Clinical and Genetic Study on 48 Children with Short Stature of Unknown Etiology / 中山大学学报(医学科学版)

ObjectiveTo explore the clinical features and causative genes of short stature children with unknown etiology， providing evidence for precise clinical diagnosis and treatment. MethodsThe study recruited children with suspected but undiagnosed short stature from the pediatric endocrinology department in our hospital between January 2018 and August 2022. A retrospective analysis was performed on the clinical manifestations， laboratory test and whole exome sequencing （WES） results. Causative genes were classified and analyzed according to different pathogenic mechanisms. ResultsA total of 48 children （30 boys and 18 girls） were enrolled， aged 7.73 ± 3.97 years， with a height standard deviation score （ HtSDS） of -3.63 ± 1.67. Of the patients， 33 （68.8%） suffered from facial anomalies， 31 （64.6%） from skeletal abnormalities， 26 ［54.2%， 61.5% of whom born small for gestational age （SGA）］ from perinatal abnormalities， 24 ［50.0%， 87.5% of whom with growth hormone （GH） peak concentration below normal］ from endocrine disorders and 21（43.8%） had a family history of short stature. Laboratory tests showed that GH peak concentration following stimulation test was （9.72 ± 7.25） ng/mL， IGF-1 standard deviation score was -0.82 ± 1.42， the difference between bone age and chronological age was -0.93 ± 1.39 years. Of the 25 cases with mutant genes found by WES， 14 （56.0%） had pathogenic mutation， 6 （24.0%） likely pathogenic mutation， and 5 （20.0%） mutation of uncertain significance. Pathogenic and likely pathogenic variants were identified in 14 genes， including 10 affecting intracellular signaling pathways （PTPN11， RAF1， RIT1， ARID1B， ANKRD11， CSNK2A1， SRCAP， CUL7， SMAD4 and FAM111A） and 4 affecting extracellular matrix （ECM） components or functions （ACAN， FBN1， COL10A1 and COMP）. ConclusionsA rare monogenic disease should be considered as the possible etiology for children with severe short stature accompanied by facial anomalies， disproportionate body types， skeletal abnormalities， SGA， GH peak concentration below normal and a family history of short stature. WES played an important role in identifying the monogenic causes of short stature. This study indicated that affecting growth plate cartilage formation through intracellular signaling pathways and ECM components or functions was the main mechanism of causative genes leading to severe short stature in children. Further research may help discover and study new pathogenic variants and gene functions.

The effects of a half palm ankle-foot orthosis and a hollow-heel ankle-foot orthosis on the gait of stroke survivors / 中华物理医学与康复杂志

Objective:To observe any effect of a half palm ankle-foot orthosis and a hollow-heel ankle-foot orthosis on the gait of stroke survivors.Methods:The walking of twenty-five stroke survivors was quantified using a gait analysis system. They walked barefoot, wearing a half palm ankle-foot orthosis and wearing a hollow-heel ankle-foot orthosis. Walking speed, step frequency, duration of the swing phase on the healthy and affected sides, risk of falling and Timed Up and Go (TUG) test times were recorded and analyzed.Results:The average gait frequency when wearing the hollow-heel ankle-foot orthosis was significantly faster than that in the other two conditions. The gait asymmetry coefficient was significantly different when the subjects wore the hollow-heel ankle-foot orthosis compared with walking barefoot. Compared with being barefoot, the average TUG time was significantly shorter when wearing either orthosis and the risk of falling was significantly less. The fall risk was significantly lower when wearing the hollow-heel orthosis compared to the half palm orthosis.Conclusion:Wearing either ankle-foot orthosis can significantly correct the gait of stroke survivors and lower their risk of falling, with better effect when wearing the hollow-heel ankle-foot orthosis.

