BACKGROUND:Mineralized collagen is the fundamental unit of bone structure and function and a major component of the extracellular matrix.Biomimetic methods have been developed to fabricate mineralized collagen with a natural bone nanostructure.Currently,mineralized collagen has been approved by regulatory authorities and applied clinically,playing a positive role in bone defect repair.OBJECTIVE:To present the integration strategies of bioactive factors with mineralized collagen,summarize schemes to enhance the osteogenic potential of mineralized collagen,emphasize the multifunctional coordination applications of mineralized collagen,and finally discuss current research focuses and future trends.METHODS:The authors searched for relevant literature in databases such as PubMed,Web of Science,Medline,WanFang,and CNKI,from 2009 to 2023,using keywords"mineralized collagen,biomimetic,functionalization,bioactive factors,osteogenesis,multi-functional coordination,bone tissue repair"in English and"mineralized collagen,biomimetic,functionalization"in Chinese.Out of 375 initially identified articles,57 were included for review after screening.RESULTS AND CONCLUSION:(1)Mineralized collagen,with its porous structure and large surface area,containing nano-hydroxyapatite,makes it an effective carrier for cells,various growth factors,and drugs.(2)Single or multiple bioactive factors can be efficiently and orderly released through different loading methods or combinations,achieving the multifunctionalization of mineralized collagen.The impact of physicochemical conditions on the bioactivity of factors and their effects on the degradability,hydroxylapatite crystal morphology,nanostructure,and content of mineralized collagen should be considered.Moreover,calcium ions in mineralized collagen can be substituted with various inorganic non-metal ions,enhancing its osteogenic,angiogenic,immunomodulatory,and anti-infective properties.(3)Ultimately,during in situ bone regeneration,functionalized mineralized collagen serves as a scaffold material,providing structural support for bone defects,and as a drug delivery system,continuously delivering various bioactive factors locally,playing roles in anti-infection,immunomodulation,promoting angiogenesis and osteogenesis,and repairing various complex bone defects.

BACKGROUND:Mineralized collagen is the fundamental unit of bone structure and function and a major component of the extracellular matrix.Biomimetic methods have been developed to fabricate mineralized collagen with a natural bone nanostructure.Currently,mineralized collagen has been approved by regulatory authorities and applied clinically,playing a positive role in bone defect repair.OBJECTIVE:To present the integration strategies of bioactive factors with mineralized collagen,summarize schemes to enhance the osteogenic potential of mineralized collagen,emphasize the multifunctional coordination applications of mineralized collagen,and finally discuss current research focuses and future trends.METHODS:The authors searched for relevant literature in databases such as PubMed,Web of Science,Medline,WanFang,and CNKI,from 2009 to 2023,using keywords"mineralized collagen,biomimetic,functionalization,bioactive factors,osteogenesis,multi-functional coordination,bone tissue repair"in English and"mineralized collagen,biomimetic,functionalization"in Chinese.Out of 375 initially identified articles,57 were included for review after screening.RESULTS AND CONCLUSION:(1)Mineralized collagen,with its porous structure and large surface area,containing nano-hydroxyapatite,makes it an effective carrier for cells,various growth factors,and drugs.(2)Single or multiple bioactive factors can be efficiently and orderly released through different loading methods or combinations,achieving the multifunctionalization of mineralized collagen.The impact of physicochemical conditions on the bioactivity of factors and their effects on the degradability,hydroxylapatite crystal morphology,nanostructure,and content of mineralized collagen should be considered.Moreover,calcium ions in mineralized collagen can be substituted with various inorganic non-metal ions,enhancing its osteogenic,angiogenic,immunomodulatory,and anti-infective properties.(3)Ultimately,during in situ bone regeneration,functionalized mineralized collagen serves as a scaffold material,providing structural support for bone defects,and as a drug delivery system,continuously delivering various bioactive factors locally,playing roles in anti-infection,immunomodulation,promoting angiogenesis and osteogenesis,and repairing various complex bone defects.

