BACKGROUND:During bone tissue healing,promoting the vascularization of new bone is a common strategy to accelerate the repair of bone tissue.However,the rapid fibrosis process during bone defect repair is often ignored.OBJECTIVE:To design and prepare a core-shell structure bionic scaffold to regulate the process of fibrosis and vascularization in new callus,characterize physical characteristics of the scaffold,and verify the anti-fibrosis and osteogenic properties in vitro and in vivo.METHODS:A core-shell structure bionic scaffold to regulate the process of fibrosis and vascularization in new callus was designed and prepared.The outer shell structure of the scaffold was composed of polycaprolactone electrospun nanofibers loaded with fibroblast activating protein inhibitor;and the inner core structure was composed of gelatin methacrylate hydrogel loaded with deferoxamine.The physical characteristics of electrospun and hydrogel were characterized,and the biocompatibility of the material was verified by live-dead staining and CCK-8 assay.The antifibrotic effect of core-shell structure was analyzed by fibroblast in vitro assay.The osteogenic effect of fibroblast activating protein inhibitor in core-shell structure was analyzed by MC3T3-E1 cells in vitro assay.The vasogenic effect of deferoxamine in core-shell structure was analyzed by human umbilical vein endothelial cells.The effect of bionic core-shell scaffold on bone repair was evaluated by critical bone defect test in rats.RESULTS AND CONCLUSION:(1)The core-shell structure bionic scaffold had good biocompatibility.Hydrophobic polycaprolactone electrospun fibers prepared by electrospinning technology could effectively block the ingrowth of exogenous fibrous tissue on the physical level.The electrospun fiber membrane could effectively release the anti-fibrosis drug fibroblast activating protein inhibitor within 2 weeks,and the released anti-fibrosis drug could inhibit the growth and adhesion of fibroblasts around bone defects,effectively reduced the expression of fibroblast-related proteins,promoted the expression of osteoblast protein in MC3T3-E1 cells,and accelerated its mineralization rate.The deferoxamine in the core-shell structure could promote the migration and vascular formation ability of human umbilical vein endothelial cells,and promoted their strong expression of"H"vascular characteristic protein.(2)In critical bone defect model of SD rats established in the femur,compared with polycaprolactone membrane,the core-shell structure bionic scaffold could effectively repair bone defects.(3)These findings indicate that the core-shell structure bionic scaffold can prevent excessive fibrosis of callus and promote the formation of"H"vessels in the new callus,which can effectively avoid the occurrence of nonunion and accelerate the repair process of critical bone defect.

BACKGROUND:Cell senescence is one of the major risk factors for osteoarthritis,but there is no widely accepted anti-osteoarthritis therapy targeting senescent cells.OBJECTIVE:To develop a feasible treatment strategy targeting senescent cells in osteoarthritis.METHODS:The cationic liposome containing rapamycin,RAPA@Lipo,was prepared by thin film dispersion method.Methylallylated hyaluronic acid hydrogel was synthesized,and RAPA@Lipo was added to the methylallylated hyaluronic acid hydrogel aqueous phase solution.The hydrogel microspheres were prepared by microfluidic equipment.Solid hydrogel microspheres(RAPA@Lipo@MS)were crosslinked under violet light.Primary human chondrocytes were co-cultured with RAPA@Lipo and RAPA@Lipo@MS,respectively.The biocompatibility of the materials was evaluated by CCK-8 assay and live/dead staining.Primary rat chondrocytes were cultured in four groups.Normal control group was cultured for 48 hours.The model group was stimulated with H2O2 for 24 hours to establish senescent cell model.RAPA@Lipo group and RAPA@Lipo@MS group were cultured for 24 hours after establishing senescent cell model with RAPA@Lipo and RAPA@Lipo@MS,respectively.After culture,immunofluorescence was used to observe the expression of p62 and type Ⅱ collagen.RT-PCR was used to detect the mRNA expression of interleukin 6,matrix metalloproteinase 13,type Ⅱ collagen,aggrecan,and ADAMTS-5.RESULTS AND CONCLUSION:(1)The results of CCK-8 assay and live/dead staining showed that RAPA@Lipo and RAPA@Lipo@MS had good biocompatibility.(2)Compared with the normal control group,the protein expression of p62 was increased(P<0.05);the expression of type Ⅱ collagen was decreased(P<0.05),and the mRNA expression levels of interleukin 6,matrix metalloproteinase 13,and ADAMTS-5 were increased(P<0.05);mRNA expression levels of type Ⅱ collagen and aggrecan were decreased(P<0.05)in the model group.Compared with the model group,the expression of p62 protein was decreased(P<0.05);the expression of type Ⅱ collagen was increased(P<0.05),and the mRNA expression levels of interleukin 6,matrix metalloproteinase 13,and ADAMTS-5 were decreased(P<0.05);mRNA expression of type Ⅱ collagen and aggrecan increased(P<0.05)in the RAPA@Lipo@MS group.(3)These findings indicate that RAPA@Lipo@MS can control the quality of cells in vivo by enhancing autophagy,reduce senescent cells in vivo,and locally eliminate senescent cells and senescence-associated secretory phenotype factors in osteoarthritis,thereby slowing the progression of osteoarthritis and creating a cartilage microenvironment that promotes regeneration.