Effect of sitagliptin phosphate combined with metformin on blood glucose control and microinflammatory status in type 2 diabetes mellitus / 中国医师进修杂志

Objective:To explore the effects of sitagliptin phosphate combined with metformin on blood glucose control and microinflammation in patients with type 2 diabetes.Methods:One hundred patients with newly diagnosed type 2 diabetes who were treated in the First Affiliated Hospital of Xingtai Medical College from March 2017 to March 2019 were randomly divided into observation group (50 cases) and control group (50 cases). The observation group was treated with sitagliptin phosphate combined with metformin for 8 weeks, while the control group was treated with metformin for 8 weeks. The changes of fasting blood-glucose (FBG) and blood glucose 2 h after meal (2 h-PBG ) in the two groups before and after treatment were observed, and the standard time of FBG and 2 h-PBG in the two groups were statistically analyzed. The levels of interleukin(IL)-1, IL-6 and high-sensitivity C-reactive protein (hS-CRP) were compared between the two groups before and after treatment.Results:After treatment, the levels of FBG and 2 h-PBG in the observation group were significantly lower than those in the control group: (6.32 ± 0.83) mmol/L vs. (7.21 ± 1.03) mmol/L, (8.61 ± 1.26) mmol/L vs. (9.63 ± 1.12) mmol/L, and the standard time of FBG and 2 h-PBG in the observation group were significantly shorter than those in the control group: (3.11 ± 0.86) weeks vs. (4.53 ± 1.31) weeks, (3.26 ± 0.36) weeks vs. (9.63 ± 1.12) weeks, and the differences were statisticlly significant ( P<0.05). After treatment, the serum levels of IL-1, IL-6 and hs-CRP in the observation group were significantly lower than those in the control group: (22.86 ± 4.07) ng/L vs. (35.13 ± 5.92) ng/L, (5.93 ± 0.84) ng/L vs. (9.67 ± 1.11) ng/L, (2.12 ± 0.25) ng/L vs. (3.57 ± 0.48) ng/L, and the differences were statistically significants ( P<0.05). Conclusions:Sitagliptin phosphate combined with metformin in the treatment of type 2 diabetes patients can rapidly and effectively control blood glucose and improve the state of microinflammation in patients.

Identification of a novel missense NIPBL variant in a juvenile with severe type of Cornelia de Lange syndrome / 中华医学遗传学杂志

OBJECTIVE@#To detect pathogenic variant in a juvenile with severe type Cornelia de Lange syndrome (CdLS).@*METHODS@#A 12-year-old female presented with comprehensive developmental retardation and deformity of lower limbs. Genomic DNA was extracted from peripheral blood sample of the patient. Whole exome sequencing was performed to identify pathogenic variants. Putative variant was verified by Sanger sequencing. The impact of variants was predicted and validated by bioinformatic analysis.@*RESULTS@#A de novo missense variant, c.1507A>G (p. Lys503Glu), was found in the NIPBL gene of the proband. The variant was unreported previously and predicted to be pathogenic by PolyPhen-2, MutationTaster and SIFT. Using HomoloGene system, the 503 loci in the NIPBL protein are highly conserved. The change of amino acid (Glu), locating in 503 locus, was found to cause the Neuromodulin_N superfamily domain destroyed, resulting in severe damage to the function of NIPBL protein.@*CONCLUSION@#The de novo missense variant c.1507A>G (p. Lys503Glu) of the NIPBL gene probably underlies the disease in this patient.

Identification of a novel de novo variant of CSNK2A1 gene in a boy with Okur-Chung neurodevelopmental syndrome / 中华医学遗传学杂志

OBJECTIVE@#To analyze pathogenic variant of CSNK2A1 gene in a boy with Okur-Chung neurodevelopmental syndrome (OCNS).@*METHODS@#The 8-year-old boy presented with growth retardation, intellectual disability and spells of breath holding. With genomic DNA extracted from peripheral blood samples of the patient and his parents, whole exome sequencing was carried out. Putative pathogenic variants were verified with Sanger sequencing. The nature and impact of detected variants were predicted through bioinformatic analysis.@*RESULTS@#A novel de novo missense variant c.149A>G (p.Tyr50Cys) of the CSNK2A1 gene was identified, which was unreported previously. The variant was predicted to be pathogenic by PolyPhen-2, Mutation Taster and SIFT software. Based on a HomoloGene system, 50 loci within the CK2alpha protein are highly conserved. The change of amino acid (Cys) at position 50 has destroyed the ATP binding loop domain, causing serious damage to its function. As predicted by a Swiss PDB viewer, the variant can significantly alter the spatial structure of CK2alpha, resulting in loss of protein function.@*CONCLUSION@#The patient's condition may be attributed to the novel de novo missense variant c.149A>G (p.Tyr50Cys) of the CSNK2A1 gene.

