Expression and Significance of Lactate Dehydrogenase A in Renal Cell Carcinoma / 中山大学学报(医学科学版)

ObjectiveTo analyze the expression of Lactate dehydrogenase A（LDHA） in both renal cell carcinoma （RCC） tissue and RCC cell lines， and to investigate the impact of LDHA expression on the progression of RCC. MethodsFrom June 2018 to June 2022， totally 52 cases of RCC tissue samples and 49 cases of para-cancerous tissue samples were collected through surgical procedures from our hospital. LDHA expression was detected using immunohistochemistry （IHC）. The expression levels of LDHA in vitro were also detected in the normal human proximal tubule epithelial cell line HK-2 and renal cell carcinoma cell lines A498， Caki-2， ACHN， and 786-O by using qRT-PCR and Western blot. A recombinant plasmid carrying LDHA-shRNA was constructed and then transfected into 786-O cells to down-regulate the expression of LDHA. Tumor proliferative capacity was monitored using CCK-8 assay， clonal formation assay and EdU assessments. Additionally， cell glycolytic activity was assessed through glucose uptake assay， lactate secretion assay， and ECAR analysis. ResultsIHC analysis revealed significantly higher expression of LDHA in RCC tissue compared to adjacent tissues（P<0.05）. Furthermore， RCC tissues with higher TNM stage exhibited greater expression of LDHA than those with lower TNM stage （P<0.05）. The results of qRT-PCR and Western blot demonstrated that the expression of LDHA in each RCC cell line was significantly higher than that in HK-2（P<0.05）. After blocking the expression of LDHA in 786-O， there was a significant down-regulation of cell proliferation and glycolysis capacity （P<0.05）. ConclusionsThe expression of LDHA in RCC tissue and RCC cell lines is significantly overexpressed compared with normal one， particularly in those with higher TNM stage. Knockdown of the expression of LDHA significantly suppresses cell proliferation and aerobic glycolysis capacity in 786-O.

Effect of improved nursing strategy on prognosis of older immunosuppressed patients with pneumonia and sepsis / 中华危重病急救医学

OBJECTIVE@#To investigate the effect of improved nursing strategy on prognosis of older immunosuppressed patients with pneumonia and sepsis.@*METHODS@#A prospective study was conducted. The older immunosuppressed patients with pneumonia and sepsis admitted to the department of intensive care medicine and emergency intensive care unit (ICU) of Peking Union Medical College Hospital from January 2017 to July 2022 were enrolled. In the first stage (from January 2017 to December 2019), patients received the original nursing strategy (original nursing strategy group), including: (1) nurses were randomly assigned; (2) routine terminal cleaning; (3) ICU environmental cleaning twice a day; (4) oral care was performed with chlorhexidine twice a day; (5) original lung physiotherapy [head of bed elevated at 30 degree angle-45 degree angle, maintaining a Richmond agitation-sedation scale (RASS) -2 to 1, sputum aspiration as needed]. After 1 month of learning and training of the modified nursing treatment strategy for nurses and related medical staff, the patients in the second stage (from February 2020 to July 2022) received the improved nursing strategy (improved nursing strategy group). The improved nursing strategy improved the hospital infection prevention and control strategy and lung physical therapy strategy on the basis of the original nursing strategy, including: (1) nurses were fixed assigned; (2) patients were placed in a private room; (3) enhanced terminal cleaning; (4) ICU environmental cleaning four times a day; (5) education and training in hand hygiene among health care workers was improved; (6) bathing with 2% chlorhexidinegluconate was performed once daily; (7) oral care with a combination of chlorhexidine and colistin was provided every 6 hours; (8) surveillance of colonization was conducted; (9) improved lung physiotherapy (on the basis of the original lung physiotherapy, delirium score was assessed to guide early mobilization of the patients; airway drainage was enhanced, the degree of airway humidification was adjusted according to the sputum properties, achieving sputum viscosity grade II; lung ultrasound was also used for lung assessment, and patients with atelectasis were placed in high lateral position and received the lung recruitment maneuver). Baseline patient information were collected, including gender, age, underlying diseases, source of admission, disease severity scores, vital signs, ventilatory parameters, blood gas analysis, life-sustaining treatments, clinical laboratory evaluation, indicators of infection and inflammation, pathogens and drug therapy. The primary outcome was 28-day mortality, and the secondary outcomes were duration of mechanical ventilation, length of ICU stay, and ICU mortality. Multivariate Logistic regression analysis was used to determine the risk factors for 28-day death in older immunosuppressed patients with pneumonia and sepsis.@*RESULTS@#Finally, 550 patients were enrolled, including 199 patients in the original nursing strategy group and 351 patients in the improved nursing strategy group. No significant differences were found in gender, age, underlying diseases, source of admission, disease severity scores, vital signs, ventilatory parameters, blood gas analysis, life-sustaining treatments, clinical laboratory evaluation, indicators of infection and inflammation, coexisting pathogens or drug therapy between the two groups. Compared with patients in the original nursing strategy group, those in the improved nursing strategy group had significantly fewer duration of mechanical ventilation and length of ICU stay [duration of mechanical ventilation (days): 5 (4, 7) vs. 5 (4, 9), length of ICU stay (days): 11 (6, 17) vs. 12 (6, 23), both P < 0.01], and lower ICU mortality and 28-day mortality [ICU mortality: 23.9% (84/351) vs. 32.7% (65/199), 28-day mortality: 23.1% (81/351) vs. 33.7% (67/199), both P < 0.05]. Multivariate Logistic regression analysis showed that the improved nursing strategy acted as an independent protective factor in 28-day death of older immunosuppressed patients with pneumonia and sepsis [odds ratio (OR) = 0.543, 95% confidence interval (95%CI) was 0.334-0.885, P = 0.014].@*CONCLUSIONS@#Improved nursing strategy shortened the duration of mechanical ventilation and the length of ICU stay, and decreased ICU mortality and 28-day mortality in older immunosuppressed patients with pneumonia and sepsis, significantly improving the short-term prognosis of such patients.

