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Zhong-Han Fang,1,2 Hong-Lin Liao,1,2 Qing-Feng Tang,1,2 Ya-Jing Liu,1,2 Yan-Yan Zhang,1,2 Jiu Lin,1,2 Hao-Peng Yu,3 Cheng Zhou,4 Chun-Jie Li,1,5 Fei Liu,1,2,* Jie-Fei Shen1,2,* 1State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, National Center for Stomatology, West China School of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 2Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 3West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 4Laboratory of Anesthesia and Critical Care Medicine, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 5Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fei Liu; Jie-Fei Shen, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China, Email liufei.hxkq@scu.edu.cn; shenjiefei@scu.edu.cnBackground: Recent studies have demonstrated the contribution of non-coding RNAs (ncRNAs) to neuropathic pain. However, the expression profile of ncRNAs in the trigeminal ganglion (TG) and their functional mechanism underlying trigeminal neuropathic pain are still unclear.Methods: In the present study, the trigeminal neuropathic pain model induced by chronic constriction injury of the infraorbital nerve (CCI-ION) was used to study the expression profile and potential regulatory mechanism of miRNAs, lncRNAs, circRNAs, and mRNAs in the TG by RNA-sequencing (RNA-seq) and bioinformatics analysis. CCI-ION mice suffered from mechanical allodynia from 3 days to 28 days after surgery.Results: The RNA-seq results discovered 67 miRNAs, 216 lncRNAs, 14 circRNAs, 595 mRNAs, and 421 genes were differentially expressed (DE) in the TG of CCI-ION mice 7 days after surgery. And 39 DEGs were known pain genes. Besides, 5 and 35 pain-related DE mRNAs could be targeted by 6 DE miRNAs and 107 DE lncRNAs, respectively. And 23 pain-related DEGs had protein–protein interactions (PPI) with each other. GO analysis indicated membrane-related cell components and binding-related molecular functions were significantly enriched. KEGG analysis showed that nociception-related signaling pathways were significantly enriched for DE ncRNAs and DEGs. Finally, the competing endogenous RNA (ceRNA) regulatory network of DE lncRNA/DE circRNA-DE miRNA-DE mRNA existed in the TG of mice with trigeminal neuropathic pain.Conclusion: Our findings demonstrate ncRNAs are involved in the development of trigeminal neuropathic pain, possibly through the ceRNA mechanism, which brings a new bright into the study of trigeminal neuropathic pain and the development of novel treatments targeting ncRNAs.Keywords: trigeminal neuropathic pain, non-coding RNAs, RNA-sequencing, trigeminal ganglion, trigeminal nerve injury, bioinformatics

Guang Sun,1 Jian-Fen Shen,2 Xiu-Fang Wei,1 Guo-Xian Qi1 1Department of Geriatric Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, 110001, People’s Republic of China; 2Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, 110001, People’s Republic of ChinaCorrespondence: Guo-Xian Qi Email xianzhanza784@126.comIntroduction: Myocardial infarction is coronary artery-related heart disease, and the leading cause of mortality globally. Circular RNAs (circRNAs) are a new type of regulatory RNAs and participate in multiple pathological cardiac progression.Methods: However, the function of circFoxo3 in MI-induced myocardial injury remains obscure.Results: Significantly, we identified that circFoxo3 was downregulated in the MI rat model and the overexpression of circFoxo3 ameliorated MI-induced cardiac dysfunction and attenuated MI-induced autophagy in rat model. Meanwhile, the overexpression of circFoxo3 repressed oxygen–glucose deprivation (OGD)-induced autophagy, apoptosis, inflammation, and injury of cardiomyocyte in vitro. Mechanically, we identified that the expression of KAT7 was reduced by circFoxo3 overexpression in cardiomyocytes. Meanwhile, the expression of HMGB1 was repressed by the depletion of KAT7 in cardiomyocytes. The enrichment of histone H3 lysine 14 acetylation (H3K14ac) and RNA polymerase II (RNA pol II) on HMGB1 promoter was inhibited by the knockdown of KAT7. Moreover, the overexpression of circFoxo3 suppressed HMGB1 expression and KAT7 overexpression rescued the expression of HMGB1 in cardiomyocytes. The enrichment of KAT7, H3K14ac, and RNA poly II on HMGB1 promoter was decreased by circFoxo3 overexpression, while the overexpression of KAT7 could reverse the effect. The overexpression of KAT7 or HMGB1 could reverse circFoxo3-attenuated cardiomyocyte injury and autophagy in vitro. Thus, we conclude that circular RNA circFoxo3 relieved myocardial ischemia/reperfusion injury by suppressing autophagy via inhibiting HMGB1 by repressing KAT7 in MI.Discussion: Our finding provides new insight into the mechanism by which circFoxo3 regulates MI-related cardiac dysfunction by targeting KAT7/HMGB1 axis.Keywords: myocardial infarction, autophagy, circFoxo3, KAT7, HMGB1

Xue-Hong Feng,1 Yang Wang,1 Lian-Yu Wang,1 Jun-Fei Shen,1 Chun-Yuan You,1 Qiu-Ting Feng2 1Department of Echocardiography, The Second Hospital of Wuxi Affiliated to Nanjing Medical University, Wuxi, Jiangsu, 214002, People’s Republic of China; 2Department of Cardiology, The Second Hospital of Wuxi Affiliated to Nanjing Medical University, Wuxi, Jiangsu, 214002, People’s Republic of ChinaCorrespondence: Qiu-Ting FengDepartment of Cardiology, The Second Hospital of Wuxi Affiliated to Nanjing Medical University, No. 68 Zhongshan Road, Wuxi, 214002, Jiangsu Province, People’s Republic of ChinaTel +86-15961823329Email fengbiqu22538573@163.comObjective: To investigate the predictive value of PTEN and echocardiography in the treatment of heart failure with trimetazidine combined with metoprolol.Methods: A total of 100 patients with coronary heart disease and HF who admitted to our hospital from August 2018 to August 2020 were enrolled into research. All patients received routine treatment according to the guidelines and were treated with trimetazidine and metoprolol for a total course of 6 months. Echocardiographic parameters and PTEN levels were measured at baseline and after treatment. The patients were divided into groups according to the quartile of basic PTEN level, and the total effective rates were compared. The echocardiographic parameters of patients with different prognosis were analyzed. Bivariate correlation analysis was used to evaluate the correlation between PTEN, echocardiography and treatment effect.Results: Compared with that before treatment, the level of PTEN increased significantly after treatment (P < 0.01). According to the quartile of basic PTEN level, the total effective rate of patients with different levels of basic PTEN was was statistically different (P < 0.01). There was a linear correlation between the level of basic PTEN and the treatment effect, and the total effective rate of patients with high level of basic PTEN was higher than that of patients with low level of PTEN. Compared with before treatment, LVEF, SV, E/A and lvfs increased significantly after treatment (P < 0.01). There was a correlation between the basic echocardiographic parameters and the treatment effect of patients. The basic echocardiographic parameters of patients with poor prognosis were worse than those with good prognosis. PTEN expression in patients’ serum was only positively correlated with E/A, but not with LVFE, SV and LVFS (P < 0.01).Conclusion: PTEN and echocardiographic parameters serve as a good method to evaluate the short-term therapeutic effect of trimetazidine combined with metoprolol in patients with heart failure.Keywords: PTEN, echocardiographic parameter, heart failure, trimetazidine, metoprolol, efficacy prediction

Crystal X Huang,1 James A Yiannias,2 Jill M Killian,3 Joanne F Shen4 1Mayo Clinic Alix School of Medicine, Scottsdale, AZ, USA; 2Department of Dermatology, Mayo Clinic, Scottsdale, AZ, USA; 3Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA; 4Department of Ophthalmology, Mayo Clinic, Scottsdale, AZ, USACorrespondence: Joanne F Shen Tel +1 480-301-8085Fax +1 480-301-7326Email Shen.Joanne@mayo.eduObjective: Eyelid dermatitis is most commonly attributed to allergic response. This retrospective clinical study identifies common allergens with eyelid involvement and addresses a literary gap by providing a clear approach for effective management of periorbital allergic contact dermatitis (ACD) recurrence.Methods: Charts of 215 patients diagnosed with periorbital dermatitis who were patch tested with Mayo Clinic Standard Series, Extended Standard Series, and personal products from 2013 to 2017 were examined. Positive reaction rates for patients with eyelid involvement were compared to those without. Findings were also compared to North American Contact Dermatitis Group (NACDG) 2013– 2014 and Mayo Clinic Contact Dermatitis Group (MCCDG) 2011– 2015 general patch test populations.Results: The 215 patients showed more common allergy to shellac, benzalkonium chloride, acrylates, and surfactants than the NACDG and MCCDG study populations. Periorbital ACD allergen groups eliciting the highest positive reaction rates were, in descending order: metals, shellac, preservatives, topical antibiotics, fragrances, acrylates, and surfactants. Of the corticosteroids, only tixocortol pivalate (the screening agent for prednisolone and fluorometholone) and budesonide elicited positive reactions.Conclusion: The top seven eyelid ACD allergen groups were identified. Avoidance of these allergens can be straightforward, with initial empiric counseling and free, online allergen avoidance programs. Patients who are unresponsive to avoidance should undergo patch testing.Keywords: allergic contact dermatitis, periorbital skin, patch test, contact allergens, allergen avoidance program

