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Abstract Background To investigate the risk factors and prognosis of clinical pseudophakic cystoid macular edema (PCME) after uneventful phacoemulsification surgery in patients without pre-existing fundus diseases. Methods This was a retrospective case-control study. Medical records between August 2020 and August 2023 were reviewed for patients who had no previous fundus diseases and developed clinical PCME. A control group was randomly chosen and the risk factors for PCME was analyzed by binary logistic regression. Structure and visual prognosis of the PCME cohort were observed and compared among subgroups undergoing different treatment measures. Results Forty-seven eyes of 47 patients with PCME were included. The development of PCME was associated with higher systolic blood pressure (OR, 1.048; 95%CI 1.002, 1.097; P = .042), no posterior vitreous detachment (OR, 0.215; 95%CI: 0.553, 0.887; P = .032) and shorter axial lengths (OR, 0.401; 95%CI 0.161, 0.997; P = .049) compared to controls. During a mean follow-up of 8.26 months, 36 eyes (76.6%) showed visual improvement with decreased macular thickness. Different treatment modalities, including observation, topical NSAIDs, and intervention therapy, have no significant differences on the visual prognosis (P = 1.000). However, the intervention group had a shorter recovery time compared to the observation group (28.6 vs. 45.9 days, P = .037). Conclusion PCME remains an encountered morbidity in patients without pre-existing fundus diseases. Shorter axial lengths, absence of posterior vitreous detachment, and higher systolic blood pressure are risk factors of PCME. Active intervention failed to improve the prognosis of PCME but could shorten the recovery time.

Objectives To investigate the effects of integrative neuromuscular training (INT) on the athletic performance of elite female boxers. Methods A before-and-after controlled experiment was conducted on 37 elite Chinese female boxers (Age: 26.00 ± 3.11 years). All included athletes have competed at the international level. The INT intervention was administered 11 times per week for 3 weeks. This training includes strength training, explosive training, core stability, agility exercises, high intensity intervals and sprint intervals. Basic physical fitness tests, including the deep squat and bench press one-repetition maximum (1RM), vertical long jump, 30 m sprint run, 400 m run, 3,000 m run, 1-minute hexagonal jump, and 3-minute double shake; as well as specialized striking ability tests, including single-punch striking and 10-second, 30-second, and 3-minute continuous punching, were conducted before and after the intervention. Results Compared with pre-intervention baseline data, significant differences were found in the athletes’ post-intervention baseline physical fitness, including squat and beach press (1RM), vertical jump, 30 m sprint run, 400 m run, 3,000 m run, 1-minute hexagonal jump, and 3-minute double shake (p 0.05). Conclusion The 3-week INT can significantly improve the maximum strength, vertical explosive power, linear acceleration, agility, and continuous punching abilities of Chinese elite female boxers. The use of INT in physical training may enhance their athletic performance.

ObjectivesThis study explored the effects of 6 weeks of variable resistance training (VRT) and constant resistance training (CRT) within complex training, on muscle strength and punch performance.MethodsTwenty-four elite female boxers from the China National team were divided randomly between an experimental group (VRT) and a control group (CRT). Maximum strength of the upper and lower limbs, countermovement jump (CMJ) performance, and punch performance (single, 10s and 30s continuous) were assessed pre- and post- intervention.ResultsVRT and CRT showed significant increases (p < 0.001) in the bench press (ES = 1.79 and 1.07, respectively), squat (ES = 1.77 and 1.10, respectively), and CMJ (ES = 1.13 and 0.75, respectively). The bench press (p < 0.05) and squat (p < 0.05) improved significantly more following VRT compared to CRT. Additionally, single punch performance (speed, force, and power) increased significantly in the experimental group (ES = 1.17–1.79) and in the control group (ES = 0.58–1.32), except for the lead punch force in the control group (p > 0.05, ES = 0.20). 10s continuous punch performance (number, speed, force, and power) increased significantly (both p < 0.05) in the experimental group (ES = 0.52–1.65) and in the control group (ES = 0.32–0.81). 30s continuous punch performance (number, force, and power) increased significantly increased significantly (both p < 0.05). However, no statistically significant differences were found between groups for punch performance.ConclusionThese findings provide evidence that VRT may improve maximum muscle strength in both upper and lower limbs, vertical jump and punch performance in elite amateur boxers.