The screening model for dopamine receptor agonists by a dopamine sensor / 药学学报

Parkinson's disease (PD) is a degenerative disease of the central nervous system due to the loss or death of dopaminergic neurons in the substantia nigra. Clinically, levodopa is the most effective and commonly used drug for PD treatment. However, long-term levodopa therapy is prone to motor complications and other side effects caused by excessive peripheral dopamine production, which has become an urgent problem to be solved in PD treatment. Dopamine receptor (DR) agonists are similar to dopamine. They can directly stimulate postsynaptic dopamine receptors, produce the same effect as dopamine, delay the application of levodopa as much as possible, and reduce complications caused by long-term use of levodopa. Therefore, screening effective dopamine receptor agonists has become a key issue in the study and treatment of PD. In order to establish a rapid, stable and reliable method for dopamine receptor agonist screening, this study used the human dopamine receptor 2 (DRD2) gene fused with a circular permuted EGFP (cpEGFP) to construct a recombinant gene, packaged with lentiviral vector, and the vector replaced the parted inner transmembrane domain of the third intracellular loop (ICL3) of genetically-encoded GPCR-activation based (GRAB) sensors. The fluorescence of GPCR-fused cpEGFP is regulated by conformational changes mediated by the interaction of dopamine receptor agonists with GPCRs without altering GPCR activity. The HEK293T cells were infected with viral vector, screened by puromycin to select highly expressed cells. Dopamine receptor agonists (including dopamine, bromocriptine mesylate, cabergoline, pramipexole) were used as positive drugs to explore the best screening and detection conditions, establishing a stable model to evaluate the dopamine receptor agonist. The results showed that the optimal filter for the dopamine receptor agonist in this study was the cell seeding count of 7×104, and the effective concentration of the positive drug was 1-100 µmol·L-1. In addition, pretreated with 10 µmol·L-1 dopamine receptor antagonists (including chlorprothixol hydrochloride, domperidone, and sulpiride), the positive fluorescence signal of overexpressed DRD2-cpEGFP HEK293T cells could not be detected when exposed to 10 µmol·L-1 dopamine receptor agonists, which proved that dopamine receptor antagonists could block the activity of dopamine receptor agonists, so they cannot activate dopamine receptor allosteric, indicating that the model has good specificity and can also be used for the screening and detection of new dopamine receptor antagonists. In summary, the study constructs a stable dopamine sensor detection system, which can effectively screen potential dopamine receptor agonists. The operation procedures are simple and rapid. And it can be used for a large-scale screening providing a fundamental methodology for drug development and PD treatment targeted on DRD2.

Exploring the key anti-fatigue components of American ginseng based on metabolomics and zebrafish models / 药学学报

The aim of this paper is to explore the key anti-fatigue active components in the saponin-like composition of American ginseng. The anti-fatigue activity of western ginseng samples was evaluated using a zebrafish model; metabolomics techniques were used to identify the main saponins in western ginseng from different origins; the active substances and relevant targets of the anti-fatigue effect of western ginseng were initially screened by constructing a PPI protein interaction network between western ginseng saponins and disease targets, and the key active ingredients were screened using a molecular docking method; finally, the anti-fatigue activity of the key active ingredients was evaluated using a zebrafish, animal experiment was approved by the Ethics Committee of Shandong Academy of Medical Sciences (SYXK20220005). The anti-fatigue activity of the key active ingredients was evaluated using a zebrafish model. The results of the zebrafish activity evaluation showed that there were significant differences in the activities of the western ginseng samples from the two origins, and a total of 10 different saponins were identified as possibly related to the anti-fatigue activity after further metabolomic testing and pattern discrimination. The core anti-fatigue targets were screened with the help of component-disease target PPI, combined with pharmacophore-like parameters and molecular docking techniques, and pseudoginsenoside F11 was found to have good binding activity to five of the targets. Finally, the zebrafish model revealed that pseudoginsenoside F11 exhibited significant anti-fatigue activity. This study used metabolomics and zebrafish model to screen the key active substances of pseudoginsenoside F11 for its anti-fatigue activity, which will provide a reference for further research on the anti-fatigue of pseudoginsenosides.

