USP1/UAF1-Stabilized METTL3 Promotes Reactive Astrogliosis and Improves Functional Recovery after Spinal Cord Injury through m6A Modification of YAP1 mRNA.

RNA N6-methyladenosine (m6A) modification is involved in diverse biological processes. However, its role in spinal cord injury (SCI) is poorly understood. The m6A level increases in injured spinal cord, and METTL3, which is the core subunit of methyltransferase complex, is upregulated in reactive astrocytes and further stabilized by the USP1/UAF1 complex after SCI. The USP1/UAF1 complex specifically binds to and subsequently removes K48-linked ubiquitination of the METTL3 protein to maintain its stability after SCI. Moreover, conditional knockout of astrocytic METTL3 in both sexes of mice significantly suppressed reactive astrogliosis after SCI, thus resulting in widespread infiltration of inflammatory cells, aggravated neuronal loss, hampered axonal regeneration, and impaired functional recovery. Mechanistically, the YAP1 transcript was identified as a potential target of METTL3 in astrocytes. METTL3 could selectively methylate the 3'-UTR region of the YAP1 transcript, which subsequently maintains its stability in an IGF2BP2-dependent manner. In vivo, YAP1 overexpression by adeno-associated virus injection remarkably contributed to reactive astrogliosis and partly reversed the detrimental effects of METTL3 knockout on functional recovery after SCI. Furthermore, we found that the methyltransferase activity of METTL3 plays an essential role in reactive astrogliosis and motor repair, whereas METTL3 mutant without methyltransferase function failed to promote functional recovery after SCI. Our study reveals the previously unreported role of METTL3-mediated m6A modification in SCI and might provide a potential therapy for SCI.SIGNIFICANCE STATEMENT Spinal cord injury is a devastating trauma of the CNS involving motor and sensory impairments. However, epigenetic modification in spinal cord injury is still unclear. Here, we propose an m6A regulation effect of astrocytic METTL3 following spinal cord injury, and we further characterize its underlying mechanism, which might provide promising strategies for spinal cord injury treatment.

Enhancing doctor-patient relationships in community health care institutions: the Patient Oriented Four Habits Model (POFHM) trial-a stepped wedge cluster randomized trial protocol.

BACKGROUND: The poor relationship between doctors and patients is a long-standing, global problem. However, current interventions tend to focus on the training of physicians, while patient-targeted interventions still need to be improved. Considering that patients play a significant role in outpatient consultations, we developed a protocol to assess the effectiveness of the Patient Oriented Four Habits Model (POFHM) in improving doctor-patient relationships. METHODS: A cross-sectional incomplete stepped-wedge cluster randomized trial design will be conducted in 8 primary healthcare institutions (PHCs). Following phase I of "usual care" as control measures for each PHC, either a patient- or doctor-only intervention will be implemented in phase II. In phase III, both patients and doctors will be involved in the intervention. This study will be conducted simultaneously in Nanling County and West Lake District. The primary outcomes will be evaluated after patients complete their visit: (1) patient literacy, (2) sense of control and (3) quality of doctor-patient communication. Finally, a mixed-effects model and subgroup analysis will be used to evaluate the effectiveness of the interventions. DISCUSSION: Fostering good consultation habits for the patient is a potentially effective strategy to improve the quality of doctor-patient communication. This study evaluates the implementation process and develops a rigorous quality control manual using a theoretical domain framework under the collective culture of China. The results of this trial will provide substantial evidence of the effectiveness of patient-oriented interventions. The POFHM can benefit the PHCs and provide a reference for countries and regions where medical resources are scarce and collectivist cultures dominate. TRIAL REGISTRATION: AsPredicted #107,282 on Sep 18, 2022; https://aspredicted.org/QST_MHW.

Comparison of image quality and radiation dose of different scanning methods used for computed tomography of the unilateral shoulder.

