High-throughput transcriptional profiling of perturbations by Panax ginseng saponins and Panax notoginseng saponins using TCM-seq / 药物分析学报

Panax ginseng(PG)and Panax notoginseng(PN)are highly valuable Chinese medicines(CM).Although both CMs have similar active constituents,their clinical applications are clearly different.Over the past decade,RNA sequencing(RNA-seq)analysis has been employed to investigate the molecular mechanisms of extracts or monomers.However,owing to the limited number of samples in standard RNA-seq,few studies have systematically compared the effects of PG and PN spanning multiple conditions at the transcriptomic level.Here,we developed an approach that simultaneously profiles transcriptome changes for multiplexed samples using RNA-seq(TCM-seq),a high-throughput,low-cost workflow to molecularly evaluate CM perturbations.A species-mixing experiment was conducted to illustrate the accuracy of sample multiplexing in TCM-seq.Transcriptomes from repeated samples were used to verify the robustness of TCM-seq.We then focused on the primary active components,Panax notoginseng sa-ponins(PNS)and Panax ginseng saponins(PGS)extracted from PN and PG,respectively.We also char-acterized the transcriptome changes of 10 cell lines,treated with four different doses of PNS and PGS,using TCM-seq to compare the differences in their perturbing effects on genes,functional pathways,gene modules,and molecular networks.The results of transcriptional data analysis showed that the tran-scriptional patterns of various cell lines were significantly distinct.PGS exhibited a stronger regulatory effect on genes involved in cardiovascular disease,whereas PNS resulted in a greater coagulation effect on vascular endothelial cells.This study proposes a paradigm to comprehensively explore the differences in mechanisms of action between CMs based on transcriptome readouts.

Network pharmacology approaches for research of Traditional Chinese Medicines / 中国天然药物

Pharmacodynamics material basis and effective mechanisms are the two main issues to decipher the mechnisms of action of Traditional Chinese medicines (TCMs) for the treatment of diseases. TCMs, in "multi-component, multi-target, multi-pathway" paradigm, show satisfactory clinical results in complex diseases. New ideas and methods are urgently needed to explain the complex interactions between TCMs and diseases. Network pharmacology (NP) provides a novel paradigm to uncover and visualize the underlying interaction networks of TCMs against multifactorial diseases. The development and application of NP has promoted the safety, efficacy, and mechanism investigations of TCMs, which then reinforces the credibility and popularity of TCMs. The current organ-centricity of medicine and the "one disease-one target-one drug" dogma obstruct the understanding of complex diseases and the development of effective drugs. Therefore, more attentions should be paid to shift from "phenotype and symptom" to "endotype and cause" in understanding and redefining current diseases. In the past two decades, with the advent of advanced and intelligent technologies (such as metabolomics, proteomics, transcriptomics, single-cell omics, and artificial intelligence), NP has been improved and deeply implemented, and presented its great value and potential as the next drug-discovery paradigm. NP is developed to cure causal mechanisms instead of treating symptoms. This review briefly summarizes the recent research progress on NP application in TCMs for efficacy research, mechanism elucidation, target prediction, safety evaluation, drug repurposing, and drug design.

Alterations of macular ganglion cell layer thickness and optic disc parameters in patients with early diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To compare the changes of optic disc parameters, peripapillary retinal nerve fibers layer(pRNFL)thickness and macular ganglion cell layer(mGCL)thickness among patients with early diabetes retinopathy and healthy controls by Cirrus HD-optical coherence tomography(OCT).METHODS: In this cross-sectional comparative study, 45 non-diabetic retinopathy(NDR), 52 mild nonproliferative diabetic retinopathy(NPDR), 55 moderate NPDR with type 2 diabetes mellitus(T2DM)and 64 age-matched healthy controls were included. The fasting blood glucose(FBG), duration of diabetes, glycosylated hemoglobin(HbA1c)and past history of the patients were collected in detail. Optic disc parameters(i.e., binocular RNFL thickness symmetry percentage, rim area, optic disc area, cup-to-disc ratio, cup volume), pRNFL thickness and mGCL thickness were measured by Cirrus HD-OCT. The comparison of different groups was performed by one-way analysis of variance.RESULTS: Compared with the control group, the binocular RNFL thickness symmetry percentage and rim area were significantly decreased, while the average C/D and vertical C/D were significantly increased in the NDR group, mild NPDR group and moderate NPDR group(all P<0.05). Compared with the control group, the peripapillary RNFL thicknesses(superior, temporal, inferior, nasal)and macular GCL thickness(average, minimum, superior, supero-temporal, infero-temporal, inferior, supero-nasal, and infero-nasal)became thinner in the NDR group, mild NPDR group, and moderate NPDR group(all P<0.05).CONCLUSION: Patients with early DR have significantly decreased binocular RNFL thickness asymmetry, rim area, pRNFL and mGCL thickness, while they have significantly increased cup-to-disc ratio when compared to healthy controls. The results support the statement that DM causes inner retinal neurodegenerative changes even in T2DM patients without overt microangiopathy.