Changes of gut microflora in newly diagnosed IgA nephropathy patients and its correlation with clinical risk factors / 北京大学学报(医学版)

OBJECTIVE@#To investigate the gut microbiota in newly diagnosed IgA nephropathy patients with chronic kidney disease (CKD) stages 1-2 and the association between the gut microbiota and the clinical risk factors of IgA nephropathy.@*METHODS@#Fresh fecal samples were collected from nineteen newly diagnosed IgA nephropathy patients with CKD stages 1-2 and fifteen age- and sex-matched healthy controls. Fecal bacterial DNA was extracted and microbiota composition were characterized using 16S ribosomal RNA (16S rRNA) high-throughput sequencing for the V3-V4 region. The Illumina Miseq platform was used to analyze the results of 16S rRNA high-throughput sequencing of fecal flora. At the same time, the clinical risk factors of IgA nephropathy patients were collected to investigate the association between the gut microbiota and the clinical risk factors.@*RESULTS@#(1) At the phylum level, the abundance of Bacteroidetes was significantly reduced (P=0.046), and the abundance of Actinobacteria was significantly increased (P=0.001). At the genus level, the abundance of Escherichia-Shigella, Bifidobacte-rium, Dorea and others were significantly increased (P < 0.05). The abundance of Lachnospira, Coprococcus_2 and Sutterella was significantly reduced (P < 0.05). (2) There was no significant difference in the abundance of gut microbiota between the newly diagnosed IgA nephropathy patients and the healthy control group (P>0.05), but there were differences in the structure of the gut microbiota between the two groups. The results of LEfSe analysis showed that there were 16 differential bacteria in the newly diagnosed IgA nephropathy patients and healthy controls. Among them, the abundance of the newly diagnosed IgA nephropathy patients was increased in Enterobacteriales, Actinobacteria, Escherichia-Shigella, etc. The healthy control group was increased in Bacteroidetes and Lachnospira. (3) The result of redundancy analysis (RDA) showed that Bifidobacterium was positively correlated with serum IgA levels, 24-hour urinary protein levels and the presence of hypertension. Lachnoclostridium was positively correlated with the presence of hypertension. Escherichia-Shigella was positively correlated with urine red blood cells account. Bifidobacterium was positively correlated with the proliferation of capillaries. Faecalibacterium was positively correlated with cell/fibrocytic crescents. Ruminococcus_2 was positively correlated with mesangial cell proliferation, glomerular segmental sclerosis and renal tubular atrophy/interstitial fibrosis.@*CONCLUSION@#The gut microbiota in the newly diagnosed IgA nephropathy patients with CKD stages 1-2 is different from that of the healthy controls. Most importantly, some gut bacteria are related to the clinical risk factors of IgA nephropathy. Further research is needed to understand the potential role of these bacteria in IgA nephropathy.

Effect of Morus alba extract sanggenon C on growth and proliferation of glioblastoma cells / 中国中药杂志

Glioblastoma is the most common primary cranial malignancy, and chemotherapy remains an important tool for its treatment. Sanggenon C(San C), a class of natural flavonoids extracted from Morus plants, is a potential antitumor herbal monomer. In this study, the effect of San C on the growth and proliferation of glioblastoma cells was examined by methyl thiazolyl tetrazolium(MTT) assay and 5-bromodeoxyuridinc(BrdU) labeling assay. The effect of San C on the tumor cell cycle was examined by flow cytometry, and the effect of San C on clone formation and self-renewal ability of tumor cells was examined by soft agar assay. Western blot and bioinformatics analysis were used to investigate the mechanism of the antitumor activity of San C. In the presence of San C, the MTT assay showed that San C significantly inhibited the growth and proliferation of tumor cells in a dose and time-dependent manner. BrdU labeling assay showed that San C significantly attenuated the DNA replication activity in the nucleus of tumor cells. Flow cytometry confirmed that San C blocked the cell cycle of tumor cells in G_0/G_1 phase. The soft agar clone formation assay revealed that San C significantly attenuated the clone formation and self-renewal ability of tumor cells. The gene set enrichment analysis(GSEA) implied that San C inhibited the tumor cell division cycle by affecting the myelocytomatosis viral oncogene(MYC) signaling pathway. Western blot assay revealed that San C inhibited the expression of cyclin through the regulation of the MYC signaling pathway by lysine demethylase 4B(KDM4B), which ultimately inhibited the growth and proliferation of glioblastoma cells and self-renewal. In conclusion, San C exhibits the potential antitumor activity by targeting the KDM4B-MYC axis to inhibit glioblastoma cell growth, proliferation, and self-renewal.

