This study used pharmacology combined with metabolomics to explore the effect of Amygdalus mongolica total extract on bleomycin induced pulmonary fibrosis in rats. The rat model of pulmonary fibrosis was established by intratracheal injection of bleomycin and treated with the total extract of Amygdalus mongolica. The pathological changes of lung tissue were evaluated by hematoxylin and eosin (HE) and Masson staining, the contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in lung tissue were detected, and transforming growth factor β1 (TGF-β1), Smad family member 3 (Smad3), α-smooth muscle actin (α-SMA) pathway index expression in lung tissue was detected by fluorescence quantitative PCR. UPLC-Q-TOF/MS was used to study serum metabolomics to explore the changing patterns of biomarkers and the metabolic pathways affected by them. The results showed that compared with the model group, the medium (1.5 g·kg^-1) and high (3.0 g·kg^-1) doses of Amygdalus mongolica total extract could significantly reduce the lung index, significantly increase the activity of SOD in serum and lung tissue, reduce the degree of alveolar inflammation and pulmonary fibrosis, and reduce MDA in serum and lung tissue, and significantly reduce TGF-β1, Smad3, α-SMA mRNA expression in lung tissue. Serum metabolomics profile analysis identified 25 significantly different metabolites, the Amygdalus mongolica total extract can participate in linoleic acid metabolism, glycerophospholipid metabolism and alpha-linolenic acid metabolism by reducing five key biomarkers: lysoPE(0∶0/22∶5(4Z,7Z,10Z,13Z,16Z)), lysoPC(20∶0/0∶0), PC(20∶5(5Z,8Z,11Z,14Z,17Z)/15∶0), 12,13-dihydroxy-9-octadecenoic acid (12,13-DHOME), 9,10-dihydroxy-12-octadecenoic acid (9,10-DHOME) to affect pulmonary fibrosis. This study preliminarily revealed the action mechanism of Amygdalus mongolica total extract against pulmonary fibrosis in rats, and provided a reference basis for the clinical application of Amygdalus mongolica. The animal experiments were approved by the Medical Ethics Committee of Baotou Medical College (No.20170315).

Carboxyl CoA ligases(CCLs) is an important branch of adenylate synthetase gene family, which mainly has two-step catalytic reactions. Firstly, in the presence of adenosine triphosphate, it can catalyze the pyrophosphorylation of carboxylateswith diffe-rent structures to form corresponding acyl adenosine monophosphate intermediates. Secondly, adenosine monophosphate was replaced by free electrons in the mercaptan group of enzyme A or other acyl receptors by nucleophilic attack to form thioesters. In this study, on the basis of the transcriptome database of Arnebia euchroma, two genes were selected, named AeCCL5(XP_019237476.1) and AeCCL7(XP_019237476.1). Bioinformatics analysis showed that their relative molecular weights were 60.569 kDa and 60.928 kDa, theoretical PI were 8.59 and 8.92, respectively. They both have transmembrane domains but without signal peptide. By multiple sequence alignment and phylogenetic tree analysis, we found that the similarity between AeCCLs and other plant homologous proteins was not high, and the substrate binding sites of AeCCLs were not highly conserved. The reasons might be that the sequence and structure need to adapt to the changes of new substrates in the process of evolution. In this study, the full-length of AeCCL5 and AecCCL7 were cloned into the expression vector pCDFDuet-1. The proteins of AeCCL5 and AeCCL7 with His-tag were expressed in Escherichia coli. The proteins of AeCCL5 and AeCCL7 were purified by nickel column. In vitro enzymatic reactions proved that both AeCCL5 and AeCCL7 can participate in the upstream phenylpropane pathway of shikonin biosynthesisby catalyzing 4-coumaric acid to produce 4-coumarin-CoA, and then to synthesis p-hydroxybenzoic acid, which is an important precursor of shikonin biosynthesis in A. euchroma.
Boraginaceae/genetics* ; Cloning, Molecular ; Coenzyme A ; Coenzyme A Ligases/genetics* ; Ligases ; Phylogeny

