Content determination and chemical pattern recognition analysis of Biantong capsules / 中国药房

OBJECTIVE To establish the method for simultaneous determination of 11 components as narirutin in Biantong capsules，to conduct chemical pattern recognition analysis and to screen differential markers affecting their quality . METHODS HPLC method was adopted . The separation was carried out on Venusil XBP C 18 column with mobile phase consisted of acetonitrile - 0.1％ phosphoric acid solution with gradient elution at flow rate of 1.0 mL/min. The sample size was 10 µL，and column temperature was set at 30 ℃. The detection wavelengths were set at 283，330，520，220 nm，respectively. Using verbascoside as an internal standard ，the contents were determined by quantitative analysis of mult -components by single marker （QAMS），and the results were compared with those of external standard method . Cluster analysis ，principle component analysis and orthogonal partial least squares -discriminant analysis were performed with SPSS 26.0 and SIMCA 14.1 software. The differential markers affecting the quality of Biantong capsules were screened using the variable importance in projection （VIP）value greater than 1 as the standard . RESULTS The contents of narirutin ，naringin，neohesperidin，echinacoside，tubuloside A ，isoacteoside，cyanidin-3-O-glucoside， cyanidin-3-O-rutoside，atractylolide Ⅲand atractylolide Ⅰ were 0.739-1.265，1.134-2.158，1.407-2.359，1.368-2.502，0.304-0.522， 0.257-0.521，0.423-0.727，0.375-0.733，0.130-0.283 and 0.062-0.166 mg/g，respectively. The relative average deviation of them from the external standard method was less than 2％. The results of cluster analysis showed that 15 batches of samples could be grouped into three categories ，S1-S7 as a category ，S8-S10 as a category ，and S 11-S15 as a category ，which was consistent with the classification results of principal component analysis . The results of orthogonal partial least squares -discriminant analysis showed that the VIP values of cyanidin -3-O-rutoside，atractylolide Ⅲ， naringin，neohesperidin，echinacoside and verbascoside were all greater than 1. CONCLUSIONS The method for simultaneous determination of 11 components in Biantongcapsules， including narirutin ， is successfully established . Combined with chemical pattern recognition analysis ，it can be used for the quality control of Biantong capsules . Six components such as cyanidin -3-O-rutoside may be the differential markers that affect the quality of Biantong capsules .

Effect of lipopolysaccharide-stimulated exosomes from human dental pulp stem cells combined with stromal cell-derived factor-1 on dental pulp regeneration / 中华口腔医学杂志

Objective: To investigate the effect of exosomes from mild-inflammation- stimulated human dental pulp stem cells (hDPSC) combined with stromal cell-derived factor-1 (SDF-1) on dental pulp regeneration in rats. Methods: Primary hDPSCs were isolated, cultured and then stimulated by using lipopolysaccharide (LPS). The exosomes from the hDPSCs with (L-EXO) or without (N-EXO) LPS were extracted by overspeed differential centrifugation and were identified by transmission electron microscopy and Western blotting. Forty SD rats, aged 6-8 weeks, were equally divided into S group (SDF-1 alone), L+S group (L-EXO combined with SDF-1), N+S group (N-EXO combined with SDF-1) and blank control group (no substance implanted into the root canal) by random number table method. Bilateral mandibular first molars were used as the experimental teeth to establish pulpless root canal models and different contents were implanted into the root canals according to the groups. All rats were over-anesthetized and sacrificed at the 30th day after content implantation. Bilateral mandibular tissues were taken for histological evaluation by means of HE, Masson and immunohistochemical stainings. Results: The HE staining showed new pulp-like tissue in the root canals of all three experimental groups. The amount of new tissues and the number of cells in the tissues were greatest in L+S group and least in S group. Masson staining showed that the mineralized tissue in L+S group was arranged longitudinally along the root canal wall and the collagen fibers were arranged in an orderly fashion, while those in N+S group showed an irregular and disordered distribution. Quantitative analysis of the area of neovascularization in each group showed that the density of vessels in the L+S group [(2.03±0.65)%] was significantly higher than that in the S group [(0.65±0.05)%] and the N+S group [(1.06±0.38)%] respectively (F=5.879, P<0.05). Immunohistochemical staining showed that the expression of CXC chemokine receptor 4 (CXCR4) was significantly lower in S and L+S groups than in N+S group, with a statistically significant difference (F=8.633, P<0.01). Conclusions: Exosomes secreted by hDPSCs combined with SDF-1 might increase the amount of new tissue in the root canal and the density of blood vessels in the tissue. L-EXO showed a stronger effect than N-EXO did. The combination of L-EXO with SDF-1 might result in more regular arrangement of mineralized tissue and collagen fibers in the regenerative tissues.