Spatial distribution characteristics of metabolities in rhizome of Paris polyphylla var. yunnanensis: based on MALDI-MSI / 中国中药杂志

In this study, a method was established for in-situ visualization of metabolite distribution in the rhizome of Paris polyphylla var. yunnanensis. To be specific, through matrix-assisted laser desorption/ionization-mass spectrometry imaging(MALDI-MSI), the spatial locations of steroidal saponins, amino acids, organic acids, phytosterols, phytoecdysones, nucleosides, and esters in rhizome of the medicinal plant were directly analyzed, and six unknown compounds with differential distribution in rhizome tissues were identified. The specific procedure is as follows: preparation of rhizome tissue section, matrix screening and optimization, and MALDI-MSI analysis. The results showed that the steroidal saponins were mainly distributed in the central, amino acids in epidermis and cortex, low-molecular-weight organic acids in central epidermis, phytosterols in the epidermis and lateral cortex, the phytoecdysones in epidermis and cortex, nucleosides(uneven distribution) in epidermis and cortex, growth hormones around the epidermis and cortex, particularly outside the cortex, and esters in cortex with unobvious difference among different tissues. In this study, the spatial distribution of meta-bolites in the rhizome of P. polyphylla var. yunnanensis was characterized for the first time. The result can serve as a reference for identifying and extracting endogenous metabolites of P. polyphylla var. yunnanensis, exploring the synthesis and metabolism mechanisms of the metabolites, and evaluating the quality of medicinal materials.

Discovery and identification of quality markers of Sparganii Rhizoma based on zebrafish thrombosis model / 中草药·英文版

Objective: The aim of the present study was to determine the quality marker (Q-Markers) of Sparganii Rhizoma against thrombus through an integration of investigations on its antithrombotic effect, content determination and spectrum-effect correlation analysis. Methods: Based on the concept of Q-Marker, Sparganii Rhizoma was investigated for the identification of chemical component. The pharmacological effects on arachidonic acid-induced thrombosis in zebrafish were also investigated. The material basis in ethanol extract was determined by HPLC-UV. Furthermore, the potential Q-Markers were analyzed and predicted according to the effect-chemical correlation analysis. Finally, the anti-thrombotic Q-Markers were verified through the anti-thrombotic test of monomer components. Results: The model of thrombosis zebrafish was established with larvae exposed to 100 µmol/L arachidonic acid for 1 h. Nine ingredients in Sparganii Rhizoma were identified as 5-hydroxymethylfurfural, vanillic acid, ferulic acid, p-hydroxybenzaldehyde, p-hydroxybenzoic acid, vanillin, protocatechuic acid, p-coumaric acid and isoferulic acid. According to the determination effect of zebrafish thrombosis model and HPLC content analysis results, all the other contents present positive correlation except 5-hydroxymethylfurfural, and the P values of three representative potential Q-Markers (ferulic acid, protocatechuic acid and p-coumaric acid) were 0.002, 0.001 and 0.026, respectively. Conclusion: Sparganii Rhizoma showed a dose-dependent effect on the recovery of reducing cardiac red blood cell on zebrafish model. Three phenolic acids (ferulic acid, protocatechuic acid and p-coumaric acid) were proved to possess the anti-thrombotic effects which could be regarded as the potential Q-Markers for quality assessment of Sparganii Rhizoma.

Effect of cardiopulmonary resuscitation on hippocampal brain after cardiac arrest in rats and its mechanism / 中国药理学通报

Aim To investigate the protective effect of cardiopulmonary resuscitation (CPR) on hippocampal brain tissues of rats after cardiac arrest and its mechanism. Methods Forty SD rats were randomly divided into control group, ischemia group, cardiopulmonary resuscitation group and Edaravone treatment group. The rats in ischemia group were subjected to cardiac arrest by suffocation for 10 min. In resuscitation group, cardiac arrest/cardiopulmonary resuscitation (CA/CPR) was performed, after 3 min of cardiac arrest, cardiopulmonary resuscitation was performed for 7 min. After 10 min, the rats in each group were sacrificed, venous blood was taken to detect oxidative stress indicators, and the pathology of rat hippocampal brain tissues were examined by HE staining and electron microscopy, and the expressions of Nrf2 and Keapl gene and proteins were detected by real-time fluorescent quantitative PCR and Western blot. Results Compared with control group, the serum oxidative stress level of the ischemic model group rats increased, the Nissl body of the hippocampal nerve cells decreased significantly, the mitochondrial cristae were destroyed significantly, and the expressions of Nrf2 and Keapl genes and proteins in the hippocampal tissues increased. Compared with ischemic group, the serum oxidative stress level of resuscitation group rats decreased. Compared with ischemic group, the serum oxidative stress level of the rats in cardiopulmonary resuscitation group decreased, the neuronal cells in the hippocampus increased, the mitochondrial cristae damage was alleviated, and the expressions of Nrf2 and Keapl genes and proteins in the hippocampus decreased. Conclusions CPR has protective effect on hippocampal tissues of rats, and its mechanism is related to the alleviation of Nrf2/Keapl pathway of oxidative stress injury.