Analysis of Fingerprint and Pattern Recognition of Different Parts of Panax notoginseng / 中国药学杂志

OBJECTIVE: To establish a chemical pattern recognition method for Panax notoginseng (P. notoginseng) and classify the main root, rhizome, and rootlet. METHODS: The fingerprints of P. notoginseng samples in three different parts were established based on HPLC method. The similarity was calculated by the Similarity Evaluation System of Chromatographic Fingerprints of Traditional Chinese Medicine (2012 edition). The pattern recognition were carried out by principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA). RESULTS: The HPLC fingerprint common pattern of 35 batches of P. notoginseng samples was established. Similarity values were in the range of 0.994 to 1.000, which indicated that similarity analysis could not classify them. The established PCA model could only identify the rhizome, besides PLS-DA can completely identify the three parts of P. notoginseng. Seven characteristic peaks, such as ginsenoside Rg1, ginsenosides Rb1 were screened as biomarkers. CONCLUSION: The combination of HPLC fingerprint and chemical pattern recognition could provide a comprehensive reference for the quality control and quality evaluation of P. notoginseng.

Analysis of clinical manifestations and gene mutations of 13 child patients with rare causes of primary adrenal insufficiency / 中华内分泌代谢杂志

Objective To analyze the clinical manifestations and gene mutations of rare causes of primary adrenal insufficiency (PAI) in childhood.Methods The clinical features,laboratory tests and gene mutation of 13 patients with PAI in our hospital from September 2010 to August 2017 were analyzed retrospectively.Patients with congenital adrenal hyperplasia,X-linked adrenoleukodystrophy with neurological onset or a clear family history,and autoimmune adrenal insufficiency were excluded.Results The median age of 13 cases (12 males,1 female) was 3 years and 10 months.Medical history or clinical manifestations on the first visit included hyperpigmentation,electrolyte imbalance/salt-wasting crisis,gastrointestinal symptoms,and fatigue,etc.All developments of external genitalia were normal.All cases presented with decreased serum cortisol and increased ACTH levels.Some of the cases showed decreased aldosterone level and plasma renin activity,while 17α-hydroxyprogesterone,testosterone,and androstenedione were in the normal range.Part of cases revealed delayed bone age and adrenal atrophy.Three gene mutations were detected in 13 patients,including NR0B 1 gene (9/13),ABCD 1 gene (3/13),and CYP 11A 1 gene (1/13).NR0B1,and ABCD1 gene mutations were pathogenic mutations,consistent with clinical characteristics.CYP11A1 gene mutation was heterozygote,which cannot fully explain the clinical features.Conclusion PAI in childhood presents common clinical manifestations of adrenal insufficiency,e.g.hyperpigmentation and electrolyte imbalance/sah-wasting crisis,but without specificity.Gene mutational analysis is necessary for precise diagnosis and prognosis estimation.NR0B1 and ABCD1 gene mutations were common in childhood with rare causes of PAI.

Clinical Characteristics and Gene Mutation Types of 11 Cases of RASopathies in Childhood / 中山大学学报(医学科学版)

@#【Objective】Through summarizing the clinical manifestations and gene mutations of 5 types of RASopathies in childhood including Neurofibromatosis type1（NF1），Noonan syndrome（NS），Noonan syndrome with multiple lentigines（NSML），Costello syndrome（CS）and cardio-facio-cutaneous syndrome（CFC）and analyzing their commonalities and characteristics，to deepen the clinician′s understanding of the RASopathies and improve the domestic doctors′ diagnosis and treatment level of RASopathies.【Methods】The clinical data and gene mutation types of 11 patients of RASopathies who were diagnosed in Sun Yat- Sen Memorial Hospital from January 2015 to May 2018 were retrospectively analyzed. 【Results】The age of onset ranged from 6 months to 12 years and the main clinical manifestations of 11 patients included： short stature，craniofacial features，congenital heart defect，café-au-lait macules，developmental delay，thrombocytopenia， seizures and dystonia，cryptorchidism，etc. Five gene mutations were detected including NF1 gene，PTPN11 gene， RAF1 gene ，BRAF gene and HRAS gene.【Conclusions】The RASopathies are a clinically defined group of medical genetic syndromes caused by germline mutations in genes that encode components or regulators of the Ras/MAPK pathway. The RAS/MAPK pathway plays an important role in regulating growth development，promoting cell proliferation，differentiation，metabolism，and signal transduction of various hormones. Therefore，they share many overlapping characteristics，including craniofacial features，growth retardation，cardiac malformations，cutaneous and musculoskeletal abnormalities，neurocognitive impairment and tumor susceptibility. However ，each RASopathy exhibits different degree phenotypes because of mutations at different points in the pathway. In addition ，tumor susceptibility is one of the typical clinical features of RASopathies. Therefore，tumor monitoring is one of the most important contents in the follow-up process.

