Structural modifications were performed with natural product of oleanolic acid to search for novel anticancer drugs. Ten oleanolic acid derivatives were designed and obtained by the reaction of oxidation, acylation or hydrolyzation, etc. The cytotoxic activity of derivatives was evaluated against HeLa, HepG2 and BGC-823 cells in vitro by MTT assay, gefitinib and etoposide used as a positive control. The results showed that compound 5a was particularly active to inhibit HepG2 cells growth, and anti-tumor activity of compound 7 on HeLa cells was significantly stronger than oleanolic acid. They are worthy to be studied further.

OBJECTIVE:To established a method for determining matrine and oxymatrine in human plasma.METHODS:The plasma was extracted with chloroform-n-butyl alcohol(98∶2) after basification and purified with neutral alumina solid-phase extraction.Then it was eluted with a Lichrosorb-NH2 column and CH3CN-CH3CH2OH-H3PO4(80∶10∶8),detected at ? 220nm.RESULTS:The linear range was 1.25mg～40mg/L and the limit of detection was 0.1mg/L(S/N=2).The average recoveries of matrine and oxymatrine were 106.96% and 105.04%,respectively.RSDs of within-day and between-day were lower than 13% and 7% respectively.CONCLUSION:The present study provides a simple and reliable method for determining concentrations of matrine and oxymatrine in human plasma.

Objective To investigate the impacts of treating stratege for non-infarct related artery on clinical prognosis in elderly patients with acute myocardial infarction (AMI) after urgent percutaneous coronary intervention (PCI). Methods From Augst 2007 to Augst 2010,a total of 75 elderly AMI patients (aged 75 years and over) were treated by urgent PCI and confirmed as multivessel coronary disease in our hospital. Among them,30 patients received medicine combined with PCI once again (PCI group) and 45 patients received only medicine treatemt (medicine group).The major adverse cardiovascular events (MACE) and results ot coronary angiography after treatment for average one year were compared between the two groups. Results There were no significant differences in the rates of in stent restenosis[1 case(2.2 ％)vs.0 case],late loss of in-segment lumen [5 cases(11.1％)vs.3 cases(10.0％)],stent thrombosis[1 case(2.2％)vs.1 case(3.3％)] and larget vessel revascularization [2 cases (4.4 ％ ) vs.1 case ( 3.3 ％) ] between medicine group and PCI group (x2=0.00,0.00.2.03 and 0.00,all P＞0.05).The propertions of angina recurrence and second hospital admission for heart diseases were lower in PCI group than in medicine group [36 cases (80.0％)vs.14 cases(46.7％),18 cases(40.0％)vs.5 cases(16.7％),x2=9.00,4.61,P＜0.01and P＜0.05].However,no differences were found in the secondary heart failure,recurrent nonfatal myocardial infarction,severe arrhythmia,all- cause death and mortality rate of cardiovascular disease between the two groups (x2 =0.09,0.00,0.00,0.00 and 0.00,all P＞ 0.05). Conclusions Compared with single medicine therapy,the medicine combined with PCI for non- infarct-related artery may decrease the rates of angina recurrence and second hospital admission for heart diseases in elderly patients with AMI.

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with N-acetylglutamate synthase deficiency. METHODS: Trio whole exome sequencing (WES) was carried out for the pedigree. Pathogenicity of the identified variant was predicted based on the latest recommendation of the American College of Medical Genetics and Genomics (ACMG). Prenatal diagnosis was provided for subsequent pregnancy through Sanger sequencing. RESULTS: Trio WES showed that the proband has carried compound heterozygous c.68delG and c.796G>C variants of NAGS gene, for which the mother and father were respectively heterozygous carriers. Neither variant was reported previously. Based on the ACMG guidelines, the c.68delG variant was classified as "likely pathogenic" (PVS1+PM2), while the c.796G>C variant was classified as with "uncertain significance" (PM2+BP4). Sanger sequencing validated the above findings, and only detected the heterozygous c.796G>C variant in the amniotic fluid sample. The fetus was followed up till 6 month after birth with no obvious abnormality. CONCLUSION The compound heterozygous c.68delG and c.796G>C variants of the NAGS gene probably underlay the disorder in this pedigree, and the resulth asenabled genetic counseling and prenatal diagnosis for this pedigree.
Amino-Acid N-Acetyltransferase/genetics* ; China ; Female ; Genetic Testing ; Humans ; Male ; Mutation/genetics* ; Pedigree ; Pregnancy ; Prenatal Diagnosis ; Urea Cycle Disorders, Inborn/genetics* ; Whole Exome Sequencing

