Accurate estimation of concrete consumption in tunnel lining using terrestrial laser scanning.

Accurate estimation of concrete (including shotcrete) consumption plays a crucial role in tunnel construction. A novel method has been introduced to accurately estimate concrete consumption with terrestrial laser scanning (TLS). The estimation needs to capture TLS data of tunnel surfaces at different stages of construction. Unrolling point clouds, a novel two-stage algorithm consisting of noise removal and hole filling has been used to generate resampled points. Furthermore, resampled points from two scans (before and after lining construction) ultimately generate an innovative computation model composed of multiple hexahedral elements, which is used for calculating volumes. The proposed technique was applied to the Tiantaishan highway tunnel and Da Fang Shan high-speed railway tunnel. The calculation relative error of the rebound rate is 0.19%, and the average relative error in predicting the demand for secondary lining concrete is 0.15%. Compared with 3D Delaunay with curve fitting, the proposed technique offers a more straightforward operation and higher accuracy. Considering factors such as tunnel geometry, support design, and concrete properties, a computational model will provide valuable insights into optimizing resource allocation and reducing material waste during construction.

Levofloxacin combined with cellulase can eradicate bacille Calmette-Guerin biofilm infection / 南方医科大学学报

OBJECTIVE@#To investigate the inhibitory effects of levofloxacin (LEV) combined with cellulase against bacille CalmetteGuerin (BCG) biofilms in vitro.@*METHODS@#The mature growth cycle of BCG biofilms was determined using the XTT method and crystal violet staining. BCG planktonic bacteria and BCG biofilms were treated with different concentrations of LEV and cellulose alone or jointly, and the changes in biofilm biomass were quantified with crystal violet staining. The mature BCG biofilm was then treated with cellulase alone for 24 h, and after staining with SYTO 9 and Calcofluor White Stain, the number of viable bacteria and the change in cellulose content in the biofilm were observed with confocal laser scanning microscopy. The structural changes of the treated biofilm were observed under scanning electron microscopy.@*RESULTS@#The MIC, MBC and MBEC values of LEV determined by broth microdilution method were 4 μg/mL, 8 μg/mL and 1024 μg/mL, respectively. The combined treatment with 1/4×MIC LEV and 2.56, 5.12 or 10.24 U/mL cellulase resulted in a significant reduction in biofilm biomass (P < 0.001). Cellulase treatments at the concentrations of 10.24, 5.12 and 2.56 U/mL all produced significant dispersion effects on mature BCG biofilms (P < 0.001).@*CONCLUSION@#LEV combined with cellulose can effectively eradicate BCG biofilm infections, suggesting the potential of glycoside hydrolase therapy for improving the efficacy of antibiotics against biofilmassociated infections caused by Mycobacterium tuberculosis.

The fliL gene significantly affects the motility and sporulation abilities of Clostridioides difficile / 生物工程学报

Flagella are the main motility structure of Clostridioides difficile that affects the adhesion, colonization, and virulence of C. difficile in the human gastrointestinal tract. The FliL protein is a single transmembrane protein bound to the flagellar matrix. This study aimed to investigate the effect of the FliL encoding gene flagellar basal body-associated FliL family protein (fliL) on the phenotype of C. difficile. The fliL gene deletion mutant (ΔfliL) and its corresponding complementary strains (: : fliL) were constructed using allele-coupled exchange (ACE) and the standard molecular clone method. The differences in physiological properties such as growth profile, antibiotic sensitivity, pH resistance, motility, and spore production ability between the mutant and wild-type strains (CD630) were investigated. The ΔfliL mutant and the : : fliL complementary strain were successfully constructed. After comparing the phenotypes of strains CD630, ΔfliL, and : : fliL, the results showed that the growth rate and maximum biomass of ΔfliL mutant decreased than that of CD630. The ΔfliL mutant showed increased sensitivity to amoxicillin, ampicillin, and norfloxacin. Its sensitivity to kanamycin and tetracycline antibiotics decreased, and the antibiotic sensitivity partially returned to the level of CD630 strain in the : : fliL strain. Moreover, the motility was significantly reduced in the ΔfliL mutant. Interestingly, the motility of the : : fliL strain significantly increased even when compared to that of the CD630 strain. Furthermore, the pH tolerance of the ΔfliL mutant significantly increased or decreased at pH 5 or 9, respectively. Finally, the sporulation ability of ΔfliL mutant reduced considerably compared to the CD630 strain and recovered in the : : fliL strain. We conclude that the deletion of the fliL gene significantly reduced the swimming motility of C. difficile, suggesting that the fliL gene is essential for the motility of C. difficile. The fliL gene deletion significantly reduced spore production, cell growth rate, tolerance to different antibiotics, acidity, and alkalinity environments of C. difficile. These physiological characteristics are closely related to the survival advantage in the host intestine, which is correlated with its pathogenicity. Thus, we suggested that the function of the fliL gene is closely related to its motility, colonization, environmental tolerance, and spore production ability, which consequently affects the pathogenicity of C. difficile.