BACKGROUND: The effect of different computed tomography (CT) scanning methods of the shoulder on image quality is uncertain. PURPOSE: To compare the effect of different methods of CT scanning of the right shoulder on image quality and radiation dose. MATERIAL AND METHODS: A total of 30 adults were divided into five groups. Group A received scans centered on the body's long axis, a scout direction of 0° + 90°, and automatic tube current modulation (ATCM). The other four groups (B, C, D, E) received isocenter scans centered on the shoulder with different scout directions (B and C: 0° + 90°, D: 0°, E: 0° + 270°) and tube currents (B: 420 mA; C, D, E: ATCM). The volume CT dose index (CTDIvol), dose-length product (DLP), image objective noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were compared. Three subjective measures were also compared (noise, stripe artifacts, diagnostic confidence). RESULTS: The five groups differed significantly in all subjective and objective indexes. The CTDIvol and DLP decreased in the order of groups C, A, B, E, and D; the differences between groups A and B were not significant (P > 0.05). Groups B, C, and E had better SNR and CNR than groups A and D (P < 0.01). Subjective evaluations indicated group D was worse than groups B, C, and E (P < 0.05). CONCLUSION: In the ATCM system that uses the last scout view, CT of the shoulder should use isocenter scanning with the lateral scout view when the tube is away from the long axis of the body as the last execution direction.

Inhibitory effect of anti-Scg3 on corneal neovascularization: a preliminary study.

BACKGROUND: Corneal neovascularization (CNV) is an important disease that causes blindness. Secretogranin III (Scg3) has emerged as a new influencing factor of neovascularization. This study analyzed the Scg3 antibody's inhibitory effect on CNV and and explored its preliminary mechanism. METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with Scg3 and anti-Scg3. Cell proliferation, wound healing migration and tube formation assays were performed. Healthy adult New Zealand rabbits were randomly selected to be alkali burned and establish the corneal neovascularization (CNV) model. The rabbits were randomly divided into 3 groups (the high concentration group, low concentration group and control group). Different doses of anti-Scg3 and PBS were administered to the rabbits. Clinical examinations, immunostaining, quantitative real-time polymerase chain reaction (qPCR) and western blotting analyses were performed postoperatively. RESULTS: In the in vitro study, the Scg3 antibody mixture inhibited Scg3-induced endothelial cell proliferation and angiogenesis. In the in vivo study, significant CNV was observed in the control group. Confocal microscopy also revealed considerable active neovascularization in the control group. There was no obvious CNV growth in the high concentration group. Additionally, CD31, LYVE1 and CD45 expression was significantly inhibited after treatment with a high concentration of Scg3 antibody. The qPCR and western blotting analyses revealed that the levels of ERK in the low concentration group and high concentration group were higher than those in the control group at 7 days and 14 days. The levels of VEGF in the control group were significantly increased compared with those in the high concentration group. In all three groups, the levels of Akt were not significantly different at any time point. CONCLUSION: The expression of Scg3 could affect the growth of HUVECs in vitro. Treatment with a high concentration (0.5 µg/mL) of Scg3 antibody reduced the inflammatory response and inhibited the growth of corneal neovascularization after corneal alkali burn injury in rabbits. The MEK/ERK pathway might play an important role in the inhibitory effect of anti-Scg3.

The technical efficiency of maternal and child health hospitals in China: a case study of Hubei Province.

BACKGROUND: Maternal and child health (MCH) hospitals play an essential role in providing MCH services in China, while the supply has become increasingly challenging in the past decade, especially among secondary MCH hospitals. In this study we aimed to evaluate the technical efficiency (TE) of secondary MCH hospitals in Hubei province (China) to generate evidence-based decision-making for efficiency improvement. METHODS: The data were collected from the Department of Maternal and Child Health of Health Commission of Hubei Province in 2019. A total of 59 out of 74 secondary MCH hospitals were included as our study sample. Four input indicators (number of health professionals, number of beds, number of equipment with value greater than 10,000 RMB Yuan, building area for hospital operations) and three output indicators (number of total diagnostic patients, number of discharged patients, and number of birth deliveries) were selected based on previous literature. TE scores of the sample hospitals were estimated by using Bootstrap-Data Envelopment Analysis (Bootstrap-DEA). RESULTS: After bias-correction with Bootstrap-DEA model, the average TE score of the MCH hospitals was 0.673. 20 (33.89%) MCH hospitals had TE scores below the average. No MCH hospitals achieved excellent efficiency; 16 (27.11%) MCH hospitals reached good efficiency; and 26 (44.06%) MCH hospitals fell into poor and failing efficiency. Besides, 17 MCH hospitals had TE scores of 1 before bias-corrections, while none of them reached 1 after bias correction. CONCLUSIONS: Significant capacity variations existed among the secondary MCH hospitals in terms of input and output indicators and their overall TE was low in Hubei of China. For better improvement, the secondary MCH hospitals in Hubei need to improve their internal management and strengthen the construction of their information systems. A series of policy supports are needed from the health and insurance administrations to optimize health resources. Third-party performance evaluation can be piloted to improve efficiency and overall performance of the MCH hospitals. The policy recommendations we raise for MCH hospitals in Hubei can be worth learning for some low- and middle- income countries.

