Construction and validation of a nomogram for blood transfusion after open reduction and internal fixation (ORIF) of proximal humeral fractures in the elderly: a cross-sectional study.

PURPOSE: Few studies have focused on the risk factors leading to postoperative blood transfusion after open reduction and internal fixation (ORIF) of proximal humeral fractures (PHFs) in the elderly. Therefore, we designed this study to explore potential risk factors of blood transfusion after ORIF for PHFs. We have also established a nomogram model to integrate and quantify our research results and give feedback. METHODS: In this study, we retrospectively analyzed the clinical data of elderly PHF patients undergoing ORIF from January 2020 to December 2021. We have established a multivariate regression model and nomograph. The prediction performance and consistency of the model were evaluated by the consistency coefficient and calibration curve, respectively. RESULTS: 162 patients met our inclusion criteria and were included in the final study. The following factors are related to the increased risk of transfusion after ORIF: time to surgery, fibrinogen levels, intraoperative blood loss, and surgical duration. CONCLUSIONS: Our patient-specific transfusion risk calculator uses a robust multivariable model to predict transfusion risk.The resulting nomogram can be used as a screening tool to identify patients with high transfusion risk and provide necessary interventions for these patients (such as preoperative red blood cell mobilization, intraoperative autologous blood transfusion, etc.).

Environmental exposure to polycyclic aromatic hydrocarbons: An underestimated risk factor for systemic lupus erythematosus onset and progression.

OBJECTIVE: To investigate the link between systemic lupus erythematosus (SLE) incidence and exposure to environmental polycyclic aromatic hydrocarbons (PAH). METHODS: A case-control study (ChiCTR2000038187) involving 316 SLE patients and 851 healthy controls (HCs) was executed. Environmental exposure was assessed via a questionnaire, stratified by gender and age (females <35 and ≥35 years, males). Blood samples collected from 89 HCs, 85 inactive, and 95 active SLE patients were used to measure serum benzo[a]pyrene diol epoxide -albumin (BPDE-Alb) adducts and PAH concentrations, indicating long-term and short-term exposure respectively. Intergroup comparisons and statistical analyses were conducted using R version 4.3.1. RESULTS: Diverse patterns were found in how environmental factors affect SLE onset across different demographics. Lifestyle exposure factors were found to be a stronger determinant of SLE onset than occupational exposure factors in women under 35. Indoor air pollution had a significant impact on SLE incidence, potentially comparable to outdoor air pollution. Lifestyle-related PAH exposure had a greater impact on SLE than occupational PAH exposure. PAH exposure levels progressively increase from HCs to inactive and active SLE patients. Active SLE patients show markedly higher BPDE-Alb levels than HCs. CONCLUSIONS: Environmental PAH, particularly lifestyle-related, are significant, yet under-recognized, risk factors for SLE. STATEMENT OF ENVIRONMENTAL IMPLICATION: We examined the relationship between exposure to environmental polycyclic aromatic hydrocarbons (PAH) and the incidence of systemic lupus erythematosus (SLE). PAH, prevalent in sources such as cigarette smoke, air pollution, and charred food, pose significant health hazards. This study is the first to investigate specific PAH exposure levels in SLE patients. We determined actual PAH exposure levels in both SLE patients and healthy individuals and indicated that long-term PAH exposure biomarker is more reliable for evaluating exposure in non-occupationally exposed groups like SLE, compared to short-term markers. These findings provide valuable insights for future research on similar non-occupationally exposed populations.

Analysis of Microbial Diversity and Community Structure of Rhizosphere Soil of Three Astragalus Species Grown in Special High-Cold Environment of Northwestern Yunnan, China.

