Objective To approach the evaluative effect of respiratory variation of superior vena cava peak flow velocity measured using transthoracic echocardiography (TTE) on fluid responsiveness in patients with mechanical ventilation.Methods A prospective cohort study was conducted.All mechanical ventilated critically ill patients whose fluid therapy was planned due to hypovolemia in Department of Critical Care Medicine of Beijing Tongren Hospital of Capital Medical University from April 2011 to April 2013 were enrolled.Volume expansion was performed with 500 mL Linger solution within 30 minutes.Patients were classified as responders if pulse pressure variation (PPV) increased ≥ 13％ before volume expansion.The respiratory variation in superior vena cava peak velocity was calculated as the difference between maximum and minimum values of velocity in peak A,peak S and peak D over a single respiratory circle,and their variations (ΔA,ΔS,ΔD) were also calculated.The receiver operating characteristic curve (ROC curve) was plotted to assess the evaluative effect of respiratory variation of superior vena cava peak velocity on fluid responsiveness.Results Twenty-seven patients were enrolled in this study.Volume expansion increased PPV ≥ 13％ happened in 14 patients (responders).The velocity of superior vena cava in peak A,peak S,peak D was significantly increased after volume expansion compared with that before volume expansion in responders [peak A (cm/s):34.6 ± 2.2 vs.31.3 ±2.1,t=-2.493,P=0.027; peak S (cm/s):39.1 ± 1.3 vs.35.3 ±2.1,t=-2.564,P=0.024; peak D (cm/s):28.1 ± 1.2 vs.23.3 ± 1.4,t=-4.995,P=0.000],but there was no significant difference in ΔA,ΔS and ΔD between before and after volume expansion.The ΔA,ΔS and ΔD were positively correlated with PPV (r＝0.040,P=0.854; r=0.350,P=0.074; r=0.749,P=0.000).The area under ROC curve (AUC) of peak S was 0.36 [95％ confidence interval (95％CI):0.11-0.52],but the AUC of ΔS was 0.68 (95％CI 0.47-0.89),the AUC of peak D was 0.41 (95％CI 0.19-0.63),but the AUC of ΔD was 0.95 (95％CI 0.86-1.00),so the aberration rate of superior vena cava in respiration was better than the flow rate in superior vena cava.When the cut-off value of ΔS was 20.7％ for predicting fluid responsiveness,the sensitivity was 78.6％ and the specificity was 61.5％.When the cut-off value of ΔD was 12.7％ for predicting fluid responsiveness,the sensitivity was 92.0％ and the specificity was 92.3％.Conclusion Respiratory variations in superior vena cava peak velocity measured by TTE could assess fluid responsiveness in patients with mechanical ventilation.

OBJECTIVETo explore the effect of dexmedetomidine combined electrical stimulation on cognitive function of neurosurgical diseases patients treated by extracerebral intervention.

METHODSTotally 122 patients with neurosurgical diseases who underwent selective intervention were randomly assigned to the observation group and the control group, 61 cases in each group. Patients in the control group recieved anesthesia by dexmedetomidine. Those in the observation group received electrical stimulation at Baihui (DU20), Yintang ( EX-HN3), and Neiguan (PC6) before dexmedetomidine anesthesia. The cognitive function of patients at preoperative day 1 and postoperative day 1 was respectively evaluated by Mini-Mental State Examinations (MMSE). Serum NSE, S-100β, IL-1β, IL-6, and TNF-α levels were detected in the two groups before intervention and immediately after intervention using ELISA.

RESULTSMMSE scores of two groups were significantly reduced at post-intervention day 1, as compared with one day before intervention. MMSE score of the observation group at post-intervention day 1 was (23.15 ± 1.87) points, significantly higher than that of the control group [ (19.34 ± 1.64) points , (P < 0.05)]. The postoperative cognitive dysfunction (POCD) incidence rate of the observation group was 16.4% (10/61), significantly lower than that of the control group [39.3% (24/61); P < 0.05]. Compared with before intervention, NSE and S-100β protein levels, IL-1β, IL-6 and α-TNF levels of the two groups increased (P < 0.05). Post-intervention NSE and S-100β protein levels, IL-1β, IL-6 and α-TNF levels were significantly lower in the observation group than in the control group (P < 0.05).

