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Rock cutting methods for disc cutters with coupled static–dynamic loads and static loads are explored and compared through rock breaking experiments to improve the TBM excavation efficiency. Results indicate that the rock breaking characteristics, including rock debris, cutting force, and rock breaking efficiency, significantly varies with different cutting methods. The average size of rock fragmentation produced under coupled static–dynamic loads is 1.6 times larger than that under static loads. The cutting forces of disc cutter under the coupled static–dynamic loads are larger than those under static loads when the cutting depth $(h)$ is lower than 4 mm, whereas is contrary when $h$ exceeds 4 mm. The specific energy of disc cutter under the coupled static–dynamic load is approximately 1.5 times smaller than that under the static load, indicating the cutting method with the coupled static–dynamic load can significantly improve the cutting performance. There is an optimal cutter spacing $(S)$ for the cutter under each cutting method. The optimal $S$ under the coupled static–dynamic loads is larger than that with static loads. This study provides new insights into improving the tunneling efficiency in high-strength rock conditions.

There is a relative lack of research aimed at developing a comprehensive index system for low-carbon development of power systems in load-intensive cities in China. First, this paper outlined the main challenges faced in the urban power system development process and determined development goals and key indexes that combined the macro goals and requirements of constructing new power systems with the development characteristics and trends of load-intensive urban power systems. Second, a comprehensive index system and evaluation method for the low-carbon development of power systems was proposed to consider the perspectives of safety, efficiency, clean energy, low carbon, and flexibility. Finally, the effectiveness of the proposed index system and evaluation method was verified by taking the development of actual power systems in ultra-large-load-intensive cities as an example, providing support for the development decision making of actual urban power system construction and transformation.

BackgroundAnnual declines in university students’ physical health have an impact on social stability and the nation’s long-term growth. Parenting style, which is crucial to a child’s growth and development, may have a big influence on physical health. This study delves into the effects of different parenting styles on the physical fitness of Chinese college students under gender differences.MethodsThrough random allocation and stratified sampling methods, this study comprehensively investigated 3,151 undergraduate students (male = 1,365; female = 1786) with an average age of 18.44 years (SD = 1.46), from a university in Jiangsu Province, China. Parenting styles of college students were evaluated by the Parental Bonding Instrument (PBI). Physical fitness tests were based on the Chinese National Student Physical Fitness Standards including body mass index, lung capacity, standing-long-jump, bent-leg-sit-up, seated forward bend, pull-ups, 50 m sprint, and 800/1,000 m run. Further investigations focused on the relationship between parenting styles and physical health by statistical analysis methods such as Pearson correlation and multiple linear regression.ResultsSignificant differences were identified in gender, family members, and academic majors in most of the correlation indicators between different parenting styles and physical health among college students. Further analysis showed that the parenting styles of democratic and authoritative mothers and democratic fathers were more conducive to the promotion of physical health among female university students. The combination of a democratic fathering style and a permissive mothering style is considered an ideal parenting model for male students.ConclusionThis study confirmed that different parenting styles have a significant impact on the physical health of college students. Positive parenting styles may improve physical health, while negative ones are likely to have adverse effects, especially among female students. It is also important to notice differentiated parenting styles with respect to male and female university students. Therefore, more attention should be raised on parenting styles to enhance physical health of the student population.

Abstract Background Our study aims to investigate the mechanisms through which Fc receptor‐like A (FCRLA) promotes renal cell carcinoma (RCC) and to examine its significance in relation to tumor immune infiltration. Materials and Methods The correlation between FCRLA and data clinically related to RCC was explored using The Cancer Genome Atlas (TCGA), then validated using Gene Expression Omnibus (GEO) gene chip data. Enrichment and protein–protein interaction (PPI) network analyses were performed for FCRLA and its co‐expressed genes. FCRLA was knocked down in RCC cell lines to evaluate its impact on biological behavior. Then the potential downstream regulators of FCRLA were determined by western blotting, and rescue experiments were performed for verification. The relevance between FCRLA and various immune cells was analyzed through GSEA, TIMER, and GEPIA tools. TIDE and ESTIMATE algorithms were used to predict the effect of FCRLA in immunotherapy. Results Fc receptor‐like A was associated with clinical and T stages and could predict the M stage (AUC = 0.692) and 1–3‐ and 5‐year survival rates (AUC = 0.823, 0.834, and 0.862) of RCC patients. Higher expression of FCLRA predicted an unfavorable overall survival (OS) in TCGA‐RCC and GSE167573 datasets (p = 0.03, p = 0.04). FCRLA promoted the malignant biological behavior of RCC cells through the pERK1/2/‐MMP2 pathway and was associated with tumor immune microenvironment in RCC. Conclusion Fc receptor‐like A is positively correlated with poor outcomes in RCC patients and plays an oncogenic role in RCC through the pERK1/2‐MMP2 pathway. Patients with RCC might benefit from immunotherapy targeting FCRLA.

