Effectiveness of physiotherapeutic scoliosis-specific exercises on three-dimensional spinal deformities in patients with adolescent idiopathic scoliosis: A systematic review and meta-analysis.

OBJECTIVE: To investigate the effects of physiotherapeutic scoliosis-specific exercises (PSSE) on coronal, horizontal, and sagittal deformities of the spine in adolescent idiopathic scoliosis (AIS) as well as how curve severity, intervention duration, and intervention type could modify these effects. DATA SOURCES: Data sources included the PubMed, Web of Science, Embase, Cochrane Library, and Scopus databases, searched from their inception to September 5, 2023. STUDY SELECTION: Clinical controlled trials reporting the effects of PSSE on the Cobb angle, angle of trunk rotation (ATR), thoracic kyphosis (TK), or lumbar lordosis (LL) in AIS patients aged 10 to 18 years. The experimental groups received PSSE; the control groups received standard care (observation or bracing) or conventional exercise such as core stabilization exercise, pilates, PNF, and other non-specific exercise. DATA EXTRACTION: Two researchers independently extracted key information from eligible studies. The quality of the studies was assessed using the Cochrane Handbook version 5.1.0 risk of bias assessment and the JBI Center for Evidence-Based Health Care (2016) of quasi-experimental research authenticity assessment tool. The level and certainty of evidence was rated according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The protocol for this study was registered in PROSPERO (CRD42023404996). DATA SYNTHESIS: Twelve randomized controlled trials (RCTs) and five non-RCTs (NRCTs) were meta-analyzed separately. The results indicated that compared with other non-surgical management, PSSE significantly improved the Cobb angle, ATR, and TK, whereas the LL improvement was not statistically significant. Additionally, the efficacy of PSSE on Cobb angle was not significant in patients with curve severity ≥30° compared with controls. Nevertheless, the pooled effect of PSSE on Cobb angle was not significantly modified by intervention duration and intervention type, and on ATR was not significantly modified by intervention duration. The overall quality of evidence according to GRADE was moderate to low for RCT and very low for NRCT. CONCLUSIONS: PSSE exhibited positive benefits on the Cobb angle, ATR, and TK in patients with AIS compared to other non-surgical therapies. In addition, the effectiveness of PSSE may be independent of intervention duration and intervention type, but may be influenced by the initial Cobb angle. However, more RCTs are needed in the future to validate the efficacy of PSSE in moderate AIS with a mean Cobb ≥30°. Current evidence is limited by inconsistent control group interventions and small sample size of the studies.

Regulatory mechanism of miR-20a-5p in neuronal damage and inflammation in lipopolysaccharide-induced BV2 cells and MPTP-HCl-induced Parkinson's disease mice.

BACKGROUND: Parkinson's disease (PD) is a prevailing neurodegenerative disorder increasingly affecting the elderly population. The involvement of microRNAs (miRNAs) in PD has been confirmed. We sought to explore the molecular mechanism of miR-20a-5p in PD. METHODS: Lipopolysaccharide (LPS)-induced BV2 cell model and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP-HCl)-induced PD mouse model were established. miR-20a-5p, inducible nitric oxide synthase (iNOS), interleukin (IL)-6, tumour necrosis factor (TNF)-α, transforming growth factor (TGF)-ß1, and IL-10 expression in BV2 cells was examined by reverse transcription - quantitative polymerase chain reaction. Cell viability was assessed by MTT assay. The apoptotic rate and levels of Bcl-2, Bax, cleaved caspase-3, and signal transducer and activator of transmission (STAT)3 were examined by flow cytometry and Western blot. Bioinformatics software predicted the potential binding sites of miR-20a-5p and STAT3. Dual-luciferase experiment verified the binding relationship. Iba1-positive and tyrosine hydroxylase (TH)-positive cell numbers in substantia nigra pars compacta were detected by immunohistochemistry. The effect of miR-20a-5p on motor function in MPTP-induced PD mice was detected by Rota-rod test, Pole test, Traction test and Beam-crossing task. RESULTS: miR-20a-5p was under-expressed in LPS-induced BV2 cells. Overexpression of miR-20a-5p increased the viability of LPS-induced BV2 cells and reduced apoptosis rates. Moreover, overexpression of miR-20a-5p reduced cleaved caspase-3, Bax, iNOS, IL-6, and TNF-α and increased Bcl-2 and TGF-ß1, and IL-10. miR-20a-5p targeted STAT3. STAT3 overexpression partially reversed miR-20a-5p overexpression-mediated effects on LPS-induced BV2 cell viability, apoptosis, and inflammatory responses. miR-20a-5p overexpression inhibited MPTP-induced STAT3 and α-synuclein levels, microglia activation, and inflammatory response, and reduced the loss of TH-positive cells in mice. miR-20a-5p overexpression ameliorated MPTP-induced dyskinesia in PD model mice. CONCLUSION: miR-20a-5p alleviates neuronal damage and suppresses inflammation by targeting STAT3 in PD.