CONCLUSIONDexmedetomidine combied electrical stimulation could effectively prevent the occurrence of postoperative cognition, and reduce levels of NSA, S-100β, IL-1β, IL-6 and TNF-α.

Acupuncture Points ; Anesthesia ; methods ; Cognition ; Cognition Disorders ; prevention & control ; Dexmedetomidine ; therapeutic use ; Electric Stimulation Therapy ; Humans ; Interleukin-1beta ; blood ; Interleukin-6 ; blood ; Neuropsychological Tests ; Neurosurgical Procedures ; Phosphopyruvate Hydratase ; blood ; Postoperative Complications ; Postoperative Period ; S100 Calcium Binding Protein beta Subunit ; blood ; Tumor Necrosis Factor-alpha ; blood

Aim To explore the effect and mechanism of antioxidant peptide AOP1 on repair of skin burn wound healing in mice.Methods Fluorescence probe DCFH-DA was used to detect the changes of intracellular reactive oxygen species (ROS).Cell proliferation and migration assay were used to detect AOP1 toxicity and its effect on wound healing.Moreover,the skin scald wound was made on the shaved dorsum of the anesthetized mice with a 1.0 cm diameter brass cylinder heated in a water bath at 80 ℃ for 2 min and pressed against the rat skin for 10 s.The effects of AOP1 on the healing of skin burns were observed by HE and Masson staining and the contents of MDA and the activity of SOD in skin tissues were measured.Results The antioxidant peptide AOP1 could significantly reduce the number of ROS in HaCaT and L929 cells,and promote cell migration and proliferation.Compared with the untreated group,the skin healing time of AOP1 group was short,the healing rate was high,the area of scab was small,and inflammation and the content of MDA in burned tissue significantly decreased.The effect of AOP1 on healing of burn wound healing was also confirmed by HE and Masson staining.Conclusion It is suggested that the antioxidant peptide AOP1 with natural activity may promote the healing of skin burns by reducing the oxidative stress caused by burns.

OBJECTIVETo evaluate the effects of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II type 1 receptor (AT-1 receptor) blocker on the progression of rat pulmonary fibrosis induced by bleomycin A5.

METHODSTwenty-four male Wistar rats were randomized into pulmonary fibrosis model, perindopril treatment, losartan treatment and control groups. In the former 3 groups, pulmonary fibrosis was induced via intratracheal injection of bleomycin A5 (5 mg/kg), after which the rats in the perindopril and losartan groups received intragastric administration of the corresponding agents at the daily dose of 2 mg/kg and 10 m/kg, respectively. The rats in the control group had intratracheal injection of normal saline only. In the 4th week, the histological changes of the lung tissues were examined microscopically with Masson staining. Hydroxyproline content in the lungs was measured, and the protein expressions of AT-1 receptor, TGF-beta1 and IkappaBalpha were examined using Western blotting. DNA binding activity of NF-kappaB was analyzed with electrophoretic gel mobility shift assay (EMSA), and zymography was used to assess the activity of matrix metalloproteinase-2 and 9 (MMP-2, 9).

RESULTSBoth perindopril and losartan treatment significantly reduced the pulmonary fibrosis score, content of hydroxyproline, protein expression of TGF-beta1, DNA binding activity of NF-kappaB and MMP-2, 9 activity, and increased cytoplasmic protein expression of IkappaBalpha. Perindopril treatment lowered the protein level of AT-1 receptor.