Objective:To study the epidemic situation of Marmota himalayana plague and Yersinias infection in Yugur Autonomous County of Sunan (Sunan County) of Gansu Province, and to provide new ideas for prevention and control of plague. Methods:From 2014 to 2018, liver and spleen, cecum, throat swabs and blood samples of Marmota himalayana were collected on the spot in Sunan County, where Yersinia strains were isolated and identified, and plague F1 antigen and antibody were detected. Results:A total of 634 liver and spleen samples, 427 cecum samples and 426 throat swabs samples were collected from Marmota himalayana, and 23 strains of Yersinia pestis, 2 strains of Yersinia marcescens, and 1 strain of Yersinia flexneri were detected, with the detection rates of 3.63% (23/634), 0.47% (2/427) and 0.23% (1/426), respectively. The detection rate of Yersinia pestis in different years was statistically significantly different (χ 2 = 13.19, P = 0.010). A total of 1 822 serum samples of Marmota himalayana were detected, and 5 F1 antibody positive samples were detected, with a positive rate of 0.27%, the difference of positive rate between different years was statistically significant (χ 2 = 25.22, P < 0.001); 282 liver and spleen tissue homogenates of Marmota himalayana were detected, 22 F1 antigen positive samples were detected, the positive rate was 7.80%, and there was no statistically significant difference between different years (χ 2 = 7.85, P = 0.097). The 23 strains of Yersinia pestis detected were distributed in Mati Tibetan Township (12 strains), Dahe Township (6 strains) and Qifeng Tibetan Township (5 strains); 1 strain of Yersinia flexneri and 2 strains of Yersinia marcescens were both located in Dahe Township. Conclusion:There is an epidemic of plague among animals in Sunan County from 2014 to 2018, and the areas where Yersinia pestis and non pathogenic Yersinia are detected overlapped.

Objective To investigate the development and application of blood purification in PICU. Methods The demographic data,diagnosis,length of stay,prognosis,patterns and frequency of blood purifi-cation and complications of PICU patients treated with blood purification in our hospital from 2010 to 2017 were retrospectively analyzed. Results The patients with blood purification accounted for 3. 1％ of hospital-ized children in the same period. From 2010 to 2017,the patients and times with blood purification increased by 370. 6％ and 398. 3％ respectively. The times of continuous veno-venous hemodiafiltration(CVVHDF), plasma exchange and hemoperfusion increased by 135. 2％,6300％ and 1600％ respectively. The frequency of CVVHDF,plasma exchange and hemoperfusion accounted for 42. 8％(492/1151),33. 5％(386/1151), and 23. 7％ (273/1151) respectively. Drug and toxic poision accounted for the highest proportion of 28. 6％(81/284),neurological diseases accounted for 20. 8％(59/284),sepsis with multiple organ dysfunction syn-drome accounted for 18. 0％( 51/284 ) , digestive system diseases, autoimmune diseases, renal diseases and metabolic diseases accounted for 14. 4％( 41/284 ) ,4. 9％( 14/284 ) ,4. 9％ ( 14/284 ) and 4. 2％( 12/284 ) respectively. The cure rate was 63. 8％. Complication included thrombus. Conclusion Blood purification has become the preferred modality for the management of critically ill children. Pediatric blood purification tech-niques have developed rapidly in our PICU and domestic pediatric. Further specification is required,so that it may represent the adequate choice for critical ill children.

Objective:To prepare the velvet antler polypeptide-collagen/chitosan composite materials,and to investigate its promotive effect on cicatrization of mandibular defect and possible mechanism.Methods:The collagen and chitosan solution were mixed.The composite material was prepared by glutaraldehyde crosslinking method.The microstructure of the composite material was observed by transmission electron microscope (SEM).The unilateral mandibular defect models of 36 rabbits were established.The rabbits were divided into experiment and control groups,and each group was divided into 4-,8-and 12-week subgroups,and there were 6 rabbits in each sub group.The rabbits in experiment group were implanted with velvet antler polypeptide-collagen /chitosan composite materials and the rabbits in control group were treated.4,8 and 12 weeks after operation,the histology of bone defect and peripheral nerve reconstruction of the rabbit models were detected by CT;the expression of vascular endothelial growth factor (VEGF) in bone tissue of the rabbits was detected by immunohistochemistry;the ultrastructure of bone defect was observed by SEM.Results:The structure of composite materials had layered folds and the inner diameter of the stent became larger and mainly dominated by sheet structure,which was the ideal structure of biological materials.4 weeks after operation,the new bone was formatted in experiment group,most of the new bone like-tissue materials were degraded,and the VEGF expression showed an increasing trend;8 weeks after operation,the trabecular bone in the bone defect of the rabbits in experiment group was increased obviously and the expression of VEGF was decreased.12 weeks after operation,the new bone formation and the density in experiment group was consistent with the normal tissue,and the expression level of VEGF returned to normal.At each the point after operation,the degree of bone defect healing and bone formation rate in experiment group were obviously prior to control group.Conclusion:Velvet antler polypeptide-collagen /chitosan composite material has the promotive effect on the fracture healing of mandibular defect of the rabbits and its possible mechanism may be related to promoting the expression of VEGF.