Samantha Sagaser,1 Richard Butterfield,2 Heidi Kosiorek,2 Yael Kusne,3 Juan Maldonado,4,5 Michael P Fautsch,6 Dharmendra Patel,3 Joanne F Shen3 1Mayo Clinic Alix School of Medicine, Scottsdale, AZ, USA; 2Research Biostatistics, Mayo Clinic, Scottsdale, AZ, USA; 3Ophthalmology, Mayo Clinic, Scottsdale, AZ, USA; 4Knowledge Enterprise, Genomics Core, Arizona State University, Tempe, AZ, USA; 5Center for Fundamental and Applied Microbiomics, The Biodesign Institute, Arizona State University, Tempe, AZ, USA; 6Ophthalmology, Mayo Clinic, Rochester, MN, USACorrespondence: Joanne F ShenMayo Clinic, 13400 East Shea Blvd, Scottsdale, AZ 85259, USAEmail Shen.Joanne@mayo.eduPurpose: To assess tear film transforming growth factor-beta (TGF-β) and ocular microbiome changes after intense pulsed light with meibomian gland expression (IPL-MGX) vs only MGX in treating ocular rosacea with dry eye symptoms.Methods: Twenty patients were randomly assigned to IPL-MGX or MGX. Patients were examined, treated, and administered the ocular surface disease index (OSDI) survey every 4– 6 weeks for four total treatments. Tear film and conjunctival samples were collected at first and last visits, and analyzed for TGF-β concentration and 16s rRNA amplicon sequencing of ocular microbiome. Wilcoxon Rank Sum and Sign-Rank were used to examine changes from baseline.Results: OSDI revealed significantly greater improvement in symptoms after IPL-MGX (p=0.030) compared to MGX. There was no significant difference in mean TGF-β 1, 2, or 3 concentration after IPL-MGX (p=0.385, 0.709, 0.948, respectively). Quantities of Clostridium, Klebsiella, Brevibacterium, Lactobacillus, Neisseria, Streptococcus, Corynebacterium, Butyricicoccus, and Actinomyces were significantly reduced from baseline in both groups but without a significant difference between the two treatment groups.Conclusion: IPL-MGX improved dry eye symptoms more than MGX alone. IPL treatment offered no additional benefit to MGX in decreasing virulent bacteria present on the ocular surface and did not influence TGF-β levels in tears. Prospective studies on IPL-MGX with larger sample sizes are needed to further investigate cytokines and IPL in patients suffering from ocular rosacea with dry eye symptoms.ClinicalTrials.gov Identifier: NCT03194698.Keywords: intense pulsed light, IPL, meibomian gland expression, dry eye disease, meibomian gland disorder, ocular rosacea, transforming growth factor-beta, TGF-β, tear cytokines, ocular microbiome, OSDI; ocular surface disease index

You-Zhi Zhang,1 Yu-Lin Zhang,1 Qi Huang,1 Cong Huang,1 Zhi-Long Jiang,1 Fei Cai,1 Jian-Fen Shen2 1School of Pharmacy, Hubei University of Science and Technology, Xianning, Hubei 437100, People’s Republic of China; 2Department of Central Laboratory, The First Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang 314001, People’s Republic of ChinaCorrespondence: Jian-Fen ShenDepartment of Central Laboratory, The First Affiliated Hospital of Jiaxing University, 1882 Zhonghuan South Road, Jiaxing, Zhejiang 314001, People’s Republic of ChinaTel +86 573 8251 9007Email shenjf2008@163.comBackground: Hypoadiponectinemia is a high risk factor for type 2 diabetes and cardiovascular disease. Although adiponectin is a protective molecule in cardiovascular diseases, it is hampered due to short plasma half-life and high cost of production. This study aimed to investigate whether AdipoRon, a small-molecule adiponectin receptor agonist, alleviated saturated free fatty acids such as palmitic acid (PA)-induced cardiomyocyte injury by suppressing Nlrp3 inflammasome activation.Methods: Cell viability was used with MTT assay. Cell apoptosis and mitochondria membrane potential were detected by flow cytometry. We also detected the ROS production and colocolization of inflammasome protein with fluorescence and immunofluorescence microscopic analysis, respectively. Then, IL-1β was detected by Elisa assay and other protein expression was analyzed by Western blot.Results: Our observations demonstrated PA dose-dependently promoted the cell injury, and such high lipotoxicity induced impairment of cardiomyocytes was significantly attenuated by AdipoRon treatment. Moreover, PA markedly activated the first phase of Nlrp3 inflammasome (NF-ƙb) signaling. Notably, the stimulation of PA enhanced ROS production as regulators of Nlrp3 inflammasome activation. In addition, treatment with PA increased the Nlrp3 inflammasome protein expression and complex formation, while AdipoRon abolished it. Lastly, the suppressive effect of AdipoRon to PA-induced cell injury and Nlrp3 inflammasome activation was significantly reversed by Nlrp3 siRNA and pan-caspase inhibitor (z-vad-fmk).Conclusion: Taken together, these data suggested that AdipoRon suppressed PA-induced myocardial cell injury by suppressing Nlrp3 inflammasome activation. Thus, AdipoRon might possess potent protective effect in lipotoxicity injury such as obesity leading to cardiac disease.Keywords: adiponectin, AdipoRon, PA, inflammasome, cardiomyocytes

Jianfen Shen,1 Youzhi Zhang,2 Hui Shen,1 Hua Pan,1 Longsheng Xu,1 Linna Yuan,1 Zhiying Ding1 1Department of Central Laboratory, The First Affiliated Hospital of Jiaxing University, Jiaxing 314000, China; 2School of Pharmacy, Hubei University of Science and Technology, Xianning 437100, China Objective: Breast cancer has been reported to be a serious disease and a threat to women’s health. 2,3,5,4'-Tetrahydroxystilbene-2-O-β-D-glucoside (THSG) is a bioactive natural compound originating from Polygonum multiflorum Thunb., which has been shown to possess anti-inflammatory and antitumor properties. Adriamycin (ADM) is a chemotherapy agent used in tumor therapy that is limited by its side effects. However, little is known about the synergistic effect of THSG combined with ADM on breast cancer. This study seeks to investigate the effects of the combination of THSG plus ADM on MCF-7 breast cancer cells and to test the mechanisms involved.Materials and methods: MTT assay was detected to determine cell viability. Furthermore, cell apoptosis was tested by flow cytometry and TUNEL assay. In addition, protein expression was measured by Western blot analysis.Results: The individual treatment of THSG and ADM induced cell injury. Moreover, cotreatment further increased it, which the effect may be associated with the elevation of the apoptotic-related protein expression such as Bax/Bcl-2 and cleaved caspase-3/caspase-3. Lastly, our results also show the reduction of vascular endothelial growth factor/phosphatidylinositol 3-kinase/Akt protein expression in the individual or synergistic treatment.Conclusion: Taken together, cotreatment of THSG and ADM may exert a synergistic reduction of cell injury via the inhibition of vascular endothelial growth factor/phosphatidylinositol 3-kinase/Akt pathway. Thus, THSG might possess potent anti-breast cancer effect with ADM. Keywords: THSG, ADM, synergistic effect, apoptosis, VEGF/PI3K/Akt, breast cancer

A surgeon describes a simple procedure to release an IOL haptic from the lens optic. [ABSTRACT FROM AUTHOR]

Purpose: Autologous serum tears (ASTs) are produced from serum obtained by blood draw and used to treat severe dry eye diseases. Multiple cases of failed AST production occurred due to serum becoming a solidified, gel-like substance after centrifugation. The aim of this study was to identify risk factors associated with inability to compound AST., Methods: From January 2019 to December 2022, 99 patients received AST produced at Mayo Clinic in Arizona. Patient demographics, medical diagnoses, medications, laboratory results, and events surrounding blood draws were obtained through an IRB-approved retrospective chart review. The laboratory and pharmacy protocol procedures were observed in person after the occurrence of the last production issue., Results: Ten total clotted serum episodes occurred in 4 patients, each with multiple occurrences. The indication for AST was chronic ocular graft-vs-host disease (n = 3) and Sjögren syndrome (n = 1). Eighty percent of episodes were associated with either a systemic infection (n = 7) or pulmonary embolism (n = 1) within the prior month. At the time of blood draw, all 4 patients were treated with antiplatelet and/or anticoagulation medications, including rivaroxaban, apixaban, aspirin, and low-molecular-weight heparin., Conclusions: The AST protocol was increased from 30 to 60 minutes of resting time to allow clotting before centrifugation. Inadequate clotting during this stasis period likely resulted in fibrinogen remaining suspended in the serum, leading to solidified plasma instead of liquid serum. We hypothesize risk of inadequate clotting would be increased in patients taking anticoagulation or antiplatelet medications. Our recommendations include ensuring 60-minute collection tube resting time for all patients, including those on anticoagulation medication., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To evaluate the published literature on the efficacy of amniotic membrane grafting (AMG) in the management of acute chemical and thermal ocular surface burns with respect to the rate of corneal re-epithelialization and improvement of visual acuity or corneal clarity., Methods: Literature searches were conducted in the PubMed database in May 2023 and updated in January 2024 and were limited to the English language without date restrictions. The searches yielded 474 citations; 58 were reviewed in full text, and 9 met the inclusion criteria. Four studies were rated level II, and 5 studies were rated level III. This assessment focuses on 3 level II articles that provided consistent primary and secondary outcomes but demonstrated suboptimal study design with respect to power calculations and lacked a priori sample-size calculations., Results: Amniotic membrane grafting significantly improved corneal re-epithelialization compared with medical therapy alone in eyes with moderate-grade burns. For severely burned eyes, AMG demonstrated no advantage over medical therapy. Additionally, AMG demonstrated no significant advantage over medical therapy for improved visual acuity or corneal clarity for moderate or severe ocular surface burns., Conclusions: The best available level II evidence suggests that AMG in the setting of acute ocular surface burns has efficacy in hastening re-epithelialization in moderate burns. As an adjuvant to medical therapy, it did not demonstrate a benefit in improving re-epithelialization in severe burns or visual acuity or corneal clarity in either moderate or severe burns., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To review the evidence on the safety and effectiveness of epithelium-off corneal collagen cross-linking (CXL) for the treatment of progressive corneal ectasia., Methods: A literature search of the PubMed database was most recently conducted in March 2024 with no date restrictions and limited to studies published in English. The search identified 359 citations that were reviewed in abstract form, and 43 of these were reviewed in full text. High-quality randomized clinical trials comparing epithelium-off CXL with conservative treatment in patients who have keratoconus (KCN) and post-refractive surgery ectasia were included. The panel deemed 6 articles to be of sufficient relevance for inclusion, and these were assessed for quality by the panel methodologist; 5 were rated level I, and 1 was rated level II. There were no level III studies., Results: This analysis includes 6 prospective, randomized controlled trials that evaluated the use of epithelium-off CXL to treat progressive KCN (5 studies) and post-laser refractive surgery ectasia (1 study), with a mean postoperative follow-up of 2.4 years (range, 1-5 years). All studies showed a decreased progression rate in treated patients compared with controls. Improvement in the maximum keratometry (Kmax) value, corrected distance visual acuity (CDVA), and uncorrected distance visual acuity (UDVA) was observed in the treatment groups compared with control groups. A decrease in corneal thickness was observed in both groups but was greater in the CXL group. Complications were rare., Conclusions: Epithelium-off CXL is effective in reducing the progression of KCN and post-laser refractive surgery ectasia in most treated patients with an acceptable safety profile., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objectives: The study compared the learning effectiveness and teaching satisfaction of dental students from three teaching methods (traditional, digital, and combined pedagogy) for instructing jaw relation recording and transferring (JRRT)., Methods: Note that, 276 fourth-year undergraduate students from three classes were randomly divided into three groups to study JRRT in complete dentures using different teaching methods: traditional pedagogy group, digital pedagogy group, and combined digital and traditional pedagogy group. After the course, the learning effectiveness of basic knowledge and satisfaction questionnaire was administered to the three groups of participants using a quick response code for online answering. The questionnaire was customized by the teacher based on the content delivered to each group., Results: The data were analyzed using the Chi-square test with Fisher's exact test. Both the digital and combined pedagogy groups showed a significant increase in basic knowledge test scores and higher satisfaction, compared to the traditional pedagogy group (p < 0.01). Particularly, the participants from combined pedagogy showed better teaching satisfaction than the digital pedagogy group (p < 0.001)., Conclusions: The use of digital technology in JRRT significantly enhanced students' learning effectiveness and teaching satisfaction., Clinical Significance: This educational innovation emphasizes digital technology to visualize vital concepts and operational intricacies related to JRRT. The findings have major implications for improving teaching methods in the field of prosthodontic dentistry., (© 2024 American Dental Education Association.)