This paper summarized the effects of ecological planting on secondary metabolism firstly and pointed out that ecological planting can increase the content of secondary metabolites in plants, especially the content of defensive secondary metabolites. The possible mechanism was analyzed subsequently. Then, we reviewed the induction and utilization of secondary metabolism in the ecological planting of Chinese materia medica from the perspectives of biological control of pests and diseases, promotion of beneficial microorganism accumulation, optimization of mixed planting, regulation of no-tillage and straw cover. In this article, we pointed out that paying close attention to secondary metabolism is the most important feature of ecological planting of Chinese materia medica. Ecological planting can promote the accumulation of secondary metabolites of Chinese materia medica which means can improve the quality of Chinese materia medica, beneficial to the prevention and control of diseases, insects and weeds. Furthermore, lacking of systemic researches,the extensive verifications and systematic in-depth researches on the ecological planting of Chinese materia medica should be carry out urgently.
Drugs, Chinese Herbal ; Materia Medica ; Medicine, Chinese Traditional ; Plants, Medicinal ; Secondary Metabolism

Objective To explore factors influencing the incidence of carotid atherosclerosis in different genders so as to provide reference for the specific prevention of the disease. Methods A nested case-control study was conducted to analyze factors influencing the incidence of carotid atherosclerosis in Jinchang cohort population who were randomly selected through stratified sampling by age and followed up. A risk prediction model was established and the goodness of fit was evaluated by the area under the receiver operator characteristic curve (ROC). Results The standardized incidence of carotid atherosclerosis in this follow-up population was 12.32%, and the incidence rate of males (13.65%) was greater than that of females (11.29%). The difference was statistically significant ( 2=4.267, P<0.001). Age, education, elevated systolic blood pressure, and elevated low-density lipoprotein cholesterol were common risk factors for carotid atherosclerosis in both men and women. Elevated fasting plasma glucose (OR=2.556, 95% CI: 1.618-4.038) and elevated triglyceride (OR=1.535, 95% CI: 1.058-2.227) were only associated with men. Abdominal obesity (OR=1.414, 95% CI: 1.013-1.974) was only associated with women. The area under ROC of male and female prediction models was 0.835 (95% CI: 0.815-0.856) and 0.809 (95% CI: 0.788-0.831), respectively. The sensitivity was 78.0% and 78.9%, the specificity was 78.8% and 73.1%, and the diagnostic coincidence rate was 91.3% and 82.4%, respectively. Conclusions There are different risk factors for carotid atherosclerosis in males and females, and targeted prevention and control measures should be taken according to gender. The risk prediction model established by Logistic regression had certain guiding value.

Objective·To evaluate the impact of one-child on body mass index (BMI), and percentage of body fat in primary school students. Methods·All the sample was recruited from 5 elementary schools in Gaohang Town, Shanghai, China. The baseline data of height, body weight, and percentage of body fat was obtained in 2013, and re-measured in 2014 and 2015, respectively. Birth weight, breast feeding, diet and time for physical activities of each children and the highest education level, height, and body weight of their parents were also collected by a self-completed questionnaire. Logistic regression and Mix model was used to analyze the relationship between one-child and BMI, BMI-Z score, and percentage of body fat. Results·A total number of 2515 (1323 boys and 1192 girls) primary school students completed the study and entered the analysis. The percent of one child in this study population was 72.0％ (1812/2515). BMI-Z score, time for physical activities, parental education level, and maternal BMI were higher, while the rate of breast feeding was lower in one-child group compared to non-one-child group. The results of Logistic regression showed boys (compared to girls), macrosomia ( ≥4000g vs normal birth weight), overweight father and mother (compared to normal BMI) were risk factors for overweight. The factor of one-child didn't increase the risk of overweight (OR=1.119, 95％ CI 0.911-1.374). After potential con-founders adjusted, the annual increase of BMI (β=0.028, 95％ CI -0.045-0.100), BMI-Z score (β=0.002, 95％CI -0.034-0.037) and percentage of body fat (β=0.013, 95％ CI -0.181-0.207) showed no obvious difference between the two groups. Conclusion·One-child factor showed no obvious relationship with BMI, BMI-Z score and percentage of body fat in primary school students.

OBJECTIVETo investigate the association between clinical outcome and gene mutations in children with Fanconi anemia (FA).

METHODSA retrospective analysis was performed for the clinical data of six children with the same severity of FA and receiving the same treatment. At first, single cell gel electrophoresis and chromosome breakage induced by mitomycin C were performed for diagnosis. Then the gene detection kit for congenital bone marrow failure diseases or complementation test was used for genotyping of FA. Finally the association between the clinical outcome at 3, 6, 9, or 12 months after treatment and gene mutation was analyzed.