Bistatic synthetic aperture radar (BiSAR) can perform remote imaging at any position, thus playing a crucial role in remote sensing applications. In BiSAR imaging with complex trajectory, an inevitable issue is the complicated correspondence between the geometry space and signal space, which will cause Doppler parameters mismatch and affect the imaging performance. To address this problem, the spatial inverse mapping relationship is skillfully constructed through the method of series reverse, which accurately describes the specific correspondence between the geometry space and signal space. On this basis, an extended time scaling algorithm is proposed. Its innovation is compensating for spatially variant Doppler phase that causes image distortion and defocusing by introducing the preprocessing and scaling functions in the time and frequency domains, respectively. Simulation experiments validate the effectiveness of the proposed method.

The involvement of Group 3 innate lymphoid cells (ILC3s) and dendritic cells (DCs) in chronic lung inflammation has been increasingly regarded as the key to understand the inflammatory mechanisms of smoke-related chronic obstructive pulmonary disease (COPD). However, the mechanism underlying the engagement of both remains unclear. Our study aimed to explore NCR−ILC3 differentiation in the lungs of mice exposed to cigarette smoke (CS) and to further investigate whether DCs activated by CS exposure contribute to the differentiation of ILCs into NCR−ILC3s. The study involved both in vivo and in vitro experiments. In the former, the frequencies of lung NCR−ILC3s and NKp46−IL-17A+ ILCs and the expression of DCs, CD40, CD86, IL-23, and IL-1β quantified by flow cytometry were compared between CS-exposed mice and air-exposed mice. In the latter, NKp46−IL-17A+ ILC frequencies quantified by flow cytometry were compared after two cocultures, one involving lung CD45+Lin−CD127+ ILCs sorted from air-exposed mice and DCs sifted by CD11c magnetic beads from CS-exposed mice and another including identical CD45+Lin−CD127+ ILCs and DCs from air-exposed mice. The results indicated significant increases in the frequencies of NCR−ILC3s and NKp46−IL-17A+ ILCs; in the expression of DCs, CD40, CD86, IL-23, and IL-1β in CS-exposed mice; and in the frequency of NKp46−IL-17A+ ILCs after the coculture with DCs from CS-exposed mice. In conclusion, CS exposure increases the frequency of lung ILCs and NCR−ILC3s. CS-induced DC activation enhances the differentiation of ILCs into NCR−ILC3s, which likely acts as a mediating step in the involvement of NCR-ILC3s in chronic lung inflammation.

Mesenchymal stem cell-derived exosomes(MSCs-Exos) offer promising therapeutic potential for a wide range of tissues and organs such as bone/cartilage, nerves, skin, fat, and endocrine organs. In comparison to the application of mesenchymal stem cells (MSCs), MSCs-Exos address critical challenges related to rejection reactions and ethical concerns, positioning themselves as a promising cell-free therapy. As exosomes are extracellular vesicles, their effective delivery necessitates the use of carriers. Consequently, the selection of hydrogel materials as scaffolds for exosome delivery has become a focal point of contemporary research. The diversity of hydrogel scaffolds, which can take various forms such as injectable types, dressings, microneedles, and capsules, leads to differing choices among researchers for treating diseases within the same domain. This variability in hydrogel materials poses challenges for the translation of findings into clinical practice. The review highlights the potential of hydrogel-loaded exosomes in different fields and introduces the advantages and disadvantages of different forms of hydrogel applications. It aims to provide a multifunctional and highly recognized hydrogel scaffold option for tissue regeneration at specific sites, improve clinical translation efficiency, and benefit the majority of patients.

