Mechanism of astragaloside Ⅳ in regulating autophagy of PC12 cells under oxygen-glucose deprivation by medicating Akt/mTOR/HIF-1α pathway / 中国中药杂志

This study explored the protective effect of astragaloside Ⅳ(AS-Ⅳ) on oxygen-glucose deprivation(OGD)-induced autophagic injury in PC12 cells and its underlying mechanism. An OGD-induced autophagic injury model in vitro was established in PC12 cells. The cells were divided into a normal group, an OGD group, low-, medium-, and high-dose AS-Ⅳ groups, and a positive drug dexmedetomidine(DEX) group. Cell viability was measured using the MTT assay. Transmission electron microscopy was used to observe autophagosomes and autolysosomes, and the MDC staining method was used to assess the fluorescence intensity of autophagosomes. Western blot was conducted to determine the relative expression levels of functional proteins LC3-Ⅱ/LC3-Ⅰ, Beclin1, p-Akt/Akt, p-mTOR/mTOR, and HIF-1α. Compared with the normal group, the OGD group exhibited a significant decrease in cell viability(P<0.01), an increase in autophagosomes(P<0.01), enhanced fluorescence intensity of autophagosomes(P<0.01), up-regulated Beclin1, LC3-Ⅱ/LC3-Ⅰ, and HIF-1α(P<0.05 or P<0.01), and down-regulated p-Akt/Akt and p-mTOR/mTOR(P<0.05 or P<0.01). Compared with the OGD group, the low-and medium-dose AS-Ⅳ groups and the DEX group showed a significant increase in cell viability(P<0.01), decreased autophagosomes(P<0.01), weakened fluorescence intensity of autophagosomes(P<0.01), down-regulated Beclin1, LC3-Ⅱ/LC3-Ⅰ, and HIF-1α(P<0.05 or P<0.01), and up-regulated p-Akt/Akt and p-mTOR/mTOR(P<0.01). AS-Ⅳ at low and medium doses exerted a protective effect against OGD-induced autophagic injury in PC12 cells by activating the Akt/mTOR pathway, subsequently influencing HIF-1α. The high-dose AS-Ⅳ group did not show a statistically significant difference compared with the OGD group. This study provides a certain target reference for the prevention and treatment of OGD-induced cellular autophagic injury by AS-Ⅳ and accumulates laboratory data for the secondary development of Astragali Radix and AS-Ⅳ.

Research progress of visual quality after SMILE / 国际眼科杂志(Guoji Yanke Zazhi)

Femtosecond laser small incision lenticule extraction(SMILE)is one of the most advanced corneal refractive operations at present. Different from other traditional corneal refractive operations, SMILE achieves minimally invasive and valveless operation. Therefore, the evaluation of postoperative visual quality of SMILE also has its own characteristics, at present, the latest research at home and abroad has confirmed that the naked eye vision can be significantly improved and the refractive status is stable after SMILE. However, there are different understandings of the objective visual quality indexes and their influencing factors, such as higher-order aberration, modulation transfer function cut off(MTF cut off)and objective scatter index(OSI)after SMILE. This paper reviews the postoperative visual quality and its influencing factors after SMILE to provide clinical help.

Systemic therapy of advanced biliary tract cancer / 国际肿瘤学杂志

The incidence rate of biliary tract cancer is increasing year by year. Systemic therapy is the most important treatment for patients with advanced or unresectable biliary tract cancer. Gemcitabine combined with cisplatin is still the standard first-line chemotherapy, while gemcitabine combined with TS-1 and gemcitabine combined with nab-paclitaxel are also the first-line treatment options. Studies have confirmed that immunotherapy as a back-line treatment has a significant advantage in survival, and the disease control rate of nivolumab is 61% and the median overall survival is more than 1 year. In addition, targeted drugs targeting FGFR2, IDH1/2, HER-2 and other major driving genes of biliary tract cancer also show good antitumor activity, and become research hotspots in the treatment of advanced biliary tract cancer. Summarizing the research progress of systematic chemotherapy, immunotherapy and molecular targeted therapy for advanced biliary tract cancer can provide help for clinical practice.

