Effective substances and mechanism of Yishen Guluo Mixture in treatment of chronic glomerulonephritis based on metabolomics and serum pharmacochemistry / 中国中药杂志

This study aimed to investigate the effective substances and mechanism of Yishen Guluo Mixture in the treatment of chronic glomerulonephritis(CGN) based on metabolomics and serum pharmacochemistry. The rat model of CGN was induced by cationic bovine serum albumin(C-BSA). After intragastric administration of Yishen Guluo Mixture, the biochemical indexes related to renal function(24-hour urinary protein, serum urea nitrogen, and creatinine) were determined, and the efficacy evaluations such as histopathological observation were carried out. The serum biomarkers of Yishen Guluo Mixture in the treatment of CGN were screened out by ultra-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry(UPLC-Q-TOF-MS) combined with multivariate statistical analysis, and the metabolic pathways were analyzed. According to the mass spectrum ion fragment information and metabolic pathway, the components absorbed into the blood(prototypes and metabolites) from Yishen Guluo Mixture were identified and analyzed by using PeakView 1.2 and MetabolitePilot 2.0.4. By integrating metabolomics and serum pharmacochemistry data, a mathematical model of correlation analysis between serum biomarkers and components absorbed into blood was constructed to screen out the potential effective substances of Yishen Guluo Mixture in the treatment of CGN. Yishen Guluo mixture significantly decreased the levels of 24-hour urinary protein, serum urea nitrogen, and creatinine in rats with CGN, and improved the pathological damage of the kidney tissue. Twenty serum biomarkers of Yishen Guluo Mixture in the treatment of CGN, such as arachidonic acid and lysophosphatidylcholine, were screened out, involving arachidonic acid metabolism, glycerol phosphatide metabolism, and other pathways. Based on the serum pharmacochemistry, 8 prototype components and 20 metabolites in the serum-containing Yishen Guluo Mixture were identified. According to the metabolomics and correlation analysis of serum pharmacochemistry, 12 compounds such as genistein absorbed into the blood from Yishen Guluo Mixture were selected as the potential effective substances for the treatment of CGN. Based on metabolomics and serum pharmacochemistry, the effective substances and mechanism of Yishen Guluo Mixture in the treatment of CGN are analyzed and explained in this study, which provides a new idea for the development of innovative traditional Chinese medicine for the treatment of CGN.

Metagenomic study on the composition and function of oral microorganisms in healthy adults / 口腔疾病防治

Objective@#Metagenomic sequencing was used to explore the species composition and internal functional metabolic pathway of saliva and supragingival plaque microbial communities in healthy adults to provide a theoretical reference for the biological prevention and treatment of oral diseases.@*Methods@#Saliva and supragingival plaque samples were collected from healthy adults, total DNA was extracted, and a metagenomic library was constructed. The qualified library was sequenced via metagenomics, and the sequencing data were analyzed using bioinformatics and statistics. @*Results @#The main bacterial phyla in healthy oral samples were Proteobacteria (32.51%), Bacteroidetes (30.81%), and Actinobacteria (16.23%), and the main bacterial species were Corynebacterium matruchotii (3.84%), Haemophilus parainfluenzae (2.91%), and Prevotella melaninogenica (2.76%). The alpha diversity of the supragingival plaque group was higher than that of the saliva group, and there was a significant difference in the composition of the microbial community between the two groups (P<0.05). At the species level, Prevotella melaninogenica, Fusobacterium periodonticum, and Prevotella intermedia were more abundant in saliva samples than in supragingival plaque samples, while Corynebacterium matruchotii, Propionibacterium acidifaciens, and Rothia dentocariosa were more abundant in supragingival plaque samples than in saliva samples (P<0.05). High-quality gene sets of saliva and supragingival plaque in healthy adults were constructed based on metagenomic sequencing. The results of KEGG pathway functional metabolic differences showed that starch and sucrose metabolism, leucine and isoleucine degradation, and arginine biosynthesis in salivary microorganisms were more abundant than in supragingival plaque, while glycolysis/gluconeogenesis and carbon metabolism in supragingival plaque were more abundant than in saliva.@* Conclusion@#There are significant differences in the species composition and functional gene metabolic pathways of saliva and supragingival plaque microecology in healthy adults. The sensitivity of dominant species in different microecological regions to the identification of oral diseases may be different. In the microbiological study of oral diseases, appropriate samples should be selected according to different diseases.