Effects of different doses of atorvastatin in patients with SAS and coronary artery disease after PCI / 实用医学杂志

Objective To assess the effect of perioperative dose atorvastatin on inflammatory status and cardiac function in patients with coronary heart disease complicated by sleep apnea syndrome(SAS)during periop-erative period.Methods A total of 102 patients were enrolled into 3 groups.Group A(n=32)received 80 mg of atorvastatin before PCI,post-PCI follow-up atorvastatin 40 mg for 4 weeks,and atorvastatin 20 mg for 20 weeks;group B(n=32)received no pre-PCI loading dose of atorvastatin but received atorvastatin 40 mg for 4 weeks and then atorvastatin 20 mg for 20 weeks;and group C(n = 38)received only post-PCI atorvastatin 20 mg for 24 weeks.Venous blood samples were collected into Vacutainer tubes from fasting patients on admission(day 0),and 1 day,7 days,4 weeks,and 24 weeks after PCI to measure BNP,MMP-9 and hs-CRP.All the patients underwent echocardiographic assessment on the third day after primary PCI and at the 24th week after a follow-up. Results No differences were found in baseline demographic and angiographic characteristics,and inflammatory factor among the 3 groups. As compared with group C,the average levels of hs-CRP,BNP and MMP-9 in group A de-creased significantly(P<0.05)at different time points during atorvastatin treatment(PCI),and the average level of MMP-9 in group B decreased significantly(P<0.05)after 7 days.At 24 weeks after PCI,LVEF was significant-ly higher in group A and group B than in group C(P<0.05).Conclusions Additional loading-dose atorvastatin before PCI may help prevent inflammatory response and improve cardiac function in patients with SAS complicated by coronary heart disease undergoing PCI.

Administration of Clopidogrel in patients after percutaneous coronary intervention / 中华老年医学杂志

Objective To provide supportive evidence for using Clopidogrel in patients with coronary heart disease(CHD)after percutaneous coronary intervention(PCI). Methods From June 2015 to May 2016,105 cases of CHD were admitted to the Department of Cardiology,the First Affiliated Hospital of Zhengzhou University.Genetic testing for CYP2C19 polymorphisms combined with thromboela-stogram was used to detect the rate of Clopidogrel resistance,and adverse cardiovascular events were recorded for 12 months after PCI.Moreover,multivariate Logistic regression was used to analyze risk factors of Clopidogrel resistance. Results A total of 98 cases completed genetic testing for CYP2C19 polymorphisms.Cases with the wild type allele,heterozygous mutations and homozygous mutations accounted for 35.7%,57.1% and 7.1%,respectively.Compared that for wild type cases(49.6 ± 18.5)%,the platelet inhibition rate was significantly reduced for hybrid mutation cases(38.4 ± 15.2)% and homozygous mutation cases(24.8 ± 12.9)%(t=3.142,3.370;P=0.002,0.001,respectively).Meanwhile,based on pharmacokinetic characteristics,the rates of Clopidogrel resistance for patients with the intermediate metabolic type(the heterozygous mutant type) and the slow metabolic type(the homozygous mutant type)were significantly higher than that for patients with the normal metabolic type(the wild type)(χ2 = 5.687,6.363;P< 0.05,respectively). Follow-up results showed that the incidences of adverse cardiovascular events for wild-type and heterozygous mutation patients were 2.9% and 3.6%,respectively,which were significantly lower than that for homozygous mutant patients(28.6%)(χ2 = 5.815,6.540;P< 0.05,respectively). Multivariate Logistic regression analysis showed that risk factors for clopidogrel resistance were glycosylated hemoglobin Alc level,total cholesterol and white blood cell count. Conclusions Genetic testing for CYP2C19 polymorphisms combined with thromboela-stogram can be used as an effective way to evaluate whether Clopidogrel should be used.It is important to measure the platelet aggregation inhibition rate for early detection of Clopidogrel resistance to insure appropriate drug use.