Hepatoprotective Effect of Portulacae Herba on Carbon Tetrachloride Induced Acute Liver Injury in Mice / 中国实验方剂学杂志

Objective::To explore the effect and mechanism of Portulacae Herba protecting carbon tetrachloride (CCl4)-induced acute liver injury. Method::Sixty Kunming mice were randomly divided into normal group, model group, silybin group (200 mg·kg-1) and Portulacae Herba high, medium, low (2, 1, 0.5 g·kg-1) dose groups. After continuous intragastric administration for 5 days, mice in each group were intraperitoneally injected with 0.2% CCl4 peanut oil solution to establish acute liver injury model, except normal mice. After 23 hours of modeling, serum and liver tissue were collected. Fully automatic analysis of serum serum liver function indicators in mice. Liver tissues were taken for hematoxylin-eosin staining (HE) staining to observe liver pathological changes. RNA Sequencing (RNA-seq) was used to analyze differential genes and functional enrichment, real-time fluorescence quantification PCR(Real-time PCR) was used to verify the mRNA expression of cytochrome P450 family members(CYP)26A1, CYP2C37, CYP2C44, CYP2C50, CYP2C54. Result::Compared with normal group, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), total bilirubin (TBIL), malondialdehyde (MDA) in model group were significantly increased (P<0.05), and the activities of triglyceride (TG) and superoxide dismutase (SOD) were significantly decreased (P<0.05). Compared with model group, Portulaca Herba significantly reduced ALT, AST, TBIL and MDA levels in mice with acute liver injury (P<0.05), significantly increased SOD activity (P<0.01), and decreased the degree of liver tissue damage in mice. Compared with normal group, the mRNA expressions of CYP2C44, CYP2C50 in mice with acute liver injury were significantly decreased (P<0.05). Compared with model group, the mRNA expressions of CYP26A1, CYP2C37, CYP2C44, CYP2C50 and CYP2C54 were significantly increased in all dose groups of Portulaca Herba (P<0.05, P<0.01). Conclusion::Portulacae Herba has significant protective effects on acute liver injury caused by CCl4, and its mechanism may be related to the regulation of cytochrome P450 related genes.

Characteristics of Atmospheric Fine Particulate Matter (PM ) Induced Differentially Expressed Proteins Determined by Proteomics and Bioinformatics Analyses / 生物医学与环境科学（英文）

Objective@#To screen the differentially expressed proteins (DEPs) in human bronchial epithelial cells (HBE) treated with atmospheric fine particulate matter (PM ).@*Methods@#HBE cells were treated with PM samples from Shenzhen and Taiyuan for 24 h. To detect overall protein expression, the Q Exactive mass spectrometer was used. Gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and Perseus software were used to screen DEPs.@*Results@#Overall, 67 DEPs were screened in the Shenzhen sample-treated group, of which 46 were upregulated and 21 were downregulated. In total, 252 DEPs were screened in the Taiyuan sample-treated group, of which 134 were upregulated and 118 were downregulated. KEGG analysis demonstrated that DEPs were mainly enriched in ubiquitin-mediated proteolysis and HIF-1 signal pathways in Shenzhen PM samples-treated group. The GO analysis demonstrated that Shenzhen sample-induced DEPs were mainly involved in the biological process for absorption of various metal ions and cell components. The Taiyuan PM -induced DEPs were mainly involved in biological processes of protein aggregation regulation and molecular function of oxidase activity. Additionally, three important DEPs, including ANXA2, DIABLO, and AIMP1, were screened.@*Conclusion@#Our findings provide a valuable basis for further evaluation of PM -associated carcinogenesis.

