OBJECTIVES: To compare the application value of the likelihood ratio (LR) method and identity by state (IBS) method in the identification involving half sibling relationships, and to provide a reference for the setting of relevant standards for identification of half sibling relationship. METHODS: (1) Based on the same genetic marker combinations, the reliability of computer simulation method was verified by comparing the distributions of cumulated identity by state score (CIBS) and combined full sibling index in actual cases with the distributions in simulated cases. (2) In different numbers of three genetic marker combinations, the simulation of full sibling, half sibling and unrelated individual pairs, each 1 million pairs, was obtained; the CIBS, as well as the corresponding types of cumulative LR parameters, were calculated. (3) The application value of LR method was compared with that of IBS method, by comparing the best system efficiency provided by LR method and IBS method when genetic markers in different amounts and of different types and accuracy were applied to distinguish the above three relational individual pairs. (4) According to the existing simulation data, the minimum number of genetic markers required to distinguish half siblings from the other two relationships using different types of genetic markers was estimated by curve fitting. RESULTS: (1) After the rank sum test, under the premise that the real relationship and the genetic marker combination tested were the same, there was no significant difference between the simulation method and the results obtained in the actual case. (2) In most cases, under the same conditions, the system effectiveness obtained by LR method was greater than that by IBS method. (3) According to the existing data, the number of genetic markers required for full-half siblings and half sibling identification could be obtained by curve fitting when the system effectiveness reached 0.95 or 0.99. CONCLUSIONS When distinguishing half sibling from full sibling pairs or unrelated pairs, it is recommended to give preference to the LR method, and estimate the required number of markers according to the identification types and the population data, to ensure the identification effect.
Humans ; Siblings ; Genetic Markers ; Computer Simulation ; Irritable Bowel Syndrome/genetics* ; Reproducibility of Results ; Genotype

The detection method of characteristic spectrum for reference samples was established by preparing 15 batches of the reference samples of Huagan Decoction, and the peak attribution and the similarity range in the characteristic spectrum were clarified. The ranges of paste-forming rate, content, and transfer rate of the index components including geniposide, paeonol, and paeoniflorin were analyzed. The key quality attribute of the reference samples of Huagan Decoction was defined. The results showed that the 15 batches of the reference samples of Huagan Decoction had good similarities in the characteristic spectrum, which were all higher than 0.9. According to the information of characteristic peak, there were 18 characteristic peaks in the whole prescription, including seven common characteristic peaks from green tangerine peel and dried tangerine peel, four characteristic peaks from tree peony root bark(three of them were common characteristic peaks from tree peony root bark and red peony root), five characteristic peaks from cape jasmine fruit, one characteristic peak from paniculate bolbostemma, and one characteristic peak from oriental waterplantain rhizome.The paste-forming rate of the 15 batches of reference samples was 14.73%-18.83%. The content of geniposide was 1.68%-2.87%, with the average transfer rate of 70.05%±11.13%. The content of paeonol was 0.10%-0.16%, with the average transfer rate of 9.38%±1.78%. The content of paeoniflorin was 1.94%-2.74%, with the average transfer rate of 36.69%±4.63%. This study analyzed the quality value transfer of the reference samples of Huagan Decoction by the evaluation mode of combining the characteristic spectrum, the paste-forming rate, and the content of index components. The findings of this study initially established a stable and feasible standard decoction evaluation method and provided references for the quality control and the subsequent development of relevant preparations of Huagan Decoction.
Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; Paeonia ; Prescriptions ; Quality Control