Astragalus is a medicinal plant with obvious rhizosphere effects. At present, there are many Astragalus plants with high application value but low recognition and resource reserves in the northwestern area of Yunnan province, China. In this study, metagenomics was used to analyze the microbial diversity and community structure of rhizosphere soil of A. forrestii, A. acaulis, and A. ernestii plants grown in a special high-cold environment of northwestern Yunnan, China, at different altitudes ranging from 3225 to 4353 m. These microbes were taxonomically annotated to obtain 24 phyla and 501 genera for A. forrestii, 30 phyla and 504 genera for A. acaulis, as well as 39 phyla and 533 genera for A. ernestii. Overall, the dominant bacterial phyla included Proteobacteria, Actinobacteria, and Acidobacteria, while the dominant fungal ones were Ascomycota and Basidiomycota. At the genus level, Bradyrhizobium, Afipia, and Paraburkholderia were the most prevalent bacteria, and Hyaloscypha, Pseudogymnoascus, and Russula were the dominant fungal genera. Some of them are considered biocontrol microbes that could sustain the growth and health of host Astragalus plants. Redundancy analysis revealed that pH, TN, and SOM had a significant impact on the microbial community structures (p < 0.05). Finally, triterpene, flavonoid, polysaccharide, and amino acid metabolisms accounted for a high proportion of the enriched KEGG pathways, which possibly contributed to the synthesis of bioactive constituents in the Astragalus plants.

Research Progress and Forensic Application of Human Vascular Finite Element Modeling and Biomechanics / 法医学杂志

The finite element method (FEM) is a mathematical method for obtaining approximate solutions to a wide variety of engineering problems. With the development of computer technology, it is gradually applied to the study of biomechanics of human body. The application of the combination of FEM and biomechanics in exploring the relationship between vascular injury and disease, and pathological mechanisms will be a technological innovation for traditional forensic medicine. This paper reviews the construction and development of human vascular FEM modeling, and its research progress on the vascular biomechanics. This paper also looks to the application prospects of FEM modeling in forensic pathology.

Highly sensitive H2O2-scavenging nano-bionic system for precise treatment of atherosclerosis

In atherosclerosis, chronic inflammatory processes in local diseased areas may lead to the accumulation of reactive oxygen species (ROS). In this study, we devised a highly sensitive H2O2-scavenging nano-bionic system loaded with probucol (RPP-PU), to treat atherosclerosis more effectively. The RPP material had high sensitivity to H2O2, and the response sensitivity could be reduced from 40 to 10 μmol/L which was close to the lowest concentration of H2O2 levels of the pathological environment. RPP-PU delayed the release and prolonged the duration of PU in vivo. In Apolipoprotein E deficient (ApoE‒/‒) mice, RPP-PU effectively eliminated pathological ROS, reduced the level of lipids and related metabolic enzymes, and significantly decreased the area of vascular plaques and fibers. Our study demonstrated that the H2O2-scavenging nano-bionic system could scavenge the abundant ROS in the atherosclerosis lesion, thereby reducing the oxidative stress for treating atherosclerosis and thus achieve the therapeutic goals with atherosclerosis more desirably.

A deep-learning model for the assessment of coronary heart disease and related risk factors via the evaluation of retinal fundus photographs / 中华心血管病杂志

Objective: To develop and validate a deep learning model based on fundus photos for the identification of coronary heart disease (CHD) and associated risk factors. Methods: Subjects aged>18 years with complete clinical examination data from 149 hospitals and medical examination centers in China were included in this retrospective study. Two radiologists, who were not aware of the study design, independently evaluated the coronary angiography images of each subject to make CHD diagnosis. A deep learning model using convolutional neural networks (CNN) was used to label the fundus images according to the presence or absence of CHD, and the model was proportionally divided into training and test sets for model training. The prediction performance of the model was evaluated in the test set using monocular and binocular fundus images respectively. Prediction efficacy of the algorithm for cardiovascular risk factors (e.g., age, systolic blood pressure, gender) and coronary events were evaluated by regression analysis using the area under the receiver operating characteristic curve (AUC) and R2 correlation coefficient. Results: The study retrospectively collected 51 765 fundus images from 25 222 subjects, including 10 255 patients with CHD, and there were 14 419 male subjects in this cohort. Of these, 46 603 fundus images from 22 701 subjects were included in the training set and 5 162 fundus images from 2 521 subjects were included in the test set. In the test set, the deep learning model could accurately predict patients' age with an R2 value of 0.931 (95%CI 0.929-0.933) for monocular photos and 0.938 (95%CI 0.936-0.940) for binocular photos. The AUC values for sex identification from single eye and binocular retinal fundus images were 0.983 (95%CI 0.982-0.984) and 0.988 (95%CI 0.987-0.989), respectively. The AUC value of the model was 0.876 (95%CI 0.874-0.877) with either monocular fundus photographs and AUC value was 0.885 (95%CI 0.884-0.888) with binocular fundus photographs to predict CHD, the sensitivity of the model was 0.894 and specificity was 0.755 with accuracy of 0.714 using binocular fundus photographs for the prediction of CHD. Conclusion: The deep learning model based on fundus photographs performs well in identifying coronary heart disease and assessing related risk factors such as age and sex.