Diagnostic efficacy of serum NT-proBNP and D-dimer for cardiogenic cerebral embolism based on population in southern Sichuan / 中国医师杂志

Objective:To investigate the diagnostic efficacy of serum N-terminal B-type brain natriuretic peptide (NT-proBNP) and D-dimer for cardiogenic cerebral embolism (CE) based on population in southern Sichuan.Methods:We selected the clinical data of 313 patients with acute cerebral infarction (ACI) for the first time, 34 patients with simple atrial fibrillation (AF) and 30 healthy people who were admitted to the Affiliated Hospital of Southwest Medical University from June 2019 to April 2021. The patients with ACI were divided into four subgroups according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) typing: large artery atherosclerosis (LAA), CE, small artery occlusion (SAO), and indeterminate subtype (UT). The differences in clinical data in the groups were compared. At the same time, the differences of NT-proBNP and D-dimer in serum in CE group, AF group and healthy group were compared; The risk factors of CE were analyzed by binary logistic regression, and the diagnostic efficacy of serum NT-proBNP and D-dimer for CE was evaluated by receiver operating characteristic (ROC) curve.Results:The prevalence of hypertension, diabetes, systolic blood pressure (SBP) and diastolic blood pressure (DBP) at admission, prothrombin time (PT), international normalized ratio (INR), fibrinogen (FIB), D-dimer, fibrinogen degradation products (FDP), National Institutes of Health Stroke Scale (NIHSS) score at admission, NT-proBNP and AF rate were significantly different among ACI subgroups (all P<0.05); There was no significant difference in PT and NIHSS score at admission between LAA group and CE group (all P>0.05). The prevalence of D-dimer, NT-proBNP and AF rate in CE group was significantly higher than those in other three groups (all P<0.05). The D-dimer, NT-proBNP, FDP and SBP level in CE group were significantly higher than those in AF group and healthy group (all P<0.05). Binary logistic regression analysis showed that D-dimer and NT-proBNP were independent risk factors for CE (both P<0.05). When the optimal cut-off value of serum D-dimer was 1.015 mg/L, the area under the ROC curve (AUC) was 0.896 (95% CI: 0.856-0.935, P<0.01); the sensitivity and specificity were 0.878 and 0.833, respectively; the positive predictive value and the negative predictive value were 0.705 and 0.953, respectively. When the best cut-off value of serum NT-proBNP was 657.145 ng/L, the AUC was 0.987 (95% CI: 0.977-0.998, P<0.01); the sensitivity and specificity were 0.959 and 0.963, respectively; the positive predictive value and the negative predictive value were 0.922 and 0.981, respectively. The accuracy of the combined detection of serum D-dimer and NT-proBNP in the diagnosis of CE was higher, and the AUC was 0.988 (95% CI: 0.978-0.998, P<0.01), sensitivity of 0.960, specificity of 0.977, positive predictive value of 0.950, negative predictive value of 0.982. Conclusions:The serum levels of NT-proBNP and D-dimer in CE patients increased significantly; NT-proBNP and D-dimer are important predictors of CE and have higher diagnostic efficacy for CE. The combination of them has a higher specificity for diagnosis.

