Magnolol and 5-fluorouracil synergy inhibition of metastasis of cervical cancer cells by targeting PI3K/AKT/mTOR and EMT pathways / 中草药·英文版

OBJECTIVE@#This study is designed to investigate the mode of action of the synergistic effect of 5-fluorouracil (5-FU) and magnolol against cervical cancer.@*METHODS@#Network pharmacological approach was applied to predict the molecular mechanism of 5-FU combined with magnolol against cervical cancer. CCK-8 assay, colony formation assay, immunofluorescence staining, adhesion assay, wound healing mobility assay, cell migration and invasion assay and Western blot analysis were conducted to validate the results of in silico study.@*RESULTS@#Phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway was identified as the key pathway in silico study. The experimental results showed that 5-FU combined with magnolol strongly inhibited cervical cancer cell proliferation, induced the morphological change of HeLa cells by down-regulating the expression of α-actinin, tensin-2 and vinculin. Moreover, magnolol enhanced inhibitory effect of 5-FU on the cell adhesion, migration and invasion. The phosphorylation of AKT and PI3K and the expression of mTOR were strongly inhibited by the combination of 5-FU and magnolol. Moreover, the expression of E-cadherin and β-catenin was upregulated and the expression of Snail, Slug and vimentin was down-regulated by the 5-FU together with magnolol.@*CONCLUSION@#Taken together, this study suggests that 5-FU combined with magnolol exerts a synergistic anti-cervical cancer effect by regulating the PI3K/AKT/mTOR and epithelial-mesenchymal transition (EMT) signaling pathways.

Cross-sectional study on the association between gut microbiota composition and blood pressure in children / 中国儿童保健杂志

【Objective】 To analyze the association between the composition of gut microbiota and blood pressure in children aged 6 - 9 years, in order to provide new ideas for childhood hypertension prevention and treatment. 【Methods】 A total of 411 children aged 6 - 9 years were recruited in Guangzhou from December 2015 to March 2017. The gut microbiota was characterized by 16S ribosomal RNA amplicon sequencing. The multivariate methods with unbiased variable selection in R (MUVR) were performed to identify the significant OTUs. Spearman correlation as well as multiple linear regression were used to explore the relationship between gut microbiota and blood pressure in children. 【Results】 Significant difference in β diversity index was observed between children with normal blood pressure and those with abnormal blood pressure (R2weighted=0.015,Pweighted=0.01; R2unweighted=0.027, Punweighted=0.001). After adjustment for covariates and controlling the false discovery rate (FDR), multiple linear regression analysis showed that blood pressure level in children decreased with the increasing abundance of OTU_3 (genus Blautia), OTU_131 (genus [Clostridium]_innocuum_group), OTU_1776 (genus Blautia), OTU_2159 (genus Prevotella) and OTU_91 (species Bifidobacterium_breve) (β:-0.18 --0.14; PFDR<0.05. In contrast, blood pressure in children increased with the increasing abundance of OTU_108(genus Sutterella), OTU_1(species Faecalibacterium_prausnitzii)、OTU_8(genus Roseburia), OTU_48 (genus Lachnoclostridium), OTU_81 (genus Coprococcus), OTU_401 (family Lachnospiraceae), OTU_1284 (family Lachnospiraceae) and OTU_2793 (family Lachnospiraceae)(β: 0.14 - 0.21; PFDR<0.05. The influence of gut microbiota on systolic pressure and diastolic pressure may be mediated by the increase of body mass index (BMI). 【Conclusions】 Pediatric blood pressure level is associated with the composition of gut microbiota, while BMI partially plays a mediating role in the relationship. It is recommended to modulate the abundance of microbiota as genus Blautia, Sutterella and so on to prevent hypertension in children.

Characteristics of changes in the demand for emergency medical services due to epidemics of sudden acute respiratory infectious diseases—Data analysis of pre hospital first aid during the period of optimizing the implementation of COVID-19 prevention and control measures in Zhejiang Province / 中华急诊医学杂志