Quality Evaluation of Aurantii Fructus Based on Fingerprint Qualitative Analysis， Multi-component Quantitative Analysis and Chemometrics / 中国实验方剂学杂志

ObjectiveTo establish an integrated method of fingerprint qualitative， multi-component quantitative analysis and chemometrics， and to evaluate the quality attributes and differences of Aurantii Fructus from different production areas and origins. MethodAnalysis was performed on COSMOSIL 5C18-MS-Ⅱ column （4.6 mm×250 mm， 5 μm） with the mobile phase of acetonitrile-0.2% phosphoric acid solution for gradient elution （0-4 min， 19%A； 4-5 min， 19%-21%A； 5-18 min， 21%A； 18-19 min， 21%-28%A； 19-27 min， 28%A； 27-28 min， 28%-40%A； 28-36 min， 40%A； 36-37 min， 40%-50%A； 37-42 min， 50%-60%A； 42-46 min， 60%-95%A； 46-55 min， 95%-100%A）， the flow rate was 1 mL·min-1， the column temperature was 30 ℃， the detection wavelength was set at 320 nm， and the injection volume was 10 μL. High performance liquid chromatography （HPLC） fingerprints of Aurantii Fructus from different production areas and origins were established. Then， the quality of 26 batches of samples was evaluated by cluster analysis （CA）， principal component analysis （PCA） and orthogonal partial least squares discriminant analysis （OPLS-DA）. A method for the determination of 12 components was developed and verified， and a thermal map-based CA of Aurantii Fructus from different production areas and origins was carried out based on the content difference of samples. ResultThe fingerprint and determination methods were well verified. The similarity of HPLC fingerprint of 12 batches of Aurantii Fructus was 0.85-0.996， 20 common peaks were calibrated and 14 of them were assigned. The resolution and linear relationship of 12 components in quantitative analysis were good. The recovery rates were 99.2%-101.0% with RSD≤2.0%. The results of CA， PCA and OPLS-DA indicated that the differentiation of Aurantii Fructus in different production areas was great， and there were differences among different cultivars. ConclusionThe qualitative analysis of fingerprint and quantitative analysis of multiple indexes based on the same chromatographic analysis conditions are convenient， accurate and reliable， and combined with chemometrics， the identification and quality analysis of Aurantii Fructus from different production areas and origins can be realized， which can provide reference for quality control and evaluation of Aurantii Fructus.

Alternative Splicing Analysis of LACTB Gene and Expression Characteristics of Different Transcripts in Leukemia Cell Lines / 中国实验血液学杂志

OBJECTIVE@#To detect the expression of different transcripts of lactamase β（LACTB) gene in leukemic cell lines.@*METHODS@#NCBI website and DNAstar software were used to detect the Bioinformatics analysis of LACTB. The expression of different transcripts of LACTB gene in leukemic cell lines (THP-1, HL60, K562, U937, Jurkat and Raji) was detected by reverse transcription PCR (RT-PCR), DNA and clone sequencing; the expression of different transcripts of LACTB gene in leukemic cell lines was detected by Quantitative Real-time PCR.@*RESULTS@#There were a variety of splicing isomers in LACTB, and it could produce a variety of protein isomers with conserved N-terminal and different C-terminal, moreover, there were many splice isoforms of LACTB in leukemia cell lines, and there were different expression patterns in different cell lines, including XR1, V1, V2 and V3. The expression of total LACTB showed high in HL60 cells, while low in Raji cells, and the difference was statistically significant (P<0.05). The V1 was high expression in U937 cells but low in Raji cells, and the difference was statistically significant (P<0.05). V2 was high expression in HL60 cells but lowly in Raji cells, and the difference was statistically significant (P<0.05). The expression of V3 was low in THP-1 cells, which was significantly different as compared with that in normal bone marrow (P<0.05).@*CONCLUSION@#The reaserch found that there are many splice isomers of LACTB in leukemic cell lines, and there are different expression patterns in different cell lines.

Correlation between electroencephalogram reactivity and early neurological deficits in elderly acute cerebral infarction patients with cerebral microbleeds / 中华老年医学杂志

Objective:To analyze the relationship between electroencephalogram(EEG)reactivity and early neurological deficits in elderly acute cerebral infarction(ACI)patients with cerebral microbleeds.Methods:Clinical data were collected from 51 elderly ACI patients with cerebral microbleeds admitted to our hospital from July 2018 to April 2020, who formed the ACI with cerebral microbleeds group, and were retrospectively analyzed.The ACI group was composed of 47 patients with ACI treated at our hospital during the same period.All patients underwent EEG examination.EEG reactivity, sleep waves and other signs were monitored.Early neurological deficits were recorded 2 hours after thrombolysis in elderly ACI patients with cerebral microbleeds, assessed using the National Institutes of Health Stroke Scale(NIHSS), and divided into subgroups.Baseline data and EEG-related findings were compared between the two groups.The relationship between the severity of early neurological deficits and EEG reactivity was analyzed.Results:EEG reactivity and the positive detection rate for sleep waves were lower(33.33% or 17/51 vs.65.96% or 31/47, 27.45% or 14/51 vs.61.70% or 29/47, χ2=10.417 and 11.652, P=0.000 and 0.001)and early neurological deficits were more serious( Z=2.381, P=0.017)in the ACI with cerebral microbleeds group than in the ACI group.The proportions of cases with EEG reactivity and negative sleep waves were higher(91.18% or 31/34 vs.8.82% or 3/34, 86.49% or 32/37 vs.13.51% 5/37, χ2=17.771 and 13.147, both P=0.000)and the levels of vWF were lower(6.24±1.79 mg/L vs.13.48±2.23 mg/L, t=12.039, P=0.000)in elderly patients with moderate and severe ACI accompanied by cerebral microbleeds than in elderly patients with mild ACI accompanied by cerebral microbleeds.Logistic regression analysis showed that absence of EEG reactivity( OR=18.994, P=0.000), negative sleep waves( OR=11.520, P=0.001)and low levels of vWF( OR=0.283, P=0.001)were correlated with the degree of early neurological deficits in elderly ACI patients with cerebral microbleeds, with absence of EEG reactivity having the most significant impact.The results of receiver operating characteristic(ROC)curve showed that the area under the ROC curve(AUC)of absent EEG reactivity for predicting early moderate and severe neurological impairment was 0.803(95% CI: 0.650-0.956, P<0.001), indicating a certain degree of predictive value. Conclusions:Elderly ACI patients with cerebral microbleeds are associated with different degrees of functional neurological deficits in early stages, and the degree of neurological deficits may be related to absence of EEG reactivity.In the future, EEG reactivity may be considered as a risk assessment tool for the progression of neurological deficits in elderly ACI patients with cerebral microbleeds.