The satellite–ground bistatic configuration, which uses geosynchronous synthetic aperture radar (GEO SAR) for illumination and ground equipment for reception, can achieve wide coverage, high revisit, and continuous illumination of interest areas. Based on the analysis of the signal characteristics of GEO satellite–ground bistatic SAR (GEO SG-BiSAR), it is found that the bistatic echo signal has problems of azimuth spectrum aliasing and 2-D spatial variability. Therefore, to overcome those problems, a novel SAR imaging method for a GEO SG-BiSAR system with severe azimuth spectrum aliasing and 2-D spatial variability is proposed. Firstly, based on the geometric configuration of the GEO SG-BiSAR system, the time-domain and frequency-domain expressions of the signal are derived in detail. Secondly, in order to avoid the increasing cost caused by traditional multi-channel reception technology and the processing burden caused by inter-channel errors, the azimuth deramping is executed to solve the azimuth spectrum aliasing of the signal under the special geometric structure of GEO SG-BiSAR. Thirdly, based on the investigation of azimuth and range spatial variability characteristics of GEO SG-BiSAR in the Range Doppler (RD) domain, the azimuth spatial variability correction strategy is proposed. The signal corrected by the correction strategy has the same migration characteristics as monostatic radar. Therefore, the traditional chirp scaling function (CSF) is also modified to solve the range spatial variability of the signal. Finally, the two-dimensional spectrum of GEO SG-BiSAR with modified chirp scaling processing is derived, followed by the SPECAN operation to obtain the focused SAR image. Furthermore, the completed flowchart is also given to display the main composed parts for GEO SG-BiSAR imaging. Both azimuth spectrum aliasing and 2-D spatial variability are taken into account in the imaging method. The simulated data and the real data obtained by the Beidou navigation satellite are used to verify the effectiveness of the proposed method.

BACKGROUND: Dyslexia in medical school is a common condition. With the COVID-19 pandemic, the medical school curriculum has changed. This might lead to differing experiences faced by medical students compared to previous literature. AIM: This paper explores the experiences of medical students with dyslexia post-COVID-19 with a focus on study methods and support. METHODS: A qualitative study involving online interviews of five medical students with a formal dyslexia diagnosis was done. Data was collected over two months from February 2023 to March 2023. Transcripts were analysed using an iterative constant comparative approach, forming themes on the experiences of these medical students. RESULTS: Participants experienced a general need to work harder than their peers in certain areas of medical school, especially those pertaining to traditional learning methods. However, some participants also acknowledged strengths in other areas compared to their peers, especially concerning more visual areas of medicine. This is translated into study strategies whereby participants opt for different learning methods, adopting more visual, kinaesthetic and auditory approaches. Participants felt that more support should be given in terms of making teaching resources more dyslexic-friendly. While participants were more open in the disclosure of dyslexia, the aspect of raising awareness of the positive aspects of dyslexia in medical school was also raised. CONCLUSION: While there are more positive findings compared to previous literature, more effort needs to be made to support dyslexic students in medical school. Education of different members in medical school on the condition could also be actioned to reduce labels and stereotypes of it.