RAAS in diabetic retinopathy: mechanisms and therapies.

Diabetic retinopathy (DR) is a complication of diabetes with a complex pathophysiology and multiple factors involved. Recently, it has been found that the upregulation of the renin-angiotensin-aldosterone system (RAAS) leads to overexpression of angiotensin II (Ang II), which induces oxidative stress, inflammation, and angiogenesis in the retina. Therefore, RAAS may be a promising therapeutic target in DR. Notably, RAAS inhibitors are often used in the treatment of hypertension. Still, the potential role and mechanism of DR must be further studied. In this review, we discuss and summarize the pathology and potential therapeutic goals of RAAS in DR.

The mitochondrial UPR induced by ATF5 attenuates intervertebral disc degeneration via cooperating with mitophagy.

Intervertebral disc degeneration (IVDD) is an aging disease that results in a low quality of life and heavy socioeconomic burden. The mitochondrial unfolded protein response (UPRmt) take part in various aging-related diseases. Our research intents to explore the role and underlying mechanism of UPRmt in IVDD. Nucleus pulposus (NP) cells were exposed to IL-1ß and nicotinamide riboside (NR) served as UPRmt inducer to treat NP cells. Detection of ATP, NAD + and NADH were used to determine the function of mitochondria. MRI, Safranin O-fast green and Immunohistochemical examination were used to determine the degree of IVDD in vivo. In this study, we discovered that UPRmt was increased markedly in the NP cells of human IVDD tissues than in healthy controls. In vitro, UPRmt and mitophagy levels were promoted in NP cells treated with IL-1ß. Upregulation of UPRmt by NR and Atf5 overexpression inhibited NP cell apoptosis and further improved mitophagy. Silencing of Pink1 reversed the protective effects of NR and inhibited mitophagy induced by the UPRmt. In vivo, NR might attenuate the degree of IDD by activating the UPRmt in rats. In summary, the UPRmt was involved in IVDD by regulating Pink1-induced mitophagy. Mitophagy induced by the UPRmt might be a latent treated target for IVDD.

Genomic analysis reveals phylogeny of Zygophyllales and mechanism for water retention of a succulent xerophyte.

Revealing the genetic basis for stress-resistant traits in extremophile plants will yield important information for crop improvement. Zygophyllum xanthoxylum, an extant species of the ancient Mediterranean, is a succulent xerophyte that can maintain a favorable water status under desert habitats; however, the genetic basis of this adaptive trait is poorly understood. Furthermore, the phylogenetic position of Zygophyllales, to which Z. xanthoxylum belongs, remains controversial. In this study, we sequenced and assembled the chromosome-level genome of Z. xanthoxylum. Phylogenetic analysis showed that Zygophyllales and Myrtales form a separated taxon as a sister to the clade comprising fabids and malvids, clarifying the phylogenetic position of Zygophyllales at whole-genome scale. Analysis of genomic and transcriptomic data revealed multiple critical mechanisms underlying the efficient osmotic adjustment using Na+ and K+ as "cheap" osmolytes that Z. xanthoxylum has evolved through the expansion and synchronized expression of genes encoding key transporters/channels and their regulators involved in Na+/K+ uptake, transport, and compartmentation. It is worth noting that ZxCNGC1;1 (cyclic nucleotide-gated channels) and ZxCNGC1;2 constituted a previously undiscovered energy-saving pathway for Na+ uptake. Meanwhile, the core genes involved in biosynthesis of cuticular wax also featured an expansion and upregulated expression, contributing to the water retention capacity of Z. xanthoxylum under desert environments. Overall, these findings boost the understanding of evolutionary relationships of eudicots, illustrate the unique water retention mechanism in the succulent xerophyte that is distinct from glycophyte, and thus provide valuable genetic resources for the improvement of stress tolerance in crops and insights into the remediation of sodic lands.

