High Performance Indium-Tin-Oxide Schottky Diodes for Terahertz Band Operation.

Schottky diode, capable of ultrahigh frequency operation, plays a critical role in modern communication systems. To develop cost-effective and widely applicable high-speed diodes, researchers have delved into thin-film semiconductors. However, a performance gap persists between thin-film diodes and conventional bulk semiconductor-based ones. Featuring high mobility and low permittivity, indium-tin-oxide has emerged to bridge this gap. Nevertheless, due to its high carrier concentration, indium-tin-oxide has predominantly been utilized as electrode rather than semiconductor. In this study, a remarkable quantum confinement induced dedoping phenomenon was discovered during the aggressive indium-tin-oxide thickness downscaling. By leveraging such a feature to change indium-tin-oxide from metal-like into semiconductor-like, in conjunction with a novel heterogeneous lateral design facilitated by an innovative digital etch, we demonstrated an indium-tin-oxide Schottky diode with a cutoff frequency reaching terahertz band. By pushing the boundaries of thin-film Schottky diodes, our research offers a potential enabler for future fifth-generation/sixth-generation networks, empowering diverse applications.

Fotagliptin monotherapy with alogliptin as an active comparator in patients with uncontrolled type 2 diabetes mellitus: a randomized, multicenter, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Dipeptidyl peptidase-4 inhibitors (DPP-4i) have become firmly established in treatment algorithms and national guidelines for improving glycemic control in type 2 diabetes mellitus (T2DM).To report the findings from a multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial, which was designed to assess the efficacy and safety of a novel DPP-4 inhibitor fotagliptin in treatment-naive patients with T2DM. METHODS: Patients with T2DM were randomized to receive fotagliptin (n = 230), alogliptin (n = 113) or placebo (n = 115) at a 2:1:1 ratio for 24 weeks of double-blind treatment period, followed by an open-label treatment period, making up a total of 52 weeks. The primary efficacy endpoint was to determine the superiority of fotagliptin over placebo in the change of HbA1c from baseline to Week 24. All serious or significant adverse events were recorded. RESULTS: After 24 weeks, mean decreases in HbA1c from baseline were -0.70% for fotagliptin, -0.72% for alogliptin and -0.26% for placebo. Estimated mean treatment differences in HbA1c were -0.44% (95% confidence interval [CI]: -0.62% to -0.27%) for fotagliptin versus placebo, and -0.46% (95% CI: -0.67% to -0.26%) for alogliptin versus placebo, and 0.02% (95%CI: -0.16% to 0.19%; upper limit of 95%CI < margin of 0.4%) for fotagliptin versus alogliptin. So fotagliptin was non-inferior to alogliptin. Compared with subjects with placebo (15.5%), significantly more patients with fotagliptin (37.0%) and alogliptin (35.5%) achieved HbA1c < 7.0% after 24 weeks of treatment. During the whole 52 weeks of treatment, the overall incidence of hypoglycemia was low for both of the fotagliptin and alogliptin groups (1.0% each). No drug-related serious adverse events were observed in any treatment group. CONCLUSIONS: In summary, the study demonstrated improvement in glycemic control and a favorable safety profile for fotagliptin in treatment-naive patients with T2DM. TRIAL REGISTRATION: ClinicalTrail.gov NCT05782192.

Pancreatic fibroblast growth factor 21 protects against type 2 diabetes in mice by promoting insulin expression and secretion in a PI3K/Akt signaling-dependent manner.

Fibroblast growth factor 21 (FGF21) is important in glucose, lipid homeostasis and insulin sensitivity. However, it remains unknown whether FGF21 is involved in insulin expression and secretion that are dysregulated in type 2 diabetes mellitus (T2DM). In this study, we found that FGF21 was down-regulated in pancreatic islets of db/db mice, a mouse model of T2DM, along with decreased insulin expression, suggesting the possible involvement of FGF21 in maintaining insulin homeostasis and islet ß-cell function. Importantly, FGF21 knockout exacerbated palmitate-induced islet ß-cell failure and suppression of glucose-stimulated insulin secretion (GSIS). Pancreatic FGF21 overexpression significantly increased insulin expression, enhanced GSIS, improved islet morphology and reduced ß-cell apoptosis in db/db mice. Mechanistically, FGF21 promoted expression of insulin gene transcription factors and soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, the major regulators of insulin secretion, as well as activating phosphatidylinositol 3-kinase (PI3K)/Akt signaling in islets of db/db mice. In addition, pharmaceutical inhibition of PI3K/Akt signaling effectively suppressed FGF21-induced expression of insulin gene transcription factors and SNARE proteins, suggesting an essential role of PI3K/Akt signaling in FGF21-induced insulin expression and secretion. Taken together, our results demonstrate a protective role of pancreatic FGF21 in T2DM mice through inducing PI3K/Akt signaling-dependent insulin expression and secretion.

Thyrotoxic periodic paralysis complicated by life-threatening acute hypercapnic respiratory failure in a Chinese male with painless thyroiditis.