Purpose: To review the published literature on the safety and outcomes of keratolimbal allograft (KLAL) transplantation and living-related conjunctival limbal allograft (lr-CLAL) transplantation for bilateral severe/total limbal stem cell deficiency (LSCD)., Methods: Literature searches were last conducted in the PubMed database in February 2023 and were limited to the English language. They yielded 523 citations; 76 were reviewed in full text, and 21 met the inclusion criteria. Two studies were rated level II, and the remaining 19 studies were rated level III. There were no level I studies., Results: After KLAL surgery, best-corrected visual acuity (BCVA) improved in 42% to 92% of eyes at final follow-up (range, 12-95 months). The BCVA was unchanged in 17% to 39% of eyes and decreased in 8% to 29% of eyes. Two of 14 studies that evaluated the results of KLAL reported a notable decline in visual acuity over time postoperatively. Survival of KLAL was variable, ranging from 21% to 90% at last follow-up (range, 12-95 months) and decreased over time. For patients undergoing lr-CLAL surgery, BCVA improved in 31% to 100% of eyes at final follow-up (range, 16-49 months). Of the 9 studies evaluating lr-CLAL, 4 reported BCVA unchanged in 30% to 39% of patients, and 3 reported a decline in BCVA in 8% to 10% of patients. The survival rate of lr-CLAL ranged from 50% to 100% at final follow-up (range, 16-49 months). The most common complications were postoperative elevation of intraocular pressure, persistent epithelial defects, and acute allograft immune rejections., Conclusions: Given limited options for patients with bilateral LSCD, both KLAL and lr-CLAL are viable choices that may provide improvement of vision and ocular surface findings. The studies trend toward a lower rejection rate and graft failure with lr-CLAL. However, the level and duration of immunosuppression vary widely between the studies and may impact allograft rejections and long-term graft survival. Complications related to immunosuppression are minimal. Repeat surgery may be needed to maintain a viable ocular surface. Reasonable long-term success can be achieved with both KLAL and lr-CLAL with appropriate systemic immunosuppression., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Temporomandibular joint inflammatory diseases are a significant subtype of temporomandibular disorders (TMD) characterized by inflammatory pain in the orofacial area. The N-methyl-D-aspartate receptor (NMDAR), specifically the NR2A subtype, was crucial in neuropathic pain. However, the exact role of NR2A in inflammatory pain in the TMJ and the molecular and cellular mechanisms mediating peripheral sensitization in the trigeminal ganglion (TG) remain unclear. This study utilized male and female mice to induce the TMJOA model by injecting Complete Freund's adjuvant (CFA) into the TMJ and achieve conditional knockout (CKO) of NR2A in the TG using Cre/Loxp technology. The Von-Frey filament test results showed that CFA-induced orofacial pain with reduced mechanical withdrawal threshold (MWT), which was not developed in NR2A CKO mice. Additionally, the up-regulation of interleukin (IL)-1β, IL-6, and nerve growth factor (NGF) in the TG induced by CFA did not occur by NR2A deficiency. In vitro, NMDA activated satellite glial cells (SGCs) with high expression of glial fibrillary acidic protein (GFAP), and both NMDA and LPS led to increased IL-1β, IL-6, and NGF in SGCs. NR2A deficiency reduced these stimulating effects of NMDA and LPS. The regulation of IL-1β involved the p38, Protein Kinase A (PKA), and Protein Kinase C (PKC) pathways, while IL-6 signaling relied on PKA and PKC pathways. NGF regulation was primarily through the p38 pathway. This study highlighted NR2A's crucial role in the TG peripheral sensitization during TMJ inflammation by mediating ILs and NGF, suggesting potential targets for orofacial inflammatory pain management., Competing Interests: Declaration of competing interest We confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The involvement of inwardly rectifying potassium channel 4.1 (Kir4.1) in neuropathic pain has been established. However, there is limited understanding of the downstream mechanism through which Kir4.1 contributes to orofacial neuropathic pain. The objective of this study was to examine the regulation of Kir4.1 on the expression of pannexin 3 (Panx3) in the trigeminal ganglion (TG) and the underlying mechanism in the context of orofacial neuropathic pain caused by chronic constriction injury of the infraorbital nerve (CCI-ION). The study observed a significant increase in Panx3 expression in the TG of mice with CCI-ION. Inhibition of Panx3 in the TG of CCI-ION mice resulted in alleviation of orofacial mechanical allodynia. Furthermore, conditional knockdown (CKD) of Kir4.1 in the TG of both male and female mice led to mechanical allodynia and upregulation of Panx3 expression. Conversely, overexpression of Kir4.1 decreased Panx3 levels in the TG and relieved mechanical allodynia in CCI-ION mice. In addition, silencing Kir4.1 in satellite glial cells (SGCs) decreased Panx3 expression and increased the phosphorylation of P38 MAPK. Moreover, silencing Kir4.1 in SGCs increased the levels of reactive oxygen species (ROS). The elevated phosphorylation of P38 MAPK resulting from Kir4.1 silencing was inhibited by using a superoxide scavenger known as the tempol. Silencing Panx3 in the TG in vivo attenuated the mechanical allodynia caused by Kir4.1 CKD. In conclusion, these findings suggest that the reduction of Kir4.1 promotes the expression of Panx3 by activating the ROS-P38 MAPK signalling pathway, thus contributing to the development of orofacial neuropathic pain., (© 2024 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Temporomandibular joint osteoarthritis (TMJOA) is a severe form of temporomandibular joint disorders (TMD), and orofacial inflammatory allodynia is one of its common symptoms which lacks effective treatment. N-methyl-D-aspartate receptor (NMDAR), particularly its subtypes GluN2A and GluN2B, along with gap junctions (GJs), are key players in the mediation of inflammatory pain. However, the precise regulatory mechanisms of GluN2A, GluN2B, and GJs in orofacial inflammatory allodynia during TMJ inflammation still remain unclear. Here, we established the TMJ inflammation model by injecting Complete Freund's adjuvant (CFA) into the TMJ and used Cre/loxp site-specific recombination system to conditionally knock out (CKO) GluN2A and GluN2B in the trigeminal ganglion (TG). Von-frey test results indicated that CFA-induced mechanical allodynia in the TMJ region was relieved in GluN2A and GluN2B deficient mice. In vivo, CFA significantly up-regulated the expression of GluN2A and GluN2B, Gjb1, Gjb2, Gjc2 and Panx3 in the TG, and GluN2A and GluN2B CKO played different roles in mediating the expression of Gjb1, Gjb2, Gjc2 and Panx3. In vitro, NMDA up-regulated the expression of Gjb1, Gjb2, Gjc2 and Panx3 in satellite glial cells (SGCs) as well as promoted the intercellular communication between SGCs, and GluN2A and GluN2B knocking down (KD) altered the expression and function differently. NMDAR regulated Gjb1 and Panx3 through ERK1/2 pathway, and mediated Gjb2 and Gjc2 through MAPK, PKA, and PKC intracellular signaling pathways. These findings shed light on the distinct functions of GluN2A and GluN2B in mediating peripheral sensitization induced by TMJ inflammation in the TG, offering potential therapeutic targets for managing orofacial inflammatory allodynia., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: In prosthodontic procedures, traditional computer-aided design (CAD) is often time-consuming and lacks accuracy in shape restoration. In this study, we combined implicit template and deep learning (DL) to construct a precise neural network for personalized tooth defect restoration., Methods: Ninety models of right maxillary central incisor (80 for training, 10 for validation) were collected. A DL model named ToothDIT was trained to establish an implicit template and a neural network capable of predicting unique identifications. In the validation stage, teeth in validation set were processed into corner, incisive, and medium defects. The defective teeth were inputted into ToothDIT to predict the unique identification, which actuated the deformation of the implicit template to generate the highly customized template (DIT) for the target tooth. Morphological restorations were executed with templates from template shape library (TSL), average tooth template (ATT), and DIT in Exocad (GmbH, Germany). RMS estimate , width, length, aspect ratio, incisal edge curvature, incisive end retraction, and guiding inclination were introduced to assess the restorative accuracy. Statistical analysis was conducted using two-way ANOVA and paired t-test for overall and detailed differences., Results: DIT displayed significantly smaller RMS estimate than TSL and ATT. In 2D detailed analysis, DIT exhibited significantly less deviations from the natural teeth compared to TSL and ATT., Conclusion: The proposed DL model successfully reconstructed the morphology of anterior teeth with various degrees of defects and achieved satisfactory accuracy. This approach provides a more reliable reference for prostheses design, resulting in enhanced accuracy in morphological restoration., Clinical Significance: This DL model holds promise in assisting dentists and technicians in obtaining morphology templates that closely resemble the original shape of the defective teeth. These customized templates serve as a foundation for enhancing the efficiency and precision of digital restorative design for defective teeth., Competing Interests: Declaration of competing interest The authors declared no potential conflicts of interest with respect to the research, author-ship, and publication of this article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: To evaluate the influence of intraoral scanning coverage (IOSC) on digital implant impression accuracy in various partially edentulous situations and predict the optimal IOSC., Methods: Five types of resin models were fabricated, each simulating single or multiple tooth loss scenarios with inserted implants and scan bodies. IOSC was subgrouped to cover two, four, six, eight, ten, and twelve teeth, as well as full arch. Each group underwent ten scans. A desktop scanner served as the reference. Accuracy was evaluated by measuring the Root mean square error (RMSE) values of scan bodies. A convolutional neural network (CNN) was trained to predict the optimal IOSC with different edentulous situations. Statistical analysis was performed using one-way ANOVA and Tukey's test., Results: For single-tooth-missing situations, in anterior sites, significantly better accuracy was observed in groups with IOSC ranging from four teeth to full arch (p < 0.05). In premolar sites, IOSC spanning four to six teeth were more accurate (p < 0.05), while in molar sites, groups with IOSC encompassing two to eight teeth exhibited better accuracy (p < 0.05). For multiple-teeth-missing situations, IOSC covering four, six, and eight teeth, as well as full arch showed better accuracy in anterior gaps (p < 0.05). In posterior gaps, IOSC of two, four, six or eight teeth were more accurate (p < 0.05). The CNN predicted distinct optimal IOSC for different edentulous scenarios., Conclusions: Implant impression accuracy can be significantly impacted by IOSC in different partially edentulous situations. The selection of IOSC should be customized to the specific dentition defect condition., Clinical Significance: The number of teeth scanned can significantly affect digital implant impression accuracy. For missing single or four anterior teeth, scan at least four or six neighboring teeth is acceptable. In lateral cases, two neighboring teeth may suffice, but extending over ten teeth, including contralateral side, might deteriorate the scan., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: In the United States, the ZIP Code has long been used to collect geospatial data revealing disparities in social determinants of health. This cross-sectional study examines the distribution of eye care access in association with local socioeconomic factors at a ZIP Code level., Methods: Data from the 2020 Centers of Medicare and Medicaid Services and American Community Survey were used to examine locations of 47,949 providers (17,631 ophthalmologists and 30,318 optometrists) and corresponding local socioeconomic variables (education, employment, and income). Multivariable zero-inflated negative binomial regression was used to model eye care provider count per capita in each ZIP Code area with socioeconomic factors as independent covariates., Results: For every 1% increase in percentage of population over 25 years with a bachelor's degree or higher, the expected number of providers increases by 4.4% (incidence rate ratio [IRR] = 1.044; 95% confidence interval [CI], 1.041-1.046; P < 0.001). For every 1% increase in percentage unemployment, the expected number of providers decreases by 2.7% (IRR = 0.973; 95% CI, 0.964-0.983; P < 0.001). However, for every $1000 increase in median household income, the expected number of providers decreases by 1.6% (IRR = 0.984; 95% CI, 0.983-0.986; P < 0.001)., Conclusions: Disparities in access exist in areas of lower employment and educational attainment, as both have positive correlations with eye care provider access. Conversely, areas of greater median household income have lower access to providers., Translational Relevance: This research contributes to a greater field studying social determinants of health and may inform public health strategies on allocation of providers to improve equitable access to vision care.

