OBJECTIVE: To assess the association of cytochrome P450 (CYP450) gene polymorphisms with the occurrence of ischemic stroke (IS). METHODS: From January 2020 to August 2022, 390 IS patients treated at the Zhengzhou Seventh People's Hospital were enrolled as the study group, and 410 healthy individuals undergoing physical examination during the same period were enrolled as the control group. Clinical data of all subjects were collected, which included age, sex, body mass index (BMI), smoking history and results of laboratory tests. Chi-square test and independent sample t test were used for comparing the clinical data. Multivariate logistic regression analysis was used to analyze the non-hereditary independent risk factors for IS. Fasting blood samples of the subjects were collected, and the genotypes of rs4244285, rs4986893, rs12248560 of the CYP2C19 gene and rs776746 of the CYP3A5 gene were determined by Sanger sequencing. The frequency of each genotype was calculated by using SNPStats online software. The association between the genotype and IS under the dominant, recessive and additive models was analyzed. RESULTS: The levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL-C), apolipoprotein B (Apo-B) and homocysteine (Hcy) of the case group were significantly higher than those of the control group, whilst the levels of high density lipoprotein (HDL-C) and Apo-A1 (APO-A1) were significantly lower (P < 0.05). Multivariate Logistic regression analysis showed that TC (95%CI = 1.13-1.92, P = 0.02), LD-C (95%CI = 1.03-2.25, P = 0.03), Apo-A1 (95%CI = 1.05-2.08, P = 0.04), Apo-B (95%CI = 1.7-4.22, P < 0.01) and Hcy (95%CI = 1.12-1.83, P = 0.04) were non-genetic independent risk factors for the occurrence of IS. Analysis of the association between the genetic polymorphisms and the risk of IS showed that the AA genotype at rs4244285 of the CYP2C19 gene, the AG genotype and A allele at rs4986893 of the CYP2C19 gene, and the GG genotype and G allele at rs776746 of the CYP3A5 gene were significantly associated with IS. Under the recessive/additive model, dominant model and dominant/additive model, polymorphisms of the rs4244285, rs4986893 and rs776746 loci were also significantly associated with the IS. CONCLUSION TC, LDL-C, Apo-A1, Apo-B and Hcy can all affect the occurrence of IS, and CYP2C19 and CYP3A5 gene polymorphisms are closely associated with the IS. Above finding has confirmed that the CYP450 gene polymorphisms can increase the risk of IS, which may provide a reference for the clinical diagnosis.
Humans ; Cytochrome P-450 CYP3A/genetics* ; Cytochrome P-450 CYP2C19/genetics* ; Ischemic Stroke ; Cholesterol, LDL/genetics* ; Polymorphism, Single Nucleotide ; Genotype ; Apolipoproteins B/genetics* ; Gene Frequency

Retinal pigment epithelium(RPE)has essential functions,such as nourishing and sup-porting the neural retina,and is of vital importance in the pathogenesis of age-related retinal degen-eration.However,the exact molecular changes of RPE during aging remain poorly understood.Here,we isolated human primary RPE(hRPE)cells from 18 eye donors distributed over a wide age range(10-67 years old).A quantitative proteomic analysis was performed to analyze changes in their intracellular and secreted proteins.Age-group related subtypes and age-associated proteins were revealed and potential age-associated mechanisms were validated in ARPE-19 and hRPE cells.The results of proteomic data analysis and verifications suggest that RNF123-and RNF149-related protein ubiquitination plays an important role in protecting hRPE cells from oxidative damage dur-ing aging.In older hRPE cells,apoptotic signaling-related pathways were up-regulated,and endo-plasmic reticulum organization was down-regulated both in the intracellular and secreted proteomes.Our work paints a detailed molecular picture of hRPE cells during the aging process and provides new insights into the molecular characteristics of RPE during aging and under other related clinical retinal conditions.