Diagnostic and prognostic value of peripheral lymphocyte subtyping for invasive candidiasis infection in critically ill patients with non-neutropenic sepsis / 中华内科杂志

Objective:To assess the diagnostic and prognostic value of lymphocyte subtyping for invasive candidiasis infection (ICI) in critically ill patients with non-neutropenic sepsis.Methods:A prospective observational cohort study was performed at Peking Union Medical College Hospital (PUMCH), 377 patients with non-neutropenic sepsis admitted to Department of Critical Care Medicine from January 2017 to November 2019 were enrolled. There were 9.0% (34/377) patients diagnosed as ICI. Vital signs, supportive care therapy and microbiological specimens were collected. Peripheral blood lymphocyte subtypes, serum globulin, complements, inflammatory factors such as interleukin(IL)-6, IL-8, IL-10 and tumor necrosis factor were detected within 24 hours after sepsis was diagnosed. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value and prognostic significance of immunological indicators for ICI. Multiple logistic regression was used to analyze the independent risk factors for ICI. Kaplan-Meier analysis was used to analyze survival.Results:The acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score was 17.0 (13.0, 21.0) in all 377 patients. The sequential organ failure score (SOFA) was 11.0 (8.0, 13.0), and the 28-day mortality rate was 27.6% (104/377). Peripheral blood CD8 +absolute T lymphocyte count≤177 cells/μl, CD28 +CD8 +T-cell count≤81 cells/μl and 1, 3-β-D-glucan (BDG) ≥88.20 ng/L were closely correlated with the diagnosis of ICI (AUC=0.793,95 %CI 0.749-0.833, P<0.000 1;AUC=0.892,95 %CI 0.856-0.921, P<0.000 1;AUC=0.761, 95 %CI 0.715-0.803, P<0.000 1, respectively), with sensitivity of diagnosis 94.12%, 100.00%, and 88.24%; the specificity of diagnosis 81.34%, 62.39%, 63.56% respectively. Multivariate logistic regression analysis identified CD8 +T-cell count≤139 cells/μl ( OR=7.463, 95 %CI 1.300-42.831, P=0.024) and CD28 +CD8 +T-cell counts≤52 cells/μl ( OR=57.494, 95 %CI 3.986-829.359, P=0.003) as independent risk factors for higher mortality. Kaplan-Meier survival analysis suggested that CD8 +T-cell count ≤139 cells/μl ( P=0.0159) and CD28 +CD8 +T-cell count≤52 cells/μl ( P=0.000 1) were associated with higher mortality within 28 days (68.8%, 91.7%). Conclusions:Low CD28 +CD8 +T cell count in peripheral blood is closely related to the development and clinical outcome of ICI in sepsis patients, which could be used as an effective indicator for the diagnosis and prognosis prediction of ICI.

Network pharmacologic molecular mechanism of Shenmai Injection in treatment of COVID-19 combined with coronary heart disease / 中草药

Objective: To analyze the molecular interaction network pathway of Shenmai Injection in the treatment of COVID-19 with coronary heart disease by using network pharmacology. Methods: Using the TCMSP and ETCM to retrieve the chemical constituents of Ginseng Radix et Rhizoma Rubra and Ophiopogonis Radix in Shenmai Injection. The target of the compound was predicted through the SwissTargetPrediction database. The target of COVID-19 with coronary heart disease was screened through the NCBI database and the GeneCards database, and the targets of compound and disease were mapped to obtain the target of the compound for treating the disease. FunRich software and DAVID database were used to perform GO function enrichment analysis and KEGG pathway enrichment analysis, and Excel software and Tableau software to draw bar charts and bubble charts for visualization. Finally, Cytoscape 3.7.1 software was used to build compound-target-pathway network. Glide was used to dock the components of Shenmai Injection with 3CL hydrolase (Mpro). Results: The results showed that ophiopogonin D', ophiopogonin D, ginsenoside Rg2, methyl ophiopogonanone A, ophiogenin-3-O-α-L-rhamnopyranosyl (1→2)-β-D-glucopyranoside, ginsenoside Rb2, ginsenoside R0, ophiopogon A, sanchinoside Rd, ophiopogonanone E, and ginsenoside Re showed higher degrees in the analysis and stronger binding with 3CL hydrolase. Those compounds were the main effective components in the treatment of COVID-19 combined with coronary heart disease, involving 77 targets such as IL6, GAPDH, ALB, TNF, MAPK1, MAPK3, TP53, EGFR, CASP3, and CXCL8. KEGG pathway enrichment analysis revealed that there were 124 (P < 0.05) signaling pathways involving HIF-1 signaling pathway, TNF signaling pathway, sphingolipid signaling pathway, Toll-like receptor signaling pathway, neurotrophin signaling pathway, VEGF signaling pathway, apoptosis, Ras signaling pathway, PI3K-Akt signaling pathway, and prolactin signaling pathway. The results of molecular docking showed that the affinity between the 17 components of Shenmai Injection and the 3CL hydrolase of SARS-CoV-2 was less than -25 kJ/mol. Conclusion: Shenmai Injection can achieve simultaneous intervention of COVID-19 and coronary heart disease by inhibiting cytokine storms, maintaining cardiac function homeostasis, regulating immunity, and antivirals. It presents the network regulation mechanism of mutual influence and complex correlation. This study can provide a scientific basis for the treatment of Shenmai Injection in critically ill patients with COVID-19.