Correlation between serum matrix metalloproteinase-9 level and location and severity of bleeding in patients with cerebral microbleeds / 中华行为医学与脑科学杂志

Objective:To investigate the relationship between serum matrix metalloproteinase-9 (MMP-9) level and the location and severity of bleeding in patients with cerebral microbleeds(CMBs).Methods:A total of 60 CMBs patients admitted to the Department of Neurology of the First Affiliated Hospital of the Xinxiang Medical University from January 2019 to August 2020 were selected as subjects as the CMBs group, and 60 healthy controls without nervous system diseases in outpatient physical examination during the same period were selected as the control group. The clinical data and biochemical indicators of the two groups were collected. Serum MMP-9 levels were measured by enzyme linked immunosorbent assay (ELISA). According to susceptibility weighted imaging (SWI), CMBs patients were divided into grade 1 group ( n=24), grade 2 group ( n=19) and grade 3 group ( n=17), and according to the micro analytical rating scale (MARS), the CMBs patients were divided into the lobar group ( n=19), the deep or infratentorial group ( n=17) and the mixed group ( n=24).The relationship between serum MMP-9 level and the location and severity of CMBs was analyzed. SPSS 19.0 software was used for data statistical analysis.One-way ANOVA, t-test and rank sum test were used for comparison. Logistic regression analysis was used to analyze the influencing factors. Pearson correlation analysis and Spearman correlation analysis were used for correlation analysis. Results:The level of MMP-9 in CMBs group was significantly higher than that in control group (208.13(142.25, 285.88) μg/L, 149.50(93.40, 186.51)μg/L), and the difference was statistically significant ( P<0.05). Serum MMP-9 level was a risk factor of CMBs ( β=1.322, OR=3.750, 95% CI=2.038-7.997, P=0.002). The difference of level of MMP-9 in different severity of CMBs was statistically significant (147.55(109.25, 266.47)μg/L, 242.12(147.55, 288.80)μg/L, 270.42(203.43, 364.27)μg/L, P=0.017). Serum MMP-9 level was positively correlated with the number of CMBs ( r=0.371, P=0.003). The difference of MMP-9 level of CMBs in different locations were statistically significant (249.77(158.43, 338.46)μg/L, 188.83(138.52, 243.15)μg/L, 210.65(144.25, 255.78)μg/L, P=0.013). The increased serum MMP-9 level was a risk factor for CMBs( β=0.401, OR=1.122, 95% CI=1.004-1.204, P=0.036). Conclusion:The increased level of serum MMP-9 may be a risk factor of CMBs, especially for CMBs in cerebral lobesand, and the level of MMP-9 is positively correlated with the severity of CMBs.

Network Meta-analysis of 14 oral Chinese patent medicines combined with Azithromycin in treatment of mycoplasma pneumonia in children / 中国中药杂志

To systematically evaluate the clinical efficacy of 14 oral Chinese patent medicines combined with Azithromycin in the treatment of mycoplasma pneumonia in children with network Meta-analysis. Computer retrieval was performed for such databases as CNKI, VIP, Wanfang, CBM, PubMed, EMbase and Cochrane Library to screen out randomized controlled trials of oral Chinese patent medicines combined with Azithromycin in the treatment of mycoplasma pneumonia in children from the time of database establishment to September 2020. The included studies were evaluated by the Cochrane Risk Assessment tool. Stata 14.0 and Review Manager 5.3 software were used for data statistical analysis. A total of 60 RCTs were included in this study, involving 14 oral Chinese patent medicines. The efficacy ranking based on network Meta-analysis was as follows:(1)in terms of total effective rate, top five Chinese patent medicines in surface under the cumulative ranking curve(SUCRA) were Xiao'er Xiaoji Zhike Oral Liquid, Xiao'er Chiqiao Qingre Granules, Xiao'er Feike Granules, Pudilan Xiaoyan Oral Liquid and Lanqin Oral Liquid;(2)in terms of antifebrile time, top five Chinese patent medicines in SUCRA were Huaiqihuang Granules, Xiao'er Magan Granules, Xiao'er Kechuanling Granules/Oral Liquid, Shuanghuang-lian Oral Liquid for children and Xiao'er Xiaoji Zhike Oral Liquid;(3)in terms of cough disappearance time, top five Chinese patent medicines in SUCRA were Xiao'er Magan Granules, Huaiqihuang Granules, Xiao'er Chiqiao Qingre Granules, Xiao'er Feire Kechuan Oral Liquid and Xiao'er Kechuanling Granules/Oral Liquid;(4)in terms of rale disappearance time, top five Chinese patent medicines in SUCRA were Xiao'er Magan Granules, Huaiqihuang Granules, Xiao'er Feire Kechuan Oral Liquid, Shuanghuanglian Oral Liquid for children and Yupingfeng Granules. The results showed that on the basis of the use of Azithromycin, combined administration with oral Chinese patent medicines could improve the overall clinical efficacy in the treatment of mycoplasma pneumonia in children. However, due to the large differences in the quality and the number of included studies among various therapeutic measures, the ranking results of SUCRA of Chinese patent medicines need to be verified by high-quality multi-center, large-sample, randomized double-blind trials in the future.