Investigation and Study on Occupational Exposure for Hazardous Drugs of Healthcare Workers in Shaanxi Province and Relative Cognition Level / 中国药房

OBJECTIVE：To understand the situation of healthcar e workers’occupational exposure of hazardous drugs （chemotherapeutic drugs and antiviral drug ）and relative cognition level ，and to provide reference for improving the level of occupational protection. METHODS ：During Oct. 2018 to Mar. 2019，healthcare workers from 12 hospitals of different levels and different departments in Shaanxi province were selected as respondents to conduct a self-designed questionnaire survey. Information we surveyed contained baseline characteristics ，hazardous drugs exposure ，physical health status ，and occupational protection. Valid questionnaires were collected and analyzed statistically. RESULTS ：A totally of 1 848 questionnaires were sent out ，and 1 767 questionnaires were collected ，including 95 were pharmacists ，100 were physicians ，and 1 572 were nurses. The frequency of diarrhea and menstrual disorders in healthcare workers with long-term exposure to antiviral drugs （antiviral drug exposure group ） and cross-exposure to antiviral drugs and chemotherapeutic drugs （cross-exposure group ）were significantly higher than unexposed group （P＜0.05）. The incidence of routine blood abnormalities in cross-exposure group ，antiviral drug exposure group and healthcare workers with long-term exposure to chemotherapy drugs （chemotherapy drug exposure group ） was higher than unexposed group by 9.13％，5.50％ and 12.34％，respectively. 84.7％ of the respondents had little knowledge of hazardous drugs ， and 8.15％ of the respondents had never received occupational protection training. Additionally ，the ratio of healthcare workers receiving occupational protection training in the cross-exposure group was significantly higher than unexposed group （P＜0.05）， and the ratio of healthcare workers receiving occupational protection training in antiviral drug exposure group were significantly lower than unexposed group （P＜0.05）. CONCLUSIONS ：Long-term exposure to hazardous drugs will cause certain occupational hazards to healthcare workers. It is necessary to improve healthcare workers ’awareness of self-protection ，increase the input of hospitals in occupational protection training and establish occupational protection standards in order to improve the current situation of occupational protection of healthcare workers.

Establishment of Acquired Aplastic Anemia SD Rat Model / 中国实验血液学杂志

OBJECTIVE@#To establish a stable and rapidly rat model acquired aplastic anemia.@*METHODS@#The SD rats were exposed to Csγ-ray at 3.5 and 4.0 Gy ( 91 cGy/min), and intraperitoneally injected with CTX at 35 mg/( kg·d) and CHL at 45 mg/( kg·d) in d 4, 6 and 8 after irradiation; the WBC, platelet and reticulocyte counts in peripheral blood, the smears and nucleated cells counts of bone marrow were observed.@*RESULTS@#The levels of peripheral blood 3-lineage cells of SD rats treated with Csγ-irradiation combined with cyclophosphamide and chloramphenicol were significantly reduced, among which white blood cells, platelets and reticulocytes decreased rapidly, and the number of bone marrow nucleated cells decreased significantly; bone marrow pathological sections showed severe reduction of hematopoietic cells, and the non-hematopoietic cells such as fat cells increased, and a serve or lightly reduction of bone marrow cells were found.@*CONCLUSION@#The rat model established by Csγ-ray irradiation combined with cyclophosphamide and chloramphenicol meets the clinical characteristics of aplastic anemia, and this study provides a stable rat model for the study of new therapeutic drugs for acquired aplastic anemia.

Small molecule proteomics quantifies differences between normal and fibrotic pulmonary extracellular matrices / 中华医学杂志(英文版)

