Objective:To investigate the effects of dual vascularized tissue-engineered bone constructed by vascular bundles and endothelial progenitor cells (EPCs) on repair of large bone defects and vascular regeneration.Methods:EPCs were seeded on the demineralized bone matrix (DBM) scaffolds and cultured for 6 days. The attachment and morphology of EPCs on DBM scaffolds were observed by electron microscopy. Next, the radial artery was implanted into a vascular groove opened inside the DBM-EPCs composite scaffolds. Finally, models of a large segmental bone defect were constructed using the radii from 18 New Zealand white rabbits. The rabbits were randomly divided into 4 groups using a simple random sampling method: DBM group, DBM+EPCs group, DBM+vascular bundle group, and DBM+EPCs+vascular bundle group. The DBM group and DBM+EPCs group shared the same rabbits so that transplantations were conducted into the left and right forearms respectively; the DBM+vascular bundle group and DBM+EPCs+vascular bundle group also shared the same rabbits so that transplantations were conducted into the left and right forearms respectively. Consequently, there were 9 experimental sites in each group. X-ray examination and gross morphological observation were performed to evaluate the bone regeneration in the experimental rabbits in each group at 4, 8, and 12 weeks after surgery, and CD31 immunofluorescence staining was used to evaluate the vascular regeneration. Micro-CT was used to analyze bone tissue parameters and reconstruct the three-dimensional structures of the defects site at 12 weeks after surgery.Results:Compared with the DBM, DBM+EPCs and DBM+vascular bundle groups, the DBM+EPCs+vascular bundle group showed new bone tissue crawling on the scaffold surface at 4 weeks after surgery, almost complete healing of the bone defect area at 8 weeks, and forming of a complete and dense bone bridge and appearance of a bone marrow cavity at 12 weeks. Micro-CT data at 12 weeks after surgery showed regular arrangement of the trabeculae, significantly improved mineralization, and increased thickness of the bone cortex in the DBM+EPCs+vascular bundle group. Additionally, in the DBM+EPCs+vascular bundle group, the number of microvessels was significantly higher than that in the other groups at 4, 8, 12 weeks after surgery ( P<0.05), and the angiogenesis and bone tissue regeneration were particularly prominent at 12 weeks after surgery. The number of CD31 cells in the DBM+EPCs+vascular bundle group increased significantly more than that in the DBM, DBM+EPCs and DBM+vascular bundle groups ( P<0.05). Conclusion:As the dual vascularized tissue-engineered bone constructed by vascular bundles and EPCs can significantly promote bone tissue regeneration and angiogenesis, it may be a potential therapeutic strategy for repair of large bone defects.

Objective:To investigate the effects of dual vascularized tissue-engineered bone constructed by vascular bundles and endothelial progenitor cells (EPCs) on repair of large bone defects and vascular regeneration.Methods:EPCs were seeded on the demineralized bone matrix (DBM) scaffolds and cultured for 6 days. The attachment and morphology of EPCs on DBM scaffolds were observed by electron microscopy. Next, the radial artery was implanted into a vascular groove opened inside the DBM-EPCs composite scaffolds. Finally, models of a large segmental bone defect were constructed using the radii from 18 New Zealand white rabbits. The rabbits were randomly divided into 4 groups using a simple random sampling method: DBM group, DBM+EPCs group, DBM+vascular bundle group, and DBM+EPCs+vascular bundle group. The DBM group and DBM+EPCs group shared the same rabbits so that transplantations were conducted into the left and right forearms respectively; the DBM+vascular bundle group and DBM+EPCs+vascular bundle group also shared the same rabbits so that transplantations were conducted into the left and right forearms respectively. Consequently, there were 9 experimental sites in each group. X-ray examination and gross morphological observation were performed to evaluate the bone regeneration in the experimental rabbits in each group at 4, 8, and 12 weeks after surgery, and CD31 immunofluorescence staining was used to evaluate the vascular regeneration. Micro-CT was used to analyze bone tissue parameters and reconstruct the three-dimensional structures of the defects site at 12 weeks after surgery.Results:Compared with the DBM, DBM+EPCs and DBM+vascular bundle groups, the DBM+EPCs+vascular bundle group showed new bone tissue crawling on the scaffold surface at 4 weeks after surgery, almost complete healing of the bone defect area at 8 weeks, and forming of a complete and dense bone bridge and appearance of a bone marrow cavity at 12 weeks. Micro-CT data at 12 weeks after surgery showed regular arrangement of the trabeculae, significantly improved mineralization, and increased thickness of the bone cortex in the DBM+EPCs+vascular bundle group. Additionally, in the DBM+EPCs+vascular bundle group, the number of microvessels was significantly higher than that in the other groups at 4, 8, 12 weeks after surgery ( P<0.05), and the angiogenesis and bone tissue regeneration were particularly prominent at 12 weeks after surgery. The number of CD31 cells in the DBM+EPCs+vascular bundle group increased significantly more than that in the DBM, DBM+EPCs and DBM+vascular bundle groups ( P<0.05). Conclusion:As the dual vascularized tissue-engineered bone constructed by vascular bundles and EPCs can significantly promote bone tissue regeneration and angiogenesis, it may be a potential therapeutic strategy for repair of large bone defects.