CONCLUSIONPerindopril and losartan may inhibit bleomycin A5-induced pulmonary fibrosis in rats by reducing the protein expression of TGF-beta1 and suppressing the DNA binding activity of NF-kappaB and MMP-2, 9 activity.

Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Animals ; Bleomycin ; analogs & derivatives ; Blotting, Western ; Losartan ; therapeutic use ; Male ; NF-kappa B ; metabolism ; Perindopril ; therapeutic use ; Pulmonary Fibrosis ; chemically induced ; drug therapy ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Receptor, Angiotensin, Type 1 ; metabolism ; Transforming Growth Factor beta1 ; metabolism

OBJECTIVETo evaluate the relationship between peroxisome proliferator-activated receptor-γ2 (PPARγ2) Pro12Ala polymorphism and type 2 diabetes mellitus (T2DM) in Chinese Han population.

METHODSPubMed, Chinese Biomedicine Database (CBM), China National Knowledge Infrastructure (CNKI) and Wanfang database were searched for all relevant articles investigating the association between PPARγ2 Pro12Ala polymorphism and T2DM that were available from January, 1990 to June, 2011. A total of 29 relevant articles were selected. A Meta-analysis was performed to estimate heterogeneity and the pooled odds ratio (OR) to evaluate the relationship between PPARγ2 Pro12Ala polymorphism and T2DM. The sensitivity analysis was also assessed.

RESULTSA total of 21 qualified articles including 3870 patients with T2DM and 3333 healthy controls were analyzed in the study. The frequencies of the allele Ala12 in T2DM and control groups were 4.13% (320/7740) and 4.56% (304/6666), respectively. There were not heterogeneity (χ(2) = 25.96, P = 0.17) among the 21 qualified articles. The pooled OR (95%CI) value of the frequencies of the PPARγ2 genotype (PA + AA)/PP calculated by fixed effects model was 0.96 (0.81 - 1.14) (P = 0.64). There was not heterogeneity among the remaining articles after excluding the article with the largest weight and the article with larger frequencies of the allele Ala12 respectively (χ(2) values were 24.23, 16.87 respectively, both P values > 0.05). The pooled OR (95%CI) value of the frequencies of the PPARγ2 genotype (PA + AA)/PP of the remaining articles were 1.01 (0.84 - 1.21) and 1.07 (0.89 - 1.28) after excluding the article with the largest weight and the article with larger frequencies of the allele Ala12 (both P values > 0.05).

CONCLUSIONPPARγ2 Pro12Ala polymorphism was not associated with type 2 diabetes mellitus in Chinese Han population.

Alleles ; Asian Continental Ancestry Group ; genetics ; China ; Diabetes Mellitus, Type 2 ; genetics ; Gene Frequency ; Genotype ; Humans ; PPAR gamma ; genetics ; Polymorphism, Single Nucleotide

Construction of mutant strain is an essential method in pathogenesis researches. The conventional method for Brucella unmarked deletion mutant construction is based on suicide plasmid, but the efficiency is very low. In the present study, we first optimized the electroporation parameters, and then, the cloning plasmid pEX18Gm containing sacB was successfully used to construct unmarked deletion mutant of the type IV secretion system. This indicated that by using conventional cloning plasmid as suicide plasmid in Brucella, unmarked deletion mutants can be constructed with high efficiency.