BACKGROUND@#Pulmonary fibrosis is a respiratory disease caused by the proliferation of fibroblasts and accumulation of the extracellular matrix (ECM). It is known that the lung ECM is mainly composed of a three-dimensional fiber mesh filled with various high-molecular-weight proteins. However, the small-molecular-weight proteins in the lung ECM and their differences between normal and fibrotic lung ECM are largely unknown.@*METHODS@#Healthy adult male Sprague-Dawley rats (Rattus norvegicus) weighing about 150 to 200 g were randomly divided into three groups using random number table: A, B, and C and each group contained five rats. The rats in Group A were administered a single intragastric (i.g.) dose of 500 μL of saline as control, and those in Groups B and C were administered a single i.g. dose of paraquat (PQ) dissolved in 500 μL of saline (20 mg/kg). After 2 weeks, the lungs of rats in Group B were harvested for histological observation, preparation of de-cellularized lung scaffolds, and proteomic analysis for small-molecular-weight proteins, and similar procedures were performed on Group C and A after 4 weeks. The differentially expressed small-molecular-weight proteins (DESMPs) between different groups and the subcellular locations were analyzed.@*RESULTS@#Of the 1626 small-molecular-weight proteins identified, 1047 were quantifiable. There were 97 up-regulated and 45 down-regulated proteins in B vs. A, 274 up-regulated and 31 down-regulated proteins in C vs. A, and 237 up-regulated and 28 down-regulated proteins identified in C vs. B. Both the up-regulated and down-regulated proteins in the three comparisons were mainly distributed in single-organism processes and cellular processes within biological process, cell and organelle within cellular component, and binding within molecular function. Further, more up-regulated than down-regulated proteins were identified in most sub-cellular locations. The interactions of DESMPs identified in extracellular location in all comparisons showed that serum albumin (Alb) harbored the highest degree of node (25), followed by prolyl 4-hydroxylase beta polypeptide (12), integrin β1 (10), apolipoprotein A1 (9), and fibrinogen gamma chain (9).@*CONCLUSIONS@#Numerous PQ-induced DESMPs were identified in de-cellularized lungs of rats by high throughput proteomics analysis. The DESMPs between the control and treatment groups showed diversity in molecular functions, biological processes, and pathways. In addition, the interactions of extracellular DESMPs suggested that the extracellular proteins Alb, Itgb1, Apoa1, P4hb, and Fgg in ECM could be potentially used as biomarker candidates for pulmonary fibrosis. These results provided useful information and new insights regarding pulmonary fibrosis.

Preliminary study of dihydroartemisin in inhibiting invasion and metastasis of hepatoma cells / 中国中药杂志

It is reported that dihydroartemisinin could reduce the expression of phosphorylated adhesion kinase and matrix metalloproteinase-2, inhibit the growth, migration and invasion of ovarian cancer cells, promote the formation of Treg cells through TGF-beta/Smad signaling pathway, and play an immunosuppressive role; dihydroartemisinin could also inhibit the growth of lung cancer cells by inhibiting the expression of vascular endothelial growth factor(VEGF) receptor KDR. However, there are few studies on dihydroartemisinin in hepatocellular carcinoma cells. In order to preliminarily explore the effect of dihydroartemisinin on invasion and metastasis of hepatocellular carcinoma cells, CCK-8 method and crystal violet staining were used to detect the effect of dihydroartemisinin on the growth of hepatocellular carcinoma cell 7402 and highly metastatic hepatocellular carcinoma cell MHCC97 H. The effects of dihydroartemisinin on the invasion and metastasis of hepatocellular carcinoma cell 7402 and highly metastatic hepatocellular carcinoma cell MHCC97 H were studied by using cell wound healing and Transwell. Western blot was used to detect the protein expression of epidermal growth factor receptor(EGFR) and its downstream signaling pathway in cells treated with dihydroartemisinin for 48 hours. The results showed that dihydroartemisinin could inhibit the growth of hepatocellular carcinoma cell 7402 and highly metastatic hepatocellular carcinoma cell MHCC97 H at 25 μmol·L~(-1). As compared with the control group, the number of cell clones was significantly reduced, and the ability of cell migration and invasion was weakened. Western blot results showed that as compared with the control group, dihydroartemisinin group could down-regulate the protein expression of EGFR and its downstream signaling pathways p-AKT, p-ERK, N-cadherin, Snail and Slug, and up-regulate the expression of E-cadherin protein, thus affecting the migration, invasion and metastasis of hepatocellular carcinoma cells 7402 and MHCC97 H.