CONTEXT: Thyrotoxic periodic paralysis (TPP) is a relatively common complication seen in Asian hyperthyroid patients. However, it is a rare occurrence to find a TPP case comprised of acute hypercapnic respiratory failure in patients with painless thyroiditis. PATIENT: A 29-year-old Chinese man presented with flaccid paralysis of all four limbs and he was brought to emergency room. Severe hypokalemia was found on admission. Although treatment had been initiated with potassium chloride supplementation, he went on to develop acute hypercapnic respiratory failure likely due to muscle fatigue. The patient was intubated for mechanical ventilatory support. Once his serum potassium levels were normalized, he was able to be weaned off ventilator support. Thyroid function tests showed elevated free thyroxine concentration and low thyroid-stimulating hormone concentration. He underwent a thyroid uptake scan with 131I which revealed decreased uptake rate of thyroid area. Based on the patient's clinical presentation and associated findings, we diagnosed him with TPP due to painless thyroiditis. We have reviewed TPP cases caused by painless thyroiditis and TPP cases associated with acute hypercapnic respiratory failure. CONCLUSION: It is important to note that potentially fatal complications such as acute hypercapnic respiratory failure might occur in acute attacks of TPP even in cases of TPP due to painless thyroiditis.

A spontaneous pregnancy and successful delivery in a Chinese female with Silver-Russell syndrome accompanied by gestational diabetes mellitus.

Silver-Russell syndrome (SRS) is a heterogeneous disorder characterized by severe intrauterine and postnatal growth retardation and typical dysmorphic features including body asymmetry, relative macrocephaly, protruding forehead, and feeding difficulties. Previous descriptions of SRS focus on the management of specific issues in children. Herein, we present clinical and metabolic characteristics of an adult woman with SRS accompanied by gestational diabetes mellitus (GDM). Given the rare circumstances presented in our case, the emerging questions concerning the management of metabolic issues and fertility potential in adult SRS patient deserve more attention. Further, long-term follow up is essential to gain future insights into the natural history and optimal management in adulthood.

Activation of PPARγ Ameliorates Spatial Cognitive Deficits through Restoring Expression of AMPA Receptors in Seipin Knock-Out Mice.

A characteristic phenotype of congenital generalized lipodystrophy 2 (CGL2) that is caused by loss-of-function of seipin gene is mental retardation. Here, we show that seipin deficiency in hippocampal CA1 pyramidal cells caused the reduction of peroxisome proliferator-activated receptor gamma (PPARγ). Twelve-week-old systemic seipin knock-out mice and neuronal seipin knock-out (seipin-nKO) mice, but not adipose seipin knock-out mice, exhibited spatial cognitive deficits as assessed by the Morris water maze and Y-maze, which were ameliorated by the treatment with the PPARγ agonist rosiglitazone (rosi). In addition, seipin-nKO mice showed the synaptic dysfunction and the impairment of NMDA receptor-dependent LTP in hippocampal CA1 regions. The density of AMPA-induced current (IAMPA) in CA1 pyramidal cells and GluR1/GluR2 expression were significantly reduced in seipin-nKO mice, whereas the NMDA-induced current (INMDA) and NR1/NR2 expression were not altered. Rosi treatment in seipin-nKO mice could correct the decrease in expression and activity of AMPA receptor (AMPAR) and was accompanied by recovered synaptic function and LTP induction. Furthermore, hippocampal ERK2 and CREB phosphorylation in seipin-nKO mice were reduced and this could be rescued by rosi treatment. Rosi treatment in seipin-nKO mice elevated BDNF concentration. The MEK inhibitor U0126 blocked rosi-restored AMPAR expression and LTP induction in seipin-nKO mice, but the Trk family inhibitor K252a did not. These findings indicate that the neuronal seipin deficiency selectively suppresses AMPAR expression through reducing ERK-CREB activities, leading to the impairment of LTP and spatial memory, which can be rescued by PPARγ activation. SIGNIFICANCE STATEMENT: Congenital generalized lipodystrophy 2 (CGL2), caused by loss-of-function mutation of seipin gene, is characterized by mental retardation. By the generation of systemic or neuronal seipin knock-out mice, the present study provides in vivo evidence that neuronal seipin deficiency causes deficits in spatial memory and hippocampal LTP induction. Neuronal seipin deficiency selectively suppresses AMPA receptor expression, ERK-CREB phosphorylation with the decline of PPARγ. The PPARγ agonist rosiglitazone can ameliorate spatial cognitive deficits and rescue the LTP induction in seipin knock-out mice by restoring AMPA receptor expression and ERK-CREB activities.

17α-HYDROXYLASE/17, 20-LYASE DEFICIENCY: CLINICAL AND MOLECULAR CHARACTERIZATION OF EIGHT CHINESE PATIENTS.

