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Ling-bin Shu,1,* Qun Lu,2,* Ren-hua Sun,3 Le-qing Lin,4 Qiao-ling Sun,1 Jie Hu,1 Hong-wei Zhou,1 Edward Wai-Chi Chan,5,6 Sheng Chen,5,6 Rong Zhang11Department of Clinical Laboratory Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China; 2Department of Hospital Infection Management, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China; 3Department of Critical Care Medicine, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, China; 4Department of Intensive Care Unit, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China; 5Shenzhen Key Lab for Food Biological Safety Control, Food Safety and Technology Research Center, Hong Kong PolyU Shen Zhen Research Institute, Shenzhen, China; 6State Key Lab of Chirosciences, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong *These authors contributed equally to this work Objective: To understand the prevalence and transmission of carbapenem-resistant Klebsiella pneumoniae (CRKP) in ICU patients in Zhejiang Province, China, and determined the genetic and phenotypic characteristics of these CRKP strains. Materials and Methods: A total of 202 ICU patients from eight tertiary hospitals were recruited and 55 non-duplicate CRKP strains were collected during July and August in 2017. These strains were subjected to determination of MICs, carriage of carbapenemase genes and tet(A) variants, PFGE, MLST and virulence potential using G. mellonella larvae infection model. Results: A total of 55 CRKP strains were recovered from 42 patients, representing a carriage rate of 20.8%. CRKP strains were recovered from both the intestinal and respiratory tract of 13 patients. Importantly, strains isolated from sputum and fecal samples often displayed identical PFGE profiles, suggesting that CRKP may also colonize the respiratory tract. The most dominant ST type of these CRKP strains was ST11, accounting for 78% (43/55) of the test strains. The majority of CRKP strains were resistant to multiple antibiotics, with the exception of tigecycline and ceftazidime/avibactam. Interestingly, 32 strains were found to harbor the tet(A) variant, which is known to confer reduced tigecycline susceptibility. Assessment of the virulence potential of these CRKP strains by string test showed that results were negative for 53 of the 55 test strains. However, further assessment of virulence potential using a G. mellonella larvae infection model showed that CRKP isolated from sputum consistently exhibited a higher virulence level than strains recovered from fecal samples. Conclusion: CRKP is highly prevalent in ICU patients in Zhejiang Province with strains isolated from respiratory exhibiting higher virulence potential than those from GI tract. These data provide essential insight into development of new infection control measures to halt the transmission of CRKP in clinical settings. Keywords: carbapenem-resistant Klebsiella pneumoniae, surveillance, sputum, feces, ICU, resistance, virulence

Recent research works in the area of experimental and computational analyses of microscale mechanisms of strength, damage and degradation of glass fiber polymer composites for wind energy applications, which were carried out in the framework of a series of Sino–Danish collaborative research projects, are summarized in this article. In a series of scanning electron microscopy in situ experimental studies of composite degradation under off-axis tensile, compressive and cyclic loadings as well as three-dimensional computational experiments based on micromechanics of composites and damage mechanics, typical damage mechanisms of wind turbine blade composites were clarified. It was demonstrated that the damage mechanisms in the composites strongly depend on the orientation angle of the applied loading with the fiber direction. The matrix cracking was observed to be the main damage mechanism for tensile axial (or slightly off-axis axial) loading; for all other cases (off-axis tensile, compressive and cyclic tensile loadings), the interface debonding and shear control the damage mechanisms. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The objectives of this study were to investigate the incidence of oral squamous cell carcinoma (OSCC) developing in lesions that were previously diagnosed as oral lichen planus (OLP), and to evaluate potential contributing factors that might be associated with an increased risk for the development of OSCC in these patients. STUDY DESIGN: We retrospectively reviewed a relatively large cohort of 518 patients with OLP who received long-term follow-up (range, 6 months-21.5 years). RESULTS: There were 353 females and 165 males. Of these, 5 (0.96%) patients developed OSCC with a mean duration of 70 months. All were females with no history of smoking or alcohol use. Four of them received corticosteroid therapy. Notably, 1 of these patients received systemic corticosteroid therapy 13 months before transformation, and died of metastatic disease 46 months after transformation. CONCLUSIONS: The incidence of OSCC developing in lesions previously diagnosed as OLP is less than 1%, and females were more commonly affected. These cases appear to represent the transformation of OLP into OSCC, however it cannot be entirely ruled out that these cases may represent de novo OSCC. [ABSTRACT FROM AUTHOR]

Mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) cause a severe neurodevelopmental disorder, yet the impact of truncating mutations remains unclear. Here, we introduce the Cdkl5 492stop mouse model, mimicking C-terminal truncating mutations in patients. 492stop/Y mice exhibit altered dendritic spine morphology and spontaneous seizure-like behaviors, alongside other behavioral deficits. After creating cell lines with various Cdkl5 truncating mutations, we found that these mutations are regulated by the nonsense-mediated RNA decay pathway. Most truncating mutations result in CDKL5 protein loss, leading to multiple disease phenotypes, and offering new insights into the pathogenesis of CDKL5 disorder., Competing Interests: Conflict of interest: The authors declare that there are no conflicts of interest., (© 2025. The Author(s).)

Purpose: To describe effects of sustained-release steroid delivery devices on intraocular pressure (IOP) in eyes with glaucoma drainage devices (GDD)., Methods: Retrospective case series of eyes with steroid implants (dexamethasone or fluocinolone acetonide) and prior GDD (Ahmed, Baerveldt) without uveitis. Outcomes included IOP, IOP rise, central foveal thickness (CFT), and IOP medications., Results: We included 14 eyes (14 patients, 38% male, 94% pseudophakic). Mean age at steroid implantation was 64 ± 12 years. Baerveldt (64%) was more common than Ahmed (36%). Tubes were in the anterior chamber (57.1%), sulcus (28.6%), and pars plana (14.3%). Ozurdex (93%) was more common than Yutiq (7%). Mean IOP was 13.5 ± 3.4 mmHg pre-implant, 11.8 ± 3.7 mmHg at month 1, 13.3 ± 3.6 mmHg at month 3 (p=0.35), and 11.3 ± 3.8 mmHg at 1 year (p=0.032). Mean antihypertensive medications was unchanged at month 3 (p = 1.0), and -0.36 medications at last follow-up (p = 0.35). Mean CFT change was -204 ± 158 μm (p = 0.001). There were no cases of endophthalmitis., Conclusions: Intravitreal steroid implants were safe and effective for the treatment of post-surgical CME in patients with pre-existing GDD. There was no increase in IOP and no increase in antihypertensive drops.

