Tanshinones are a large class of hydrophobic natural products isolated from traditional Chinese herb Salvia miltiorrhiza Bunge and related plants. Tanshinones include tanshinone ⅡA, cryptotanshinone, tanshinone I, dihydrotanshinone, and so on. Both the tanshinones and the salvianolic acids have been identi-fied as the characteristic and main active ingredients of Salvia miltiorrhiza Bunge with cardiovascular protective activities. Ac-cumulated data in recent years have revealed that tanshinones possess remarkable anti-cancer activities both in vivo and in vitro. In this review, we summarize the latest progress of the an-ti-cancer effect and the underlying mechanisms of tanshinones, particularly with emphasis on tanshinone ⅡA, which might pro-vide reference for the further research and development of these compounds.

We systematically analyse and summarize on the literature(1996-2016) by reading and analysing them.Active ingredients and pharmacological activity of traditional Chinese medicine pigment composition(Saffower Yellower Injection) is introduced and its response characteristics, factors and potential causes of ADR are revealed, which provides the reference for safe, rational clinical management of drugs.Also it reminds that clinicians should master the characteristics of adverse reactions of traditional Chinese medicine pigment and grasp the ADR potential causes and control measures, in order to reach the goal of rational drug use.

Objective: To investigate neglect among preschool children in two-child families in southwest Shandong Province, and to provide reference is for improving nursing parenting quality of two-child families. Methods: A questionnaire survey was conducted among 2 646 parents of two-child families and 2 074 parents of one-child families from 16 kindergartens in southwest Shandong Province. Results: The total neglect rate of two-child family preschool children in southwest Shandong Province was 27.37%, and the degree score of neglect was(40.15±5.51). The physical neglect rate(10.39%), emotional neglect rate(40.15±5.51), total neglect (38.15±4.88) and emotional neglect (46.12±6.91) of boys were higher than those of girls, and the difference was statistically significant(χ2/t=4.57, 6.65, 4.58, 4.72, P<0.05); No significant frequencies were found in total neglect rate, total neglect, neglect rate and neglect at all levels among all age groups(P>0.05); Among preschool children with siblings aged 7-<13, ≥13, total neglect rate(30.44%, 32.77%), emotional neglect rate(10.20%,12.00%), total neglect degree (44.71±5.98, 45.33±5.20) and emotional neglect degree (45.95±7.12, 48.86±4.97) of preschool children in two-child families have higher than those in onechild families, and the differences were of statistical significance(χ2/t=31.10, 4.55, 27.92, 24.13, 19.83, P<0.05); the total neglect rate(27.37%), emotional neglect rate(23.47%), emotional neglect (43.68±6.83) of twochild families and the total neglect (40.15±5.51) were higher than those of one-child families, and the differences were of statistical significance(χ2/t=4.98, 4.96, 3.76, 8.53, P<0.05). The age of siblings(OR=0.58), the education level of mothers(OR=0.64), and the main executor of family education (OR=1.54) were main factors to influence the child neglect of preschool children in two-child families(P<0.05). Conclusion Neglect of preschool children in two-child families is higher than that in one-child families in southwest Shandong, especially among those preschool boys and preschool children whose siblings were of school age.

OBJECTIVETo explore the phenotype, genotype and molecular mechanism for two pedigrees affected with hereditary antithrombin (AT) deficiency.

METHODSClinical diagnosis was validated by assaying of coagulation parameters including prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen, antithrombin activity (AT:A) and specific antigen (AT:Ag), protein C activity, as well as protein S activity. To detect potential mutations in the probands, all exons, exon-intron boundaries and the 3', 5' untranslated regions were amplified by PCR and subjected to direct sequencing. Suspected mutation was confirmed by reverse sequencing and silver staining. The effect of mutations on the AT protein was analyzed with bioinformatics software.

RESULTSThe AT:Ag of pedigree 1 was normal, but its AT:A has reduced to 30%. A heterozygous c.235C>T mutation in exon 2 causing p.Arg47Cys, in addition with two single nucleotide polymorphisms (c.981G>A, c.1011G>A) in exon 5 were identified in the patient. His four children, except for the elder daughter, were heterozygous for the mutations. The plasma levels of AT:A and AT:Ag in proband 2 have decreased to 39% and 103 mg/L, respectively. A heterozygous deletion (g.5890-5892delCTT) leading to loss of p.Phe121 was also detected in his father. Bioinformatic analysis suggested that the missense mutation Arg47Cys can affect the functions of AT protein. Meanwhile, lacking of Phe121 will result in loss of hydrogen bonds with Ala124, Lys125 and the cation π interactions with Lys125, Arg47, which may jepordize the stability of the protein.