Objective:To study characteristics of changes in the demand for emergency medical services during epidemic prevention and control "10 new measures" in Zhejiang province.Methods:The data of 26 emergency centers connected to the provincial integration platform of Zhejiang Province (hereinafter referred to as "provincial platform" ) were retrospectively analyzed, and the data were collected from one week before the implementation of "10 new measures" to the sixth week after implementation (December 1, 2022 to January 18, 2023). The collected information included: the number of 120 calls and ambulance services, the types of disease, age composition of patients, performance of emergency medical services.Results:From the second week of the implementation of "10 new measures" (December 15 to 21, 2022), the number of 120 calls and ambulance services were increased rapidly, and the peak occurred in the third week of implementation (December 21 to 28, 2022). Among the types of diseases, the number and proportion of patients with abnormal symptoms and respiratory diseases increased significantly, reaching the highest peak in the third week (December 21 to 28, 2022) and the fourth week (December 29, 2022 to January 4, 2023) of implementation, respectively. After the second week of implementation, the number of elderly patients aged 71 to 100 increased significantly, reaching a peak in the fourth week (December 29, 2022 to January 4, 2023), accounting for 60.76% of the total. During the epidemic period, the quality control indicators such as emergency dispatch time, ambulance dispatch time and medical treatment all fluctuated, but the changes were not significant.Conclusions:During the implementation of epidemic prevention and control "10 new measures", there were obvious characteristic changes in the demand for pre-hospital emergency in Zhejiang Province, but the quality of pre-hospital emergency medical was basically stable.

Activation of the complement C3/C3aR pathway in the prefrontal cortex mediates methamphetamine addiction in rats / 中国药理学与毒理学杂志

OBJECTIVE To investigate the role of the complement C3/C3aR signaling pathway in the prefrontal cortex and colon neuroglia cell interactions during meth-amphetamine(METH)addiction,to observe the effects of TLR4 inhibitors as well as complement C3 elimination on METH reward and relapse behavior,and to explore the neuroinflammatory mechanisms of complement C3 acti-vation in METH addiction.METHODS ①A 14 d and 28 d rat METH addiction model was established to observe the effects of TLR4 antagonist ibudilast 3 mg·kg-1 and 10 mg·kg-1 on self-administration,reward motivation,relapse,and natural reward behavior in METH-trained 14 d rats and the effects of 0.02 mg·kg-1 complement C3 antago-nist on self-administration behavior in METH-trained 28 d rats.② Differences in the expression of TLR4,NF-κB,GRP94,C3,cathepsin L,CD68,and GFAP in the pre-frontal cortex of each group were examined using West-ern blotting.③ In addition,the expression of ATF6 in the prefrontal cortex of each group and the effects on neuro-nal and microglia/macrophage INOS,CD206 GRP94,and complement C3/C3aR.RESULTS ① Endoplasmic reticulum stress occurred in neurons and microglia after METH exposure depending on GRP94 and unfolded pro-tein responses to the ATF6 pathway.In addition,it acti-vates the TLR4-NF-κB pathway.② Microglia with high complement C3/C3aR expression in the prefrontal cortex were recruited to synaptic pruning and phagocytic responses around neurons with high GRP94,comple-ment C3/C3aR expression and these effects were blocked by complement C3 antagonists.③ In the rec-tum,GRP94 functions as a molecular chaperone for com-plement C3 and cathepsin L.Crosstalk occurs between enteric neurons high in GRP94,complement C3,and macrophages high in C3aR,located in the submucosa,lamina propria,and muscular,respectively,and all of these effects are blocked by complement C3 antago-nists.④ Treatment with the TLR4 antagonist ibudilast inhibits self-administration,reward motivation,and cue-or METH-priming in METH-trained 14 d rats,but fails to affect natural reward behavior.Ibudilast treatment attenu-ates the TLR4-NF-κB inflammatory pathway and comple-ments C3/C3aR pathway in the prefrontal cortex.CON-CLUSION Activation of the complement C3/C3aR signal-ing pathway by TLR4-NF-κB inflammatory signaling in the prefrontal cortex mediates the METH addiction pro-cess,providing an experimental basis for the clinical treatment of METH addiction,and targeting TLR4/NF-κB inflammatory signaling and complement C3/C3aR may be a new way to intervene in METH addiction.

Best evidence summary for the management of injection site pain in subcutaneous patients / 中国实用护理杂志

Objective:To retrieve, evaluate and summarize the relevant evidence of subcutaneous injection in patients to reduce pain at the injection site, so as to provide reference for clinical practice.Methods:According to the evidence pyramid "6S" model, all evidence on subcutaneous injection and injection site pain, including guidelines, expert consensus, summary of evidence, clinical decision, systematic review, etc were retrieved from domestic and international guideline networks and databases. The search period was from database establishment to October 2, 2022. The literature quality evaluation and evidence grading system of Joanna Briggs Institute (JBI) Evidence-based Health Care Center was used to evaluate the literature quality and classify the evidence level.Results:A total of 12 articles were included, including 2 expert consensus, 6 systematic reviews, 2 best evidence summaries and 2 clinical guidelines. A total of 21 pieces of best evidence were summarized from 8 aspects, including pre-subcutaneous injection assessment, injection site, injection needle, injection position, injection method, precautions, personnel training and health education.Conclusions:This study summarized a comprehensive and practical subcutaneous injection method. Clinical practitioners can use evidence to administer subcutaneous injection to patients, reduce pain and improve patients ′ comfort.