Purpose: To review the published literature on the diagnostic capabilities of the newest generation of corneal imaging devices for the identification of keratoconus., Methods: Corneal imaging devices studied included tomographic platforms (Scheimpflug photography, OCT) and functional biomechanical devices (imaging an air impulse on the cornea). A literature search in the PubMed database for English language studies was last conducted in February 2023. The search yielded 469 citations, which were reviewed in abstract form. Of these, 147 were relevant to the assessment objectives and underwent full-text review. Forty-five articles met the criteria for inclusion and were assigned a level of evidence rating by the panel methodologist. Twenty-six articles were rated level II, and 19 articles were rated level III. There were no level I evidence studies of corneal imaging for the diagnosis of keratoconus found in the literature. To provide a common cross-study outcome measure, diagnostic sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were extracted. (A perfect diagnostic test that identifies all cases properly has an AUC of 1.0.) RESULTS: For the detection of keratoconus, sensitivities for all devices and parameters (e.g., anterior or posterior corneal curvature, corneal thickness) ranged from 65% to 100%. The majority of studies and parameters had sensitivities greater than 90%. The AUCs ranged from 0.82 to 1.00, with the majority greater than 0.90. Combined indices that integrated multiple parameters had an AUC in the mid-0.90 range. Keratoconus suspect detection performance was lower with AUCs ranging from 0.66 to 0.99, but most devices and parameters had sensitivities less than 90%., Conclusions: Modern corneal imaging devices provide improved characterization of the cornea and are accurate in detecting keratoconus with high AUCs ranging from 0.82 to 1.00. The detection of keratoconus suspects is less accurate with AUCs ranging from 0.66 to 0.99. Parameters based on single anatomic locations had a wide range of AUCs. Studies with combined indices using more data and parameters consistently reported high AUCs., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To review the literature to determine the efficacy and safety of thermal pulsation technologies in improving signs or symptoms of meibomian gland dysfunction (MGD) and dry eye compared with no therapy or with conventional warm compress therapy or eyelid hygiene., Methods: A literature search was conducted in the PubMed database in June 2022 and again in March 2023 to identify all studies in the English language on the use of thermal pulsation to treat MGD or dry eye. The search yielded 59 citations, and 11 articles met all of the inclusion criteria. The panel methodologist then assigned a level of evidence rating for each study; 8 studies were rated level I evidence and 3 studies were rated level II evidence., Results: All included studies evaluated a single 12-minute session using the LipiFlow automated thermal pulsation system (TearScience, Inc, or Johnson & Johnson). Improvements were detected in subjective and objective metrics of MGD or dry eye in patients within 1 to 12 months of thermal pulsation treatment compared with nontreatment. Most of the studies (9/11) reported greater efficacy with thermal pulsation than with standard warm compress therapy and eyelid hygiene. Four of these studies showed relevant industry conflicts of interest. Two of the 4 level I studies without direct industry participation concluded that thermal pulsation treatment was not significantly different from conventional hygiene or warm compress therapy control treatments (in symptoms in one of the studies and in objective findings in the second study). No serious adverse events were reported in any of the 11 studies., Conclusions: According to the current literature, a single thermal pulsation session may improve subjective or objective parameters of MGD and dry eye safely. However, industry support and participation were present in 4 of the 8 level I studies. The durability beyond several months and cost efficacy remain uncertain. Because the inclusion parameters of this assessment captured only the LipiFlow system, the conclusions are limited to that product. High-quality independent studies are needed to assess the long-term benefits of this intervention., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