To investigate the effects of different habitat processing methods of Salviae Miltiorrhizae Radix et Rhizoma on acute myocardial ischemia induced by pituitrin in rats. In this experiment, the tail vein injection of pituitrin was used to induce acute myocardial ischemia in rats. Electrocardiograph(ECG) heart rate and ΔST changes were recorded, and the levels of creatine kinase isoenzyme(CK-MB), lactate dehydrogenase(LDH), superoxide dismutase(SOD) and malondialdehyde(MDA) in serum of rats were detected to comprehensively evaluate the effects of six processing methods of Salviae Miltiorrhizae Radix et Rhizoma on serum biochemical indexes of rats with acute myocardial injury. The ECG results showed that the Salviae Miltiorrhizae Radix et Rhizoma dried in a drying oven had a good effect on the improvement of heart rate and ΔST of electrocardiogram after ischemia, and all the other groups had some protective effects to different degrees. The results of biochemical indexes in serum of each group after ischemia showed that the activity of CK-MB decreased most significantly in Salviae Miltiorrhizae Radix et Rhizoma high-dose group with drying in a drying oven after sweating and losing weight in a drying oven, high-dose group with drying in the shade and low-dose group with drying in the shade. The activity of LDH decreased most significantly in Salviae Miltiorrhizae Radix et Rhizoma high-dose group with drying in the shade and low-dose group of drying in the shade. The activity of SOD increased most significantly in Salviae Miltiorrhizae Radix et Rhizoma low-dose group with drying in sun, low-dose group with drying in sun after sweating and losing weight in sun, and low-dose group with drying in a drying oven. The activity of MDA decreased most significantly in Salviae Miltiorrhizae Radix et Rhizoma low-dose group with drying in sun. The comprehensive scoring results showed that the highest score was obtained in Salviae Miltiorrhizae Radix et Rhizoma high-dose group with drying in the shade while the scores of other treatment groups were higher than that of the model group. It could be seen that the Salviae Miltiorrhizae Radix et Rhizoma dried in a drying oven had a good improvement effect on electrocardiograph indexes after acute myocardial injury, the Salviae Miltiorrhizae Radix et Rhizoma dried in the shade had a good improvement effect on serum myocardial enzymes after acute myocardial injury, and the other processing methods had a certain protective effect on myocardial injury. The six processing methods evaluated by pharmacodynamics showed that the Salviae Miltiorrhizae Radix et Rhizoma dried in the shade and dried in a drying oven had good efficacy.
Animals ; Drugs, Chinese Herbal ; Ecosystem ; Myocardial Ischemia ; Rats ; Rhizome ; Salvia miltiorrhiza

To investigate the effects of exogenous NaHS on myelin basic protein (MBP) and learning and memory of hippocampal neurons in mice with spinocerebellar ataxia type 3 (SCA3) and its therapeutic significance. Twelve male normal mice were randomly selected as normal control group (NC Group), and 48 SCA3 mice were randomly selected as SCA3 model group (M Group), low dose group (NL Group, 10 μmol/kg), medium dose group (NM Group, 50μmol/kg) and high dose group (NH Group, 100 μmol/kg), 12 rats in each group. The drug treated groups were injected with NaHS intraperitoneally once a day for 4 weeks. The changes of learning and memory ability of SCA3 mice before and after the intervention of different doses of NaHS were determined by Morris water maze, the content of hydrogen sulfide (HS) in hippocampus was measured by spectrophotometry, the expression of MBP was detected by immunohistochemistry, and the morphological changes of neuron myelin sheath were observed by electron microscope. Compared with the control group, the learning and memory ability of SCA3 mice was decreased significantly (P＜0.05), and the content of HS in hippocampus was decreased (P＜0.05). After different doses of exogenous NaHS treatment, the learning and memory ability was improved in different degrees (P＜0.05), and the contents of HS and MBP in hippocampus of SCA3 mice were also improved in different degrees (P＜0.05). Exogenous NaHS may increase the contents of HS and MBP in the hippocampus of SCA3 mice, which may have a protective effect on the neurons, and then improve the learning and memory ability of SCA3 mice, and provide a new idea for the treatment of SCA3.

【Objective】This study aimed to explore copy number variations（CNV）in fetuses with conotruncal heart defect （CTD）. 【Methods】 Fetuses with ascertained CTD were investigated for chromosomal aberrations including copy number variations with chromosomal microarray analysis（CMA）and QF-PCR. Based on clinical significance of CNV，Fetuses were divided into two subgroups：non- benign CNV group ［（pathogenic CNV and CNV of unknown significance（VOUS）］and benign CNV group. Data on fetal structural malformations，copy number variations，and pregnancy out? comes were collected and compared.【Results】Among 128 cases without chromosomal aneuploidies ，pathogenic CNV ， CNV of VOUS ，and benign CNV were identified in 5.5% ，4.7% ，and 3.9% ，respectively. Compared with cases in benign CNV group（n=115），fetuses in non- benign CNV（n=13）had a significantly higher rate of overall extra- cardiac anomalies（76.9% vs. 43.5%，P=0.037），structural extra-cardiac anomalies（61.5% vs. 24.2%，P=0.022），softer mark? er anomalies（61.5% vs. 20.9% ，P=0.004），and thymus anomalies（30.8% vs. 0.87% ，P=0.000），whereas，no significant difference in that of intra- cardiovascular anomalies was noted（53.9% vs. 53.9%，P=1.000）excepted for that of persistent left superior vena cava（46.2% vs. 13.9% ，P=0.010）. The incidence of natural death in non- benign group was higher than but not statistically different from that of benign group.【Conclusions】Pathogenic CNV contributed to the pathogenesis of CTD. The presence of associated extra-cardiac anomalies including thymus abnormalities correlated with a higher probability of non-benign CNV.

