Mutations in CLCN6 as a Novel Genetic Cause of Neuronal Ceroid Lipofuscinosis.

OBJECTIVE: The aim of this study was to explore the pathogenesis of CLCN6-related disease and to assess whether its Cl-/H+-exchange activity is crucial for the biological role of ClC-6. METHODS: We performed whole-exome sequencing on a girl with development delay, intractable epilepsy, behavioral abnormities, retinal dysfunction, progressive brain atrophy, suggestive of neuronal ceroid lipofuscinoses (NCLs). We generated and analyzed the first knock-in mouse model of a patient variant (p.E200A) and compared it with a Clcn6-/- mouse model. Additional functional tests were performed with heterologous expression of mutant ClC-6. RESULTS: We identified a de novo heterozygous p.E200A variant in the proband. Expression of disease-causing ClC-6E200A or ClC-6Y553C mutants blocked autophagic flux and activated transcription factors EB (TFEB) and E3 (TFE3), leading to autophagic vesicle and cholesterol accumulation. Such alterations were absent with a transport-deficient ClC-6E267A mutant. Clcn6E200A/+ mice developed severe neurodegeneration with typical features of NCLs. Mutant ClC-6E200A, but not loss of ClC-6 in Clcn6-/- mice, increased lysosomal biogenesis by suppressing mTORC1-TFEB signaling, blocked autophagic flux through impairing lysosomal function, and increased apoptosis. Carbohydrate and lipid deposits accumulated in Clcn6E200A/+ brain, while only lipid storage was found in Clcn6-/- brain. Lysosome dysfunction, autophagy defects, and gliosis were early pathogenic events preceding neuron loss. INTERPRETATION: CLCN6 is a novel genetic cause of NCLs, highlighting the importance of considering CLCN6 mutations in the diagnostic workup for molecularly undefined forms of NCLs. Uncoupling of Cl- transport from H+ countertransport in the E200A mutant has a dominant effect on the autophagic/lysosomal pathway. ANN NEUROL 2024.

A systematic review and meta-analysis of the efficacy of ketamine and esketamine on suicidal ideation in treatment-resistant depression.

PURPOSE: To systematically assess the evidence of efficacy and safety of the use of ketamine and esketamine for patients with treatment-resistant depression (TRD) with suicidal ideation (SI). METHODS: We independently searched for clinical trials from inception to January 2023 using electronic databases, e.g., PubMed and EMBASE. A systematic review and meta-analysis were performed to assess SI scores of depression rating scales, which were regarded as the outcomes. RESULTS: A total of five independent double-blind, placebo controlled randomized clinical trials (RCTs) are eligible for inclusion. Four of the studies used ketamine as an intervention and one used esketamine as an intervention. Three hundred ninety-one patients with TRD were included (the intervention group with ketamine or esketamine is 246, and the control group is 145). No statistically significant interaction between the subscales of suicide ideation (SMD = - 0.66, 95% CI (- 1.61, 0.29); Z = 1.36, P = 0.17) and antidepressant effects (SMD = - 0.99, 95% CI (- 2.33, 0.34); Z = 1.46, P = 0.15) based on the results of ketamine and esketamine, compared with placebo groups. CONCLUSION: This meta-analysis suggested that esketamine and ketamine have failed to reduce suicidal ideation in patients with TRD. Further studies are desirable to confirm the effects of ketamine and esketamine in TRD patients.

Proteomic and phosphoproteomic landscape of salivary extracellular vesicles to assess OSCC therapeutical outcomes.