Asiatic acid inhibits LPS-induced inflammatory response via Cardiology, regulating TLR4 and PPAR-γin VSMCs / 中国药理学通报

Aim To observe whether asiatic acid ( AA) can inhibit lipopolysaccharide ( LPS )-induced inflammatory response in VSMCs , and explore its mechanism of action .Methods The VSMCs isolated from aorta of SD rats were primarily cultured . The effect of AA on the cell viability of VSMCs was meas-ured by MTT assay .The protein and mRNA expression of IL-6, MCP-1, and TNF-α, were measured by ELISA assay and real-time PCR, respectively.The protein and mRNA of TLR4 and PPAR-γwere meas-ured by Western blot and real-time PCR, respectively . Results AA exhibited no effect on cellular viability between the concentration from 0 to 30 μmol · L-1 . After treating VSMCs with LPS (500μg· L-1 ) for 6h or 24 h, the protein and mRNA expression of IL-6, MCP-1, TNF-α, and TLR4 significantly increased ( P<0.05 );and on the contrary , the activity of PPAR-γwas significantly reduced ( P<0.05 ) .Treatment with AA (10, 20, 30 μmol· L-1 ) could concentration-de-pendently inhibit LPS-induced protein and mRNA ex-pression of IL-6, MCP-1, TNF-α.AA could also re-duce LPS-induced protein and mRNA expression of TLR4, and pretreatment of the cells with TLR4-siRNA could reduce LPS-induced inflammation . Moreover , treatment with AA could up-regulate the mRNA and protein expression of PPAR-γin VSMCs; however , GW9662 , a PPAR-γantagonist , partially attenuated AA' s anti-inflammatory effect .Conclusion AA can significantly inhibit LPS-induced mRNA and protein expression of IL-6, MCP-1, TNF-α, in VSMCs, which is partially dependent on suppressing TLR 4 and up-regulating PPAR-γ.

Effect of astaxanthin on expression of type Ⅰ and type Ⅲ collagen in cardiac fibroblasts and its mechanism based on TGF-β1/Smad3 signaling pathway / 中国药理学通报

Aim To observe the effects of astaxanthin ( ASTX) on the expression of collegeⅠ( ColⅠ) and type Ⅲcollagen ( Col Ⅲ) of cardiac fibroblasts( CFs) which caused by transforming growth factor β1 ( TGF-β1) and to explore its mechanism of action. Methods CFs were induced by TGF-β1 , and then pretreated with different concentrations of ASTX ( 0 , 5 , 10 , 20 , 40, 80, 160 μmol·L-1) for 24 h. MTT assay was used to determine the activity of CFs. The activation of ROS in CFs cells was detected by DCFH-DA kit. Smad3 gene was silenced by siRNA technique, and re-al-time PCR was used to detect the expression of ColⅠ, Col Ⅲ mRNA before and after Smad3 silencing. Western blot was used to detect the expression of ColⅠ, Col Ⅲ and Smad3 protein levels before and after Smad3 silencing. Results ASTX had no obvious cyto-toxicity in the range of 0 ～20 μmol · L-1 , and could significantly reduce ROS production induced by TGF-β1 in CFs (P<0.05). In addition, ASTX significant-ly inhibited the expression of ColⅠand ColⅢmRNA and protein ( P<0.01 ) of TGF-β1-induced CFs in a concentration-dependent manner. Also, ASTX could significantly down-regulate phosphorylation of Smad3 in TGF-β1-induced CFs ( P <0.01 ) . The expression of Col Ⅰ and Col Ⅲ mRNA and protein was also signifi-cantly down-regulated by Smad3 gene silencing ( P <0.01 ) . Conclusions ASTX can effectively inhibit the expression of Col Ⅰ, Col Ⅲ mRNA and protein of TGF-β1-induced CFs, and the possible mechanism may involve the down-regulation of Smad3 phosphoryla-tion.