Objective To investigate the correlation between biofilm gene,efflux pump gene,biofilm forming ability and drug resistance of Acinetobacter baumarmii(AB)isolated from the patients of clinical infectious diseases.Methods A total of 119 non-repeating Acinetobacter baumannii isolates(74 MDR-AB strains and 45 non-multi-drug resistant strains)were collected.The effector pump genes(adeB,adeJ,adeG,adeS and adeR)and biofilm-related genes(bap,ompA,csuA,csuB,csuC,csuD,csuE,abaI,bfmR,bfmS)were detected by PCR.Bacterial biofilm was constructed in vitro with 24-well cell culture plates,and the formation of biofilm was qualitatively observed by crystal violet staining.Results Acinetobacter baumannii was resistant to most of the commonly used antibiotics and sensitive to tigacycline,polymyxin B and minocycline.The overall detection rate of biofilm-related genes was about 80％,and the detection rates of bap,csuB,csuC and csuD genes in multi-drug resistant bacteria were significantly higher than those in non-multi-drug resistant bacteria(P＜0.05).The detection rate of active effector pump genes was less than 70％,and the detection rate of adeB,adeJ,adeS and adeR genes in multidrug-resistant bacteria was significantly higher than that in non-multidrug-resistant bacteria(P＜0.05).The adeG carrying rate was opposite.Three multidrug-resistant strains and five non-multidrug-resistant strains did not carry the above efflux pump related genes,and no abeM gene was detected in all strains.The formation of biofilm was observed in 95.80％of strains.Conclusion Acinetobacter baumannii in hospital is mostly multidrug-resistant strains,most of which have strong biofilm forming ability.Multidrug-resistant bacteria have higher biofilm gene and effluent-pump gene carrying rate,which may be involved in the regulation and formation of multidrug resistance.

Stapled peptides with significantly enhanced pharmacological profiles have emerged as promising therapeutic molecules due to their remarkable resistance to proteolysis and performance to penetrate cells. The all-hydrocarbon peptide stapling technique has already widely adopted with great success, yielding numerous potent peptide-based molecules. Based on our prior efforts, we conceived and prepared a double-stapled peptide in this study, termed FRNC-1, which effectively attenuated the bone resorption capacity of mature osteoclasts in vitro through specific inhibition of phosphorylated GSK-3β. The double-stapled peptide FRNC-1 displayed notably improved helical contents and resistance to proteolysis than its linear form. Additionally, FRNC-1 effectively prevented osteoclast activation and improved bone density for ovariectomized (OVX) mice after intravenous injection and importantly, after oral (intragastric) administration. The double-stapled peptide FRNC-1 is the first orally effective peptide that has been validated to date as a therapeutic candidate for postmenopausal osteoporosis (PMOP).