Population genetic characteristics of Hainan medaka with whole-genome resequencing.

The DMY gene is deleted in all males of the Sanya population (SY-medaka) of the Hainan medaka, Oryzias curvinotus, as recently reported by us. However, due to limited knowledge regarding their population genetic background, it is difficult to explore the possible evolutionary pathway. Herein, we resequenced the whole genome of four populations, including SY-medaka. A total of 56 mitogenomes and 32,826,105 SNPs were identified. We found that the genetic differentiation is highest between SY-medaka and the other populations. The results of the population history of the O. curvinotus suggest that the SY-medaka has been in a bottleneck period recently. Further analysis shows that SY-medaka are the most strongly affected by environmental selection. Moreover, we screened some potential genomic regions, and the genes contained in these regions may explain the potential mechanism of the selection process of the SY-medaka. In conclusion, our study can provide new clues for the adaptation process of medaka in the new environment of Sanya.

Transcriptomic analysis of the ΔPaLoc mutant of Clostridioides difficile and verification of its toxicity / 中华预防医学杂志

Objective: Comparative analyses of wild-type Clostridioides difficile 630 (Cd630) strain and pathogenicity locus (PaLoc) knockout mutant (ΔPaLoc) by using RNA-seq technology. Analysis of differential expression of Cd630 wild-type strain and ΔPaLoc mutant strain and measurement of its cellular virulence changes. Lay the foundation for the construction of an toxin-attenuated vaccine strain against Clostridioides difficile. Methods: Analysis of Cd630 and ΔPaLoc mutant strains using high-throughput sequencing (RNA-seq). Clustering differentially expressed genes and screening differentially expressed genes by DESeq software. Further analysis of differential genes using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Finally, cytotoxicity assays of ΔPaLoc and Cd630 strains were performed in the African monkey kidney epithelial cell (Vero) and the human colonic cell (Caco-2) lines. Results: The transcriptome data showed that the ΔPaLoc mutant toxin genes tcdA and tcdB were not transcribed. Compared to the wild-type strain, CD630_36010, CD630_020910,CD630_02080 and cel genes upregulated 17.92,11.40,8.93 and 7.55 fold, respectively. Whereas the hom2 (high serine dehydrogenase), the CD630_15810 (spore-forming protein), CD630_23230 (zinc-binding dehydrogenase) and CD630_23240 (galactitol 1-phosphate 5-dehydrogenase) genes were down-regulated by 0.06, 0.075, 0.133 and 0.183 fold, respectively. The GO and KEGG enrichment analyses showed that the differentially transcribed genes in ΔPaLoc were enriched in the density-sensing system, ABC transport system, two-component system, phosphotransferase (PTS) system, and sugar metabolism pathway, as well as vancomycin resistance-related pathways. Cytotoxicity assays showed that the ΔPaLoc mutant strain lost its virulence to Vero and Caco-2 cells compared to the wild-type Cd630 strain. Conclusion: Transcriptional sequencing analysis of the Cd630 and ΔPaLoc mutant strains showed that the toxin genes were not transcribed. Those other differential genes could provide a reference for further studies on the physiological and biochemical properties of the ΔPaLoc mutant strain. Cytotoxicity assays confirmed that the ΔPaLoc mutant lost virulence to Vero and Caco-2 cells, thus laying the foundation for constructing an toxin-attenuated vaccine strain against C. difficile.