Genomic data and ecological niche modeling reveal an unusually slow rate of molecular evolution in the Cretaceous Eupteleaceae.

Living fossils are evidence of long-term sustained ecological success. However, whether living fossils have little molecular changes remains poorly known, particularly in plants. Here, we have introduced a novel method that integrates phylogenomic, comparative genomic, and ecological niche modeling analyses to investigate the rate of molecular evolution of Eupteleaceae, a Cretaceous relict angiosperm family endemic to East Asia. We assembled a high-quality chromosome-level nuclear genome, and the chloroplast and mitochondrial genomes of a member of Eupteleaceae (Euptelea pleiosperma). Our results show that Eupteleaceae is most basal in Ranunculales, the earliest-diverging order in eudicots, and shares an ancient whole-genome duplication event with the other Ranunculales. We document that Eupteleaceae has the slowest rate of molecular changes in the observed angiosperms. The unusually low rate of molecular evolution of Eupteleaceae across all three independent inherited genomes and genes within each of the three genomes is in association with its conserved genome architecture, ancestral woody habit, and conserved niche requirements. Our findings reveal the evolution and adaptation of living fossil plants through large-scale environmental change and also provide new insights into early eudicot diversification.

Insulin resistance is associated with the presence and severity of retinopathy in patients with type 2 diabetes.

BACKGROUND: To assess the relationship between novel insulin resistance (IR) indices and the presence and severity of diabetic retinopathy (DR) in patients with type 2 diabetes. METHODS: This is a cross-sectional study involving 2211 patients. The study outcomes were DR events. The study exposures were IR indices including estimated glucose disposal rate (eGDR), natural logarithm of glucose disposal rate (lnGDR), metabolic insulin resistance score (METS-IR), triglyceride glucose index-body mass index (TyG-BMI), triglyceride glucose index-waist-to-hip ratio (TyG-WHR), and triglyceride/high-density lipoprotein cholesterol(TG/HDL-c ratio). We used binary and multivariate ordered logistic regression models to estimate the association between different IR indices and the presence and severity of DR. Subject work characteristic curves were used to assess the predictive power of different IR indices for DR. RESULTS: DR was present in 25.4% of participants. After adjusting for all covariates, per standard deviation (SD) increases in eGDR (ratio [OR] 0.38 [95% CI 0.32-0.44]), lnGDR (0.34 [0.27-0.42]) were negatively associated with the presence of DR. In contrast, per SD increases in METS-IR (1.97 [1.70-2.28]), TyG-BMI (1.94 [1.68-2.25]), TyG-WHR (2.34 [2.01-2.72]) and TG/HDL-c ratio (1.21 [1.08-1.36]) were positively associated with the presence of DR. eGDR was strongly associated with severity of DR. Of all variables, eGDR had the strongest diagnostic value for DR (AUC = 0.757). CONCLUSIONS: Of the six IR indices, eGDR was significantly associated with the presence and severity of DR in patients with type 2 diabetes. eGDR has a good predictive value for DR. Thus, eGDR maybe a stronger marker of DR.

Optimizing percutaneous vertebroplasty: extra-facet puncture for osteoporotic vertebral compression fractures.

PURPOSE: To assess the safety and efficacy of the extra-facet puncture technique applied in unilateral percutaneous vertebroplasty (PVP) for treating osteoporotic vertebral compression fractures. METHODS: Demographics (age, gender, body mass index and underlying diseases) were recorded for analyzing. Visual analog scale (VAS) and Oswestry Disability Index (ODI) scores as well as their corresponding minimal clinically important difference (MCID) were used to evaluate clinical outcomes. The segmental kyphotic angle, the vertebral compression ratio and bone cement distribution pattern were evaluated by the plain radiographs. The facet joint violation (FJV) was defined by the postoperative computed tomography scan. Binary logistic regression analysis was performed to investigate relationships between multiple risk factors and residual back pain. RESULTS: VAS and ODI scores in both traditional puncture group and extra-facet puncture group were significantly decreased after PVP surgery (p < 0.05). However, no significant difference was observed between the two groups according to VAS and ODI scores. The proportion of patients achieving MCID of VAS and ODI scores was higher in extra-facet puncture group as compared to traditional puncture group within a month (p < 0.05). Finally, multivariate logistic regression analysis showed that FJV (odds ratio 16.38, p < 0.001) and unilateral bone cement distribution (OR 5.576, p = 0.020) were significant predictors of residual back pain after PVP surgery. CONCLUSIONS: Extra-facet puncture percutaneous vertebroplasty can decrease the risk of FJV and it also has the advantage of more satisfied bone cement distribution.