Epidural analgesia failure followed by intracranial subdural hematoma: a case report / 中华围产医学杂志

We report the diagnosis and treatment of a rare case of epidural analgesia failure followed by postpartum subdural hematoma. The patient underwent vaginal delivery under epidural analgesia at 32 +6 gestational weeks due to threatened premature labor, during which an unexpected dural rupture occurred. She gave no history of headache and there was no obvious abnormality during the pregnancy. However, on postpartum day 4, the patient complained of headache that could not be relieved when supine, but without any other neurological symptoms. A prompt cranial CT examination showed a left frontotemporal subdural hematoma. After conservative management with intravenous drip of mannitol, re-examination of cranial CT showed that the left frontotemporal subdural hematoma was mostly absorbed and the patient was discharged on postpartum day 18. The patient was healthy during follow up. Intracranial subdural hematoma after dural puncture is a rare and serious complication that requires early recognition and treatment.

Influencing factors associated with delayed time in pre-hospital emergency medical care for hypertensive emergency in the main urban area of Chongqing / 上海预防医学

ObjectiveTo investigate the influencing factors associated with delayed time in pre-hospital emergency medical care in patients with hypertensive emergency in the main urban area of Chongqing. MethodsA total of 1 246 patients with hypertension in the main urban area of Chongqing from March 2018 to August 2021 were included in this study. The delayed time in the pre-hospital emergency medical care was determined. A multivariate linear regression model was used to analyze the influencing factors. ResultsThe delayed time in the pre-hospital emergency medical care for the patients with hypertensive emergency was concentrated in 0‒12 h， with the average of （5.89±1.96） h. The delayed time differed significantly by gender， age， history of atrial fibrillation， diabetes， educational level， time of onset， mode of transportation， awareness of hypertensive emergency， blood pressure at the onset， and presence of persons at the onset of emergency （P<0.05）. Multivariate linear regression analysis showed that educational level， time of onset， blood pressure at the onset， awareness of hypertensive emergency， presence of persons at the onset were linearly correlated with delayed time in the pre-hospital medical care for hypertensive emergencies （P<0.05）. ConclusionDelay in pre-hospital medical care is prevalent for patients with hypertensive emergency in the main urban area of Chongqing. The delayed time is associated with multiple factors， such as educational level， time of onset， blood pressure at onset， awareness of hypertensive emergency， and presence of persons at onset. It warrants further improvement in the interventions to reduce the delay in the pre-hospital medical care.

Effect of γδ T cells on the Proliferation, Apoptosis and Autophagy of Multiple Myeloma Cells / 中国实验血液学杂志

AbstractObjective: To investigate the effect of γδ T cells on the proliferation, apoptosis and autophagy of multiple myeloma cells.@*METHODS@#Peripheral blood mononuclear cells (PBMNC) were isolated from healthy volunteers, and stimulated with zoledronic acid (Zol) in combination with rhIL-2. Flow cytometry analysis was used to detected the purity of γδ T cells. γδ T cells were collected and co-cultured with RPMI-8226 or U-266 cells at different effector target ratios. The proliferation of RPMI-8226 or U-266 cell lines were detected by CCK-8. Cell cycle and cell apoptosis were detected by flow cytometry and Western blot．The expressions of autophagy-related proteins were detected by Western blot.@*RESULTS@#γδ T cells can be expanded in vitro. γδ T cells could inhibit the proliferation of RPMI-8226 or U-266 cells, induced cell cycle arrest and promoted apoptosis in an effector target-dependent manner. In addition, γδ T cells could induce autophagy of myeloma cells, inhibited the expression of autophagy-related PI3K, P-AKT and P-mTOR, while increased the expression of AMPK and Beclin-1.@*CONCLUSION@#γδ T cells can inhibit the proliferation of RPMI-8226 and U-266 myeloma cells, induce cell cycle arrest, promote apoptosis, and enhance autophagy in vitro. The mechanism may be related to inhibition of PI3K/AKT/mTOR signaling pathway and/or activation of AMPK/Beclin-1 signaling pathway.