Biotransformation and enzymatic mechanism of protoberberine alkaloids / 中国中药杂志

Protoberberine alkaloids belong to the quaternary ammonium isoquinoline alkaloids, and are the main active ingredients in traditional Chinese herbal medicines, like Coptis chinensis. They have been widely used to treat such diseases as gastroenteritis, intestinal infections, and conjunctivitis. Studies have shown that structural modification of the protoberberine alkaloids could produce derivative compounds with new pharmacological effects and biological activities, but the transformation mechanism is not clear yet. This article mainly summarizes the researches on the biotransformation and structure modification of protoberberine alkaloids mainly based on berberine, so as to provide background basis and new ideas for studies relating to the mechanism of protoberberine alkaloids and the pharmacological activity and application of new compounds.

Preparation and characterization of calcined bone/chitosan composite material / 中国组织工程研究

BACKGROUND: Chitosan exhibits good physiochemical properties and biocompatibility, but it has poor biological activity of osseointegration. Therefore, it needs to combine with other materials for bone repair. OBJECTIVE: Calcined bone/chitosan composite was prepared and its physiochemical properties and biocompatibility were analyzed. METHODS: Calcined bone/chitosan composite was prepared at a mass ratio of 1:2, 1:1, 2:1 respectively by solution blending method. The physicochemical properties of three composite materials were characterized. Passage 5 mouse L929 fibroblasts were treated with the leaching solution of three composite materials. The cytotoxicity of three composite materials was detected by the CCK-8 test. RESULTS AND CONCLUSION: (1) X-ray diffraction and Fourier Transform Infrared Spectroscopy showed that the essential components of three composite materials were hydroxyapatite and β-tricalcium phosphate. The characteristic diffraction peaks of hydroxyapatite/β-tricalcium phosphate increased with the increase of the proportion of calcined bone. (2) Scanning electron microscopy showed that calcined bone particles were evenly dispersed in chitosan medium. (3) With the increase of the proportion of calcined bone, the compressive strength of the composite decreased gradually. (4) After 7 days of culture, the cells in the leaching solution of three composite materials grew well without obvious change in morphology. By the ninth day, the relative proliferation rate of the cells in the leaching solution of three composite materials was over 90%. Cytotoxicity was grade 1, which meets the safety standard of biomaterials. (5) These results suggest that the calcined bone/chitosan composite has good structural characteristics, physicochemical properties and suitable compressive strength and is safe and non-toxic.

Clinical Observation on Modified Shoutaiwan with Si Junzitang Combined with Didroxyprogesterone Tablets in Treating Threatened Abortion in Advanced Age Patients / 中国实验方剂学杂志

Objective:To observe the immune factors， coagulation and curative effect of modified Shoutaiwan with Si Junzitang combined with dydrogesterone tablets in advanced age patients with early threatened abortion， and to explore its mechanism of action. Method:The 90 advanced age patients with threatened abortion and kidney deficiency and blood stasis syndrome differentiation in traditional Chinese medicine （TCM） were randomly divided into control group and observation group by random number table， with 45 cases in each group. Both groups took oral dydrogesterone tablets for luteal support. The control group additionally received natural vitamin E soft capsules by oral administration， while observation group received modified Shoutaiwan with Si Junzitang. The course of treatment was 10 days in both groups. The clinical efficacy， TCM syndrome score， immune factors and coagulation factors of the two groups were compared before and after treatment. Result:There was no statistically significant difference in TCM symptom scores， immune factors， and coagulation factors between two groups before treatment. After treatment， the scores of TCM syndromes were reduced in both groups （P<0.05）， the proportion of helper T lymphocyte （Th）， Th/Ts ratio， D-dimer （D-D） level and fibrinogen （FIB） were reduced while prothrombin time （PT） and the ratio of suppressor T lymphocyte （Ts） were increased in observation group （P<0.05）. After treatment， the proportion of Th， Th/Ts， D-D， and FIB levels in observation group were lower than those in control group， while PT and the proportion of Ts were higher than those in control group （P<0.05）. The proportion of natural killer cells （NK） had no significant change after treatment， also with no significant difference between two groups. The total effective rate was 84.4%（38/45） in observation group， higher than 64.4%（29/45） in control group （χ2=4.398，P<0.05）. There was no obvious adverse reaction in both groups during the treatment. Conclusion:Modified Shoutaiwan with Si Junzitang combined with dydrogesterone tablets can improve symptoms and the therapeutic effect for fetal protection by regulating the immune balance and coagulation function in advanced age patients with threatened abortion.

