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.

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.

OBJECTIVETo investigate the outcomes, survival status, and the prognostic factors of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) patients.

METHODSA retrospective study was carried out to analyze the clinical data of 61 EBV-HLH cases, from January 2008 to July 2014. Prognostic factors were analyzed through COX model (single factor and multiple factors).

RESULTSA total of 246 patients with HLH were diagnosed, among which 102 cases were with EBV infection (including 61 EBV-HLH, 36 lymphoma associated HLH, 5 primary HLH. Among the 61 cases, 40 were male and 21 were female, with a ration of 1.9:1. The median age was 28 years (range, 12-78). 1, 3, 6 and 12-month overall survival rates of 61 EBV-HLH were 65.6%, 47.5%, 32.4%, and 25.0%, respectively. The median follow-up time was 3 (0.5-28) months. 12 patients didn't use etoposide within 4 weeks after diagnosis, while HLH-94 protocol was used in 33 patients and HLH-2004 protocol was used in 16 patients. Response rates of theses three groups were 33.3%, 51.5%, and 43.8%, respectively (P=0.401). There was statistically difference between the group without etoposide and the HLH-94/ HLH-2004 group in the overall survival rate (P=0.033). Serum albumin level (P=0.033) and whether EBV could became negative (P=0.010) were independent predictors for EBV-HLH.

CONCLUSIONEBV-HLH patients have severe clinical feature and poor prognosis. Early application of immune chemotherapy based on etoposide can improve survival. Serum albumin level and whether EBV can become negative are independent prognostic factors for survival.

Adolescent ; Adult ; Aged ; Child ; Epstein-Barr Virus Infections ; Etoposide ; Female ; Herpesvirus 4, Human ; Humans ; Lymphohistiocytosis, Hemophagocytic ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Survival Rate ; Treatment Outcome ; Young Adult

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.

OBJECTIVETo analyze the clinical manifestations, laboratory data, therapy, and prognosis in patients with hemophagocytic lymphohistiocytosis (HLH).

METHODSA retrospective study was carried out in 192 adult patients with HLH between 2003 and 2013.

RESULTSOf the 192 cases, 70 cases were secondary to cancer and 64 cases secondary to infection. According to HLH-2004 criteria, the coincidence rate of indices were: fever (98.96%), high level of serum ferritin (94.27%), increased level of soluble interleukin- 2 receptor(sCD25) (94.79%), decreased or absent activity of NK cells (94.27%), cytopenias (80.73%), splenomegaly (80.21%), emophagocytosis in bone marrow, spleen or lymph nodes (74.48%), hypofibrinogenemia (50.52%), hypertriglyceridemia (37.50%). In addition, 94.27% of patients were presented with liver dysfunction, 96.35% with infections, and 75.52% with coagulopathy. Incidences of central nervous system symptoms and rash were 19.27% and 20.31%, respectively. Among cancer, infection and rheumatic group, there were statistically differences on white blood cells (WBC), platelet (PLT), sCD25, alanine aminotransferase, aspartate aminotransferase, total bilirubin and globulin(GLO) (P<0.05). The differences of WBC, PLT, albumin (ALB), GLO, brain natriuretic peptide, creatinine, urea nitrogen between survival group and death group had statistical significance.

CONCLUSIONThe secondary HLH occurs from various underlined diseases. Cancer, especially T- cell lymphoma, is the main cause, Secondly, it is EB virus infection. The diagnostic sensitive indicators are Persistent fever, higher level of serum ferritin, low or absent NK-cell activity, and increased sCD25 were the most valuable parameters for diagnosis. Cytopenias were not common in early phase of HLH secondary to rheumatic diseases. WBC, PLT, ALB, GLO could be used as the preliminary parameters for diagnosis. Cardiac insufficiency, renal insufficiency and coagulation dysfunction play important roles in prognosis.

Adult ; Bone Marrow ; Fever ; Humans ; Killer Cells, Natural ; Lymphohistiocytosis, Hemophagocytic ; Prognosis ; Retrospective Studies

Objective To investigate the reason of fracture internal fixation of locking plates and conventional plate in the treatment of femoral fractures.Methods A total of 198 patients with femoral fracture taken plate fixation were selected as our subjects.Of which,the locking plate were used in 87 cases served as control group and 111 cases had traditional plate fixation served as study group.Fracture fixation rate in patients were follow-up and the reasons for broken were analyzed.Results Fracture fixation occurred 5 cases (4.5％,5/111) in the locking plate,and 3 cases (3.4％,3/87) in traditional plate,and the difference was not significant (x2 =0.053,P =0.987).Fracture reason included plate fracture (4 cases),fracture of screws (2 cases) and plate fracture complicated with breakage of screw (2 cases).Iatrogenic factors lead fracture fixation was 30.0％ (3/10),significantly higher in patients with rehabilitation exercises errors (6.9％,2/29; x2 =3.851 ; P =0.046).Both iatrogenic factors and rehabilitation exercises errors caused fracture fixation rate was 100％.Conclusion Iatrogenic factors combined rehabilitation exercises error was the main reasons in fracture fixation.We should properly choose fixation methods and correctly guide the postoperative functional exercise for patients.

Objective To investigate the efficacy and safety of photodynamic therapy (PDT) in the treatment of different types of rosacea,and to evaluate its benefit by comparing its efficacy with 10％ sodium sulfacetamide and 5％ sulfur emollient foam.Methods Forty-three subjects with rosacea were enrolled in this study.They were randomized to be treated with PDT (twenty-three subjects) or 10％ sodium sulfacetamide and 5％ sulfur emollient foam (twenty subjects).PDT group subjects received PDT once every seven to ten days for three times while the 10％ sodium sulfacetamide or 5％sulfur emollient foam was applied 2 times per day for thirty days in the other group.Digital photographs were taken before and after one month of treatment in both groups.Blinded independent physicians graded improvement based on these photographs utilizing a percentile evaluation scale.A more than sixty percent remission proved the treatment to be effective.All the complications occurred during the therapy were taken notes and their severity was classified by the subjects.Two dermatology life quality index forms were completed before and after treatment by the subjects to evaluate the change in terms of their quality of life.Results After one month of treatment,PDT proved to be effective on sixty-five percent of subjects (seventy-one percent on papulopustular rosacea and fifty percent on erythematotelangiectatic rosacea).The emollient foam proved to be effective on thirty-five percent of subjects.Statistically significant difference was observed between the overall effective rate of PDT and emollient foam (P＜0.05).In addition,a greater improvement in terms of the quality of life was experienced by the PDT group subjects.No irreversible adverse event was observed in both groups during the study.Conclusions PDT proves to be an effective and safe treatment for rosacea with satisfactory efficacy,significant improvement in patients' quality of life and few irreversible side effects.