Chemical constituents from acid hydrolyzates of Panax quinquefolius total saponins and their inhibition activity to α-glycosidase and protein tyrosine phosphatase 1B / 中草药·英文版

Objective: To investigate the hypoglycemic components from the acid hydrolyzates of Panax quinquefolius total saponins, and screen the active compounds by in vitro inhibitory activities to α-glycosidase enzymes and protein tyrosine phosphatase-1B (PTP1B). Methods: The hydrolyzates were chromatographed repeatedly over silica gel column, and the structures of the compounds were determined by means of NMR. The in vitro bioassay was performed through the inhibitory effects on α-glucosidase or/and PTP1B. Results: Eight compounds were isolated, which identified as 20(S)-panaxadiol (1), (20S,24R)-dammarane-20,24-epoxy-3β,6α,12β,25-tetraol (2), 20(R)-dammarane-3β,12β,20,25-tetraol (3), 20(S)-dammarane-3β,6α,12β,20,25-pentol (4), 20(R)-dammarane-3β,12β,20,25-tetrahydroxy-3β-O-β-D-glucopyranoside (5), β-sitosterol (6), oleanolic acid (7) and 20(S)-protopanaxadiol (8). Compound 5 was ginseng triterpenoid isolated from the acid hydrolysates of total saponins from P. quinquefolius for the first time. In this paper, the possible in vitro inhibitory activities were investigated. Compound 5 exhibited significantly inhibitory activity against α-glucosidase, and the IC50 value [(0.22 ± 0.21) µmol/L] was about 43-fold lower than positive control. For the PTP1B inhibition assay, compound 5 indicated the strongest inhibitory effect with IC50 of (5.91 ± 0.38) µmol/L, followed by compound 4 with IC50 of (6.21 ± 0.21) µmol/L, which were all showed competitive inhibitory pattern by using a Lineweaver-Burk plot. Conclusion: These results supported the potential application of dammaranes from acid hydrolyzates of P. quinquefolius total saponins can be used as ingredients of ancillary anti-diabetic agent or functional factor.

Segmental Zoster Paresis:Report of One Case and Literature Review / 中国医学科学院学报

Segmental zoster paresis(SZP)is a rare complication in herpes zoster infection,with its symptoms often neglected due to the co-existence of pain.Here we reported a case of SZP.Also,we analyzed 42 Chinese SZP cases in literature,which revealed that the male to female ratio of SZP patients was 13∶8,and the median age of disease onset was 65 years.The most commonly affected region is upper limb.The diagnosis depends mainly on typical medical history and clinical symptoms.Although there is no definite therapy for SZP,the antiviral therapy is the most commonly used treatment,which achieved complete recovery in 78.6% of the patients and partial recovery in 14.3% of the patients.

TCM chemical biology--emerging interdiscipline of "TCM chemistry" and "biology" / 中国中药杂志

Traditional Chinese medicine(TCM) is a research area with highly original innovation features,and is also a Chinese name card to the world. However,TCM owns a unique theoretical system which is quite different from western modern medicine,leading to an awkward situation of deficient modern social identity as well as poor international spread. Therefore,how to establish a research strategy in line with the characteristics of TCM itself to systematically interpret the unique scientific connotation of TCM is always a public hot topic. Based on persistent practical exploration and scientific consideration in TCM,our group firstly promoted the concept of traditional Chinese medicine chemical biology(TCM chemical biology,TCMCB). The major idea of TCMCB is to clarify the nature of TCM regulating life progress to link TCM to modern medicine by using TCM components as chemical tools. Notably,TCMCB mainly focuses on TCM target identification and TCM-guided disease molecular mechanism exploration,further to clarify the basic law of TCM mediating disease process. Finally,TCMCB-guided scientific studies can help explain TCM theory and promote the developmentof modern innovative drugs based on identified targets using TCM active components. Moreover,TCMCB is of vital importance for investigating the scientific nature of biological progress and the pattern of disease occurrence and development,indicating a key significance for modern life science and medicine. This review introduces the definition of TCMCB as well as its academic thought,research method,technology system and scientific significance,for providing new research ideas and scientific thoughts for TCM development.

Clinical control study of water colonoscopy and gas colonoscopy / 中国实用内科杂志

OBJECTIVE: To evaluate the satisfaction and performance of water colonoscopy and gas colonoscopy. METHODS: 240 continuous cases were randomly divided into two groups(gas colonoscopy group, water colonoscopy group). Record the general condition, success rate, period of performance and abdominal pain score. Investigate the degree of abdominal pain, distension and the will of receiving anesthetic colonoscopy next time in the follow-up. RESULTS: There were no significant difference between two groups in the general condition, success rate, depth of insertion, abdominal pain after examination or the will of receiving anesthetic colonoscopy next time(P>0.05). The period of insertion, period of withdrawal and period of performance in water colonoscopy group was longer than those in the gas colonoscopy group(P<0.001, P=0.013, P<0.001). The degree of abdominal distension at 1 hour after colonoscopy in water colonoscopy group was higher than those in the gas colonoscopy group(P<0.001), but no significant difference was found at6 hours after examination. CONCLUSION: Patients undergoing water colonoscopy have better outcomes with less abdominal pain and abdominal distension except for longer time of performance.