Artificial intelligence in breast imaging: potentials and challenges.

Breast cancer, which is the most common type of malignant tumor among humans, is a leading cause of death in females. Standard treatment strategies, including neoadjuvant chemotherapy, surgery, postoperative chemotherapy, targeted therapy, endocrine therapy, and radiotherapy, are tailored for individual patients. Such personalized therapies have tremendously reduced the threat of breast cancer in females. Furthermore, early imaging screening plays an important role in reducing the treatment cycle and improving breast cancer prognosis. The recent innovative revolution in artificial intelligence (AI) has aided radiologists in the early and accurate diagnosis of breast cancer. In this review, we introduce the necessity of incorporating AI into breast imaging and the applications of AI in mammography, ultrasonography, magnetic resonance imaging, and positron emission tomography/computed tomography based on published articles since 1994. Moreover, the challenges of AI in breast imaging are discussed.

High Endplate Hounsfield Units Value Indicate Intervertebral Disc Degeneration Following Transforaminal Lumbar Interbody Fusion Surgery.

OBJECTIVE: Lumbar disc degeneration (LDD) is a common cause of low back pain and disability, and its prevalence increases with age. The aim of this study is to investigate whether endplate Hounsfield unit (HU) values have an effect on lumbar disc degeneration (LDD) after transforaminal lumbar interbody fusion (TLIF) surgery in patients with degenerative lumbar stenosis. METHODS: This study was a retrospective analysis of patients who underwent TLIF surgery in January 2016 to October 2019. One hundred and fifty-seven patients who underwent TLIF surgery for degenerative lumbar stenosis were enrolled in this study. Demographic data was recorded. VAS and ODI values were compared to assess the surgical outcomes in patients with or without process of LDD after TLIF surgery. Correlation analysis was performed to investigate associations between LDD and endplate HU value. Binary logistic regression analysis was carried out to study relationships between the DDD and the multiple risk factors. RESULTS: There was a statistically significant correlation between LDD, body mass index (BMI), age, paraspinal muscle atrophy, and total endplate scores (TEPS). Also, a strong and independent association between endplate HU value and LDD was found at every lumbar disc level (p < 0.01). After conditioning on matching factors, multivariate logistic regression analysis showed that higher endplate HU (odds ratio [OR]: 1.003, p = 0.003), higher TEPS (OR: 1.264, p = 0.002), higher BMI (odds ratio [OR]: 1.202, p = 0.002), a smaller cross-sectional area (CSA) of the paraspinal muscle preoperatively (OR: 0.096, p < 0.001) were significant predictors of LDD development after TLIF surgery. CONCLUSIONS: There is a significant association between LDD and endplate HU value after TLIF surgery in patients with degenerative lumbar stenosis. Beyond that, results from this study provide a mechanism by which high endplate HU value predisposes to LDD after TLIF surgery.

Impaired Sensitivity to Thyroid Hormones is Associated with Mild Cognitive Impairment in Euthyroid Patients with Type 2 Diabetes.

Purpose: The prevalence of mild cognitive impairment (MCI) in patients with type 2 diabetes (T2D) is rapidly increasing. Thyroid hormones are key regulators of cognitive function in adults. The purpose of this study was to investigate the relationship between thyroid hormone sensitivity and MCI in euthyroid T2D patients. Patients and Methods: A total of 400 euthyroid T2D patients were enrolled in this cross-sectional study, including 218 patients with normal cognition and 182 MCI patients. The Montreal Cognitive Assessment (MoCA) was used to evaluate cognitive function. The free triiodothyronine to free thyroxine (FT3/FT4) ratio was calculated as a measure of peripheral sensitivity to thyroid hormones; the thyroid-stimulating hormone index (TSHI), thyrotrophic thyroxine resistance index (TT4RI) and thyroid feedback quantile-based index (TFQI) were calculated as measures of central sensitivity to thyroid hormones. Linear regression analysis and logistic regression analysis were performed to explore the relationships between these indices of thyroid hormone sensitivity and the MoCA score and MCI, respectively. Results: Compared with the normal cognitive function group, patients in the MCI group had higher TSHI, TT4RI and TFQI but a lower FT3/FT4 ratio (P<0.05). The MoCA score was positively correlated with the FT3/FT4 ratio but negatively correlated with TSHI, TT4RI and TFQI (P< 0.05). Multivariate logistic regression analysis showed that a low FT3/FT4 ratio and high TSHI, TT4RI and TFQI were independently associated with MCI (P<0.05). After adjustment for confounding factors, the odds ratio (OR) for the association between MCI and the highest tertile of the FT3/FT4 was 0.455 (95% CI: 0.264-0.785), for the highest tertile of TSHI, the OR was 2.380 (95% CI: 1.376-4.119), for the highest tertile of TT4RI, the OR was 2.342 (95% CI:1.353-4.054), and for the highest tertile of TFQI, the OR was 2.536 (95% CI: 1.466-4.387) (P< 0.05). Conclusion: Impaired sensitivity to thyroid hormones is associated with MCI in euthyroid T2D patients.