CONCLUSIONThe proband 1 had type II AT deficiency, while proband 2 had type I AT deficiency. The p.Arg47Cys and g.5890-5892delCTT mutations of the AT gene are significantly correlated with the levels of AT in the two probands, respectively.

Adult ; Aged, 80 and over ; Antithrombin III ; genetics ; metabolism ; Antithrombin III Deficiency ; enzymology ; genetics ; physiopathology ; Exons ; Female ; Genetic Testing ; Genotype ; Humans ; Male ; Mutation ; Partial Thromboplastin Time ; Pedigree ; Phenotype ; Protein C ; genetics ; metabolism ; Protein S ; genetics ; metabolism

OBJECTIVETo identify potential mutation underlying coagulation factor X (FX) deficiency in a consanguineous Chinese pedigree.

METHODSProthrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, FX activity (FX:C) and other coagulant parameters were determined with a one-stage clotting assay. The FX antigen (FX:Ag) was determined with an ELISA assay. All coding exons and exon-intron boundaries of the F10 gene were amplified with PCR and subjected to direct sequencing. Suspected mutation was confirmed by reverse sequencing and analyzed with CLC Genomics Workbench 7.5 software.

RESULTSThe PT and APTT in the proband were prolonged to 67.2 s and 102.9 s, respectively. Further study showed that her FX:C and FX:Ag were reduced by 1% and 8%, respectively. The PT of her father, mother, and little brother were slightly prolonged to 14.5 s, 14.4 s and 14.4 s, respectively. The FX:C and FX:Ag in her father, mother and little brother were all slightly reduced. Genetic analysis of the proband has revealed a homozygous G>A change at nucleotide 27881 in exon 8 of the F10 gene, which predicted a p.Val298Met substitution. The proband's father, mother, and little brother were all heterozygous for the p.Val298Met mutation. The proband has inherited the homozygous mutation from her parents by consanguineous marriage. Other family members were all normal. Bioinformatics analysis has indicated that this mutation may result in changes in the secondary structure of the FX protein.

CONCLUSIONA homozygous mutation g.27881G>A(p.Val298Met) of the F10 gene has been identified, which probably accounts for the low FX concentrations in this pedigree.

Adult ; Amino Acid Sequence ; Consanguinity ; Factor X ; genetics ; Factor X Deficiency ; genetics ; Female ; Homozygote ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Mutation, Missense ; Pedigree ; Prothrombin Time

OBJECTIVETo identify potential mutation underlying hereditary coagulation factor XII (FXII) deficiency in a pedigree and explore its molecular pathogenesis.

METHODSActivated partial thromboplastin time (APTT), FXII activity (FXII:C) and FXII antigen(FXII:Ag) and other coagulant parameters of the proband and 5 family members were measured. Potential mutations in the 14 exons and intron-exon boundaries of the FXII gene were screened with polymerase chain reaction (PCR) and direct DNA sequencing. Suspected mutations were confirmed with reverse sequencing. Corresponding PCR fragments from other family members were also sequenced.

RESULTSAPPT of the proband and his son were significantly prolonged to 121.5 s and 98.5 s, respectively. FXII:C and FXII:Ag of the proband and his son have reduced to 5%, 6.8% and 9%, 12.2%, respectively. Plasma plasminogen activity (PLG:A) in both individuals was slightly higher than the normal reference range. FXII:C of his second daughter and grandson were slightly reduced to 64% and 60%. FXII:C of the other family members were all in the normal range (72%-113%). A heterozygous missense mutation, g.8597G>A, was identified in exon 13 of the FXII gene in the proband, which resulted in an p.Asp538Asn substitution. For the promoter regions of the FXII gene, the genotype of the proband was 46TT. The same mutations and 46T/T were also found in the proband's son but not in other members of the family. The genotypes of the proband's spouse, eldest daughter and grandson were 46CT, and his second daughter was 46TT.