The application and research of using "creating significant learning experiences" in medical general education curriculum / 中华医学教育探索杂志

To improve the phenomenon of low participation and lack of innovation in education mode in general medical education elective courses, we have applied "creating significant learning experiences" to the design and implementation of medical general education curriculum, starting from six dimensions of learning including basic knowledge, application, synthesis, humanistic dimension, humanistic care, and learning to learn, setting learning goals, developing assessment tools and finally choosing teaching methods, thus forming a closed-loop teaching. And through the curriculum reform, collection of feedback and collation of data, the teaching activities designed according to this method fully meet and serve the teaching purposes, and assessment methods become more diverse and the content is more comprehensive, which reflects the multi-dimensional evaluation of the needs of general education.

Exploring the miRNA-mRNA regulatory network in schizophrenia based on GEO database / 四川精神卫生

ObjectiveTo provide a new idea for exploring the molecular genetic approach to the pathogenesis of schizophrenia via construction of microRNA-messenger RNA （miRNA-mRNA） regulatory network in schizophrenia. MethodsThe microarray datasets of GSE54578 miRNA expression profiles in peripheral blood and GSE145554 mRNA expression in the anterior cingulate in postmortem brain of schizophrenic subjects were downloaded from Gene Expression Omnibus （GEO） database since July 2021. The GEO2R was used to identify the differentially expressed miRNAs and mRNAs， screen the miRNA with target differentially expressed mRNA， and predict their potential upstream transcription factors. The overlapping genes from the mRNA targeted by the differentially expressed miRNA and the mRNA differentially expressed in GSE145554 dataset were collected. Then the biological features of hub genes were analyzed via Gene Ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis， and the protein-protein interaction （PPI） network and miRNA-mRNA regulatory network of hub genes were constructed. ResultsA total of 8 up-regulated differentially expressed miRNAs with targeted mRNA were screened out in GSE54578 datasets regarding schizophrenia， which involved in the regulation of 10 transcription factors， 247 down-regulated differentially expressed mRNAs were screened out in GSE145554 datasets， and 17 overlapping mRNAs were obtained. GO analysis showed that the target mRNAs were mainly involved in astrocyte differentiation and development. KEGG pathway enrichment analysis showed that the target mRNAs were mainly involved in Rap1 and Ras signaling pathways. PPI network analysis showed that the mRNAs （KRAS and CD28） might be key genes in schizophrenia. ConclusionThe integrated bioinformatics analysis based on GEO database can identify potential susceptibility genes in schizophrenia， and it also contributes to the construction of miRNA-mRNA regulatory network in schizophrenia.

Second-trimester termination due to conjoined twins in a woman with twice previous cesarean sections / 中华围产医学杂志

We report the induced labor of conjoined twins in the second trimester in a woman with a history of two previous cesarean sections, the last one of which was performed in 2017. This 25-year-old patient was found to have thoracolumbar conjoined fetuses with one heart and polyhydramnios through the routine ultrasound examination at 19 +5 gestational weeks and was admitted at 20 +1 gestational weeks. After a full assessment of the fetal and maternal condition through multidisciplinary consultation, it was determined to attempt a vaginal delivery as no absolute contraindication for induction of labor. The patient was given 300 mg mifepristone orally plus an amniotic cavity injection of 100 mg ethacridine lactate. Regular contractions occurred 28 hours after medication. The patient delivered a pair of dead female conjoined twins at 20 +6 gestational weeks following successful induction of labor, with an assisted vaginal breech delivery. There was no soft tissue damage in the birth canal, and the estimated blood loss was 150 ml. Pathological examination and autopsy showed thoracolumbar conjoined deformity twins with a common heart and liver. Adequate prenatal evaluation, a detailed understanding of the indications for induction of labor and vaginal delivery, closed monitoring during labor, and preparation for emergency cesarean section, are essential safety measures for induced labor of conjoined twins in women with a scarred uterus in the second trimester.