Background Upper abdominal surgical treatment may reduce respiratory muscle function and mucociliary clearance, which might be a cause of postoperative pulmonary complications (PPCs). Threshold inspiratory muscle training (IMT) may serve as an effective modality to improve respiratory muscle strength and endurance in patients. However, whether this training could help patients with upper abdominal surgery remains to be determined. The aim of the present investigation was to determine the effect of a fully engaged IMT on PPCs and respiratory function in patients undergoing upper abdominal surgery. We hypothesized that the fully engaged IMT could reduce PPCs and improve respiratory muscle function in patients with upper abdominal surgery.Methods This is a randomized controlled trial (RCT) with 28 patients who underwent upper abdominal surgery. Patients were randomly assigned to the control (CLT) group or the IMT group. The CTL group received regular health care. The IMT group received 3 weeks of IMT with 50% of MIP as the initial intensity before the operation. The intensity of MIP increased by 5–10% per week. The IMT was continued for 4 weeks after the operation. The study investigated the outcomes including PPCs, respiratory muscle strength, diaphragmatic function, cardiopulmonary function, and quality of life (QoL).Results We found that IMT improved respiratory muscle strength and diaphragmatic excursion. IMT also had a beneficial effect on the incidence of postoperative pulmonary complications (PPCs) compared to CLT care.Conclusion The results from this study revealed that IMT provided positive effects on parameters associated with the respiratory muscle function and reduced the incidence of PPCs. We propose that fully engaged IMT should be a part of clinical management in patients with upper abdominal surgery.KEY MESSAGESThe fully engaged inspiratory muscle training reduces postoperative pulmonary complications rate in patients with upper abdominal surgery.The fully engaged inspiratory muscle training increases maximal inspiratory pressure in patients with upper abdominal surgery.The fully engaged inspiratory muscle training increases diaphragm function in patients with upper abdominal surgery.The fully engaged inspiratory muscle training increases the quality of life in patients with upper abdominal surgery.

Abstract Background Data from the Global Burden of Disease, Injury, and Risk Factor Study 2019 (GBD 2019) was used to assess the burden and change in prevalence, incidence, deaths, disability-adjusted life years, and risk factors for atrial fibrillation/flutter in 204 countries and territories between 1990 and 2019. Methods Incidence, prevalence, deaths, disability-adjusted life years (DALYs), and their age-standardized rates of AF/AFL were analyzed by age, sex, socio-demographic index (SDI), and human development index (HDI) using the Global Burden of Disease study 2019 (GBD2019) results，and risk factors for AF/AFL (mainly high systolic blood pressure, high body-mass index, alcohol use, smoking and diet high in sodium) were differentially analyzed. Results There are 59.70 million (95% uncertainty interval (UI) 45.73–75.29 million) AF/AFL patients worldwide in 2019, with 4.72 million (95% uncertainty interval (UI) 3.64–5.96 million) new cases and 0.315 million deaths (95% uncertainty interval (UI) 0.268–0.361 million) and 8.39 million disability-adjusted years (95% uncertainty interval (UI) 6.69–10.54 million). The highest risk factor for deaths, DALYs attributable to AF/AFL in 2019 was high systolic blood pressure, high body-mass index, alcohol use, smoking, and diet high in sodium. It is estimated that between 2030 and 2034, the total incidence of male AF/ AFL will be 16.08 million, and the total number of deaths will be 1.01 million. For females, the total number of incidence is 16.85 million, and the total number of deaths is 1.49 million. Conclusions AF/AFL remains a major global public health problem, although the ASR of prevalence, incidence, and DALY at the worldwide level showed a decreasing trend from 1990 to 2019(the ASR of deaths increased slightly). However, the unfavorable trend observed in this study in countries with lower SDI suggests that current prevention and treatment strategies should be reoriented. Some countries should develop more targeted and specific strategies to prevent the increase of AF/AFL.

Background/Purpose: This study examined the prevalence and related factors of multiple (two or three) types of harassment victimization, including school bullying, cyberbullying, and teacher harassment, and their cumulative effects on depression, anxiety, self-esteem, and suicidality in adolescents with autism spectrum disorder (ASD) but without intellectual disability. Methods: A total of 219 adolescents with ASD but without intellectual disability and their parents participated in this study. Their experiences of school bullying, cyberbullying, and teacher harassment were evaluated. The related factors of multiple types of harassment victimization, including demographic characteristics, socio-communicative skills, comorbid attention-deficit/hyperactivity disorder (ADHD), and oppositional defiant disorder (ODD) symptoms, were examined. Moreover, the effects of multiple types of harassment victimization on depression, anxiety, self-esteem, and suicidality were examined. Results: In total, 20.54% of participants were victims of multiple types of harassment. Hyperactivity or impulsivity and ODD symptoms were positively associated with multiple types of harassment victimization. Adolescents with ASD who experienced multiple types of harassment victimization had higher severities of depression and anxiety and were more likely to have suicidality than nonvictims and those who experienced only one type of harassment victimization. Conclusion: Experiencing more than one type of harassment victimization was significantly associated with the development of mental health problems in adolescents with ASD. ODD and hyperactivity/impulsivity symptoms predicted the risk of experiencing multiple types of harassment.

