Aim To investigate the effect of theaflavin on oxidized low density lipoprotein(ox-LDL)-induced foam cell formation and oxidative stress in THP-1 macrophages and its mechanism.Methods THP-1 derived macro-phages were pretreated with 50 μmol/L theaflavin and(or)10 μmol/L nuclear factor erythroid 2-related factor 2(NRF2)inhibitor ML385,then 100 mg/L ox-LDL was added to the cells for 24 h to establish the foam cell model.The effect of theaflavin on THP-1 macrophages viability was evaluated by CCK-8 assay and LDH release.The expression of inflamma-tory cytokines interleukin-6(IL-6),interleukin-1 β(IL-1β),tumor necrosis factor-α(TNF-α)were analyzed by real-time quantitative polymerase chain reaction(RT-qPCR)and Western blot.The release of inflammatory cytokines were detected by enzyme linked immunosorbent assay(ELISA).Intracellular lipid accumulation was detected by Oil red O staining,and lipid absorption was observed by DiL-labeled oxidized low density lipoprotein(DiL-ox-LDL)staining.Re-active oxygen species(ROS)level was detected by DCFH-DA probe.The expression of lipid uptake,cholesterol efflux and oxidative stress-related proteins were detected by Western blot and RT-qPCR.Results Treatment with 100 mg/L ox-LDL significantly decreased cell viability and cholesterol efflux-related protein expressions,increased lipid uptake,ac-cumulation and lipid uptake-related protein expressions,and significantly promoted inflammation and ROS level,as well as the expressions of myeloperoxidase(MPO),NADPH oxidase 2(NOX2)in THP-1 macrophages(all P＜0.05).After pretreatment with theaflavin,cell viability was increased,intracellular lipid uptake,accumulation and lipid uptake-related protein expressions were significantly reduced,cholesterol efflux-related protein expressions were significantly increased,the expression and release of IL-6,IL-1β and TNF-α were significantly decreased,ROS level was significantly decreased,and the expression of MPO and NOX2 were decreased(all P＜0.05).Pretreatment with theaflavin effectively alleviated intracellular oxidative stress by altering the expression of NRF2,heme oxygenase-1(HO-1)and Kelch-like ECH-associated protein 1(KEAP1)in NRF2 signaling pathway,and enhanced the translocation of NRF2 into the nucleus.After pretreat-ment with ML385,the expression levels of NRF2,HO-1,KEAP1 and CD36 were significantly decreased.Conclusion Theaflavin can significantly inhibit ox-LDL-induced foam cell formation,inflammation,and oxidative stress through NRF2/HO-1 signaling pathway in THP-1 macrophages.

Objective:To establish standard spatial brain template and ROIs template of 11C-methyl- N-2β-carbomethoxy-3β-(4-fluorophenyl)tropane (CFT) PET images for automated quantitative analysis of dopamine transporter (DAT) distribution. Methods:From May 2014 to December 2015, 11C-CFT PET and MRI T 1 brain images of 16 healthy volunteers (3 males, 13 females; age (63.3±6.9) years) from Huashan Hospital, Fudan University were co-registered and smoothed using statistical parametric mapping(SPM)5 software based on MATLAB to create a standard spatial brain template. The ROIs template was established by ScAnVp procedures. These templates were clinically verified by using 11C-CFT PET images of 37 healthy volunteers (23 males, 14 females; age (61.7±7.1) years), 32 Parkinson′s disease (PD) patients (20 males, 12 females; age (61.1±5.4) years), 10 multiple system atrophy with predominant parkinsonism (MSA-P) patients (7 males, 3 females; age (60.8±7.1) years) and 10 progressive supranuclear palsy (PSP) patients (5 males, 5 females; age (58.4±6.1) years) from Huashan Hospital, Fudan University between January 2014 and March 2019. One-way analysis of variance was used to analyze data. Results:Based on the 11C-CFT PET images and MRI T 1 images of healthy volunteers, a standard spatial brain template for normalization of 11C-CFT PET images was created. The ROIs template was established including seven regions: bilateral caudate, anterior putamen, posterior putamen (along the long axis) and the occipital cortex. The ROIs template was accurately aligned in each verification group. The normal reference values of semi-quantitative DAT distribution in caudate, anterior putamen and posterior putamen were obtained (1.84±0.13, 2.18±0.16, 1.77±0.11). The semi-quantitative values of 11C-CFT uptake in each ROI in patients were significantly lower than those in healthy volunteers ( F values: 49.79-283.83, all P<0.05). Conclusion:The established brain templates with accurate spatial alignment for 11C-CFT image analysis can provide foundational tools for the application of 11C-CFT PET imaging in clinical practice and scientific research.