Dryness comparison of different fractions of Aurantii Fructus extract on normal mice and gastrointestinal motility disorder rats and spectrum-dryness study / 中国中药杂志

Aurantii Fructus is a commonly used qi-regulating medicinal herb in China. Both traditional Chinese medicine theory and modern experimental research demonstrate that Aurantii Fructus has dryness effect, the material basis of which remains unclear. In recent years, spectrum-effect relationship has been widely employed in the study of active ingredients in Chinese medicinal herbs, the research ideas and methods of which have been constantly improved. Based on the idea of spectrum-effect study, the ultra-high perfor-mance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS) fingerprints of different fractions of Aurantii Fructus extract were established for the identification of total components. Then, the dryness effects of the fractions on normal mice and gastrointestinal motility disorder(GMD) rats were systematically compared. Finally, principal component analysis(PCA), Pearson bivariate correlation analysis and orthogonal partial least squares analysis(OPLS) were integrated to identify the dryness components of Aurantii Fructusextract. The results showed that narirutin, naringin, naringenin, poncirin, oxypeucedanin, and eriodictyol-7-O-glucoside had significant correlations with and contributed to the expression of AQP2 in kidney, AQP3 in colon, and AQP5 in submandibular gland, which were the main dryness components in Aurantii Fructus.

Molecular Mechanism of Nelumbinis Plumula Alkaloids in Prevention and Treatment of Non-Small Cell Lung Cancer： an Analysis Based on Network Pharmacology and Cell Experiment / 中国实验方剂学杂志

Objective:To explore the potential molecular mechanism of Nelumbinis Plumula alkaloids （NAPs） in the prevention and treatment of non-small cell lung cancer （NSCLC） based on network pharmacology and cell experiment. Method:The main active components of NAPs were obtained by searching Traditional Chinese Medicine System Pharmacology Database and Analysis Platform （TCMSP） and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）， and their main targets were predicted and analyzed by employing Swiss Target Prediction. The main target genes of NSCLC were retrieved from GeneCards， Online Mendelian Inheritance in Man （OMIM） and DrugBank databases. The resulting common targets were imported into STRING platform for constructing the protein-protein interaction （PPI） network， followed by gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis based on Database for Annotation， Visualization， and Integrated Discovery （DAVID）. The NAPs-common target -pathway network was constructed by Cytoscape 3.7.1. After NSCLC cell line A549 was treated with isoliensinine， the cell morphology was observed under an inverted fluorescence microscope. The effect of isoliensinine on A549 vitality was detected by cell counting kit-8 （CCK-8） assay and the target protein changes were verified by Western blot. Result:The main active components for NAPs against NSCLC were lysicamine， liensinine， and isoliensinine. The phosphatidylinositol-3-kinase-protein kinase B （PI3K-AKT）， RAS-related protein 1 （Rap1）， epidermal growth factor family of receptor tyrosine kinases （ErbBs）， and hypoxia inducible factor-1 （HIF-1） pathways were mainly involved for binding adenosine triphosphate （ATP） and regulating protein kinase activity. The main targets included protein kinase B-1 （AKT1）， alpha catalytic subunit of phosphoinositol-3-kinase （PIK3CA）， cyclin-dependent kinase 2 （CDK2）， mitogen-activated protein kinase-1 （MAPK1）， epidermal growth factor receptor （EGFR）， adenosine triphosphate-binding cassette B1 （ABCB1）， mammalian target of rapamycin （mTOR）， tyrosine kinase （Src）， Janus kinase 1 （JAK1）， and G1-phase-specific gene cyclin-D₁ （CCND1）. The <italic>in vitro</italic> cell experiment also revealed that isoliensinine down-regulated the expression of phosphorylated AKT （p-AKT） and phosphorylated mTOR （p-mTOR） in a concentration- and time-dependent manner and inhibited the growth of A549 cells. Conclusion:NAPs exert the preventive and therapeutic effects against NSCLC through multiple components， multiple targets， and multiple pathways， especially the PI3K-AKT pathway.