Deubiquitinase USP18 regulates reactive astrogliosis by stabilizing SOX9.

Reactive astrogliosis is a pathological feature of spinal cord injury (SCI). The ubiquitin-proteasome system plays a crucial role in maintaining protein homeostasis and has been widely studied in neuroscience. Little, however, is known about the underlying function of deubiquitinating enzymes in reactive astrogliosis following SCI. Here, we found that ubiquitin-specific protease 18 (USP18) was significantly upregulated in astrocytes following scratch injury, and in the injured spinal cord in mice. Knockdown of USP18 in vitro and conditional knockout of USP18 in astrocytes (USP18 CKO) in vivo significantly attenuated reactive astrogliosis. In mice, this led to widespread inflammation and poor functional recovery following SCI. In contrast, overexpression of USP18 in mice injected with adeno-associated virus (AAV)-USP18 had beneficial effects following SCI. We showed that USP18 binds, deubiquitinates, and thus, stabilizes SRY-box transcription factor 9 (SOX9), thereby regulating reactive astrogliosis. We also showed that the Hedgehog (Hh) signaling pathway induces expression of USP18 through Gli2-mediated transcriptional activation after SCI. Administration of the Hh pathway activator SAG significantly increased reactive astrogliosis, reduced lesion area and promoted functional recovery in mice following SCI. Our results demonstrate that USP18 positively regulates reactive astrogliosis by stabilizing SOX9 and identify USP18 as a promising target for the treatment of SCI.

Small extracellular vesicles encapsulating CCL2 from activated astrocytes induce microglial activation and neuronal apoptosis after traumatic spinal cord injury.

BACKGROUND: Spinal cord injury (SCI) is a severe traumatic disease which causes high disability and mortality rates. The molecular pathological features after spinal cord injury mainly involve the inflammatory response, microglial and neuronal apoptosis, abnormal proliferation of astrocytes, and the formation of glial scars. However, the microenvironmental changes after spinal cord injury are complex, and the interactions between glial cells and nerve cells remain unclear. Small extracellular vesicles (sEVs) may play a key role in cell communication by transporting RNA, proteins, and bioactive lipids between cells. Few studies have examined the intercellular communication of astrocytes through sEVs after SCI. The inflammatory signal released from astrocytes is known to initiate microglial activation, but its effects on neurons after SCI remain to be further clarified. METHODS: Electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting were applied to characterize sEVs. We examined microglial activation and neuronal apoptosis mediated by astrocyte activation in an experimental model of acute spinal cord injury and in cell culture in vitro. RESULTS: Our results indicated that astrocytes activated after spinal cord injury release CCL2, act on microglia and neuronal cells through the sEV pathway, and promote neuronal apoptosis and microglial activation after binding the CCR2. Subsequently, the activated microglia release IL-1ß, which acts on neuronal cells, thereby further aggravating their apoptosis. CONCLUSION: This study elucidates that astrocytes interact with microglia and neurons through the sEV pathway after SCI, enriching the mechanism of CCL2 in neuroinflammation and spinal neurodegeneration, and providing a new theoretical basis of CCL2 as a therapeutic target for SCI.

Associations between SNP83 of phosphodiesterase 4D gene and carotid atherosclerosis in a southern Chinese Han population: a case-control study.