Objective:To construct a multi-label learning MRI model for assisting diagnosis of sports injury in knee.Methods:A total of 1 391 knee MRI cases from 1 343 young adults with sports injury in Affiliated Jinling Hospital Nanjing University School of Medicine were retrospectively enrolled. The image cases were randomly divided into training set ( n=973), validation set ( n=139) and test set ( n=279) with ratio of 7∶1∶2. The knee injuries were divided into six categories: meniscus injury, tendon injury, ligament injury, osteochondral injury, synovial bursa disorder and soft tissue injury. Using PyTorch V1.1.0 algorithm package, the Yolo model of deep learning was used to construct the MRI knee joint sports injury detection model. The model was validated on the test set, and the sensitivity, specificity and mean average precision of lesion detection were evaluated. Results:Among the 279 patients in test set, the mean average precision of meniscus injury, tendon injury, ligament injury, osteochondral injury, synovial bursa disorder and soft tissue injury were 83.1%, 89.0%, 88.0%, 85.8%, 85.5% and 83.2%, respectively, and the overall mean average precision was 85.8%. The model was most effective in detecting tendon injury. The sensitivity and specificity of the model for tendon injury were 91.2% and 87.1% respectively.Conclusions:The multi-label MRI knee joint exercise-related injury detection model based on deep learning can effectively assist in detecting the exercise-related injury of knee joint in each tissue structure, and is expected to improve the efficiency of diagnosis and treatment in orthopedics.

Objective:To investigate the clinical effect of liver transplantation from organ donors in elderly patients.Methods:The clinical data of 346 patients who underwent liver transplantation in the general surgery center of Beijing You′an Hospital Affiliated to Capital Medical University from January 2018 to November 2020 were retrospectively analyzed. After screening, they were divided into the elderly donor group (30 cases) aged 60-70 years and the non elderly donor group (60 cases) aged < 60 years. The observation indexes were operation time, anhepatic phase time and operation bleeding. The prognosis indexes were: postoperative ICU stay, length of hospital stay, primary graft nonfunction (PNF), delayed graft function recovery (DGF) and in-hospital mortality. The measurement data in accordance with normal distribution are expressed as ( Mean± SD). The comparison between the two groups was analyzed by t-test. The measurement data that did not conform to the normal distribution were expressed as median (range). Mann Whitney U test was used for comparison between the two groups. The counting data were collected by the computer χ2 test or Fisher′s exact test analysis. Results:The operation time, anhepatic period and blood loss in the elderly group were (444.33±72.44) min, 56.0 (30-170) min, 1 992.1(400-9 000) mL, respectively and the non elderly group were (460.88±91.32) min, 58.45 (35-140) min, 1 885.8(400-12 000) mL, respectively, there were no significant difference between the two groups ( P>0.05); Among the prognostic indicators, the length of stay in ICU, the length of stay in hospital and the in-hospital mortality of the elderly group were 4.9 (2-21) d, 20.4 (3-40) d and 10% respectively, while the length of stay in ICU, the length of stay in hospital and the in-hospital mortality of the non elderly group were 5.3(1-32) d, 22.1(3-61) d and 10% respectively, with no significant difference between the two groups ( P>0.05); No PNF occurred in the two groups, but the incidence rate of DGF in the elderly group was 13.33%(4/30), and the non elderly group was 1.67%(1/60). There was a significant difference between the two groups ( P<0.05). Conclusion:Under strict preoperative donor evaluation and accurate recipient selection, 60-70 years old donors can achieve similar short-term effect as non elderly donors, but the long-term effect needs further observation.

Objective To evaluate the safety of programmed cell death protein 1 (PD-1) inhibitor in the treatment of primary liver cancer (liver cancer) before liver transplantation. Methods Clinical data of 7 recipients given with PD-1 inhibitor before liver transplantation for liver cancer were retrospectively analyzed. The incidence of immune-related adverse event (irAE) and clinical prognosis of the recipients were summarized. The safety of PD-1 inhibitor in recipients prior to liver transplantation for liver cancer was evaluated. Results Seven recipients were treated with PD-1 inhibitor with 1-20 courses before liver transplantation for liver cancer. The time interval from drug withdrawal to liver transplantation was 6-120 d. Five recipients suffered from irAE of different degrees, including fatigue in 3 cases, fever in 2 cases, alopecia in 2 cases, rash in 1 case, nausea in 1 case and myocarditis in 1 case, respectively. A majority of these irAE were classified as grade Ⅰ-Ⅱ. One recipient died from grade Ⅴ irAE (fatal myocarditis). One recipient developed rejection at postoperative 7 d, which were mitigated after glucocorticoid pulse therapy combined with increased dosage of tacrolimus. Conclusions PD-1 inhibitor can be applied in preoperative treatment before liver transplantation for liver cancer. Nevertheless, the incidence of irAE and postoperative rejection should be intimately monitored.