[ ABSTRACT] AIM:To investigate the effect of microwave radiation at different intensities on the rat myocardium and its possible mechanism.METHODS:The rats were radiated by the intensity of 500, 1 000, 1 500 and 2 000 W/m2 with 2 450 MHz microwave for 6 min.The heart tissue was collected 6 h after microwave radiation.ATP and mitochondria complexⅣandⅤwere measured.The changes of the tissue structures were observed under transmission electron micro-scope.The apoptosis of the myocardial cells was detected by a cell analyzer.The protein level of cleaved caspase-3 was de-termined by Western blotting.RESULTS:The concentration of ATP and activity of mitochondria complexⅣandⅤsigni-ficantly decreased compared with control group in the cardiac tissues.The decreased number, morphological abnormalities such as dissolved cavitation, matrix and obvious tumefaction of mitochondria were observed under transmission electron mi-croscope.The microwave radiation induced the apoptosis of myocardial cells in the rats.The cell apoptotic rate and the pro-tein level of cleaved caspase-3 increased with increasing intensity of microwave radiation ( P<0.05 ) .CONCLUSION:Microwave radiation has obvious injury effect on the rat heart, which can cause cardiac energy metabolism dysregulation and cardiac myocyte apoptosis.

OBJECTIVE To explore the pro-apoptotic mechanism of juglone in SiHa cells and to in?vestigate its associated signal transduction pathways. METHODS SiHa cells were treated with juglone 20μmol·L-1 for 24,48 and 72 h. Cellular morphology was detected by inverted microscopy.The cell viability was detected by methyl thiazolyl tetrazolium (MTT) assay. After 24 h treatment with juglone 20μmol·L-1,the cell apoptosis was detected by flow cytometry while the expressions of apopto?sis-related protein BCL-2,BAX and cleave-caspase-3,PI3K/AKt pathway-related protein PTEN,AKT and pAKT were detected by Western blotting. RESULTS After treatment with juglone for 24, 48 and 72 h,the growth of SiHa cells was significantly inhibited. Compared with cell control group,cells in juglone treated gruop were sparse,slipped off the wall,became round and the cell proliferation inhibitory rate was 43.3%,63.0%and 73.1%(P<0.05,P<0.01),respectively. Twenty-four hours post treatment, the early apoptosis rate of juglone treated gruop cells was increased by(6.47±1.79)%(P<0.01)compared with cell control group. Western blotting results showed that the expression of BCL-2 decreased by 53.0%while the expression of BAX and caspase-3 increased by 85.5%and 183.3%,respectively. The expression of PTEN was increased by 75.0% but the pAKt was decreased by 45.8%(P<0.01). CONCLUSION Juglone can upregulate the expression of PTEN, thus inhibiting PI3K/AKt pathway and promoting apoptosis of SiHa cells.

Aim To explore the protective effects of LPPC ( procyanidins extracted from the litchi pericarp) on cardiomyocyte apoptosis in septic rats and its mech-anisms. Methods The rats were randomly divided in-to 5 groups, and were given orally the drug for two weeks continuously. The control group ( control) and sepsis model group ( LPS ) were given distilled water once a day. LPPC low, medium and high dose groups were given LPPC 50 , 100 , 200 mg · kg-1 · d-1 re-spectively which were prepared freshly every day. After the treatment, sepsis animal models were established. Except for the control group, other groups were injec-ted LPS (lipopolysacchride, 10mg·kg-1) intraperito-neally to induce acute sepsis model. 4hrs later, rat se-rum was collected, isoenzyme ( CK-MB ) , lactate de-hydrogenase ( LDH ) and activity of aspertate amin-otransferase ( AST/GOT) were detected. Then rat car-diac tissue was obtained and cardiac tissue malondial-dehyde ( MDA ) , total antioxidant capacity ( T-AOC ) and reduced glutathione ( GSH ) content were deter-mined. TUNEL staining was performed to analyze the apoptosis of myocardial cells. Cleaved caspase-3 and TNF alpha protein expressions were analyzed by West-ern blot. Results Compared with the control group ( control) , serum of sepsis model group rats CK-MB, LDH, AST/GOT and cardiac tissue MDA content were significantly increased (P<0. 01). At the same time, the activity of cardiac tissue T-AOC and GSH de-creased obviously ( P<0. 01 ) . The apoptotic myocar-dial cells increased significantly ( P<0. 01 ) , and the expression level of cleaved caspase-3 and TNF alpha decreased obviously ( P <0. 01 ) . LPPC pretreatment significantly decreased the serum CK-MB, LDH, AST/GOT and tissue MDA content, increased tissue T AOC and GSH activity, attenuated apoptosis of rat myocardi-al cells significantly, and decreased expression level of cleaved caspase-3 and TNF alpha. Conclusion LPPC pretreatment can significantly attenuate rat myocardial cell apoptosis induced by sepsis, and the underlying mechanisms may be related to its anti-oxidative effects.