Adjuvant therapy of acupoint catgut embedding for threatened abortion after in vitro fertilization-embryo transfer: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the effects of acupoint catgut embedding on miscarriage prevention and pregnancy outcome in patients with threatened abortion after in vitro fertilization-embryo transfer (IVF-ET).@*METHODS@#Sixty cases of patients with threatened abortion after IVF-ET were randomly divided into an observation group and a control group, 30 cases in each group. The patients in the control group were treated with intramuscular injection of progesterone (40 mg) once every day, while the patients in the observation group, on the basis of the treatment of control group, were treated with catgut embedding at Geshu (BL 17), Ganshu (BL 18), Shenshu (BL 23), Pishu (BL 20), Weishu (BL 21), Xuehai (SP 10), Diji (SP 8) and Fuliu (KI 7), once every two weeks, six times as a course of treatment. The treatment was given until 12 weeks into pregnancy. The level of serum human chorionic gonadotropin (HCG), estradiol (E) and progesterone (P) before and after treatment was recorded; the TCM syndrome score before and after treatment was compared; the successful pregnancy rate and spontaneous abortion rate after treatment were observed in the two groups.@*RESULTS@#Compared before treatment, the scores of TCM syndrome in both groups were reduced after treatment (both <0.01), and score in the observation group was superior to that in the control group (<0.05). After treatment, the clinical efficacy in the observation group was superior to that in the control group (<0.05). After treatment, the hormone levels (β-HCG, E, P) in both groups were increased steadily; the hormone levels in 6-week pregnancy, 8-week pregnancy and 10-week pregnancy were significantly higher than those in 4-week pregnancy (all <0.05); except the levels of P and β-HCG in 10-week pregnancy, the hormone levels in the observation group were superior to those in the control group (all <0.05). After treatment, the early abortion rate was 16.7% (5/30) in the observation group, which was lower than 33.3% (10/30) in the control group (<0.01); the pregnancy rate was 96.0% (24/25) in the observation group, which was higher than 80.0% (16/20) in the control group (<0.01).@*CONCLUSION@#Acupoint catgut embedding is effective for preventing threatened abortion, which could significantly reduce the spontaneous abortion rate, improve the pregnancy success rate, regulate hormone levels in patients after IVF-ET.

Maxillary sinus floor augmentation: with or without bone grafting / 中国组织工程研究

BACKGROUND: Insufficient bone mass in the posterior maxilla region often increases the difficulty of dental implantation. The application of maxillary sinus floor elevation successfully solves this problem. In the surgery bone grafting can be used to obtain sufficient bone mass. However, nonuse of graft materials can shorten the cycle of patient's treatment and reduce trauma and cost. OBJECTIVE: Combining the latest relevant research trends, to review the advances in the study of maxillary sinus floor elevation with and without bone grafting. METHODS: The first author searched PubMed, VIP, WanFang and CNKI databases using computer for relevant articles published from January 1985 to August 2018. The key words were "dental implant, maxillary sinus, bone augmentation, bone substitute" in English and Chinese, respectively. Finally, 78 articles were included in result analysis after screening and summarizing. RESULTS AND CONCLUSION: Ideal results can be achieved in the maxillary sinus floor elevation with or without simultaneous bone grafting In addition, the nonuse of grafting materials have the advantages of simplifying surgical procedures, shortening treatment cycles, reducing trauma and pain, reducing treatment costs, reducing complications and failure rates, thus gaining the favor of doctors and patients. Therefore, the maxillary sinus floor elevation without simultaneous bone grafting will be the primary choice of the doctors engaged in dental implantation in the future.

