) -9-heptadecene-4, 6-diyn-3-one (2) angenomalin (3), scopoletin (4), O-methylnotopterol (5).

CONCLUSIONCompound 5 was a new natural product and compounds 2-4 were isolated from the roots and rhizomes of N. incisum for the first time.

Apiaceae ; chemistry ; Coumarins ; analysis ; isolation & purification ; Plant Extracts ; analysis ; isolation & purification ; Plant Roots ; chemistry ; Rhizome ; chemistry

Objective: To explore the clinical phenotypes and the genetic causes for a 5 years old boy with unexplained growth retardation, developmental delay, special face, and hypothyroidism. Methods: Routine G-banding was performed to analyze the karyotype of the patient and his parents. In addition, whole exome sequencing and low-coverage massively parallel CNV sequencing (CNV-seq) were used to determine the potentially pathogenic variants as well as the copy number variations (CNVs). Results: The child′s karyotype was 46, XY, and his parents′ karyotypes were normal.However, CNV-seq identified a heterozygous deletion of 1.56 Mb on chromosome region 7q11.23 in the patient, including 24 protein-coding genes, which were associated with Williams-Beuren syndrome. His parents′ results of CNV-seq were normal, indicating a de novo CNVs. Conclusion A Williams-Beuren syndrome child presenting with hypothyroidism was diagnosed by CNV-seq, which would contribute to further understanding the clinical phenotypes and pathogenesis of this disease.

Objective: Autoimmune polyendocrine syndrome type Ⅰ(APS-Ⅰ) is caused by mutations in the autoimmune regulator gene (AIRE) gene. In this study, phenotype and AIRE gene analysis were performed in two patients with APS-Ⅰ. Methods: Peripheral blood samples were collected from two patients with APS-Ⅰ and their families. All exons of the AIRE gene and adjacent exon-intron sequences were amplified by PCR and subsequently sequenced. The silico analysis was performed to predict the possible impact of the mutations on the function of the AIRE protein. At the same time, 100 healthy controls were selected to confirm the mutation. Results: Case 1 was a 31-year-old female who exhibited chronic mucocutaneous candidiasis, hypoparathyroidism, Addison′s disease, Hashimoto′s thyroiditis, and premature ovarian failure. A homozygous c. 483_484insC mutation in exon 4 of AIRE gene was identified in this patient. Her parents, siblings and son were heterozygous for this mutation, which is consistent with the autosomal recessive inheritance pattern. Case 2 was a 34-year-old male who had mucocutaneous candidiasis, Addison′s disease, primary hypoparathyroidism, and Hashimoto′s thyroiditis. A compound heterozygous AIRE mutation (c.179A>G/C.463+ 2T>C) were identified in this patient. His father was heterozygous for c. 179A>G mutation, and his mother was heterozygous for C. 463+ 2T>C, which is consistent with autosomal recessive inheritance mode. The c. 483_484insC and c. 463+ 2T>C have been reported to be pathogenic. The c. 179A>G mutation was predicted pathogenic by SIFT and PolyPhen2 software, which was not detected in 100 healthy controls. It has not been reported in the HGDM database and is a novel mutation. Conclusion We identified a novel AIRE gene mutation (c.179A>G), which contributed to further understanding of the pathogenesis of APS-Ⅰ. The clinical variation and rarity of APS-Ⅰ makes the syndrome hard to recognize. Early recognition of symptoms and screening for AIRE mutation in patients with APS-Ⅰ has important clinical implications for the diagnosis and treatment.

Objective:Kallmann syndrome(KS) is a complex genetic disease characterized by congenital hypogonadotropic hypogonadism and anosmia. More than 20 genes have been reported to be associated with KS. Herein, we explore potential genetic aberration in 3 KS patients using the whole-exome sequencing. The potentially pathogenic variants filtered were validated by Sanger sequencing.Methods:Genomic DNA was extracted from the peripheral blood of 3 patients with KS and their family members. Sanger sequencing and pedigree verification were performed on the pathogenic variants identified using whole-exome sequencing. The function of the mutation sites were analyzed with bioinformatics software.Results:The proband 1 was a 25 years old male, characterized by lower gonadotropin gonad hypofunction, early grey hair and bilateral sensorineural hearing loss. A heterozygous mutation c. 475C>T(p.R159W) of SOX10 gene was detected in the proband 1. His mother, sister and cousin who had KS phenotype were also found carrying this mutation, showing an autosomal dominant inheritance. The proband 2 was a 15-year-old male with hypogonadotropic hypogonadism and unilateral renal agenesis. The proband was hemizygous for c. 844delC(p.R282Vfs*28) of ANOS1 gene, his mother was heterozygous for the mutation, which was consistent with the X-linked recessive inheritance. The proband 3 was a 21 years old female, characterized by hypogonadotropic hypogonadism and anosmia. A heterozygous missense mutation c. 149G>A(p.R50Q) was detected in FGF17 gene. The mutation p. R50Q was predicted to be pathogenic by the SIFT and PolyPhen2 programs, and has not been reported in HGDM database yet, which considered to be a novel mutation.Conclusion:KS is a clinically and genetically heterogeneous disease. In this study, ANOS1 c. 844delC, SOX10 c. 475C>T and FGF17 c. 149G>A mutations were found in 3 patients with KS by whole exome sequencing, which would expand the genotypic and phenotype spectrum of KS.

Tumor-induced osteomalacia(TIO)is a rare paraneoplastic syndrome in which tumor-induced osteochondrosis is a metabolic bone disease caused by increased renal excretion of phosphorus due to excessive secretion of fibroblast growth factor 23(FGF23)by tumor tissue.We report here a rare case of TIO in which the tumor was found in the hyoid body and the patient had tertiary hyperparathyroidism.The patient's symptoms did not improve after removal of the tumor from the hyoid body,and the patient's hypophosphatemia was gradually improved after subsequent removal of the left parathyroid gland.TIO derived from the tongue tumor is very rare,and also subsequent tertiary hyperparathyroidism is even rarer.This report helps to improve the understanding of TIO and provides reference in the diagnosis and treatment of TIO.