Status and challenges of neoadjuvant immunotherapy for hepatocellular carcinoma / 中华外科杂志

With the development of modern liver surgical techniques and the progress of perioperative management,the survival rate after resection of hepatocellular carcinoma has been greatly improved,but the high recurrence and metastasis rate still limits the long-term survival after surgery. Preoperative neoadjuvant therapy has been confirmed to significantly reduce the postoperative recurrence rate and prolong survival in other types of cancer,but there has been a lack of effective systemic therapy for hepatocellular carcinoma for a long time,so the efficacy and regimen of neoadjuvant therapy for hepatocellular carcinoma are still controversial. PD-1/PD-L1 monoclonal antibody combined with anti-angiogenic targeted drugs has become a first-line regimen in systemic therapy for advanced hepatocellular carcinoma. This regimen has definite efficacy and high safety,bringing hope for neoadjuvant therapy of hepatocellular carcinoma. Recently,three clinical trials of neoadjuvant immunotherapy for hepatocellular carcinoma have been published internationally,which preliminarily suggest the efficacy and safety of neoadjuvant immunotherapy for hepatocellular carcinoma and lay a solid foundation for carrying out larger sample clinical studies in the future.

Metabonomics research of gabex mesylate on septic-induced acute lung injury in rats / 中华急诊医学杂志

Objectve:To study the effect of gabexate mesylate (GM) on acute lung injury (ALI) in septic rats based on metabonomics.Methods:Fifty-seven SD rats were randomly(random number) divided into three groups: sham operation group (SC group), cecal ligation puncture induced septic ALI group (CLP group), and intraperitoneal administration of GM at 1 h after CLP (CLP-GM group). Twenty-four h after the experiment, the survival of rats in the SC, CLP and CLP-GM groups was observed, the lung tissue was collected for HE staining to observe the pathological changes, and the plasma was collected for metabonomics detection to analyze the characteristics of metabolites.Results:Compared with the SC group, the infiltration of inflammatory cells in the lung tissue of rats in the CLP groupincreased significantly, and the metabolic profile of plasma changed significantly. However, the pathological and metabonomic characteristics of the CLP-GM group showed that the above changes were reversed after the application of GM. Twelve major differential metabolites were found in plasma. The metabolic pathways involved in the disorder included biosynthesis of phenylalanine, tyrosine and tryptophan, phenylalanine metabolism and sphingolipid metabolism.Conclusions:GM may improve septic ALI by regulating amino acid metabolism, sphingolipid metabolism and other metabolic pathways.

Quality of life and determinants among children with dyslexia in China / 中国学校卫生

Objective@#To examine the Quality of life among school-aged children with dyslexia in target city and to provide scientific evidence for improving the quality of life of children with dyslexia.@*Methods@#By using cluster sampling,students from grade 3 to grade 6 from 6 primary schools in a middle-sized were selected and administered with questionnaire survey. According to the criteria of dyslexia, dyslexic children and non-dyslexic children were identified and the difference of the Quality of Life was compared.@*Results@#Totally 3 673 children were collected, and 119 of them were identified as dyslexia(3.24%).The prevalence of dyslexia differed by gender,grades,educational level of parents(χ2=24.77,11.75,18.50,9.79,P<0.05). The Quality of Life which below the average proportion accounted for 30.3% of dyslexic children and 16.7% of normal children. Quality of life scored signiticantly different between dyslexic children and non-dyslexia children, including psychosocial functioning domain(134.54±30.88)(143.49±32.53), physical and mental health domain(2.71±0.84)(2.92±0.81) vs (2.83±0.90)(3.06±0.87), the living satisfaction domain(2.95±0.87)(3.14±0.87)(t=-6.09，-5.48，-5.44，-4.50，P<0.01),with dyslexic group significantly lower than that of non-dyslexic group.@*Conclusion@#The Quality of Life of Dyslexic children was in a poor condition.

Research on the Termination of Drug Supported Medical Policy from the Perspective of Multiple Streams Theory / 中国卫生经济

Using the multiple streams theory to better understand the termination of drug supported medical policy and to draw a conclusion that the drug supported medical policy finally came true with the active promotion of policy entrepreneurs,such as government,experts and scholars under the organic combination of problems,policy plans and political situation.The termination of drug supported medical policy would inevitably lead to the obstruction of relevant interest groups.To eliminate the resistance of the termination of drug supported medical policy,it needed to completely abolish drug supported medical policy.After the completion of the top-level design,the reform of financial system and the optimization of doctor's performance incentive mechanism must be done well.