Effective substance and mechanism of Ziziphi Spinosae Semen extract in treatment of insomnia based on serum metabolomics and network pharmacology / 中国中药杂志

This study aims to study the effective substance and mechanism of Ziziphi Spinosae Semen extract in the treatment of insomnia based on serum metabolomics and network pharmacology. The rat insomnia model induced by p-chlorophenylalanine(PCPA) was established. After oral administration of Ziziphi Spinosae Semen extract, the general morphological observation, pentobarbital sodium-induced sleep test, and histopathological evaluation were carried out. The potential biomarkers of the extract in the treatment of insomnia were screened by ultra-high performance liquid chromatography-mass spectrometry(UHPLC-MS) combined with multivariate analysis, and the related metabolic pathways were further analyzed. The "component-target-pathway" network was constructed by ultra-high performance liquid chromatography coupled with quadrupole-Exactive mass spectrometry(UHPLC-Q-Exactive-MS/MS) combined with network pharmacology to explore the effective substances and mechanism of Ziziphi Spinosae Semen in the treatment of insomnia. The results of pentobarbital sodium-induced sleep test and histopathological evaluation(hematoxylin and eosin staining) showed that Ziziphi Spinosae Semen extract had good theraputic effect on insomnia. A total of 21 endogenous biomarkers of Ziziphi Spinosae Semen extract in the treatment of insomnia were screened out by serum metabolomics, and the metabolic pathways of phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, and nicotinate and nicotinamide metabolism were obtained. A total of 34 chemical constituents were identified by UHPLC-Q-Exactive-MS/MS, including 24 flavonoids, 2 triterpenoid saponins, 4 alkaloids, 2 triterpenoid acids, and 2 fatty acids. The network pharmacological analysis showed that Ziziphi Spinosae Semen mainly acted on target proteins such as dopamine D2 receptor(DRD2), 5-hydroxytryptamine receptor 1 A(HTR1 A), and alpha-2 A adrenergic receptor(ADRA2 A) in the treatment of insomnia. It was closely related to neuroactive ligand-receptor interaction, serotonergic synapse, and calcium signaling pathway. Magnoflorine, N-nornuciferine, caaverine, oleic acid, palmitic acid, coclaurine, betulinic acid, and ceanothic acid in Ziziphi Spinosae Semen may be potential effective compounds in the treatment of insomnia. This study revealed that Ziziphi Spinosae Semen extract treated insomnia through multiple metabolic pathways and the overall correction of metabolic disorder profile in a multi-component, multi-target, and multi-channel manner. Briefly, this study lays a foundation for further research on the mechanism of Ziziphi Spinosae Semen in treating insomnia and provides support for the development of innovative Chinese drugs for the treatment of insomnia.

Research progress on 3D printing in minimally invasive endodontics / 口腔疾病防治

@#Minimally invasive endodontics (MIE) can preserve dental tissue to a greater extent and improve the success rate of endodontics and has thus attracted increasing attention. 3D printing is a technology that is based on a digital model and uses powdered metal, plastic and other materials to construct objects by printing layer by layer. This article reviews the application of 3D printing technology in minimally invasive endodontics to provide a reference for the application of 3D printing technology in clinical minimally invasive endodontics in the future. In recent years, 3D printing technology has been widely used in various professional fields of stomatology, such as maxillofacial surgery, prosthodontics, and orthodontics. Using cone beam computed tomography (CBCT) and oral scanners to obtain accurate data on the internal and external structures of teeth combined with 3D printing to construct a tooth diagnostic model and pulp opening guide plate, we can accurately locate the position of the root canal and provide a new method for minimally invasive endodontics. At present, 3D printing technology is mainly used to guide the pulp opening pathway, assist in the minimally invasive treatment of malformed teeth and calcified root canals, and assist with apical surgery in the field of minimally invasive endodontics. However, its accuracy and clinical prognosis still need to be verified with a large number of clinical cases.