Surveillance on the adverse events following immunization in Dazu District of Chongqing， 2016‒2020 / 上海预防医学

ObjectiveTo determine the incidence and characteristics of adverse events following immunization （AEFI） in 2016‒2020 in Dazu District of Chongqing， and evaluate the AEFI surveillance information system and provide scientific evidence for vaccine safety. MethodsDescriptive epidemiological analysis was performed on the cases collected by the AEFI surveillance system. Incidence and coverage of AEFI were then presented. ResultsA total of 319 AEFI cases were reported in 2016‒2020. Reported incidence of AEFI was determined to be 24.64/105 doses. The proportion of timely reporting AEFI within 48 hours was 94.04% and that of timely investigation within 48 hours was 98.41%. The proportion of completing the AEFI survey was 100.00% and that of AEFI classification was 99.69%. The male to female ratio was 1.28∶1. Majority of the AEFI cases were less than 1 year old （64.26%， 205/319）， from April to September （68.97%， 220/319）， and reported at 0‒1 day post-immunization （89.34%， 285/319）. Moreover， the reported incidence differed significantly between time periods （χ2=32.481，P<0.05） and time intervals from vaccination to occurrence of AEFI （χ2=961.408， P<0.05）. Coverage of reporting AEFI at county level reached 100％. In addition， non-severe AEFI cases accounted for 98.43% （314/319） and no death case was reported. General events， such as fever， redness， and scleroma， accounted for 80.56% （257/319）， whereas rare adverse events accounted for 15.99% （51/319）. The reported incidence of NIP vaccines was highest in the diphtheria tetanus acellular pertussis combined vaccine， followed by measles and rubella combined attenuated vaccine and diphtheria tetanus combined vaccine. Clinical diagnosis of rare adverse events was mainly allergic rashes. ConclusionThe AEFI surveillance information system in Dazu District of Chongqing achieves efficient monitoring of AEFI. It has proven that the vaccines are generally safe and immunization strategies may be continuously implemented. Furthermore， the sensitivity of AEFI surveillance should be improved through multiple approaches.

Oral administration of TRPV4 inhibitor improves atrial calcium handling abnormalities in sterile pericarditis rats / 生理学报

Atrial Ca2+ handling abnormalities, mainly involving the dysfunction of ryanodine receptor (RyR) and sarcoplasmic reticulum Ca2+-ATPase (SERCA), play a role in the pathogenesis of atrial fibrillation (AF). Previously, we found that the expression and function of transient receptor potential vanilloid subtype 4 (TRPV4) are upregulated in a sterile pericarditis (SP) rat model of AF, and oral administration of TRPV4 inhibitor GSK2193874 alleviates AF in this animal model. The aim of this study was to investigate whether oral administration of GSK2193874 could alleviate atrial Ca2+ handling abnormalities in SP rats. A SP rat model of AF was established by daubing sterile talcum powder on both atria of Sprague-Dawley (SD) rats after a pericardiotomy, to simulate the pathogenesis of postoperative atrial fibrillation (POAF). On the 3rd postoperative day, Ca2+ signals of atria were collected in isolated perfused hearts by optical mapping. Ca2+ transient duration (CaD), alternan, and the recovery properties of Ca2+ transient (CaT) were quantified and analyzed. GSK2193874 treatment reversed the abnormal prolongation of time to peak (determined mainly by RyR activity) and CaD (determined mainly by SERCA activity), as well as the regional heterogeneity of CaD in SP rats. Furthermore, GSK2193874 treatment relieved alternan in SP rats, and reduced its incidence of discordant alternan (DIS-ALT). More importantly, GSK2193874 treatment prevented the reduction of the S2/S1 CaT ratio (determined mainly by RyR refractoriness) in SP rats, and decreased its regional heterogeneity. Taken together, oral administration of TRPV4 inhibitor alleviates Ca2+ handling abnormalities in SP rats primarily by blocking the TRPV4-Ca2+-RyR pathway, and thus exerts therapeutic effect on POAF.

An ultra-robust fingerprinting method for quality assessment of traditional Chinese medicine using multiple reaction monitoring mass spectrometry / 药物分析学报

Chromatographic fingerprinting has been perceived as an essential tool for assessing quality and chemical equivalence of traditional Chinese medicine.However,this pattern-oriented approach still has some weak points in terms of chemical coverage and robustness.In this work,we proposed a multiple reaction monitoring(MRM)-based fingerprinting method in which approximately 100 constituents were simultaneously detected for quality assessment.The derivative MRM approach was employed to rapidly design MRM transitions independent of chemical standards,based on which the large-scale finger-printing method was efficiently established.This approach was exemplified on QiShenYiQi Pill(QSYQ),a traditional Chinese medicine-derived drug product,and its robustness was systematically evaluated by four indices:clustering analysis by principal component analysis,similarity analysis by the congruence coefficient,the number of separated peaks,and the peak area proportion of separated peaks.Compared with conventional ultraviolet-based fingerprints,the MRM fingerprints provided not only better discriminatory capacity for the tested normal/abnormal QSYQ samples,but also higher robustness under different chromatographic conditions(i.e.,flow rate,apparent pH,column temperature,and column).The result also showed for such large-scale fingerprints including a large number of peaks,the angle cosine measure after min-max normalization was more suitable for setting a decision criterion than the unnormalized algorithm.This proof-of-concept application gives evidence that combining MRM tech-nique with proper similarity analysis metrices can provide a highly sensitive,robust and comprehensive analytical approach for quality assessment of traditional Chinese medicine.