Mitochondrial respiratory chain deficiency is a common cause of mitochondrial disease in children. This study aimed to review the clinical, enzymatic and genetic characteristics of a Chinese boy with progressive intrahepatic cholestasis due to mitochondrial respiratory chain complex I deficiency. The boy developed diarrhea from the age of 13 months, followed by progressive body weight loss, jaundice and weakness. His urine organic acids, blood amino acids and acylcarnitines profiles were normal. Mitochondrial respiratory chain complexes I to V activities in peripheral leukocytes were measured using spectrophotometric assay. Complex I activity was reduced. 5821G>A mutation was indentified by gene sequencing on tRNA-cys of mitochondrial gene in the patient and his mother. Vitamin supplements, liver protection, antibiotics and plasma infusion were not effective in the patient. Unfortunately, the boy died at the age of 17 months. Mitochondrial respiratory chain complex I deficiency is the most common mitochondrial respiratory chain disorder. This was the first case of intrahepatic cholestasis due to complex I deficiency confirmed by mitochondrial respiratory chain enzyme activity assay and gene analysis in China. It was concluded that mitochondrial hepatopathy is one of major causes of metabolic hepatopathy. Biochemical assay, mitochondrial respiratory chain complex activities assay and genetic analysis are crucial for the etiological diagnosis of metabolic hepatopathy.
Cholestasis, Intrahepatic ; diagnosis ; etiology ; Diagnosis, Differential ; Electron Transport Complex I ; deficiency ; Humans ; Infant ; Male ; Mitochondrial Diseases ; complications

This study reports a boy with psychomotor retardation and epilepsy due to maternal phenylketonuria (PKU). The boy was admitted at the age of 20 months because of psychomotor retardation and epilepsy. He had seizures from the age of 1 year. His development quotient was 43. He presented with microcephaly, normal skin and hair color. Brain MRI scan showed mild cerebral white matter demyelination, broadening bilateral lateral ventricle and foramen magnum stricture. Chromosome karyotype, urine organic acids, blood amino acids and acylcarnitines were normal. His mother had mental retardation from her childhood. She presented with learning difficulties and yellow hair. Her premarriage health examinations were normal. She married a healthy man at age of 26 years. When she visited us at 28 years old, PKU was found by markedly elevated blood phenylalanine (916.54 μmol/L vs normal range 20-120 μmol/L). On her phenylalanine hydroxylase (PAH) gene, a homozygous mutations c.611A>G (p.Y204C) was identified, which confirmed the diagnosis of PAH-deficient PKU. Her child carries a heterozygous mutation c.611A>G with normal blood phenylalanine. Her husband had no any mutation on PAH. It is concluded that family investigation is very important for the etiological diagnosis of the children with mental retardation and epilepsy. Carefully clinical and metabolic survey should be performed for the parents with mental problems to identify parental diseases-associated child brain damage, such as maternal PKU.
Adult ; Epilepsy ; etiology ; Female ; Humans ; Infant ; Intellectual Disability ; etiology ; Male ; Phenylalanine Hydroxylase ; genetics ; Phenylketonuria, Maternal ; Pregnancy

Methylmalonyl CoA mutase deficiency due to MUT gene defect has been known as the main cause of isolated methylmalonic acidemia in Mainland China. This study reported a patient with isolated methylmalonic aciduria (MUT type) characterized as acute brainstem encephalitis and myelitis. The previously healthy girl presented with fever, lethargy and progressive weakness in her extremities at the age of 3 years and 2 months. Three day later, she had respiratory distress and consciousness. Cranial MRI revealed bilateral symmetrical lesion of pallidum, brain stem and spinal cord, indicating acute brainstem encephalitis and myelitis. Her blood propionylcarnitine (6.83 μmol/L vs normal range 1.0 to 5.0 μmol/L) and urinary methylmalonic acid (133.22 mmol/mol creatinine vs normal range 0.2 to 3.6 mmol/mol creatinine) increased significantly. Plasma total homocysteine was normal. On her MUT gene, a reported mutation (c.1630_1631GG>TA) and a novel mutation (c.1663C>T, p.A555T) were identified, which confirmed the diagnosis of methylmalonic aciduria (MUT type). After cobalamin injection, protein-restricted diet with the supplements of special formula and L-carnitine, progressive improvement has been observed. The clinical manifestation of patients with methylmalonic aciduria is complex. Metabolic study and gene analysis are keys for the diagnosis and treatment of the disorder.
Acute Disease ; Amino Acid Metabolism, Inborn Errors ; etiology ; Brain Stem ; pathology ; Child, Preschool ; Encephalitis ; etiology ; Female ; Humans ; Methylmalonyl-CoA Mutase ; genetics ; Mutation ; Myelitis ; etiology