Uric acid index is a risk for mild cognitive impairment in type 2 diabetes.

BACKGROUND: A new uric acid (UA) index has recently been proposed, while serum uric acid (SUA), fasting triglyceride, and fasting blood glucose levels in the index are shown to affect cognitive function. This study aims to investigate the clinical value of the UA index for assessing mild cognitive impairment (MCI) in type 2 diabetes (T2D) patients. METHODS: This was an observational cross-sectional study with 616 participants. A generalized additive model was used to determine a linear or curvilinear relationship between cognitive performance and the UA index. Logistic regression and random forest models were both developed. A receiver operating characteristic curve (ROC) was delineated and the area under the curve (AUC) was calculated. RESULTS: MCI was diagnosed in 313 participants (50.81%). Compared with the T2D-normal cognitive function group, MCI subjects had higher UA indexes, lower cognitive scores, and lower education levels (p < 0.001). Generalized additive models showed the UA index and the Montreal Cognitive Assessment (MoCA) score to be decreased linearly (p < 0.001). The UA index AUC was 0.751 (95% CI = 0.713-0.789, p < 0.001). The optimal cut-off point for the identification of MCI based on the UA index was 11.26 (sensitivity: 62.3%, specificity: 75.9%). Results for females in the cohort yielded an AUC change of + 2.5%, the less-educated population (AUC change of + 4.7%), and the hypertensive population (AUC change of + 1.1%). The AUCs were 0.791 (95% CI = 0.720-0.863) for the random forest model and 0.804 (95% CI = 0.770-0.837) for the logistic regression model, and no statistical significance was found (p = 0.758). CONCLUSION: This study showed that the increased UA index was independently associated with MCI in patients with T2D, especially among female, less-educated, and hypertensive patients. It could be a potential indicator of MCI in T2D patients.

Safety and Efficacy of Polyetheretherketone (PEEK) Cages and Cadaveric Allografts in Transforaminal Lumbar Interbody Fusion (TLIF) for Treating Lumbar Pyogenic Spondylodiscitis.

Purpose: There have been many studies in the operative management of pyogenic spondylodiscitis with foreign materials. However, it still remains an issue of debate on whether the allografts may be used in pyogenic spondylodiscitis. This study sought to evaluate the safety and effectiveness of PEEK cages and the cadaveric allograft in transforaminal lumbar interbody fusion (TLIF) for treating lumbar pyogenic spondylodiscitis. Methods: From January 2012 to December 2019, 56 patients underwent surgery for lumbar pyogenic spondylodiscitis. The posterior debridement of all patients and their fusion with allografts, local bone grafts, and bone chip cages were performed before posterior pedicle screw fusion. An assessment of the residual pain, the grade of neurological injury, and the resolution of infection was conducted on 39 patients. The clinical outcome was evaluated using a visual analog scale (VAS) and the Oswestry Disability Index (ODI), and neurological outcomes were appraised based on Frankel grades. The radiological outcomes were evaluated via focal lordosis, lumbar lordosis, and the state of the fusion. Results: Staphylococcus aureus and Staphylococcus epidermidis were the most common causative organisms. The mean preoperative focal lordosis was -1.2° (-11.4° to 5.7°), and the mean postoperative focal lordosis increased to 10.3° (4.3°-17.2°). At the final follow-up, there were five cases with subsidence of the cage, no case of recurrence, and no case with cage and screw loosening or migration. The mean preoperative VAS and ODI scores were 8.9 and 74.6%, respectively, and improvements in VAS and ODI were 6.6 ± 2.2 and 50.4 ± 21.3%, respectively. The Frankel grade D was found in 10 patients and grade C in 7. Following the final follow-up, only one patient improved from Frankel grade C to grade D while the others recovered completely. Conclusion: The PEEK cage and cadaveric allograft combined with local bone grafts is a safe and effective choice for intervertebral fusion and restoring sagittal alignment without increased incidence of relapse for treating lumbar pyogenic spondylodiscitis.