AIM: To verify the feasibility and safety of staged lensectomy and vitrectomy in stage 5C retinopathy of prematurity (ROP) with corneal opacification. METHODS: This was a retrospective, interventional, consecutive case series. Twenty-two eyes of 18 stage 5C ROP patients with corneal opacification were included. Regular combined lensectomy and vitrectomy were not prescribed due to the invisible fundus. Staged lensectomy and posterior vitrectomy were performed. The anatomical and visual outcomes were reviewed at the final follow-up visit. RESULTS: The mean gestational age of ROP patients was 29.3±1.6wk (range: 27-32wk), comprising 8 males and 10 females. The average birth weight was 1363.0±300.0 g. All the eyes had corneal opacity and flat or disappeared anterior chambers pre-operatively. Two eyes had complicated cataract and 7 eyes had retrolental fibroplasia. Six eyes had posterior pupillary synechiae or membranes. Seven (31.8%) eyes had vascularly active retinas. The average interval between two procedures was 6.8±4.6mo (2.5-18.5mo). After surgeries, all the patients had normal anterior chambers. Fourteen eyes had clear corneas. The intraocular pressure of 3 eyes with glaucoma was controlled by medication. Two eyes had ocular phthisis. The retina was reattached in 3 eyes and partially attached in 11 eyes. Visual acuity ranged from no light perception to hand motion. CONCLUSION: Staged lensectomy and vitrectomy are procedures that can halt progression to further complications and preserve some useful eyesight in stage 5C ROP patients with corneal opacification. The earlier the lensectomy is performed, the better the prognosis is.

In this article, we consider a two-dimensional inverse heat conduction problem that determines the surface temperature distribution from measured data at the fixed location. This problem is severely ill-posed, i.e., the solution does not depend continuously on the data. A quasi-boundary value regularization method in conjunction with the a posteriori parameter choice strategy is proposed to solve the problem. A Hölder-type error estimate between the approximate solution and its exact solution is also given. The error estimate shows that the regularized solution is dependent continuously on the data.

AIM: To evaluate the effectiveness and corticosteroid-sparing capabilities of methotrexate (MTX) in the treatment of chronic non-necrotizing anterior scleritis in Chinese patients. METHODS: A retrospective chart review of all patients with active anterior scleritis between January 2015 and June 2019 was conducted. All patients received 10 to 15 mg/wk MTX orally, and corticosteroids (10 to 40 mg/d prednisolone or equivalent methylprednisolone) with slow tapering. Topical corticosteroid eye drops (1% prednisolone actate, 0.1% dexmathosone or 0.1% fluoromethalone) were applied to control comorbid anterior uveitis at presentation or during follow up. The main outcomes were inflammation control and corticosteroid-sparing success, and secondary outcomes were reduction of immunosuppression load and best-corrected visual acuity (BCVA). RESULTS: Thirty-two eyes (22 patients) were included. The proportion of patients who achieved corticosteroid-sparing success was 50.0% at 3mo and 77.3% at 12mo [8 (36.4%) patients discontinued corticosteroid]. The proportion of eyes that achieved inflammation control was 59.4% at 3mo and 78.1% at 12mo. The immunosuppression load was 5.14±0.87 at presentation and 2.76±2.34 at 12mo (P