Study on improvement effects and mechanism of rhein on immunoglobulin A nephropathy / 中国药房

OBJECTIVE To study the improvement effects and mechanism of rhein on immunoglobulin A nephropathy （IgAN） model rat based on signal transducer and activator of transcription 3 （STAT3） signaling pathway. METHODS Rats were randomly divided into normal control group， IgAN model group and rhein treatment group， with 10 rats in each group. IgAN model group and rhein treatment group were given combination of bovine serum albumin+lipopolysaccharide+carbon tetrachloride to induce IgAN model. Since the 7th week， rhein treatment group rats were intragastrically given relevant medicine， and normal control group and model group rats were given equal amount of normal saline intragastrically， for consecutive 4 weeks. After the last administration， the count of urine sediment erythrocyte， 24 h-urine total protein （UTP）， the levels of immunoglobulin A （IgA） in serum and secretory immunoglobulin A （sIgA） in intestinal mucosa were detected. The pathological changes of Peyer’s patch in renal cortex and intestinal mucosa and IgA deposition in renal cortex were observed. The expressions of interleukin-17 （IL-17）， IL- 6 and transforming growth factor β （TGF-β） in Peyer’s patch of intestinal mucosa in rats were detected. The expressions of STAT3 and related orphan receptor γt （RORγt） mRNA in Peyer’s patch were detected. The expressions of p-STAT3 and RORγt proteins in Peyer’s patch were detected. RESULTS Compared with normal control group， the count of urine sediment erythrocyte， 24 h-UTP， the levels of IgA in serum and sIgA in intestinal mucosa were increased significantly in IgAN model group （P＜0.01）； enlarged renal corpuscles， dilated renal sacs， obvious intratubular mesangial hyperplasia and fibrosis were observed in renal cortex； the volume and germinal center of Peyer’s patch in intestinal mucosa increased； IgA deposition of renal cortex zxyylxk20220103） was obvious； the expressions of IL-17， IL-6 and TGF-β in Peyer’s patch， mRNA expressions of STAT3 and RORγt， protein expressions of p-STAT3 and RORγt were increased significantly （P＜0.01）. Compared with IgAN model group，above indexes were decreased significantly in rhein treatment group （P＜0.01）， pathological damage of renal cortex was improved， the volume of Peyer’s patch and germinal center of intestinal mucosa were reduced， and IgA deposition in renal cortex was weakened. CONCLUSIONS Rhein can improve IgAN model rats， the mechanism of which may be associated with inhibiting STAT3 signaling pathway and regulating immune function of Peyer’s patch in intestinal mucosa.

Experimental study on synergistic inhibition of tumor growth by microbubble cavitation induced by low intensity ultrasound combined with hemocoagulase and Endostar / 中华超声影像学杂志

Objective:To investigate the synergistic effect of physical intervention and chemotherapeutic drug therapy on tumor growth by blocking tumor microvessels and injecting chemotherapy drug Endostar (ecombinant human vascular endostatin injection) to inhibit tumor neovascularization by low intensity ultrasound induced microbubble cavitation combined with hemocoagulase.Methods:Seventy-five male NU/NU mice bearing human-derived lung adenocarcinoma, weighing 25-30 g, were randomly divided into microbubble-enhanced ultrasonic cavitation+ Endostar group (MEUC+ Endostar), microbubble-enhanced ultrasonic cavitation+ hemocoagulase+ Endostar group (MEUC+ HC+ Endostar), microbubble-enhanced ultrasonic cavitation (MEUC), Endostar group (Endostar) and sham group. Fifteen mice in each group were given the corresponding treatment intervention for 4 consecutive days followed by 4 days of aseptic feeding. Two-dimensional ultrasound and contrast-enhanced ultrasound (CEUS) were performed before intervention, immediately after intervention and 4 days after intervention, respectively. Tumor tissues were obtained for vascular endothelial growth factor immunofluorescence staining, and microvessel density (MVD) was observed.Results:There was no difference in tumor volume between the groups before the intervention ( P>0.05). Immediately after the intervention, filling defects were observed in MEUC+ Endostar group, MEUC+ HC+ Endostar group and MEUC group, while filling was good in Endostar group and sham group; 4 days after the intervention, filling defects were observed in MEUC+ Endostar group and MEUC+ HC+ Endostar group. The filling defect was still present in Endostar group, while partial recovery of perfusion was performed in MEUC group, and PI and AUC were still significantly lower in MEUC+ HC+ Endostar group than in the other groups ( P<0.05). When tumor tissues were obtained 4 days after the intervention, the MVD in MEUC+ HC+ Endostar group was significantly lower than that in the remaining groups, and the difference of MVD in tumor tissue was statistically significant ( P<0.05). Conclusions:Low intensity ultrasound induced microbubble cavitation combined with hemocoagulase and Endostar can produce a synergistic effect in blocking tumor microvessels and inhibiting tumor angiogenesis, which can more effectively inhibit tumor growth.