Safety of transcatheter aortic valve replacement through different approaches: A systematic review and meta-analysis / 中国胸心血管外科临床杂志

@#Objective    To evaluate the early and mid-term safety of transcatheter aortic valve replacement via transfemoral (TF), transapical (TAp) and transsubclavian (TSc) approaches by meta-analysis. Methods    We systematically searched the clinical comparative trials published from inception to June 2019 from PubMed, Web of Science, EMbase and The Cochrane Library, to evaluate the safety of transcatheter aortic valve replacement through TF, TAp or TSc approaches. The information of all-cause mortality at 30 days, 1 year, 2 years and the incidence of common complications at 30 days after operation (including pacemaker-dependent block, major vascular complications, severe bleeding events, acute renal injury and stroke) were exacted, and a meta-analysis was conducted by RevMan 5.3 software. Results    This study included 11 literatures, with a total of 7 833 patients, among whom 5 348 patients were treated by TF TAVR, 1 796 patients by TAp TAVR and 689 patients by TSc TAVR. The results of the meta-analysis were as follows: (1)  at 30 days after operation, the mortality of TF and TSc approaches were lower than that of the TAp approach (TF vs. TAp:OR=0.57, 95%CI 0.39-0.84, P=0.004; TSc vs. TAp: OR=4.12, 95%CI 1.93-8.79, P=0.000 3). There was no statistical difference between the TF and TSc approaches (TF vs. TSc: OR=0.98, 95%CI 0.38-2.51, P=0.97); at 1 year, there was no statistical difference in mortality among the three approaches (P>0.05); at 2 years, there was no statistical difference between TSc and TF or TAp approaches (TF vs. TSc: OR=1.21, 95%CI 0.95-1.54, P=0.13; TSc vs. TAp: OR=1.02, 95%CI 0.76-1.36, P=0.91). (2) The incidence of acute kidney injury after TF approach was lower than that of the TAp approach (OR=0.30, 95%CI 0.22-0.41, P<0.000 01). (3) There was no statistical difference in major vascular complications between TSc and TF or TAp approaches (TF vs. TSc: OR=0.75, 95%CI 0.38-1.49, P=0.41; TSc vs. TAp: OR=1.37, 95%CI 0.56-3.32, P=0.49). (4) There was no statistical difference in severe bleeding events between TF and TSc (OR=0.97, 95%CI 0.53-1.76, P=0.92). (5) There was no statistical difference in the incidence of postoperative stroke, pacemaker dependent block among the three approaches (P>0.05). Conclusion    TAp and TSc approaches are safe and effective. They are not only an alternative to TF approach, but also the first choice in some patients with poor condition of iliofemoral artery.

Acute Adverse Effects and Prognosis of Locally Advanced Nasopharyngeal Carcinoma Patients Treated with GP Regimen: A Meta-analysis / 肿瘤防治研究

Objective To compare the adverse effects and prognosis of locally advanced nasopharyngeal carcinoma (LANC) patients between the gemcitabine combined platinum (GP) regimen and other platinum-containing chemotherapy regimens by meta-analysis. Methods We searched relevant databases and included the studies about comparing GP and other chemotherapy regimens in the treatment of LANC. Methodological quality was assessed for each included study. Statistical analysis was carried out using RevMan5.3 and Stata15 software. Results The patients on GP regimen had a lower incidence of severe leukopenia and severe gastrointestinal reaction but a higher incidence of severe thrombocytopenia and hepatoxicity than those on other regimens (P < 0.05). The patients on GP regimen had a higher distant metastasis-free survival (P=0.004). Conclusion GP regimen can be used as a safe, alternative and economical induction chemotherapy regimen for locally advanced nasopharyngeal carcinoma.

Efficacy and Safety of Remdesivir for COVID-19 Treatment: An Analysis of Randomized, Double-Blind, Placebo-Controlled Trials