Purpose: To assess the value of increased perifoveal retinal vascular tortuosity in optical coherence tomography angiography (OCTA) images as a biomarker of early hypertensive retinopathy and compare its clinical sensitivity and accuracy with traditional morphological changes used for Scheie classification., Methods: OCTA images of 81 eyes (40 eyes from 20 hypertensive subjects and 41 eyes from 21 control subjects) were obtained retrospectively. Hypertensive retinopathy changes in randomized eyes were graded according to the Scheie classification, and perifoveal vessels were traced in a masked fashion. Tortuosity values of the perifoveal vessels were then calculated along with interobserver agreement in determining the morphometric values., Results: There were no differences in perifoveal venular tortuosity between the hypertensive and control groups (Mean = 1.13 ± 0.04 vs. 1.13 ± 0.03), but significant differences existed for arterioles (Mean = 1.14 ± 0.05 vs. 1.11 ± 0.04). Tortuosity measurements demonstrated a significant interobserver agreement (p < 0.001), while Scheie ratings had a poor interobserver agreement (p = 0.735). There was a significant difference in Scheie classification between the hypertensive and control groups (Mean = 1.06 ± 0.54 vs. 0.50 ± 0.43, p = 0.005)., Conclusions: OCTA-based perifoveal retinal arteriolar tortuosity may be a potential reliable biomarker with certain advantages for detecting early hypertensive retinopathy than morphological changes used for the Scheie classification. This may have broad applications and establish important parameters in utilizing OCTA for screening protocols, considering the importance of early detection of systemic hypertension., Competing Interests: Declarations. Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the Columbia University Institutional Review Board (IRB) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study is approved by Columbia University IRB. Informed consent: A waiver of informed consent was obtained from the Columbia University IRB. Conflict of interest: All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest, or non-financial interest in the subject matter or materials discussed in this manuscript., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

GLP-1 receptor agonists are primarily used clinically for the treatment of type 2 diabetes and have the potential for weight loss, while they are currently expanding their horizons in the treatment of hypertension, non-alcoholic liver disease, depression, and neurodegenerative diseases. In particular, in the treatment of Alzheimer's disease, a large number of animal models and a handful of clinical studies have demonstrated the potential efficacy of GLP-1 receptor agonists, making it highly probable that they will become a new entrant in the drug list for Alzheimer's disease. At present, the research on the mechanism of GLP-1 receptor agonist in the treatment of Alzheimer's disease is mainly based on in-depth analysis of the pathogenesis of Alzheimer's disease and exploration of the mechanism of its comorbidity with diabetes. This article mainly reviews the latest advances in the mechanism of GLP-1 receptor agonists in the treatment of Alzheimer's disease, introduces the latest achievements in animal studies and clinical studies, and aims to provide reference for the subsequent relevant basic research and clinical application.

Key Points: Penetrating orbital trauma from marine creatures, especially needlefish, should be considered after injuries sustained in open water. Advances in endoscopic sinus surgery have enabled surgeons to remove certain orbital foreign bodies through endoscopic endonasal approaches. 3D segmentation is a valuable pre-operative tool in complex endoscopic orbital cases., (© 2024 ARS‐AAOA, LLC.)

Purpose: Report of a case of central retinal artery occlusion following sphenopalatine artery (SPA) embolization. A review of the literature describing complications following SPA embolization and ligation., Methods: Retrospective case report and literature review., Results: A 68-year-old woman with a history notable for hypertension, hyperlipidemia, and eight years of intermittent right-sided epistaxis previously requiring blood transfusions underwent right-sided embolization of the SPA with the neurosurgery service. SPA embolization was achieved with Embosphere microspheres and Concerto coils. No thromboembolic complications were noted at the conclusion of the case. On waking from general anesthesia, the patient reported painless right sided vision loss and was found to have best-corrected visual acuity of light perception, a relative afferent pupillary defect, and a cherry-red spot with vascular attenuation consistent with central retinal artery occlusion (CRAO)., Conclusions: CRAO can be a complication of ipsilateral SPA embolization.

Purpose: To perform an outcome-and-cost analysis of follow-up visits and associated imaging in patients presenting to the Massachusetts Eye and Ear (MEE) emergency department with commotio retinae. Methods: This retrospective consecutive case series comprised consecutive patients presenting to the emergency department from January 1, 2020, to January 1, 2022, who were diagnosed with contusion or other injuries of the eye or orbit (International Classification of Diseases, 10th edition, codes S05.1 and S05.8). Cost analysis was performed using Medicare fee data and previously described methods. Costs considered included follow-up examinations, optical coherence tomography (OCT), and fundus photography. Results: Of the 490 patients presenting to the emergency department, 201 had findings of commotio retinae on examination and were included in this study. Of the 201 patients with initial commotio retinae, 142 (70.6%) returned for follow-up. OCT was performed in 34% of patients and fundus photography in 33%. A total of 254 follow-up visits were conducted. Four patients (2.8%) had retinal tears on follow-up, with only 1 (0.7%) developing a retinal detachment. Complications requiring intervention were always heralded by worsening symptoms. The total cost of follow-up was $60,436 for the cohort and $425.60 per patient. Conclusions: Patients with commotio retinae infrequently develop retinal complications and have a high rate of loss to follow-up. Significant resources are dedicated to following up and imaging patients with commotio retinae. Our results underscore the low utility in multiple follow-up visits among asymptomatic patients., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of the article: Dr. Armstrong is a consultant to Kriya Therapeutics, Ocular Technologies, Optomed Inc, Chart Biopsy, DynaMed, Xenon-VR, Genentech, and McKinsey & Company. Dr. Miller is a consultant to Carl Zeiss, Alcon, Allergan, Sunovion, Radius, Topcon, and Genentech. Dr. Patel is a consultant to Atheneum, Alcon, Allergan, Alimera, EyePoint, Lifesciences, Guidepoint, and Gerson Lehrman Group, Inc, Regeneron, Dutch Ophthalmic, Genentech, EyePoint Pharmaceuticals. None of the other authors declared potential conflicts of interest with respect to the research, authorship, and/or publication of the article., (© The Author(s) 2024.)