Analysis of the influence of iron overload in glucose metabolism in thalassemia major patients / 中华儿科杂志

Objective@#This study aimed at determining the characteristics of the glucose homeostasis and its relationship with iron overload of the patients with β-thalassemia major (β-TM).@*Method@#From Sun Yat-sen Memorial Hospital between January 2014 and December 2015, a total of 57 transfusion-dependent β-TM patients with 5-18 years old were enrolled in this study and fasting blood glucose(FBG) and insulin level, serum ferritin (SF), serum iron, transferrin, total iron binding capacity, unsaturated iron binding capacity were determined.Insulin resistance index (IRI), insulin sensitivity index and β-cell function index (BFI) were also estimated. Besides, in 36 patients cardiac T2* and liver T2* were estimated.@*Result@#(1) Four patients(7%) with β-TM were diagnosed diabetes mellitus, and 14(24%) had impaired fasting glucose. (2) The incidence of abnormal glucose metabolism was significantly different according to levels of SF and degrees of the cardiac iron overload(χ2=9.737, P<0.05; χ2=17.027, P<0.05). It rose while the level of SF increased and the degree of cardiac iron overload aggravated. (3) The incidence of abnormal glucose level was not significantly different in cases with different degree of liver iron overload.The severe group of liver iron overload had significantly higher levels of INS, HOMA-βFI, HOMA-ISI, HOMA-βFI than the non-severe group (Z=-2.434, -2.515, F=8.658, all P<0.05), while no differences were found in the level of FBG, HOMA-βFI between two groups. (4) The result of logistic regression analysis indicated that the cardiac T2* was a significant predictor for the incidence of abnormal glucose metabolism in TM patients (P=0.035, OR=1.182%, 95%CI=1.048 to 1.332).@*Conclusion@#The high prevalence of abnormal glucose metabolism in β-TM patients was mainly closely related with the internal iron overload, especially in organs.The cardiac T2* was an independent risk factor for the incidence of abnormal glucose metabolism in TM patients.

Changes of thyroid autoantibodies and its relationship with dyslipidaemia in children with Turner syndrome / 中华实用儿科临床杂志

Objective To investigate the changes of thyroid autoantibody(TAA)in children with Turner syndrome(TS),and its association between TAA and thyroid dysfunction,age,karyotype and dyslipidaemia.Methods Thirty-two patients with TS diagnosed by chromosome analysis hospitalized at Sun Yat-Sen Memorial Hospital,Sun Yat-Sen University from July 2007 to July 2015 were divided into 2 groups based on TAA-positive or TAA-negative,then the thyroid dysfunction,the age,the karyotype and the lipid metabolism were compared between 2 groups.Results Of the 23 cases of TAA-positive girls(23/32 cases,71.88％),9 girls(39.13％)suffered from thyroid dysfunction;of the 9 cases of TAA-negative girls(9/32 cases,28.12％),3 girls(33.33％)had thyroid dysfunction.As compared with the girls in TAA-negative group,the age in TAA-positive group was significantly higher[(12.08±2.90)years old vs.(8.89±4.17)years old],and the difference was significant(t=101.500,P=0.047).The patients were divided into 4 age groups:0-5 years old,>5-10 years old,>10-15 years old and >15 years old;the rates with TAA-positive were 25.00％(1/4 cases),75.00％(6/8 cases),82.35％(14/17 cases)and 66.67％(2/3 cases)respectively.Twenty patients received the lipid metabolism test,and 11 cases(11/20 cases,55.00％)of them suffered from dyslipidaemia,9 cases of them were TAA-positive(9/11 cases,81.82％),and 2 cases were TAA-negative(2/11 cases,18.18％).The differences in the prevalence of dyslipidaemia between the 2 groups were significant(x2=4.848,P=0.028).There was no significant difference in the numbers of TAA-positive cases among different karyotypes(x2 =4.246,P=0.120).Conclusions Patients with TS are prone to suffer from thyroid dysfunction and dyslipidaemia.Timely detection of TAA and thyroid function is recommended,as well as the lipid metabolism if necessary.