BACKGROUNDRemdesivir, an inhibitor of viral RNA-dependent RNA polymerases, has been identified as a candidate for COVID-19 treatment. However, the therapeutic effect of remdesivir is controversial. METHODSWe searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials, from inception to June 11, 2020 for randomized controlled trials on the clinical efficacy of remdesivir. The main outcomes were discharge rate, mortality, and adverse events. This study is registered at INPLASY (INPLASY202060046). RESULTSData of 1075 subjects showed that remdesivir significantly increased the discharge rate of patients with COVID-19 compared with the placebo (50.4% vs. 45.29%; relative risk [RR] 1.19 [95% confidence interval [CI], 1.05-1.34], I2 = 0.0%, P = 0.754). It also significantly decreased mortality (8.18% vs. 12.70%; RR 0.64 [95% CI, 0.44-0.92], I2 = 45.7%, P = 0.175) compared to the placebo. Data of 1296 subjects showed that remdesivir significantly decreased the occurrence of serious adverse events (RR 0.77 [95% CI, 0.63-0.94], I2 = 0.0%, P = 0.716). CONCLUSIONRemdesivir is efficacious and safe for the treatment of COVID-19. TRIAL REGISTRATION NUMBERThis study is registered at the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY202060046).

Application value of "four doors of the liver" approach in the laparoscopic anatomical hepatectomy / 中华消化外科杂志

Objective:To investigate the application value of "four doors of the liver" approach in the laparoscopic anatomical hepatectomy.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 52 patients with liver cancer who were admitted to West China Hospital of Sichuan University from September 2018 to September 2019 were collected.Patients underwent laparoscopic anatomical hepatectomy by opening "four doors of the liver" approach. There were 36 males and 16 females, aged (53±16)years, with a range from 35 to 78 years. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) follow-up and survival. Follow-up using outpatient examination or telephone interview was conducted to detect the physical situations, liver function and recurrence of liver cancer in patients up to March 2020. Measurement data with normal distribution were represented as Mean± SD, and measurment data with skewed distribution were represented as M (range). Count data were expressed as absolute numbers or percentages. Results:(1) Surgical situations: all the 52 patients underwent laparoscopic anatomical hepatectomy successfully, without perioperative death. Eight and 8 patients underwent laparoscopic left hemihepatectomy and right hemihepatectomy by opening "the first door of the liver" respectively, the operation time of which was (151±31)minutes and (190±43)minutes, the volume of blood loss was (151±20)mL and (361±51)mL. Eight and 8 patients underwent laparoscopic left inner hepatic lobotomy and left outer hepatic lobotomy by opening "the second door of the liver" respectively, the operation time of which was (171±41)minutes and (90±26)minutes, the volume of blood loss was (221±31)mL and (111±21)mL. Eight and 8 patients underwent laparoscopic right posterior hepatic lobotomy and right anterior hepatic lobotomy by opening "the third door of the liver" respectively, the operation time of which was (172±29)minutes and (220±40)minutes, the volume of blood loss was volume of (351±41)mL and (451±47)mL. Four patients underwent laparoscopic hepatic caudate lobotomy by opening "the fourth door of the liver" , the operation time of which was (246±36)minutes, the volume of blood loss was (261±31)mL. None of the 52 patients had blood transfusion. (2) Postoperative situations: all the 52 patients recovered well after surgery, with no complications such as bleeding, biliary fistula, infection or liver failure. The duration of postoperative hospital stay was (7±4)days. (3) Follow-up and survival: all the 52 patients were followed up for 6-17 months, with a median follow-up time of 10 months. At 6 months after operation, all the 52 patients achieved of Eastern Cooperative Oncology Group performance status grade 1, Child-Pugh A of liver function, without tumor recurrence or metastasis. The overall survival rate was 100%(52/52).Conclusion:It is safe and feasible to perform laparoscopic anatomical hepatectomy by the "four doors of the liver" approach.

Assessment tools and surgical treatment strategies of synchronous colorectal cancer liver metastasis / 国际外科学杂志

At present, the medical system vigorously promotes multidisciplinary diagnosis and treatment model(MDT), and the timing of liver surgery for synchronous colorectal cancer with liver metastasis(sCRLM) is the focus of expert discussion. The same sCRLM case in different hospital or the different experts is likely to be a different treatment. On the one hand, that reflects the individualized characteristics of MDT. But on the other hand, it also reflects the lack of objective evaluation tools in sCRLM. The purpose of this study is to review the commonly used scoring tools of sCRLM, and to discuss the controversies of simultaneous or staged surgery for liver metastases, so as to inspire the clinical practice in this field.