The α-amino-3-hydroxy-5-methylisoxazole-4-isoxazolepropionic acid receptor (AMPAR) has been recognized to play a vital role in the development of neuropathic pain. Recent studies have indicated that protein kinase C (PKC) and protein interacting with C-kinase 1 (PICK1) are involved in the phosphorylation of AMPARs. However, whether PKC and PICK1 were involved in the AMPAR phosphorylation in the trigeminal ganglion (TG) to participate in orofacial neuropathic pain remains enigmatic. A behavioral test was utilized to evaluate the head withdrawal threshold (HWT) after chronic constriction injury of the infraorbital nerve (CCI-ION). The distribution and expression of GluA1, GluA2, PKC, and PICK1 were examined in the trigeminal ganglion (TG) by immunofluorescence, real-time reverse transcription-quantitative polymerase chain reaction, immunoblotting, and co-immunoprecipitation. Intra-ganglionic injections of drugs were performed to investigate the regulation mechanism. The present study demonstrated that CCI-ION-induced mechanical allodynia was maintained over at least 21 days. GluA1 and GluA2 were mainly expressed in the neurons. Trigeminal nerve injury potentiated the phosphorylation of GluA1, GluA2, and PKC in the TG, which was prevented by inhibiting PKC with chelerythrine chloride. Additionally, PICK1 colocalized and interacted with GluA2 in the TG. Following blocking PICK1 with FSC-231, the phosphorylation of GluA2 decreased. Finally, inhibition of PKC and PICK1 both alleviated mechanical allodynia in the whisker pad of CCI-ION mice. In conclusion, activation of PKC and PICK1 contribute to orofacial allodynia by regulating AMPAR phosphorylation in the TG of male mice, which provides potential therapeutic targets for alleviating orofacial neuropathic pain., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Preoperative immunotherapy has shed light on the management of resectable non-small cell lung cancer (NSCLC). However, whether neoadjuvant immunotherapy benefits patients with oncogene-positive NSCLC remains unknown., Methods: Data were retrieved from 4 institutions in the period from August 2018 to May 2021. Eligible patients were aged ≥18 years with histologically confirmed stage IIA to stage IIIB (T1-2 N1-2 or T3-4 N0-2) NSCLC that was deemed to be surgically resectable. The neoadjuvant regimen included immune checkpoint inhibitors alone or in combination with platinum-based doublets. Surgical resection was performed 4 to 6 weeks after the first day of the last cycle of treatment. The primary end point was major pathologic response (MPR; ≤10% viable tumor cells). Analyses were categorized according to the patients' oncogene (EGFR, ALK, KRAS, MET, BRAF, ROS1, RET) status., Results: Overall, 137 patients were identified; 46 (33%) patients had nonsquamous cell cancer, and 114 (83%) had stage IIIA/B disease. Oncogene alterations were identified in 22 (16%) patients, of whom only 2 patients (2/22 [9%]) had an MPR compared with 65 (65/115 [56.5%]) in the oncogene-negative population (P < .001). Similar results were retained after propensity score matching for age, sex, smoking status, histologic type, stage, and cycles of neoadjuvant treatment. Squamous cell carcinoma (odds ratio, 2.54; 95% CI, 1.08-5.99) and positive oncogene status (odds ratio, 0.13; 95% CI, 0.03-0.64) were found to be indicators for MPR by logistic regression. The 1-year event-free survival rate was 75.4% in the oncogene-positive group, which was not significantly different from 85.5% in the oncogene-negative population (P = .23)., Conclusions: Patients with stage II-III oncogene-positive NSCLCs respond less than patients with oncogene-negative NSCLCs after neoadjuvant immunotherapy., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Inward-rectifying K + channel 4.1 (Kir4.1), which regulates the electrophysiological properties of neurons and glia by affecting K + homeostasis, plays a critical role in neuropathic pain. Metabotropic glutamate receptor 5 (mGluR5) regulates the expression of Kir4.1 in retinal Müller cells. However, the role of Kir4.1 and its expressional regulatory mechanisms underlying orofacial ectopic allodynia remain unclear. This study aimed to investigate the biological roles of Kir4.1 and mGluR5 in the trigeminal ganglion (TG) in orofacial ectopic mechanical allodynia and the role of mGluR5 in Kir4.1 regulation. An animal model of nerve injury was established via inferior alveolar nerve transection (IANX) in male C57BL/6J mice. Behavioral tests indicated that mechanical allodynia in the ipsilateral whisker pad lasted at least 14 days after IANX surgery and was alleviated by the overexpression of Kir4.1 in the TG, as well as intraganglionic injection of an mGluR5 antagonist (MPEP hydrochloride) or a protein kinase C (PKC) inhibitor (chelerythrine chloride); Conditional knockdown of the Kir4.1 gene downregulated mechanical thresholds in the whisker pad. Double immunostaining revealed that Kir4.1 and mGluR5 were co-expressed in satellite glial cells in the TG. IANX downregulated Kir4.1 and upregulated mGluR5 and phosphorylated PKC (p-PKC) in the TG; Inhibition of mGluR5 reversed the changes in Kir4.1 and p-PKC that were induced by IANX; Inhibition of PKC activation reversed the downregulation of Kir4.1 expression caused by IANX (p < .05). In conclusion, activation of mGluR5 in the TG after IANX contributed to orofacial ectopic mechanical allodynia by suppressing Kir4.1 via the PKC signaling pathway., (© 2023 Wiley Periodicals LLC.)

Impairments of translating emotional salience into effortful behavior are core features of anhedonia in cohorts with major depressive disorder. Glutamate metabolism is considered to be involved in this process, but the empirical study is relatively few. Therefore, the present study aimed to examine the correlations between glutamate level in pregenual anterior cingulate, anhedonia, and emotion-behavior decoupling in patients with major depressive disorder. Fifteen individuals diagnosed with major depressive disorder and ten healthy individuals were recruited. All participants were asked to complete self-report instruments for anhedonia and the computerized anticipatory and consummatory pleasure task, and the in vivo glutamate levels were measured by proton magnetic resonance spectroscopy. Thus, a potential lower glutamate levels in pregenual anterior cingulate in individuals with major depressive disorder were founded to be positively correlated with the ability of pleasure experiencing. The mechanism of glutamate in pregenual anterior cingulate in anhedonia in patients with major depressive disorder may be reflected in the early pleasurable experience stage, rather than in the transformation of emotional experience to motivation or reward-seeking behavior, which may be different from that in schizophrenia., Competing Interests: Declaration of interest All authors declare no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The spinal N-methyl-d-aspartate receptor (NMDAR), particularly their subtypes NR2A and NR2B, plays pivotal roles in neuropathic and inflammatory pain. However, the roles of NR2A and NR2B in orofacial pain and the exact molecular and cellular mechanisms mediating nervous system sensitization are still poorly understood. Here, we exhaustively assessed the regulatory effect of NMDAR in mediating peripheral and central sensitization in orofacial neuropathic pain. Von-Frey filament tests showed that the inferior alveolar nerve transection (IANX) induced ectopic allodynia behavior in the whisker pad of mice. Interestingly, mechanical allodynia was reversed in mice lacking NR2A and NR2B. IANX also promoted the production of peripheral sensitization-related molecules, such as interleukin (IL)-1β, tumor necrosis factor (TNF)-α, brain-derived neurotrophic factor (BDNF), and chemokine upregulation (CC motif) ligand 2 (CCL2), and decreased the inward potassium channel (Kir) 4.1 on glial cells in the trigeminal ganglion, but NR2A conditional knockout (CKO) mice prevented these alterations. In contrast, NR2B CKO only blocked the changes of Kir4.1, IL-1β, and TNF-α and further promoted the production of CCL2. Central sensitization-related c-fos, glial fibrillary acidic protein (GFAP), and ionized calcium-binding adaptor molecule 1 (Iba-1) were promoted and Kir4.1 was reduced in the spinal trigeminal caudate nucleus by IANX. Differential actions of NR2A and NR2B in mediating central sensitization were also observed. Silencing of NR2B was effective in reducing c-fos, GFAP, and Iba-1 but did not affect Kir4.1. In contrast, NR2A CKO only altered Iba-1 and Kir4.1 and further increased c-fos and GFAP. Gain-of-function and loss-of-function approaches provided insight into the differential roles of NR2A and NR2B in mediating peripheral and central nociceptive sensitization induced by IANX, which may be a fundamental basis for advancing knowledge of the neural mechanisms' reaction to nerve injury., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Peripheral and central sensitizations of the trigeminal nervous system are the main mechanisms to promote the development and maintenance of chronic orofacial pain characterized by allodynia, hyperalgesia, and ectopic pain after trigeminal nerve injury or inflammation. Although the pathomechanisms of chronic orofacial pain are complex and not well known, sufficient clinical and preclinical evidence supports the contribution of the N-methyl-D-aspartate receptors (NMDARs, a subclass of ionotropic glutamate receptors) to the trigeminal nociceptive signal processing pathway under various pathological conditions. NMDARs not only have been implicated as a potential mediator of pain-related neuroplasticity in the peripheral nervous system (PNS) but also mediate excitatory synaptic transmission and synaptic plasticity in the central nervous system (CNS). In this review, we focus on the pivotal roles and mechanisms of NMDARs in the trigeminal nervous system under orofacial neuropathic and inflammatory pain. In particular, we summarize the types, components, and distribution of NMDARs in the trigeminal nervous system. Besides, we discuss the regulatory roles of neuron-nonneuronal cell/neuron-neuron communication mediated by NMDARs in the peripheral mechanisms of chronic orofacial pain following neuropathic injury and inflammation. Furthermore, we review the functional roles and mechanisms of NMDARs in the ascending and descending circuits under orofacial neuropathic and inflammatory pain conditions, which contribute to the central sensitization. These findings are not only relevant to understanding the underlying mechanisms, but also shed new light on the targeted therapy of chronic orofacial pain., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Li, Fang, Liao, Zhang, Lin, Liu and Shen.)

Sacubitril valsartan (lcz696) has been demonstrated as a substitute for angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for the treatment of heart failure. This research is aimed at examining the effects of lcz696 and its target molecules on myocardial infarction (MI). A rat model of MI was induced by left anterior descending artery ligation and treated with lcz696. Lcz696 treatment significantly reduced cardiac injury and heart failure, restored the left ventricular fractional shortening and ejection fraction, and reduced oxidative stress and inflammatory responses in rat myocardium. By analyzing the heart failure-related GSE47495 dataset and performing gene ontology (GO) functional enrichment analysis, we obtained histone lysine methyltransferase SUV39H1 and secreted phosphoprotein 1 (SPP1) as two molecules implicated in the oxidative stress and inflammation processes. An elevation of SUV39H1 whereas a decline of SPP1 were detected in cardiac tissues after lcz696 treatment. Enrichments of SUV39H1 and H3K9me3 at the SPP1 promoter were identified by chromatin immunoprecipitation assay. SUV39H1 catalyzed H3K9me3 modification to suppress the expression of SPP1. Preconditioning of SUV39H1 silencing blocked the protective roles of lcz696, but SPP1 silencing alleviated the myocardial injury. In conclusion, this study demonstrates that lcz696 enhances cardiac function and alleviates MI in rats through a SUV39H1/SPP1 axis., Competing Interests: The authors declare that they have no conflicts of interests., (Copyright © 2022 Jian-Fen Shen et al.)