Inhibitory Effect of Duanteng Yimu Decoction on Pannus Formation in Mice with Collagen-induced Arthritis Based on VEGF Pathway / 中国实验方剂学杂志

Objective:To investigate the mechanism of Duanteng Yimu decoction （DTYM） in the inhibition of pannus formation in collagen-induced arthritis （CIA） mice. Method:Twenty-four SPF-grade DBA/1 male mice were randomly divided into the following four groups： a blank group （NC group）， a model group （CIA group）， a methotrexate group （MTX group）， and a DTYM group， with six mice in each group. The mice， except for those in the NC group， were modeled. From the second immunization， the medium， MTX （1 mg·kg^-1）， and DTYM （15.4 g·kg^-1） were administered at an equal volume by gavage for 35 days. Mice were observed for general condition and the arthritis index. The knee and ankle joints were scanned by microcomputed tomography （micro CT）. Hematoxylin-eosin （HE） and safranin O/fast green staining were performed to observe pathological changes. Immunohistochemistry was performed to detect the expression of platelet/endothelial cell adhesion molecule-1 （CD31）， vascular endothelial growth factor-<italic>α</italic> （VEGF-<italic>α</italic>）， vascular endothelial growth factor receptor 2 （VEGFR2）， and phosphorylated（p）-VEGFR2. Result:Compared with the NC group， the CIA group showed red and swollen ankle joints， increased arthritis index scores （<italic>P</italic><0.05， <italic>P</italic><0.01）， manifest injury in the knee and ankle joints， reduced cartilage thickness， elevated Micro CT bone destruction scores of knee and ankle joints （<italic>P</italic><0.01）， and up-regulated absorbance values of synovial CD31， VEGF-<italic>α</italic>， VEGFR2， and p-VEGFR2 （<italic>P</italic><0.01）. Compared with the CIA group， the DTYM group showed relieved ankle joint redness and swelling， reduced arthritis index scores of mice three weeks after administration （<italic>P</italic><0.05， <italic>P</italic><0.01）， intact joint surfaces of the knee and ankle joints， thickened cartilage， declining Micro CT bone destruction scores in both the knee and ankle joints （<italic>P</italic><0.05， <italic>P</italic><0.01）， and lowered absorbance values of CD31， VEGF-<italic>α</italic>， VEGFR2， and p-VEGFR2 in the synovium （<italic>P</italic><0.01）. Conclusion:DTYM can inhibit the pannus formation in CIA mice presumedly by regulating the VEGF pathway.

Mechanism of Duanteng Yimu Decoction on Human Umbilical Vein Endothelial Cell Model / 中国实验方剂学杂志