Objective:To explore the effects of mechanical factors on the morphology of the growth plate and proximal femur development, in order to provide a mechanical basis for the mechanism of Cam lesions in femoral acetabular impingement (FAI).Methods:Using CT scan data of hip joint from adolescents, we constructed three-dimensional finite element models of normal and extended proximal femoral epiphyseal growth plates. Dynamic mechanics and position data from daily activities (walk, stand on one and two feet, go upstairs and downstairs, sit and stand up, squat and stand up) and basketball layup drills were collected from five healthy volunteers using the Vicon system. The mean values of femoral head mechanical loads and positions at peak values, movement onset, and termination were selected for finite element analysis to observe the distribution of equivalent stress, normal stress, and shear stress on the two growth plate models under different activity modes.Results:Successful construction of three-dimensional finite element models for normal and extended proximal femoral epiphyseal growth plates was achieved. Mechanical load values and spatial positions of the femoral head during daily activities and layup movements were obtained. In daily activities, peak equivalent stress values for normal and extended growth plates ranged from 1.6 to 11.0 MPa; compressive stress ranged from 1.7 to 12.0 MPa; tensile stress ranged from 0.5 to 10.0 MPa; and shear force ranged from 0.4 to 7.1 MPa. The compressive stress during walking, standing on one or both feet, going up and down stairs, sitting and standing, and squatting was concentrated in the central and lateral areas; tensile stress was concentrated in the central and medial areas; shear force was concentrated in the medial area and the anterior and posterior edges of the growth plate. During a layup, the compressive stress in the center, outer upper side, and medial edge of the growth plate of the normal model was notably concentrated, with peaks fluctuating between 5.5-19.0 MPa, 5.7-11.0 MPa, and 5.4-7.3 MPa respectively; tensile stress and shear force were concentrated at the inner and outer edges as well as in the central area, with peaks fluctuating between 3.0-24.0 MPa and 3.0-26.0 MPa respectively, these values were significantly different from those observed during daily activities. For the elongated growth plate, compressive stress was concentrated at the central and lateral edges with peaks fluctuating between 17.0-41.0 MPa and 17.0-38.0 MPa respectively; simulated shear stress and tensile stress showed significant concentration at peaks fluctuating between 4.9-34.0 MPa, also significantly different from those observed during daily activities.Conclusion:The difference in mechanical distribution between daily activities, basketball layup training, as well as between normal and extended growth plates may be the mechanical initiating factor in the development of extended growth plates and the formation of Cam lesions, it may be the mechanical initiating factor for the development of extended growth plates and the collision of Cam lesions in FAI.

Objective To analyze the characteristics of the muscle strength around the knee joint of chondromalacia patellae patients, and to explore the difference with normal people.Methods In March, 2021, 70 knee-onset chondromalacia patellae patients (experimental group) and 35 normal people (control group) were measured isokinetic muscle strength of flexion and extension of knee in angular velocities of 60°/s and 180°/s.Results At 60°/s and 180°/s, the peak torque, the peak torque-to-weight ratio and the total work of the flexor and extensor muscles on the affected side in the experimental group were lower than that of the control group (U > 1097.0, P<0.001). The peak torque, the peak torque-to-weight ratio and the total work of the flexor and extensor muscles at 60°/s and extensor muscles at 180°/s were lower on the affected side than on the healthy side in the experimental group (|Z| > 2.121, P<0.05). The peak torque ratios at 60°/s and 180°/s were more in the affected knees than in the healthy knees of experimental group and in the control group (U > 1810.0, |Z| >3.691, P<0.01).Conclusion The explosive force and endurance of the knee flexor and extensor has weakened in patients with chondromalacia patellae, and there is imbalance in knee joint muscle strength.

Multi-centre clinical trials on PET/CT brain imaging are complex to organize and require careful co-ordination and management. This article describes considerations, which are necessary when designing and starting a multi-centre clinical trial on PET/CT brain imaging, based on guidelines and multi-center clinical brain imaging studies, providing references for further studies.