This paper compared and analyzed the relevant records of Chinese medicine pharmacy in the Han,Tang and Song dynasties,and summarized the changes of the dosage forms,preparation techniques and administration methods of Chinese medicine with the development of history.In this study,three classic medical works in the Han,Tang and Song dynasties,including Treatise on Febrile Diseases Caused by Cold,Valuable Prescriptions for Emergency and Formularies of the Bureau of People's Welfare Pharmacies,were taken as the research objects,and the development of the dosage forms,auxiliary materials,preparation technology and medication theory were summarized and explored by the ways of content analysis,comparative analysis and case analysis.The comparison showed that in the development process,the dosage forms gradually increased,but the liquid dosage forms gradually decreased,the solid dosage forms gradually increased.Not only the dosage forms varied in the number,types of excipients used more and more,but the level of preparation had been constantly improved while the methods of taking became more detailed.This evolution of dosage forms and pharmaceutical technologies in Chinese history is worth learning and thinking about it.Through exploring the traditional Chinese medicine(TCM) technologies and theories in the Han,Tang and Song dynasties,we can contribute to the inheritance of traditional preparations and it can provide the basis for the development of modern preparations with TCM characteristics.

OBJECTIVE: To evaluate the efficacy and safety of salvianolate in elderly patients with unstable angina pectoris (UAP). METHODS: A prospective double-blind randomized placebo-controlled multicenter trial in elderly patients with UAP from 13 third-grade class-A hospitals in China was performed. A total of 318 patients were randomly allocated in a 1:1 ratio to an experimental group (160 patients) and a control group (158 patients). The experimental group was treated with salvianolate for 14 days on the basis of conventional medicine, and the control group was given a placebo for 14 days with the same criteria. Follow-up was lasted 28 days in both groups. The primary endpoint was biweekly frequency of angina pectoris attacks. The secondary endpoints included biweekly dosage of nitroglycerin, the Seattle Angina Questionnaire, angina pectoris severity and duration, myocardial injury markers, high-sensitivity C-reactive protein (hs-CRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), as well as major adverse cardiovascular events (MACEs). Safety was assessed according to adverse events and serious adverse events. RESULTS: Baseline characteristics were similar between treatment groups. Compared with those in the control group, the frequency of biweekly angina attacks (2.92 vs . 4.08, P=0.025), the biweekly dosage of nitroglycerin, as well as the severity and duration of angina attacks (P<0.01) were reduced by salvianolate. The Seattle Angina Questionnaire score was also significantly improved in the experimental group than in the control group (P<0.05). No significant differences were observed between the two groups with respect to the incidence of MACEs. Salvianolate was well tolerated. CONCLUSIONS Salvianolate appear to have efficacy and well tolerated for elderly patients with UAP. [ClinicalTrials.gov identifier: NCT03037047].

Objective:To explore the effect of aerobic exercise on behavioral function in rats with cerebral small vessel disease and its mechanism. Methods:Eight-week-old male Sprague-Dawley rats were randomly divided into sham group (n = 16), model group (n = 16) and swimming group (n = 16). The model was developed with bilateral common carotid artery ligation. They were assessed with burrowing test after four weeks of swimming exercise. The levels of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) protein in hippocampus were detected with Western blotting. The development of dendrites and synaptic spines in hippocampal neurons was observed with Golgi staining. The expression of Ki67, doublecortin (DCX) and Neun in hippocampal dentate gyrus was detected with immunofluorescence. Results:Compared with the model group, the burrowing ability improved in the swimming group (P < 0.05), with increase of levels of BDNF and TrkB in hippocampus (P < 0.05), Ki67/DCX and Neun positive cells in hippocampal dentate gyrus (P < 0.05), and extension of dendrites and length of synaptic spine in hippocampal neurons (P < 0.05). Conclusion:Aerobic exercise may promote the proliferation and differentiation of hippocampal neurons through BDNF/TrkB signaling pathway, expression of Ki67/DCX and Neun and development of hippocampal neurons, to improve behavioral function in rats with cerebral small vessel disease.