Objective:To explore the effect of Duanteng Yimu decoction （DTYM） on the activation of the human umbilical vein endothelial cell （HUVEC） model and the effect on related activated proteins and vascular endothelial growth factor （VEGF） signaling pathway. Method:After DTYM （200， 400 g·mL^-1） treatment of HUVEC induced by VEGF and tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>）， cell proliferation， migration， and tubulogenesis were detected by cell counting kit-8 （CCK-8） assay， 5-ethynyl-2'-deoxyuridine （EdU） assay， transwell migration assay， phalloidin staining， and matrix gel card method. The mRNA expression of adhesion factors， including E-selectin， intercellular adhesion molecule-1 （ICAM-1）， and vascular cell adhesion molecule-1 （VCAM-1） was detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expression of von Willebrand factor （VWF）， platelet-endothelial cell adhesion molecule-31 （CD31）， angiogenic factor cysteine-rich-61 （CYR61）， angiopoietin-1 （ANG-1）， VEGF， and VEGF receptor-2 （VEGFR2） was detected by Western blot. Immunofluorescence was used to determine CD31 expression. Result:Compared with the normal group， the model group showed potentiated proliferation， migration， and tubulogenesis of HUVEC （<italic>P</italic><0.05， <italic>P</italic><0.01）， elevated mRNA expression of E-selectin， ICAM-1， and VCAM-1 （<italic>P</italic><0.01）， up-regulated protein expression of VWF， CD31， ANG-1， CYR61， VEGF-<italic>α</italic>， and phospho （p）-VEGFR2 （<italic>P</italic><0.05，<italic> P</italic><0.01）， and increased CD31 immunofluorescence intensity （<italic>P</italic><0.01）. Compared with the model group， the DTYM groups displayed blunted proliferation， migration， and tubulogenesis of HUVEC （<italic>P</italic><0.05，<italic> P</italic><0.01）， decreased mRNA expression of E-selectin， ICAM-1， and VCAM-1 （<italic>P</italic><0.05， <italic>P</italic><0.01）， down-regulated protein expression of VWF， CD31， ANG-1， CYR61， VEGF-<italic>α</italic>， and p-VEGFR2 （<italic>P</italic><0.05， <italic>P</italic><0.01）， and weakened CD31 immunofluorescence intensity （<italic>P</italic><0.01）. Conclusion:DTYM inhibits HUVEC proliferation， migration， adhesion， and tubulogenesis， which is associated with the regulation of CD31， VWF， CYR61， and ANG-1 expression in HUVEC and the VEGF signaling pathway.

New avenues for systematically inferring cell-cell communication: through single-cell transcriptomics data

For multicellular organisms, cell-cell communication is essential to numerous biological processes. Drawing upon the latest development of single-cell RNA-sequencing (scRNA-seq), high-resolution transcriptomic data have deepened our understanding of cellular phenotype heterogeneity and composition of complex tissues, which enables systematic cell-cell communication studies at a single-cell level. We first summarize a common workflow of cell-cell communication study using scRNA-seq data, which often includes data preparation, construction of communication networks, and result validation. Two common strategies taken to uncover cell-cell communications are reviewed, e.g., physically vicinal structure-based and ligand-receptor interaction-based one. To conclude, challenges and current applications of cell-cell communication studies at a single-cell resolution are discussed in details and future perspectives are proposed.

Pediatric projects funded by National Natural Science Foundation of China from 2009 to 2018: retrospect and prospects / 中国当代儿科杂志

OBJECTIVE@#To perform a review and data analysis of the pediatric projects funded by National Natural Science Foundation of China from 2009 to 2018, and to investigate the changes in key support areas, research interest, and research hotspots in pediatrics.@*METHODS@#The database of National Natural Science Foundation of China was searched to screen out pediatric research projects in 2009-2018, and the changes in funding intensity and research direction were analyzed.@*RESULTS@#From 2009 to 2018, a total of 1 017 pediatric projects were funded by National Natural Science Foundation of China, with 485 (47.69%) General Projects, 426 (41.89%) Youth Fund Projects, 73 (7.18%) Regional Research Programs, 16 (1.57%) Key Programs, 6 (0.59%) Outstanding Youth Fund Projects, 7 (0.69%) Overseas Programs, and 4 (0.39%) other programs. There was a seven-fold increase in the total amount of subsidies, which increased from 8.42 million yuan in 2009 to 66.25 million yuan in 2018. The projects with the Primary Discipline Code of reproductive system/perinatology/neonatology, nervous system and mental illness, or circulatory system received the highest amount of fund.@*CONCLUSIONS@#The support of pediatric projects by National Natural Science Foundation of China continues to increase in the past ten years, and the main types of projects are General Projects and Youth Fund Projects. Neonatology, nervous system/mental illness, and circulatory diseases are the main directions of funded projects.

Effects of Cyclosporine A on the Development of Metanephros in the Pregnant BALB/c Mice / 中华医学杂志(英文版)