Photothermal therapy has the characteristics of minimal invasiveness, controllability, high efficiency, and strong specificity, which can effectively make up for the toxic side effects and tumor resistance caused by traditional drug treatment. However, due to the limited tissue penetration of infrared light, it is difficult to promote and apply in clinical practice. The eye is the only transparent tissue in human, and infrared light can easily penetrate the eye tissue, so it is expected that photothermal therapy can be used to treat fundus diseases. Here in, a new nano-platform assembled by liposome and indocyanine green (ICG) was used to treat retinoblastoma. ICG was assembled in liposomes to overcome some problems of ICG itself. For example, ICG is easily quenched, self-aggregating and instability. Moreover, liposomes can prevent free ICG from being cleared through the systemic circulation. The construction of the nano-platform not only ensured the stability of ICG in vivo, but also realized imaging-guide photothermal therapy, which created a new strategy for the treatment of retinoblastoma.

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) protein system, as an emerging gene editing system, can be divided into class 1 and class 2 systems according to the number of Cas protein. The CRISPR/Cas9 in class 2 system can cleave target nucleic acid only with the help of Cas9 protein and single-stranded guide RNA, which is currently the most widely used CRISPR/Cas system. In addition to gene editing in the treatment of genetic diseases, a variety of CRISPR/Cas system derived technologies have vast application prospect in the fields of disease-related gene screening, gene expression regulation, and rapid detection, prevention, and control of pathogens. This article summarizes the discovery process of CRISPR/Cas system and applications of several major CRISPR/Cas derived technologies, aiming to provide a reference for researchers in the field of life science.

[Objective]To investigate the relationship of baseline antimullerian hormone(AMH)and live birth rate of IVF/ICSI and further explore the prognostic effect of AMH on live birth rate.[Methods]All non-polycystic ovary patients who underwent their first embryo transfers in our unit and had basal serum AMH evaluated between 2010 and 2015 were evaluated in this retrospective study. Patients were grouped according to their AMH level,i.e. low AMH group with AMH less than 1.1 ng/mL(n = 485),middle AMH group with AMH between 1.1 ng/mL and 7.0 ng/mL (n = 1 989),and high AMH group with AMH higher than 7.0 ng/mL (n=468). For age subgroup analysis,patients were stratified as follow:group A(age≤29 years),group B(30~34 years),group C(35~39 years)and group D(over 40 years). We compared clinical outcomes between AMH groups in different age groups usingunivariate and multivariate analysis. ROC analysis was utilized to assess predictive value of AMH on live birth rate.[Results](1)In both fresh and frozen embryo transfers,baseline AMH was significantly related to clinical outcomes. The lower AMH was,the lower implantation rate,clinical pregnancy rate,and live birth rate. However,higher miscarriage rate was observed. All difference reached statistically significant.(2)In age subgroup analysis,we demonstrated AMH was related to live birth rate in patients in group A,B, and C,regardless of fresh or frozen embryo transferred. In those over 40 years,AMH was related to live birth rate in frozen cycles (P < 0.05)but not fresh cycles(P = 0.092). The further multivariate analysis confirmed the above results after controlling po?tential confounding variables.(3)The AUC of ROC analysis for AMH predicting live birth rate were 0.647,0.633 for fresh and fro?zen cycles respectively.[Conclusion]Baseline AMH as one of excellent ovarian reserve markers ,was significantly related to live birth rate in fresh or frozen cycles. Baseline AMH was an independent prognostic factor of live birth rate,but its predictive value on live birth rate was of limited clinical value.

Mizoribine(MZR), as an orally prescribed immunosuppressive agent, has been applied in the prevention of rejection after kidney transplantation.MZR requires individual dosing due to the variation of bioavailability.However, therapeutic drug monitoring (TDM) of MZR is not well developed in China, as compared to other clinically used immunosuppressive agents.To our knowledge, this is the first TDM review of MZR.Pharmacokinetic characteristic, concentration determination methods and sample selection of MZR were summarized, also the rational therapeutic window was proposed.Furthermore, gene polymorphism and population pharmacokinetics of MZR were estimated.This review will provide reference for TDM-based individual dosing of MZR in renal transplant recipients.

Objective To explore the rehabilitation for chorea after bilateral thalamus hemorrhage. Methods A case was reviewed. Re-sults The score of Fugl-Meyer Assessment of balance increased from 0 to 7, the modified Barthel Index increased from 25 to 50, and the co-ordination of movement improved significantly after rehabilitation treatment. Conclusion Early comprehensive rehabilitation may reduce the chorea movement, improve the activities of daily living and balance for chorea after bilateral thalamus hemorrhage.