Cascading Robustness Analysis of Wireless Sensor Networks with Varying Multisink Placement.

In practical wireless sensor networks (WSNs), cascading failures are closely related to network load distribution, which in turn strongly relies on the locations of multiple sink nodes. For such a network, understanding how the multisink placement affects its cascading robustness is essential but still largely missing in the field of complex networks. To this end, this paper puts forward an actual cascading model for WSNs based on the multisink-oriented load distribution characteristics, in which two load redistribution mechanisms (i.e., global routing and local routing) are designed to imitate the most commonly used routing schemes. On this basis, a number of topological parameters are considered to quantify the sinks' locations, and then, the relationship between these quantities with network robustness is investigated on two typical WSN topologies. Moreover, by employing the simulated annealing approach, we find the optimal multisink placement for maximizing network robustness and compare the topological quantities before and after the optimization to validate our findings. The results indicate that for the sake of enhancing the cascading robustness of a WSN, it is better to place its sinks as hubs and decentralize these sinks, which is independent of network structure and routing scheme.

Extracellular vesicles released by glioma cells are decorated by Annexin A2 allowing for cellular uptake via heparan sulfate.

Extracellular vesicles (EVs) play a crucial role in regulating cell behavior by delivering their cargo to target cells. However, the mechanisms underlying EV-cell interactions are not well understood. Previous studies have shown that heparan sulfate (HS) on target cell surfaces can act as receptors for exosomes uptake, but the ligand for HS on EVs has not been identified. In this study, we isolated EVs from glioma cell lines and glioma patients and identified Annexin A2 (AnxA2) on EVs as a key HS-binding ligand and mediator of EV-cell interactions. Our findings suggest that HS plays a dual role in EV-cell interactions, where HS on EVs captures AnxA2, and on target cells, it acts as a receptor for AnxA2. Removal of HS from the EV surface inhibits EV-target cell interaction by releasing AnxA2. Furthermore, we found that AnxA2-mediated binding of EVs to vascular endothelial cells promotes angiogenesis, and that antibody against AnxA2 inhibited the ability of glioma-derived EVs to stimulate angiogenesis by reducing the uptake of EVs. Our study also suggests that the AnxA2-HS interaction may accelerate the glioma-derived EVs-mediated angiogenesis and that combining AnxA2 on glioma cells with HS on endothelial cells may effectively improve the prognosis evaluation of glioma patients.

Constitutive and conditional gene knockout mice for the study of intervertebral disc degeneration: Current status, decision considerations, and future possibilities.

There have been an increasing number of patients with degenerative disc diseases due to the aging population. In light of this, studies on the pathogenesis of intervertebral disc degeneration have become a hot topic, and gene knockout mice have become a valuable tool in this field of research. With the development of science and technology, constitutive gene knockout mice can be constructed using homologous recombination, zinc finger nuclease, transcription activator-like effector nuclease technology and clustered regularly interspaced short palindromic repeats/Cas9 (CRISPR/Cas9) system, and conditional gene knockout mice can be constructed using the Cre/LoxP system. The gene-edited mice using these techniques have been widely used in the studies on disc degeneration. This paper reviews the development process and principles of these technologies, functions of the edited genes in disc degeneration, advantages, and disadvantages of different methods and possible targets of the specific Cre recombinase in intervertebral discs. Recommendations for the choice of suitable gene-edited model mice are presented. At the same time, possible technological improvements in the future are also discussed.

Relationship Between Index of Cardiac Electrophysiological Balance, Frontal QRS-T Angle and Retinopathy in People with Type 2 Diabetes.