BACKGROUND:During bone tissue healing,promoting the vascularization of new bone is a common strategy to accelerate the repair of bone tissue.However,the rapid fibrosis process during bone defect repair is often ignored.OBJECTIVE:To design and prepare a core-shell structure bionic scaffold to regulate the process of fibrosis and vascularization in new callus,characterize physical characteristics of the scaffold,and verify the anti-fibrosis and osteogenic properties in vitro and in vivo.METHODS:A core-shell structure bionic scaffold to regulate the process of fibrosis and vascularization in new callus was designed and prepared.The outer shell structure of the scaffold was composed of polycaprolactone electrospun nanofibers loaded with fibroblast activating protein inhibitor;and the inner core structure was composed of gelatin methacrylate hydrogel loaded with deferoxamine.The physical characteristics of electrospun and hydrogel were characterized,and the biocompatibility of the material was verified by live-dead staining and CCK-8 assay.The antifibrotic effect of core-shell structure was analyzed by fibroblast in vitro assay.The osteogenic effect of fibroblast activating protein inhibitor in core-shell structure was analyzed by MC3T3-E1 cells in vitro assay.The vasogenic effect of deferoxamine in core-shell structure was analyzed by human umbilical vein endothelial cells.The effect of bionic core-shell scaffold on bone repair was evaluated by critical bone defect test in rats.RESULTS AND CONCLUSION:(1)The core-shell structure bionic scaffold had good biocompatibility.Hydrophobic polycaprolactone electrospun fibers prepared by electrospinning technology could effectively block the ingrowth of exogenous fibrous tissue on the physical level.The electrospun fiber membrane could effectively release the anti-fibrosis drug fibroblast activating protein inhibitor within 2 weeks,and the released anti-fibrosis drug could inhibit the growth and adhesion of fibroblasts around bone defects,effectively reduced the expression of fibroblast-related proteins,promoted the expression of osteoblast protein in MC3T3-E1 cells,and accelerated its mineralization rate.The deferoxamine in the core-shell structure could promote the migration and vascular formation ability of human umbilical vein endothelial cells,and promoted their strong expression of"H"vascular characteristic protein.(2)In critical bone defect model of SD rats established in the femur,compared with polycaprolactone membrane,the core-shell structure bionic scaffold could effectively repair bone defects.(3)These findings indicate that the core-shell structure bionic scaffold can prevent excessive fibrosis of callus and promote the formation of"H"vessels in the new callus,which can effectively avoid the occurrence of nonunion and accelerate the repair process of critical bone defect.