Exploiting a photocatalyst with high stability and excellent activity for Cr(VI) reduction under mild conditions is crucial yet challenging. Herein, the rigid aromatic multicarboxylate ligand with chromophore anthracene was selected to coordinate with multivalent metal ion manganese and to obtain a stable two-dimensional (2D) Mn-based metal-organic framework (MOF), LCUH-120 , which can efficiently and quickly convert Cr(VI) into Cr(III) under light without the need for any additional photosensitizer. The efficient photosensitive anthracene group serves as a photosensitizer center and multivalent Mn(II) ion as a photocatalyst center in LCUH-120 , and the conversion of Cr(VI) to Cr(III) can be realized completely in just 40 min. Specifically, the rate constant ( k ) and reduction rate of the Cr(VI) photocatalytic reaction can be high up to 0.134 min -1 and 2.50 mg Cr(VI) g -1 cata min -1 in an acidic environment (pH = 2), respectively. Compared to our previously reported three-dimensional (3D) Sm-MOF , LCUH-120 exhibits a significantly higher catalytic reaction rate, which might be ascribed to the fact that the photocatalyst center Mn node can improve the rate of electron transfer and promote the separation of holes and photogenerated electrons. In an acidic environment, the reaction mechanism can be verified through various contrast experiments and theoretical simulations.

Gynostemma pentaphyllum has been used as an herbal tea, vegetable, and dietary supplement for hundreds of years in East Asia. The sweet variety, grown in large areas in Fujian Province, China, is an essential source of "Jiaogulan" herbal tea. However, its sweet components are unknown. To investigate the sweet constituents of Fujian "Jiaogulan" and discover new natural high-potency sweeteners, phytochemical and sensory evaluations were combined to obtain 15 saponins, of which 11 ( 1 - 11 ) were sweet-tasting, including 2 new ones with sweetness intensities 20-200 times higher than that of sucrose, and four ( 12 - 15 ) were bitter-tasting. Their structures were elucidated using spectroscopic methods (NMR, MS, IR, UV), hydrolysis, and comparison with literature data. The contents of the 15 saponins were quantitatively analyzed using UPLC-MS/MS in multiple reaction monitoring mode. The contents of 1 and 2 sweet-tasting gypenosides were 9.913 ± 1.735 and 35.852 ± 1.739 mg/kg, respectively. The content of the sweetest compound ( 6 ) was 124.969 ± 0.961 mg/kg. Additionally, compound 4 was the most abundant sweet component (422.530 ± 3.702 mg/kg). Furthermore, molecular docking results suggested interactions of sweet saponins with sweet taste receptors. In general, this study revealed the material basis of the Fujian "Jiaogulan" taste.

Introduction: This study aimed to investigate the incidence of and risk factors for epiretinal membrane (ERM) formation following primary rhegmatogenous retinal detachment (RRD) repair., Methods: This comparative, retrospective, single-center cohort study included eyes with primary RRD treated between 2011 and 2023 at Massachusetts Eye and Ear, Boston, Massachusetts, with pars plana vitrectomy (PPV), scleral buckle (SB), PPV+SB, or pneumatic retinopexy (PnR). Demographic, clinical, and surgical parameters were collected from medical records. The primary outcome was the risk of ERM formation, while the secondary outcome was the risk of ERM requiring surgery. Univariable and multivariable Cox regression were performed, and a hazard ratio (HR) and 95% confidence interval (95% CI) were reported., Results: Overall, 394 eyes were included. The mean age was 58.49 ± 12.8 years, and most patients were male. There was a significantly lower risk of ERM formation following SB compared to PPV in the univariable analysis (HR = 0.2, 95% CI = 0.08-0.60, p = 0.003); however, there was no significant association between treatment modality and ERM formation on multivariable Cox regression controlling for confounding factors (p = 0.24). ERM formation was found more commonly in patients who were older (HR = 1.0 per 1 year increase in age, 95% CI = 1.01-1.04, p = 0.001), those with worse baseline visual acuity (HR = 1.3, 95% CI = 1.09-1.71, p = 0.008), and those with macula-off RRDs (HR = 2.1, 95% CI = 1.41-3.32, p &lt; 0.001)., Conclusion: Surgical modality does not have a significant impact on the risk of ERM following retinal detachment repair. However, age, baseline visual acuity, and macular status are important predictors of ERM formation after RRD repair., (© 2024 S. Karger AG, Basel.)

Nodulation begins with the initiation of infection threads (ITs) in root hairs. Though mutual recognition and early symbiotic signaling cascades in legumes are well understood, molecular mechanisms underlying bacterial infection processes and successive nodule organogenesis remain largely unexplored. We functionally investigated a novel pectate lyase enzyme, GmNPLa, and its transcriptional regulator GmPTF1a/b in soybean (Glycine max), where their regulatory roles in IT development and nodule formation were elucidated through investigation of gene expression patterns, bioinformatics analysis, biochemical verification of genetic interactions, and observation of phenotypic impacts in transgenic soybean plants. GmNPLa was specifically induced by rhizobium inoculation in root hairs. Manipulation of GmNPLa produced remarkable effects on IT and nodule formation. GmPTF1a/b displayed similar expression patterns as GmNPLa, and manipulation of GmPTF1a/b also severely influenced nodulation traits. LI soybeans with low nodulation phenotypes were nearly restored to HI nodulation level by complementation of GmNPLa and/or GmPTF1a. Further genetic and biochemical analysis demonstrated that GmPTF1a can bind to the E-box motif to activate transcription of GmNPLa, and thereby facilitate nodulation. Taken together, our findings potentially reveal novel mediation of cell wall gene expression involving the basic helix-loop-helix transcription factor GmPTF1a/b acts as a key early regulator of nodulation in soybean., (© 2023 The Authors New Phytologist © 2023 New Phytologist Foundation.)

Importance: Microorganisms inhabited various tissues of plants and play a key role in promoting plant growth, nutritional absorption, and resistance. Our research indicates that the diversity of Camellia oleifera endophytic bacterial communities is highly dependent on the plant compartment. Proteobacteria , Acidobacteria , Actinobacteria , Bacteroidetes , Firmicutes , Chloroflexi , and Verrucomicrobia are dominant bacteria phyla. The tissues of Camellia oleifera contain various bacteria with nitrogen fixation potential, host life promotion, and plant defense. This study provides a scientific theoretical basis for an in-depth discussion of plant-endosphere microbial interaction and better exploration of benign interaction of beneficial microorganisms and plants., Competing Interests: The authors declare no conflict of interest.