Self-referential network characteristics in patients with subjective cognitive decline accompanied by metacognitive impairment / 中华神经医学杂志

Objective:To explore the characteristics of self-referential network (SRN) functional connectivity in subjective cognitive decline (SCD) patients with normal and impaired metacognition.Methods:Seventy-one subjects were selected from Alzheimer's Disease Neuroimaging Initiative (ADNI) database, with 25 cognitively normal controls and 46 SCD patients. The metacognitive level of SCD patients was assessed by Everyday Cognition Scale (ECog), and then, they were divided into a metacognitively normal group ( n=25, metacognitive scores>-0.074) and a metacognitively impaired group ( n=21, metacognitive scores≤-0.074). Results of Geriatric Depression Scale (GDS), Montreal Cognitive Scale (MoCA), Mini‐Mental State Examination (MMSE), Rey Auditory Word Learning Test (RAVLT), Logical Memory Scale, expressions of pathological markers (cerebrospinal fluid β-amyloid protein [Aβ], total tau protein [t-tau] and phosphorylated tau protein [p-tau]), brain glucose metabolism, and functional magnetic resonance imaging (fMRI) were collected and compared among the 3 groups. Independent component analysis (ICA) was used to extract SRN and analyze the different brain regions among the 3 groups; Pearson correlation was used to analyze the correlations of SRN functional connectivity changes with cognitive scales and pathological markers. Results:No significant differences in demographic characteristics (age and gender), scores of GDS, MoCA and MMSE, or levels of Aβ, t-tau, p-tau and brain glucose metabolism were noted among the 3 groups ( P>0.05). The metacognitive scores in metacognitively impaired group were significantly lower than those in metacognitively normal group and cognitively normal controls ( P<0.05). Significant difference in the functional connectivity of bilateral anterior cingulate gyrus and bilateral orbitofrontal cortex was noted among the 3 groups (TFCE-FWE correction, P<0.01, voxel>100); compared with the cognitively normal controls, the metacognitively impaired group showed significantly decreased functional connectivity of bilateral orbitofrontal cortex, while the metacognitively normal group showed enhanced functional connectivity of bilateral orbitofrontal cortex (TFCE-FWE correction, P<0.01, voxel>100); compared with the metacognitively normal group, the metacognitively impaired group had statistically decreased functional connectivity of bilateral orbitofrontal cortex (TFCE-FWE correction, P<0.01, voxel>100). Further correlation analysis showed that difference value of functional connectivity of bilateral orbitofrontal cortex between metacognitively impaired group and cognitively normal controls was negatively correlated with RAVLT-immediate scores ( r=-0.445, P=0.043); difference value of functional connectivity of bilateral orbitofrontal cortex between metacognitively impaired group and metacognitively normal group was negatively correlated with RAVLT-immediate scores ( r=-0.463, P=0.034). Conclusion:SCD patients with different metacognitive levels have characteristic SRN functional connectivity changes; impaired metacognition may be an early feature of Alzheimer's disease.

Construction of a noninvasive predictive model for liver fibrosis in chronic hepatitis B patients with HBeAg positive and alanine aminotransferase lower than 2 upper limit of normal / 中华临床感染病杂志