Decitabine combined with arsenious acid in the treatment of patients with higher-risk myelodysplastic syndromes and chronic myelomonocytic leukemia / 中国实用内科杂志

OBJECTIVE: To evaluate the clinical efficacy of decitabine combined with arsenious acid in the treatment of patients with higher-risk myelodysplastic syndromes(MDS) and chronic myelomonocytic leukemia(CMML). METHODS: Totally 39 patients with MDS and 8 patients with CMML received the treatment of decitabine and arsenious acid from April 2016 to December 2018. Decitabine [20 mg/(m~2·d)] and arsenious acid [0.15 mg/(m~2·d)] were administered intravenously for 5 consecutive days every 4-6 weeks. Patients who achieved complete or partial remission entered into the consolidation cycle. Efficacy and influencing factor were analyzed. RESULTS: Clinical response were observed in 31 patients after a median of 2 courses(ranging 1-12) of treatment. The overall response rate(ORR) was 66.0%. The median duration of response was 16 weeks(ranging 2-52 weeks). There were 8 cases(17.0%) of complete remission(CR), 10 cases(21.3%) of partial remission(PR),12 cases(25.5%) of hematological improvement(HI), 1 case(2.1%) of marrow complete remission(mCR), 8 cases(17.0%) of stable disease(SD), and 1 case(2.1%) of progressive disease(PD). By next generation sequencing, 25 genes mutated with 70 times in 33 cases. The mutation frequency of epigenetic regulators(57.6%) was higher than splicing factors(33.5%), transcription factors and kinase signaling(54.5%),and TP53(21.2%)(P<0.01). There was no significant difference in response rates among these patients(47.4%, 54.5%, 50.0% and85.7%, P=0.977). Gene mutation frequency(VAF) of patients who responded to the regimen declined significantly(16.67% vs. 10.26%,P=0.014). CONCLUSION: Decitabine combined with arsenious acid has significant effect in the treatment of patients with higher-risk MDS and CMML and is well-tolerated. Gene mutation test results by next generation sequencing might be related to clinical response.

A brief history of artemisinin: Modes of action and mechanisms of resistance / 中国天然药物

The cornerstone of antimalarial treatment, artemisinin, has reduced malaria associated morbidity and mortality worldwide. However, Plasmodium falciparum parasites with reduced sensitivity to artemisinin have emerged, and this threatens malaria control and elimination efforts. In this minireview, we describe the initial development of artemisinin as an antimalarial drug, its use both historically and currently, and our current understanding of its mode of action and the mechanisms by which malaria parasites achieve resistance.

Analysis of Mechanism of Artesunate in Treatment of Liver Cancer Based on Metabolomics / 中国实验方剂学杂志

Objective: To study on the antitumor mechanism of artesunate in the treatment of liver cancer based on gas chromatography-mass spectrometry (GC-MS). Method: CellTiter-Glo® Luminescent Cell Viability Assay was used to detect activity of artesunate with different concentrations (0, 12.5, 25, 50, 100 μmol·L-1) on human liver cancer Huh7, SMMC-7721 cells for 24, 48, 72 h. GC-MS was employed to analyze the changes of metabolites of artesunate in two kinds of hepatoma cells (Huh7, SMMC-7721) for 24 h. The data was preprocessed by Postrun Analysis 4.41 workstation. Partial least squares-discriminant analysis (PLS-DA) was used to analyze two sets of differential metabolites and to analyze metabolic pathways of differential metabolites based on MetaboAnalyst 3.0 software. Result: Compared with the normal group, after two kinds of liver cancer cells was treated by artesunate, a total of 39 identical metabolites in the cells have undergone significant changes, which were mainly related to five metabolic pathways,including biosynthesis of aminoacyl-transfer RNA (tRNA), metabolism of alanine, aspartic acid and glutamic acid, metabolism of glycine, serine and threonine, metabolism of arginine and proline, metabolism of glutathione. Conclusion: Artesunate (12.5-100 μmol·L-1) can inhibit the growth of liver cancer cells (Huh7, SMMC-7721), it mainly involves five metabolic pathways, which may be the pathway of artesunate against liver cancer.