RESULTSOf all the six FA children, five had FANCA type disease, and one had FANCM type disease; four children carried two or more FA gene mutations. Among the children with the same severity of FA, those with more FA mutations had a younger age of onset and poorer response to medication, and tended to progress to a severe type.

CONCLUSIONSChildren carrying more than two FA mutations have a poor clinical outcome, and hematopoietic stem cell transplantation should be performed as soon as possible.

Child ; Child, Preschool ; Fanconi Anemia ; genetics ; Female ; Humans ; Male ; Mutation ; Retrospective Studies

To evaluate the effects of glutamine-supplemented parenteral nutrition (PN) and probiotics in adult autoimmune enteropathy (AIE) patients. Four adult AIE patients were identified from April 2006 to January 2012. Clinical and nutritional data were obtained from the patients' medical records. Glutamine-supplemented PN started immediately when the AIE diagnosis was confirmed. The total PN duration was 351 days. According to the PN prescription, the average caloric intake ranged from 20 to 25 kcal/kg/day, and the protein intake ranged from 1.2 to 1.5 g/kg/day. Alanyl-glutamine (20 g/day) was administered to AIE patients for 4 weeks followed by a 2-week break, and this treatment schedule was repeated when PN lasted for more than 6 weeks. Body weight gain and an increased serum albumin level were achieved after PN, and defecation frequency and quality also improved. Each patient received oral supplements, 250 mL of Ensure and two probiotics capsules (each capsule containing 0.5x10(8) colonies) three times a day when enteral nutrition started. Three AIE patients were successfully weaned off PN, and one patient died of pneumonia. Glutamine-supplemented PN and probiotics show promise in managing patients with AIE and related malnutrition.
Adult ; Bifidobacterium ; Enterococcus faecalis ; Female ; Glutamine/*administration & dosage ; Humans ; Lactobacillus acidophilus ; Length of Stay ; Male ; Malnutrition/therapy ; Parenteral Nutrition/*methods ; Polyendocrinopathies, Autoimmune/*therapy ; Probiotics/*administration & dosage ; Young Adult

BACKGROUNDBacteremia remains a significant cause of morbidity and mortality after kidney transplantation. This study was conducted to investigate whether the polymorphisms of tumor necrosis factor (TNF)-β, interleukin (IL)-1β, and IL-1 receptor antagonist (IL-1ra) gene predicted the susceptibility to bacteremia within the first 6 months after kidney transplantation.

METHODSSubjects comprised 82 infected kidney transplant recipients and 60 non-infected kidney transplant recipients. Bacteremia was diagnosed in 16 of the 82 infected recipients. Genomic DNA from these 142 kidney transplant recipients was extracted from peripheral blood leukocytes. Regions containing the NcoI polymorphic site at position +252 of TNF-β gene and the AvaI polymorphic site at position -511 of IL-1β gene were amplified by polymerase chain reaction (PCR) and subsequently digested with NcoI and AvaI restriction enzymes, respectively. The polymorphic regions within intron 2 of IL-1ra gene containing variable numbers of a tandem repeat (VNTR) of 86 base pairs were amplified by PCR.

RESULTSGenotypic and allelic frequencies were similar between infected recipients and non-infected ones. Individual locus analysis showed that recipient TNF-β and IL-1ra gene polymorphisms were not associated with the presence of bacteremia (P = 0.684 and P = 0.567, respectively). However, genotype analysis revealed that recipient IL-1β-511CC genotype was strongly associated with susceptibility to develop bacteremia (P = 0.003). Recipient IL-1β-511CC genotype (odds ratio 5.242, 95% confidence intervals 1.645-16.706, P = 0.005) independently predicted the risk for bacteremia within the first 6 months after kidney transplantation.

CONCLUSIONSThese findings indicate a critical role of IL-1β gene polymorphisms in susceptibility to bacteremia after kidney transplantation, which may be useful to screen for patients at higher risk for post-transplant bacteremias. Thus, the identified individuals can benefit from preventive treatment and a less potent immunosuppressive regimen.