Abstract OBJECTIVE To analyze and summarize the research history, development status, trends and hotspots of Codonopsis Radix by bibliometrics. METHODS Search and screen the related literatures of Codonopsis Radix from the CNKI database and the Web of Science core collection database from Januar 1, 1992 to June 30, 2022. VOSviewer and CiteSpace softwares were used for visual analysis of the number of publications, authors, institutions, countries, funding funds, published journals, literature citation frequency, keywords, clustering and emergent word, and a visual graph was drew. RESULTS A total of 594 effective literature, 484 in Chinese and 110 in English were included. GAO Jianping and ZOU Yuanfeng were the scholars with the largest amount of Chinese and English literature. China was the country with the most published researches on Codonopsis Radix. The School of Pharmaceutical Science of Shanxi Medical University and the Chinese Academy of Sciences were the institutions with the largest number of Chinese and English literature publications respectively. The National Science Foundation of China was the largest fund to support the research of Codonopsis Radix. The journal that received the most Chinese and English literature were Journal of Chinese Medicinal Materials and International Journal of Biological Macromolecules respectively. The most frequently cited Chinese literature was a summary of the chemical constituents and pharmacological effects of Codonopsis Radix. The most frequently cited English literature was a study on the structure identification and pharmacological effects of Codonopsis Radix polysaccharides. The map of key words, clustering and emergent words in Chinese literature showed that the main research directions of Codonopsis Radix were compatibility formula, resource planting, pharmacological action and quality control. The map of key words, clustering and emergent words in English literature indicated that the study of Codonopsis Radix always focused on the material basis and mechanism of its active ingredients. CONCLUSION The annual publications on of Codonopsis Radix show an increasing trend, and the main research institutions are distributed in many universities and research institutes in China. Both Chinese and English literature have their own research directions, and the pharmacological effects of active ingredients are the common trend hotspots.

Objective To observe the level changes and clinical diagnostic value of follicular statin -1 (FSTL1)in the serum of patients with different types of acute coronary syndrome(ACS).Methods Collected the clinical diagnosis of acute coronary syndrome patients 98 cases,which contained ST segment elevation my-ocardial infarction(STEMI)in 34 cases,non ST elevation myocardial infarction(NSTEMI)in 28 cases,unsta-ble angina pectoris(UA)in 36 cases,while the examination resuLts of healthy people as a control group of 20 cases.The Venous blood was collected and the FSTL1 levels of the 4 groups were detected by ELISA.Results The levels of Serum FSTL1 in ACS group was significantly higher than that in normal control group(P<0.05).Serum FSTL1 of the ACS group were significant correlated with Gensini score,cTNT,hs-CRP(related coefficient:0.210,0.236,0.219 separately).The AUC of FSTL1 was 0.910(95% CI:0.832 -0.988),which was lower than cTNT.The best cut-off value of FSTL1 as a biomarker was 5.65 μg/L(specificity:84.2% and sensitivity:77.5%).Moreover the combination of FSTL1,HDL and cTNT exhibited significantly higher AUC=0.945(95% CI:0.909 -0.981)than did other biomarkers alone or pair combinations.Conclusion In pa-tients with acute coronary syndrome,serum FSTL1 levels has a positive correlation with the degree of coro-nary stenosis and inflammation reaction,and has certain value in the diagnosis of acute coronary syndrome.

Objective To evaluate the diagnostic performances of seven estimation formulas for glomerular filtration rate (GFR) in pre-operative patients with renal cell carcinoma.Methods A total of 386 pre-operative patients with renal cell carcinoma in the first affiliated hospital of Chongqing medical university from January 2012 to October 2014 were selected.All the patients' GFRs were measured by the renal dynamic imagingwith 99mTc-DTPA as reference (rGFR) and the seven GFR estimation equations (eGFR) were compared with the rGFR respectively.Their correlations and consistencies were observed with spearman correlation analysis and Bland and Altman analysis.The diagnostic sensitivity,specificity and likelihood ratios were calculated and the eGFR accuracies were assessed with receiver operator curve (ROC) analysis.Results The correlations between the rGFR and eGFRs were significantly (P＜0.001).In addition,CKD-EPI-Asian Crea and Ruijin formula were more accurate than others in different stages with larger ROC area in diagnosing renal cell carcinoma.Conclusion There were significant correlations between the eGFRs and rGFR,but some deviations existed.CKD-EPI-Asian Crea and Ruijin formula were more suitable for assessment of eGFR of pre-operative patients with renal cell carcinoma.However,both of these equations had a few limitations.