Objective: To explore the association between hair trace element and all-cause death in the elderly in Hainan Province. Methods: The subjects of the study were elderly people from China Hainan Centenarian Cohort Study, a total of 163 elderly were included. The association between hair trace element level and all-cause death was analyzed by using Cox proportional risk regression model. Results: After fully adjusting the covariates, the multiple Cox proportional hazards regression analyses showed that selenium (Se), manganese (Mn), strontium (Sr) concentrations in hair were significantly associated with all-cause mortality, the hazard ratio ( HR ) were 0.72 (95% CI : 0.54-0.98, P =0.035), 1.50 (95% CI : 1.07-2.11, P =0.020) and 0.54 (95% CI : 0.37-0.79, P =0.001), respectively. Subgroup and cross analysis showed that hair copper (Cu) were significant association with death in the people with anemia, the HR were 1.81 (95% CI : 1.13-2.88, P =0.013). And, hair Mn interacted with anemia, the HR was 0.46 (95% CI : 0.22-0.94, P =0.033). Conclusions: Se, Mn and Sr concentrations in hair were associated with the elevated risk for all-cause death in the elderly in Hainan. Se, Mn and Sr concentrations in hair can be used as a reference index for the prediction of the death risk of long-lived elderly in community, suggesting that the daily diet of elderly people are rich and diverse, in order to maintain normal and balanced trace element content in the body.

Objective: The pathogenesis of sepsis is complex, and the sepsis-induced systemic proinflammatory phase is one of the key drivers of organ failure and consequent mortality. Akkermansia muciniphila (AKK) is recognised as a functional probiotic strain that exerts beneficial effects on the progression of many diseases; however, whether AKK participates in sepsis pathogenesis is still unclear. Here, we evaluated the potential contribution of AKK to lethal sepsis development., Design: Relative abundance of gut microbial AKK in septic patients was evaluated. Cecal ligation and puncture (CLP) surgery and lipopolysaccharide (LPS) injection were employed to establish sepsis in mice. Non-targeted and targeted metabolomics analysis were used for metabolites analysis., Results: We first found that the relative abundance of gut microbial AKK in septic patients was significantly reduced compared with that in non-septic controls. Live AKK supplementation, as well as supplementation with its culture supernatant, remarkably reduced sepsis-induced mortality in sepsis models. Metabolomics analysis and germ-free mouse validation experiments revealed that live AKK was able to generate a novel tripeptide Arg-Lys-His (RKH). RKH exerted protective effects against sepsis-induced death and organ damage. Furthermore, RKH markedly reduced sepsis-induced inflammatory cell activation and proinflammatory factor overproduction. A mechanistic study revealed that RKH could directly bind to Toll-like receptor 4 (TLR4) and block TLR4 signal transduction in immune cells. Finally, we validated the preventive effects of RKH against sepsis-induced systemic inflammation and organ damage in a piglet model., Conclusion: We revealed that a novel tripeptide, RKH, derived from live AKK, may act as a novel endogenous antagonist for TLR4. RKH may serve as a novel potential therapeutic approach to combat lethal sepsis after successfully translating its efficacy into clinical practice., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To investigate the association between age and clinical activity score (CAS) in patients with active, untreated thyroid eye disease., Methods: A retrospective review was conducted of patients with active, untreated thyroid eye disease at a single institution between 2010 and 2020 whose ophthalmologic symptoms began no more than 9 months prior to the initial visit. Exclusion criteria included surgical or systemic thyroid eye disease treatment before or during the study period. Demographic and clinical data were collected for all patients, including a 7-point CAS at visit 1 (CAS1) and a 10-point score at visit 2 (CAS2). Patients were stratified by age: Group 1 (18-45), Group 2 (46-70), and Group 3 (71-85)., Results: A total of 156 patients were included: mean age 51.7 ± 15.8 years, 79.5% female. CAS1 differed significantly across groups: 1.9 ± 1.0 (Group 1), 2.7 ± 1.4 (Group 2), and 2.2 ± 1.6 (Group 3), p = 0.005. Findings were similar for CAS2: 2.2 ± 1.4 (Group 1), 3.0 ± 1.8 (Group 2), and 2.8 ± 1.9 (Group 3), p = 0.030. Post hoc analysis showed a statistically significant difference between Groups 1 and 2 (p = 0.004, visit 1; p = 0.025, visit 2) but not between other pairs. Patients with CAS1 of 0-3 (n = 129) were younger on average than those with CAS1 4-7 (n = 27): 50.4 ± 16.2 versus 58.2 ± 12.8 years (p = 0.009). Conjunctival redness (p = 0.019) and chemosis (p ≤ 0.001) were more common in older patients at both visits., Conclusions: Patients aged 46-70 years with active, untreated thyroid eye disease had significantly higher CAS1 and CAS2 than younger patients in this study, largely driven by differences in conjunctival redness and chemosis., Competing Interests: The authors have no financial or conflicts of interest to disclose., (Copyright © 2023 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

The field of anion supramolecular chemistry has received more and more attention in recent years. Anions with diverse types and geometries have been widely used for the synthesis of ionic spin crossover (SCO) complexes. This review is devoted to anion effects on the molecular, supramolecular structures and magnetic properties of discrete SCO compounds. Firstly, typical anions used in the synthesis of these compounds are briefly summarized according to their various geometries. This is followed by a collection of representative examples of anion-based SCO compounds, whose SCO properties are analyzed in terms of supramolecular interactions, geometry and charge of anions. In the third part, anion effects on SCO complexes of different kinds of metal centers and ligands are outlined and finally remarks on the synthesis new type of ionic SCO complexes in the future are described., (© 2023 Wiley-VCH GmbH.)

Purpose: To assess the evolution of proptosis asymmetry during the active phase of bilateral thyroid eye disease (TED)., Methods: A retrospective study was conducted on patients with bilateral, active TED. Patients were measured by a single observer, using Hertel exophthalmometry from the time of initial presentation, during the active phase of TED, to the stable phase, 24-months later. Asymmetric proptosis was defined as a >2 mm intra-orbital difference in Hertel measurements., Results: Fifty-one patients were enrolled. Patients presented at a mean time of 1.1 ± 2.9 months following the onset of TED symptoms. Stability of TED was established at 15.7 ± 12.3 months. At initial presentation, 41% of patients demonstrated asymmetric proptosis. Upon reaching the stable phase, asymmetric proptosis persisted in only 22% of patients. A decline in the rate asymmetric proptosis was greatest within the first 3 months of the active phase., Conclusions: Asymmetric proptosis is common in the setting of early active TED and decreases by 50% when the stable phase is reached. Therefore, diagnostic imaging is not routinely required to exclude alternative pathology in the cases of asymmetric TED. Perhaps more importantly, this finding supports the surgical paradigm of stable phase, graded orbital decompression, performed when the ultimate globe positions are achieved to avoid late postoperative asymmetry, resulting from the unanticipated evolution of proptosis when surgery is performed during the active phase of TED.