Adolescent ; Adult ; Bacteremia ; genetics ; Female ; Genotype ; Humans ; Interleukin 1 Receptor Antagonist Protein ; genetics ; Interleukin-1 ; genetics ; Kidney Transplantation ; Lymphotoxin-alpha ; genetics ; Male ; Middle Aged ; Multigene Family ; genetics ; Polymorphism, Genetic ; genetics ; Young Adult

OBJECTIVETo study the clinical and laboratory characteristics of cases with warts, hypogammaglobulinemia, infections and myelokathexis (WHIM) syndrome.

METHODAn 11-year-old boy was diagnosed as WHIM syndrome and CXCR4 gene mutation analysis was performed.

RESULTSince 3 years of age, the patient had recurrent fever and persistent cough. Since 6 years of age, he had warts on his fingers, the warts increased gradually. His complete blood count showed: white blood cell (WBC) 0.65×10(9)/L, neutrophil 0.15×10(9)/L, hemoglobin 116 g/L, platelet 200×10(9)/L, reticulocyte 0.62%. Results of serum biochemical tests: total protein (TP) 72.2 g/L (reference value 60 - 80 g/L), albumin 20.4 g/L (reference value 20 - 35 g/L), gammaglobulin 20.4 g/L (reference value 20 - 35 g/L). IgG 5.56 g/L (reference value 7.51 - 15.6 g/L), IgA 0.48 g/L (reference value 0.82 - 4.53 g/L), IgM 0.29 g/L (reference value 0.46 - 3.04 g/L). Peripheral blood lymphocyte subsets: CD3(+)T lymphocyte 43.6% (reference value 64.01% - 75.95%), CD19(+)B lymphocyte 1.00% (reference value 9.02% - 14.1%). Bone marrow smears showed that many of the neutrophils had a reactive appearance, with cytoplasmic vacuolation. Most neutrophils had hypersegmentation with four or five nuclear lobules. In some cells, the filaments connecting the nuclear lobes were long. CXCR4 mutation was detected.

CONCLUSIONWHIM syndrome is a rare immunodeficiency disorder with an autosomal-dominant pattern of inheritance. The disease is less progressive, and may accompany the patients' whole life.

Agranulocytosis ; genetics ; pathology ; Amino Acid Sequence ; Child ; Humans ; Immunoglobulins ; blood ; Immunohistochemistry ; Immunologic Deficiency Syndromes ; genetics ; pathology ; Leukocyte Count ; Male ; Mutation ; Receptors, CXCR4 ; genetics ; Warts ; genetics ; pathology

BACKGROUNDThe Red Cross of China and Ministry of Health jointly started a pilot program of organ donation after cardiac death to overcome the shortage of available organs since 2010. The purpose of this qualitative study were to compare the consent rate of organ donation between young donor families and adult donor families; to explore and determine factors associated with differences in willingness to donate organs between them. Research objective was to provide a rationale for further preparation of professionals involved in this sensitive work.

METHODSBetween March 2010 and June 2012, 24 young deceased patients including donors and non-donors and 96 potential adult donors were collected, and consent rates of young donors' families and adult donors' families were calculated. A χ(2) test analysis to compare the consent rates of the two groups was conducted. We studied through semistructured interviews 15 parents of young donors and 15 relatives of old donors who were interviewed for petition of consent. Data collection and analysis of the overall study were performed according to the grounded theory methodology. Factors that influenced the families' decisions were identified and classified. We found the differences in willingness to donate organs between the two groups.

RESULTSThe consent rate of young donor families was 66.67%, while the consent rate of adult donor families was 26.04%. Young donor families easily consented to organ donation than adult donor families (P < 0.005). The donors' families had been affected by various factors throughout the process of deciding to give consent for donation. The findings led to the formulation of an empirically based model of interlinking categories that influence families' decision-making process in organ donation. These factors are grouped into five main categories: (1) personal factors, (2) conditions of organ request, (3) interpersonal factors, (4) ethical factors, and (5) traditional views. The funeral tradition influenced the young donor parents' consent to donation, but had no relation with family decision of adult donors. And the family members of young donors are relatively less, who are more likely to reach a consensus.

CONCLUSIONSYoung donor families influenced by traditional funeral beliefs are easier to consent to organ donation than adult donor families. Family members of young donors are relatively less who are more likely to reach a consensus. Acceptance of the expanded criteria donors may improve the organ donation rates, especially those of the advanced age.

Adolescent ; Adult ; Age Factors ; Aged ; Cadaver ; China ; Family ; psychology ; Humans ; Middle Aged ; Tissue and Organ Procurement