Correlation between serum MMP-9 protein level and vascular cognitive impairment with no dementia in patients with cerebral small vessel diseases / 中华行为医学与脑科学杂志

Objective:To investigate the relationship between serum matrix metalloproteinase-9(MMP-9) level and vascular cognitive impairment with no dementia (VCIND) in patients with cerebral small vessel diseases (CSVD).Methods:A total of 374 patients with CSVD treated in the First Affiliated Hospital of Xinxiang Medical University from January 2016 to January 2020 were collected and 150 healthy subjects in the same period were used as general data of the control group. All subjects were detected for serum MMP-9 level using enzyme linked immunosorbent assay and received cognitive function scoring using Montreal cognitive assessment (MoCA). The 374 patients with CSVD were divided into the Group A(186 cases with vascular cognitive impairment with no dementia) and the Group B(188 cases without cognitive impairment). The general data, serum MMP-9 level and cognitive function score were compared among the three groups and the correlation between MMP-9 level and cognitive function was analyzed.Results:The MMP-9 levels of Groups A and B ( (335.10±105.10)μg/L, (261.62±80.32)μg/L) were higher than those of the control group ( (168.23±48.85)μg/L), and the MMP-9 level of Group A was higher than that of Group B ( P<0.05). The MoCA scores of Groups A and B ( (18.45±5.24), (28.31±1.52) ) were lower than those of the control group (29.49±0.90), and the MoCA scores of Group A were lower than those of Group B ( P<0.05). The serum MMP-9 level, a risk factor for VCIND in patients with CSVD ( β=1.505, OR=1.323, 95% CI=1.149-1.527, P<0.05), was negatively correlated with total score of MoCA scale, visual-spatial and executive function, naming, language, abstract thinking, delayed recall, and directive force factor score ( r=-0.299, r=-0.155, r=-0.383, r=-0.358, r=-0.192, r=-0.259, r=-0.246 respectively, all P<0.05). Conclusion:The increased level of MMP-9 may be a risk factor of VCIND in CSVD patients, and it is closely related to cognitive impairment.

Study on Mechanism of Taoren Chengqitang in Regulating Intestinal Myoelectrical Activity and Microenvironment Homeostasis in Intestinal Sepsis Rats Based on HMGB1/TLR4/NF-κB Pathway / 中国实验方剂学杂志

Objective:To study the mechanism of Taoren Chengqitang in regulating intestinal myoelectric activity and microenvironment homeostasis in intestinal sepsis rats based on high mobility group protein 1(HMGB1)/Toll-like receptor 4(TLR4)/nuclear factor -κB(NF-κB) pathway. Method:The 60 SD rats were randomly divided into sham operation group, model group, glycyrrhizic acid (HMGB1 inhibitor, 0.03 g·kg-1) group, Taoren Chengqitang group (10 g·kg-1), glycyrrhizic acid+Taoren Chengqitang group (0.03 g·kg-1+10 g·kg-1), with 12 rats in each group. Except the sham operation group, the other groups established intestinal sepsis rat models, each group was treated with medicine, hematoxylin-eosin (HE) staining was used to detect the histopathological changes of small intestinal mucosa in rats of each group, the changes of mucosal thickness and villus height were compared, the levels of secretory immunoglobulin A (sIgA), diamine oxidase (DAO) and D-lactic acid in intestinal mucosa of rats were detected by kit, the intestinal myoelectrical activity of rats in each group was measured, the slow wave frequency and amplitude of small intestinal smooth muscle were compared, the intestinal flora of rats in each group was detected, the contents of E. coli, Bifidobacterium and Lactobacillus were compared, and the expressions of HMGB1/TLR4/NF-κB pathway proteins HMGB1, TLR4, MyD88 and NF-κB p65 in small intestinal tissues were detected by Western blot. Result:Compared with sham operated group, the villus height, mucosal thickness, sIgA content, slow wave frequency and amplitude of smooth muscle, Bifidobacterium and Lactobacillus contents in intestinal mucosa of model group rats were significantly decreased, and serum DAO and D-lactic acid levels, intestinal E. coli content, intestinal tissue HMGB1, TLR4, MyD88 and NF-κB p65 proteins were significantly increased (P<0.05). Compared with the model group, the villus height, mucosal thickness, sIgA content, slow wave frequency and amplitude of smooth muscle, Bifidobacterium and Lactobacillus contents in intestinal mucosa of the Taoren Chengqitang group, glycyrrhizic acid group, and glycyrrhizic acid + Taoren Chengqitang group were significantly increased, and serum DAO and D-lactic acid levels, intestinal E. coli content, intestinal tissue HMGB1, TLR4, MyD88 and NF-κB p65 proteins were significantly decreased (P<0.05). Compared with the Taoren Chengqitang group and the glycyrrhizic acid group, the villus height, mucosal thickness, sIgA content, slow wave frequency and amplitude of smooth muscle, Bifidobacterium and Lactobacillus contents in intestinal mucosa of glycyrrhizic acid+Taoren Chengqitang group were significantly increased, and serum DAO and D-lactic acid levels, intestinal E. coli content, intestinal tissue HMGB1, TLR4, MyD88 and NF-κB p65 proteins were significantly decreased, the differences were statistically significant (P<0.05). Conclusions:Taoren Chengqitang can alleviate intestinal mucosal injury, regulate intestinal myoelectrical activity and microenvironment homeostasis, restore intestinal function and maintain flora balance in intestinal sepsis rats, which may be achieved by down-regulating HMGB1/TLR4/NF-κB pathway.