Circulating extracellular vesicles (EVs) have emerged as an appealing source for surrogates to evaluate the disease status. Herein, we present a novel proteomic strategy to identify proteins and phosphoproteins from salivary EVs to distinguish oral squamous cell carcinoma (OSCC) patients from healthy individuals and explore the feasibility to evaluate therapeutical outcomes. Bi-functionalized magnetic beads (BiMBs) with Ti (IV) ions and a lipid analog, 1,2-Distearoyl-3-sn-glycerophosphoethanolamine (DSPE) are developed to efficiently isolate EVs from small volume of saliva. In the discovery stage, label-free proteomics and phosphoproteomics quantification showed 315 upregulated proteins and 132 upregulated phosphoproteins in OSCC patients among more than 2500 EV proteins and 1000 EV phosphoproteins, respectively. We further applied targeted proteomics by coupling parallel reaction monitoring with parallel accumulation-serial fragmentation (prm-PASEF) to measure panels of proteins and phosphoproteins from salivary EVs collected before and after surgical resection. A panel of three total proteins and three phosphoproteins, most of which have previously been associated with OSCC and other cancer types, show sensitive response to the therapy in individual patients. Our study presents a novel strategy to the discovery of effective biomarkers for non-invasive assessment of OSCC surgical outcomes with small amount of saliva.

A presumed missense variant in the U2AF2 gene causes exon skipping in neurodevelopmental diseases.

U2 small nuclear RNA auxiliary factor 2 (U2AF2) is an indispensable pre-mRNA splicing factor in the early process of splicing. Recently, U2AF2 was reported as a novel candidate gene associated with neurodevelopmental disorders. Herein, we report a patient with a novel presumed heterozygous missense variant in the U2AF2 gene (c.603G>T), who has a similar clinical phenotype as the patient reported before, including epilepsy, intellectual disability, language delay, microcephaly, and hypoplastic corpus callosum. We reviewed the phenotypic and genetic spectrum of patients with U2AF2-related neurological diseases, both newly diagnosed and previously reported. To investigate the possible pathogenesis, EBV-immortalized lymphoblastoid cells were derived from the peripheral blood obtained from the patient and control groups. Furthermore, according to the results of WB, RT-PCR, Q-PCR, and cDNA sequencing of RT-PCR products, the presumed missense variant c.603G>T caused exon 6 skipping in the U2AF2 mRNA transcript and led to a truncated protein (p.E163_E201del). Cell Counting Kit-8 (CCK-8) and cell cycle detection demonstrated that the variant c.603G>T inhibited the proliferation of patient lymphocyte cells compared with the control group. This study is aimed at expanding the phenotypic and genetic spectrum of U2AF2-related neurodevelopmental diseases and investigating the potential effects. This is the first report of the possible pathogenesis of a U2AF2 gene pathogenic variant in a patient with neurodevelopmental diseases and shows that a novel presumed missense variant in the U2AF2 gene causes exon skipping.

Silencing of miR-132-3p protects against neuronal injury following status epilepticus by inhibiting IL-1ß-induced reactive astrocyte (A1) polarization.

Mesial temporal lobe epilepsy (MTLE) is one of the most common refractory epilepsies and is usually accompanied by a range of brain pathological changes, such as neuronal injury and astrocytosis. Naïve astrocytes are readily converted to cytotoxic reactive astrocytes (A1) in response to inflammatory stimulation, suppressing the polarization of A1 protects against neuronal death in early central nervous system injury. Our previous study found that pro-inflammatory cytokines and miR-132-3p (hereinafter referred to as "miR-132") expression were upregulated, but how miR-132 affected reactive astrocyte polarization and neuronal damage during epilepsy is not fully understood. Here, we aimed to explore the effect and mechanism of miR-132 on A1 polarization. Our results confirmed that A1 markers were significantly elevated in the hippocampus of MTLE rats and IL-1ß-treated primary astrocytes. In vivo, knockdown of miR-132 by lateral ventricular injection reduced A1 astrocytes, neuronal loss, mossy fiber sprouting, and remitted the severity of status epilepticus and the recurrence of spontaneous recurrent seizures. In vitro, the neuronal cell viability and axon length were reduced by additional treatment with A1 astrocyte conditioned media (ACM), and downregulation of astrocyte miR-132 rescued the inhibition of cell activity by A1 ACM, while the length of axons was further inhibited. The regulation of miR-132 on A1 astrocytes may be related to its target gene expression. Our results show that interfering with astrocyte polarization may be a breakthrough in the treatment of refractory epilepsy, which may extend to the research of other astrocyte polarization-mediated brain injuries.

p-AKT/VPS4B regulates the small extracellular vesicle size in venous malformation endothelial cells.