OBJECTIVE: To assess the value of single sperm sequencing in preimplantation genetic testing for monogenic disease (PGT-M). METHODS: A Chinese couple with two children whom had died of Spinal muscular atrophy (SMA) and attended the Jiangxi Provincial Maternal and Child Health Care Hospital in June 2020 was selected as the subject. Eleven single sperm samples were isolated by mechanical immobilization and subjected to whole genome amplification. Real-time PCR and Sanger sequencing were used to detect the SMN1 variants in the single sperm samples. Genomic DNA of the wife, her parents and the husband, as well as one single sperm sample harboring the SMN1 variant and two single sperm samples without the variant were used for the linkage analysis. Targeted capture and high-throughput sequencing were carried out to test 100 single nucleotide polymorphisms distributed within 2 Mb up- and downstream the variant site. The haplotypes linked with the SMN1 variants were determined by linkage analysis. Blastocyst embryos were harvested after fertilizing by intracytoplasmic sperm injection. Cells from the trophoblasts of each embryo were biopsied and subjected to whole genome amplification and targeted capture and high-throughput sequencing to determine their carrier status. Chromosomal aneuploidy of wild-type embryos was excluded. An euploid embryo of high quality was transferred. Amniotic fluid sample was taken at 18 weeks of gestation to confirm the status of the fetus. RESULTS: Genetic testing showed that the couple both had deletion of exons 7 ~ 8 of the SMN1 gene. The wife has inherited the deletion from her father, while the husband was de novo. The haplotypes of the husband were successfully constructed by single sperm sequencing. Preimplantation genetic testing has indicated that 5 embryos had harbored the heterozygous variant, 4 embryos were of the wild type, among which 3 were euploid. Prenatal diagnosis during the second trimester of pregnancy has confirmed that the fetus did not carry the deletion. CONCLUSION By single sperm sequencing and PGT-M, the birth of further affected child has been successfully avoided.
Humans ; Pregnancy ; Female ; Child ; Male ; Preimplantation Diagnosis ; East Asian People ; Semen ; Genetic Testing ; Muscular Atrophy, Spinal/genetics* ; Aneuploidy ; Blastocyst/pathology* ; High-Throughput Nucleotide Sequencing ; Spermatozoa