Effect of BMI-1 on radiosensitization of esophageal carcino-ma cells after silencing of BMI-1 gene / 中华放射肿瘤学杂志

Objective To investigate the effects of BMI-1 expression inhibition by RNA interference on the radiosensitivity of esophageal cancer TE-13 cells and its mechanism.Methods The siRNA based on the sequence of BMI-1 mRNA was synthesized to transfect cultured TE-13 cells as BMI-1 siRNA group,a negative one was synthesized to transfect cultured TE-13 cells as negative control group (NC group),and untransfected TE-13 cells were named as control group.The expression of the BMI-1 mRNA and protein in TE-13 cells was measured by quantitative real-time PCR and Western blot,respectively.The cell proliferation and the radiosensitivity of TE-13 cells were measured by MTS and colony-forming assay,respectively.Flow cytometry was used to analyze cell cycle and apoptosis.The expression of BCL-2 and BAX in TE-13 cells was measured by Western blot.Comparison between groups was made by analysis of variance.Results The BMI-1 siRNA group had significantly lower expression of BMI-1 mRNA and protein than the control group and the NC group (P=0.000,0.000).The proliferation of TE-13 cells in the BMI-1 siRNA group decreased significantly after irradiation (P=0.031).The colony-forming assay showed that the BMI-1 siRNA group had a significantly higher radiosensitivity than the control group and the NC group (P=0.000).After irradiation,the BMI-1 siRNA group had a significantly lower percentage of cells in G2/M phase than the control group and the NC group (P=0.000,0.000).The BMI-1 siRNA group had a significantly increased apoptosis rate (P=0.000,0.000),significantly reduced expression of BCL-2(P=0.000,0.000),and significantly increased expression of BAX after irradiation (P=0.000,0.000).Conclusions BMI-1 siRNA can inhibit the expression of BMI-1 gene in esophageal cancer TE-13 cells,eliminate the cell cycle arrest in G2/M phase,induce cell apoptosis after ionizing irradiation in vitro,and increase the radiosensitivity,which may be related to the regulation of the expression of BCL-2 and BAX.

Synthesis and biological evaluation of H2S donor ADT-OH derivatives / 中国药科大学学报

5-(4-Hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADT-OH) is a slowly releasing H2S donor with some neuroprotective effect.In order to study the structure-activity relationships,seventeen compounds (Y1-Y17) were synthesized by modification of ADT-OH at the aromatic ring position,and their structures were confirmed by 1H NMR,13C NMR and HR-MS.Among them,6 compounds (Y4,Y13-Y17) were novel compounds.Their effects had been evaluated on HT-22 hippocampal neuron cells damaged by glutamate with MTF method.The pharmacological results demonstrated that all the Y compounds had potent neuroprotection at most of the tested concentrations (1-100 μmol/L).Compounds Y1-Y9 and Y11 significantly improved the survival rates of the damaged cells at 1-100 μmol/L (P ＜0.01).Specially,compounds Y1,Y4,Y6-Y9,Yu are more potent than their parent compound ADT-OH at concentration of 1-10 μmol/L,which is worthy of further study.

Prognostic Impact of Progesterone Receptor Status in Chinese Estrogen Receptor Positive Invasive Breast Cancer Patients / 한국유방암학회지

PURPOSE: Estrogen receptor (ER) and progesterone receptor (PR) have been used as indicators of endocrine system status since the mid-1970s in the clinical management of breast cancer. The predictive role of ER in endocrine therapy is undisputed, but the prognostic value of PR is still debated. The aim of this study was to investigate the clinical characteristics and prognosis of ER positive breast cancer with different PR expression levels. METHODS: A population cohort of 3,030 primary invasive ER positive breast cancer patients from a single cancer center underwent surgery and received adjuvant endocrine therapy from 2004 to 2010. The clinical and biological features of these patients with high PR-expressing tumors were compared with those of patients with low PR-expressing tumors. The follow-up data for disease-free survival (DFS), overall survival (OS), and breast cancer specific survival (BCSS) was obtained from 2,778 patients. Cox regression analysis was used to correlate biomarkers and tumor characteristics with DFS, OS, and BCSS. RESULTS: Tumors with low PR expression had more invasive pathological features and biological indexes than those with high PR expression. Low PR expression was an independent poor prognostic factor for DFS (p=0.014; hazard ratio [HR], 0.781; 95% confidence interval [CI], 0.641–0.950), OS (p=0.002; HR, 0.699; 95% CI, 0.560–0.873), and BCSS (p=0.005; HR, 0.714; 95% CI, 0.566–0.902). Furthermore, in low PR expressing tumors, patients who received chemotherapy had better DFS (p=0.002; HR, 0.449; 95% CI, 0.268–0.751), OS (p<0.001; HR, 0.341; 95% CI, 0.192–0.606), and BCSS (p<0.001; HR, 0.292; 95% CI, 0.156–0.549) than patients who did not received chemotherapy. CONCLUSION: Patients with ER positive invasive breast cancer with low PR expressing tumors have a worse prognosis than those with high PR expressing tumors, and these patients can benefit from chemotherapy.