Atherosclerosis was an important pathophysiological basis of atherothrombotic stroke, and phosphodiesterase 4D (PDE4D) polymorphism (SNP83/rs966221) was reported to be associated with the susceptibility to atherothrombotic stroke. Aim of the present study was to explore the potential association between SNP83 and carotid atherosclerosis (CAS). 204 southern Chinese Han participants were divided into two groups according to the carotid intima-media thickness (IMT) of the carotid artery: CAS group (carotid IMT ≥ 1.0 mm) and non-CAS group (carotid IMT < 1.0 mm). Carotid IMT was measured by color Doppler ultrasound. The PDE4D SNP83 polymorphism was determined by SNaPshot technique. Our study found that SNP83 was associated significantly with CAS susceptibility under the dominant, overdominant and codominant models. After adjusting for age, gender, low-density lipoprotein cholesterol, Hemoglobin A1c, cigarette smoking, hypertension history, and diabetes mellitus history, the association still remained significant (dominant model: crude OR = 2.373, 95% CI: 1.268-4.442, P = 0.007; adjusted OR = 3.129, 95% CI: 1.104-8.866, P = 0.032; overdominant model: crude OR = 1.968, 95% CI: 1.043-3.714, P = 0.037; adjusted OR = 2.854, 95% CI: 1.005-8.108, P = 0.049; codominant: crude OR = 2.102, 95% CI: 1.110-3.979, P = 0.023; adjusted OR = 2.984, 95% CI: 1.047-8.502, P = 0.041). Carotid IMT of carriers with CT + CC genotypes was higher than carriers with TT genotype (P = 0.016). Our results indicated that the SNP83/rs966221 located on PDE4D gene was significantly associated between CAS susceptibility and carotid IMT independently of conventional risk factors in a southern Chinese Han population.

Association of four gene polymorphisms in Chinese Guangxi population with diabetic retinopathy in type 2 diabetic patients.

BACKGROUND: Diabetic retinopathy (DR) is one of the most common chronic microvascular complications of diabetes. Many studies have suggested that genetic factors are important in the context of DR. This study evaluated the associations of GWAS (Genome-wide association study) -identified DR-associated SNPs in a Chinese population in Guangxi Province with type 2 diabetes mellitus (T2DM). METHODS: A total of 386 hospitalized T2DM patients without proliferative diabetic retinopathy (PDR) and 316 hospitalized T2DM patients with PDR were included in this case-control study. Four tag SNPs, including rs1800896 in the IL-10 gene, rs2010963 in the VEGFA gene, rs2070600 in the RAGE gene and rs2910164 in the miR-146a gene, were examined using KASP (kompetitive allele specific PCR) genotyping assays. RESULTS: There were no significant differences in the genotype or allele frequencies of the miR-146a polymorphism (rs2910164) between subjects with PDR and those without DR. The TC genotype of rs1800896 was determined to be associated with an increased risk of PDR (the odds ratio (OR) was 2.366, with a 95% confidence interval (CI) ranging from 1.144 to 4.894). The CG genotypes of rs2010963 was associated with an decreased risk of PDR (the OR was 0.588, with a 95% CI ranging from 0.366 to 0.946). Regarding rs2070600, 2 genotypes (TT and CT) were associated with a decreased risk of PDR (the OR of the TT genotype was 0.180, with a 95% CI ranging from 0.037 to 0.872, and the OR of the CT genotype was 0.448, with a 95% CI ranging from 0.266 to 0.753). CONCLUSIONS: The rs1800896 polymorphisms in the IL-10 gene, rs2010963 in the VEGFA gene and rs2070600 in the RAGE gene are associated with the risk of PDR in the Han Chinese population of Guangxi Province. Our findings provide suggestive evidence that these polymorphisms may be involved in the pathogenesis of PDR and should be investigated further.

Establishment of a nomogram for predicting the surgical difficulty of anterior cervical spine surgery.