Type Ⅰ collagen combined titanium dioxide nanotube composite coating modified titanium surface improves osteoblast adhesion and osseointegration / 中国组织工程研究

BACKGROUND: Simple nanotube surface modification of titanium implant has been shown to promote adhesion, proliferation and differentiation of osteoblasts. Collagen coating can promote osteoblast adhesion and osseointegration in vivo. OBJECTⅠVE: To observe the effects of type collagen combined titanium dioxide nanotube composite coating modified titanium surface on osteoblast adhesion in vitro and osseointegration in vivo. METHODS: The titanium dioxide nanotube was fabricated on the pure titanium surface, then type Ⅰ collagen was combined with the nanotube structure to form composite coating. Scanning electron microscope observation was used to characterize the surface topography of the pure titanium, titanium dioxide nanotube and type Ⅰ collagen combined titanium dioxide nanotube surfaces. Contact angle test was employed to evaluate the hydrophilicity of different samples. MC3 T3-E1 murine preosteoblasts were seeded on the three kinds of materials for 4 hours. Cell adhesion morphology was examined by scanning electron microscope. Adherent cell counting was detected under inverted fluorescence microscope. Expression of actin cytoskeleton and vinculin was observed under laser scanning confocal microscope. The gene expression of vinculin and osteoprotegerin mRNA was detected by real-time quantitative PCR. The three kinds of samples were implanted into the tibia of Sprague-Dawley rats (provided by Laboratory Animal Center, Ⅰnstitute of Radiation Medicine, Chinese Academy of Medical Sciences) , and tibia samples were removed after 4 weeks of implantation for biological push-out test and histological observation. RESULTS AND CONCLUSⅠON: (1) Scanning electron microscope: There was mechanical scratch on the pure titanium surface. There was controllable, and uniform vertical arrangement of nanotubular structures with a diameter of approximately 70 nm on the titanium dioxide nanotube surface, and collagen adhered surrounding the nanotubular structures on the type Ⅰ collagen combined titanium dioxide nanotube substrate, and partial tubule orifices were closed. (2) The hydrophicility of type Ⅰ collagen combined titanium dioxide nanotube was significantly larger than those of the other two materials (P < 0.05) . (3) Compared with the pure titanium and titanium dioxide nanotube surfaces, the type Ⅰ collagen combined titanium dioxide nanotube substrate displayed increased adherent cell number, much well-organized cytoskeleton, enhanced immunofluorescence intensity of vinculin protein staining, and increased expression levels of vinculin and osteoprotegerin mRNA levels (all P < 0.05) . (4) Ⅰn vivo test revealed that the maximum push-out force in the type Ⅰ collagen combined titanium dioxide nanotube group was significantly higher than that in the pure titanium and titanium dioxide nanotube groups (P < 0.05) . Hematoxylin-eosin staining results showed that there were few bones, but many fibrous connective tissue surrounding the implant in the pure titanium group; there were more newly-born bones, and less fibrous connective tissue surrounding the implant in the titanium dioxide nanotube group; there were dense newly-born bones, and few thin fibrous connective tissue surrounding the implant in the type Ⅰ collagen combined titanium dioxide nanotube group. (5) These results indicate that type Ⅰ collagen combined titanium dioxide nanotube surface can facilitate osteoblast cell adhesion and promote osseointegration in vivo.

Effect of electrical stimulation at auricular points combined with sound masking on the expression of CREB, BDNF and TrkB in the auditory cortex of tinnitus rats / 中国针灸

OBJECTIVE@#To explore the effect of electrical stimulation at auricular points (EAS) combined with sound masking on the expression of cAMP-response element binding protein (CREB), brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB) in the auditory cortex of tinnitus rats.@*METHODS@#A total of 27 adult male SD rats were randomly divided into a control group, a model group and an EAS group. The rats in the model group and the EAS group were intervened with intraperitoneal injection of sodium salicylate to induce tinnitus model, while the rats in the control group were intervened with injection of 0.9% NaCl solution. After the model was successfully established, the rats in the EAS group were treated with electrical stimulation at "Shenmen" (TF) and "Yidan" (CO), combined with sound masking; the treatment was given once a day for 15 days. The gap prepulse inhibition of acoustic startle (GPIAS) and prepulse inhibition (PPI) testing were performed using the acoustic startle reflex starter package for rats. The expression of BDNF, TrkB, CREB and p-CREB in the auditory cortex of each group were measured with Western Blot analysis.@*RESULTS@#① Compared with the control group, the GPIAS values in 12 kHz, 16 kHz, 20 kHz and 28 kHz were significantly decreased in the model group (all 0.05).@*CONCLUSION@#EAS could improve the GPIAS values of high-frequency background sound in tinnitus rats, which may be related with the upregulation of the BDNF/TrkB/CREB signaling pathway in the auditory cortex, leading to the reversion of the maladaptive plasticity.