Study on blood enrichment mechanism of steamed notoginseng based on metabolomics method / 中国中药杂志

In this paper,ultra performance liquid chromatography coupled with time-of-flight mass spectrometry( UPLC-Q-TOFMS) technique was used to study the effects of steamed notoginseng on endogenous markers in plasma of rats with hemolytic anemia induced by N-acetyl phenyl hydrazine( APH). The aim was to find out the potential biomarkers and possible blood enriching mechanism of steamed notoginseng on hemolytic anemia rats. In the experiment,steamed notoginseng medicine pair( steamed notoginseng-ginseng)and compound medicines( Sanqi Yangxue Capsules) were used respectively to intervene in APH-induced hemolytic anemia model rats.Then blood routine indexes such as red blood cells( RBC),hemoglobin( Hb) and related organ indexes were determined. As compared with the blank group,the RBC and Hb levels in the model group were substantially decreased( P< 0. 01),while the liver and spleen organ indexes were increased( P< 0. 05). The results of blood routine and organ index demonstrated that the blood deficiency model was successfully established. Steamed notoginseng can significantly increase the RBC level of rats( P<0. 01),and the related indicators of each drug group had a trend of returning to normal levels,verifying the blood enriching effect of steamed notoginseng. The UPLC-Q-TOF-MS technique,principal component analysis( PCA) and partial least squares-discrimination analysis( PLS-DA) were used to analyze the metabolic profiles between the normal group and the model group. Twenty-six potential biomarkers for hemolytic anemia were screened in plasma. Nine metabolites such as retinol,L-valine,and arachidonic acid were down-regulated in the blood deficiency rats,and 17 metabolites such as protoporphyrin Ⅸ and niacinamide were up-regulated. The metabolic level of biomarkers could be changed to a normal state after rats were given with steamed notoginseng,drug pairs,and compound prescriptions. It can be speculated that steamed notoginseng may play a role of blood tonifying by improving biosynthesis of valine,leucine and isoleucine,as well as metabolic pathways such as retinol metabolism and arachidonic acid metabolism.

Acute toxicity mechanism of Panax notoginseng saponins in larvae zebrafish based on metabonomics / 中国中药杂志

Based on metabolomics,the metabolites of larvae zebrafish with overdose of Panax notoginseng saponins( PNS) were compared with those in normal group of larvae zebrafish to investigate the possible toxicity mechanism of overdose PNS in larvae zebrafish. An experimental animal model of long-term toxicity induced by PNS overdose was established by administering 1-6 dpf at low,medium and high doses of PNS,respectively. The ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry( UPLC-Q-TOF-MS) technique was combined with principal component analysis( PCA) and orthogonal partial least squares discriminant analysis( OPLS-DA) to screen and identify biomarkers associated with toxicity,and then the MetaboAnalyst database was used to analyze metabolism-related pathways. The results showed that the metabolites of each group could be distinguished distinctly,and they deviated more from the normal group in a time and dose dependent manner. Twenty-nine potential biomarkers related to toxicity( VIP>1,P<0. 05) were identified preliminarily,mainly involving six metabolic pathways. From the metabonomics point of view,the toxicity mechanism of overdose PNS may be related to the disorders of lipid metabolism,amino acid metabolism and energy metabolism.

The clinical analysis of haploidentical stem cell transplantation in myelodysplastic syndrome-associated acute myeloid leukemia / 中华血液学杂志