BACKGROUND: For a long time, surgical difficulty is mainly evaluated based on subjective perception rather than objective indexes. Moreover, the lack of systematic research regarding the evaluation of surgical difficulty potentially has a negative effect in this field. This study was aimed to evaluate the risk factors for the surgical difficulty of anterior cervical spine surgery (ACSS). METHODS: This was a retrospective cohort study totaling 291 consecutive patients underwent ACSS from 2012.3 to 2017.8. The surgical difficulty of ACSS was defined by operation time longer than 120 min or intraoperative blood loss equal to or greater than 200 ml. Evaluation of risk factors was performed by analyzing the patient's medical records and radiological parameters such as age, sex, BMI, number of operation levels, high signal intensity of spinal cord on T2-weighted images, ossified posterior longitudinal ligament (OPLL), sagittal and coronal cervical circumference, cervical length, spinal canal occupational ratio, coagulation function index and platelet count. RESULTS: Significant differences were reported between low-difficulty and high-difficulty ACSS groups in terms of age (p = 0.017), sex (p = 0.006), number of operation levels (p < 0.001), high signal intensity (p < 0.001), OPLL (p < 0.001) and spinal canal occupational ratio (p < 0.001). Multivariate logistic regression analysis revealed that number of operation levels (OR = 5.224, 95%CI = 2.125-12.843, p < 0.001), high signal intensity of spinal cord (OR = 4.994, 95%CI = 1.636-15.245, p = 0.005), OPLL (OR = 6.358, 95%CI = 1.932-20.931, p = 0.002) and the spinal canal occupational ratio > 0.45 (OR = 3.988, 95%CI = 1.343-11.840, p = 0.013) were independently associated with surgical difficulty in ACSS. A nomogram was established and ROC curve gave a 0.906 C-index. There was a good calibration curve for difficulty estimation. CONCLUSION: This study indicated that the operational level, OPLL, high signal intensity of spinal cord, and spinal canal occupational ratio were independently associated with surgical difficulty and a predictive nomogram can be established using the identified risk factors. Optimal performance was achieved for predicting surgical difficulty of ACSS based on preoperative factors.

Exosome-shuttled miR-216a-5p from hypoxic preconditioned mesenchymal stem cells repair traumatic spinal cord injury by shifting microglial M1/M2 polarization.

BACKGROUND: Spinal cord injury (SCI) can lead to severe motor and sensory dysfunction with high disability and mortality. In recent years, mesenchymal stem cell (MSC)-secreted nano-sized exosomes have shown great potential for promoting functional behavioral recovery following SCI. However, MSCs are usually exposed to normoxia in vitro, which differs greatly from the hypoxic micro-environment in vivo. Thus, the main purpose of this study was to determine whether exosomes derived from MSCs under hypoxia (HExos) exhibit greater effects on functional behavioral recovery than those under normoxia (Exos) following SCI in mice and to seek the underlying mechanism. METHODS: Electron microscope, nanoparticle tracking analysis (NTA), and western blot were applied to characterize differences between Exos and HExos group. A SCI model in vivo and a series of in vitro experiments were performed to compare the therapeutic effects between the two groups. Next, a miRNA microarray analysis was performed and a series of rescue experiments were conducted to verify the role of hypoxic exosomal miRNA in SCI. Western blot, luciferase activity, and RNA-ChIP were used to investigate the underlying mechanisms. RESULTS: Our results indicate that HExos promote functional behavioral recovery by shifting microglial polarization from M1 to M2 phenotype in vivo and in vitro. A miRNA array showed miR-216a-5p to be the most enriched in HExos and potentially involved in HExos-mediated microglial polarization. TLR4 was identified as the target downstream gene of miR-216a-5p and the miR-216a-5p/TLR4 axis was confirmed by a series of gain- and loss-of-function experiments. Finally, we found that TLR4/NF-κB/PI3K/AKT signaling cascades may be involved in the modulation of microglial polarization by hypoxic exosomal miR-216a-5p. CONCLUSION: Hypoxia preconditioning represents a promising and effective approach to optimize the therapeutic actions of MSC-derived exosomes and a combination of MSC-derived exosomes and miRNAs may present a minimally invasive method for treating SCI.

Neuron-derived exosomes-transmitted miR-124-3p protect traumatically injured spinal cord by suppressing the activation of neurotoxic microglia and astrocytes.