Background/Objectives: Due to the character of the taekwondo, the adenosine triphosphate–phosphocreatine system provides the energy for each kick, the glycolytic system supports the repeated execution of kicks, and the aerobic system promotes recovery between these movements and the bout. Therefore, taekwondo athletes require high explosive power and anaerobic capacity in order to carry out sustained and powerful attacks. So, the purpose of this study is to compare the effects of APRE and VBRT on lower-limb explosive power and anaerobic capacity in college taekwondo players. Methods: A total of 30 taekwondo players completed an 8-week training intervention with autoregulatory progressive resistance exercise (APRE; n = 15) and velocity-based resistance training (VBRT; n = 15). Testing included the one-repetition maximum squat, countermovement jump (CMJ), taekwondo anaerobic intermittent kick test (TAIKT), and 30-s Wingate anaerobic test (WAnT). Results: (1) Intragroup comparisons revealed significant effects for one-repetition maximum squat, peak power of CMJ (CMJPP), relative peak power of CMJ (CMJRPP), and total number of TAIKT (TAIKTTN) in both the APRE and VBRT groups. The VBRT group exhibited small effect sizes for time at peak power of WAnT (WAnTPPT) and moderate effect sizes for peak power of WAnT (WAnTPP), relative peak power of WAnT (WAnTRPP), and fatigue index of TAIKT (TAIKTFI), whereas the APRE group exhibited small effect sizes for TAIKTFI. (2) Intergroup comparisons revealed no significant effects in any of the results. However, VBRT demonstrated a moderate advantage in WAnTPP and WAnTRPP, whereas APRE had a small advantage in CMJPP and CMJRPP. Conclusions: These findings suggest that APRE improved explosive power (CMJPP and CMJRPP) more, whereas VBRT improved anaerobic power output (WAnTPP and WAnTRPP) more. Both methods were found to have similar effects in improving the anaerobic endurance (WAnTPPT and TAIKTTN) and fatigue index (power drop of WAnT and TAIKTFI).

Abstract Background This study aimed to investigate the functional and anatomical outcomes of subthreshold micropulse laser (SMPL) therapy in eyes with early postoperative macular thickening after idiopathic epiretinal membrane (iERM) removal. Methods This was a prospective and interventional study. Forty-eight eyes from 48 patients with macular edema at 1 month after iERM removal were randomly divided into two groups. Patients in the SMPL group (n = 24) received SMPL therapy while no special intervention was used for the observation group (n = 24). Baseline demographic data and clinical findings before and at 1 and 3 months after SMPL treatment or observation, including best-corrected visual acuity (BCVA) and the changes in central subfield thickness (CST) and average macular thickness (AMT), were analyzed. Results An improvement in BCVA with a decrease in CST and AMT from baseline to the 3-month follow-ups were observed in both SMPL and observation groups. No significant difference in BCVA was observed between the SMPL group and observation group either in the 1-month (0.26 [0.15, 0.52] vs. 0.26 [0.15, 0.39], P = 0.852) or the 3-month (0.15 [0.10, 0.30] vs. 0.23 [0.15, 0.30], P = 0.329) follow-up. There was a greater reduction in CST in the SMPL group versus observation group between baseline and the 3-month follow-up (-77.8 ± 72.3 μm vs. -45.0 ± 46.9 μm, P = 0.049). The alteration in AMT did not differ between the two groups in either 1-month (-16.5 ± 20.1 μm vs. -19.7 ± 16.3 μm, P = 0.547) or 3-month (-36.9 ± 26.9 μm vs. -34.0 ± 20.1 μm, P = 0.678) follow-up. Conclusions SMPL therapy led to a significant decrease in CST at the 3-month follow-up while did not significantly improve the visual acuity in patients with postoperative macular thickening following iERM surgery. Trial registration The study was registered on Aug 27, 2020 (Trial Registration Number: ChiCTR 2000037227).

Abstract Plyometric training boosts adolescents' jumping ability, crucial for athletic success and health. However, the best total ground contact frequency (TGCF) and overall intervention time (OIT) for these exercises remain unclear. This meta-analysis aims to identify optimal TGCF and OIT in plyometric training for adolescents, focusing on countermovement jump (CMJ) and squat jump (SJ) outcomes. This systematic review encompassed five databases and included 38 studies with 50 randomized controlled experiments and 3347 participants. We used the Cochrane risk assessment tool for study quality and Review Manager 5.4 for data analysis. The current meta-analysis incorporated a total of 38 studies, comprising 50 sets of randomized controlled trials, to investigate the influence of different TGCFs and OITs on plyometric training. The Cochrane risk assessment tool indicated that all the included studies were classified as low risk. Various TGCFs in plyometric training positively affected CMJ and SJ heights in adolescents. The TGCF of less than 900 was ideal for enhancing CMJ, whereas more than 1400 was effective for SJ. The optimal OIT was 400–600 min, specifically, 500–600 min for CMJ and 400–500 min for SJ. Plyometric training improves jumping ability in adolescents. Lower ground contact frequency ( 1400 contacts) is more effective for SJ. Optimal intervention time ranges from 400 to 600 min, with 500 to 600 min benefiting CMJ and 400 to 500 min improving SJ.