The diagnostic evaluation of magnetic resonance enteroclysis in inflammatory bowel disease / 中国医师杂志

Objective This study aims to investigate diagnosis accuracy of magnetic resonance enteroclysis (MRE) and evaluation of image quality in inflammatory bowel disease (IBD).Methods A total of 132 patients were assumed inflammatory bowel disease and their MRE were retrospectively evaluated.Imaging feature of MRE and histopathologic results by surgery and endoscope were compared.The sensitivity,specificity and diagnostic performance were calculated and image quality of MRE were evaluated by using the quadrature method.Results A total of 530 small intestine segments were analyzed according to evaluation criteria.Imaging quality of 323,170,29 and 8 small intestine segments were graded 1,2,3 and 4 respectively.Consistency for scoring of imaging quality and evaluation of IBD in intestine segments between observers was pretty good (k =0.73).Scoring of imaging quality was the highest in distal ileum (1.12) and terminal ileum(1.15) and scoring was the lowest in duodenum (1.92) and jejunum(1.6).The sensitivity,specificity and diagnostic agreement rate of MRE in inflammatory bowel disease were 94.3％,92.6％ and 94.7％ respectively,including 2 false positive and 6 false negative result.Conclusions MRE can provide high performance in diagnosis of inflammatory bowel disease and good image quality.

Secondary metabolites of petri-dish cultured Antrodia camphorata and their hepatoprotective activities against alcohol-induced liver injury in mice / 中国天然药物

Antrodia camphorata, a well-known and highly valued edible medicinal mushroom with intriguing activities like liver protection, has been traditionally used for the treatment of alcoholic liver disease. A. camphorata shows highly medicinal and commercial values with the demand far exceeds the available supply. Thus, the petri-dish cultured A. camphorata (PDCA) is expected to develope as a substitute. In this paper, nineteen triterpenes were isolated from PDCA, and thirteen of them were the unique anthroic acids in A. camphorata, including the main content antcin K, which suggested that PDCA produced a large array of the same anthroic acids as the wild one. Furthermore, no obvious acute toxicity was found suggesting the edible safety of PDCA. In mice alcohol-induced liver injury model, triglyceride (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA) had been reduced by the PDCA powder as well as the main content antcin K, which indicated that the PDCA could protect alcoholic liver injury in mice model and antcin K could be the effective component responsible for the hepatoprotective activities of PDCA against alcoholic liver diseases.

Effect on immune factors and serum CA125 in patients of threatened abortion in early pregnancy complicated with subchorionic hematoma treated with auricular acupuncture combined with dydrogesterone / 中国针灸

OBJECTIVE@#To evaluate the therapeutic effect of auricular acupuncture combined with dydrogesterone for threatened abortion in early pregnancy complicated with subchorionic hematoma.@*METHODS@#A total of 80 patients were randomized into an observation group and a control group, 40 cases in each one. In the control group, dydrogesterone was taken orally twice a day, 10 mg a time until 12-week into pregnancy. In the observation group，auricular acupuncture was applied at penqiang (TF), pizhixia (AT), shen (CO), xin(CO), gan (CO), jiaogan (AH) and neifenmi (CO) on the basis of the control group, the auricular points on both sides were used alternatively. The auricular points were replaced every 3 days with 1 day break, totally 3 weeks (20 days) were required. Before treatment and after 10, 20 days of treatment, the percentage of helper T lymphocyte (Th) and inhibitory T lymphocyte (Ts), ratio of Th and Ts and serum level of CA125 were compared in the two groups. The areas of subchorionic hematoma and gestational sac were evaluated by B ultrasound. The therapeutic effect in the two groups were compared.@*RESULTS@#The effective rate in the observation group was 80.0% (32/40), which was superior to 65.0% (26/40) in the control group (<0.05). After 10, 20 days of treatment, the percentage of Th and ratio of Th and Ts were lower than before treatment, the percentage of Ts were increased in the two groups (<0.01). After 20 days of treatment, the percentage of Th and ratio of Th and Ts in the observation group were lower than the control group (<0.01), the percentage of Ts was higher than the control group (<0.01). After 10, 20 days of treatment, the serum levels of CA125 were reduced compared before treatment in the two groups (<0.01), and the serum levels of CA125 in the observation group were lower than the control group (<0.01). After 10, 20 days of treatment, the ratio of subchorionic hematoma area and gestational sac area in the observation group was lower than the control group (<0.01).@*CONCLUSION@#Auricular acupuncture combined with dextroprogesterone can improve the effective rate of patients with threatened abortion in early pregnancy complicated with subchorionic hematoma, regulate immune factors, promote the hematoma absorption, and has a better synergistic effect with dextroprogesterone.