Identification of Prototype Compounds and Their Metabolites in Rat Plasma After Oral Administration of Aurantii Fructus Extract by UPLC-Q-TOF/MS / 中国实验方剂学杂志

Objective:To study the serum pharmacochemistry of Aurantii Fructus （AF）， and to investigate the pharmacological material basis of AF extract in rats. Method:Rapid identification and speculation of the prototype constituents and their metabolites in vivo were carried out according to the relative retention time， accurate relative molecular mass， cleavage fragments of MS/MS and neutral loss of metabolites with ultrahigh performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry （UPLC-Q-TOF/MS） technique by comparing the differences between different samples such as AF extracts， blank plasma， and administered plasma under the same chromatographic and mass spectrometric conditions. Result:After oral administration of the AF extract， 74 transitional constituents absorbed into the blood were detected in serum， in which 49 compounds were prototype constituents and the other 25 were metabolites. The prototype constituents could be divided into dihydroflavones， polymethoxyflavonoids， limonins， coumarins and alkaloids. The identified metabolites included glucuronic acid conjugates， sulfuric acid conjugates， hydroxylated products of flavonoid glycosides and polymethoxyflavonoids， as well as the simultaneous glucuronidation and sulfation products. Conclusion:The constituents absorbed into the blood and their metabolites may be the pharmacodynamic components of AF. Among them， alkaloids， polymethoxyflavonoids and coumarins are mainly introduced into the blood in the prototype form， while naringin and neohesperidin （the index components） exert effect mainly through hydrolysis into aglycones. This work will help to further elucidate the material basis of AF.

Clinical application of bone morphogenetic protein 2: Adverse reaction / 第二军医大学学报

Bone morphogenetic protein 2 (BMP2) is an active protein inducing bone formation, and it can regulate the proliferation of mesenchymal stem cells into osteoblasts. In 2002 BMP2 was approved by the US Food and Drug Administration for single-segment anterior lumbar intervertebral fusion surgery. However, during the clinical application, BMP2 was found to have the following adverse reactions: heterotopic ossification, osteolysis and graft sinking, formation of bone cysts, inflammation-related complications, radiculitis, retrograde ejaculation and carcinogenesis. These adverse reactions may be due to the off-label use of BMP2 and use of off-physiological dose. This review mainly sums up the adverse reactions in the clinical application of BMP2, hoping to provide reference for safer and more effective clinical medication.

Correlation between spinopelvic sagittal parameters and adjacent segment disease after lumbar fusion / 第二军医大学学报

Objective To analyze the correlation between adjacent segment disease (ASDis) after lumbar fusion and spinopelvic sagittal parameters, and to explore the risk factors. Methods From Jan. 2013 to Oct. 2017, the patients undergoing revision surgery for ASDis after lumbar fusion in Changhai Hospital of Naval Medical University (Second Military Medical University) were enrolled as ASDis group, and the patients who did not have ASDis after lumbar fusion during the same follow-up period were taken as controls. The clinical data of the patients in the two groups were retrospectively analyzed. The differences of the general data (age, gender, body mass index [BMI], follow-up time and the etiology of the first operation) and the spinopelvic sagittal parameters (thoracic kyphosis [TK], sagittal vertical axis [SVA], lumbar lordosis [LL], segmental lumbar lordosis [sLL], pelvic incidence [PI], pelvic tilt [PT] and sacral slope [SS]) were compared between the two groups. Results There were 25 patients in the ASDis group and 50 patients in the control group. There were no significant differences in the age, gender, BMI, follow-up time or the etiology of the first operation between the two groups (all P>0.05). Compared with the control group, the LL, sLL and SS were significantly lower in the ASDis group (36.00°±5.44°vs 43.88°±10.62°, 17.80°±5.79°vs 27.62°±6.74°, 27.50°±5.30°vs 31.06°±7.48° all P0.05). Meantime, the proportion of patients with SVA>50 mm, the difference of PT and LL (PT-LL)=10°, and the ratio of sLL to LL (RL)<60% were significantly higher in the ASDis group than those in the control group (18/25 vs 21/50, 16/25 vs 11/50, 21/25 vs 17/50; all P<0.05). Conclusion The sagittal imbalance after lumbar fusion is closely associated with ASDis, and compensatory kyphosis of adjacent lumbar segments due to surgical segmental lordosis may be one of the causes of ASDis after lumbar fusion.