BACKGROUND:Cell senescence is one of the major risk factors for osteoarthritis,but there is no widely accepted anti-osteoarthritis therapy targeting senescent cells.OBJECTIVE:To develop a feasible treatment strategy targeting senescent cells in osteoarthritis.METHODS:The cationic liposome containing rapamycin,RAPA@Lipo,was prepared by thin film dispersion method.Methylallylated hyaluronic acid hydrogel was synthesized,and RAPA@Lipo was added to the methylallylated hyaluronic acid hydrogel aqueous phase solution.The hydrogel microspheres were prepared by microfluidic equipment.Solid hydrogel microspheres(RAPA@Lipo@MS)were crosslinked under violet light.Primary human chondrocytes were co-cultured with RAPA@Lipo and RAPA@Lipo@MS,respectively.The biocompatibility of the materials was evaluated by CCK-8 assay and live/dead staining.Primary rat chondrocytes were cultured in four groups.Normal control group was cultured for 48 hours.The model group was stimulated with H2O2 for 24 hours to establish senescent cell model.RAPA@Lipo group and RAPA@Lipo@MS group were cultured for 24 hours after establishing senescent cell model with RAPA@Lipo and RAPA@Lipo@MS,respectively.After culture,immunofluorescence was used to observe the expression of p62 and type Ⅱ collagen.RT-PCR was used to detect the mRNA expression of interleukin 6,matrix metalloproteinase 13,type Ⅱ collagen,aggrecan,and ADAMTS-5.RESULTS AND CONCLUSION:(1)The results of CCK-8 assay and live/dead staining showed that RAPA@Lipo and RAPA@Lipo@MS had good biocompatibility.(2)Compared with the normal control group,the protein expression of p62 was increased(P<0.05);the expression of type Ⅱ collagen was decreased(P<0.05),and the mRNA expression levels of interleukin 6,matrix metalloproteinase 13,and ADAMTS-5 were increased(P<0.05);mRNA expression levels of type Ⅱ collagen and aggrecan were decreased(P<0.05)in the model group.Compared with the model group,the expression of p62 protein was decreased(P<0.05);the expression of type Ⅱ collagen was increased(P<0.05),and the mRNA expression levels of interleukin 6,matrix metalloproteinase 13,and ADAMTS-5 were decreased(P<0.05);mRNA expression of type Ⅱ collagen and aggrecan increased(P<0.05)in the RAPA@Lipo@MS group.(3)These findings indicate that RAPA@Lipo@MS can control the quality of cells in vivo by enhancing autophagy,reduce senescent cells in vivo,and locally eliminate senescent cells and senescence-associated secretory phenotype factors in osteoarthritis,thereby slowing the progression of osteoarthritis and creating a cartilage microenvironment that promotes regeneration.

Objective To explore the effect of enhanced external counterpulsation(EECP)on ser-um vascular endothelial growth factor(VEGF)level and cardiopulmonary function in patients with stable angina pectoris(SAP).Methods A prospective double-blind controlled trial was con-ducted on 300 SAP patients admitted to Departments of Cardiovascular Medicine and Geriatrics of Jincheng People's Hospital from January 2021 to December 2023.They were randomly divided in-to study group(150 cases)and control group(150 cases).Coronary angiography or coronary CT angiography indicated that there were 101,101 and 98 cases,respectively,of one-,two-and three-vessel diseases.The patients of both groups were given conventional drug therapy(secondary pre-ventive drug for coronary heart disease),and those of the study group received EECP therapy ad-ditionally.The changes in serum VEGF level and related indicators of cardiopulmonary exercise test before and after one course of standardized treatment(36 h)were observed and compared be-tween the two groups.Results The VEGF level was significantly higher in the patients with three-vessel disease than those with two-and one-vessel diseases(P＜0.05).The level was obvi-ously increased in the study group and control group after intervention than before(238.41±82.57 ng/L vs 218.75±82.58 ng/L,224.47±85.08 ng/L vs 218.96±83.04 ng/L,P＜0.01),and the former group obtained better improvement of VEGF than the latter group(P＜0.01).The level in the study group and the control group with one-,two-and three-vessel lesions was notably higher than those before intervention(P＜0.05,P＜0.01).The study group with one-,two-and three-vessel lesions had statistical differences in the VEGF level after intervention when compared with that in the control group(P＜0.01).The levels of Peak VO2/kg and VO2/kg@AT were sig-nificantly increased in both groups after intervention than before(P＜0.01),with those of the study group notably higher than those of the control group[19.87±5.18 ml/(kg·min)vs 17.15±5.18 ml/(kg·min),P＜0.01;14.33±2.24 ml/(kg·min)vs 12.81±1.57 ml/(kg·min),P＜0.01].Conclusion EECP treatment is helpful to increase VEGF level and improve cardiopul-monary function in SAP patients.