BACKGROUND: Spinal cord injury (SCI) is a catastrophic injury that can cause irreversible motor dysfunction with high disability. Exosomes participate in the transport of miRNAs and play an essential role in intercellular communication via transfer of genetic material. However, the miRNAs in exosomes which derived from neurons, and the underlying mechanisms by which they contribute to SCI remain unknown. METHODS: A contusive in vivo SCI model and a series of in vitro experiments were carried out to explore the therapeutic effects of exosomes. Then, a miRNA microarray analysis and rescue experiments were performed to confirm the role of neuron-derived exosomal miRNA in SCI. Western blot, luciferase activity assay, and RNA-ChIP were used to investigate the underlying mechanisms. RESULTS: The results indicated that neuron-derived exosomes promoted functional behavioral recovery by suppressing the activation of M1 microglia and A1 astrocytes in vivo and in vitro. A miRNA array showed miR-124-3p to be the most enriched in neuron-derived exosomes. MYH9 was identified as the target downstream gene of miR-124-3p. A series of experiments were used to confirm the miR-124-3p/MYH9 axis. Finally, it was found that PI3K/AKT/NF-κB signaling cascades may be involved in the modulation of microglia by exosomal miR-124-3p. CONCLUSION: A combination of miRNAs and neuron-derived exosomes may be a promising, minimally invasive approach for the treatment of SCI.

MicroRNA-421-3p-abundant small extracellular vesicles derived from M2 bone marrow-derived macrophages attenuate apoptosis and promote motor function recovery via inhibition of mTOR in spinal cord injury.

BACKGROUND: Spinal cord injury (SCI) has a very disabling central nervous system impact but currently lacks effective treatment. Bone marrow-derived macrophages (BMDMs) are recruited to the injured area after SCI and participate in the regulation of functional recovery with microglia. Previous studies have shown that M2 microglia-derived small extracellular vesicles (SEVs) have neuroprotective effects, but the effects of M2 BMDM-derived sEVs (M2 BMDM-sEVs) have not been reported in SCI treatment. RESULTS: In this study, we investigated the role of M2 BMDM-sEVs in vivo and in vitro for SCI treatment and its mechanism. Our results indicated that M2 BMDM-sEVs promoted functional recovery after SCI and reduced neuronal apoptosis in mice. In addition, M2 BMDM-sEVs targeted mammalian target of rapamycin (mTOR) to enhance the autophagy level of neurons and reduce apoptosis. MicroRNA-421-3P (miR-421-3p) can bind to the 3' untranslated region (3'UTR) of mTOR. MiR-421-3p mimics significantly reduced the activity of luciferase-mTOR 3'UTR constructs and increased autophagy. At the same time, tail vein injection of inhibitors of SEVs (Inh-sEVs), which were prepared by treatment with an miR-421-3p inhibitor, showed diminished protective autophagy of neuronal cells in vivo. CONCLUSIONS: In conclusion, M2 BMDM-sEVs inhibited the mTOR autophagy pathway by transmitting miR-421-3p, which reduced neuronal apoptosis and promoted functional recovery after SCI, suggesting that M2 BMDM-sEVs may be a potential therapy for SCI.

Propranolol suppresses infantile hemangioma cell proliferation and promotes apoptosis by upregulating miR-125b expression.

Propranolol could repress infantile hemangioma cell growth and induce apoptosis. miR-125b could inhibit cell proliferation in some tumors. However, whether propranolol exerts its proliferation inhibition and apoptosis-promoting effect by regulating the expression of miR-125b needs to be further investigated. In tumor tissue and endothelial cells isolated from infantile hemangioma patients, we found that the expression levels of miR-125b were significantly decreased. In-vitro analysis revealed that propranolol increased the expression of miR-125b in hemangioma cells in a dose-dependent and time-dependent manner. Interestingly, it was observed that regression of miR-125b expression by its inhibitor could abrogate the effect of propranolol on hemangioma cell growth and apoptosis. In addition, our data further identified TFAP4 as a direct target of miR-125b. Collectively, our data provided evidence that propranolol may repress infantile hemangioma cell growth and promote apoptosis through upregulating the miR-125b expression, which exerted its suppression of tumor development by targeting TFAP4.