Activated nuclear factor-κB (NF-κB) plays an important role in the development of cardiovascular disease (CVD) through its regulated genes and microRNAs (miRNAs). However, the gene regulation profile remains unclear. In this study, primary mouse vascular endothelial cells (pMVECs) were employed to detect CVD-related NF-κB-regulated genes and miRNAs. Genechip assay identified 77 NF-κB-regulated genes, including 45 upregulated and 32 downregulated genes, in tumor necrosis factor α (TNFα)-treated pMVECs. Ten of these genes were also found to be regulated by NF-κB in TNFα-treated HeLa cells. Quantitative real-time PCR (qRT-PCR) assay confirmed the up-regulation of Egr1, Tnf, and Btg2 by NF-κB in the TNFα-treated pMVECs. The functional annotation revealed that many NF-κB-regulated genes identified in pMVECs were clustered into classical NF-κB-involved biological processes. Genechip assay also identified 26 NF-κB-regulated miRNAs, of which 21 were upregulated and 5 downregulated, in the TNFα-treated pMVECs. Further analysis showed that nine of the identified genes are regulated by seven of these miRNAs. Finally, among the identified NF-κB-regulated genes and miRNAs, 5 genes and 12 miRNAs were associated with CVD by miRWalk and genetic association database analysis. Taken together, these findings show an intricate gene regulation network raised by NF-κB in TNFα-treated pMVECs. The network provides new insights for understanding the molecular mechanism underlying the progression of CVD.
Animals ; Cardiovascular Diseases/genetics* ; Cells, Cultured ; Endothelial Cells/drug effects* ; Gene Regulatory Networks ; Mice ; MicroRNAs/physiology* ; NF-kappa B/physiology* ; Tumor Necrosis Factor-alpha/pharmacology*

Objective:By observing the changes of hyperthermia on serum carbohydrate antigen 125(CA125),human epididymal protein 4(HE4),chitinase protein(YKL) and immune function index effects,to investigate its effect on cancerous ascites and its antitumor effect of cytoreductive surgery combined with intraperitoneal hyperthermic perfusion chemotherapy and in elderly patients with advanced ovarian cancer.Methods: A total of 72 elderly patients with advanced ovarian cancer were enrolled in the study.They were randomly divided into contrast treatment group and combined treatment group,36 cases in each group.The patients in contrast treatment group were treated with cytoreductive surgery combined with intraperitoneal hyperthermic perfusion chemotherapy.The combined treatment group was treated with partial radiofrequency hyperthermia on the basis of the treatment of the control group.The efficacy was evaluated after 2 courses.The changes of CA125,HE4 and YKL contents and T cell subsets were compared between the two groups before and after treatment,and the safety was evaluated.Results: There was no difference in the operation between the two groups.The total effective rate was 80.0% in combined treatment group,which was significantly better than 55.6% in contrast treatment group(χ2=5.175,P<0.01).The effective rate of ascites control was 80.6% in combined treatment group,which was significantly higher than that in contrast treatment group 52.4%(χ2=3.962,P<0.05).After treatment,the levels of CA125,HE4 and YKL in the two groups were significantly lower than those before treatment,and the decrease of the combined treatment group was more significant than contrast treatment group(P<0.05).After treatment,the levels of CD3+,CD4+,CD4+/CD8+in both groups were lower than those before treatment,CD8+was lower than that before treatment,and the improvement of the indexes in combined treatment group was more significant than contrast treatment group(P<0.05).There was no significant difference between the two groups in the adverse effects of bone marrow suppression,gastrointestinal reaction and liver and kidney dysfunction(P> 0.05).Conclusion: CRS combined with IPHC and hyperthermia can significantly improve the immunosuppression of ovarian cancer,reduce the level of CA125,HE4,YKL, improve clinical efficacy of elderly patients with advanced ovarian cancer.