Abstract Aims Diabetic retinopathy (DR) is a significant global public health concern. Alternative, safe, and cost‐effective pharmacologic approaches are warranted. We aimed to investigate the therapeutic potential of nattokinase (NK) for early DR and the underlying molecular mechanism. Methods A mouse model of diabetes induced by streptozotocin was utilized and NK was administered via intravitreal injection. Microvascular abnormities were evaluated by examining the leakage from blood–retinal barrier dysfunction and loss of pericytes. Retinal neuroinflammation was examined through the assessment of glial activation and leukostasis. The level of high mobility group box 1 (HMGB1) and its downstream signaling molecules was evaluated following NK treatment. Results NK administration significantly improved the blood–retinal barrier function and rescued pericyte loss in the diabetic retinas. Additionally, NK treatment inhibited diabetes‐induced gliosis and inflammatory response and protected retinal neurons from diabetes‐induced injury. NK also improved high glucose‐induced dysfunction in cultured human retinal micrangium endothelial cells. Mechanistically, NK regulated diabetes‐induced inflammation partially by modulating HMGB1 signaling in the activated microglia. Conclusions This study demonstrated the protective effects of NK against microvascular damages and neuroinflammation in the streptozotocin‐induced DR model, suggesting that NK could be a potential pharmaceutical agent for the treatment of DR.

Conclusions: Intravitreal conbercept injection presents dual effects of antiangiogenesis and anti-inflammation and can be served as an adjuvant treatment to vitrectomy for PDR patients.

ObjectiveThis study explores the age effects of the sport education model(SEM) on the impact of basic psychological needs (autonomy, competence, relatedness) and intrinsic motivation (interest, enjoyment, satisfaction) among adolescent students.MethodRetrieval of relevant literature from PubMed, Web of Science, Scopus, and China National Knowledge Infrastructure (CNKI). The search period ranged from the starting year to January 7, 2024. Subsequently, literature screening, data extraction, and quality assessment will be conducted, and data analysis will be performed using "Review Manager 5.4" software.ResultOverall, SEM has a positive and statistically significant impact on the basic psychological needs (MD = 0.36,95% CI [0.22, 0.50]) and intrinsic motivation (MD = 0.75, 95% CI [0.58, 0.93]) of adolescent students (PConclusionThe SEM is an effective approach to enhancing the basic psychological needs and intrinsic motivation of adolescent students. However, it exhibits age effects among students at different developmental stages. Specifically, in terms of enhancing basic psychological needs, the model has the greatest impact on POST-PHV students, followed by PRE-PHV students, while the improvement effect is relatively lower for MID-PHV students. The enhancement effect on intrinsic motivation diminishes with increasing age.

Diabetic retinopathy (DR) remains the leading cause of blindness among the global working-age population. Emerging evidence underscores the significance of diabetic retinal neurodegeneration (DRN) as a pivotal biomarker in the progression of vasculopathy. Inflammation, oxidative stress, neural cell death, and the reduction in neurotrophic factors are the key determinants in the pathophysiology of DRN. Non-apoptotic programmed cell death (PCD) plays a crucial role in regulating stress response, inflammation, and disease management. Therapeutic modalities targeting PCD have shown promising potential for mitigating DRN. In this review, we highlight recent advances in identifying the role of various PCD types in DRN, with specific emphasis on necroptosis, pyroptosis, ferroptosis, parthanatos, and the more recently characterized PANoptosis. In addition, the therapeutic agents aimed at the regulation of PCD for addressing DRN are discussed.

Abstract Diabetic retinopathy (DR) is a leading cause of blindness that poses significant public health concerns worldwide. Increasing evidence suggests that neuroinflammation plays a key role in the early stages of DR. Microglia, long-lived immune cells in the central nervous system, can become activated in response to pathological insults and contribute to retinal neuroinflammation. However, the molecular mechanisms of microglial activation during the early stages of DR are not fully understood. In this study, we used in vivo and in vitro assays to investigate the role of microglial activation in the early pathogenesis of DR. We found that activated microglia triggered an inflammatory cascade through a process called necroptosis, a newly discovered pathway of regulated cell death. In the diabetic retina, key components of the necroptotic machinery, including RIP1, RIP3, and MLKL, were highly expressed and mainly localized in activated microglia. Knockdown of RIP3 in DR mice reduced microglial necroptosis and decreased pro-inflammatory cytokines. Additionally, blocking necroptosis with the specific inhibitor GSK-872 improved retinal neuroinflammation and neurodegeneration, as well as visual function in diabetic mice. RIP3-mediated necroptosis was activated and contributed to inflammation in BV2 microglia under hyperglycaemic conditions. Our data demonstrate the importance of microglial necroptosis in retinal neuroinflammation related to diabetes and suggest that targeting necroptosis in microglia may be a promising therapeutic strategy for the early stages of DR.