Aim To study the mechanisms of the pro-tective effect of procyanidin B2 ( PCB2 ) on the myocar-dial cell apoptosis induced by lipopolysaccharide ( LPS) . Methods Using the primary culture rat myo-cardial cells, myocardial cell injury model was induced by LPS. PCB2 low, medium and high dose groups, were cultured with 6. 25 , 12. 5 , 25. 0 μmol · L-1 PCB2 respectively in DMEM medium for 24 h continu-ously. Myocardial cell survival rate was determined by MTT colorimetric method. Cardiacmyocyte NOX activi-ty was determined by lucigen chemiluminescence meth-od . Western blot analysis was used to detect myocardi-al NADPH oxidase p47phox expression. TUNEL method was used to detect apoptosis and flow cytometry was used to determine the content of myocardial cells ROS. Results Compared with control group, the cell dam-age induced by LPS group myocardial cell survival rate significantly decreased ( P <0. 01 ) , and myocardial cell NOX activity, p47phox expression, apoptotic cell number and ROS content were significantly increased (P<0. 01). PCB2 low, medium and high dose groups cell survival rates were significantly elevated, myocar-dial cell NOX activity and p47phox expression, apoptotic cell number and the ROS content decreased significant-ly in a dose-dependent manner ( P <0. 01 ) . Conclu-sion PCB2 protects myocardial cell apoptosis induced by LPS via inhibiting the expression of NADPH oxidase activation, p47phox expression and reactive oxygen spe-cies generation.

OBJECTIVE To investigate the protective effect of velvet antler polypeptides(VAP)on hydrogen peroxide( H2 O2 )-induced injury in vascular endothelial cells and the possible mechanism.METHODS The EVC-304 cells cultured invitrowere incubated with H2 O2 for another 12 h after pretreat-ment with VAP 20,40 and 80 mg·L-1 for 24 h. Cell viability was determined by MTT assay, Hoechst333258 staining was used to observe cell morphology,the activity of superoxide dismutase (SOD)and the level of malondialdehyde( MDA)were detected with kits and the expression of heat shock protein(HSP70)and caspase 3 was detected by Western blotting. RESULTS Compared with the normal control group,the cell survival rate was decreased significantly in H2 O2 injury group( P ﹤0.01),cell shrinkage,chromatin condensation,and nuclear fragmentation were seen,the intracellular SOD activity decreased while MDA content increased(P﹤0.01),and caspase 3 and HSP70 expression increased(P﹤0.01). Compared with H2 O2 group,the cell survival rate in VAP 20,40 and 80 mg·L-1 pre-treatment groups increased significantly(P﹤0.01),the apoptosis ratio declined from(25.3±1.0)% to (15.2±1.2)%,(10.3±0.9)% and(7.9±1.4)%(P﹤0.01),the SOD activity increased to 19.2±0.5,22.3± 1.7 and(24.9±0.6)kU·g-1 protein(P﹤0.01),MDA concentration decreased to 1.51±0.2,1.48±0.3 and (1.02±0.1)μmol·g-1 protein(P﹤0.01),and the expression of caspase 3 and HSP70 declined significant-ly(P﹤0.01). CONCLUSION VAP has exert protective effect on H2 O2-induced injury in vascular endothe-lial cells. The possible mechanism might be related to improvement of intracellular oxidative stress level.