Objective To evaluate the diagnostic value of combination detection of alpha-fetoprotein (AFP),Golgi protein 73 (GP73) and a-L-fucosidase (AFU) for early hepatocellular carcinoma (HCC).Methods A total of 222 patients with liver diseases in this hospital from March 2016 to March 2017 were collected and divided into the early stage HCC group (74 cases),late stage HCC group (27 cases),liver cirrhosis group (74 cases) and chronic hepatitis B group (47 cases),and contemporaneous 49 individuals undergoing physical examination were selected as the healthy control group.The levels of serum GP73,AFP and AFU were detected in each group.The ROC curve was drawn.The diagnostic values of single detection and combined detection of 3 indicators for diagnosing early HCC were evaluated.Results The serum GP73,AFP and AFU levels in the early stage HCC group were significantly higher than those in the liver cirrhosis group,chronic hepatitis B group and healthy control group (P＜0.05).In the HCC screening,the area under the curve (AUC) of AFP ROC curve for singly diagnosing HCC was 0.910(95％CI:0.864-0.936),AUC of GP73 and AFP combined diagnosis was maximal [0.925 (95％ CI:0.889-0.950)] and the sensitivity was the highest (95.0％).In the differentiation diagnosis between early HCC and liver cirrhosis,AUC of GP73 for single diagnosis was maximal [0.842(95％CI:0.746-0.879)] and the specificity was the highest (86.5％);AUC of GP73 and AFU combined diagnosis was maximal[0.901(95％CI:0.788-0.907)].Conclusion GP73 and AFP for combined detection of HCC can increase the diagnostic efficiency of HCC screening.GP73 and AFU combined diagnosis can increase the diagnosis efficiency of early HCC,which has an important significance for the differentiation diagnosis between early HCC and liver cirrhosis.

Objective To investigate the significance of CD44v6 expression in acute leukemia( AL) and it's relation with the prognosis of AL. Methods Sixty AL patients were treated by enzyme linked immunosorbent assay( ELISA)as initial treatment group. Fourty-seven cases were remission as remission group, and 20 cases with no-remission group. Meanwhile,45 healthy people were served as the control group. The level of CD44v6 was measured by ELISA. Results The serum CD44v6 in initial treatment patients,remission group, no-remission group and control group were( 179. 34 ± 39. 41 )μg/L,( 190. 61 ± 28. 05 )μg/L,( 106. 72 ± 26. 38)μg/L and(98. 31 ± 21. 78)μg/L respectively,and the difference was significant( F =56. 303,P﹤0. 01),and the CD44v6 of initial treatment group and remission group were higher than that of no-remission group and control group(P﹤0. 05). The leukocyte levels was positive related to CD44v6 levels in 60 patients(r=0. 826,P﹤0. 01),and it was also related to disease stage,extramedullary infiltration(( r=0. 485,0. 512;P﹤0. 01). Conclusion The level of CD44v6 is closely related with the occurrence and development of acute leukemia. The assay of CD44v6 in serum of AL patients is helpful in diagnosing and predicting the risk of metastasis and prognosis in AL.

Objective　To investigate the response of multiple myeloma (MM) cells to arsenic trioxide (As2O3) and their possible mechanisms. Methods　Two MM-derived cell lines RPMI8226 and U266 cells were used as in vitro models. Cell apoptosis was assessed by morphology, flow cytometry, and DNA gel electrophoresis. Mitochondrial transmembrane potentials (△Ψm) were evaluated by measuring cellular Rhodamine 123 staining intensity. Protein expression was analyzed using Western blot. Results　Zero point one to 0.5?μmol/L As2O3 inhibited cell proliferation and 2.0?μmol/L As2O3 induced cell apoptosis, while 1.0?μmol/L As2O3 inhibited proliferation with a weak degree of apoptosis induction in RPMI8226 and U266 cell lines. As2O3-induced apoptosis was accompanied by mitochondrial transmembrane potentials (△Ψm) collapse and caspase-3 activation in the presence of intact membrane. Glutathione depleter buthionine sulfoximine enhanced, while disulfide bond-reducing agent dithiothreitol partially antagonized As2O3-induced △Ψm collapse and apoptosis in MM cells. All-trans retinoic acid (ATRA) could also induce apoptosis in RPMI8226 cells, but it did not show any cooperative effects with As2O3. Conclusion　As2O3 exerts apoptosis-inducing and growth-inhibiting effects on MM cells, and mitochondrium is a pivotal and common target of As2O3 for apoptosis induction.