<p><b>Background:</b>Cyclosporine A (CsA) is a commonly used clinical immunosuppressant. However, CsA exposure in rabbits during the gestation period was shown to cause a postnatal decrease in the number of nephrons, with the effects remaining unknown. In this study, we aimed to explore the effects of CsA on metanephros development in the pregnant BALB/c mice.</p><p><b>Methods:</b>Pregnant mice were randomly divided into two groups, and CsA (10 mg·kg·d) was subcutaneously injected from gestation day 10.5 to day 16.5 in the CsA group, whereas a comparable volume of normal saline was given to the control group. All of the mice were sacrificed on gestation day 17.5 and serum CsA concentration was measured. The fetuses were removed and weighed, and their kidneys were prepared for histological assessment and polymerase chain reaction assay. In an in vitro experiment, embryo kidneys of fetal mice on gestation day 12.5 were used, and CsA (10 μmol/L) was added in the culture of the CsA group. The growth pattern of the ureteric bud and nephrons was assessed by lectin staining.</p><p><b>Results:</b>No significant differences in the weight of embryo (4.54 ± 1.22 vs. 3.26 ± 1.09 mg) were observed between the CsA and control groups, the thickness of the cortical (510.0 ± 30.3 vs. 350.0 ± 29.7 μm, P < 0.05) and nephrogenic zone (272.5 ± 17.2 vs. 173.3 ± 24.0 μm, P < 0.05), and the number of glomeruli (36.5 ± 0.7 vs. 27.5 ± 2.1, P < 0.05) were reduced in the CsA group when compared to the control group. The cell proliferation of Ki-67 positive index between control and CsA group (307.0 ± 20.0 vs. 219.0 ± 25.0, P < 0.05) in the nephrogenic zone was decreased with the increase of apoptotic cells (17.0 ± 2.0 vs. 159.0 ± 33.0, P < 0.05). The mRNA expression of WT-1, Pax2, and Pax8 was downregulated by CsA treatment. As for the in vitro CsA group, the branch number of the ureteric bud was decreased in the CsA-treated group with the nephrons missing in contrast to control after the incubation for 24 h and 72 h (all P < 0.0001).</p><p><b>Conclusion:</b>Treatment of CsA suppressed metanephros development in the pregnant mice; however, the potential action of mechanism needs to be further investigated.</p>

Effects of serum starvation on cell cycle synchronization in primary human umbilical vein endothelial cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the optimal starvation conditions of human umbilical vein endothelial cells (HUVECs) and establish a highly efficient and stable method for separating HUVECs.</p><p><b>METHODS</b>HUVECs harvested from human umbilical cords by digestion with 0.1% collagenase II for 15 min were cultured in endothelial culture medium (ECM) containing 5% fetal bovine serum (FBS), 1% endothelial cell growth factor (ECGS) and 1% penicillin/streptomycin solution(P/S) at 37 degrees celsius; in 5% CO2. The cells were observed for cell morphology under an inverted microscope and identified with immunofluorescence assay. The purity of HUVECs was detected using flow cytometry (FCM). The cell cycles of HUVECs cultured in the presence of 0, 0.1%, 0.5%, and 1% FBS for 0, 6, 12, 18, and 24 h were analyzed with flow cytometry.</p><p><b>RESULTS</b>s The purity of HUVECs harvested by digestion with 0.1% collagenase II reached 99.67%. The primary HUVECs showed a cobblestone or volute appearance in vitro. Immunocytochemistry showed that HUVECs highly expressed VIII-related antigen. Cell culture in the presence of different concentrations of FBS for 6 h resulted in 70% G0/G1 phase cells, which increased to 80%-90% at 12 h of cell culture, and further to around 95% at 18 and 24 h.</p><p><b>CONCLUSION</b>Digestion with 0.1% collagenase II can obtain high-purity primary HUVECs. Culturing HUVECs in serum-free medium for 12 h can result in a high purity (over 80%) of G0/G1 phase cells.</p>