Potential synergic mechanism of Wutou-Gancao herb-pair by inhibiting efflux transporter P-glycoprotein / 药物分析学报

Wutou-Gancao herb-pair is extensively used to attenuate the toxicity and enhance the efficacy of aconite. In this study, potential synergic mechanism of the herb pair was investigated by utilizing multiple ap-proaches. In silico and in vitro Caco-2 cell models were applied to study the potential binding mode of bioactive ingredients existing in liquorice with P-glycoprotein (P-gp), as well as the inhibition effects on P-gp. Additionally, anti-inflammatory activity of aconitine (AC) combined with active ingredients of liquorice, as well as pharmacokinetic patterns of AC after co-administration was investigated. Anti-inflammatory effect of AC (1 mg/kg) in rats was enhanced in combination with bioactive ingredients of liquorice (10 mg/kg). In the meanwhile, the exposure of AC in vivo was altered, in terms of Cmax and AUC. For instance, the Cmax and AUC were increased to 1.9 and 1.3 folds, respectively, when used in combination with liquiritigenin. The in silico study revealed the potential binding mode with outward facing conformation of P-gp. The resulting data obtained from transport of rhodamine-123 (Rh-123) across Caco-2 cell monolayer further indicated that the function of P-gp was inhibited by chemicals in liquorice. The synergic effect was therefore proposed to be attributed to inhibition of P-gp by liquorice since AC has been demonstrated to be the substrate of P-gp. The resuls revealed that potential synergic mechanism of Wutou-Gancao herb-pair by inhibiting function of key efflux transporter P-gp to enhance the exposure of AC in systematic circulation, and further the anti-inflammatory effect, which helps clarify the compatibility rationale of these two herbs.

Synergistic Effect of Baicalin and Wogonoside on NF-κB Signaling Pathway Based on Medium-efficiency Equation / 中国实验方剂学杂志

Objective:Quantitative analysis of anti-inflammatory synergistic pharmacodynamics mechanism of baicalin and wogonoside by medium efficiency principle. Method:inflammatory cell model was constructed by stimulating RAW264.7 cells by lipopolysaccharide （LPS） 100 μg·L-1 in vitro. The experiment was performed in the normal group， the model group， the andrographolide group （10 μmol·L-1）， the baicalin group （2.06，4.13，8.25，16.5，33，66，132 μmol·L-1） and the wogonoside group （2.94，5.88，11.75，23.5，47，94，188 μmol·L-1） and the baicalin-wogonoside combination group ［（2.06+2.94）（4.13+5.88）（8.25+11.75）（16.5+23.5）（33+47）（66+94）（132+188） μmol·L-1］. The levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in the cell culture supernatants after drug intervention for 50 min and 4 h were detected by enzyme-linked immunosorbent assay （ELISA） method. The level of nitric oxide （NO） in the cell culture supernatant after drug intervention for 24 h were detected by Griess method. Western blot was used to detect the activation levels of phosphorylation of nuclear factor-κB p65（p-NF-κB p65） and inducible nitric oxide synthase（iNOS） in cells after drug intervention for 2 h and 12 h. The fa/fu-dose profile of each indicator was drawn to observe the increase or decrease of effect. Result:Compared with normal group， the expression of p-NF-кB p65， iNOS and cytokines including TNF-α， IL-6 and NO （P<0.05，P<0.01） in the model group were significantly up-regulated. Compared with the model group， each group at high doses could inhibit the phosphorylation of NF-кB p65 protein（P<0.05），the baicalin group and the combined group could down-regulate the expression of iNOS protein in a concentration-dependent manner（P<0.01） and the baicalin group had no obvious inhibitory effect. each administration group at high dose could significantly inhibit the production of NO（P<0.05），but each group had no inhibitory effect on IL-6 production. The baicalin group and the combined group could significantly Inhibit the production of TNF-α（P<0.05） and there was no significant difference between the baicalin group and the model group. At the experimental dose， the fa/fu-dose table showed that the fa/fu value of p-NF-кB p65 and IL-6 in the combined group was not greater than the baicalin group and the wogonoside group. The fa/fu value of iNOS， TNF-α and NO in the combined group is higher than the baicalin group and the wogonoside group. Conclusion:The baicalin and wogonoside have different effects on different targets in the NF-κB pathway. The wogonoside is the main pharmacological substance in this combination and the combination shows different degrees of synergy or antagonism effects on different targets.