AIM:To observe the effect and mech-anism of cuttlebone extract regulating vascular en-dothelial growth factor(VEGF)/phosphatidylinosi-tol 3-kinase(PI3K)/protein kinase B(AKT)pathway on refractory wounds in rats.METHODS:Cuttle-bone extract(CE)was obtained by water extraction of cuttlebone.Fifty SD rats were randomly divided into negative Control group,Model group,Cuttle-bone extract low-dose(CE(L))group,Cuttlebone extract high-dose(CE(H))group,and cuttlebone ex-tract high-dose+inhibitor(CE(H)+LY294002)group.After the refractory wound model was successfully established,0.02％furacillin solution or cuttlebone extract solution were applied to the wound area of rats in each group,and the treatment was adminis-tered once a day.After 14 days of treatment for re-fractory wounds,the changes in wound healing,angiogenesis,inflammation and expression of relat-ed regulatory proteins were quantitatively ana-lyzed by measuring skin ulcer wound area,patho-logical sections,immunofluorescence staining,Eli-sa,Western blot,RT-qPCR and other methods.RE-SULTS:Compared with Model group,CE(L)and CE(H)groups can increase the number of epithelial cells and collagen,and promote the healing of re-fractory wound in rats.Serum VEGF,skin tissue mi-crovascular density,P-PI3K,P-AKT,VEGF protein ex-pression and mRNA expression levels of PI3K,Akt,VEGF and eNOS were increased(P＜0.05),while se-rum TNF-α and IL-6 levels were decreased(P＜0.05).LY294002 could partially reverse the repair-ing effect of high dose cuttlebone extract on refrac-tory wound(P＜0.05).CONCLUSION:Cuttlebone ex-tract can regulate the VEGF/PI3K/AKT signaling pathway,inhibit the inflammatory response of re-fractory wounds in rats,induce angiogenesis and promote wound healing.

AIM:To observe the effect and mech-anism of cuttlebone extract regulating vascular en-dothelial growth factor(VEGF)/phosphatidylinosi-tol 3-kinase(PI3K)/protein kinase B(AKT)pathway on refractory wounds in rats.METHODS:Cuttle-bone extract(CE)was obtained by water extraction of cuttlebone.Fifty SD rats were randomly divided into negative Control group,Model group,Cuttle-bone extract low-dose(CE(L))group,Cuttlebone extract high-dose(CE(H))group,and cuttlebone ex-tract high-dose+inhibitor(CE(H)+LY294002)group.After the refractory wound model was successfully established,0.02％furacillin solution or cuttlebone extract solution were applied to the wound area of rats in each group,and the treatment was adminis-tered once a day.After 14 days of treatment for re-fractory wounds,the changes in wound healing,angiogenesis,inflammation and expression of relat-ed regulatory proteins were quantitatively ana-lyzed by measuring skin ulcer wound area,patho-logical sections,immunofluorescence staining,Eli-sa,Western blot,RT-qPCR and other methods.RE-SULTS:Compared with Model group,CE(L)and CE(H)groups can increase the number of epithelial cells and collagen,and promote the healing of re-fractory wound in rats.Serum VEGF,skin tissue mi-crovascular density,P-PI3K,P-AKT,VEGF protein ex-pression and mRNA expression levels of PI3K,Akt,VEGF and eNOS were increased(P＜0.05),while se-rum TNF-α and IL-6 levels were decreased(P＜0.05).LY294002 could partially reverse the repair-ing effect of high dose cuttlebone extract on refrac-tory wound(P＜0.05).CONCLUSION:Cuttlebone ex-tract can regulate the VEGF/PI3K/AKT signaling pathway,inhibit the inflammatory response of re-fractory wounds in rats,induce angiogenesis and promote wound healing.

Objective:To study the application of 3D printing technology in multi-center fenestrated/branched endovascular repair (F/B-EVAR) for endovascular repair of abdominal aortic diseases.Methods:From Feb 2018 to Mar 2023, The clinical and followup data of 316 cases of abdominal aortic lesions undergoing repair with F/B-EVAR at 69 medical centers nationwide using 3D printing technology to guide physician-modified stent graft were retrospectively analyzed.Results:The mean follow-up time of the patients was 23 months (2-60 months), and 24 cases were lost to follow up, the follow-up rate was 92.4% (292/316), the mean postoperative hospitalization time was (8.2±4.9) days. A total of 944 main abdominal branch arteries were reconstructed. Intraoperative reconstruction of 11 branches failed, with a success rate of 98.8% (933/944). Within 30 days after surgery, 8 patients died (2.5%), and 6 patients died during follow-up, a total of 14 patients died (4.4%). There were 11 cases (3.5%) of spinal cord ischemia and no patient suffered from permanent paraplegia. There were 19 patients (6.0%) with postoperative renal function injury. Internal leakage was found in 26 patients, and the rate of internal leakage was 8.2%.Conclusion:3D printing technology can accurately locate the location of branch arteries, simplifing the surgical process, shortening the learning curve , and improving clinical efficacy.