Objective: To investigate the clinical and pathologic characteristics of obese adults with nonalcoholic fatty liver disease (NAFLD) and to aid the diagnosis of nonalcoholic steatohepatitis (NASH). Methods: A total of 262 patients eligible for inclusion who received volume reduction metabolism surgery and liver biopsy in the First Affiliated Hospital of Nanjing Medical University from June 2018 to September 2019 were selected. HE staining, reticular fiber staining and Masson staining were performed. Statistical analysis was performed using SPSS 20.0. Results: The patients ranged in age from 18 to 66 years. Among the 262 cases, 65 cases (65/262, 24.8%) were male and 197 cases (197/262, 75.2%) were female. Sixty-one cases (61/262, 23.3%) were non-NAFLD, 201 cases (201/262, 76.7%) were NAFLD including 27 cases (27/201, 13.4%) of nonalcoholic fatty live (NAFL) and 174 cases (174/201, 86.6%) of NASH. The main lesions of NAFLD were in hepatic acinus zone 3. There were significant differences in age, alanine aminotransferase (ALT), glutamic oxaloacetic transaminase (AST), body mass index (BMI), fasting blood-glucose (FPG) and apolipoprotein A (APOA) levels among the non-NAFLD group, NAFL group and NASH group ( P <0.05). Patients with BMI≥35 m/kg 2 combined with type 2 diabetes had a higher prevalence of NASH. Multiple logistic regression showed that ALT and APOA were independent predictors of NASH ( P< 0.001, OR= 1.05, 95% CI : 1.020-1.082; P= 0.027, OR= 0.916, 95% CI : 0.878-0.941). Total cholesterol (CHO) and high-density lipoprotein (HDL) were independent predictors of lobular inflammation ( P= 0.043, 95% CI : 0.010-0.634; P= 0.024, 95% CI :-3.068--0.216). AST and HDL were independent predictors of fibrosis stage ( P= 0.029, 95% CI : 0.001-0.021; P< 0.001, 95% CI :-2.670--0.645). Conclusions: Biochemical indicators of NAFLD are closely related to its pathology. The histological lesions of NAFLD are mainly present in hepatic acinar area 3. The diagnosis of NASH is supported by extensive steatosis and high levels of CHO, ALT, AST and BMI, low levels of HDL and ApoA in biochemical markers, but pathological examination is still the gold standard for it.

Background: Sepsis-related AKI is related to short-term mortality and poor long-term prognoses, such as chronic renal insufficiency, late development of end-stage renal disease, and long-term mortality. In this study, we aimed to investigate the association of hyperuricemia with acute kidney injury (AKI) in patients with sepsis., Methods: The retrospective cohort study included 634 adult sepsis patients hospitalized in the intensive care unit (ICU) of the First Affiliated Hospital of Guangxi Medical University from March 2014 to June 2020 and the ICU of the Second Affiliated Hospital of Guangxi Medical University from January 2017 to June 2020. Based on the first serum uric acid level within 24 h of admission to the ICU, patients were divided into groups with or without hyperuricemia, and the incidence of AKI within seven days of ICU admission was compared between the two groups. The univariate analysis analyzed the effect of hyperuricemia on sepsis-related AKI, and the multivariable logistic regression model analysis was used., Results: Among the 634 patients with sepsis, 163 (25.7%) developed hyperuricemia, and 324 (51.5%) developed AKI. The incidence of AKI in the groups with and without hyperuricemia was 76.7% and 42.3%, respectively, with statistically significant differences (2 = 57.469, P < 0.001). After adjusting for genders, comorbidities (coronary artery disease), organ failure assessment (SOFA) score on the day of admission, basal renal function, serum lactate, calcitonin, and mean arterial pressure, hyperuricemia was showed to be an independent risk factor for AKI in patients with sepsis (OR = 4.415, 95%CI 2.793 ~ 6.980, P < 0.001). For every 1 mg/dL increase in serum uric acid in patients with sepsis, the risk of AKI increased by 31.7% ( OR = 1.317, 95%CI 1.223 ~ 1.418, P < 0.001)., Conclusion: AKI is a common complication in septic patients hospitalized in the ICU, and hyperuricemia is an independent risk factor for AKI in septic patients., (© 2023. The Author(s).)

Aim: To evaluate independent risk factors specific for early-stage nasopharyngeal carcinoma (NPC). Methods: A total of 566 patients with early-stage NPC from 2004 to 2019 were identified using the Surveillance, Epidemiology and End Results database. Results: Older ages (70-79 and >80 years) were independent risk factors, with hazard ratios of 1.961 and 5.011, respectively. The hazard ratio for early-stage NPC in Asian and Pacific Islander residents (0.475) was lower than that for White residents. A tumor size <3 cm was a protective factor for overall and cancer-specific survival in the current study. Conclusion: In patients with early-stage NPC, age >70 years, race and tumor size were independent prognosticators for cancer-specific survival.

Purpose: To examine the clinical and histopathologic characteristics of lacrimal gland biopsies at a tertiary academic center., Methods: A retrospective chart review of patients undergoing lacrimal gland biopsy or excision between 1962 and 2017 was performed via the ocular pathology specimen log. All cases were reviewed for demographics, clinical presentation, and histopathologic diagnoses., Results: Four hundred and two eyes in 356 patients were included in the analysis. Median age was 49 (range 5-91) with a female predominance (255, 72%, p < .001). Most had unilateral involvement (308, 86.5%) and visual acuity of 20/50 or better (332 eyes, 83%). Limitation in extraocular motility was present in 71 eyes (18%), relative afferent pupillary defect in 10 eyes (2.5%), and intraocular pressure 20 mmHg or above in 80 eyes (20%). The pre-operative radiology report commented on the enlargement of the lacrimal gland in 236 eyes (58.7%), and lack thereof in 73 eyes (18.2%). The most common histopathologic diagnoses were nonspecific inflammation or orbital pseudotumor (170, 42%), lymphoma (65, 16%), pleomorphic adenoma (22, 5.5%), adenoid cystic carcinoma (19, 4.7%), granulomatous inflammation (19, 4.7%), and normal lacrimal gland (16, 4%). Three hundred and seven cases were benign (76%) and 95 malignant (24%). The biopsy specimen was diagnostic in 343 (85%), and non-diagnostic in 59 (15%)., Conclusions: This is a comprehensive review of one of the largest ocular pathology databases of lacrimal gland lesions. This study confirms the wide range of inflammatory and neoplastic conditions affecting the lacrimal gland and highlights the nuances of histopathologic diagnoses and diagnostic yield of biopsies in clinical practice.