Objective:To construct a non-invasive predictive model for liver fibrosis in HBeAg positive chronic hepatitis B (CHB) patients with alanine aminotransferase (ALT) lower than 2 upper limit of normal (ULN).Methods:The clinical data of 279 HBeAg positive CHB patients with ALT<2×ULN admitted in Zhejiang Provincial People’s Hospital from October 2014 to December 2020 were retrospectively analyzed. According to the pathological results of liver biopsy, there were 117 cases of mild liver fibrosis (S0-S1) and 162 cases of significant liver fibrosis (S2-S4). The independent predictors of liver fibrosis were analyzed by multivariate logistic regression analysis and a noninvasive predictive model was constructed. The model for predicting the severity of liver fibrosis was evaluated by receiver operating characteristic curve (ROC).Results:Multivariate logistic regression analysis showed that age, prothrombin time (PT), aspartate aminotransferase (AST), anti-HBc and HBV DNA were independent predictors of liver fibrosis ( OR=1.055, 1.365, 1.027, 1.231, 0.763, all P<0.05). The area under the ROC curve (AUR) of the model was 0.772 (95% CI: 0.716-0.828, P<0.05), the sensitivity and specificity for the diagnosis of significant liver fibrosis were 79.5% and 70.9% at the cut-off value of 0.504. The AUC of APRI model and FIB-4 index model for assessing significant liver fibrosis in CHB patients with HBeAg-positive and ALT<2×ULN were 0.720 and 0.671, respectively, which were lower than that of the current model (all P<0.05). Conclusion:The noninvasive predictive model constructed in this study has a high diagnostic value for evaluating the severity of liver fibrosis in CHB patients with HBeAg positive and ALT<2×ULN.

Barriers to implement early mobilization by nursing in adult ICUs:A systematic review and summary analysis / 中国实用护理杂志

Objective:To systematically review the barriers encountered by nursing staff in the implementation of early activities in adult ICU units.Methods:A systematic search was conducted on CNKI, Wanfang Database, VIP Database, China Biomedical Database, PumMed, Web of Science, Cochrane Library and EMBASE for the research on the obstacles of early activity nursing implementation in adult ICU from the establishment of the database to July 2020, and the final integrated analysis of the included literature was carried out.Results:A total of 26 articles were included, and 59 obstacles in 5 categories were integrated, including 6 kinds of technical level, 13 kinds of organizational culture level, 7 kinds of personnel level, 4 kinds of structural level, and 29 kinds of 6 sub categories of patients level. The most frequent obstacles were unstable condition of patients, sedation or continuous deep sedation, low staffing level, disturbance of consciousness of patients, insufficient equipment related to early activities, and low willingness or compliance of patients to participate.Conclusion:The nursing staff are facing with many obstacles in guiding and assisting ICU adult patients to carry out early activities. It is necessary to formulate modified policies aiming at changeable factors in order to promote the application of early activities in adult ICU units.

Expression and significance of granulocyte colony-stimulating factor and granulocyte- macrophage colony-stimulating factor in patients with acute respiratory distress syndrome / 中国基层医药

Objective:To investigate the expression and significance of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with acute respiratory distress syndrome (ARDS).Methods:The clinical data of 81 patients with ARDS who received treatment between February 2018 and July 2020 in Linhai Second People's Hospital, China (group A) and 69 healthy controls who concurrently received physical examination (group B) were retrospectively analyzed. Serum levels of G-CSF, GM-CSF and oxygenation index (OI) measured before treatment in the group A were compared with the levels measured in the control group. Serum levels of G-CSF and GM-CSF measured before treatment were compared between patients with different disease severities in the group A. The correlation between serum G-CSF and GM-CSF levels and disease condition was analyzed. The significance of serum G-CSF and GM-CSF levels in the diagnosis of ARDS was investigated.Results:Before treatment, serum G-CSF and GM-CSF levels in the group A were (201.89 ± 19.44) ng/L, (48.95 ± 6.03) ng/L, respectively, which were significantly higher than those in the group B [(38.13 ± 5.22) ng/L, (7.71 ± 0.92) ng/L, t = 67.889, 56.228, both P < 0.001]. OI in the group A was significantly lower than that in the group B [(159.09 ± 16.81) mmHg vs. (385.13 ± 20.34) mmHg, t = 74.519, P < 0.001). In group A, serum levels of G-CSF and GM-CSF were (271.99 ± 23.15) ng/L and (65.07 ± 8.38) ng/L respectively in patients with severe acute respiratory distress syndrome ( n = 13), (203.14 ± 18.36) ng/L and (50.91 ± 7.18) ng/L respectively in patients with moderate acute respiratory distress syndrome ( n = 30), and (176.92 ± 15.98) ng/L and (41.89 ± 6.02) ng/L, respectively in patients with mild acute respiratory distress syndrome ( n = 38). There was significant difference among patients with severe, moderate and mild acute respiratory distress syndrome ( F = 133.201, 57.116, both P < 0.05). Serum levels of G-CSF and GM-CSF in group A were negatively correlated with OI ( r = -0.819, -0.824, both P < 0.05). The area under the receiver operating characteristic curve of serum levels of G-CSF and GM-CSF and their combination were 0.780 (95% CI: 0.628-0.933), 0.752 (95% CI: 0.590-0.913) and 0.912 (95% CI: 0.835-0.989), respectively. The Youden index was 0.686, 0.696 and 0.739, respectively. The area under the receiver operating characteristic curve and the Youden index of the combined detection of serum levels of G-CSF and GM-CSF were highest. Conclusion:Serum levels of G-CSF and GM-CSF in patients with ARDS were higher than those in healthy controls. Higher serum levels of G-CSF and GM-CSF led to more severe disease condition. Serum levels of G-CSF and GM-CSF in combination has a higher value in the diagnosis of ARDS than serum levels of G-CSF and GM-CSF alone.