Effect of Diosgenin on Expressions of PPARγ, C/EBPα and Adipokine Secretion in Aplastic Anemia Mice / 中国实验方剂学杂志

Objective: To observe the effect of diosgenin on aplastic anemia (AA) mice and peroxisome proliferator activated receptor γ (PPARγ), CCAAT-enhancer binding protein α (C/EBPα), Adiponectin, Leptin, in order to discuss the potential mechanism of bone marrow mesenchymal stem cells in the process of adipemia. Method: BALB/c mice were randomly divided into control group and model group. The model group was established by 60Coy irradiation combined with tail vein infusion with lymphatic suspension cells of DBA/2 mice. After successful evaluation of the model, the mice were randomly divided into 6 groups:model group, low, medium and high-dose diosgenin groups (37.44,74.88,149.76 mg·kg-1·d-1), cyclosporine group (23.5 mg·kg-1·d-1), and tripterygium glycoside group (9.36 mg·kg-1·d-1), and given corresponding drugs by gavage for 14 days. After the intervention, the peripheral blood of mice in each group was detected, and bone marrow smears were collected to evaluate the proliferation of bone marrow. Bone marrow mesenchymal stem cells (BMMSCs) were isolated and cultured by adherent method and induced by adipogenesis. The mRNA and protein expressions of PPARγ, C/EBPα, Adiponectin, Leptin in BMMSCs were detected by quantitative real-time fluorescent quantitative polymerase chain reaction(Real-time PCR) and Western blot. Result: The white blood cell (WBC), hemoglobin (HGB) and blood platelet (PLT) in peripheral blood of model group were significantly lower than those of normal group (PPγ, C/EBPα, Adiponectin and Leptin in BMMSCs of the model group increased significantly (Pγ, C/EBPα, Adiponectin and Leptin in the middle-dose group diosgenin decreased obviously, which was better than those of Tripterygium glycoside group (P0.05). Conclusion: Diosgenin can promote the recovery of peripheral blood in aplastic anemia mice and improve the hematopoiesis of bone marrow. Diosgenin can reduce the expressions of PPARγ and C/EBPα, the formation of adipocytes and the secretion of Adiponectin and Leptin in adipocytes, and effectively inhibit the process of adipose tissue derived from bone BMMSCs.

Establishment of Cs γ ray Combined with Cyclophosphamide and Chloramphenicol-Mediated Mouse Model of Acquired Aplastic Anemia / 中国实验血液学杂志

OBJECTIVE@#To improve and establish the mouse model with aplastic anemia (AA) mediated by Cs γ-ray irradiation combined with cyclophosphamide (CTX) and chloramphenicol (CHL) injection,so as to provide a stable model for studying the pathogenesis and treatment of AA .@*METHODS@#The BALB/c mice were exposed to Cs γ-ray of 3-5 Gy(91 cGy/min) and were intraperitoneally injected with CTX of 25 mg/(kg.d) and CHL of 62.5 mg/(kg.d) at D 4,5 and 6 after irradiation; the WBC, platelet and reticulocyte counts in peripheral blood as well as the mucleated cell count in bone marrow and bone marrow smears were detected .@*RESULTS@#The 3-lineage cells in peripheral blood of BALB/c mouse model with acquired AA were rapidly reduced, especially WBC, platelet and reticulocyte counts were lowest at D 14,the 3-lineage cells in peripheral blood were still severely reduced at D 28; the nucleated cell count in bone marrow significantly dcreased,the bone marrow hyperplasia was reduced or severely reduced; the pathological sections of bone marrow showed the severe reduction of hematopoietic cells and the increased of non-hematopoietic cells such as fat cells.@*CONCLUSION@#The mouse model with acquired AA has been established by Cs γ-ray irradiation combined with CTX and CHL injection. All detection indicators of this model reach to diagnostic criteria for acquired AA,therefore this mouse model may be used as the model for study of pathogenesis and treatment of acquired AA.