Postoperative complications of phacoemulsification, such as corneal edema caused by human corneal endothelial cell (CEC) injury, are still a matter of concern. Although several factors are known to cause CEC damage, the influence of ultrasound on the formation of free radicals during surgery should be considered. Ultrasound in aqueous humor induces cavitation and promotes the formation of hydroxyl radicals or reactive oxygen species (ROS). ROS-induced apoptosis and autophagy in phacoemulsification have been suggested to significantly promote CEC injury. CEC cannot regenerate after injury, and measures must be taken to prevent the loss of CEC after phacoemulsification or other CEC injuries. Antioxidants can reduce the oxidative stress injury of CEC during phacoemulsification. Evidence from rabbit eye studies shows that ascorbic acid infusion during operation or local application of ascorbic acid during phacoemulsification has a protective effect by scavenging free radicals or reducing oxidative stress. Both in experiments and clinical practice, hydrogen dissolved in the irrigating solution can also prevent CEC damage during phacoemulsification surgery. Astaxanthin (AST) can inhibit oxidative damage, thereby protecting different cells from most pathological conditions, such as myocardial cells, luteinized granulosa cells of the ovary, umbilical vascular endothelial cells, and human retina pigment epithelium cell line (ARPE-19). However, existing research has not focused on the application of AST to prevent oxidative stress during phacoemulsification, and the related mechanisms need to be studied. The Rho related helical coil kinase inhibitor Y-27632 can inhibit CEC apoptosis after phacoemulsification. Rigorous experiments are required to confirm whether its effect is realized through improving the ROS clearance ability of CEC., Competing Interests: Conflict-of-interest statement: Chen K has received research funding from Scientific Research Project of Lianshui County Health Committee in 2022; Xu WY, Sun SS, and Zhou HW have nothing to disclose., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

This paper proposes a normal oriented impact stiffness of a three-supporting cable flexible barrier under a small pretension stress to estimate the structural load behaviour, and employs two categories of small-scale debris flows (coarse and fine) to explore the stiffness evolution through physical model experiments with high-speed photography and load sensing. Results suggest that the particle-structure contact is essential to the normal load effect. Coarse debris flow performs more frequent particle-structure contact and exerts evident momentum flux, while fine debris flows with few physical collisions impart much smaller one. The middle-sited cable that receives only tensile force from vertical equivalent cable-net joint system exhibits indirect load behaviour. The bottom-sited cable shows high load feedback due to the sum of direct contact of debris flow and tensile forces. The relationship between impact loads and maximum cable deflections can be explained by power functions according to quasi-static theory. The impact stiffness is not just affected by the particle-structure contact but by the flow inertia and particle collision effect. Savage number N sav and Bagnold number N bag manage to depict the dynamical effects on the normal stiffness D i . Experiments indicate that N sav has positive linear correlation with the nondimensionalization of D i , whilst N bag has positive power correlation with the nondimensionalization of D i . This idea is an alternative scope for the study on flow-structure interaction and may contribute to the parameter identification in numerical simulation of the debris flow-structure interaction and the optimization of the design standardization., (© 2023. The Author(s).)

An individual's functional vision may be measured via visual assessment and performance on mobility tasks. Since traditional mobility performance tests neglect to examine the effects of illumination on performance, the multi-luminance mobility test (MLMT) was designed to quantitatively assess the effects of illumination levels on an individual's mobility performance. In this chapter, we describe how the MLMT is conducted and scored in order to properly evaluate a participant's mobility under various light conditions., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Ecto-5'-nucleotidase (NT5E) encodes the cluster of differentiation 73 (CD73), whose overexpression contributes to the formation of immunosuppressive tumor microenvironment and is related to exacerbated prognosis, increased risk of metastasis and resistance to immunotherapy of various tumors. However, the prognostic significance of NT5E in pan-cancer is obscure so far. Methods: We explored the expression level of NT5E in cancers and adjacent tissues and revealed the relationship between the NT5E expression level and clinical outcomes in pan-cancer by utilizing the UCSC Xena database. Then, correlation analyses were performed to evaluate the relationship between NT5E expression and immune infiltration level via EPIC, MCP-counter and CIBERSORT methods, and the enrichment analysis were employed to identify NT5E-interacting molecules and functional pathways. Furthermore, we conducted single-cell analysis to explore the potential role of NT5E on single-cell level based on the CancerSEA database. Meanwhile, gene set enrichment analysis (GSEA) in single-cell level was also conducted in TISCH database and single-cell signature explorer was utilized to evaluate the epithelial-mesenchymal transition (EMT) level in each cell type. Results: The expression level of NT5E was aberrant in almost all cancer types, and was correlated with worse prognosis in several cancers. Notably, NT5E overexpression was related to worse overall survival (OS) in pancreatic adenocarcinoma (PAAD), head and neck squamous cell carcinoma (HNSC), mesothelioma (MESO), stomach adenocarcinoma (STAD), uveal melanoma (UVM) and cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) ( p < 0.01). NT5E-related immune microenvironment analysis revealed that NT5E is associated positively with the degree of infiltration of cancer-associated fibroblasts (CAFs) and endothelial cells in most cancers. Enrichment analysis of cellular component (CC) demonstrated the critical part of NT5E played in cell-substrate junction, cell-substrate adherens junction, focal adhesion and external side of plasma membrane. Finally, single-cell analysis of NT5E illuminated that EMT function of CAFs was elevated in basal cell carcinoma (BCC), skin cutaneous melanoma (SKCM), HNSC and PAAD. Conclusion: NT5E could serve as a potential prognostic biomarker for cancers. The potential mechanism may be related to the upregulated EMT function of CAFs, which provides novel inspiration for immunotherapy by targeting CAFs with high NT5E expression., 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 Xue, Liu, Chen, Tao, Liu, Zhou, Zhang, Wang, Jiang, Ding, Shen, Zhang, Yang and Wang.)