Synthesis and biological evaluation of H2S donor memantine derivatives / 中国药科大学学报

@#H2S has a role of protecting neurons from ischemia-reperfusion injury and significantly reducing the cerebral infarction area, but high concentration of H2S can induce neurotoxicity. Memantine, a N-methyl-D-aspartic acid(NMDA)receptor antagonist, could reduce the neurotoxicity of H2S at high concentration. Nine novel structures(compounds I1-I9)were designed by coupling(4-hydroxy phenyl)-3H-1, 2-dithiole-3-thione(ADT-OH)with memantine through alkanes as linkers and synthesized by four-step reactions from ADT-OH. Their neuroprotection against damage induced by glutamate on HT-22 cells was evaluated by MTT method. The results indicated that these compounds markedly increased the survival rates of damaged HT-22 cells at the concentration of 1 μmol/L(P< 0. 01), which suggested that these compounds could preferably protect neurons against damage induced by glutamate.

Effect of RNAi targetingBMI-1 gene on radiosensitivity of esophageal carcinoma cells / 中国癌症杂志

Background and purpose:B cell-specific MLV integration site 1 (BMI-1) gene plays an important role in DNA damage after exposure to irradiation. The present study aimed to investigate the effect ofBMI-1 on radio-sensitivity of esophageal carcinoma cell after down-regulation of BMI-1 expression by silencing siRNA.Methods:Three pairs of siRNA based on the sequences of the BMI-1 mRNA were synthesized (siRNA1, siRNA2 and siRNA3) by compa-ny, and transfected into cultured TE13 cells as the BMI-1 siRNA groups, and a negative one was synthesized to be used as the negative control (NC) group. The untransfected group was named as the control group. BMI-1 mRNA and protein expression in esophageal cancer TE13 cells were detected by reverse transcription polymerase chain reaction (RT-PCR) and Western blot in different groups. This study used flow cytometry assay to analyze cell cycle of transfected cells, and examined cellular growth and radiosensitivityin vitro by MTT and clone formation assay. mRNA and protein expression of p16 and CDK4 in esophageal cancer TE13 cells were detected by RT-PCR and Western blot.Results:The results of RT-PCR and Western blot showed that the expressions of BMI-1 at gene and protein levels were inhibited after silencing the BMI-1 gene. The mRNA and protein expression of BMI-1 in BMI-1 siRNA3 group were both significantly lower than that in BMI-1 siRNA1 and 2 groups. There was no significant difference in the cell proliferation among control, NC and BMI-1 siRNA3 groups. The values ofD0,Dq, and SF2 in BMI-1 siRNA3 group were 1.761, 2.122 and 0.6255, respectively, obvi-ously lower than those in control group (2.514, 2.694 and 0.8268) and those in NC group (2.506, 2.664 and 0.8231), while the value of N in BMI-1 siRNA3 group (3.336) was higher than that in control group (2.92) and that in NC group (2.895), which showed higher radiosensitivity in BMI-1 siRNA3 group. In addition, the cell cycle was arrested at G2/M phase after irradiation in control and NC groups. The percentage of G0/G1 phase in BMI-1 siRNA3 group was higher than that of control group and NC group, while the percentage of G2/M phase was lower than those in the latter. The up-regulation of p16 and down-regulation of CDK4 at gene and protein levels were detected after knockdown of BMI-1 expression by siRNA (P<0.01).Conclusion:siRNA could inhibitBMI-1 gene expression in esophageal cancer TE13 cells and enhance radiosensitivity, followed by eliminating the cell cycle arrest at G2/M stage after irradiationin vitro, which is related to the regulation of the protein expression ofp16 andCDK4.