Background: Diabetic retinopathy (DR) is strongly associated with cardiovascular disease, which is a risk factor for sudden cardiac death (SCD). The index of cardiac electrophysiological balance (iCEB) and the frontal QRS-T angle are recommended to predict the risk of ventricular arrhythmias more than other ECG parameters. However, the relationships between these two markers and DR have not yet been explored. The aim of this study was to investigate the variation in the iCEB, corrected iCEB (iCEBc) and frontal QRS-T angle in different stages of DR and determine whether there are associations between these markers and DR. Methods: The sample comprised 665 patients with Type 2 diabetes mellitus (T2DM) who were classified into three groups: no DR (NDR), mild to moderate non-proliferative DR (NPDR), and vision-threatening DR (VTDR). Twelve-lead ECG was performed and the QT, QTc, QRS duration, iCEB, iCEBc and frontal QRS-T angle were recorded and compared across the groups. Results: The VTDR group had a significantly higher iCEBc and frontal QRS-T angle than the NDR and NPDR groups. After controlling for confounding variables, the correlations between the iCEBc (OR=2.217, 95% CI=1.464-3.358, P<0.001), frontal QRS-T angle (OR=1.017, 95% CI=1.008-1.025, P<0.001) and DR risk remained (P<0.05). Subjects in the fourth iCEBc quartile (adjusted OR=2.612, 95% CI=1.411-4.834, p=0.002) had a much higher chance of developing DR compared to those in the first quartile. In comparison to the first frontal QRS-T angle quartile, subjects in the third (adjusted OR=1.998, 95% CI=1.167-3.422, P=0.012) and fourth (adjusted OR=2.430, 95% CI=1.420-4.160, P=0.001) frontal QRS-T angle quartiles had significantly greater risks of DR. Conclusion: With the progression of DR, the iCEBc and frontal QRS-T angle increase. An increased iCEBc and frontal QRS-T angle are associated with an increased risk of DR.

Novel Mutations of PAX6 and WFS1 Associated With Congenital Cataract in a Chinese Family.

BACKGROUND: Congenital cataract is a common cause of blindness in childhood. About half of the cases have a genetic etiology, and more than 100 genes have been associated with congenital cataracts. This study reports the clinical and genetic findings of a two-generation Chinese family affected by congenital cataract. METHODS: Ophthalmologic examinations were performed for clinical evaluation of the cataract patients. Whole exome sequencing (WES) and Sanger sequencing were used to identify potentially relevant mutations. The online programsProtein Variation Effect Analyzer (PROVEAN) and Sorting Intolerant from Tolerant (SIFT) were employed to predict the impact of variation on protein function. RESULTS: Both the proband and her mother were blind because of bilateral nuclear cataracts, and the elder brother of the proband also manifested obvious bilateral cataracts. Sanger sequencing confirmed the mutations in the proband as well as in her mother. The elder brother simply carried the PAX6 c.221G>A variation. The WFS1 c.2070_2079del variation potentially generates a loss-of-function mutant. CONCLUSION: The novel PAX6mutation (c.221G>A) is associated with congenital cataract, and the WFS1 mutation (c.2070_2079del) may interactively aggravates this process. These findings may increase our understanding of the genetic etiology of congenital cataract.

Sesn2 Serves as a Regulator between Mitochondrial Unfolded Protein Response and Mitophagy in Intervertebral Disc Degeneration.

Mitochondrial unfold protein response (UPRmt) can induce mitophagy to protect cell from unfold protein. However, how UPRmt induces mitophagy to protect cell is not yet clear. Herein, Sesn2 was considered to be a key molecule that communicated UPRmt and mitophagy in the intervertebral disc. Silencing of Sesn2 was able to reverse the protective effects of Nicotinamide riboside (NR) on nucleus pulposus (NP) cells and inhibit mitophagy induced by UPRmt. UPRmt upregulated Sesn2 through Eif2ak4/eIF2α/Atf4, and further induced mitophagy. Sesn2 promoted the translocation of cytosolic Parkin and Sqstm1 to the defective mitochondria respectively, thereby enhancing mitophagy. The translocation of cytosolic Sqstm1 to the defective mitochondria was dependent on Parkin. The two functional domains of Sesn2 were necessary for the interaction of Sesn2 with Parkin and Sqstm1. The cytosolic interaction of Sesn2 between Parkin and Sqstm1 was independent on Pink1 (named as PINK1 in human) but the mitochondrial translocation was dependent on Pink1. Sesn2-/- mice showed a more severe degeneration and NR did not completely alleviate the intervertebral disc degeneration (IVDD) of Sesn2-/- mice. In conclusion, UPRmt could attenuate IVDD by upregulation of Sesn2-induced mitophagy. This study will help to further reveal the mechanism of Sesn2 regulating mitophagy, and open up new ideas for the prevention and treatment of IVDD.