Clinical study on the correlation of peripheral blood circulating tumor cells and theirchemokine receptor CCR9 with non-small cell lung cancer / 医学研究生学报

Objective Circulating tumor cells (CTCs) have potential value in the clinical application of various tumors. This study was to investigate the role of CTCs and their chemokine receptor CCR9 in the invasion and metastasis of non-small cell lung cancer (NSCLC). Methods From May 2018 to June 2019, a total of 62 patients with NSCLC in the clinical oncology center of The People's Hospital of Guangxi Zhuang Autonomous Region were enrolled in this study. The CanpatrolTM CTC technique was used to detected the expressions of CTCs and CCR9 in CTCs in peripheral blood of patients. Furthermore, the relationships between expression levels of CTCs, CCR9 and clinical, pathological characteristics of NSCLC patients were analyzed. Results CTCs were detected in 56 of 62 (90.3%) NSCLC patients. CTCs counts were associated with TNM stage, lymph node metastasis and distant metastasis of NSCLC (P<0.05). In the analysis of clinical correlation between CTC subtypes and NSCLC, epithelial CTCs counts were related to TNM stage and distant metastasis of NSCLC (r=0.296 and r=0.273, P<0.05). Additionally, counts of mixed type CTCs were also correlative with NSCLC tumor metastasis (r =0.253, P =0.047). Finally, we found that the positive rate of CCR9 in mixed type CTCs was associated with distant metastasis of NSCLC (r=0.353, P=0.038). Conclusion CTCs counts and subtypes were correlated with TNM stage and metastasis of NSCLC. The expression level of CCR9 on CTC was expected to be a biomarker to evaluate the risk of tumor metastasis in NSCLC.

Treatment strategy of mechanical hemolysis after mitral valve repair / 医学研究生学报

Objective　In recent yaers, mitral valve repair has been widely used in the surgical treatment of congenital and secondary mitral valve lesions. To investigate the mechanism and treatment strategy of mechanical hemolysis after mitral valve repair.　Methods　A total of 451 consecutive patients registrated in general hospital of southern theatre command who underwent mitral valve repair surgery between August 2010 and June 2018,of whom 16(3.5%) had complicated mechanical hemolysis(hemoglobinuria, jaundice, anemia), were retrospectively analyzed. Echocardiographic examination showed that there were 3 cases of mild mitral regurgitation(MR), 9 cases of moderate MR and 4 cases of severe MR, among which 75% of mitral regurgitation flow were rapid regurgitant jets (Vmax>4m/s). According to the treatment strategy,all cases were divided into two groups: the aggressive reoperation group（n=10）,patients received re-repair procedures within 1 week after hemolysis diagnosis. The conservative treatment group(n=6), patients received symptomatic treatment of hemodialysis, blood transfusion, diuresis, alkalization of urine, liver protection and oral metoprolol et al. All patients were followed up for 2 to 36 months, with an average (16±7.5) months, and the postoperative echocardiographic results, hemolysis symptom improvement and cardiac function were compared.　Results　No death occurred in the two groups after operation. The symptoms of patients in the aggressive reoperation group receded rapidly and discharged from hospital. 4 patients in the conservative treatment group received reoperation 3~11 weeks after surgery due to poor treatment effect (1 patient underwent re-repair and 3 patients underwent replacement), the other 2 patients received long-term conservative treatment. The cardiac function of the patients undergoing reoperation was maintained at level I~II. Echocardiographic examination showed that mild MR(n=10), mild~moderate MR(n=3), and no recurrence of mechanical hemolysis. Two patients with long-term conservative treatment, mild~moderate anemia, urinogen +~++, moderate MR, cardiac function at level II, were in a subclinical hemolytic state.　Conclusion　Mechanical hemolysis frequently occurs immediately or soon after mitral valve repair. Hemoglobinuria, jaundice, anemia and postoper echocardiography found the mitral regurgitant flow with high-shear stress, these helpful to the diagnosis. Surgery is an important factor affecting hemolysis. Hemolysis can be a sign of surgical failure, re-repair operation is the best treatment as soon as possible after the hemolysis has been diagnosed.Conservative treatment is not the priority choice.

Efficacy and Safety of Lanqin Oral Liquid for Herpangina in Children ：a Meta-analysis / 中国药房

OBJECTIVE： To systematically evaluate the efficacy and safety of Lanqin oral liquid in the treatment of herpangina in children. METHODS： Randomized controlled trials （RCTs） involving Lanqin oral liquid or routine symptomatic treatment combined with Lanqin oral liquid （trial group） versus routine treatment （control group） in the treatment of pediatric herpangina were retrieved  from PubMed， Embase， CBM， CNKI， Wanfang database， VIP database， etc. Meta-analysis was performed by using Rev Man 5.3 software after literature screening， data extraction and quality evaluation with Cochrane system evaluator manual 5.1.0. RESULTS： A total of 11 RCTs were included， involving 1 204 patients. Meta-analysis showed that total response rate [RR＝1.17， 95％CI（1.10， 1.24）， P＜0.000 01]， fade time of herpes [MD＝－2.17， 95％CI（－2.63， －1.72）， P＜0.000 01] and fade time of fever [MD＝－1.52， 95％CI（－1.72， －1.31）， P＜0.000 01] in trial group was significantly higher than in control group. There was no statistical significance in the incidence of ADR between 2 groups [RR＝1.00， 95％CI（0.52， 1.93）， P＝1.00]. Subgroup analysis based on rehydration symptomatic treatment showed that without rehydration， fade time of herpes in trial group was significantly shorter than control group [MD＝－1.64， 95％CI （－2.03， －1.26）， P＜0.000 01]； with rehydration， fade time of herpes in trial group was significantly shorter than control group [MD＝－2.79， 95％CI（－2.97， －2.61），P＜0.000 01]. CONCLUSIONS： Lanqin oral liquid can effectively improve therapeutic efficacy of herpangina patients， effectively shorten fade time of fever and herpes， without increasing the occurrence of ADR.