OBJECTIVE: Small extracellular vesicle (sEV)-mediated intercellular communication is increasingly the key for the understanding of venous malformations (VMs). This study aims to clarify the detailed changes of sEVs in VMs. SUBJECTS AND METHODS: Fifteen VM patients without treatment history and twelve healthy donors were enrolled in the study. sEVs were isolated from both fresh lesions and cell supernatant, and were examined by western blotting, nanoparticle tracking analysis and transmission electron microscopy. Western blot analysis, immunohistochemistry and immunofluorescence were adopted to screening candidate regulator of sEV size. Specific inhibitors and siRNA were employed to validate the role of dysregulated p-AKT/vacuolar protein sorting-associated protein 4B (VPS4B) signaling on the size of sEVs in endothelial cells. RESULTS: The size of sEVs derived from both VM lesion tissues and cell model was significantly increased. VPS4B, whose expression level was mostly significantly downregulated in VM endothelial cells, was responsible for the size change of sEVs. Targeting abnormal AKT activation corrected the size change of sEVs by recovering the expression level of VPS4B. CONCLUSION: Downregulated VPS4B in endothelial cells, resulted from abnormally activated AKT signaling, contributed to the increased size of sEVs in VMs.

m6A transferase METTL3 regulates endothelial-mesenchymal transition in diabetic retinopathy via lncRNA SNHG7/KHSRP/MKL1 axis.

Diabetic retinopathy is one of the microvascular complications in diabetic patients and the leading cause of blindness worldwide. The levels of METTL3, lncRNA SNHG7, KHSRP, MKL1, endothelial and mesenchymal markers were determined by RT-qPCR or western blot assays in vitro and in vivo. H&E staining was used to observe the retinal structure in a mouse model of DR. The expression levels of METTL3 and SNHG7 were significantly downregulated in DR patients, DR mice and high glucose-induced HRMECs cells. Notably, METTL3 installed the m6A modification and enhanced the stability of SNHG7. Besides, METTL3 inhibited HRMECs EndoMT by promoting the expression of SNHG7. Additionally, SNHG7 was found to weaken MKL1 mRNA stability by binding to the RNA-binding protein KHSRP. Furthermore, we verified that METTL3 regulated EndoMT in DR through the SNHG7/MKL1 axis. We conclude that METTL3 regulates endothelial-mesenchymal transition in DR via the SNHG7/KHSRP/MKL1 axis, providing a new target for DR treatment.

A Novel Ensemble Fault Diagnosis Model for Main Circulation Pumps of Converter Valves in VSC-HVDC Transmission Systems.

The intelligent fault diagnosis of main circulation pumps is crucial for ensuring their safe and stable operation. However, limited research has been conducted on this topic, and applying existing fault diagnosis methods designed for other equipment may not yield optimal results when directly used for main circulation pump fault diagnosis. To address this issue, we propose a novel ensemble fault diagnosis model for the main circulation pumps of converter valves in voltage source converter-based high voltage direct current transmission (VSG-HVDC) systems. The proposed model employs a set of base learners already able to achieve satisfying fault diagnosis performance and a weighting model based on deep reinforcement learning that synthesizes the outputs of these base learners and assigns different weights to obtain the final fault diagnosis results. The experimental results demonstrate that the proposed model outperforms alternative approaches, achieving an accuracy of 95.00% and an F1 score of 90.48%. Compared to the widely used long and short-term memory artificial neural network (LSTM), the proposed model exhibits improvements of 4.06% in accuracy and 7.85% in F1 score. Furthermore, it surpasses the latest existing ensemble model based on the improved sparrow algorithm, with enhancements of 1.56% in accuracy and 2.91% in F1 score. This work presents a data-driven tool with high accuracy for the fault diagnosis of main circulation pumps, which plays a critical role in maintaining the operational stability of VSG-HVDC systems and satisfying the unmanned requirements of offshore flexible platform cooling systems.