Objective@#To investigate the prognosis of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in the treatment of acute myeloid leukemia with myelodysplasia-related changes (AML-MRC).@*Method@#The data of 102 patients with high-risk AML in the first complete remission phase (CR1) who received haplo-HSCT from January 2009 to July 2015 in Peking University People's Hospital were retrospectively analyzed.@*Results@#These 102 cases included 17 AML-MRC cases (AML-MRC group) and 85 other types of AML cases (control group). There were 8 males and 9 females in the AML-MRC group, and the median age was 35 (17-61) years. There were 52 males and 33 females in other high-risk AML group, and the median age was 31 (11-60) years. No difference was observed between the two groups after haploidentical stem cell transplantation in the rates of cytomegalovirus, EBV (Epstein-Barr virus), blood flow infection rate and hematopoietic reconstitution (P>0.05). The overall 2-year survival rate after transplantation was 80.8% (95%CI 51.6%-93.4%) and 72.5% (95%CI 62.8%-80.1%) (P=0.650), the disease-free survival rate was 79.4% (95%CI 48.8%-92.9%) and 65.9% (95%CI 54.3%-75.2%) (P=0.573), cumulative recurrence rate was 13.0%(95%CI 1.9%-34.7%) and 13.3%(95%CI 7.0%-21.5%) (P=0.623), and non-relapse mortality was 6.7% (95%CI 0.3%-27.0%) and 20.0% (95%CI 12.0%-29.4%) (P=0.436).@*Conclusion@#The prognosis of haplo-HSCT in patients with AML-MRC in CR1 is similar to that of other types of high-risk AML patients. Haplo-HSCT is an ideal choice for patients with AML-MRC in CR1.

Effects of Polyene Phosphatidylcholine on Hepatic Injury of Tumor?bearing Nude Mice Induced by Oxaliplatin and 5?fluorouracil Chemotherapy / 中国医科大学学报

Objective To study the protective effect of polyene phosphatidylcholine on hepatic injury induced by oxaliplatin and 5?fluorouracil. Methods A subcutaneous tumor model was established by transplanting colocarcinoma HCT116 cells into 30 nude mice,which were random?ized into three groups. The polyene phosphatidylcholine group was injected with polyene phosphatidylcholine(85 mg · kg-1 · d-1)and 5?fluorouracil (20 mg·kg-1·d-1)for 7 days,and then injected with oxaliplatin(6 mg·kg-1·d-1)for 1 day. The hepatic injury group was injected with 5?fluoroura?cil(20 mg·kg-1·d-1)for 7 days and oxaliplatin(6 mg·kg-1·d-1)for 1 day. The tumor?bearing blank group was injected with normal saline. Hepat?ic injury was observed with ultrathin pathological sections. Liver homogenates were prepared to detect superoxide dismutase(SOD)and catalase (CAT)activity. Results In the hepatic injury group,pathological sections revealed dissolved cellular cytoplasm,mitochondrial membrane dam?age,cell membrane edema,and fuzzy,sinusoidal cell expansion . There were no obvious hepatic injuries observed in the polyene phosphatidylcho?line group. The expression of SOD and CAT were lower in the hepatic injury and polyene phosphatidylcholine groups compared to the tumor?bear?ing blank group(P<0.05). The expression of SOD and CAT were higher in the polyene phosphatidylcholine group compared to the hepatic injury group(P<0.05). Conclusion Polyene phosphatidylcholine has a protective effect on hepatic injury induced by oxaliplatin and 5?fluorouracil, which may be related to its effect on membrane repair and inhibition of oxidative stress.

Expression of CXCR7 in Acute Monocytic Leukemia and Its Effects on THP-1 Cell Functions / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To study the expression of stromal cell derived factor-1α (SDF-1α) receptor CXCR7 in acute monocytic leukemia (AML-M5), and its effects on proliferation, apoptosis, invasion of acute monocytic leukemia cell line THP-1.</p><p><b>METHODS</b>CXCR7 protein and mRNA expression levels in THP-1 cells and peripheral blood mononuclear cells (PBMNC) from the newly diagnosed AML-M5 patients and normal individuals were detected by flow cytometry, Western blot and RT-PCR respectively. CCK8, Annexin V/PI double staining and Transwell assay were used to observe the effects of CXCR7 on the proliferation, apoptosis, and invasion of THP-1 cells in vitro.</p><p><b>RESULTS</b>The expression of CXCR7 on immature cell surface of the newly diagnosed AML-M5 patients was significantly higher than that in the control group (P<0.05). CXCR7 was also highly expressed on THP-1 cells surface. The CXCR7 protein and mRNA levels in THP-1 cells and PBMNC of AML-M5 patients were significantly higher than those in the control group (P<0.05). The THP-1 cell proliferation activity was higher in SDF-1α-treated group, but this activity could be inhibited by CXCR7 antibody (P<0.01). CXCR7 antibody did not affect THP-1 cell apoptosis (P>0.05). CXCR7 antibody could inhibit SDF-1α -induced THP-1 cell invasiveness (P<0.01).</p><p><b>CONCLUSION</b>CXCR7 highly expresses in AML-M5 patients and THP-1 cells, and involves in cell proliferation and invasion. The blocking CXCR7 expression can reduce the risk of AML-M5 cell infiltration.</p>