Abstract Background Vitrectomy and peeling of the internal limiting membrane (ILM) was an effective therapeutic approach for myopic foveoschisis with progressive visual loss. This study investigated the anatomical and visual outcomes of fovea-sparing ILM peeling with or without the inverted flap technique for patients with symptomatic myopic foveoschisis (MF). Methods We retrospectively reviewed the clinical data of patients with MF. Vitrectomy with fovea-sparing ILM peeling and air tamponade was performed in all patients. The primary outcome measures included best-corrected visual acuity (BCVA), mean macular thickness (MMT), and central foveal thickness (CFT). Depending on whether an inverted ILM flap technique was utilized, further subgroup comparisons between the inverted flap group and the non-inverted flap group were conducted. Results Twenty-six eyes of 22 patients were included. Fifteen eyes were underwent fovea-sparing ILM peeling without inverted ILM flap and 11 of the 26 eyes were treated with fovea-sparing ILM peeling and an inverted ILM flap technique. In the mean follow-up period of 10.74 ± 4.58 months, a significant improvement in BCVA was observed from 0.97 ± 0.45 logMAR to 0.58 ± 0.51 logMAR (P 0.05). Conclusion Fovea-sparing ILM peeling with or without inverted flap technique resulted in favorable visual and anatomical outcomes for the treatment of MF. An important factor affecting the postoperative visual outcome was the preoperative visual acuity. Our study found no significant difference between the presence and absence of the inverted ILM flap.

Objectives Jumping ability has been identified as a key factor that influences the performance of badminton athletes. Autoregulatory progressive resistance exercise (APRE) and velocity-based resistance training (VBRT) are commonly used approaches to enhance muscle strength and have been shown to accurately monitor the development of explosive power to improve jumping ability. This study aims to investigate the effects of APRE and VBRT on badminton athletes’ jumping ability and to provide practical insights into improving their jumping performance during competitions. Methods Upon completing familiarization and pretesting, 18 badminton athletes were included and completed the training intervention (age, 21.4 ± 1.4 years; stature, 170.1 ± 7.3 cm; body mass, 65.9 ± 12 kg); they were randomly divided into the APRE group (n = 9) and VBRT group (n = 9). Jumping performance was assessed during the countermovement jump (CMJ), squat jump (SJ), and drop jump (DJ) via SmartJump, with CMJ ’s and SJ’s jump height, eccentric utilization ratio (EUR), and reactive strength index (RSI). All participants then completed a 4-week in-season resistance training intervention. Results (1) The results of the within-group indicated that only the CMJ (pre: 41.56 ± 7.84 vs post: 43.57 ± 7.85, p < 0.05) of the APRE group had significant differences, whereas the SJ, EUR, and RSI were not significantly different (p > 0.05). (2) The results of the intergroups revealed that all indicators had no significant differences (p > 0.05), but APRE had a moderate effect size on the improvement of the CMJ (η2 = 0.244) and EUR (η2 = 0.068) when compared with VBRT. Conclusions The results showed that, compared to VBRT, APRE can effectively improve the performance of the reactive athletes’ lower limb explosive power in the CMJ in a shorter period of time. The findings indicate that APRE may be useful for coaches seeking to improve the CMJ performance of athletes in the short term.

Abstract Background Capillary non-perfusion is an important characteristic for diabetic retinopathy (DR) indicating microvascular damage and ischemia. Data on the description and treatment outcomes of DR with large area of non-perfusion are lacking to date. We aim to describe the characteristics and treatment outcomes in a series of patients with DR who presented extensively large area of capillary non-perfusion (LACNP). Methods Fundus fluorescein angiograms from medical charts in patients diagnosed with DR between Jan 2017 and Dec 2019 were retrospectively reviewed. Clinical data in eyes with LACNP including imaging and laboratory findings at the first presentation were analyzed. The LACNP was defined as over 70% area of capillary non-perfusion throughout the whole image retina. The mean follow-up duration was 12.4 ± 16.7 months. Follow-up data including extensive pan-retinal photocoagulation and surgical intervention and treatment outcomes were evaluated. Results A total of 43 eyes in 24 patients with LACNP were included, accounting for 3.3% of DR populations in the same period. The overall percentage of non-perfusion area was 79.1 ± 8.1%. All patients received proper control of diabetes and hypertension, and extensive pan-retinal laser photocoagulation. During the follow-up periods, 20 eyes (46.5%) developed severe neovascular complications, of which 15 eyes (34.9%) underwent vitrectomy and/or anti-glaucoma surgeries. Conservative therapies including glycemic control and supplemental laser photocoagulation were conducted in 23 eyes (53.5%) without neovascular complications. In the final follow-up, best corrected visual acuity improved or maintained stable in 19 eyes (44.2%) while deteriorated in 24 eyes (55.8%). Conclusions The presence of LACNP is the hallmark of advanced DR and often indicates a poor visual outcome, although aggressive treatments may slow DR progression and maintain central vision for some time.

