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It is noteworthy that despite many efforts to screen biochemical plasma markers for PD diagnosis, there is still not an accepted and validated surrogate biomarker. To decipher the role of the mitophagy-associated proteins (MAPs) in idiopathic PD subjects and investigate whether the diagnosis is related to MAP levels and whether the levels predict motor and cognitive progression. This prospective study totally enrolled 150 PD patients. 71 age-matched controls (CN) alongside 41 PDs in two cohorts: modeling cohort (cohort 1), including 121 PD, 52 CN, and 29 PDs; validated cohort (cohort 2), including 29 PD, 19 CN, and 12 PDs. The MAPs (PINK1, Parkin, PGAM5, BNIP3, and p-TBK1) and a-synuclein-related proteins (ASPs: total a-synuclein, phosphorylated a-synuclein, and a-synuclein oligomer) levels were measured using an electrochemiluminescence immunoassay. MAPs are elevated in the plasma of PD patients. The PINK1, Parkin, and PGAM5 displayed the top three measurable increase trends in amplitude compared to BNIP3 and p-TBK1. Moreover, the AUCs of PINK1, PGAM5, and Parkin were ranked the top three MAP candidates in diagnosis accuracy for PD from CN, but the MAPs hard to differentiate the PD from PDs. In addition, Plasma PINK1 positively correlated with total UPDRS, UPDRS part III, and H-Y stage, with no significant correlations with HAMA, HAMD, and RBD scores. As expected, higher plasma PINK1-Parkin levels and prominent diagnostic accuracy in A-synuclein (+) subjects than in A-synuclein (-) subjects. These results uncover that plasma MAPs (PINK1, Parkin, and PGAM5) may be potentially useful target biomarkers for PD diagnosis. Studies on larger cohorts would be required to test whether elevated plasma MAP levels are related to PD risk or prediction.

The main histopathology of Alzheimer's disease (AD) is featured by the extracellular accumulation of amyloid-β (Aβ) plaques and intracellular tau neurofibrillary tangles (NFT) in the brain, which is likely to result from co-pathogenic interactions among multiple factors, e.g., aging or genes. The link between defective autophagy/mitophagy and AD pathologies is still under investigation and not fully established. In this review, we consider how AD is associated with impaired autophagy and mitophagy, and how these impact pathological hallmarks as well as the potential mechanisms. This complicated interplay between autophagy or mitophagy and histopathology in AD suggests that targeting autophagy or mitophagy probably is a promising anti-AD drug candidate. Finally, we review the implications of some new insights for induction of autophagy or mitophagy as the new therapeutic way that targets processes upstream of both NFT and Aβ plaques, and hence stops the neurodegenerative course in AD.

Objective Physical exercise has obvious effects on bone loss, pain relief, and improvement of bone metabolism indexes in patients with osteoporosis, but currently lacks sufficient evidence. The aim of this systematic review and meta‐analysis was to synthesize and present the best available evidence on the effectiveness and safety of exercises in the treatment of primary osteoporosis. Methods Publications pertaining to the effectiveness of exercise on bone mineral density (BMD), visual analog scores (VAS), and biochemical markers of bone metabolism in primary osteoporosis (POP) from PubMed, Cochrane Library, Embase, VIP, CNKI, and Wanfang Database were retrieved from their inception to April 2020. Results A total of 20 studies with 1824 participants were included. The results of the meta‐analysis revealed that exercise therapy for lumbar spine and femoral neck BMD is statistically different from conventional therapy (lumbar spine BMD: SMD = 0.78, 95%CI: 0.46, 1.10, P, The results of this meta‐analysis show that different types of exercise therapies significantly improved lumbar spine and femoral neck BMD, and relieve the pain of patients in the current low‐quality evidence. Additional high‐quality evidence is required to confirm the effect of exercise therapy on the biochemical markers of bone metabolism in POP patients. Therefore, more multicenters, larger samples, long‐term, single‐blind RCTs are needed to evaluate the effects of exercise therapy on BMD, VAS and biochemical markers of bone metabolism in POP patients.