Objectives: A direct evaluation of insulin sensitivity on pituitary response to gonadotropin relasing hormone (GnRH) has not been shown in congenital hypogonadotropic hypogonadism (CHH), despite a growing body of evidence in the association of testosterone concentrations with insulin sensitiviy. The objective of the study was to explore whether increased testosterone concentrations in men with CHH improve insulin sensitivity, or vice versa., Design: A retrospective study at a tertiary centre., Patients: Series of male CHH patients were included from Jannuary 2014 to December 2019., Measurements: Insulin sensitivity indices calculated from oral glucose tolerance test and steroid hormone levels were examined in 52 patients with newly diagnosed CHH and 22 healthy controls. Thirty-two of the 52 CHH patients received pulsatile GnRH therapy with follow-up every 3-6 months., Results: Compared to healthy controls, CHH patients had elevated 2 h post-load glucose, HbA1c, fasting insulin, HOMA of insulin resistance (HOMA-IR) and decreased Matsuda index and testosterone (p ≤ .01). The median follow-up for patients (n = 32) who received pulsatile GnRH therapy was 13.5 (11.3-24) months (432 person-months in total). GnRH therapy increased testosterone and Matsuda index (p ≤ .0001), whilst decreased platelet count (p = .04), leptin (p = .04), fasting glucose (p = .01) and HOMA-IR (p &lt; .0001) compared with baseline. The median treatment duration first time to reach the lower limit of normal testosterone concentrations of patients with high and low baseline insulin sensitivity was 15 (95% CI: 8.1-21.9) and 30 months (21.2-38.8), respectively. Correspondingly, after GnRH therapy, luteinizing hormone responsiveness to GnRH provocative test was more vigorous in patients with high insulin sensitivity than those with low insulin sensitivity [17.0 (9.5-25.9) vs. 8.2 (3.3-13.0), p = .01]., Conclusion: Pulsatile GnRH therapy elevated testosterone levels in male CHH patients, ameliorated impaired insulin sensitivity and attenuated subclinical inflammatory response, increased insulin sensitivity, in turn, may benefit the efficacy of pulsatile GnRH therapy., (© 2022 John Wiley & Sons Ltd.)

Coalbed methane (CBM) exploitation leads to permanent stress redistributions in the coal bodies connected with fracturing processes and permeability changes due to deformation induced internal pore-fracture networks. Gas permeability evolution of coal samples is investigated with a newly developed three-dimensional fluid-mechanical coupled experimental system. X-ray CT is used to investigate the internal structure of the coal samples and delivers the basis to set-up numerical twins. The work focuses on coal samples with inclusions. A novel coupling procedure between two different tools-discontinuum and continuum codes-is established to simulate the permeability evolution. The permeability is related to the crack pattern in general, and crack width in particular. A prediction of permeability is proposed based on fracture distribution and microcrack behavior. The experimental studies validated the coupling approach. Shear fractures cause substantial permeability enhancement. Piecewise relations between permeability and volumetric strain can be used to fit the whole process, where a nonlinear exponential relation is established after the expansion point. The inclusions as important structural characteristics influence this relation significantly.

Glycogen storage disease type V is an autosomal recessive genetic disorder caused by muscle glycogen phosphorylase (PYGM) deficiency, which is characterized by exercise intolerance, second wind phenomena and high level of serum creatine kinase. In this study, we reported a Chinese young man with glycogen storage disease type V, with lower extremity weakness after exercise, increased creatine kinase, and slight fat infiltration in the posterior group of thigh muscle by magnetic resonance imaging (MRI). The proband had complex heterozygous PYGM disease-causing mutations, including c.308T>C (p.L103P) variant transmitted from the mother and c.260&#95;261delCT (p.S87Ffs*23) from the father, of which the former was a novel PYGM mutation. This study enriched the PYGM pathogenic gene mutation spectrum, contributed to improve clinicians' understanding of glycogen storage disease type V and provided a reference for further genetic study of the disease.

Congenital generalized lipodystrophy (CGL) is an extremely rare genetic disease mainly characterized by absence of whole-body adipose tissue and metabolic dysfunctions such as insulin resistance, diabetes mellitus, hypertriglyceridemia, hepatic steatosis, and acanthosis nigricans. In this study, we reported a novel case of a young woman patient with CGL. The patient came to the hospital for early-onset lipodystrophy and diabetes. She was 19-year-old with a height of 160 cm, a weight of 46 kg, BMI of 17.9 kg/m 2 , and a serum leptin level of 0.14 μg/L. Genomic DNA was extracted from blood samples of the patient and her family members, including her mother, father and brother. Genetic analysis revealed compound heterozygous mutations of the BSCL2 gene (c.560A>G and c.565G>T) in the patient. Her father carried a heterozygous mutation (c.565G>T), and her mother carried a heterozygous mutation (c.560A>G) in the BSCL2 gene. The mutant p.Y187C plasmid was transfected into HEK293T cells. The protein expression of SEIPIN and its interaction with glycerol-3-phosphate acyltransferase (GPAT3) were observed to be reduced. In addition, based on primary cultured skin fibroblasts from the patient, SEIPIN protein was decreased, and lipid droplets were much smaller when fatty acid was stimulated compared with those observed from healthy subject controls. However, histone deacetylase inhibitors (HDACis) was found capable of rescuing SEIPIN protein in fibroblasts of the patient. In addition, we further summarized and discussed gene mutations of BSCL2 reported in the current literature. Collectively, these findings have expanded the clinical phenotype and pathogenic gene spectrum of CGL, which might help clinicians to achieve better management of lipodystrophy.

Glucose metabolism plays a central role in energy supply and metabolism regulation in various tissues and organs. Besides, insulin is the sole hormone lowering blood glucose in the body, and islet function and insulin sensitivity are the key steps modulating glucose metabolism. Since the development of glucose clamp technology, it has been recognized as the gold standard for evaluating insulin metabolism. The main categories include hyperinsulinemia-euglycemia clamp, hyperglycemia clamp, and hyperinsulinemia-hypoglycemia clamp. These can be done on either anesthetized mice or conscious and unrestricted mice. This protocol focuses on the establishment and operation of the mouse glucose clamp technique, including preparation of instrument consumables, surgical operations, clamping procedures, and precautions, serving as reference and guidance.