TransFNN: A Novel Overtemperature Prediction Method for HVDC Converter Valves Based on an Improved Transformer and the F-NN Algorithm.

Appropriate cooling of the converter valve in a high-voltage direct current (HVDC) transmission system is highly significant for the safety, stability, and economical operation of a power grid. The proper adjustment of cooling measures is based on the accurate perception of the valve's future overtemperature state, which is characterized by the valve's cooling water temperature. However, very few previous studies have focused on this need, and the existing Transformer model, which excels in time-series predictions, cannot be directly applied to forecast the valve overtemperature state. In this study, we modified the Transformer and present a hybrid Transformer-FCM-NN (TransFNN) model to predict the future overtemperature state of the converter valve. The TransFNN model decouples the forecast process into two stages: (i) The modified Transformer is used to obtain the future values of the independent parameters; (ii) the relation between the valve cooling water temperature and the six independent operating parameters is fit, and the output of the Transformer is used to calculate the future values of the cooling water temperature. The results of the quantitative experiments showed that the proposed TransFNN model outperformed other models with which it was compared; with TransFNN being applied to predict the overtemperature state of the converter valves, the forecast accuracy was 91.81%, which was improved by 6.85% compared with that of the original Transformer model. Our work provides a novel approach to predicting the valve overtemperature state and acts as a data-driven tool for operation and maintenance personnel to use to adjust valve cooling measures punctually, effectively, and economically.

Adeno-associated virus-mediated gene therapy for rare pediatric neurogenetic diseases: Current status and outlook. / è ºç›¸å ³ç— æ¯’ä»‹å¯¼çš„åŸºå› æ²»ç–—åœ¨å„¿ç«¥ç¥žç»é—ä¼ ç½•è§ç— ä¸­åº”ç”¨çš„çŽ°çŠ¶ä¸Žå±•æœ›.

Rare pediatric neurogenetic diseases always have early onset, no specific therapy, high mortality, and pose a severe risk to the health and survival of children. Adeno-associated virus (AAV)-mediated gene therapy, a type of disease-modifying therapy, provides a new option for the treatment of rare pediatric neurogenetic diseases and represents a significant advancement in the field. Currently, the US Food and Drug Administration (FDA) and the European Medicines Association (EMA) have approved AAV-mediated gene therapy medications for treating spinal muscular atrophy, aromatic L-amino acid decarboxylase deficiency, and Duchenne muscular dystrophy. Numerous preclinical and clinical trial research findings from recent years indicate that AAV-mediated gene therapy has a promising future in treating genetic disorders. The quick approval process for rare diseases medications may bring hope for the treatment of children with rare neurogenetic diseases. AAV-mediated gene therapy is an emerging technology with certain risks and challenges. It is necessary to establish a standardized regulatory system and a sound long-term follow-up system to evaluate the efficacy and safety of gene therapy.

[Autosomal dominant mental retardation type 5 caused by SYNGAP1 gene mutations: a report of 8 cases and literature review]. / SYNGAP1åŸºå› å˜å¼‚ç›¸å ³å¸¸æŸ“è‰²ä½“æ˜¾æ€§æ™ºåŠ›éšœç¢5型8ä¾‹å¹¶æ–‡çŒ®å¤ä¹ .