Objective To investigate the application of treatment modalities for patients with osteonecrosis of the femoral head (ONFH) in mainland China. Methods This cross‐sectional study was based on the online application of China Osteonecrosis of the Femoral Head Database (CONFHD). Between July 2016 to December 2018, the CONFHD program planned to recruit ONFH patients from 12 administrative areas across mainland China. Real‐world medical records of treatment regimens for these patients, including surgeries and prescriptions, were approved to upload to the CONFHD application for further analysis. The surgeries performed on these patients were classified into total hip arthroplasty and hip‐preserving procedures, and the latter was further classified into core decompression, bone grafting, and tantalum rod implantation. Prescription medications were classified into chemical medicine and Chinese herbal medicine (CHM); chemical medicine was further classified according to their chemical compounds, and CHM was classified according to therapeutic functions based on traditional Chinese medicine theory. Descriptive analysis was performed to summarize the application of different treatment regimens on the overall sample. Results A total of 1491 patients (2381 hips) who fulfilled the protocol criteria were included. There were 1039 males and 452 females with a mean age of 47.29 ± 12.69 years. The causes of ONFH were alcoholism in 642 patients (43%), corticosteroid in 439 patients (29%), trauma in 239 patients (16%), and idiopathic ONFH in 171 patients (11%). Operative treatments (including total hip arthroplasty and hip‐preserving procedures) were performed on 49% of patients (43% of hips), chemical medicine therapy (including bisphosphonate, statins, and prostacyclin) was given to 37% of patients (37% of hips), and CHM was administrated to 72% of patients (75% of hips). The aforementioned interventions were not always used alone, since 47% of patients (52% of hips) received combined regimens with multiple interventions. Among hips treated by surgery, all hips with ARCO stage IV ONFH received THA (305 hips), and THA was also performed on 63 hips with stage II ONFH. Over half of hips with stage I (81%), II (91%), and III (92%) ONFH had received pharmacological treatments. Prostacyclin and bisphosphonate were the top two most prescribed medicines used alone. CHM therapies with multiple CHM functions were more commonly prescribed. Conclusion Current treatment modalities for ONFH patients in mainland China include operative treatment, chemical medicine, and CHM. Combined regimens with different treatment modalities are common in real‐world clinical practices., A cross‐sectional study to investigate the application of treatment modalities for patients with osteonecrosis of the femoral head in mainland China based on the China Osteoncrosis of the Femoral Head Database's (CONFHD) online platform.

Osteonecrosis of the Femoral Head (ONFH) is a refractory disease of orthopedics, and its incidence is gradually increasing. Often due to lack of timely intervention, the femoral head collapses, eventually causing hip pain and difficulty in activities. At present, the treatment of hip preservation after the collapse of osteonecrosis of the femoral head has received everyone's attention, but many hip-preserving measures are controversial in terms of efficacy and indications. Needle-knife therapy is a kind of hip-protection therapy with low risk, small trauma, bleeding, and less and shorter treatments. This article reviews the literatures related to needle-knife therapy for osteonecrosis of the femoral head, and summarizes the clinical treatment of osteonecrosis of the femoral head based on needle-knife, and prospects for its research

OBJECTIVE To develop a prediction method for femoral head collapse by using patient-specific finite element analysis of osteonecrosis of the femoral head (ONFH). METHODS The retrospective study recruited 40 patients with ARCO stage-II ONFH (40 pre-collapse hips). Patients were divided into two groups according to the 1-year follow-up outcomes: patient group without femoral head collapse (noncollapse group, n = 20) and patient group with collapse (collapse group, n = 20). CT scans of the hip were performed for all patients once they joined the study. Patient-specific finite element models were generated based on these original CT images following the same procedures: segmenting the necrotic lesion and viable proximal femur, meshing the computational models, assigning different material properties according to the Hounsfield unit distribution, simulating the stress loading of the slow walking gait, and measuring the distribution of the von Mises stress. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive performance of the maximum level of the von Mises stress. The optimal cut-off value was selected based on the Youden index and the corresponding predictive accuracy was reported as well. RESULTS The mean level of the maximum von Mises stress in the collapse group was 2.955 ± 0.539 MPa, whereas the mean stress level in the noncollapse group was 1.923 ± 0.793 MPa (P

Mounting evidence suggests that mitochondrial dysfunction and impaired mitophagy lead to Parkinson's disease (PD). Quercetin, one of the most abundant polyphenolic flavonoids, displays many health-promoting biological effects in many diseases. We explored the neuroprotective effect of quercetin in vivo in the 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD and in vitro in 6-OHDA-treated PC12 cells. In vitro, we found that quercetin (20 μM) treatment improved mitochondrial quality control, reduced oxidative stress, increased the levels of the mitophagy markers PINK1 and Parkin and decreased α-synuclein protein expression in 6-OHDA-treated PC12 cells. Moreover, our in vivo findings demonstrated that administration of quercetin also relieved 6-OHDA-induced progressive PD-like motor behaviors, mitigated neuronal death and reduced mitochondrial damage and α-synuclein accumulation in PD rats. Furthermore, the neuroprotective effect of quercetin was suppressed by knockdown of either Pink1 or Parkin.