Hypoxia-induced retinal neovascularization is a leading cause of blindness worldwide. Oxygen-induced retinopathy (OIR) mouse, a well-established angiogenesis model, has been extensively used to evaluate the effect of anti-angiogenic agents through intravitreal injection. Here, we serendipitously found that the needles used for intravitreal injection caused an unexpected “anti-angiogenic” effect in the OIR mice. To evaluate the effects of various intravitreal puncture sizes on retinal neovascularization and explore the potential underlying mechanism, intravitreal punctures using 0.5 mm (25 G), 0.3 mm (30 G), or 0.21 mm (33 G) needles were performed in OIR mice. Compared with 0.3 mm and 0.21 mm puncture, the 0.5 mm puncture remarkably suppressed the formation of pathological angiogenesis, inhibited vascular leakage, and remodeled the retinal vasculature. Mechanistically, the 0.5 mm puncture induced a substantial reduction in intraocular pressure (IOP), leading to an improvement in oxygen partial pressure (pO2) and significant reduction in Hif1a expression, resulting in resolution of angiogenic and inflammatory responses. Furthermore, IOP-lowering drugs, Travatan or Azarga, also promoted the alleviation of hypoxia and exhibited a potent anti-angiogenesis efficacy. Our study revealed an acute and significant reduction in IOP caused by a large puncture, which could remarkably suppress HIF-1α-mediated retinal neovascularization, indicating that lowering IOP may be a promising therapeutic avenue for treating retinal neovascular diseases.

As the fundamental part of other Intelligent Transportation Systems (ITS) applications, short-term traffic volume prediction plays an important role in various intelligent transportation tasks, such as traffic management, traffic signal control and route planning. Although Neural-network-based traffic prediction methods can produce good results, most of the models can’t be explained in an intuitive way. In this paper, we not only proposed a model that increase the short-term prediction accuracy of the traffic volume, but also improved the interpretability of the model by analyzing the internal attention score learnt by the model. we propose a spatiotemporal attention mechanism-based multistep traffic volume prediction model (SAMM). Inside the model, an LSTM-based Encoder-Decoder network with a hybrid attention mechanism is introduced, which consists of spatial attention and temporal attention. In the first level, the local and global spatial attention mechanisms considering the micro traffic evolution and macro pattern similarity, respectively, are applied to capture and amplify the features from the highly correlated entrance stations. In the second level, a temporal attention mechanism is employed to amplify the features from the time steps captured as contributing more to the future exit volume. Considering the time-dependent characteristics and the continuity of the recent evolutionary traffic volume trend, the timestamp features and historical exit volume series of target stations are included as the external inputs. An experiment is conducted using data from the highway toll collection system of Guangdong Province, China. By extracting and analyzing the weights of the spatial and temporal attention layers, the contributions of the intermediate parameters are revealed and explained with knowledge acquired by historical statistics. The results show that the proposed model outperforms the state-of-the-art model by 29.51% in terms of MSE, 13.93% in terms of MAE, and 5.69% in terms of MAPE. The effectiveness of the Encoder-Decoder framework and the attention mechanism are also verified.

Abstract Background Signal transducer and activator of transcription 3 (Stat3) is a cytoplasmic transcription factor that participates in various biologic processes. Loss of Stat3 causes hyperimmunoglobulin E syndrome, presenting with skeletal disorders including osteoporosis, recurrent fractures, scoliosis, and craniosynostosis. The objective of this study is to explore the effect and mechanism of Stat3 on osteogenesis of mesenchymal progenitors. Methods Stat3 was conditionally knockout (CKO) in mesenchymal progenitors by crossing the pair-related homeobox gene 1-cre (Prx1-Cre) with Stat3-floxed strain mice. Whole-mount-skeletal staining, histology, and micro-CT were used to assess the differences between Stat3 CKO and control mice. Further, in vitro experiments were conducted to evaluate the osteogenesis potential of primary isolated bone marrow mesenchymal stem cells (BMSCs) from both control and Stat3 CKO mice. After osteogenic induction for 14d, alizarin red staining was used to show the calcium deposit, while the western blotting was applied to detect the expression of osteogenic markers. Results Compared with the control, Stat3 CKO mice were present with shortened limbs, multiple fractures of long bone, and open calvarial fontanels. The abnormal growth plate structure and reduced collagen fiber were found in Stat3 CKO limbs. According to micro-CT analysis, the reduced cortical bone thickness and bone volume were found on Stat3 CKO mice. The in vitro osteogenic differentiation of BMSCs was inhibited in Stat3 CKO samples. After osteogenic induction for 14d, the significantly diminished calcium deposits were found in Stat3 CKO BMSCs. The decreased expression of osteogenic markers (OPN and COL1A1) was observed in Stat3 CKO BMSCs, compared with the control. Conclusions Stat3 played a critical role in bone development and osteogenesis. Loss of Stat3 impaired the osteogenesis of mesenchymal progenitors in vivo and in vitro.