Background: Theta burst stimulation (TBS), a patterned repetitive transcranial magnetic stimulation (rTMS) protocol with shorter simulation duration and lower stimulus intensity, could be a better protocol for individuals with autism spectrum disorder (ASD). Our study aimed to explore the impacts of intermittent TBS (iTBS) over the bilateral posterior superior temporal sulcus (pSTS) on intellectually able adults with ASD. Methods: In this randomized, single-blinded, sham-controlled crossover trial, 13 adults with ASD completed iTBS for 5 consecutive days over the bilateral pSTS and inion (as a sham control) in a 16-weeks interval and in a randomly assigned order. The neuropsychological function was measured with the Wisconsin Card Sorting Test (WCST) for cognitive flexibility while the clinical outcomes were measured with both self-rate and parents-rate Autism Spectrum Quotient (AQ) before and after 5-day iTBS interventions. Results: The results revealed significantly immediate effects of multi-session iTBS over the bilateral pSTS on parent-rate autistic symptoms in adults with ASD. The post-hoc analysis revealed the impacts of multi-session iTBS on cognitive flexibility were affected by baseline social-communicative impairment and baseline cognitive performance. Besides, the impacts of multi-session iTBS on clinical symptoms was affected by the concurrent psychotropic medication use and baseline autistic symptoms. Conclusions: Given the caveat of the small sample size and discrepancy of multiple informants, this pilot study suggests the therapeutic potential of 5-day multi-session iTBS over the pSTS in adults with ASD. Individual factors modulating the response to rTMS should be explicitly considered in the future trial.

Abstract Aims Long non‐coding RNA HOXA11‐AS participated in heart disease. In this study, we aim to evaluate the potential roles of HOXA11‐AS in atherosclerosis and its underlying mechanisms. Methods and results The expression levels of HOXA11‐AS in ox‐LDL‐treated HUVECs and arch tissues of high‐fat diet‐fed ApoE−/− mice (n = 10) were assessed by qRT‐PCR. The effects of HOXA11‐AS knockdown on the development of atherosclerosis were evaluated using in vitro and in vivo models. Luciferase reporter and RNA immunoprecipitation (RIP) assays verified the potential relationships between HOXA11‐AS or ROCK1 and miR‐515‐5p. The interactive roles between HOXA11‐AS and miR‐515‐5p and between miR‐515‐5p and ROCK1 were further characterized in ox‐LDL‐treated HUVECs. Our data showed that HOXA11‐AS was significantly up‐regulated (P

The effect of sputtering power on the microstructure, anti-corrosion and anti-fouling properties of TiO2 films deposited on 5083 aluminum (Al) alloy by reactive magnetron sputtering at room temperature were investigated systematically. The results show that the TiO2 film mainly consists of anatase, and it is composed of spherical shaped and pyramidal particles. Both the anti-corrosion and anti-bacterial properties first improve with increasing sputter power. As the power is 12 kW, the combination of anti-corrosion and anti-bacterial properties is the best, the corrosion potential (Ecorr), current density (Icorr), polarization resistance (Rp) and density of bacteria are −0.25 V, 0.36 μA/cm2, 2255.5 Ω/cm2 and 73 cell/mm2, respectively.

Abstract Background The aims of this study were to evaluate the levels of preretinal oxygen tension in patients with diabetes who did not have hypertension by using three-dimensional spoiled gradient-recalled (3D-SPGR) echo sequence imaging and to explore the correlation between diabetic retinopathy (DR) and changes in preretinal oxygen tension. Method This study involved 15 patients with type 2 diabetes without hypertension, who were divided into a diabetic retinopathy (DR) group (n = 10 eyes) and a diabetic non-retinopathy (NDR) group (n = 20 eyes), according to the results of a fundus photography test. Another healthy control group (n = 14 eyes) also participated in the study. The preretinal vitreous optic disc area, nasal side, and temporal side signal intensity of the eyes was assessed before and after oxygen inhalation with the use of 3D-SPGR echo magnetic resonance imaging (MRI). The signal acquisition time was 10, 20, 30, 40, and 50 min after oxygen inhalation. Results The results showed that, in the DR and NDR groups, the preretinal vitreous oxygen tension increased rapidly at 10 min after oxygen inhalation and peaked at 30–40 min, and the increased slope of the DR group was higher than that of the NDR group. The oxygen tension of the preretinal vitreous gradually increased after oxygen inhalation, and the difference between the DR and NDR groups and the control group was statistically significant (P