Associations between GUCY1A3 genetic polymorphisms and large artery atherosclerotic stroke risk in Chinese Han population: a case-control study.

BACKGROUND: Previous genome-wide association studies have found two single nucleotide polymorphisms (SNP) rs7692387 and rs1842896 located on or near the GUCY1A3 gene were associated with coronary artery disease (CAD). GUCY1A3 was considered to be involved in the process of atherosclerosis, but there was little information about the association between genotypic polymorphisms of the GUCY1A3 and large artery atherosclerotic (LAA) stroke. This study aimed to investigate the associations between the GUCY1A3 rs7692387, rs1842896 polymorphisms and LAA stroke susceptibility. METHODS: A total of 298 LAA stroke patients and 300 control subjects from a southern Chinese Han population were included. SNaPshot technique was used for genotype analysis. Associations between genotypes and LAA stroke susceptibility were analyzed with logistic regression model. RESULTS: Our study found that under the recessive model (TT vs. GT + GG), the GUCY1A3 rs1842896 polymorphism was significantly correlated with LAA stroke (OR = 1.48, 95%CI: 1.07-2.04, P = 0.018). After adjustment for its effects on age, gender, cigarette smoking, total cholesterol, low-density lipoprotein cholesterol, HbA1c, hypertension, diabetes mellitus, and CAD, the rs1842896 TT genotype retained association with increased susceptibility to LAA stroke (recessive model: adjusted OR = 1.96, 95%CI: 1.22-3.17, P = 0.006). However, association between rs7692387 polymorphism with LAA stroke was not observed. CONCLUSION: Our results indicate that the GUCY1A3 rs1842896 polymorphism is an LAA stroke risk factor in Southern Han Chinese.

The effect of the back optic zone diameter on the treatment zone area and axial elongation in orthokeratology.

PURPOSE: To investigate the influence of corneal parameters on the treatment zone area (TZA) after Corneal Refractive Therapy (CRT) with a 5.0-mm back optical zone diameter (BOZD) were worn and to compare changes in the axial length (AL) with traditional 6.0-mm BOZD lenses. METHODS: This retrospective study involved 146 subjects (7-12 years) who wore orthokeratology (ortho-K) lenses for one year: 86 subjects were treated with CRT 5.0-mm lenses, and 60 subjects were treated with CRT 6.0-mm lenses. The TZA was measured after one year of ortho-K treatment. Both TZA and AL elongation after wearing the two kinds of lenses was compared. The parameters were recorded in the CRT 5.0 group: flat K, steep K, corneal toricity, e value, and anterior corneal elevation values at the 3-, 4-, and 5-mm chords along the principal meridians of the superior, inferior, nasal, and temporal sides. The relationships between these data and the TZA were analyzed. RESULTS: The TZA was 12.90 ± 5.15 mm2 and 20.61 ± 4.54 mm2, and the AL elongation was 0.15 ± 0.18 mm and 0.26 ± 0.18 mm in the CRT 5.0 group and the CRT 6.0 group, respectively (all p < 0.001). The one-year AL elongation was significantly associated with initial age and the TZA (r =  - 0.394, 0.393; all p < 0.001) in the CRT 5.0 group. The following corneal parameters were found to have statistically significant correlations with the TZA: the e value, difference in corneal elevation (nasal-temporal at the 3-, 4-, and 5-mm chord), and the absolute value of elevation difference (nasal-temporal at the 3- and 4-mm chord and inferior-superior at the 3-, 4-, and 5-mm chord). The e value was the only relevant factor for the TZA by multiple regression analysis (unstandardized ß = 14.219, p = 0.008). In the CRT 6.0 group, the one-year AL elongation was statistically significantly associated only with initial age (r =  - 0.605, p = 0.005), but not with the TZA (p = 0.161). CONCLUSIONS: A smaller TZA induced by a smaller BOZD may be beneficial for retarding AL elongation in children undergoing ortho-K treatment. The morphology and eccentricity of the cornea may show effects on the TZA.

Different efficacy in myopia control: Comparison between orthokeratology and defocus-incorporated multiple segment lenses.