Cancer therapies targeting human epidermal growth factor receptor 2 (HER2) have been attracting increasing attention worldwide, especially in lung adenocarcinoma. Disitamab vedotin is an antibody-drug conjugate designed for targeting HER2 that has been approved for urothelial carcinoma and gastric cancer. However, there is still a lack of clinical evidence for applying Disitamab vedotin in lung adenocarcinoma. Herein, we reported a case of a 52-year-old man with advanced lung adenocarcinoma carrying HER2 amplification as well as HER2 immunohistochemistry (IHC) 2 + who underwent treatment with Disitamab vedotin after disease progression. The patient was treated with chemotherapy, anti-angiogenesis therapy, and immunotherapy as first-line therapy, achieving a remarkable progression-free survival of 16 months. After the disease continued to continuous progress, the patient was administrated with Disitamab vedotin, which resulted in improvement of both the lung lesions and the brain lesions. Our findings provide a valuable reference for the utilization of Disitamab Vedotin in HER2 IHC2+ lung adenocarcinoma.

Inflammation plays a pivotal role in ischemia-induced retinal neovascularization. Targeting microglia/macrophage-based neuroinflammation presents a promising therapeutic strategy. Ferulic acid (FA), a natural and active ingredient in plants, exerts favorable anti-oxidative and anti-inflammatory activities. In this study, we investigated the inhibitory effect of FA against hypoxia-induced retinal angiogenesis using cultured retinal vascular endothelial cells and an oxygen-induced retinopathy mouse (OIR) model. The immunoregulatory effect of FA on microglia/macrophage polarization was evaluated by detecting the expression of specific markers for both pro-inflammatory “M1” and anti-inflammatory “M2” phenotypes using co-immunostaining and polymerase chain reaction assays. The underlying molecular mechanism upon FA treatment was also explored. The results showed that FA supplement markedly inhibited retinal pathological angiogenesis both in vivo and in vitro. In addition, FA switched microglia/macrophage polarization from “M1” towards “M2” phenotype and alleviated the inflammatory response. Mechanically, the anti-angiogenic and anti-inflammatory properties of FA were mainly due to blockade of the ROS/NF-κB pathway. Our data demonstrated an anti-angiogenic effect of FA through regulating M1-to-M2 microglia/macrophage polarization, suggesting a potential therapeutic strategy for retinal neovascular diseases.

Abstract Background Receptor tyrosine kinase-like orphan receptor 2 (Ror2) plays a key role in bone formation, but its signaling pathway is not completely understood. Signal transducer and activator of transcription 3 (Stat3) takes part in maintaining bone homeostasis. The aim of this study is to reveal the role and mechanism of Ror2 in the osteogenic differentiation from mouse bone marrow mesenchymal stem cells (mBMSCs) and to explore the effect of Stat3 on Ror2-mediated osteogenesis. Methods Ror2 CKO mice were generated via the Cre-loxp recombination system using Prrx1-Cre transgenic mice. Quantitative real-time PCR and western blot were performed to assess the expression of Stat3 and osteogenic markers in Ror2-knockdown mBMSCs (mBMSC-sh-Ror2). After being incubated in osteogenic induction medium for 3 weeks, Alizarin Red staining and western blot were used to examine the calcium deposit and osteogenic markers in Stat3 overexpression in mBMSC-sh-Ror2. Results Loss of Ror2 in mesenchymal or osteoblast progenitor cells led to a dwarfism phenotype in vivo. The mRNA expression of osteogenic markers (osteocalcin, osteopontin (OPN), and collagen I) in the ulna proximal epiphysis of Ror2 CKO mice was significantly decreased (P

Objective To evaluate the apical surgery-related anatomy of two-rooted and three-rooted mandibular first molars (MFMs) in a Mongoloid population. Methods A total of 502 cone-beam computed tomographic images were used to evaluate the root configuration, the distance from the buccal bone to each root, root dimensions, and the complete root resection distance at the resection level for roots of MFMs. Results The prevalence of two-rooted and three-rooted MFMs was 85.1% and 14.9%, respectively. At the resection level, the distance from the buccal bone to the mesial and distal roots of two-rooted MFMs was 2.24 and 3.15 mm, respectively, while the distance was 2.44, 2.01, and 8.55 mm for the mesial, distobuccal, and distolingual roots of three-rooted MFMs, respectively. The distance from the buccal bone to each root was longer in men than in women. The largest distance for complete root resection was detected for the distal root in two-rooted MFMs and for the distolingual root in three-rooted MFMs. Conclusions The prevalence of three-rooted MFMs is common in the Mongoloid population. The distance from the buccal bone to root apex differs according to root configurations and sex. Surgical access to the distolingual root is difficult because of the long access distance.