Purpose: To perform a retrospective characterization of one-star reviews of ophthalmologists on Yelp.com and to increase understanding of patient complaints on Yelp.com., Methods: A search was performed for reviews on Yelp.com using the keyword "ophthalmologist" for the top 8 most population-dense metropolitan areas in the United States. One-star reviews were collected and classified as procedural or nonprocedural. Complaints were also categorized as clinical, nonclinical, or both. Clinical complaints cited issues such as complications, reoperations, uncontrolled pain, misdiagnosis, unclear treatment plan, etc. Nonclinical complaints included comments such as physician bedside manner, other staff interpersonal manner, wait time, brevity of appointment time, etc., Results: 5,532 total reviews were assessed, of which 477 (9%) one-star reviews were included in the study for analysis. These reviews amounted to 1,120 distinct complaints. 287 (26%) were clinical in nature and 833 (74%) were nonclinical. Technical incompetence or error (50: 4%), unsatisfactory results (46: 4%), and complications (43: 4%) represented the most common clinical complaints while office staff interpersonal manner (182: 16%), wait time (174: 16%), and physician interpersonal manner (141: 13%) were the most common nonclinical complaints. Refractive surgery was the most frequently mentioned subspecialty (89: 8%). Patients undergoing an ophthalmic procedure (surgery, injection, etc.) wrote 64 reviews that resulted in 193 (17%) complaints. Nonprocedural patients wrote 413 reviews that resulted in 927 (83%) complaints. Compared with procedural reviews, nonprocedural reviews were less likely to include a clinical complaint (rate ratio, 0.3: P < .001)., Discussion: The majority of one-star reviews of ophthalmologists included in this study were nonclinical. Complaints referencing a procedural episode were more likely to include a clinical component in the review. In the era of intense medical consumerism and increased physician and health care institution competition for patient acquisition and retention, the characterization of excessively negative reviews allows identification of potential areas of concern for patients that use online review sites such as Yelp.com.

Neuropathic and inflammatory pain are major clinical challenges due to their ambiguous mechanisms and limited treatment approaches. N-methyl-D-aspartate receptor (NMDAR) and calcium-calmodulin-dependent protein kinase II (CaMKII) are responsible for nerve system sensation and are required for the induction and maintenance of pain. However, the roles of NMDAR and CaMKII in regulating orofacial pain are still less well known. Here, we established a neuropathic pain model by transecting a mouse inferior alveolar nerve (IAN) and an inflammatory pain model by injecting complete Freund ' s adjuvant (CFA) into its whisker pad. The Cre/loxp site-specific recombination system was used to conditionally knock out (KO) NR2B in the trigeminal ganglion (TG). Von Frey filament behavioral tests showed that IANX and CFA-induced mechanical allodynia were altered in NR2B-deficient mice. CFA upregulated CaMKIIα and CaMKIIβ in the mouse TG and spinal trigeminal caudate nucleus (SpVc). CaMKIIα first decreased and then increased in the TG after IANX, and CaMKIIβ decreased in the TG and SpVc. CFA and IANX both greatly enhanced the expression of phospho (p)-NR2B, p-CaMKII, cyclic adenosine monophosphate (cAMP), p-ERK, and p-cAMP response element binding protein (CREB) in the TG and SpVc. These neurochemical signal pathway alterations were reversed by the conditional KO of NR2B and inhibition of CaMKII. Similarly, IANX- and CFA-related behavioral alterations were reversed by intra-ganglionic (i.g.) -application of inhibitors of CaMKII, cAMP, and ERK. These findings revealed novel molecular signaling pathways (NR2B-CaMKII-cAMP-ERK-CREB) in the TG- and SpVc-derived latent subsequent peripheral and spinal central sensitization under nerve injury and inflammation, which might be beneficial for the treatment of orofacial allodynia., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Response inhibition, a crucial component of executive function, is closely related to personal impulse control, social adaption, and mental health. Previous studies have found response inhibition deficit in patients with major depressive disorder, but whether it also exists in individuals with subclinical depression (SD) remains unclear. This study aimed to identify the ability of response inhibition to emotional face stimuli both under explicit and implicit conditions in individuals with SD. Thirty-six subclinical depressed college students and 39 healthy individuals were recruited and administered the non-emotional, explicit, and implicit emotional stop-signal tasks (SSTs). Mixed-model analyses of variance were used to analyze the differences between and within groups. In implicit emotional SST, the results showed a significant longer stop-signal response time, a shorter stop-signal delay time, a shorter go reaction time, and a similar proportion of stop success in the SD group compared to healthy controls. However, the above indices showed no significant difference between the two groups in the non-emotional SST and explicit emotional SST. These findings suggest a possible defect of response inhibition in implicit emotional processing in individuals with SD, which may potentially serve as a marker of susceptibility to depression and thus be applied to early screening and intervention for major depressive disorder., (© 2022 Institute of Psychology, Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.)

Suicide is commonly found in patients with major depressive disorder (MDD), while the associations among depressive symptoms and their relationships with suicidal risk remain unclear. This study identified the symptoms associated with suicidal risk and the most central symptoms in the MDD networks based on both self-reported and clinical-interview scales. A total of 446 outpatients with MDD were recruited. The Mini International Neuropsychiatric Interview (MINI) was used to assess the suicidal risk. The 13-item Beck Depression Inventory (BDI-13) and 17-item Hamilton Depression Rating Scale (HAMD-17) were used to measure the depressive symptoms. Network analysis was used to estimate the network models. Ten symptoms in the BDI-13 network were related to suicidal risk, among which sadness had the strongest association. Among the six symptoms in the HAMD-17 network that were associated with suicidal risk, guilty feeling was the strongest. Sense of failure was the most central symptom in the BDI-13 network, while depressed mood had the highest centrality in the HAMD-17 network. The depressive symptoms related to suicide risk and the clinical features of MDD showed different characteristics based on different assessment types. Combining self-reported and clinician-rated assessments in future studies and clinical practice might lead to some new findings., (© 2021 Institute of Psychology, Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.)

Background: Orofacial ectopic pain induced by trigeminal nerve injury is a serious complication of dental treatment. C-X-C motif chemokine ligand 1 (CXCL1) and its primary receptor C-X-C motif chemokine receptor 2 (CXCR2) contribute to the development and maintenance of neuropathic pain in the spinal nervous system, but their roles in trigeminal neuropathic sensation are still poorly understood., Objectives: This study aimed to investigate the exact role of CXCL1 and CXCR2 in the regulation of orofacial ectopic mechanical allodynia and their potential downstream mechanisms in the trigeminal ganglion (TG)., Methods: The head withdrawal threshold (HWT) of C57BL/6 mice was evaluated after inferior alveolar nerve (IAN) transection (IANX). Then, the distribution and expression of CXCL1 and CXCR2, and their potential downstream mechanisms in the TG were further measured using immunohistochemistry, real-time reverse transcription-quantitative polymerase chain reaction and Western blotting. Moreover, the effect of SB225002 (an inhibitor of CXCR2) on mechanical allodynia was examined. The data were analysed using the Student's t test and a analysis of variance (ANOVA)., Results: IANX triggered persistent (>21 days) mechanical allodynia and upregulation of CXCL1 and CXCR2 in the TG. In addition, exogenous CXCL1 also lowered the HWT, which was alleviated by CXCR2 and protein kinase C (PKC) antagonists (p < .05). In addition, IANX increased the phosphorylated PKC (p-PKC) levels and decreased the expression of voltage-gated potassium channels (Kv), and these effects were reversed by inhibition of CXCR2 (p < .05)., Conclusion: Our results demonstrated that CXCR2 participated in orofacial ectopic mechanical allodynia via downregulation of Kv1.4 and Kv1.1 through the PKC signalling pathway. This mechanism may be a potential target in developing a treatment strategy for ectopic orofacial pain., (© 2021 John Wiley & Sons Ltd.)

Cattle temperament is an interesting trait due to its correlation with production efficiency, labor safety, and animal welfare. To date, however, its genetic basis is not clearly understood. Here, we performed a genome-wide association study for a series of temperament traits in cattle, assessed with via open field and novel object tests, using autosomal single nucleotide polymorphisms (SNPs) derived from the whole-genome sequence. We identified 37 and 29 genome-wide significant loci in the open field and novel object tests, respectively. Gene set analysis revealed the most significant pathway was the neuroactive ligand-receptor interaction pathway, which may be essential for emotional control in cattle. Analysis of the expression levels of 18 tissue-specific genes based on transcriptomic data showed enrichment in the brain, with some candidate genes involved in psychiatric and neurodegenerative diseases in humans. Based on principal component analysis, the first principal component explained the largest variance in the open field and novel object test data, and the most significant loci were assigned to SORCS3 and SESTD1 , respectively. Our findings should help facilitate cattle breeding for sound temperament by pyramiding favorable alleles to further improve cattle production.

The irradiance of powered polymerisation activators for chairside use affects composite resin adhesive curing during the restorative process, whereas radiant accumulated temperature rise relates to clinical safety. Irradiance reduction and high radiant accumulated temperature will compromise the treatment results as there is a lack of curing output efficacy and safety awareness for powered polymerisation activators. Insufficient attention has been paid to the activator's quality control, irradiance attenuation and radiant accumulated temperature excessive temperature rise during its lifetime. The present manuscript has been drafted by the Society of Dental Equipment, Chinese Stomatological Association to fill the quality control gap and guide the quality control process, following tested steps, using a metered radiometer and a thermometer to record the irradiance and radiant accumulated temperature separately. The testing result may indicate the equipment's situation in service and provide information about the irradiance values and performance of the powered polymerisation activator for its usage and maintenance.