OBJECTIVES: To summarize the clinical phenotype and genetic characteristics of children with autosomal dominant mental retardation type 5 caused by SYNGAP1 gene mutations. METHODS: A retrospective analysis was performed on the medical data of 8 children with autosomal dominant mental retardation type 5 caused by SYNGAP1 gene mutations who were diagnosed and treated in the Department of Pediatrics, Xiangya Hospital of Central South University. RESULTS: The mean age of onset was 9 months for the 8 children. All children had moderate-to-severe developmental delay (especially delayed language development), among whom 7 children also had seizures. Among these 8 children, 7 had novel heterozygous mutations (3 with frameshift mutations, 2 with nonsense mutations, and 2 with missense mutations) and 1 had 6p21.3 microdeletion. According to the literature review, there were 48 Chinese children with mental retardation caused by SYNGAP1 gene mutations (including the children in this study), among whom 40 had seizures, and the mean age of onset of seizures was 31.4 months. Frameshift mutations (15/48, 31%) and nonsense mutations (19/48, 40%) were relatively common in these children. In terms of treatment, among the 33 children with a history of epileptic medication, 28 (28/33, 85%) showed response to valproic acid antiepileptic treatment and 16 (16/33, 48%) achieved complete seizure control after valproic acid monotherapy or combined therapy. CONCLUSIONS: Children with autosomal dominant mental retardation type 5 caused by SYNGAP1 gene mutations tend to have an early age of onset, and most of them are accompanied by seizures. These children mainly have frameshift and nonsense mutations. Valproic acid is effective for the treatment of seizures in most children.

Mitophagy, a Form of Selective Autophagy, Plays an Essential Role in Mitochondrial Dynamics of Parkinson's Disease.

Parkinson's disease (PD) is a severe neurodegenerative disorder caused by the progressive loss of dopaminergic neurons in the substantia nigra and affects millions of people. Currently, mitochondrial dysfunction is considered as a central role in the pathogenesis of both sporadic and familial forms of PD. Mitophagy, a process that selectively targets damaged or redundant mitochondria to the lysosome for elimination via the autophagy devices, is crucial in preserving mitochondrial health. So far, aberrant mitophagy has been observed in the postmortem of PD patients and genetic or toxin-induced models of PD. Except for mitochondrial dysfunction, mitophagy is involved in regulating several other PD-related pathological mechanisms as well, e.g., oxidative stress and calcium imbalance. So far, the mitophagy mechanisms induced by PD-related proteins, PINK1 and Parkin, have been studied widely, and several other PD-associated genes, e.g., DJ-1, LRRK2, and alpha-synuclein, have been discovered to participate in the regulation of mitophagy as well, which further strengthens the link between mitophagy and PD. Thus, in this view, we reviewed mitophagy pathways in belief and discussed the interactions between mitophagy and several PD's pathological mechanisms and how PD-related genes modulate the mitophagy process.

[Application of adeno-associated virus-mediated gene therapy in lysosomal storage diseases]. / è ºç›¸å ³ç— æ¯’ä»‹å¯¼çš„åŸºå› ç–—æ³•åœ¨æº¶é ¶ä½“è´®ç§¯ç—‡ä¸­çš„åº”ç”¨.

Lysosomal storage disorders (LSDs) are a group of single-gene inherited metabolic diseases caused by defects in lysosomal enzymes or function-related proteins. Enzyme replacement therapy is the main treatment method in clinical practice, but it has a poor effect in patients with neurological symptoms. With the rapid development of multi-omics, sequencing technology, and bioengineering, gene therapy has been applied in patients with LSDs. As one of the vectors of gene therapy, adeno-associated virus (AAV) has good prospects in the treatment of genetic and metabolic diseases. More and more studies have shown that AAV-mediated gene therapy is effective in LSDs. This article reviews the application of AAV-mediated gene therapy in LSDs.

Parkin, an E3 Ubiquitin Ligase, Plays an Essential Role in Mitochondrial Quality Control in Parkinson's Disease.

Parkinson's disease (PD), as one of the complex neurodegenerative disorders, affects millions of aged people. Although the precise pathogenesis remains mostly unknown, a significant number of studies have demonstrated that mitochondrial dysfunction acts as a major role in the pathogeny of PD. Both nuclear and mitochondrial DNA mutations can damage mitochondrial integrity. Especially, mutations in several genes that PD-linked have a closed association with mitochondrial dysfunction (e.g., Parkin, PINK1, DJ-1, alpha-synuclein, and LRRK2). Parkin, whose mutation causes autosomal-recessive juvenile parkinsonism, plays an essential role in mitochondrial quality control of mitochondrial biogenesis, mitochondrial dynamics, and mitophagy. Therefore, we summarized the advanced studies of Parkin's role in mitochondrial quality control and hoped it could be studied further as a therapeutic target for PD.