Superparamagnetic iron oxide labeling influences in vitro differentiation of induced pluripotent stem cells / 中国组织工程研究

BACKGROUND: Superparamagnetic iron oxide (SPIO) labeling technology is a classic noninvasive tracing method, which has been widely used in the stem cell transplantation. Induced pluripotent stem cells (iPSCs) are currently one of the most promising seed cells for cell transplantation. Whether SPIO labeling can also be used to noninvasively trace induced pluripotent stem cells is rarely reported, and concern has been raised about whether SPIO markedly impacts the differentiation of iPSCs. OBJECTIVE:To investigate the effects of SPIO labeling on the differentiation of iPSCs in vitro. METHODS: Rat fibroblasts were isolated and cultured. Efficient recombinant vector and plasmids that were packaged by virus and contained target genes (Oct4, Sox2, Klf4 and c-Myc) were transfected into 293T cells for virus packaging and production. The packaging lentiviral vectors that contained target genes infected rat fibroblasts to obtain iPSCs. SPIO-labeled (experimental) or unlabeled (control) iPSCs were subjected to neural induction and differentiation. Prussian blue staining and transmission electron microscope observation were performed for SPIO-labeled iPSCs. Immunohistochemical method was used to detect neuron-specific enolase expression after induced differentiation. Flow cytometry was used to detect the proportion of neurons and glial cells differentiated from iPSCs. RESULTS AND CONCLUSION: There were dense iron particles in the cytoplasm of SPIO-labeled iPSCs shown by Prussian staining and under transmission electron microscope. Differentiated iPSCs were positive for neuron-specific enolase. In addition, the proportion of neurons and glial cells showed no difference between the experimental and control groups. To conclude, SPIO labeling has no obvious effect on the capacity of iPSCs differentiating into neurons. Reasonable application of this new cell labeling technique will promote the development of seed cells in regenerative medicine.

The therapy of auxiliary partial orthotopic liver transplantation for acute liver failure in mice / 中华器官移植杂志

Objective Auxiliary partial orthotopic liver transplantation (APOLT) is an effective treatment for fulminant liver failure.However,information on the experimental problem and hepatocyte proliferation mechanism of native and donor liver is lacking.In this study,an effective APOLT model for acute liver failure (ALF) in mice is established to address these issues.Methods We created an ALF mouse model wherein about 82％ of liver tissue was resected with total hepatic vascular exclusion.The procedure lasted 25 min.Donor liver was transplanted to the left lateral lobe of the C57BL of the recipient.Results In the ALF group,most mice died within 2-day because of liver failure.Of the 33 mice that received APOLT,27 lived for more than 7-day.Significantly increased the levels of transaminases,serum ammonia,total bilirubin and liver cell apoptosis were observed in the ALF group,whereas treatment with APOLT reduced all these parameters.In addition,significant regeneration of the native liver with the auxiliary liver graft was observed in the APOLT group.Conclusion It was proved that APOLT could totally meliorate the liver functions,reduce the native liver apoptosis,and facilitate the native liver proliferation in acute liver failure by means of mouse APOLT model.

Correlation between pulmonary vascular permeability index and calcitonin in acute respiratory distress syndrome associated with septic shock / 上海交通大学学报（医学版）

Objective · To analyze the assessment value of pulmonary vascular permeability index (PVPI) and procalcitonin (PCT) levels to the severity and prognosis of acute respiratory distress syndrome (ARDS) associated with septic shock.Methods·Clinic data of 100 ARDS patients admitted to Affiliated Hospital of Nantong University was analyzed retrospectively.The clinical data was collected as follows:gender,age,infection site,acute physiology,chronic health evaluation Ⅱ (APACHE Ⅱ),sequential organ failure (SOFA) score,serum PCT level,and hemodynamic parameters which were monitored by pulse indicator continuous cardiac output (PiCCO).Patients with septic shock associated with ARDS patients were divided into mild,moderate and severe groups.The patients were divided into survival group and death group according to the 28-day prognosis,and the differences in the parameters between two groups were analyzed,to evaluate PVPI and PCT in predicting the severity and prognosis of septic shock associated ARDS.Results · There were significant differences in PVPI and PCT between ARDS group associated with septic shock and not (P=0.000).PVPI and PCT increased with the severity of ARDS,and there was a statistically significant difference between the ARDS groups in different degrees of PVPI (P=0.000).Pearson correlation analysis showed that PVPI was positively correlated with APACHE Ⅱ score and SOFA score (r=0.554,P=0.000;r=0.431,P=0.000),and PCT was positively correlated with APACHE Ⅱ score and SOFA score (r=0.313,P=0.004;r=0.320,P=0.004).Receiver operating characteristic (ROC) curve analysis showed that the area under the ROC curve of the prognosis of ARDS patients with sepsis was significantly higher than those of the two groups.Conclusion · PVPI can assess the severity of ARDS in patients with septic shock,and PVPI and PCT are predictive factors of prognosis.The combination of PVPI and PCT contributes to early stage diagnosis of ARDS associated with septic shock.