Congenital hyperinsulinemia (CHI) is a disease phenotype characterized by persistent or recurrent hypoglycemia due to abnormal secretion of insulin by β cells of the pancreas. CHI induced by activation mutation of a single allele of glucokinase (GCK) is the rarest type. In this paper, the clinical data of a patient with hypoglycemia of unknown cause were collected without obvious clinical symptoms. And a heterozygous missense mutation (c.295T> C:p.W99R) was detected in exon 3 of the GCK gene. The mutation was found in both the son and daughter of the proband, and the blood glucose level was low, while the others were normal. By summarizing and analyzing the characteristics of this case and the genetic pedigree of the family, the possibility of congenital hyperinsulinemia caused by a single gene mutation should be considered for hypoglycemia whose etiology is difficult to be determined clinically. This case also provides new clinical data for subsequent genetic studies of the disease.

Competing Interests: None

Objective: The effects of intravitreal ranibizumab (IVR) as a pretreatment for vitrectomy in proliferative diabetic retinopathy (PDR) need further study. The aim of this study is to further analyze this topic., Patients and Methods: The study group (n=26) was treated with IVR, while the control group (n=28) was not. The best corrected visual acuity (BCVA) at different time points within each group was compared. Operation time, intraoperative bleeding, silicone oil usage, iatrogenic retinal rupture and complications were compared between the groups., Results: BCVA at the 1st month after vitrectomy was significantly improved in the study group (t=2.081, p=0.047) but not in the control group (I=0.164, p=0.871). At the 1st month after vitrectomy, the BCVA of the study group was significantly higher than that of the control group (t=2.1467, p=0.0365). At the 6th month after vitrectomy, the BCVA of the study group was significantly higher than that of the control group (t=2.0424, p=0.0462). The operation time in the study group was significantly shorter than that in the control group (W=2.212, p<0.05). The rates of mild and severe intraoperative bleeding in the study group were significantly lower than those in the control group (p<0.05, respectively). There was no significant difference in complications between the two groups (p>0.05)., Conclusions: IVR before vitrectomy in patients with PDR can significantly improve BCVA in the early stage, improve BCVA at the 6th month after the operation, reduce the operation time and reduce intraoperative bleeding.

Background: In spite of a growing number in the use of percutaneous coronary intervention (PCI) in China, the mortality of acute myocardial infarction (AMI) has not decreased. Traditional Chinese medicine injections for Activating Blood Circulation (TCMi-ABC), equivalent effect of anticoagulation or antiplatelet, are widely used in China; however, the improvement of fatality towards AMI is unclear. Therefore, we intend to conduct a systematic review and meta-analysis to evaluate the efficacy and safety of TCMi-ABC in treatment with AMI., Methods: Based on the "National Medical Products Administration of China," TCMi-ABC with AMI treatment indication will be selected, including Danhong injection, Sodium Tanshinone IIA Sulfonate injection, Danshen Chuanxiongqin injection, and Puerarin injection. Randomized controlled studies will be searched from as follows: PubMed, Embase, the CENTRAL in Cochrane Library, Chinese Biomedical Literature Database (SinoMed), China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and Wanfang Data Knowledge Service Platform. Two researchers will work independently on literature selection, data extraction, and quality assessment. The outcomes focus on the effects of TCMi-ABC on fatality of patients with AMI in hospitalization and in the long term, the incidence of malignant arrhythmia, left ventricular ejection fraction, and adverse events. RevMan 5.4.1 software was used for mate analysis., Results: This study will conduct a comprehensive literature search and provide a systematic synthesis of current published data to explore the efficacy and safety of TCMi-ABC for AMI., Conclusion: This study will provide high-quality evidence for treatment of AMI with TCMi-ABC in terms of efficacy and safety, which may help clinicians make a better complementary treatment schedule of patients with AMI., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Recent evidence indicates that long-term visit-to-visit blood pressure variability (BPV) may be associated with risk of cardiovascular disease. We, therefore, aimed to determine the potential associations of long-term BPV from childhood to middle age with subclinical kidney damage (SKD) and albuminuria in adulthood., Methods: Using data from the ongoing cohort of Hanzhong Adolescent Hypertension study, which recruited children and adolescents aged 6 to 18 years at baseline, we assessed BPV by SD and average real variability (ARV) for 30 years (6 visits). Presence of SKD was defined as estimated glomerular filtration rate between 30 and 60 mL/min per 1.73 m 2 or elevated urinary albumin-to creatinine ratio at least 30 mg/g. Albuminuria was defined as urinary albumin-to creatinine ratio ≥30 mg/g., Results: During 30 years of follow-up, of the 1771 participants, 204 SKD events occurred. After adjustment for demographic, clinical characteristics, and mean BP during 30 years, higher SD SBP , ARV SBP , SD DBP , ARV DBP , SD MAP , ARV MAP , and ARV PP were significantly associated with higher risk of SKD. When we used cumulative exposure to BP from childhood to adulthood instead of mean BP as adjustment factors, results were similar. In addition, greater long-term BPV was also associated with the risk of albuminuria. Long-term BPV from childhood to middle age was associated with higher risk of SKD and albuminuria in adulthood, independent of mean BP or cumulative exposure to BP during follow-up., Conclusions: Identifying long-term BPV from early age may assist in predicting kidney disease and cardiovascular disease in later life.

The prognostic value of mutations in G-protein genes GNAQ and GNA11 in patients with intracranial and orbital melanocytomas is unknown. The authors present a case of GNA11 mutation (GNA11Q209L) in a 32-year-old male suffering from a meningeal melanocytoma with orbital involvement and ipsilateral Nevus of Ota. The patient underwent gamma knife stereotactic radiosurgery without biopsy and later partial transcranial resection of the melanocytic tumor that was subject to immunohistochemical and molecular analysis. A 50-gene next-generation sequencing panel revealed a 626A>T mutation in the GNA11 gene. One year later, intracranial extension of the melanocytoma necessitated a ventriculoperitoneal shunt and immunotherapy. Future work is needed to determine how GNA11 mutations in melanocytomas influence prognosis and monitoring strategies., Competing Interests: The authors have no financial or conflicts of interest to disclose., (Copyright © 2021 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)