Feasibility of assessing health state by detecting redox state of human body based on Chinese medicine constitution / 中国结合医学杂志

This article discussed the feasibility of assessing health state by detecting redox state of human body. Firstly, the balance of redox state is the basis of homeostasis, and the balance ability of redox can reflflect health state of human body. Secondly, the redox state of human body is a sensitive index of multiple risk factors of health such as age, external environment and psychological factors. It participates in the occurrence and development of multiple diseases involving metabolic diseases and nervous system diseases, and can serve as a cut-in point for treatment of these diseases. Detecting the redox state of high risk people is signifificantly important for early detection and treatment of disease. The blood plasma and urine could be selected to detect, which is convenient. It is pointed that the indexes not only involve oxidation product and antioxidant enzyme but also redox couple. Chinese medicine constitution reflflects the state of body itself and the ability of adapting to external environment, which is consistent with the connotation of health. It is found that there are nine basic types of constitution in Chinese population, which provides a theoretical basis of health preservation, preventive treatment of disease and personalized treatment. With the combination of redox state detection and the Chinese medicine constitution theory, the heath state can be systemically assessed by conducting large-scale epidemiological survey with classifified detection on redox state of human body.

Expressions of TNF-alpha, IL-6, CRP, and MCP-1 in phlegm-damp constitution population detected by multiplexed Luminex assay / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the expression changes of tumor necrosis factor-alpha (TNF-(alpha), interleukin-6 (IL-6), C-reactive protein (CRP), monocyte chemotactic protein 1 (MCP-1), and their correlation with obesity in 20 -50 years old population of phlegm-damp constitution (PDC) and of normal constitution (NC) using Luminex technique.</p><p><b>METHODS</b>Totally 101 population were recruited from Health Examination Center of Puren Hospital from April to December 2011. Based on body mass index (BMI), the subjects were assigned to four groups, i.e., the obesity of PDC group (Group OBT, BMI > or = 24 kg/m2, 30 cases), the non-obesity of PDC group (Group NOBT, BMI < 24 kg/m2, 25 cases), the obesity of non-PDC group (Group OBNT, BMI > or = 24 kg/m2, 28 cases), the NC group (Group P, BMI < 24 kg/m2, 18 cases). The BMI and body fat percent (FAT%) were compared among the 4 groups. Serum levels of TNF-alpha, IL-6, CRP, and MCP-1 were measured with Luminex technique.</p><p><b>RESULTS</b>BMI was significantly higher in Group OBT and Group OBNT than in Group NOBT and Group P (all P < 0.05). The FAT% was significantly higher in Group OBT and Group OBNT than in Group P (P < 0.01). The serum TNF-alpha level in Group OBT was higher than in Group P (P < 0.01). The serum CRP and MCP-1 levels were significantly higher in Group OBT, NOBT, and OBNT than in Group P (P < 0.05, P < 0.01). The score for PDC was positively correlated with TNF-alpha, IL-6, and MCP-1 levels (P < 0.05).</p><p><b>CONCLUSIONS</b>Abnormal higher levels of inflammatory factors exist in 20 -50 years old population of PDC. Chronic inflammation exists in population of PDC and obesity people.</p>

Protective effect of ademetionine 1, 4-butanedisulfonate on liver injury caused by chemotherapeutic agents / 中国实验血液学杂志