CONCLUSIONThe heterozygous mutation of g.8597G>A identified in exon 13 of FXII gene is a novel mutation. Heterozygous p.Asp538Asn mutation and 46TT in the FXII gene can cause hereditary FXII deficiency, which was probably responsible for the low FXII concentrations in this pedigree.

Adult ; Base Sequence ; Exons ; Factor XII ; genetics ; Factor XII Deficiency ; congenital ; genetics ; Female ; Genotype ; Heterozygote ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Pedigree ; Point Mutation ; Young Adult

OBJECTIVETo identify the genetic mutation underlying congenital hypofibrinogenamia in a Chinese pedigree.

METHODSStandard coagulation tests including the prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), plasminogen activity (PLG:A), D-Dimer (DD) and fibrin degradation products (FDP) were tested with fresh plasma using a STA-R analyzer. The activity of fibrinogen (Fg:C) and fibrinogen antigen (Fg:Ag) were measured respectively with the Clauss method and immunoturbidimetry. All exons and exon-intron boundaries of the fibrinogen Aα-, Bβ-, and γ-chain genes (FGA, FGB and FGG) were amplified by PCR followed by direct sequencing. Suspected mutation was confirmed by reverse sequencing and analyzed with a Swiss-PdbViewer.

RESULTSThe PT level in the proband was normal, while the APTT and TT were slightly prolonged. The functional and antigen fibrinogen levels were both significantly reduced (0.91 g/L and 0.95 g/L, respectively). Similar abnormalities were also found in her father, elder sister, son and niece. The coagulant parameters of her mother were all within the normal range. Genetic analysis has reveled a heterozygous A>C change at nucleotide 5864 in exon 7 of γ gene in the proband, predicting a novel Lys232Thr mutation. The proband's father, elder sister, son and niece were all carriers of the same mutation. Protein model analysis indicated that the Lys232Thr mutation did not disrupt the native network of hydrogen bonds, but has changed the mutual electrostatic forces, resulting in increased instability of the protein.

CONCLUSIONThe heterozygous Lys232Thr mutation identified in the FGG gene probably underlies the hypofibrinogenemia in this pedigree.

Adult ; Afibrinogenemia ; congenital ; genetics ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; China ; Female ; Fibrinogen ; genetics ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Pedigree ; Peptide Fragments ; genetics ; Young Adult

OBJECTIVETo identify potential mutations in a family affected with inherited factor Ⅶ (FⅦ) deficiency.

METHODSProthrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, FⅦ activity (FⅦ:C) and other coagulant parameters of the proband and 15 family members were measured. Potential mutations were screened in the pedigree by polymerase chain reaction and direct DNA sequencing.

RESULTSThe PT of the proband and his younger brother was significantly prolonged to 39.0 s and 30.1 s, respectively. FⅦ:C of the proband and his younger brother was obviously reduced to 2% and 3%, respectively. FⅦ:C of his grandmother, maternal grandmother, aunt, father, mother, maternal uncle and maternal aunt was all below the normal range (80%-108%), which measured 68%, 54%, 71%, 73%, 62%, 72% and 59%, respectively. The other coagulant parameters were in the normal range. Two heterozygous mutations, g.11349G>A and g.11482T>G, both reside in exon 8 of the F7 gene, have resulted in p.Arg304Gln and p.His348Gln substitutions, were identified in the proband. The same mutations were also found in the proband's younger brother. Four maternal members in this family (grandmother, mother, maternal uncle and maternal aunt of the proband) were heterozygous for the p.Arg304Gln mutation, while three paternal members (grandmother, aunt and father of the proband) were heterozygous for the p.His348Gln mutation.

CONCLUSIONThe proband had inherited two independent mutations of the F7 gene including g.11349G>A and g.11482T>G from his mother and father, respectively. The compound heterozygous mutation probably explains the low FⅦ concentrations in this pedigree.

Adult ; Base Sequence ; Blood Coagulation Tests ; Factor VII ; genetics ; metabolism ; Factor VII Deficiency ; blood ; genetics ; Female ; Genetic Testing ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Pedigree ; Young Adult

Factor VII ; Factor VII Deficiency ; Genotype ; Humans ; Pedigree