Research progress on 26S proteasome inhibitors / 药学学报

The 26S proteasome is a 2.5 MDa complex of the protease family members and is central to a vast array of vital cellular processes including cell-cycle progression and antigen presentation. It has been proven to be a target for therapeutic agents in the treatment of cancers and autoimmune diseases. Most inhibitors are designed to target the 20S proteolytic core complex while the efforts to target the 19S regulatory particle subunits are less successful so far. This is, in part, due to the complexity of molecular architecture and poor understanding of the mechanism of this subcomplex. This review attempts to summarize the development of inhibitory molecules that target both the 20S and 19S subunits of the proteasome, especially highlight the recent progress in the proteasome structure and development of the new inhibitors.

Splenectomy suppresses growth and metastasis of hepatocellular carcinoma through decreasing myeloid-derived suppressor cells in vivo / 华中科技大学学报（医学）（英德文版）

The function of the spleen in tumor development has been investigated for years. The relationship of the spleen with hepatocellular carcinoma (HCC), a huge health burden worldwide, however, remains unknown. The present study aimed to examine the effect of splenectomy on the development of HCC and the possible mechanism. Mouse hepatic carcinoma lines H22 and Hepa1-6 as well as BALB/c and C57 mice were used to establish orthotopic and metastatic mouse models of liver cancer. Mice were divided into four groups, including control group, splenectomy control group (S group), tumor group (T group) and tumor plus splenectomy group (T+S group). Tumor growth, metastases and overall survival were assessed at determined time points. Meanwhile, myeloid-derived suppressor cells (MDSCs) were isolated from the peripheral blood (PB), the spleen and liver tumors, and then measured by flow cytometery. It was found that liver cancer led to splenomegaly, and increased the percentage of MDSCs in the PB and spleen in the mouse models. Splenectomy inhibited the growth and progression of liver cancer and prolonged the overall survival time of orthotopic and metastatic models, which was accompanied by decreased proportion of MDSCs in the PB and tumors of liver cancer-bearing mouse. It was suggested that splenectomy could be considered an adjuvant therapy to treat liver cancer.

The effects of sacral nerve root electrostimulation on the colon function and its mechanisms in a rat model of spinal cord injury / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To study the effects of sacral nerve root electrostimulation (SNS) on the colon function and its mechanisms in rats with spinal cord injury (SCI).</p><p><b>METHODS</b>One hundred and four Wistar rats were divided into three groups: A, B and C. A group ( n = 24) was divided into three subgroups (n = 8) for studying the bioelectricity: Normal group (NG), SCI group (SCI) and SCI group with SNS(SNS); B group( n = 24) was divided into three subgroups( n = 8) for studying the colon motility: NG, SCI and SNS. C group( n = 56) were divided into three groups for studying the change of morphology and neurotransmitters(SP and VIP): NG (n = 8), SCI (n = 24), and SNS (n = 24) . In SCI and SNS, included of three subgroups: 24, 48, 72 h after spinal cord injury (n = 8).</p><p><b>RESULTS</b>In SCI group, the activity of bioelectricity in proximal and distal colon was reduced; the colon motility was lessened, and colon mucosa appeared different degree of damage; cell-cell connections between intestinal epithelial cells were destroyed. The expressions of substance P(SP) and vasoactive intestinal peptide (VIP) in colon were decreased obviously. SNS was found to activate the bioelectricity, promote the colon motility, improve the intestinal mucosal, and increase the expressions of SP and VIP. Conclusion: SNS can activate the peristalsis, rehabilitate the motility of denervated colon, protection of the intestinal mechanical barrier between intestinal epithelial cells and tight junction, rebuild the colon function through activating the bioelectricity and increase the expressions of SP and VIP.</p>