Immunological balance of CD8CD28/CD8CD28T lymphocytes can predict gastrointestinal hemorrhage in patients with inflammatory bowel disease / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the sensitivity and specificity of CD8CD28/CD8CD28T lymphocyte balance in predicting the gastrointestinal hemorrhage (GH) in patients with inflammatory bowel disease (IBD).</p><p><b>METHODS</b>Forty-nine IBD patients, including 30 with ulcerous colitis (UC) and 19 with Crohn's disease (CD), were enrolled to test peripheral blood CD8CD28and CD8CD28T cells using flow cytometry. All the patients were followed up for one year. The receiver-operating characteristic (ROC) curves were used to test the efficiency of CD8CD28/CD8CD28T lymphocyte balance to predict GH. The differences in lasting time of remission (LTR) under different factors were compared using Kaplan-Meier survival analysis, and the correlation between CD8T lymphocytes and the factors were analyzed.</p><p><b>RESULTS</b>The utilization rates of immunosuppressant, steroids, and biological agent (BA) were significantly higher in CD patients than in UC patients (P=0.003, 0.043 and 0.002, respectively). The frequencies of CD8CD28T cells were obviously higher in UC patients than those in CD patients (t=3.022, P=0.004). CD8CD28T cells, CD8CD28T cells, and especially CD8CD28/CD8CD28ratio (area under curve of 0.977, P=0.000; cut-off value of 1.14 [13.95%/12.24%] with a sensitivity of 93.3% and a specificity of 91.2%) showed good efficiencies in predicting GH (P<0.01). The mean and median of LTR of IBD patients who did not receive BA or surgical treatment were significantly longer (Χ=9.730, P=0.002; Χ=15.981, P=0.000). CD8CD28/CD8CD28ratio was significantly related to both BA (P=0.009) and surgery (P=0.038).</p><p><b>CONCLUSION</b>Both decreased CD8CD28T cells and elevated CD8CD28T cells are closely correlated with GH, and their ratio can predict the occurrence of GH with a high sensitivity and specificity and is correlated with BA and surgery at the cut-off value of 1.14.</p>

Simultaneous determination of 3-chlorotyrosine and 3-nitrotyrosine in human plasma by direct analysis in real time-tandem mass spectrometry

A novel method for the simultaneous determination of 3-nitrotyrosine (NT) and 3-chlorotyrosine (CT) in human plasma has been developed based on direct analysis in real time-tandem mass spectrometry (DART-MS/MS). Analysis was performed in the positive ionization mode using multiple reaction monitoring (MRM) of the ion transitions at m/z 216.2/170.1 for CT, m/z 227.2/181.1 for NT and m/z 230.2/184.2 for the internal standard, d (3)-NT. The assay was linear in the ranges 0.5-100 μg/mL for CT and 4-100 μg/mL for NT with corresponding limits of detection of 0.2 and 2 μg/mL. Intra- and inter-day precisions and accuracies were respectively <15% and ±15%. Matrix effects were also evaluated. The method is potentially useful for high throughput analysis although sensitivity needs to be improved before it can be applied in clinical research.

Dissecting functional chemome of Xiaoqinglong decoction analogous formulae using network formulaology approach / 中国中药杂志

Analogous formulae (AF) refer to a set of traditional Chinese medicine (TCM) formulae sharing similar herbs and/or indications. Dissecting functional chemome of analogous formulae could enhance the understanding of the intrinsic nature of TCM. In this study, taking 5 Xiaoqinglong decoction analogous formulae (XQL AF) including Xiaoqinglong decoction, Mahuang Xingren Shigao Gancao decoction, Mahuang Fuzi decoction, Houpu Mahuang decoction and Daqinglong decoction as example, we systematically investigated the relationship between compounds and indications using network formulaology approach. The functional chemome of XQL AF were revealed by network analysis and molecular docking. This successful application in XQL AF suggests network formulaology could be a useful tool for AF-related research and therefore provide a new way to discover the scientific foundation of Zhang Zhongjing's herbal formulae.

HPV16 E5 peptide vaccine in treatment of cervical cancer in vitro and in vivo / 华中科技大学学报（医学）（英德文版）

Human papillomavirus (HPV)-induced cervical cancer is the second most common cancer among women worldwide. Despite the encouraging development of the preventive vaccine for HPV, a vaccine for both prevention and therapy or pre-cancerous lesions remains in high priority. Thus far, most of the HPV therapeutic vaccines are focused on HPV E6 and E7 oncogene. However these vaccines could not completely eradicate the lesions. Recently, HPV E5, which is considered as an oncogene, is getting more and more attention. In this study, we predicted the epitopes of HPV16 E5 by bioinformatics as candidate peptide, then, evaluated the efficacy and chose an effective one to do the further test. To evaluate the effect of vaccine, rTC-1 (TC-1 cells infected by rAAV-HPV16E5) served as cell tumor model and rTC-1 loading mice as an ectopic tumor model. We prepared vaccine by muscle injection. The vaccine effects were determined by evaluating the function of tumor-specific T cells by cell proliferation assay and ELISPOT, calculating the tumor volume in mice and estimating the survival time of mice. Our in vitro and in vivo studies revealed that injection of E5 peptide+CpG resulted in strong cell-mediated immunity (CMI) and protected mice from tumor growth, meanwhile, prolonged the survival time after tumor cell loading. This study provides new insights into HPV16 E5 as a possible target on the therapeutic strategies about cervical cancer.