Endovascular Aneurysm Repair (EVAR) has become an important treatment method for abdominal aortic aneurysms due to its advantages of shorter operative time,faster postoperative recovery,and lower early postoperative mortality. However,the incidence of complications and the postoperative reintervention rates are higher than those of open surgery. The main complications after EVAR include access vessel injury,post-implantation syndrome,stent migration,endoleaks,visceral branch artery occlusion,lower limb ischemia,and stent infection,which are also the primary causes of reintervention. In recent years,the causes and associated risk factors of various postoperative complications of EVAR have attracted widespread attention and discussion,which are of great significance for improving surgical techniques,enhancing postoperative monitoring,and improving patient outcomes. This paper provides a review of the current complications,associated risk factors,and management strategies after EVAR.

Endovascular Aneurysm Repair (EVAR) has become an important treatment method for abdominal aortic aneurysms due to its advantages of shorter operative time,faster postoperative recovery,and lower early postoperative mortality. However,the incidence of complications and the postoperative reintervention rates are higher than those of open surgery. The main complications after EVAR include access vessel injury,post-implantation syndrome,stent migration,endoleaks,visceral branch artery occlusion,lower limb ischemia,and stent infection,which are also the primary causes of reintervention. In recent years,the causes and associated risk factors of various postoperative complications of EVAR have attracted widespread attention and discussion,which are of great significance for improving surgical techniques,enhancing postoperative monitoring,and improving patient outcomes. This paper provides a review of the current complications,associated risk factors,and management strategies after EVAR.

Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer's disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and noncarriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia. Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.
Humans ; Apolipoprotein E4/genetics* ; Cytosine ; Mutation ; Blastocyst ; Heterozygote ; Gene Editing ; CRISPR-Cas Systems

Objective:To investigate the effects of blood pressure variability (BPV), serum reactive oxygen species (ROS) and superoxide dismutase (SOD) levels on cognitive function in patients with subcortical ischemic vascular disease (SIVD).Methods:A total of 133 patients with SIVD confirmed by craniocranial MRI admitted to Department of Neurology, Red Flag Hospital Affiliated to Mudanjiang Medical University from October 2021 to October 2022 were selected. According to Montreal Cognitive Assessment scores, they were divided into SIVD without cognitive impairment group (SIVD-NC group, n=39) and subcortical vascular cognitive impairment group (SVCI group, n=94); and 23 healthy volunteers with normal cognition who had normal brain MRI in the Physical Examination Center during the same period were chosen as control group. General data of all subjects and vascular risk factors in each group were collected, routine biochemical indexes of peripheral blood were detected, 24 h ambulatory blood pressure monitoring was performed, and serum ROS and SOD levels were detected by enzyme-linked immunosorbent assay. Statistical methods were used to analyze the risk factors for cognitive impairment, correlations of independent risk factors with cognitive function, and diagnostic value of risk factors in cognitive impairment in patients with SIVD. Results:(1) Compared with control group, SIVD-NC group had significantly increased percentages of patients with hypertension history or lacunar stroke history, and significantly increased hypersensitive C-reactive protein (hs-CRP) level ( P<0.05). Compared with control group and SIVD-NC group, patients in SVCI group had significantly older age, lower years of education, higher proportion of patients with lacunar stroke history, and increased hs-CRP level ( P<0.05). Compared with control group, SVCI group had significantly higher proportion of patients with hypertension history ( P<0.05). (2) SIVD-NC group had significantly higher ROS level than control group ( P<0.05); Compared with control group and SIVD-NC group, SVCI group had significantly increased ROS level ( P<0.05). (3) SIVD-NC group had significantly increased nighttime systolic blood pressure (nSBP) compared with control group ( P<0.05); SVCI group had significantly increased 24 h SBP, nSBP and nSBP-variable coefficient (CV) compared with control group and SIVD-NC group ( P<0.05). Compared with SIVD-NC group, SVCI group had significantly increased 24 h SBP-CV ( P<0.05). (4) The nSBP, nSBP-CV, serum hs-CRP and ROS, and lacunar stroke history were independent risk factors for cognitive impairment in SIVD patients ( OR=1.096, P<0.001, 95% CI: 1.042-1.154; OR=1.231, P=0.010, 95% CI: 1.050-1.443; OR=2.303, P=0.004, 95% CI: 1.311-4.039; OR=1.026, P<0.001, 95% CI: 1.014-1.039; OR=2.954, P=0.041, 95% CI: 1.045-8.348), and education level was a protective factor for that ( P<0.05). (5) Serum ROS and hs-CRP, nSBP, and nSBP-CV were negatively correlated with MoCA scores in SIVD patients ( r s=-0.336, P<0.001; r s=-0.503, P<0.001; r s=-0.204, P=0.018; r s=-0.309, P=0.001). (6) Serum ROS and hs-CRP, nSBP, and nSBP-CV had high diagnostic values in cognitive impairment in SIVD patients (areas under the curves: 0.874, 0.847, 0.804 and 0.702, P<0.05); combined diagnosis efficacy of multiple indexes was better (area under the curve: 0.948, P<0.05). Conclusion:Serum ROS and hs-CRP, nSBP and nSBP-CV are highly likely to be hemodynamic and serological monitoring indexes for screening of cognitive impairment in SIVD patients.