Seed size play a significant role in maize yield production. Two maize inbred lines with distinct seed size and weight, V671 (a large-seed inbred line) and Mc (a small-seed inbred line), were investigated by RNA-seq at 14 days after pollination (DAP), when maize endosperm undergoes an active transition from mitosis to storage accumulation. RNA-seq expression data showed that the small-seed line Mc had a higher storage accumulation activity, whereas the large-seed kernel line V671 possessed a higher DNA synthesis activity. An investigation of the pattern of increasing kernel width at serial DAPs showed that V671 experienced an increased kernel width later than did Mc, but the rate and duration of increase were longer in V671. SDS-PAGE of the storage proteins and quantitative RT-PCR of cell cycle-related genes and indole-3-acetic (IAA) synthesis genes certified that the transition from mitosis to storage accumulation starts earlier in Mc. We hypothesized that the difference in the mitosis-to-storage accumulation transition accounts for the larger seed size in V671 vs. Mc.

Essential oils were extracted from white and black peppers (Piper nigrum L.) by green and solvent-free ultrasonic-microwave assisted extraction (UMAE), microwave assisted extraction (MAE) and ultrasonic assisted extraction (UAE), and the efficiency and free radical scavenging activities of the essential oils by different extraction methods were compared in order to illuminate their advantages and disadvantages. The oil yield and superoxide radical scavenging activity of white pepper by UMAE were both significantly higher than those oil extracted by MAE and UAE, implying that UMAE was far more efficient extracting method than MAE and UAE. The same trends were also found for black pepper. Meanwhile, the bioactive compounds of the essential oils from white and black peppers were also characterized and compared by GC coupled with mass spectrometry (GC–MS) and electronic nose based on fast gas chromatography (GC). The essential oil from black pepper contained more monoterpenes than the oil from white pepper, while white pepper oil showed higher content of sesquiterpenes than black pepper. For the different extraction methods, generally, UMAE could obtain more monoterpenes and sesquiterpenes than MAE and UAE. UMAE should be an emerging effective green extraction technique for essential oil from P. nigrum because of the maximum extraction yields, shortest extraction time and solvent-free. The electronic nose has been proven as a useful tool for quick analysis and discrimination of the essential oils by different extraction methods.

Alzheimer’s disease (AD) is the most common cause of dementia in elderly that serves to be a formidable socio-economic and healthcare challenge in the 21st century. Mitochondrial dysfunction and impairment of mitochondrial-specific autophagy, namely mitophagy, have emerged as important components of the cellular processes contributing to the development of AD pathologies, namely amyloid-β plaques (Aβ) and neurofibrillary tangles (NFT). Here, we highlight the recent advances in the association between impaired mitophagy and AD, as well as delineate the potential underlying mechanisms. Furthermore, we conduct a systematic review the current status of mitophagy modulators and analyzed their relevant mechanisms, evaluating on their advantages, limitations and current applications in clinical trials for AD patients. Finally, we describe how deep learning may be a promising method to rapid and efficient discovery of mitophagy inducers as well as general guidance for the workflow of the process.

Image-based finite element modelling has been commonly used to determine the biomechanical behaviours of human femora, particularly for the diagnosis of femoral head necrosis. One of the fundamental aspects of biomechanical modelling is the relationship between bone density, which is obtained from images, and elastic modulus. While there exist some empirical equations relating density with elastic modulus, the characterization of this relationship remains incomplete, especially for necrotic femoral heads. The objective of this study was to determine the relationship between density and elastic modulus by combining ultrasonic scanning and computed tomography (CT). Bone specimens were surgically removed from the femora of eight persons (seven females and one male in the age range of 55-68 years old) and underwent both ultrasonic and CT scanning. The images were processed with MATLAB scripts, and a bilinear interpolation algorithm was used to determine the relationship between the CT-measured densities and ultrasound-measured elastic moduli. The results showed different density-elastic modulus relations between the hardening strap of the necrotic region and non-hardening strap areas of the necrotic region. The uniqueness of this study is the characterization of mechanical properties (in the present study, the density-modulus relationship) from clinical images, which would be valuable in computational biomechanics used for the diagnosis and treatment evaluation of femoral head necrosis.

In femoral head necrosis, the cortical shell of the femoral head collapses and buckles into the cancellous bone. The purpose of this study is to explore the biomechanical characteristics of the femoral head and the necrosis region by comparing the results before and after drug treatment. In this paper, we study two patient cases with femoral head necrosis disease and establish the corresponding computational three-dimensional models. The results show that the deformation of the femur decreases slightly after the treatment, the equivalent stress distributes more evenly, and the stress magnitude reduces. The results also reveal that the volume of the necrosis in the femoral head decreases after treatment, the overall necrosis presents relatively lower equivalent stress, and the area with the relatively high equivalent stress is smaller comparing to the necrosis in femoral head before treatment.