HPV16 E5 peptide vaccine in treatment of cervical cancer in vitro and in vivo / 华中科技大学学报（医学）（英德文版）

Human papillomavirus (HPV)-induced cervical cancer is the second most common cancer among women worldwide. Despite the encouraging development of the preventive vaccine for HPV, a vaccine for both prevention and therapy or pre-cancerous lesions remains in high priority. Thus far, most of the HPV therapeutic vaccines are focused on HPV E6 and E7 oncogene. However these vaccines could not completely eradicate the lesions. Recently, HPV E5, which is considered as an oncogene, is getting more and more attention. In this study, we predicted the epitopes of HPV16 E5 by bioinformatics as candidate peptide, then, evaluated the efficacy and chose an effective one to do the further test. To evaluate the effect of vaccine, rTC-1 (TC-1 cells infected by rAAV-HPV16E5) served as cell tumor model and rTC-1 loading mice as an ectopic tumor model. We prepared vaccine by muscle injection. The vaccine effects were determined by evaluating the function of tumor-specific T cells by cell proliferation assay and ELISPOT, calculating the tumor volume in mice and estimating the survival time of mice. Our in vitro and in vivo studies revealed that injection of E5 peptide+CpG resulted in strong cell-mediated immunity (CMI) and protected mice from tumor growth, meanwhile, prolonged the survival time after tumor cell loading. This study provides new insights into HPV16 E5 as a possible target on the therapeutic strategies about cervical cancer.

Citrate versus unfractionated heparin for anticoagulation in continuous renal replacement therapy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Unfractionated heparin is the most commonly used anticoagulant in continuous renal replacement therapy (CRRT), but it can increase the risk of bleeding. Citrate is a promising substitute. Our study was to assess the efficacy and safety of citrate versus unfractionated heparin in CRRT.</p><p><b>METHODS</b>We searched the MEDLINE, the EMBASE, the Cochrane Central Register of Controlled Trials, and the China National Knowledge Infrastructure Database until up to November 2011 for randomized controlled trials comparing citrate with unfractionated heparin in adult patients with acute kidney injury prescribed CRRT. The primary outcome was mortality and the secondary outcomes included circuit survival, control of uremia, risk of bleeding, transfusion rates, acid-base statuses, and disturbance of sodium and calcium homeostasis.</p><p><b>RESULTS</b>Four trials met the inclusion criteria. Meta-analysis found no significant difference between two anticoagulants on mortality. Less bleeding and more hypocalcemic episodes were with citrate. Citrate was superior or comparable to unfractionated heparin in circuit life.</p><p><b>CONCLUSIONS</b>Citrate anticoagulation in CRRT seems to be superior in reducing bleeding risk and with a longer or similar circuit life, although there is more metabolic derangement. Mortality superiority has not been approved.</p>

Effect of blood glucose fluctuation and the sustained high blood glucose on renal pathological change and collagen IV expression in diabetic rats / 中南大学学报(医学版)

Objective:To observe the effect of blood glucose lfuctuation and the sustained high blood glucose on renal pathological change and collagen IV (Col IV) expression in diabetic rats. Methods:hTe 60 male Sprague-Dawley (SD) rats were randomly assigned into a normal control group (NC) and a model group (DM). hTe rats in the normal control group were fed with normal diet, while the rats in the model group were fed with high-sucrose-high-fat diet for 6 weeks. Atfer that,streptozocin (STZ, 30 mg/kg) was injected to induce diabetic model. The model group was then randomly divided into 2 subgroups:a sustained high blood glucose group and a fluctuation blood glucose group (animals in the latter group were subcutaneously injected with insulin twice daily). Rats were sacriifced atfer 3 months and kidney tissues were dissected for HE and PAS staining, Col IV immunohistochemistry and Western blot. Results:Compared with the normal control group, the renal glomeruli and capillary basal membrane in the diabetic rats was getting larger and thicker, respectively;the capsular space and ground substance was extended and increased, respectively;the volume of renal tubule, kidney hypertrophy index, glomeruler sclerosis index and Col IV content were all increased in the diabetic rats (P Conclusion:The capillary basal membrane of kidney in diabetic rats is thicker and the ground substance is increased. The degree of glomeruler sclerosis is more serious in the blood glucose lfuctuation group compared with the sustained high blood glucose group, which is conifrmed by the increased level of Col IV.