Objective To investigate the clinical effectiveness of autologous platelet-rich-plasma (PRP) combined with iliac autograft in reconstruction of bony defective nonunion of humeral condyle.Methods The 27 patients who had been admitted to our department from January 2004 to June 2015 for bony defective nonunion of humeral condyle were analyzed retrospectively.Of them,15 underwent reconstruction with PRP combined with iliac autograft (experimental group) and 12 reconstruction with only iliac autograft (control group).The preoperative demographic data of the 2 groups were not significantly different (P ＞ 0.05).The 2 groups were compared in terms of operation time,hospital stay,bony union time,range of motion of the elbow,and modified Cassebaum scoring.Results The patients were followed up for 12 to 90 months (average,24.6 months).No such complications were observed as displacement of bone blocks,loosening or breakage of implants,re-nonunion,malunion,delayed ulnar neuritis,or olecranon nonunion.There were no statistic differences between the 2 groups regarding operation time,hospital stay,range of motion of the elbow and modified Cassebaum scoring (P ＞ 0.05).The clinical healing time (4.2 ± 1.3 months) and bony healing time (4.8 ± 1.4 months) for the experimental group were significantly shorter than for the control group (6.0 ± 1.1 months and 6.2 ± 1.0 months,respectively) (P ＜ 0.05).Conclusion Autologous PRP combined with iliac autograft can speed up the healing of bony defective nonunion of humeral condyle,promoting functional recovery of the elbow.

BACKGROUND:The traditional treatment for thoracolumbar vertebral fractures is posterior short-segment pedicle screw fixation. This method uses vertebral soft tissue stretch through distraction reduction mechanism, makes shift bone reset, and restores shape and height of vertebral body. Long-term folow-up found that part of cases experience complications such as vertebral height loss, loss of spinal correction of Cobb angle, the pedicle screw breakage and loosening. OBJECTIVE:To explore clinical effects of pedicle screw fixation combined with the implantation of artificial bone composite for the treatment of thoracolumbar fractures, and to compare with conventional pedicle screw. METHODS: A total of 80 patients with thoracolumbar fractures, who were treated in the Yantaishan Hospital from March 2011 to May 2014, were randomly divided into two groups. In the experimental group, patients received pedicle screw fixation combined with the implantation of artificial bone composite. In the control group, patients received routine pedicle fixation. Pain visual analog scale score was evaluated before treatment and at 6 months after treatment in patients of both groups, and easement of pain was evaluated after treatment. Vertebral body height (normal anterior flange height and up and down the front cone height and the ratio of the average multiplied by 100%) and sagittal Cobb angle (sagittal measurements of X-ray film) were measured in patients of both groups before treatment and at 1 and 12 months after treatment. According to conventional hierarchical evaluation criteria used al over the world, prognosis was assessed at 6 months after treatment, including basic cure, powerfuly, effectively, and invalid. RESULTS AND CONCLUSION: At 6 months after treatment, significant differences in pain visual analog scale scores were detected in the experimental group (2.4 points) and control group (3.7 points) (P < 0.05). No significant difference in height of the injured vertebra and Cobb angle was detected between the two groups before treatment (P> 0.05). The height of the injured vertebra and Cobb angle were better in the experimental group compared with the control group at 1 and 12 months after treatment (P < 0.05). Significant differences in treatment efficiency were detectable between the experimental group (90%) and the control group (73%) at 6 months after treatment (P < 0.05). These data indicate that pedicle screw fixation combined with the implantation of artificial bone composite in the treatment of thoracolumbar fractures can be used to fix fracture reduction, effectively restore height of injured vertebral body, prevent postoperative Cobb angle loss, and improve the treatment efficiency.

Objective To investigate the influence of intra-articular injection of hyaluronic acid at early stage on articular cartilage cells apoptosis in elderly patients with articular injury.Methods A total of 89 elderly patients with articular injury from Jan.2013 to Oct.2014 were randomly divided into observation group and control group.In control group,40 cases were treated with conventional surgery and anti-inflammatory therapy.In observation group,49 cases were treated intraarticular injection of hyaluronic acid added to conventional therapy.The apoptosis rate of articular cartilage cells,cell cycle and proliferation index were compared between the two groups.Results The apoptosis rate of articular cartilage cells was lower in observation group than in control group [(4.08±0.74)％ vs.(6.41±0.54)％,t=16.403,P＜0.001].The ratio of G0/Giin articular cartilage cells was lower in observation group than in control group[(83.5 ± 3.5)％ vs.(91.7± 4.3)％,t10.275,P＜0.001].The ratios of S and G2/M and the proliferation index in articular cartilage cells were lower in control group than in observation group[(3.5 ± 0.3)％ vs.(8.2± 2.4)％,(4.7±0.6)％ vs.(8.5±1.8)％ and (9.1±1.1)％ vs.(16.7±1.9)％,t=12.293,12.731 and 22.198,respectively,all P＜0.001].Conclusions Intra articular injection of hyaluronic acid at early stage decreases the apoptosis rate of articular cartilage cells,helps articular cartilage cells turnover and improves the recovery of articular injury in elderly patients.