Clinical therapeutic effects of endoscopic drug therapy for treatment of patients with acute esophageal and gastric variceal bleeding / 中国中西医结合急救杂志

Objective To observe the effects of endoscopic drug therap on hemostasis, re-bleeding and the risk of occurrence of complication in patients with acute esophageal and gastric variceal bleeding (EGVB). Methods A retrospective method was conducted, and 100 patients with EGVB who were admitted to the Affiliated Hospital of Yan'an University from June 2015 to June 2017 were enrolled. According to the difference in treatment methods, they were divided into an endoscopy Sclerotherapy and Ligation group and transjugular intrahepatic portosystemic shunt (TIPS) group, 50 cases in each group. The TIPS group was treated with TIPS; the endoscopy Sclerotherapy and Ligation group underwent endoscopic variceal sclerotherapy, endoscopic esophageal variceal ligation and postoperative non-selective β blockers oral administration. After 2 years of follow-up, the patients' hemostasis, re-bleeding at acute stage, survival situation and the incidences of complications were recorded. Before treatment and 2 weeks after treatment, the levels of serum albumin (Alb), total bilirubin (TBil) and platelet count (PLT) were measured by Hitachi automatic biochemical analyzer in the two groups. Results The success rate of hemostasis in the endoscopy Sclerotherapy and Ligation group was significantly higher than that in the TIPS group [98.0% (49/50) vs. 82.0% (41/50) ], and the recurrence rate of varices, during 1- and 2-year follow-up, the recurrence rate of bleeding and the incidences of complications were significantly lower than those in TIPS group [the recurrence rate of varicose veins: 6.0% (3/50) vs. 24.0 (12/50), 1-year re-bleeding rate: 12.0% (6/50) vs. 30.0% (15/50), 2-year re-bleeding rate: 42.0% (21/50) vs. 66.0% (33/50), esophageal ulcer: 2.0% (1/50) vs. 14.0% (7/50), upper abdominal discomfort: 2.0% (1/50) vs. 14.0% (7/50), hepatic encephalopathy:4.0% (2/50) vs. 16.0% (8/50), chest pain: 6.0% (3/50) vs. 20.0% (10/50), all P < 0.05]. After treatment, the levels of Alb and PLT in the endoscopy Sclerotherapy and Ligation group were higher than those in the TIPS group [Alb (g/L):43.84±4.34 vs. 40.83±3.21, PLT (×109/L): 26.33±3.37 vs. 21.12±3.89, both P < 0.05], and the TBil was lower than that in the TIPS group (μmol/L: 13.82±4.32 vs. 19.33±4.59). Conclusion Endoscopic Sclerotherapy and Ligation can significantly improve the effect of hemostasis of patients with acute EGVB, the rate of re-bleeding does not increase compared with that of western medicine group using TIPS, and the incidences of complications are significantly lower than those of applying TIPS.

Study on liver protection and hepatotoxicity of saikosaponin a based on zebrafish model / 中国中药杂志

Bupleuri Radix has both liver protection and hepatotoxicity. Saponins are the main pharmacodynamic and toxic components of Bupleuri Radix. Based on zebrafish physical model and the model of alcoholic fatty liver( AFL) pathology,the liver toxic and protective effect of saikosaponin a( SSa) were assessed. The results indicated that 1. 77 μmol·L-1 SSa showed protective effect to AFL zebrafish. 5. 30 μmol·L-1 SSa was hepatotoxic to healthy zebrafish,but it showed protective effect to AFL zebrafish. 5. 62 μmol·L-1 SSa was hepatotoxic to healthy and AFL zebrafish. This study is benefit for clinical safety of saikosaponin a.

Antioxidant xanthones and anthraquinones isolated from a marine-derived fungus Aspergillus versicolor / 中国天然药物

Chemical examination of an EtOAc extract of cultured Aspergillus versicolor fungus from deep-sea sediments resulted in the isolation of four xanthones, eight anthraquinones and five alkaloids, including a new xanthone, oxisterigmatocystin D (1) and a new alkaloid, aspergillusine A (13). High resolution electron impact mass spectrometry (HR-EI-MS), FT-IR spectroscopy, and NMR techniques were used to elucidate the structures of these compounds, and the absolute configuration of compound 1 was established by its NMR features and coupling constant. Furthermore, the biosynthesis pathway of these xanthones and anthraquinones were deduced, and their antioxidant activity and cytotoxicity in human cancer cell lines (HTC-8, Bel-7420, BGC-823, A549, and A2780) were evaluated. The trolox equivalent antioxidant capacity (TEAC) assay indicated most of the xanthones and anthraquinones possessing moderate antioxidant activities. The Nrf2-dependent luciferase reporter gene assay revealed that compounds 6, 7, 9, and 12 potentially activated the expression of Nrf2-regulated gene. In addition, compounds 5 and 11 showed weak cytotoxicity on A with the IC values of 25.97 and 25.60 μmol·L, respectively.