Objective Some patients have been found to develop intraoperative amaurosis under sub-Tenon’s anesthesia. We explored whether these patients have poor surgical outcomes during mid- to long-term postoperative follow-up. Methods In this case series, 74 of 85 patients with macular diseases who underwent phacoemulsification combined with vitrectomy under sub-Tenon’s anesthesia developed intraoperative amaurosis. The surgical outcomes at the 2- and 4-month follow-ups in these patients were investigated and compared with the outcomes in patients without amaurosis using best-corrected visual acuity (BCVA), optical coherence tomography (OCT), and pattern visual evoked potential (PVEP). Results Both BCVA and the OCT-based macular structure in patients with intraoperative amaurosis showed significant postoperative improvement comparable with that of patients without amaurosis. The presence of intraoperative amaurosis was not associated with either macular hole closure or macular edema regression. PVEP revealed no significant changes in the wave latency or amplitude before and after surgery. Conclusion Intraoperative amaurosis following sub-Tenon’s block is commonly seen but does not predict a poor surgical prognosis. When a patient develops amaurosis during surgery, the surgeon should increase patient comfort through verbal communication rather than perform an additional intervention to help relieve the patient’s anxiety.

Background/Aims: Platelet-derived growth factors (PDGFs) have emerged as pivotal in pathological angiogenesis, which is a hallmark of various tumors and retinal diseases. Here we evaluated the anti-angiogenic effect of imatinib, an inhibitor of PDGF receptors α and β (PDGFR-α and -β), in retinal neovascularization using an oxygen-induced retinopathy (OIR) model. Methods: The OIR model was established and given imatinib or vehicle treatments daily from P12 to P16. At the peak of angiogenesis at P17, the neovascularization area was quantified on retinal whole-mounts with isolectin B4 staining. Immunofluorescence staining and western blots were used to determine the effect of imatinib on different vascular cells and the pathway molecules involved. Results: Imatinib effectively suppressed pathological angiogenesis in OIR mice and reduced the number of all three types of vascular cells, including endothelial cells, pericytes, and smooth muscle cells. Moreover, the expression and activation of PDGFR-α and -β were inhibited by imatinib. The imatinib-treated OIR mice presented with reduced expression of other potent pro-angiogenic factors such as VEGF and FGF2. No obvious retinal or systemic side effects were observed in the imatinib treatment group. Conclusions: Imatinib appears to be safe and effective in suppressing retinal neovascularization. Targeting PDGFs/PDGFRs may also be important for anti-angiogenic treatment and offer a viable alternative treatment for retinal angiogenic diseases.

Neurodegenerative diseases are a set of disorders characterized by progressive neuronal death and are associated with microglia-mediated neuroinflammation. Recently, neuroinflammation is proposed as a promising therapeutic target for many neurodegenerative diseases. Alpha-1 antitrypsin (AAT) is recognized as a novel immunomodulatory agent in autoimmune diseases and transplantation, however, its impact on neuroinflammation and neurodegeneration remains unknown. This study aims to explore the effects of AAT on microglia-mediated neuroinflammation and retinal degeneration in rd1 mouse model. We found reduced expression of AAT in rd1 retina, and AAT supplement exhibited certain protective effect on retinal degeneration, presenting with increased amount of photoreceptor nuclei, and amplified wave amplitudes in electroretinogram analysis. Of note, AAT shifted microglia phenotype from pro-inflammatory M1 (CD16/CD32+, iNOS+) to anti-inflammatory M2 (CD206+, Arg1+) both in vivo and in vitro, underscoring the concept of immunomodulation on microglia polarization by AAT during neurodegeneration. Furthermore, AAT suppressed the activation of STAT1, promoted the expression of IRF4 while inhibited IRF8 expression, indicating the involvement of these signaling pathways in AAT immunomodulation. Collectively, our data provided evidence for a novel protective role of AAT through immunomodulation on microglia polarization. Attenuating neuroinflammation by AAT may be beneficial to retard neurodegeneration in rd1 mice.