OBJECTIVEMethylmalonic aciduria is the most common disorder of organic acidurias in the mainland of China. It is also the one of treatable metabolic disorders. The clinical spectrum of the patients varies from severe neonatal-onset forms with neonatal brain injury and high mortality to milder forms with adult-onset. The clinical manifestations of neonates with methylmalonic aciduria are non-specific. Early diagnosis and adequate treatment contribute a lot to improving the prognosis of the patients. In this study, the abnormal clinical and laboratory findings in neonatal period of 160 Chinese patients with early-onset methylmalonic aciduria were investigated.

METHODFrom 1996 to 2011, a total of 398 patients with methylmalonic aciduria were diagnosed in our hospital; 286 (71.9%) patients had early-onset before 1 year of age. Among 286 patients, 160 (55.9%) presented symptoms in neonatal period. Their urine organic acids were analyzed by gas chromatography-mass spectrometry. Blood amino acids and acylcarnitine profiles were determined by liquid chromatography tandem mass spectrometry. Serum and urine total homocysteine were measured using a fluorescence polarization immunoassay. In some patients, gene analysis was performed. Based on the disease types and general condition, individual dietary and medical interventions were started soon after diagnosis.

RESULTOut of the 160 patients, 131 (81.9%) had combined methylmalonic aciduria and homocysteinemia. Isolated methylmalonic aciduria was found in 29 cases (18.1%). The common presentations in neonatal period were feeding difficulty, seizures, lethargy and dyspnea. Megaloblastic anemia, liver dysfunction, hyperammonemia and metabolic acidosis were the frequent findings in the routine laboratory test. The most common initial clinical diagnosis was suspected hypoxic-ischemic encephalopathy. Even in 36 cases with abnormal family history, only 3 patients were admitted with suspected inborn errors of metabolism. Five cases (3.1%) were diagnosed by postmortem metabolic examination; 7 cases (4.4%) were detected by newborn screening. In 148 cases (92.5%), the diagnosis was much delayed to the age of one month to 8 years and 5 months (mean 13 months). Methylmalonic aciduria combined with homocysteinemia (MMACHC) gene analyses were performed in 31 cases with combined methylmalonic aciduria. CblC defect was confirmed. The patients with isolated methylmalonic aciduria were treated with protein-restricted diet, cobalamin and L-carnitine. The patients of methylmalonic aciduria combined with homocysteinemia were treated with cobalamin, L-carnitine, calcium folinate, betaine and common diet. Seven patients died without treatment. Clinical improvement was observed in 153 patients. Only 2 patients detected by newborn screening had normal mental and physical development. Mild to severe psychomotor retardation was observed in 151 cases.

CONCLUSIONHigh mortality and disability rates were observed in the patients with early-onset methylmalonic aciduria. Combined methylmalonic aciduria and homocysteinemia is the common type of methylmalonic aciduria. The clinical manifestation in neonatal period of the patients with early-onset methylmalonic aciduria is complex. Feeding difficulty, seizures, lethargy and dyspnea are the common symptoms in neonatal period of the patients. Megaloblastic anemia, liver dysfunction, hyperammonemia and metabolic acidosis were the frequent laboratory findings.

Amino Acid Metabolism, Inborn Errors ; complications ; diagnosis ; genetics ; therapy ; Carnitine ; therapeutic use ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Folic Acid ; therapeutic use ; Gas Chromatography-Mass Spectrometry ; Homocysteine ; blood ; urine ; Humans ; Hyperhomocysteinemia ; diagnosis ; etiology ; therapy ; Infant ; Infant, Newborn ; Male ; Methylmalonic Acid ; urine ; Neonatal Screening ; Retrospective Studies ; Vitamin B 12 ; therapeutic use