Objective To explore the predictive efficacy of XGboost model in predicting risk of relapse and re-admission within 90 d in patients with ischemic stroke,and provide basis for early screening and prevention of high-risk population with ischemic stroke.Methods The clinical data of 6070 primary ischemic stroke patients admitted to our hospital from January 2007 to July 2017 were retrospectively collected.XGboost model and multivariate Logistic regression model were utilized to screen out the influencing factors of relapse and re-admission within 90 d in patients with ischemic stroke.A predictive model was set up.Receiver operating characteristic (ROC) curve was drawn and compared.Sensitivity,specificity and Youden index were calculated and compared to evaluate the prediction performance of XGboost model.Results During the observation period,a total of 520 patients with relapsed ischemic stroke were observed within a period of 90 d,and the incidence density was 8.57％.Multivariate Logistic regression analysis showed that length of first hospital stay,hypertension,pulmonary infection,neutrophil percentage,red blood cell distribution width (variable coefficient),and alkaline phosphatase level were independent influencing factors for re-hospitalization within 90 d of ischemic stroke,(OR=1.016,P=0.000,95％CI:1.008-1.025;OR=4.598,P=0.000,95％CI:3.717-5.687;OR=1.452,P=0.025,95％CI:1.048-2.012;OR=1.013,P=0.006,95％CI:1.004-1.022;OR=1.161,P=0.000,95％CI:1.090-1.237;OR=1.003,P=0.023,95％CI:1.000-1.005).Analysis of importance of risk factors for re-admission of ischemic stroke using XGboost model showed that the top 6 factors were hypertension,red blood cell distribution width,direct bilirubin,length of hospital stay,pulmonary infection,and alkaline phosphatase,and the corresponding importance scores were 32,20,19,18,15 and 14,respectively.ROC curve analysis results indicated that the area under the ROC for re-admission for XGboost model was 0.792 (95％CI:0.717-0.762),which was improved by 5％ as compared with that for multivariate Logistic regression model (0.739 [95％CI:0.764-0.818]).The sensitivity was 89.30％ and the Youden index was 0.444 for XGboost model,which were significantly higher than those for multivariate Logistic regression model (77.3％,0.405).Conclusions XGboost model is superior to multivariate Logistic regression model in predicting recurrence and re-admission of first ischemic stroke patients within 90 d.This model is suitable for prediction and early diagnosis of re-admission of ischemic stroke,which is of great clinical value.

Objective: To summarize the best evidence of risk assessment of pressure injury among surgical patients. Methods: We searched JBI Library、Cochrane Library、NGC、SIGN、PubMed、CNKI, CBM, etc., to collect documents including guidelines, evidence summaries, best practice information sheets, systematic reviews and expert consensus. Three researchers independently reviewed studies and extracted data from the publications meeting inclusion criteria. Results: 8 publications were recruited, including 5 clinical guidelines and 3 evidence summaries. Finally,12 items of best evidence were summarized, as follows. Health care professionals should involve in assessing of patients who are at risk of developing pressure ulcers, including pain related to pressure ulcers, complaints and skin inspections. Use a valid/reliable risk assessment tool in conjunction with the identifcation of additional risk factors (e.g., perfusion and oxygenation, increased body temperature, and advanced age), along with clinical judgment. Consider additional risk factors specific to individuals undergoing surgery including: duration of time immobilized before surgery, length of surgery, increased hypotensive episodes during surgery, low core temperature during surgery; and reduced mobility on day one postoperatively. Assess for intrinsic/extrinsic risk factors. Undertake a reassessment if there is any significant change in the individual′s condition. Include a comprehensive skin assessment as part of every risk assessment to evaluate any alterations to intact skin. Undertake a comprehensive skin assessment that includes skin temperature, color, edema, change in tissue consistency in relation to surrounding tissue, skin moisture, and skin integrity. Inspect the skin under and around medical devices at least twice daily for the signs of pressure related injury on the surrounding tissue. Assess and document physical characteristics including: location, category/stage, size, tissue types, color, periwound condition, wound edges, sinus tracts, undermining, tunneling, exudate, and odor. Staff education should be a core component of any quality improvement project aimed to improve the accuracy of pressure injury classification and quality of documentation. Health professionals should receive education regarding the prevention, assessment and management of pressure injury. The use of multi-component strategies or a computerized clinical decision support can be considered in quality improvement initiatives for improving pressure injury classification and documentation. Conclusions Medical institutions should strengthen training of nursing staff, especially pressure ulcer assessment and standardization of nursing records. It is also needed to raise awareness of relevant risks. Nursing staff should perform risk assessment dynamically and professionally, in order to timely identify the occurrence of pressure injuries to and ensure patients′ safety. Since best evidence would be updated along with research project, researchers should selectively apply evidence based on clinical settings and hospital conditions.