Microglia activation is recognized as the hallmark of neuroinflammation. However, the activation profile and phenotype changes of microglia during the process of retinal degeneration are poorly understood. This study aimed to elucidate the time-spatial pattern of microglia distribution and characterize the polarized phenotype of activated microglia during retinal neuroinflammation and degeneration in rd1 (Pde6βrd1/rd1) mice, the classic model of inherited retinal degeneration. Retinae of rd1 mice at different postnatal days (P7, P14, P21, P28, P56, and P180) were prepared for further analysis. We found most CD11b+ or IBA1+ microglia expressed Ki-67 and CD68 in rd1 mice and these cells migrated toward the layer of degenerative photoreceptors at the rapid rods degeneration phase from P14 to P28. These microglia exhibited typical ameboid activated shape with round bodies and scarce dendrites, while at late phase at P180, they displayed resting ramified morphology with elongated dendrites. Flow cytometry revealed that the percentage of CD86+CD206- M1 microglia increased markedly in rd1 retinae, however, no significant change was observed in CD206+CD86- M2 microglia. Interestingly, CD86+CD206+ microglia, an intermediate state between the two extremes of M1 and M2, increased markedly at the rapid rods degeneration phase. The immunofluorescence images revealed that microglia in rd1 mice highly expressed M1 markers including CD16/32, CD86, and CD40. In addition, increased expression of pro-inflammatory cytokines (TNF-α, IL-6, and CCL2) was observed in rd1 mice. Our findings unfolded a panorama for the first time that microglia conducted distinctive behaviors with the progression of retinal degeneration in rd1 mice. Microglia is activated and particularly polarized to a pro-inflammatory M1 phenotype at the rapid rods degenerative phase, suggesting that the involvement of M1 microglia in the retinal neuroinflammation and degeneration. Most microglia adopted an intermediate polarization “M1½” state in rd1, revealing that microglia orchestrated a complicated continuous spectrum in degenerative retina.

This study aimed to compare the effects of power loss (PL) autoregulated volume (PL10 and PL20) with standardized fixed-load (FL) prescription on strength, sports performance, and lean body mass (LBM). Thirty-five female basketball players from a sports college were randomly assigned to 3 experimental groups (PL10, n = 12; PL20, n = 12; and FL, n = 11, respectively) that performed a resistance training (RT) program with wave-like periodization for 10 weeks using the back squat exercise. Assessments performed before (Pre) and after (Post) intervention included assessed 1 repetition maximum (1RM), body composition, 20-m sprint (T20M), change of direction (COD), and jump performance, including countermovement jump with arm swing, maximum vertical jump, and reactive strength index. Three groups showed significant improvements in strength (effect size [ES]: PL10 = 2.98, PL20 = 3.14, and FL = 1.90; p < 0.001) and jump performance (ES: PL10 = 0.74, PL20 = 1.50, and FL = 0.50; p <0.05-0.001). However, PL10 and PL20 demonstrated different advantages in sports performance compared with FL (group x time interaction, p <0.05). Specifically, PL10 significantly improved COD performance (ES = -0.79 ~ -0.53, p <0.01), whereas PL20 showed greater improvements in sprint (ES = -0.57, p <0.05) and jump performance (ES = 0.67-1.64, p <0.01-0.001). Moreover, PL10 resulted in similar gains to PL20 and beneficial improvements compared with FL in LBM, despite performing the least repetitions. Overall, the study indicates that power loss-based autoregulation induces greater gains in LBM and sports performance, as well as eliciting a higher efficiency dose response than standardized FL prescriptions, particularly for PL10. Therefore, incorporating PL monitoring in training programs is recommended, and further studies on power-based RT would be worthwhile. [ABSTRACT FROM AUTHOR]

Background: 5-Methylcytosine (m5C) methylation contributes to the development and progression of various malignant tumors. This study aimed to explore the potential role of m5C methylation regulators (m5CMRs) in head and neck squamous cell carcinoma (HNSCC). Methods: The transcription data of HNSCC samples were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Subsequently, the m5C patterns in HNSCC were evaluated based on 14 m5CMRs. Then, the m5Cscore was developed to quantify m5C patterns by using principal component analysis (PCA) algorithms. Two single-cell RNA sequencing datasets and various methods were employed to assess the prognostic value and sensitivity to immunotherapy. Finally, key prognostic m5CMRs were identified using univariate COX regression analysis, and their clinical significance was validated based on the Human Protein Atlas (HPA) database and by using immunohistochemistry. Results: Two distinct m5C clusters were identified. m5C cluster A is characterized by an immune-activated microenvironment and is associated with a favorable prognosis. Notable differences were observed in prognosis, immune infiltration, and immunotherapy response between the high- and low-m5Cscore groups. Patients in the high-m5Cscore group exhibited high TMB, which is correlated with poor prognosis. The m5Cscore of epithelial cells in HNSCC was higher than that in other cells. Key prognostic m5CMRs, including NSUN2, DNMT3B, ALKBH1, and Y-Box Binding Protein 1 (YBX1), were associated with poor prognosis. Conclusion: Our research indicates that in head and neck squamous cell carcinoma, the m5C modification profoundly affects the TME's diversity and complexity, influencing prognosis and the success of immunotherapy. Targeting m5C regulatory elements may be a new method for enhancing the efficacy of immunotherapy in HNSCC. [ABSTRACT FROM AUTHOR]