Objective: To evaluate the influence of crown coverage of surgical guides on the accuracy of static computer-assisted implant surgeries (sCAISs) in different partially edentulous situations., Methods: Acrylic models with five types of partially edentulous situations were fabricated in this study. In coDiagnostiX software (Dental Wings, Montreal, Canada), surgical templates were designed and fabricated with reduced crown coverage (RCC), standard crown coverage (SCC) and extended crown coverage (ECC). Then, fully guided implant placement into the acrylic models was performed by dental surgeons with more than 10 years of experience. In total, 120 models and 120 guides were manufactured, and 168 bone-level Straumann replica implants (4.1 × 10 mm, Institut Straumann AG, Basel, Switzerland) were inserted. Postoperative implant positions were scanned (Trios 3, 3 shape, Copenhagen, Denmark) and compared with the preplanned virtual positions via coDiagnostiX (Dental Wings, Montreal, Canada). The angular, coronal and apical deviations were measured and analyzed to evaluate the accuracy of implant insertion. Statistical analysis was performed using one-way ANOVA and Tukey's test., Results: For single tooth missing situations, the RCC group was similar to the SCC group and ECC group in anterior sites. In premolar or molar sites, the SCC and ECC groups had no statistically significant difference (p > .05), while the RCC group had more coronal and apical deviation (p < .05). For multiple teeth missing situations, there was no difference among the RCC, SCC and ECC groups (p > .05). No difference was found among the five edentulous situations with different CCs (p > .05)., Conclusion: The CC of templates can significantly affect the accuracy of guided surgeries when implants are inserted in a single gap at posterior sites. Templates with CC extended to the undercut line may be an optimal choice for static guided surgeries., Clinical Significance: The accuracy of static guided implant surgery can be influenced by the CC of templates, and proper CC with the guide covering extending to the undercut line may contribute to improved accuracy. CC should be taken into consideration when designing surgical templates., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Ocular melanoma (OM) is a rare noncutaneous malignancy and consists of 2 different subtypes based on the anatomic location in the eye: uveal melanoma and conjunctival melanoma. Like cutaneous melanoma, OM benefits from nuclear medicine and molecular imaging in nodal staging and clinical management. Through the illustration of 2 distinctive cases, we aim to demonstrate the complementary roles of standard lymphoscintigraphy, advanced SPECT/CT, 18 F-FDG PET/CT, and 18 F-FDG PET/MRI in accurate nodal staging and surveillance of OM. We also review the epidemiology, existing staging guidelines, and management of uveal melanoma and conjunctival melanoma., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

The N-methyl-d-aspartate receptor (NMDAR) is a glutamate-gated receptor channel that plays a role in peripheral neuropathic pain. Src, a protein tyrosine kinase, can regulate the activation of NMDARs in chronic pain conditions. Pannexin 1 (Panx1), a plasma membrane channel, plays an important role in neuropathic pain and functionally interacts with NMDARs in the pathological condition of epilepsy. In this study, the roles of NMDAR1 (NR1), Src, and Panx1 and their interactions in the trigeminal ganglion (TG) in orofacial ectopic pain attributed to inferior alveolar nerve transection (IANX) were investigated. IANX induced mechanical allodynia in the whisker pad with increased expression levels of NR1, Src phosphorylation (p-Src), and Panx1 in the TG. Double immunostaining revealed that NR1, Src, and Panx1 all colocalized with glutamine synthetase (GS) and neuronal nuclei (NeuN), and they overlapped in the TG, suggesting that they might be structurally connected to one another. In addition, trigeminal injection of memantine, PP2, or 10 Panx attenuated IANX-induced mechanical allodynia in the whisker pad. Continuous intraganglionic administration of memantine (an antagonist of NMDAR) decreased IANX-induced upregulated expression of p-Src and Panx1. Similarly, PP2 (an inhibitor of Src) also decreased Panx1 protein expression but had no effect on NR1. In addition, intraganglionic injection of 10 Panx (a blocker of Panx1) decreased NR1 protein expression but did not affect Src. In general, our findings demonstrated that NR1, Src, and Panx1 all contributed to orofacial ectopic pain following IANX and that they composed a signalling pathway in the TG involved in mechanical allodynia., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 IBRO. Published by Elsevier Ltd. All rights reserved.)

Orofacial ectopic pain can often arise following nerve injury. However, the exact mechanism responsible for orofacial ectopic pain induced by trigeminal nerve injury remains unknown. The α2δ-1 and glutamate N-methyl-d-aspartic acid receptor (NMDAR) interactions have been demonstrated to participate in neuropathic pain regulation in the spinal cord. In this study, a rat model of inferior alveolar nerve transection (IANX) was used to investigate the role of α2δ-1-NMDAR1 interaction in the trigeminal ganglion (TG) in regard to the regulation of orofacial ectopic pain. Western blot (WB) analysis indicated that α2δ-1 and NMDAR1 in the TG were substantially higher in IANX rats than they were in sham/naive rats. Additionally, immunofluorescence (IF) results revealed that α2δ-1 and NMDAR1 were co-expressed and distributed within neurons and activated satellite glial cells in the TG. Co-immunoprecipitation (Co-IP) results indicated that α2δ-1-NMDAR1 complex levels in the TG were higher in IANX rats than they were in sham rats. Furthermore, the results of behavioral tests demonstrated that intra-TG injection of gabapentin (α2δ-1 inhibitory ligand) or memantine hydrochloride (NMDAR antagonist) reversed the decrease in mechanical head-withdrawal threshold (HWT) in IANX rats. Moreover, inhibition of α2δ-1 by intra-TG administration of gabapentin suppressed the upregulation of the NMDAR1 protein, and the inhibition of NMDAR by intra-TG administration of memantine hydrochloride inhibited the increased expression of α2δ-1 protein induced by IANX. In conclusion, the physical and functional interaction between α2δ-1 and NMDAR1 is critical for the development of orofacial ectopic pain, indicating that α2δ-1, NMDAR1, and the α2δ-1-NMDAR1 complex may represent potential targets for the treatment of orofacial ectopic pain., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Although metal nanoclusters (MNCs) have shown great promise for the further development of photochemical techniques to be applied in diverse areas (e.g., photoelectronic devices, photochemical sensors, photocatalysts, and energy storage and conversion systems), the fundamental problem of their electron transfer behavior still remains unsolved. Herein, a driving force-dependent photoinduced electron transfer process of gold nanoclusters (AuNCs) is clarified for the first time from a rational-designed opposite-charged system. It was found that the electron transfer dynamic of carboxylated chitosan and dithiothreitol-commodified AuNCs (CC/DTT-AuNCs) can be satisfactorily described by the Marcus electron transfer theory. This proved model was applied to estimate the ultrafast charge separation process between CC/DTT-AuNCs and mitoxantrone, which was confirmed by fluorescence quenching and femtosecond transient absorption spectroscopy measurements. We envision that this work will open a new door for understanding the electron transfer behavior of MNCs and facilitate the design of advanced optoelectronic devices.

This study explores the effects of oxytocin receptor (OXTR) in the trigeminal ganglion (TG) on orofacial neuropathic pain. We demonstrate that OXTR activation in the TG relieves the orofacial ectopic pain as well as inhibits the upregulated expression of calcitonin gene-related peptide (CGRP), IL-1β, and TNFα in the TG and spinal trigeminal nucleus caudalis (SpVc) of rats with inferior alveolar nerve transection. OXTR, a G protein-coupled receptor, has been demonstrated to play a significant role in analgesia after activation by its canonical agonist oxytocin (OXT) in the dorsal root ganglion. However, the role of OXTR in the trigeminal nervous system on the orofacial neuropathic pain is still little known. In the present study, we aimed to investigate the regulation effect and mechanism of OXTR in the TG) and SpVc) on orofacial ectopic pain induced by trigeminal nerve injury. The inferior alveolar nerve (IAN) was transected to establish a ectopic pain model. A behavioral test with electronic von Frey filament demonstrated IAN transection (IANX) evoked mechanical hypersensitivity in the whisker pad from day 1 to at least day 14 after surgery. In addition, administration of OXT (50 and 100 μM) into the TG attenuated the mechanical hypersensitivity induced by IANX, which was reversed by pretreatment with L-368,899 (a selective antagonist of OXTR) into the TG. In addition, immunofluorescence showed the expression of OXTR in neurons in the TG and SpVc. Furthermore, Western blot analysis indicated that the upregulated expression of OXTR, CGRP, IL-1β, and TNFα in the TG and SpVc after IANX was inhibited by the administration of OXT into the TG. And the inhibition effect of OXT on the expression of CGRP, IL-1β, and TNFα was abolished by preapplication of OXTR antagonist L-368,899 into the TG. NEW & NOTEWORTHY This study explores the effects of oxytocin receptor (OXTR) in the trigeminal ganglion (TG) on orofacial neuropathic pain. We demonstrate that OXTR activation in the TG relieves the orofacial ectopic pain as well as inhibits the upregulated expression of calcitonin gene-related peptide, IL-1β, and TNF-α in the TG and spinal trigeminal nucleus caudalis of rats with inferior alveolar nerve transection.

Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) play vital roles in the tumorigenesis of esophageal squamous cell carcinoma (ESCC). Nevertheless, the mechanism and regulatory network associated with this process remain largely unknown. In this study, we performed a comprehensive analysis of the expression of mRNAs, lncRNAs, and circRNAs by RNA-seq. A total of 3265 mRNAs, 1084 lncRNAs, and 38 circRNAs were found to be differentially expressed. Among these, 269 mRNAs were found to encode transcription factors (TFs). Functional enrichment analysis indicated that the dysregulated TFs are associated with the Hedgehog, Jak-STAT, TGF-beta, and MAPK signaling pathways. Furthermore, we constructed co-expression networks to screen the core lncRNAs and circRNAs involved in the regulation of transcription factors in these four pathways. Finally, we constructed a competing endogenous RNA (ceRNA) network of ESCC based on the abovementioned pathways. Our findings provide important insight into the role of lncRNAs and circRNAs in ESCC; the differentially expressed lncRNAs and circRNAs may represent potential targets for ESCC diagnosis and therapy.