Relationship between arterial atheromatous plaque morphology and platelet-associated miR-126 and miR-223 expressions

Objective: To study the expression of miR-126 and miR-223 in platelet of rabbit arterial plaque models, and explore its correlation with plaque morphology. Methods: Rabbit arterial plaque models were established, peripheral blood of models and control animals was collected. Plaque morphologies were divided into type I, type II and type III based on angiography plaque morphology and Ambrose method. Platelet isolation kit was applied to isolate and purify peripheral blood platelets, CD45 immunomagnetic beads were used to remove the residual white blood cells. The miRNAs of platelets was extracted by miRNA Isolation Kit, and expressions of miR-126 and miR-223 of the platelets samples were detected by Real-time PCR. The correlation between plaque morphology and platelet-associated miR-126 and miR-223 expressions were analyzed. Expressions of target gene VCAM-1 and P2Y12 receptors of miR-126 and miR-223 in the atherosclerosis plaque of rabbit model were detected by Western blot. Results: Relative expression levels of miR-126 and miR-223 in the model group were 0.27±0.10 and 0.71±0.14, respectively. Plaque morphology was divided into types I, II and III; and miR-126 and miR-223 expression levels were detected in each type. Expression levels of miR-126 in each type were 0.42±0.07, 0.17±0.11 and 0.22±0.15, respectively; and expression levels of miR-223 in each type are 0.68±0.02, 0.57±0.06 and 0.88±0.10, respectively. Relative to the control group, miR-126 and miR-223 known target genes in VCAM-1 and P2Y12 receptors increased platelets in rabbit atherosclerotic plaque models (P<0.05). Conclusions: Relative to normal control animals, miR-126 and miR-223 platelets were reduced in the rabbit atherosclerotic plaque model group (P<0.05). In the type II plaque morphology group, miR-126 was greatly reduced; and there is no significant correlation between miR-223 and plaque morphology.

Relationship between arterial atheromatous plaque morphology and platelet-associated miR-126 and miR-223 expressions

OBJECTIVE@#To study the expression of miR-126 and miR-223 in platelet of rabbit arterial plaque models, and explore its correlation with plaque morphology.@*METHODS@#Rabbit arterial plaque models were established, peripheral blood of models and control animals was collected. Plaque morphologies were divided into type I, type II and type III based on angiography plaque morphology and Ambrose method. Platelet isolation kit was applied to isolate and purify peripheral blood platelets, CD45 immunomagnetic beads were used to remove the residual white blood cells. The miRNAs of platelets was extracted by miRNA Isolation Kit, and expressions of miR-126 and miR-223 of the platelets samples were detected by Real-time PCR. The correlation between plaque morphology and platelet-associated miR-126 and miR-223 expressions were analyzed. Expressions of target gene VCAM-1 and P2Y12 receptors of miR-126 and miR-223 in the atherosclerosis plaque of rabbit model were detected by Western blot.@*RESULTS@#Relative expression levels of miR-126 and miR-223 in the model group were 0.27±0.10 and 0.71±0.14, respectively. Plaque morphology was divided into types I, II and III; and miR-126 and miR-223 expression levels were detected in each type. Expression levels of miR-126 in each type were 0.42±0.07, 0.17±0.11 and 0.22±0.15, respectively; and expression levels of miR-223 in each type are 0.68±0.02, 0.57±0.06 and 0.88±0.10, respectively. Relative to the control group, miR-126 and miR-223 known target genes in VCAM-1 and P2Y12 receptors increased platelets in rabbit atherosclerotic plaque models (P<0.05).@*CONCLUSIONS@#Relative to normal control animals, miR-126 and miR-223 platelets were reduced in the rabbit atherosclerotic plaque model group (P<0.05). In the type II plaque morphology group, miR-126 was greatly reduced; and there is no significant correlation between miR-223 and plaque morphology.

Monte Carlo simulation for elastic modulus of double-stranded DNA biofilm / 医用生物力学

Objective To investigate elastic modulus of double-stranded DNA (dsDNA) biofilm adsorbed on microcantilever substrate. Methods Parsegian’s empirical potentials based on mesoscopic continuum liquid crystal theory was employed to describe the interaction energy among coarse-grained DNA cylinders; Monte Carlo method was used to simulate the distribution pattern of DNA chains before and after loading. The thought experiment method combined with the compression bar model in the sense of macroscopic continuum mechanics was adopted to predict the elastic modulus of DNA biofilm. Results The elastic modulus of dsDNA biofilm ranged from 0.1 MPa to 80 MPa. Conclusions It was found out that the classic hypothesis with uniform hexagonal pattern may underestimate the elastic modulus of DNA biofilm when compared with that in random pattern. Moreover, either the increase of packing density or the decrease of buffer salt concentration will help to enhance elastic modulus of DNA biofilm. These results have great significances in further understanding the mechanical properties and regulation rules of DNA biofilm related with clinical work.