Current status and future perspectives of daptomycin development / 药学学报

Due to the potent bactericidal activity and low incidence of drug resistance, the novel cyclic lipopeptide antibiotic - daptomycin has emerged as one of the first line antimicrobial agents in the treatment of serious infections caused by gram-positive resistant pathogens. This review summarizes the research advances of daptomycin in recent years, mainly including spectrum of antimicrobial activity, biosynthesis, mode of action, mechanism of drug resistance, structure-activity relationships, surotomycin and siderophore-daptomycin conjugate to kill multidrug resistant Acinetobacter baumannii. The findings summarized in this review highlight the directions of next-generation of daptomycin derivatives.

Zoledronic acid promotes dental implant osseointegration in osteoporosis / 中国组织工程研究

BACKGROUND: Zoledronic acid can effectively enhance dental implant osseointegration, but it can also impair soft tissue and blood supply around the implant, eventually leading to bisphosphonate-associated osteonecrosis of the jaw. Therefore, it is a problem highly valued in implant restorations. OBJECTIVE: To review the application of zoledronic acid in the dental implantation after osteoporosis. METHODS: The first author searched PubMed and CNKI using computer for relevant articles concerning the potential mechanism by which zoledronic acid promotes dental implant osseointegration as well as its application in vitro and in vivo. The key words were "bisphosphonate, zoledronic acid, implant, osseointegration" in English and Chinese, respectively. RESULTS AND CONCLUSION: Zoledronic acid has been demonstrated to inhibit bone resorption and promote bone formation via local or systemic use, single or combined use with other drugs. However, the inhibition of osteoclasts by zoledronic acid is associated with the dose and action time of zoledronic acid. Thus, further investigation on the specific mechanisms of zoledronic acid at different dose and with different action time are warranted. We should further elucidate the risk factors and determinants of osteonecrosis of the jaw through clinical studies, and then find effective approaches to reduce the risk of jaw osteonecrosis and to maximize the positive effect of zoledronic acid in the dental implantation.

Novel antifungal agents against cryptococcal infections / 药学学报

Cryptococcal meningitis, caused by fungus Cryptococcus neoformans, is responsible for over a million infections and 600 000 deaths annually. Largely due to the limited treatment options and the intrinsic drawbacks coupled with drug resistance to current therapies, it is urgent to discover novel antifungal agents against cryptococcosis. An ideal antifungal drug should at least satisfy the following criteria: fungicidal, fungus-specific, permeable for the host barriers such as cell membranes of phagocytes and the blood-CNS barrier. Both discovery of candidates with novel mode of action and repurposing existing molecules with potent anti-cryptococcal activity are effective ways in discovery of new anti-cryptococcal agents. Here, we summarized recent advances in the study of anti-fungal activities, mechanisms of action, and clinical developments of new anti-cryptococcal drugs.

Immunoserology and RHD Genotype Analysis of DVI Type 3 Genotype Pregnant Women with Anti-D / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To performe the immuneserological and RHD Genotype analyses for DVI type 3 genotype pregnemt women with anti-D.</p><p><b>METHODS</b>RhD blood type of this pregnant women was identified by common serological methods, then the blood group specific antibodies was screened and identified; the polymerase chain reaction-sequence specific primer(PCR-SSP) was used to identify the pregnant women's RHD genotype; RhD blood group for the pregnant women, her spouse and daughter was genogrouped and genetically analyzed by multiplex ligation-dependent probe amplification(MLPA). The heredity of this family was analyzed finally.</p><p><b>RESULTS</b>The titer of IgG anti-D in the pregnant woman serum was 1:8; the PCR-SSP showed that the 3rd to 6th exons of RHD gene were missing in the pregnant woman. the genotype of pregnant woman was identified as DVI type 3; the MLPA analysis showed that this pregnant women owned only one RHD allele with 3rd to 6th exons missed, and her genotype was identified as CDe/cde; her spouse was identified as CDe/CDe homozygous genotype, and her daughter as CDe/CDe.</p><p><b>CONCLUSION</b>Accurate identification of RhD blood type is of great significance for a safe and effective clinical blood transfusion strategy, and for taking appropriate measures to prevent hemolytic disease of newborn (HDN) at women childbearing age.</p>

Liver and cardiac iron overload is harmful to HLA-identical hematopoietic stem cell transplantation in thalassemia children: an MRI detection / 中国组织工程研究