In the spinal nervous system, the expression of galanin (GAL) and galanin receptors (GALRs) that play important roles in the transmission and modulation of nociceptive information can be affected by nerve injury. However, in the trigeminal nervous system, the effects of trigeminal nerve injury on the expression of GAL are controversy in the previous studies. Besides, little is known about the effects of trigeminal nerve injury on the expression of GALRs. In the present study, the effects of trigeminal nerve injury on the expression of GAL and GALRs in the rat trigeminal ganglion (TG) were investigated by using quantitative real-time reverse transcription-polymerase chain reaction and immunohistochemistry. To identify the nerve-injured and nerve-uninjured TG neurons, activating transcription factor 3 (ATF3, the nerve-injured neuron marker) was stained by immunofluorescence. The levels of GAL mRNA in the rostral half and caudal half of the TG dramatically increased after transection of infraorbital nerve (ION) and inferior alveolar nerve (IAN), respectively. Immunohistochemical labeling of GAL and ATF3 revealed that GAL level was elevated in both injured and adjacent uninjured small and medium-sized TG neurons after ION/IAN transection. In addition, the levels of GAL 2 R-like immunoreactivity were reduced in both injured and adjacent uninjured TG neurons after ION/IAN transection, while levels of GAL 1 R and GAL 3 R-like immunoreactivity remained unchanged. Furthermore, the number of small to medium-sized TG neurons co-expressing GAL- and GAL 1 R/GAL 2 R/GAL 3 R-like immunoreactivity was significantly increased after ION/IAN transection. In line with previous studies in other spinal neuron systems, these results suggest that GAL and GALRs play functional roles in orofacial neuropathic pain and trigeminal nerve regeneration after trigeminal nerve injury., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Three-dimensional computed tomography bronchography and angiography (3D-CTBA) is a powerful tool to analyze pulmonary anatomy. We used 3D-CTBA to analyze variations of the pulmonary veins of the left upper division (LUD) and created a simplified LUD vein model., Methods: Between January 2019 and October 2019, 124 patients with left-sided pulmonary lesions were admitted and underwent 3D-CTBA prior to surgery. We reviewed the anatomical variations of the LUD veins in these patients using 3D-CTBA images and classified them according to their position in relation to the bronchus. To facilitate this process, the same nomenclature as that used to describe the veins of the right upper lobe (RUL) is used for the LUD., Results: The pattern of LUD veins could be classified into three forms: an anterior + central form, an anterior form and a central form. For the central form, V 1+2 a, V 1+2 b, V 1+2 c and V 1+2 d drained into V. cent. For the anterior form, V 1+2 d drained into V. ant. The anterior + central form could be further classified into three subtypes (V abc, V ab and V a)., Conclusions: This is the first report to categorize the pattern of veins in the LUD. This may facilitate the creation of simplified models for use in pre-operative planning for segmentectomy., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-6925). The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

Objective: To investigate the recurrence and influencing factors of diabetic foot ulcer in patients with type 2 diabetes mellitus. Methods: Totally 185 type 2 diabetes patients with new-onset of diabetic foot ulcers admitted to Fuyang People's Hospital of Anhui Province from January 2011 to December 2015 were enrolled in this study, including 120 males and 65 females, aged 40-79 years. All the patients were followed up for 3 years, and their clinical data were retrospectively analyzed by the case-control study. The Kaplan-Meier cumulative recurrence curve was drawn according to the 3-year cumulative recurrence rate of diabetic foot ulcers. The time to visit, toe involvement, and amputation of involved toes in patients with recurrent diabetic foot ulcer were counted at the initial onset and the recurrence of the ulcers, respectively, and the data were statistically analyzed with t test and chi-square test. According to the recurrence of diabetic foot ulcers, the patients were divided into foot ulcer recurrence group and foot ulcer non-recurrence group. The gender, age, course of diabetes mellitus, length of hospital stay, visit time, body mass index, glycosylated hemoglobin HbA1c, total bilirubin, albumin, creatinine, cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), triglycerides, hemoglobin, white blood cell count, toe involvement, toe amputation, ankle-brachial index, diabetic retinopathy (DR), diabetic peripheral neuropathy (DPN), diabetic nephropathy (DN), history of hypertension, cardio-cerebrovascular disease, smoking, residence, solitary life, and walking disorder of patients between the two groups were compared, and the data were statistically analyzed with t test and chi-square test. Log-rank test was performed on the indexes with P <0.1 in comparison between two groups, and the indexes with statistically significant differences in Log-rank test were analyzed by multivariate Cox regression analysis to screen the influencing factors of recurrence of diabetic foot ulcer. Results: (1) The 3-year cumulative recurrence rate of diabetic foot ulcers in 185 patients with type 2 diabetes mellitus was 47.0% (87/185). (2) For 87 patients with diabetic foot ulcer recurrence, compared with that at the initial onset of the ulcers, the visit time was significantly shorter ( t =10.593, P <0.01), the toe amputation rate was significantly increased ( χ (2)=5.118, P <0.05), but there was no obvious change in toe involvement at the recurrence of the ulcers. (3) There were statistically significant differences in age, course of diabetes mellitus, length of hospital stay, body mass index, glycosylated hemoglobin HbA1c, total bilirubin, albumin, creatinine, cholesterol, LDL, HDL, hemoglobin, white blood cell count, gender, toe amputation, ankle-brachial index, DR, history of cardio-cerebrovascular disease, solitary life, and walking disorder of patients between foot ulcer recurrence group (87 patients) and foot ulcer non-recurrence group (98 patients) ( t =5.123, 4.242, 5.324, -24.572, 6.102, -1.984, -9.747, 3.226, 3.076, 3.646, -4.683, -7.502, 8.095, χ (2)=5.621, 18.433, 4.546, 5.785, 9.655, 7.625, 7.886, P <0.05 or P <0.01), while the rest of the indexes of patients between the two groups were similar. Log-rank test showed that the two groups had statistically significant differences in age, course of diabetes mellitus, length of hospital stay, glycosylated hemoglobin HbA1c, total bilirubin, albumin, creatinine, ankle-brachial index, DPN, and walking disorder ( χ (2)=210.046, 44.837, 34.107, 98.685, 66.532, 294.451, 260.554, 5.012, 6.818, 11.160, P <0.05 or P <0.01). Age, total bilirubin, albumin, DPN, and walking disorder were the influencing factors for the recurrence of diabetic foot ulcers in patients with type 2 diabetes mellitus (hazard ratio=1.024, 0.678, 0.849, 2.335, 4.099, 95% confidence interval=1.001-1.047, 0.558-0.823, 0.797-0.904, 1.280-4.258, 2.044-8.223, P <0.05 or P <0.01). Conclusions: The 3-year cumulative recurrence rate of diabetic foot ulcers in patients with type 2 diabetes mellitus is relatively high, with the influencing factors being age, total bilirubin, albumin, DPN, and walking disorder.

Purpose: To review the published literature on the visual acuity results and complications of different surgical techniques for intraocular lens (IOL) implantation in the absence of zonular support., Methods: Peer-reviewed literature searches were conducted last in PubMed and the Cochrane Library in July 2019. The searches yielded 734 citations of articles published in English. The panel reviewed the abstracts of these mostly retrospective case series studies, and 45 were determined to be relevant to the assessment objectives. Three articles were rated as level II evidence, and 42 articles were rated as level III evidence., Results: Eight different types of IOL fixation techniques with at least 6-month follow-up were evaluated: anterior chamber IOL (ACIOL), iris-claw IOL, retropupillary iris-claw IOL, 10-0 polypropylene iris-sutured posterior chamber IOL (PCIOL), 10-0 polypropylene scleral-sutured PCIOL, 8-0 polypropylene scleral-sutured PCIOL, CV-8 polytetrafluoroethylene, and intrascleral haptic fixation (ISHF). Eight articles reported data comparing 2 techniques. The 45 studies had insufficient statistical power to compare the techniques conclusively. A qualitative analysis of similar types showed that trends in visual acuity outcomes were not inferior to those of ACIOL implantation, but the severity of preoperative pathologic features was not controlled for. Compared with ACIOL, complications of cystoid macular edema were higher in 10-0 polypropylene iris-sutured PCIOL and 8-0 polypropylene scleral-sutured PCIOL. Non-anterior chamber IOL techniques were less likely to report chronic uveitis. Chronic glaucoma was highest in the 8-0 polypropylene scleral-sutured PCIOL group. Although retinal detachment was infrequent overall, it was twice as common in both iris- and scleral-sutured PCIOLs (except CV-8 polytetrafluoroethylene suture) compared with nonsutured methods: ACIOL, iris-clipped IOL, and ISHF PCIOL., Conclusions: The evidence reviewed shows no superiority of any single IOL implantation technique in the absence of zonular support. The various techniques seem to have equivalent visual acuity outcomes and safety profiles. Each technique has its own profile of inherent risk of postoperative complications. Surgeons must educate patients on the importance of close, long-term follow-up as a result of the uncertain nature of these techniques. Large prospective studies are needed to confirm the long-term complication profiles of these various IOL implantation techniques., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To explore the method and effect of small incision TightRope fixation in the treatment of fresh acromioclavicular joint dislocation., Methods: From January 2016 to May 2018, 28 cases of fresh acromioclavicular dislocation were treated, including 20 males and 8 females, aged 26 to 87 years with an average age of 51.3 years. The modified Rockwood classification included 1 case of typeⅡ, 22 cases of typeⅢand 4 cases of type V. The average time from injury to operation was 2.4 days. The operative time, shoulder function recovery time and postoperative complications were recorded, and the immediate reduction effect and Karlsson function of shoulder joint were evaluated., Results: In 28 patients, only one Rockwood typeⅡ was used to reconstruct the pyramidal ligament, and the other 27 were used to reconstruct the pyramidal ligament and the trapezoid ligament. The average operation time was (66.50±12.62) min (including intraoperative fluoroscopy time). Twenty-eight cases were followed up for 11 to 20 (16.7±4.6) months. The recovery time of shoulder function was 2 to 7 months with an average of 4 months. During the follow-up period, 1 case had osteolysis and loss of reduction at the clavicular plate site, and the rest had no complications such as re-dislocation and button plate prolapse. Immediate reduction effect after operation:6 cases with reduction insufficiency, 17 cases with complete reduction and 5 cases with excessive reduction;Karlsson function evaluation of shoulder joint in the last follow-up:excellent in 21 cases, good in 6 cases and poor in 1 case;Pearson analysis r =0.060, suggesting that the immediate reduction effect of fresh acromioclavicular dislocation operation has no significant correlation with Karlsson function evaluationof shoulder joint in the last follow-up., Conclusion: TightRope fixation through a small incision in the base of coracoid process is a simple and effective method for the treatment of dislocation of acromioclavicular joint. There was no significant correlation between the slight difference of immediate reduction effect within 5 mm and Karlsson function evaluation of shoulder joint in the last follow-up. It is suggested to pay attention to the loss of reduction and osteolysis of clavicular plate in clinical follow-up.