Free-Standing Photocrosslinked Protein Polymer Hydrogels for Sustained Drug Release.

The fabrication of protein hydrogels consisting of different properties and functional motifs is critical in the development of protein-based materials for biomedical applications. Here, we report the design and characterization of a triblock protein polymer, CEC, composed of two different self-assembling domains derived from elastin protein (E) and coiled-coil protein (C), photopolymerized with a NHS-diazirine (D) crosslinker into a CEC-D hydrogel. The optimal photocrosslinker concentration and exposure time is determined to fabricate a free-standing hydrogel. Upon increasing the concentration of the CEC-D monomer and environmental temperature, the CEC-D hydrogel's conformation decreases in helical content from 58.0% to 44.8% and increases in ß-content from 25.9% to 38.1%. These gels experience 55 ± 6% protein erosion from the free-standing gel in 13 days as the gel films gradually decrease in size. The swelling ratio of 12 ± 1% denotes that the gel has a swelling ability comparable to other protein hydrogels. These photocrosslinked CEC-D hydrogels can be employed for drug delivery with high encapsulation and 14 ± 2% release of curcumin into the supernatant in a week long study. Overall, the photocrosslinked CEC-D hydrogels exhibit stability, swelling ability, and sustained release of drug.

Role of mitophagy in mitochondrial quality control: Mechanisms and potential implications for neurodegenerative diseases.

Neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis) commonly characterized by the gradual loss of neurons have a seriously bad impact on motor and cognitive abilities of affected humans and bring great inconvenience to their lives. Mitochondrial dysfunction has been considered the key and common factor for the pathologies of neurodegenerative diseases for that neurons are extremely energy-intensive due to their unique properties in structures and functions. Thus, mitophagy, as a central role of mitochondrial quality control and currently believed to be the most effective pathway to clear dysfunctional or unwanted mitochondria, is rather crucial in the preservation of neuronal health. In addition, mitophagy establishes an intimated link with several other pathways of mitochondrial quality control (e.g., mitochondrial biogenesis and mitochondrial dynamics), and they work together to preserve mitochondrial health. Therefore, in this review, we summarized the recent process on the mechanisms of mitophagy pathways in mammals, it's linking to mitochondrial quality control, its role in several major neurodegenerative diseases, and possible therapeutic interventions focusing on mitophagy pathways. And we expect that it can provide us with more understanding of the mitophagy pathways and more promising approaches for the treatment of neurodegenerative diseases.

Novel rapid-acting glutamatergic modulators: Targeting the synaptic plasticity in depression.

Major depressive disorder (MDD) is severely prevalent, and conventional monoaminergic antidepressants gradually exhibit low therapeutic efficiency, especially for patients with treatment-resistant depression. A neuroplasticity hypothesis is an emerging advancement in the mechanism of depression, mainly expressed in the glutamate system, e.g., glutamate receptors and signaling. Dysfunctional glutamatergic neurotransmission is currently considered to be closely associated with the pathophysiology of MDD. Biological function, pharmacological action, and signal attributes in the glutamate system both regulate the neural process. Specific functional subunits could be therapeutic targets to explore the novel glutamatergic modulators, which have fast-acting, and relatively sustained antidepressant effects. Here, the present review summarizes the pathophysiology of MDD found in the glutamate system, exploring the role of glutamate receptors and their downstream effects. These convergent mechanisms have prompted the development of other modulators targeting on glutamate system, including N-methyl-d-aspartate receptor antagonists, selective GluN2B-specific antagonists, glycine binding site agents, and regulators of metabotropic glutamate receptors. Relevant researches underly the putative mechanisms of these drugs, which reverse the damage of depression by regulating glutamatergic neurotransmission. It also provides further insight into the mechanism of depression and exploring potential targets for novel agent development.