Effect of mecobalamin on diabetic peripheral neuropathy and its effect on plasma homocysteine / 中国生化药物杂志

Objective To study the correlation analysis of mecobalamin in treatment of diabetic peripheral neuropathy and its plasma homocysteine level. Methods 100 patients were selected from January 2013 to August 2016 treatment of diabetic peripheral neuropathy, according to admission ID, were randomly divided into control group and observation group, each group of 50 people. At the same time, 50 healthy persons were collected as normal control group and two groups were given routine treatment of Western medicine. The observation group was given mecobalamin. The plasma levels of plasma homocysteine were detected in the three groups, and the improvement degree of neuropathy was assessed by clinical and electrophysiological methods. Results The observation group and the control group of patients before treatment, plasma homocysteine levels were significantly higher than normal control group; the observation group with Mecobalamin after treatment of plasma homocysteine level in patients were significantly better than the control group (P<0.05); through clinical and electrophysiological evaluation method of observation group of patients in the neuropathic symptoms and nerve conduction velocity is the control group improved significantly (P<0.05). Conclusion The levels of plasma homocysteine and diabetic peripheral neuropathy have a strong correlation, and the use of mecobalamin in treating diabetic peripheral neuropathy can decrease homocysteine levels in patients with, and is effective for the treatment of diabetic peripheral neuropathy, and can be widely applied in clinical treatment.

Effect of mecobalamin on diabetic peripheral neuropathy and its effect on plasma homocysteine / 中国生化药物杂志

Objective To study the correlation analysis of mecobalamin in treatment of diabetic peripheral neuropathy and its plasma homocysteine level. Methods 100 patients were selected from January 2013 to August 2016 treatment of diabetic peripheral neuropathy, according to admission ID, were randomly divided into control group and observation group, each group of 50 people. At the same time, 50 healthy persons were collected as normal control group and two groups were given routine treatment of Western medicine. The observation group was given mecobalamin. The plasma levels of plasma homocysteine were detected in the three groups, and the improvement degree of neuropathy was assessed by clinical and electrophysiological methods. Results The observation group and the control group of patients before treatment, plasma homocysteine levels were significantly higher than normal control group; the observation group with Mecobalamin after treatment of plasma homocysteine level in patients were significantly better than the control group (P<0.05); through clinical and electrophysiological evaluation method of observation group of patients in the neuropathic symptoms and nerve conduction velocity is the control group improved significantly (P<0.05). Conclusion The levels of plasma homocysteine and diabetic peripheral neuropathy have a strong correlation, and the use of mecobalamin in treating diabetic peripheral neuropathy can decrease homocysteine levels in patients with, and is effective for the treatment of diabetic peripheral neuropathy, and can be widely applied in clinical treatment.

Clinical phenotypes and copy number variations in children with microdeletion and microduplication syndromes: an analysis of 50 cases / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the association between genotype and phenotype of microdeletion and microduplication syndromes (MMSs) and the pathogenesis of pathogenic copy number variations (CNVs).</p><p><b>METHODS</b>A total of 50 children with MMSs diagnosed by chromosomal microarray analysis (CMA) from June 2013 to September 2015 were enrolled, and the clinical manifestations and features of pathogenic CNVs were analyzed.</p><p><b>RESULTS</b>The main clinical manifestations of children with MMSs included mental retardation, developmental delay, short stature, and unusual facies, with the presence of abnormalities in multiple systems. There were 54 pathogenic CNVs in total, consisting of 36 microdeletion segments and 18 microduplication segments, with sizes ranging from 28 kb to 48.5 Mb (mean 13.86 Mb). Pathogenic CNVs often occurred in chromosomes X, 15, and 1.</p><p><b>CONCLUSIONS</b>The clinical manifestations of MMSs are not specific, and a genotype-first approach can be used for diagnosis. Mode of inheritance, type of recombination (deletion or duplication), size of segment, and functional genes included helps with the interpretation of CNVs of de novo mutations, and in-depth research on rare pathogenesis may become breakthrough points for the identification of new MMSs.</p>

Curcumin inhibits AngⅡ-induced proliferation and oxidative stress in vascular smooth muscle cells / 西安交通大学学报(医学版)