Clinical application of dexmedetomidine in pediatrics / 中国小儿急救医学

Dexmedetomidine(DEX) is a new type of highly selective α2 adrenergic receptor agonist with multiple effects, such as sedation, analgesic, anti-anxiety and inhibition of sympathetic nervous system activity.DEX is usually used as an anesthetic adjuvant and as an sedative and analgesic in PICU, also possessing effects of preventing and treating emergence agitation, counteracting postoperative shivering and organ protection.This paper summarized the clinical application of DEX in pediatric field.

Treatment of vascular cognitive impairment / 国际脑血管病杂志

The pathogenesis of vascular cognitive impairment (VCI) remains unclear. There is a lack of specific treatment methods, and there is no unified evaluation standard for its clinical efficacy. In recent years, in addition to traditional drug therapy, the role of non-drug therapy in VCI therapy has gradually attracted attention. This article reviews the drug therapy, non-drug therapy and preventive interventions to improve the cognitive symptoms of VCI.

Clinical application of dexmedetomidine in pediatrics / 中国小儿急救医学

Dexmedetomidine(DEX) is a new type of highly selective α 2 adrenergic receptor agonist with multiple effects, such as sedation, analgesic, anti-anxiety and inhibition of sympathetic nervous system activity.DEX is usually used as an anesthetic adjuvant and as an sedative and analgesic in PICU, also possessing effects of preventing and treating emergence agitation, counteracting postoperative shivering and organ protection.This paper summarized the clinical application of DEX in pediatric field.

Feasibility and toxicity of EC-T dose-dense adjuvant chemotherapy: A real world study in Chinese early-stage breast cancer patients with high recurrence risk / 中华肿瘤杂志

Objective@#We aimed to examine the feasibility and toxicity of EC-T dose-dense regimen and to demonstrate the suitable dose of epirubicin in a Chinese early-stage breast cancer population with high recurrence risk.@*Methods@#370 patients with early-stage breast cancer at high risk of recurrence were treated with EC-T dose-dense adjuvant chemotherapy and prophylactic administration of recombinant human granulocyte stimulating factor (G-CSF). The incidence of delayed chemotherapy, drug reduction and adverse reactions were retrospectively analyzed.@*Results@#370 patients completed the planned eight cycles of chemotherapy, 50 patients experienced chemotherapy delay, and 90 had chemotherapy dose reductions. Overall, 61.1% of the patients experienced grade 3 or 4 hematology toxicities, 4.1% of the patients experienced grade 3 gastrointestinal toxicity, 16.3% experienced grade 3 or 4 liver malfunction, and 1.9% experienced grade 3 alopecia. In the multivariate analysis, pretreatment epirubicin levels were associated with comprehensive and hematology toxicity risk (OR=1.268, P=0.046; OR=1.244, P=0.036). With G-CSF support, the probability of grade 3-4 dose limiting toxicity, i. e. neutropenia, abnormal liver function, and gastrointestinal adverse effects did not increase as the epirubicin dose level increased(P>0.05). However, there were no statistically significant associations between epirubicin grade and treatment delay (P=0.814) or dose reduction (P=0.282).@*Conclusions@#EC-T dose-dense chemotherapy shows tolerable toxicity. High dose level is not a limiting factor for this regimen. With G-CSF support, epirubicin 85-90 mg/m2 is appropriate tolerance dose for Chinese early breast cancer patients with high recurrence risk.