The Link between Circadian Clock Genes and Autophagy in Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD), a progressive respiratory disease, is characterized by the alveolar epithelium injury and persistent airway inflammation. It is documented that oscillation and dysregulated expression of circadian clock genes, like Bmal1, Per1, and Per2, involved in COPD pathogenies, including chronic inflammation and imbalanced autophagy level, and targeting the associations of circadian rhythm and autophagy is promising strategies in the management and treatment of COPD. Herein, we reviewed the mechanisms of the circadian clock and the unbalance of the autophagic level in COPD, as well as the link between the two, so as to provide further theoretical bases for the study on the pathogenesis of COPD.

Closing-wedge distal femoral osteotomy combined with medial patellofemoral ligament reconstruction for recurrent patellar dislocation with genu valgum.

BACKGROUND: Medial patellofemoral ligament reconstruction (MPFLR) is a well-established procedure for addressing recurrent patellar dislocation (RPD) in young patients. However, despite being a promising procedure for RPD with genu valgum, there is a scarcity of reports on simultaneous MPFLR and closing-wedge distal femoral osteotomy (CWDFO). The purpose of the present study was to observe and analyse the clinical and imaging findings of CWDFO combined with MPFLR for RPD with genu valgum. METHODS: From May 2015 to April 2018, 25 patients with RPD and genu valgum were surgically treated in our department. Anteroposterior long-leg, weight-bearing, lower-extremity radiographs, lateral radiographs and computed tomography (CT) scans of the patellofemoral joint were obtained, and the anatomical femorotibial angle (aFTA), mechanical lateral distal femoral angle (mLDFA), weight-bearing line rate (WBLR), patellar height, patellar lateral shift (PLS) and tibial tubercle-trochlear groove (TT-TG) distance were analysed. Validated knee scores, such as the Kujala, Lysholm, visual analogue scale (VAS) scores and Tegner socres, were evaluated preoperatively and 2 years postoperatively. RESULTS: 25 patients, with an average age of 19.8 years (14-27), were evaluated. During the 2-year follow-up period, all patients were able to achieve a better sports level without any problems, with no recurrence of patellar instability. Compared with preoperation, the aFTA, mLDFA, WBLR and PLS showed statistically significant improvement following the procedure (p < 0.001). Meanwhile, no significant differences in the Insall index and TT-TG distance were found. The mean Kujala score, average Lysholm score, VAS score and Tegner socres showed significant postoperative improvement. CONCLUSIONS: CWDFO combined with MPFLR is a suitable treatment for RPD with genu valgum, and can lead to significant improvement in the clinical and imaging findings of the knee in the short term.

Multi-shot diffusion-weighted MRI reconstruction with magnitude-based spatial-angular locally low-rank regularization (SPA-LLR).

PURPOSE: To resolve the motion-induced phase variations in multi-shot multi-direction diffusion-weighted imaging (DWI) by applying regularization to magnitude images. THEORY AND METHODS: A nonlinear model was developed to estimate phase and magnitude images separately. A locally low-rank regularization (LLR) term was applied to the magnitude images from all diffusion-encoding directions to exploit the spatial and angular correlation. In vivo experiments with different resolutions and b-values were performed to validate the proposed method. RESULTS: The proposed method significantly reduces the noise level compared to the conventional reconstruction method and achieves submillimeter (0.8mm and 0.9mm isotropic resolutions) DWI with a b-value of 1,000  s/mm2 and 1-mm isotropic DWI with a b-value of 2,000  s/mm2 without modification of the sequence. CONCLUSIONS: A joint reconstruction method with spatial-angular LLR regularization on magnitude images substantially improves multi-direction DWI reconstruction, simultaneously removes motion-induced phase artifacts, and denoises images.