Objective:To explore the anti-epidemic preventions and perioperative management strategies of organ donation and liver transplantation during the pandemic period of novel coronavirus pneumonia (NCP) and summarize the experiences.Methods:On the basis of guidance of National Health Commission and Organ Transplantation Committee of Chinese Medical Association, anti-epidemic preventions and perioperative management strategies of organ donation and liver transplantation were adjusted under the background of NCP pandemic and the anti-epidemic preventions and treatment outcomes were evaluated. Eight organ donations and 7 liver transplantations were performed from February 4 to March 7, 2020. NCP infection screening results were negative in all pre-donation and pre-transplantation cases.Results:All donation operations and liver transplantations were successfully performed without postoperative complications. No NCP occurred during hospitalization period. Postoperative pulmonary infection occurred in 1 case (1/7) and the following novel coronavirus screening result was negative. Pulmonary inflammation became partially absorbed after antibacterial therapy.Conclusions:Through strict and effective anti-epidemic preventions and perioperative managements, organ donation and transplantation could be successfully performed during the pandemic period of NCP.

BACKGROUND: In previous studies, we succeeded in repairing a long bone defect with tissue-engineered periosteum (TEP), fabricated by incorporating rabbit mesenchymal stem cells with small intestinal submucosa. In this study, we investigated the feasibility of allogeneic irregular bone defect repair using TEP. METHODS: We performed a subtotal resection of the scapula in 36 rabbits to establish a large irregular bone defect model. The rabbits were then randomly divided into three groups (n = 12 per group) and the defects were treated with TEP (Group 1), allogeneic deproteinized bone (DPB) (Group 2) or a hybrid of TEP and DPB (Group 3). At 4, 8, and 12 weeks after surgery, the rabbits were sacrificed, and the implants were harvested. X-ray radiographic and histological examinations were performed to detect bone healing. Ink-formaldehyde perfusion was introduced to qualitatively analyze vascularization in TEP engineered new bone. RESULTS: The repair of scapular defects was diverse in all groups, shown by radiographic and histological tests. The radiographic scores in Group 1 and Group 3 were significantly higher than Group 2 at 8 and 12 weeks (p < 0.05).Histological scores further proved that Group 1 had significantly greater new bone formation compared to Group 3 (p < 0.05), while Group 2 had the lowest osteogenesis at all time-points (p < 0.001). Ink-formaldehyde perfusion revealed aboundant microvessels in TEP engineered new bone. CONCLUSION We conclude that TEP is promising for the repair of large irregular bone defects. As a 3D scaffold, DPB could provide mechanical support and a shaping guide when combined with TEP. TEP engineered new bone has aboundant microvessels.

Objective To evaluate the safety and efficacy based on cytochrome P450(CYP)3A5*1 gene polymorphisms in guiding the individualized medication of tacrolimus (FK506) after liver transplantation. Methods Clinical data of 100 consecutively enrolled recipients who underwent liver transplantation for the first time were analyzed and randomly divided into experimental group and control group, with 50 cases in each group. The donors and recipients in the experimental group received preoperative CYP3A5 gene detection, and determined the FK506 medication regimen according to the CYP3A5*1 genotype. The compliance rate of FK506 target blood concentration, the recovery rate of liver function in the two groups of recipients at 7, 14, 28 d and 3, 6, 9, 12 months postoperatively, as well as the number of FK506 dosage adjustment during the follow-up were observed. The 1-year graft survival rate and the incidence of complications were recorded in both groups of recipients, such as acute rejection, infection, acute kidney injury, gastrointestinal symptoms, de novo hypertension, de novo diabetes, colds and rash, etc. Results The differences of the compliance rate of FK506 target blood concentration between the two groups of recipients at 7, 14 d after operation were statistically significant (both P < 0.05). There was no statistically significant difference between the two groups in the compliance rate of FK506 target blood concentration at 28 d and 3, 6, 9, 12 months and the recovery rate of liver function at the 7 observation time points after operation (all P > 0.05). The difference between the two groups of recipients in number of FK506 dose adjustment during follow-up was statistically significant (P=0.021). There were no statistically significant differences in 1-year graft survival rate and incidence of complications between the two groups of recipients after operation and during follow-up (all P > 0.05). Conclusions It is safe to guide individualized medication of FK506 after liver transplantation according to CYP3A5*1 gene polymorphism. It can increase the compliance rate of FK506 target blood concentration of recipients in the early postoperative stage, and can effectively reduce the number of dose adjustment duringfollow-up.