BACKGROUND: The majority of children with β-thalassemia major have iron overload, and iron overload may have negative effects on hematopoietic stem cell transplantation. OBJECTIVE: To assess the effects of liver and cardiac iron overload detected by magnetic resonance imaging (MRI) T2* on HLA-identical allogeneic hematopoietic stem cell transplantation in children with β-thalassemia major. METHODS: Eighty-one children with β-thalassemia major who were over 3 years of age and could cooperate with MRI detection were subjected to liver and heart MRI T2* tests before or after HLA-identical allogeneic hematopoietic stem cell transplantation. According to the test results, we calculated the liver and cardiac iron content, defined as an indicator of liver and heart iron overload. Then, there was a correlation analysis between the liver and cardiac iron content and serum ferritin, time of hematopoietic reconstitution, mortality rate, implantation rate and the morbidity of transplantation related complications, such as graft-versus-host disease, infections, autoimmune hemolysis, pancytopenia, hepatic veno-occlusive disease, septicemia. RESULTS AND CONCLUSION: The liver iron content was positively correlated with the time of hemoglobin implantation (r=0.229, P=0.043), and the cardiac iron content were positively correlated with the mortality rate (r=0.266, P=0.017); the serum ferritin level was negatively correlated with the implantation rate (r=-0.289, P=0.009), and positively correlated with the morbidity of septicemia (r=0.251, P=0.024) and pancytopenia (r=0.276, P=0.013). Therefore, iron overload exerts negative effects on HLA-identical allogeneic hematopoietic stem cell transplantation in β-thalassemia major children, and it is necessary to detect serum ferritin level and assess liver and cardiac iron overload before cell transplantation.

Therapeutical effect of Irbesartan for coronary atherosclerosis mice (ApoE-/-) and its possible mechanisms / 中国免疫学杂志

Objective:To analyze the therapeutical effect of Irbesartan for coronary atherosclerosis mice ( ApoE-/-) and its possible mechanisms. Methods: A total of 16 male ApoE-/- mice were randomly divided into control group and Treatment group [Irbesartan,50 mg/(kg·d),4 weeks]. HE,immunofluorescence,Western blot and ELISA were performed to analyze the effect of Irbesartan on ApoE-/- and the changes of related signaling pathways. Results: Compared with control group,the treatment group had lower atheroma macular areas and inflammatory cytokines in blood vessel (P<0. 05). Treatment group had lower levels of leptin,but higher levels of PPAR-γ and adiponectin in perivascular adipose tissues ( PVAT ) than these of control group, the difference were statistically significant ( P<0. 05 ) . Western blot and immunofluorescence analysis shown that Irbesartan treatment significantly depressed the expression of p-p65 and p-IKK in PVAT when compared with these of control group (P<0. 05). Conclusion:Irbesartan has significantly therapeutic effect on ApoE-/-mice,the possible mechanisms including anti-inflammatory effects in PVAT,improved the adipose tissue function and regulated the PPAR-γ-NF-κB signaling pathways.

Novel liposomal drug delivery system actively targeting Cryptococcus neoformans and elimination of infection / 药学学报

The purpose of this study is to develop a liposomal drug delivery system actively targeting Cryptococcus neoformans and explore its feasibility in therapy of cryptococcal infection. The specific fungibinding peptide was screened from 12-mer random phage display library, and linked to PEG-DSPE as the functional material of liposomes. The targeting capability of peptide-modified liposomes were investigated by fungi binding assay in vitro and fluorescence imaging in vivo. Itraconazole as a model drug were then encapsulated in the liposomes and were evaluated in pharmacodynamic test in vitro and for therapeutic effects against cryptococcal meningitis complicated with pulmonary cryptococcosis in vivo. The results showed that the peptide (sequence:NNHREPPDHRTS) could selectively recognize Cryptococcus and effectively mediate the corresponding liposomal formulation to accumulate in the infection site in vivo. This peptide-modified liposome has a small particle size (mean diameter of 88.25±2.43 nm) with a homogeneous distribution and high encapsulation efficiency (88.05±0.25%) of itraconazole. After intravenous administration, the pathogens were obviously eliminated in lung and brain, and the life-span of model mice were significantly prolonged, suggesting a promising potential of this cryptococcosis targeting strategy.