Tetramethylpyrazine promotes bone marrow repair in a C57 mouse model of X-rayinduced immune-mediated bone marrow failure / 南方医科大学学报

OBJECTIVE@#To observe the therapeutic effect of tetramethylpyrazine on immune-mediated bone marrow failure (BMF) induced by different doses of X-ray exposure in C57 mice.@*METHODS@#C57BL6 mice were randomized into 4 groups, including a blank control group and 3 X-ray exposure groups with X-ray exposure at low (5.0 Gy), moderate (5.75 Gy), and high (6.5 Gy) doses. After total body irradiation with 0.98 Gy/min X-ray. The mice as recipient received injections of 4×10 lymphocytes from DBA/2 mice via the tail vein within 4 h. The survival rate of the recipient mice, peripheral blood cell counts, bone marrow nucleated cell count, and bone marrow pathology were examined at 14 days after the exposure. In the subsequent experiment, C57 mice were exposed to 5.0 Gy X-ray and treated with intraperitoneal injection of tetramethylpyrazine at the low (5 mg/mL), moderate (10 mg/mL), or high (20 mg/mL) doses (12 mice in each group) for 14 consecutive days, and the changes in BMF were observed.@*RESULTS@#X-ray exposure, especially at the high dose, resulted in significantly lowered survival rate in the mouse models of BMF at 14 days. As the X-ray dose increased, the mice showed significantly reduced peripheral blood counts of red blood cells, white blood cells, platelets and lowered bone marrow nucleated cell counts with obvious bone marrow congestion and reduction of nucleated cells ( < 0.05 or 0.001). In the mice exposed to 5.0 Gy X-ray, tetramethylpyrazine at the high dose most obviously increased bone marrow nucleated cells ( < 0.01) and red blood cells ( < 0.001), and even at the low dose, tetramethylpyrazine significantly increased the counts of white blood cells ( < 0.05) and platelets ( < 0.01) following the exposure. Tetramethylpyrazine dose-dependently alleviated bone marrow hyperemia, increased bone marrow nucleated cell counts, and lowered Fas protein expression in the bone marrow.@*CONCLUSIONS@#X-ray irradiation at 5.0 Gy is suitable for establish mouse models of immune-mediated BMF. Tetramethylpyrazine promotes bone marrow repair by regulating Fas cell apoptosis signals, which further expands the traditional Chinese medicine theory of "removing blood stasis to create new."

Biodegradable Magnesium Alloy Stents as a Treatment for Vein Graft Restenosis

PURPOSE: To explore the effects of biodegradable magnesium alloy stents (BMAS) on remodeling of vein graft (VG) anastomotic restenosis. MATERIALS AND METHODS: To establish a VG restenosis model, seventy two New Zealand rabbits were randomly divided into three groups according to whether a stent was implanted in the graft vein or not. BMASs and 316L stainless steel stents were implanted in BMAS and 316L groups, respectively, while no stent was implanted in the no-treatment control group (NC group). Loss of lumen diameter in the graft vein was measured in all three groups. Upon harvesting VG segments to evaluate intimal proliferation and re-endothelization, the degradation and biological safety of the stents were observed to explore the effects of BMAS on VG remodeling. RESULTS: Model establishment and stent implantation were successful. The BMAS reduced lumen loss, compared with the control group (0.05±0.34 mm vs. 0.90±0.39 mm, p=0.001), in the early stage. The neointimal area was smaller in the BMAS group than the 316L group after 4 months (4.96±0.66 mm2 vs. 6.80±0.69 mm2, p=0.017). Re-endothelialization in the BMAS group was better than that in the 316L group (p=0.001). Within 4 months, the BMAS had degraded, and the magnesium was converted to phosphorus and calcium. The support force of the BMAS began to reduce at 2–3 months after implantation, without significant toxic effects. CONCLUSION: BMAS promotes positive remodeling of VG anastomosis and has advantages over the conventional 316L stents in the treatment of venous diseases.

Effects of monobutyl phthalate on migration and invasion of mouse Leydig tumor cells / 中华预防医学杂志

Objective@#This study aimed to investigate the influence of monobutyl phthalate (MBP) on the expressions of epithelial-mesenchymal transition (EMT)-related proteins, migration and invasion of mouse Leydig tumor cells (MLTC-1) cells.@*Methods@#After exposed to different doses of MBP (0、10-7、10-6, 10-5, 10-4, 10-3 mol/L) for 24 h or 48 h, cell viability was determined by 3-(4 5-dimethyl-2-thiazolyl)-2 5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Expressions of vimentin, E-cadherin, N-cadherin and Snail proteins related to EMT were detected by Western blot. The ability of migration and invasion of MLTC-1 were assessed by wound healing assay and Transwell Boyden chamber assay, respectively.@*Results@#Relative expressions of vimentin, Snail and N-cadherin proteins were promoted ((1.56±0.07) vs (1.78±0.08), (1.22±0.06) vs (1.44±0.07), (1.33±0.11) vs (2.19±0.06), all P values were<0.001) and E-cadherin (0.66±0.09) vs (0.47±0.06), P<0.001,protein was inhibited after the cells stimulated with MBP (0, 10-7 and 10-6 mol/L). The capability of wound closure of MLTC-1 cells were (6.64±2.07)%, (15.61±2.83)%, (39.91±0.33)%, respectively and the invading/migrating cells were (32.67±3.51), (57.67±2.52), (82.67±6.51), respectively, which were obviously increased under MBP treatments (0, 10-7 and 10-6 mol/L) (all P values were <0.001).@*Conclusion@#Monobutyl phthalate affected the expressions of EMT-related proteins and enhanced the migration and invasion of MLTC-1 cells.