BACKGROUND: In previous studies, we succeeded in repairing a long bone defect with tissue-engineered periosteum (TEP), fabricated by incorporating rabbit mesenchymal stem cells with small intestinal submucosa. In this study, we investigated the feasibility of allogeneic irregular bone defect repair using TEP. METHODS: We performed a subtotal resection of the scapula in 36 rabbits to establish a large irregular bone defect model. The rabbits were then randomly divided into three groups (n = 12 per group) and the defects were treated with TEP (Group 1), allogeneic deproteinized bone (DPB) (Group 2) or a hybrid of TEP and DPB (Group 3). At 4, 8, and 12 weeks after surgery, the rabbits were sacrificed, and the implants were harvested. X-ray radiographic and histological examinations were performed to detect bone healing. Ink-formaldehyde perfusion was introduced to qualitatively analyze vascularization in TEP engineered new bone. RESULTS: The repair of scapular defects was diverse in all groups, shown by radiographic and histological tests. The radiographic scores in Group 1 and Group 3 were significantly higher than Group 2 at 8 and 12 weeks (p < 0.05).Histological scores further proved that Group 1 had significantly greater new bone formation compared to Group 3 (p < 0.05), while Group 2 had the lowest osteogenesis at all time-points (p < 0.001). Ink-formaldehyde perfusion revealed aboundant microvessels in TEP engineered new bone. CONCLUSION We conclude that TEP is promising for the repair of large irregular bone defects. As a 3D scaffold, DPB could provide mechanical support and a shaping guide when combined with TEP. TEP engineered new bone has aboundant microvessels.

Objective To evaluate the role of non?invasive fractional flow reserve (FFR) derived from coronary CT angiography (CCTA) in assessing the hemodynamic relevance of myocardial bridging (MB). Methods A total of 60 patients without obstructive coronary artery disease but with CCTA?confirmed MB of the left anterior descending coronary artery and 30 patients with negative CCTA findings as control group were retrospectively included in this study. The 60 patients with MB were divided into 2 groups (superficial and deep MB group) according to the depth of MB. Age and sex were matched among three groups. The location, length, depth, and degree of systolic compression of the MB were measured. The FFRCT values (including systolic and diastolic phases) were measured at three points (segments 1 to 2 cm proximal to a MB, mid?tunneled segment and segments 1 to 2 cm distal to the MB) by cFFR software. Patients with FFRCT<0.75 were deemed to have hemodynamic relevance (abnormal group). χ2 test, ANOVA test, Mann?Whitney U test, Kruskal?Wallis H test and logistic regression model were used for statistical analysis. Results The FFRCT values decreased from diastolic phase to systolic phase in deep MB group [0.90 (0.81-0.94) vs. 0.93 (0.91-0.97), Z=-2.172, P=0.03]. Compared to control group, the FFRCT values decreased in both diastolic phase and systolic phase in superficial MB group as well as deep MB group [systole 0.92 (0.90-0.94) control vs. 0.84 (0.77-0.88) superficial vs. 0.67 (0.50-0.88) deep, H=37.193, P<0.001; diastole 0.93 (0.89-0.94) control vs. 0.85 (0.73-0.92) superficial vs. 0.81 (0.65-0.87) deep, H=26.508, P<0.001]. Abnormal FFRCT values (<0.75) were found in 28 (47.7%) MB patients (9 superficial vs. 19 deep). The length (OR=1.067, 95% CI: 1.016-1.122, P=0.010) and depth (OR=2.028, 95%CI: 1.129-3.644, P=0.018) of MB were associated with the abnormal FFRCT values.Conclusions The FFRCT values of coronary artery distal to MB were lower than that without MB. Abnormal FFRCT values are more prevalent in deep MB. MB length and depth demonstrate moderate predictive value for an abnormal FFRCT value.