Objective To explore the effect of enhanced external counterpulsation(EECP)on ser-um vascular endothelial growth factor(VEGF)level and cardiopulmonary function in patients with stable angina pectoris(SAP).Methods A prospective double-blind controlled trial was con-ducted on 300 SAP patients admitted to Departments of Cardiovascular Medicine and Geriatrics of Jincheng People's Hospital from January 2021 to December 2023.They were randomly divided in-to study group(150 cases)and control group(150 cases).Coronary angiography or coronary CT angiography indicated that there were 101,101 and 98 cases,respectively,of one-,two-and three-vessel diseases.The patients of both groups were given conventional drug therapy(secondary pre-ventive drug for coronary heart disease),and those of the study group received EECP therapy ad-ditionally.The changes in serum VEGF level and related indicators of cardiopulmonary exercise test before and after one course of standardized treatment(36 h)were observed and compared be-tween the two groups.Results The VEGF level was significantly higher in the patients with three-vessel disease than those with two-and one-vessel diseases(P＜0.05).The level was obvi-ously increased in the study group and control group after intervention than before(238.41±82.57 ng/L vs 218.75±82.58 ng/L,224.47±85.08 ng/L vs 218.96±83.04 ng/L,P＜0.01),and the former group obtained better improvement of VEGF than the latter group(P＜0.01).The level in the study group and the control group with one-,two-and three-vessel lesions was notably higher than those before intervention(P＜0.05,P＜0.01).The study group with one-,two-and three-vessel lesions had statistical differences in the VEGF level after intervention when compared with that in the control group(P＜0.01).The levels of Peak VO2/kg and VO2/kg@AT were sig-nificantly increased in both groups after intervention than before(P＜0.01),with those of the study group notably higher than those of the control group[19.87±5.18 ml/(kg·min)vs 17.15±5.18 ml/(kg·min),P＜0.01;14.33±2.24 ml/(kg·min)vs 12.81±1.57 ml/(kg·min),P＜0.01].Conclusion EECP treatment is helpful to increase VEGF level and improve cardiopul-monary function in SAP patients.

Objective:To explore the pregnancy outcome of intracytoplasmic sperm injection (ICSI)/rescure-ICSI (Re-ICSI) patients with gear-like transparent dense zona pellucida and small perivitelline oocytes.Methods:Totally 6 couples with abnormal zona pellucida came to the Reproductive Medicine Center of Shijiazhuang the Fourth Hospital from January 2015 to June 2020 were retrospectively case control analyzed. A total of 8 cycles had zona pellucida abnormalities, of which 5 couples, the proportion of M I oocytes was ≥50% (part oocytes M I arrest) in 6 cycles and 1 couple (2 cycles) was all oocytes M I arrest. ICSI or in vitro fertilization (IVF) short-term fertilization was performed on M II oocytes with abnormal zona pellucida in controlled superovulation, IVF short-time fertilization failed completely, and Re-ICSI was performed. M I oocytes were performed ICSI/Re-ICSI simultaneously. The ICSI/Re-ICSI fertilization rate, degeneration rate, cleavage rate, high-quality embryo rate and blastocyst rate were compared between the two groups of M II oocytes and M I oocytes, as well as all oocytes M I arrest and part oocytes M I arrest groups, respectively. Results:Totally 37 M II oocytes and 65 M I oocytes underwent ICSI/Re-ICSI. M I oocytes fertilization and 2PN fertilization rates were lower than M II oocytes [46.2%(30/65) vs. 89.2% (33/37); 32.3% (21/65) vs. 83.8% (31/37), all P<0.001]. Both groups had high-quality embryos and blastocyst formation. Compared with part oocytes M I arrest and all oocytes M I arrest, there was no statistical difference in fertilization rate, degeneration rate, high-quality embryo rate and blastocyst formation rate between the two groups (all P>0.05). Conclusion:ICSI/Re-ICSI for patients with abnormal zona pellucida with a high proportion of M I oocytes can increase the patients' oocytes utilization rate and available embryos.