Temporal expression of triggering receptors expressed by myeloid cells-1 during the development of experimental periodontitis in rat / 中华口腔医学杂志

Objective@#To illuminate the temporal expression of the triggering receptor expressed on myeloid cells-1 (TREM-1) in the experimental periodontitis in rat and to investigate the function of TREM-1 in the pathogenesis of experimental periodontitis in rat.@*Methods@#The experimental periodontitis model was established in the maxillary first molar by means of 'wire ligation + vaccination periodontal pathogen Porphyromanus gingivalis (Pg) + high-sugar diet' in Sprague-Dawley (SD) rats. The experimental animals were divided into six groups: the control group and each of the time points of establishing the models for one week and two to five weeks. There were six rats for each of the six groups. The bone loss of the palatal site was calculated to estimate whether the periodontitis model was successfully established. The expression of TREM-1, proinflammatory cytokines: tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6, anti-inflammatory cytokines: IL-4, IL-10 and transforming growth factor-β (TGF-β) were examined by using quantitative real-time PCR. The expression level of TREM-1 protein was analyzed by the method of immunohistochemistry.@*Results@#The average bone loss area of the palatal site was (0.17±0.04) mm2 in the group of three weeks and was statistically significant (P<0.05) compared to the control group [(0.10±0.01) mm2]. The experimental periodontitis model was successfully established in the group of three weeks. The expression of TREM-1 increased significantly in the inflamed periodontal tissues and reached to its maximum expression in the three weeks group accounting for 159.50±38.26 in protein expression and 4.35±0.60 in mRNA expression, respectively. TREM-1 expression difference between the three weeks group and control group was statistically significant (P<0.01). The expression of IL-6 by gingival tissues was correlated with the mRNA level of TREM-1 (r=0.813 P=0.049).@*Conclusions@#TREM-1, as a proinflammatory receptor, could facilitate the periodontal inflammatory response. The possible way of TREM-1 to promote inflammation may be through controling the expression of IL-6.

Genetic polymorphisms of autophagy-related gene 5 (ATG5) rs473543 predict different disease-free survivals of triple-negative breast cancer patients receiving anthracycline- and/or taxane-based adjuvant chemotherapy / 癌症

BACKGROUND@#Autophagy plays a crucial role in chemotherapy resistance of triple-negative breast cancer (TNBC). Hence, autophagy-related gene 5 (ATG5), an essential molecule involved in autophagy regulation, is presumably associated with recurrence of TNBC. This study was aimed to investigate the potential influence of single-nucleotide polymorphisms in ATG5 on the disease-free survival (DFS) of early-stage TNBC patients treated with anthracycline- and/or taxane-based chemotherapy.@*METHODS@#We genotyped ATG5 SNP rs473543 in a cohort of 316 TNBC patients treated with anthracycline- and/or taxane-based chemotherapy using the sequenom's MassARRAY system. Kaplan-Meier survival analysis and Cox proportional hazard regression analysis were used to analyze the association between ATG5 rs473543 genotypes and the clinical outcome of TNBC patients.@*RESULTS@#Three genotypes, AA, GA, and GG, were detected in the rs473543 of ATG5 gene. The distribution of ATG5 rs473543 genotypes was significantly different between patients with and without recurrence (P = 0.024). Kaplan-Meier survival analysis showed that patients carrying A allele of ATG5 rs473543 had an increased risk of recurrence and shorter DFS compared with those carrying the variant genotype GG in rs473543 (P = 0.034). In addition, after adjusting for clinical factors, multivariate Cox regression analyses revealed that the AA/GA genotype of rs473543 was an independent predictor for DFS (hazard risk [HR], 1.73; 95% confidence interval [CI], 1.04-2.87; P = 0.034). In addition, DFS was shorter in node-negative patients with the presence of A allele (AA/GA) than in those with the absence of A allele (P = 0.027).@*CONCLUSION@#ATG5 rs473543 genotypes may serve as a potential marker for predicting recurrence of early-stage TNBC patients who received anthracycline-and/or taxane-based regimens as adjuvant chemotherapy.