Background: Urinary catheterization after vaginal prolapse surgery can cause inconvenience for patients, elevate the risk of urinary tract infections, and potentially prolong the hospitalization. In China, there is no consensus on the optimal time to remove the urinary catheter after vaginal prolapse surgery. Thus, it will be valuable to gain insight into the nationwide catheterization management after the vaginal prolapse surgery. Methods: From March to May 2020, an online questionnaire was shared and purposive non-probabilistic sampling was used to recruit the participants. The urogynecologists currently performing vaginal prolapse surgery and involved nurses were included in this study. Results: 1363 urogynecologists and 436 nurses responded and 99.5% of them reported using transurethral indwelling catheters (TIC) for post-operative bladder drainage in their practices. The duration of initial catheterization after vaginal prolapse surgery was generally 1–7 days, with a median duration of 3 days for anterior colporrhaphy (AC) and anterior & posterior colporrhaphy (APC), and 2 days for other procedures. For the same type of surgery, the median duration of catheterization varied by region. For AC, it was shorter by 1 day in West China and South China (P ​

Misfolded SOD1 has been linked to both familial and sporadic ALS. Here the authors have determined the cryo-EM structure of SOD1 fibrils, providing insights into the conversion of SOD1 from its immature form into an aggregated form during pathogenesis of ALS.

Abstract Background More and more evidence indicates sodium-glucose co-transporter 2 inhibitors (SGLT2is) may display clinical benefits for heart failure with preserved ejection fraction (HFpEF). However, the mechanisms of the action remain unclear. Methods A systematic pharmacology-based strategy was applied for predicting the potential molecular mechanisms of SGLT2is in HFpEF. The potential targets of SGLT2is and HFpEF were contained from diverse databases. After networks were constructed, Metascape was applied to functional enrichment. Moreover, the key findings were validated through molecular docking. Results We obtained 487 SGLT2is related targets and 1505 HFpEF related targets. The networks showed the complex relationship of HFpEF-target-HFpEF. The results of functional enrichment analysis suggested that several biological processes, including muscle system process, inflammatory response, vasculature development, heart development, regulation of MAPK cascade, positive regulation of ion transport, negative regulation of cell population proliferation, cellular response to nitrogen compound, apoptotic signaling pathway, multicellular organismal homeostasis, response to oxidative stress, regulation of cell adhesion, positive regulation of cell death, response to growth factor, and cellular response to lipid, and signaling pathways, such as cardiomyopathy, cAMP signaling pathway, cytokine-cytokine receptor interaction, apoptosis, MAPK signaling pathway, HIF-1 signaling pathway, calcium signaling pathway, and NF-kappa B signaling pathway. Finally, we validated the interactions and combinations of SGLT2is and core targets. Conclusion SGLT2is play the potential role of anti-HFpEF through the direct or indirect synergy of multiple targets and pathways. Our study promotes the explanation of the molecular mechanisms of SGLT2is in HFpEF.

AIM: To determine the anatomic and visual outcomes of prophylactic juxtapapillary laser photocoagulation treatment alone in the prevention of retinal detachment (RD) in a cohort of pediatric patients diagnosed with morning glory syndrome (MGS). METHODS: A total of 24 eyes of 22 consecutive patients aged 0-15y diagnosed with MGS treated with prophylactic juxtapapillary laser photocoagulation alone were reviewed. Data including demographics, ocular examination, anatomic and visual outcomes, following treatment and complications were collected. RESULTS: Two patients had bilateral laser treatment and 20 had monocular laser treatment. The age at treatment of 13 (59.1%) patients was less than 12mo. The presenting symptoms included strabismus (6/22, 27.3%), decreased vision (2/22, 9.1%), and routine fundus screening (14/22, 63.6%). Fifteen (68.2%) patients underwent cranial magnetic resonance imaging (MRI) examinations, and 3 of those 15 (20.0%) had abnormal findings in the nervous system. Based on preoperative wide-field fundus photography and B-scan echography, all (100.0%) eyes had no obvious RD. On postoperative 1mo and 6mo and the following follow-ups, the anatomic outcomes of all eyes remained stable. The mean follow-up duration was 27.7±17.5mo. No severe complications were found. Preoperative visual acuity acquired from 2 (9.1%) patients ranged from light perception to 20/200. Postoperative acuity acquired from 11 (50.0%) patients ranged from light perception to 20/125. CONCLUSION: The preliminary anatomic and visual outcomes of prophylactic juxtapapillary laser treatment alone in pediatric MGS patients are relatively stable in a short-term follow-up. Further long-term clinical observation will be needed to confirm its efficacy and safety.