Objective:To explore the pregnancy outcome of intracytoplasmic sperm injection (ICSI)/rescure-ICSI (Re-ICSI) patients with gear-like transparent dense zona pellucida and small perivitelline oocytes.Methods:Totally 6 couples with abnormal zona pellucida came to the Reproductive Medicine Center of Shijiazhuang the Fourth Hospital from January 2015 to June 2020 were retrospectively case control analyzed. A total of 8 cycles had zona pellucida abnormalities, of which 5 couples, the proportion of M I oocytes was ≥50% (part oocytes M I arrest) in 6 cycles and 1 couple (2 cycles) was all oocytes M I arrest. ICSI or in vitro fertilization (IVF) short-term fertilization was performed on M II oocytes with abnormal zona pellucida in controlled superovulation, IVF short-time fertilization failed completely, and Re-ICSI was performed. M I oocytes were performed ICSI/Re-ICSI simultaneously. The ICSI/Re-ICSI fertilization rate, degeneration rate, cleavage rate, high-quality embryo rate and blastocyst rate were compared between the two groups of M II oocytes and M I oocytes, as well as all oocytes M I arrest and part oocytes M I arrest groups, respectively. Results:Totally 37 M II oocytes and 65 M I oocytes underwent ICSI/Re-ICSI. M I oocytes fertilization and 2PN fertilization rates were lower than M II oocytes [46.2%(30/65) vs. 89.2% (33/37); 32.3% (21/65) vs. 83.8% (31/37), all P<0.001]. Both groups had high-quality embryos and blastocyst formation. Compared with part oocytes M I arrest and all oocytes M I arrest, there was no statistical difference in fertilization rate, degeneration rate, high-quality embryo rate and blastocyst formation rate between the two groups (all P>0.05). Conclusion:ICSI/Re-ICSI for patients with abnormal zona pellucida with a high proportion of M I oocytes can increase the patients' oocytes utilization rate and available embryos.

Aim To study the effect of high salt diet during pregnancy on the development of renal vessels in offspring rats and its mechanism.Methods Natural pregnant Sprague-Dawley rats were randomly divided into high-salt group and control group.The pregnant rats in the high-salt group were given high-salt diet of 8% NaCl content , while the control group normal diet with 1% NaCl content.In both groups, pregnant rats were given normal drinking water.After delivery, all mothers returned to normal diet and all neonatal rats were breast-fed until one month old.The adult male off springs were used as experimental animals.The vessel tone of renal interlobar arteries and electrophysiological behavior of single vascular smooth muscle cells (VSMCs) were detected respectively.Results The contractile response of renal arteries to phenylephrine(Phe) in high-salt group was stronger than that in the control group(P<0.05).The effect of protein kinase C(PKC) non selective blocker GF109203X on Phe-induced contraction in two groups also showed significant difference(P<0.05).In electrophysiology experiments, Phe inhibited high-conductance Ca2+-activated K+ channel(BK channel) currents in renal arteriolar smooth muscle cells in two groups, and the inhibitory effect was more pronounced in high-salt offsprings (P<0.05).GF109203X could eliminate the response of Phe on BK currents in both groups(P>0.05).Conclusions High-salt diet during pregnancy could increase the sensitivity of renal interlobar arterial contractile response to Phe in adult male offsprings, which is associated with PKC-mediated BK channels pathway.Maternal high-salt diet during pregnancy may increase the risk of renal vascular diseases in adult offsprings.

Objective To systematically compare the efficacy of three-dimensional conformal radiotherapy (3D-CRT) versus intensity-modulated radiotherapy (IMRT) in the treatment of prostate cancer (PCa).Methods Clinical comparative studies of IMRT and 3D-CRT in the treatment of PCa were collected from PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), and Wanfang Data after two independent researchers developed the strategy and inclusion and exclusion criteria for the literature search.Articles published up to February 2017 were searched for, and the languages of publications were restricted to English and Chinese.Clinical meta-analysis of the data from the relevant studies was performed using the RevMan5.3 software.Results A total of 15 relevant retrospective cohort studies were collected from the databases in strict accordance to the search strategy and inclusion and excluding criteria.There were 4608 PCa patients, including 2229 in the IMRT group and 2379 in the 3D-CRT group.IMRT and 3D-CRT had similar adverse effects in terms of early-stage (odds ratio[OR]=0.77, 95% confidence interval[CI]:0.43-1.40, P=0.390) and late-stage (OR=0.75, 95%CI:0.55-1.04, P=0.080) urinary tract injury.However, IMRT led to reduced early-stage (OR=0.47, 95%CI:0.27-0.82, P=0.008) and late-stage (OR=0.52, 95%CI:0.35-0.78, P=0.001) intestinal injury compared with 3D-CRT.Meanwhile, the biochemical recurrence-free survival rate was also significantly higher in the IMRT group than in the 3D-CRT group (OR=1.87, 95%CI:1.51-2.32, P=0.000).Conclusions IMRT is more protective against intestinal injury with a higher biochemical recurrence-free survival rate compared with 3D-CRT during the treatment of PCa.