Objective To investigate the effect of curcumin (Cur)on AngⅡ-induced proliferation and oxidative stress of vascular smooth muscle cells (VSMCs).Methods Primary rat VSMCs were cultured and divided into control group,AngⅡ group,AngⅡ+Cur 5μmol/L group,AngⅡ+Cur 10μmol/L group,AngⅡ+Cur 20μmol/L group,and Cur 20μmol/L group.The proliferation of AngⅡ-induced VSMCs was measured by MTT assay.The mRNA and protein expressions of inducible nitric oxide synthase (iNOS)and p47phox were detected by real-time PCR and Western blot.Nitric oxide (NO)production was measured by Griess reaction.Production of intracellular reactive oxygen species (ROS)was measured by DCFH-DA staining,and the activities of superoxide dismutase (SOD)and glutathione peroxidase (Gpx)were detected by xanthine oxidase assay and visible spectrophotometer. small interfering RNA (siRNA)was used to silence the expression of p47phox to further explore the mechanism for Cur inhibiting the proliferation of AngⅡ-induced VSMCs and oxidative stress.Results VSMCs activities were not significantly affected by Cur at the concentration between 0 and 80μmol/L.Cur (5,10 and 20μmol/L)significantly inhibited AngⅡ-induced proliferation of VSMCs.Cur had an inhibitory effect on the overexpression of NO,iNOS, p47phox and ROS in VSMCs and upregulated the activities of SOD and Gpx in a concentration-dependent manner. AngⅡ-induced ROS production in VSMCs was significantly attenuated by pretreatment with p47phox specific siRNA.Conclusion Cur can inhibit the proliferation and oxidative stress of AngⅡ-induced VSMCs.

Curcumin inhibits LPS-induced inflammation in VSMCs via Toll-like receptor 4/NADPH oxidase/reactive oxygen species signaling pathway / 西安交通大学学报(医学版)

Objective To explore the inhibitory effect of curcumin on LPS-induced inflammation and the activation of Toll-like receptor 4 (TLR4 )/NADPH oxidase/reactive oxygen species (ROS)signaling pathway in vascular smooth muscle cells (VSMCs).Methods Primary VSMCs were cultured and divided into control group, LPS group,LPS + curcumin 5 μmol/L group,LPS + curcumin 10 μmol/L group and LPS + curcumin 30 μmol/L group.Cell activity was observed by MTT assay.The secretion of tumor necrosis factor-α(TNF-α)and interleukin-1 (IL-1)was measured by enzyme linked immunosorbent assay (ELISA)kits.The mRNA expressions of TLR4 and p22phox were detected by real-time PCR.Expression of intracellular ROS was measured by flow cytometry. Results The activities of VSMCs were not significantly affected by curcumin at the concentration between 0 and 80 μmol/L.Curcumin (5,10 and 30 μmol/L)significantly inhibited LPS-induced oversecretion of TNF-αand IL-1, as well as overexpression of TLR4 and p22phox at the mRNA and protein levels,and ROS production in VSMCs in a concentration-dependent manner.Conclusion Curcumin has a concentration-dependent inhibitory effect on the secretion of inflammatory cytokine,overexpressions of TLR4 and p22phox,and production of ROS in VSMCs stimulated by LPS.Furthermore,curcumin may partly depend on TLR4/NADPH oxidase/ROS signaling pathways to inhibit inflammation in LPS-induced VSMCs.

The progress and prospect of prepulse inhibition in autism / 生理学报

Prepulse inhibition (PPI) is suppression of the startle reflex when an intense startling stimulus is preceded by a weaker sensory stimulus (the prepulse). It is an operational measurement of sensorimotor gating mechanism to help human adapt to complex environment. This weak prepulse protect central cognitive processing by damping the effect of intense stimuli. Autistics cannot select out behaviorally important information from a lot of irrelevant resources and reflect abnormal gating mechanism and attentional abnormalities. Previous studies have not made agreement on whether autistic patients demonstrated deficits in PPI, because the results depend on age, sex, severity of the disease as well as the experimental parameters used. Moreover, these studies have not covered whether autistics have suffered deficits in higher-order processing. In this review, the "top-down" modulation of selective attention and subjective emotion are introduced into the PPI experiment. We also introduce fear conditioning and perceived spatial separation paradigm to further explore the interaction between autistic cognitive process and gating mechanism.