To optimize a measuring method of osteonecrotic area by analyzing the average osteonecrotic areas and osteonecritic volume using multi layer MR images.The MRI images of 87 cases (120 hips) of ONFH(ARCO II) were collected retrospectively from January 2011 to January 2012 in Wangjing Hospital of China Academy of Chinese Medicine Science. PHILIPS Achieval 1.5T MR was used to obtain coronal TSE T1 weighted (T1W) images. The scanning parameters were shown as follows:slice thickness, 3.5 mm; gap, 0.3 mm; images repetition time(TR), 500 ms;echo time(TE), 20 ms;field of view (FOV), 374 mm;total 12 layers. According to the distribution rule of osteonecrotic lesion, the layer of coronal T1-weighted imaging showing most of femoral neck was marked as layer 0(L0). The layers before L0 were marked in sequence L1, L2, L3, L4... , and the layers after L0 were marked in sequence L-1, L-2, L-3, L-4... . Auto CAD 2007 was used to measure the percentage of osteonecrotic area and calcu late the average data, and then decreased the layer from low to high layer successively based on frequency of osteonecrotic occurrences. First, the layer with lowest frequency of osteonecrotic occurrenoses L3 was removed, then calculated the average osteonecrotic area of the ramaining 8 layers. L5, L4, L-2, L-1, L3 layers were gradually removed, resulting in the calculation of avereage osteonecrotic areas in 7, 6, 5, 4, 3 layers. These areas were compared to the osteonecrotic volume in MR imagings, leading to the optimization of the fewest layer measuring method of osteonecrotic area using a statistical analysis.The percentage of osteonecrotic volume in 120 hips was 0.333±0.151. The average osteonecrotic areas of 9 to 3 layers were 0.321±0.117, 0.317±0.136, 0.312±0.147, 0.333±0.153, 0.348±0.172, 0.365±0.174, 0.377±0.202 respectively. There were no statistical differences of the average osteonecrotic areas and osteonecrotic volume in 9 to 3 layers(The results of 4(L0, L1, L2, L3) layers measuring method and osteonecrotic volume measuring method are similar. The 4 layers measuring method is an accurate, convenient, valuable method measuring the esteonecrotic area with the fewest layers, which is worth to be popularized in clinical application.

It was performed nonlinear finite element analysis for K-shape eccentrically braced steel frames on link beam. Analysis indicates that the strength, rigidity, ductility and energy-dissipation performance of K shape eccentrically braced steel frames deteriorate differently with the length increase of link beam. The shorter the link beam is, the larger plastic deformation of it, so it makes plastic collapse easily, while a long link beam has a poor cyclic behavior. At the end of this paper, compared with the experimental results show that the finite element method is feasible, the results can provide a reference for the engineering design and related research.

The seismic performance of K-shape eccentrically frames were researched by cyclic loading test method, in order to understand earthquake performance, stiffness degradation and dissipation mechanism of energy. It can be concluded that K-shape eccentrically frames provide high elastic stiffness and demonstrate excellent energy dissipation capacity in the plastic stage, the different length of the link beam of different layers has great influence on the energy dissipation capacity of the structure, when shear yielding of link beam occurs, stiffness degradation become apparent, the hysteretic curves were plump in shapes. Therefore, K-shape eccentrically frames have better hysteretic behavior and energy dissipation capacity, the results can provide a reference for the engineering design and related research.

To observe the efficacy and features of treating early-to-middle stage nontraumatic osteonecrosis of femoral head (NONFH) patients by Jianpi Huogu Recipe (JHR).Using retrospective paired control method, early-to-middle stage NONFH patients treated by JHR and followed-up for 2 years were recruited as the test group (47 cases). Those accepted surgery of core decompression, focus debridement and bone graft were recruited as the control group (48 cases). Radiographic images and clinical data of patients were collected before and after treatment. The stable rate and excellent rate of Harris score were taken as efficacy evaluation indicators.(1) There was no statistical difference in excellent rate of Harris score between the two groups (95.74% vs. 79.17%, P0.05). But better effects were obtained in the test group in relieving pain, improving joint deformation, joint mobility, and total Harris score (P0. 05, P0. 01). There was no statistical difference in the stable rate of radiography between the two groups (74.47% vs. 75.00%, P0.05). (2) There was no statistical difference in the stable rate of radiography at phase II and Ill [staging by Association Research Circulation Osseous (ARCO)] between the two groups (82.05% vs. 80.00%, 37.50% vs. 50.00%, P0.05). (3) The stable rate of radiography and excellent rate of Harris score were obviously higher in ARCO phase II patients than in ARCO phase Il patients (82.05% vs. 37.50%,97.44% vs. 87.50%, P0.01).Equivalent stable rate of radiography to that of surgery could be obtained in treating early-to-middle stage NONFH patients by JHR. But it was better than surgery in relieving pain, improving joint deformation and joint mobility.