PURPOSE: To compare the efficiency of orthokeratology (OK) and defocus-incorporated multiple segment (DIMS) lenses in myopia control in children. METHODS: This prospective study involved 540 subjects (7-14 years) categorized into three groups: DIMS lenses (180 cases), OK lenses (180 cases), or single-vision spectacles (SVS) (180 cases). After a one-year follow-up, changes in axial length (AL) and differences among the groups were analyzed. The subjects were further divided into a low myopia degree subgroup (LM, -1.50 D ≤ SE ≤ -0.50 D), a moderate myopia degree subgroup (MM, -3.00 D ≤ SE ＜ -1.50 D), and a high myopia degree subgroup (HM, -5.00 D ≤ SE ＜ -3.00 D). A one-way ANOVA and multiple linear regression analysis were used to compare AL elongation and the factors influencing the different groups. RESULTS: A total of 496 (92 %) subjects completed the study. The mean AL change in the OK lenses, DIMS lenses, and SVS were 0.20±0.18 mm, 0.30±0.22 mm, and 0.38±0.19 mm, respectively (P < 0.001). In the LM subgroup, the OK and DIMS groups showed similar AL changes, but both exhibited slower changes than the SVS group (P = 0.001). In the MM and HM subgroups, the OK lens performed the shortest AL elongation compared with the DIMS lenses and SVS (P < 0.001). Multiple regression analysis showed that the AL change was associated with age (ß = -0.038 and P = 0.005), initial AL (ß = -0.010 and P = 0.011), initial SE (ß = 0.028 and P = 0.007), and interventions using OK lenses (ß = -0.172 and P = 0.020) and DIMS lenses (ß = -0.089 and P = 0.020). CONCLUSION: Over a one-year treatment period, OK and DIMS lenses can significantly retard AL elongation compared with SVS. In addition, the OK lenses were more effective than the DIMS lenses in controlling AL in patients with higher degrees of myopia.

Research of the crankshaft high cycle bending fatigue experiment design method based on the modified unscented Kalman filtering algorithm and the SAFL approach.

In modern engineering application, enough high cycle bending fatigue strength is the necessary factor to provide the basic safety security for the application of the crankshaft in automobile engines (both diesel and gasoline types). At present, this parameter is usually obtained through the standard bending fatigue experiment process, which is time consuming and expensive. In this paper, a new accelerated crankshaft bending fatigue experiment was proposed step by step. First the loading procedure was quickened through the prediction of the residual fatigue life based on the UKF (unscented Kalman filtering algorithm). Then the accuracy of the predictions was improved based on the modified sampling range and the theory of fracture mechanics. Finally the statistical analysis method of the fatigue limit load was performed based on the above predictions. The main conclusion of this paper is that the proposed accelerated bending fatigue experiment can save more than 30% of the bending fatigue experiment period and provide nearly the same fatigue limit load analysis result. In addition, compared with the particle filtering algorithm method, the modified UKF can provide much higher accuracy in predicting the residual bending fatigue life of the crankshaft, which makes this method more superior to be applied in actual engineering.

Crankshaft High-Cycle Bending Fatigue Experiment Design Method Based on Unscented Kalman Filtering and the Theory of Crack Propagation.

The high-cycle bending fatigue experiment is one of the most important necessary steps in guiding the crankshaft manufacturing process, especially for high-power engines. In this paper, an accelerated method was proposed to shorten the time period of this experiment. First, the loading period was quickened through the prediction of the residual fatigue life based on the unscented Kalman filtering algorithm approach and the crack growth speed. Then, the accuracy of the predictions was improved obviously based on the modified training section based on the theory of fracture mechanics. Finally, the fatigue limit load analysis result was proposed based on the predicted fatigue life and the modified SAFL (statistical analysis for the fatigue limit) method. The main conclusion proposed from this paper is that compared with the conventional training sections, the modified training sections based on the theory of fracture mechanics can obviously improve the accuracy of the remaining fatigue life prediction results, which makes this approach more suitable for the application. In addition, compared with the system's inherent natural frequency, the fatigue crack can save the experiment time more effectively and thus is superior to the former factor as the failure criterion parameter.