The aim of this study was to observe the protective effect of ademetionine 1, 4-butanedisulfonate on liver injury caused by chemotherapy in patients with leukemia. The clinical data of protective effect were analyzed retrospectively from January 2010 to April 2012. A total of 62 acute leukemia patients were divided into A group (27 cases) and B group (35 cases), the polyene phosphatidyl choline combined with ademetionine or combined with compound glycyrrhizin were given in A and B group, respectively. The changes of liver function were observed after 2 weeks, 5 patients in B group suffered from acute liver injury were treated by ademetionine as rescue therapy. Liver function was compared before and after treatment. The results showed that ALT and AST levels were significantly reduced in A group (P < 0.05), none of the patients (0/27) suffered from acute liver injury, but 14.29% (5/35) patients in B group suffered from acute liver injury, and liver function could be recovered by substitution treatment of ademetionine (the median time is 8 days, 5-14 days). It is concluded that the protective and therapeutic effect of ademetionine against liver injury caused by chemotherapy in patients with leukemia is better than that of compound glycyrrhizin.

Analysis of clinical characteristics and prognosis of 13 cases of acute erythroleukemia / 中国实验血液学杂志

The aim of this study was to investigate the clinical characteristics and prognosis of acute erythroleukemia (AEL, AML-M6). The clinical features and results of morphologic, immunophenotypic, cytogenetic and molecular biologic detections were retrospectively analyzed in 13 cases of AEL from 305 acute leukemia patients hospitalized between October 2007 and October 2012. The results showed that the expression of erythroid and non-erythroid cells increased at the same time. The myeloid antigens mainly expressed CD13/CD33/CD117/CD34, while the erythroid antigens expressed Gly and CD71. The karyotypic detection indicated that there were 1 case with normal karyotype, 3 cases with simple karyotypic abnormality and 2 cases with complex karyotypic abnormality, the other cases were not detected. The molecular biological detection found that the poor prognosis gene existed in 5 cases [38.5% (5/13)], including 3 cases with MLL-MLL fusion gene, 1 case with MLL mutation, and 1 cases with NRAS gene mutation, the abnormal genes were not detected in remainder 8 cases. After chemotherapy with decitabine, the complete remission (CR) rate achieved 53.5% (7/13), partial remission (DR) rate achieved 15.4% (2/13). Finally, 8 patients received allo-HSCT, the median overall survival (OS) was 20.7 months, 3 year survival rate was 79%, 3 year disease-free survival rate was 78%. It is concluded that the acute erythroleukemia is a rare subtype of AML, which is transformed from MDS and has harmful genes and poor prognosis. Allo-HSCT and treatment with decitabine may enhance the survival rate of AEL.

Polymorphism of KIR gene family in Korean ethnic group of Jilin area / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the polymorphism of natural killer cell immunoglobulin-like receptor (KIR)gene and the characteristics of its genotypes and haplotypes in Korean ethnic group of Jilin area, and to compare with that of Han nationality.</p><p><b>METHODS</b>DNA samples randomly collected from 214 Han and 160 Korean populations were genotyped with PCR-SSP method, and KIR genotypes and haplotypes were assigned according to the standard model by Hsu et al.</p><p><b>RESULTS</b>All individuals contain KIR 3DL3, KIR 2DL4, KIR 3DL2 with the genotype frequency of 100%; the most common genotypes were 2DL1, 2DL3, 3DL1, 3DP1(*)003 and 2DP1; the genotypes with low frequency were 2DL2, 2DS2, 2DS3, 3DP1(*)001/002/004. Thirty-nine different KIR genotype and 16 haplotypes had been found in Korean and Han individuals. The most common KIR genotypes were AJ and AF with frequency of 18.1%, 19.4% and 31.8%, 19.6%, respectively. The most common KIR haplotype was haplotype 2 with frequency of 41.8% (n = 127) and 51.2% (n = 216) (P < 0.05), respectively.</p><p><b>CONCLUSION</b>KIR gene distribution in Jilin Korean ethnic group showed some common features of KIR gene polymorphisms in Chinese Han population, but also showed this nation's unique characteristics of KIR gene polymorphism.</p>

Recent development of targeted drug delivery system / 药学学报

Targeted drug delivery can significantly increase the concentration of the drug in treatment site, and decrease the dosage of drugs, cost of treatment and the drug's adverse effects on the body. So targeted drug delivery is the hotspot of recent studies. This paper reviews the development of targeted drug delivery research in recent years, including three areas: passive targeting, active targeting, and physical and chemical targeting.