Establishment of a visualized of prediction model for postpyloric placement of spiral nasoenteral feeding tube in neurocritical care patients / 中国实用内科杂志

OBJECTIVE: To analyze the factors influencing postpyloric placement of spiral nasoenteral feeding tube(NET) in neurocritical care patients and establish a visualized prediction model. METHODS: Patients in Neurological Intensive Care Unit(NICU)who undertook postpyloric placement of NET after receiving prokinetics from Apr 2012 to Mar 2018 were included for retrospective analysis. The patients were divided into the success and failure group base on whether the tube tip entered into duodenum(or beyond)or not confirmed by bedside X-ray 24 hours later. The baseline data, APACHE Ⅱ score(acute physiology and chronic health evaluation Ⅱ), AGI grade(acute gastrointestinal injury), therapeutic measures and agents administered were recorded. Univariate and multivariate Logistic regression analysis was used to identify the potential factors affecting the postpyloric placement of NET. Based on those factors, a predicting model was established and visualized into an easy-to-use nomogram. RESULTS: A total of 241 patients including146 male and 95 female were enrolled for the study, with an median age of 58 years, median APACHEⅡscore of 20, median AGI of Ⅰ.The placement succeeded in 119(49.4%) of 241 patients. Logistic regression analysis demonstrated that APACHE Ⅱ score, sedatives and analgesics, vasopressors and AGI grade were among the influencing factors. A prediction model with a ROC-AUC of 0.8002 were established and visualized into a nomogram. CONCLUSION: APACHE Ⅱ score, sedatives and analgesics, vasopressors and AGI grade are the factors influencing success of postpyloric NET placement in neurocritical care patients, which incorporate a predicting model that can be visualized into a nomogram. The nomogram provided intensivists an easy-to-use decision support tool in NET placements.

A prospective cohort study on the effect of epidural labor analgesia on syndecan-1 in patients with preeclampsia / 复旦学报（医学版）

Objective To evaluate the treatment effects of epidural labor analgesia on syndecan-1 in patients with preeclampsia.Methods During Jan.,2016 and Dec.,2017,150 unipara females with preeclampsia and gestational age＞37 weeks were enrolled in the prospective cohort study.They were devided into intervention and control group (n =75 in each group) with and without epidural labor analgesia,based on whether epidural labor analgesia applications were made by the patients at the first examination of cervical dilation of 2 cm.The primary outcomes were mean change and change rate of syndecan-1 from baseline to 2 h post-treatment,and the secondary outcomes were visual analogue scale (VAS),IL-6 level and mean arterial pressure (MAP).Results Absolute change of syndecan-1 from baseline to 2 h post-baseline was (-11.49 ± 82.80) ng/mL in the intervention group and (45.09 ± 55.14) ng/mL in the control group,respectively.There was a significant difference in mean change of syndecan-1 between the two groups (P＜0.001).Similarly,the intervention group exhibited a greater reduction in change rate of syndecan-1 compared with the control group (P＜0.001).Moreover,the intervention group had greater reduction in VAS and MAP compared with the control group (P＜0.001 for both).There was no significant difference in IL-6 level between the two groups.Conclusions Epidural labor analgesia was associated with greater reduction in syndecan-1,VAS and MAP compared with the control condition.In contrast,administration of epidural analgesia did not significantly change IL-6 level.

Mechanisms of eleutheroside for treatment of diabetes mellitus type 2 based on network pharmacology / 药学学报

Seven main components in eleutheroside were used as research objects, and the mechanism of action of total eleutheroside for treatment of diabetes mellitus type 2 was investigated by network pharmacology. The SwissTargetPrediction, GeneCard, and String platforms were used to predict the 35 potential targets of these 7 components that are related to diabetes mellitus type 2. Then we used cytoscape 3.6.1 to build a "component-target" network map and used the Networkanalyzer tool for topology analysis. Gene ontology (GO) enrichment analysis and KEGG pathway enrichment analysis were performed on the DAVID6.8 platform, and the "component-target-path" network map was constructed based on the enrichment results. Those components mainly used in diabetes mellitus type 2 were screened as core components, and the core components were docked with key disease target proteins to verify the potential mechanism of the total eleutheroside. After screening, 8 important pathways associated with diabetes mellitus type 2 were identified. This study showed that eleutheroside A, eleutheroside D, eleutheroside E and sesamin played key roles in insulin resistance, apoptosis and inflammation pathways. The total eleutheroside may ameliorate type 2 diabetes mainly through regulating signal transducer and activator of transcription factors (STATs), non-receptor protein tyrosine phosphatase (PTPN) 1, PTPN2, c-Jun N-terminal kinase (JNK), and p38 mitogen activate protein kinase. These components worked together through multiple signaling pathway. Based on our data, eleutheroside is proposed as a novel therapeutic strategy for treatment of type 2 diabetes.