OBJECTIVE: 17α-hydroxylase/17, 20-lyase deficiency (17OHD) is caused by mutations in the cytochrome P450 17A1 (CYP17A1) gene. To better understand 17OHD, a rare disease, we described the clinical features and performed CYP17A1 gene analysis in 8 affected Chinese patients. METHODS: Patients with complete (7/8) or partial (1/8) 17OHD were derived from 6 families. The diagnosis was established according to their clinical, biochemical, hormonal, and radiological characteristics. Long-term follow-up of some patients was also designed. RESULTS: Patients with 17OHD suffered from varying degrees of hypokalemia and hypertension. Symptoms in female patients with partial 17OHD manifested as secondary amenorrhea, recurrent ovarian cysts, elevated estradiol level, and lower follicle-stimulating hormone and luteinizing hormone levels; primary amenorrhea was typical in patients with complete 17OHD. Adrenal masses and decreased bone mineral density (BMD) were discovered in 2 patients, respectively. During long-term follow-up, 4 patients developed low BMD, while 3 individuals underwent respiratory infections and recurrent urinary tract infections. CYP17A1 gene analysis revealed 7 different kinds of mutation, including 1 novel mutation, L266V. CONCLUSION: The clinical characteristics of partial 17OHD were different from those of complete 17OHD. Low BMD and infections were common in patients with 17OHD on long-term steroid treatment. Seven mutations were identified in the CYP17A1 gene, and 1 was novel. ABBREVIATIONS: ACTH = adrenocorticotropic hormone BMD = bone mineral density CAH = congenital adrenal hyperplasia CT = computed tomography DEXA = dual-energy X-ray absorptiometry DEX = dexamethasone 17OHD = 17α-hydroxylase/17, 20-lyase deficiency.

Lack of testicular seipin causes teratozoospermia syndrome in men.

Obesity impairs male fertility, providing evidence for a link between adipose tissue and reproductive function; however, potential consequences of adipose tissue paucity on fertility remain unknown. Lack of s.c. fat is a hallmark of Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2), which is caused by mutations in BSCL2-encoding seipin. Mice with a targeted deletion of murine seipin model BSCL2 with severe lipodystrophy, insulin resistance, and fatty liver but also exhibit male sterility. Here, we report teratozoospermia syndrome in a lipodystrophic patient with compound BSCL2 mutations, with sperm defects resembling the defects of infertile seipin null mutant mice. Analysis of conditional mouse mutants revealed that adipocyte-specific loss of seipin causes progressive lipodystrophy without affecting fertility, whereas loss of seipin in germ cells results in complete male infertility and teratozoospermia. Spermatids of the human patient and mice devoid of seipin in germ cells are morphologically abnormal with large ectopic lipid droplets and aggregate in dysfunctional clusters. Elevated levels of phosphatidic acid accompanied with an altered ratio of polyunsaturated to monounsaturated and saturated fatty acids in mutant mouse testes indicate impaired phospholipid homeostasis during spermiogenesis. We conclude that testicular but not adipose tissue-derived seipin is essential for male fertility by modulating testicular phospholipid homeostasis.

[Analysis of AVPR2 gene mutation in a pedigree affected with congenital nephrogenic diabetes insipidus].

OBJECTIVE: To detect potential mutation in a pedigree affected with congenital nephrogenic diabetes insipidus (NDI). METHODS: Clinical data of a male patient affected with NDI was collected. Genomic DNA was extracted from peripheral blood samples from the patient and five family members. The whole coding region of the arginine vasopressin receptor 2 (AVPR2) gene was amplified by PCR and directly sequenced. RESULTS: The patient presented polyuria and polydipsia postnatally. Computerized tomography revealed bilateral hydronephrosis and hydroureter. The patient was responsive to hydrochlorothiazide but not to desmopressin. DNA analysis identified a hemizygous missence mutation c.295 T>C in exon 2 of the AVPR2 gene in the proband. His mother and grandmother were both heterozygous for the same mutation. CONCLUSION: The congenital NDI in the patient was probably due to mutation of the AVPR2 gene.

Biological characterization and in vitro fungicide screening of a new causal agent of walnut leaf spot in Guizhou Province, China.

Walnut (Juglans regia L.) is a widely grown nut plant worldwide, including in Guizhou Province, located in southwest China. The high quality and special taste make Guizhou walnuts, particularly those produced in Hezhang County, a "Chinese National Geographical Indication Product" that substantially contributes to the local economy and grower's income. In July 2022, a serious occurrence of leaf spot disease was observed in a walnut plantation area, Shuitang Town, Hezhang County, Guizhou Province, China (27°07'67″N, 104°64'61″E). The causal agent was identified as Didymella segeticola through morphological characterization and amplification and sequencing of the internal transcribed spacer (ITS) region, beta-tubulin (TUB) gene, and glyceraldehyde-3-phosphate dehydrogenase (G3PD) gene. Koch's postulates, including re-isolation and identification, were performed to confirm its pathogenicity on healthy leaves. To our knowledge, this is the first report of D. segeticola causing leaf spot on walnuts worldwide. Further, to determine its biological characteristics, which could be utilized for future disease management, the effects of temperature, light, and carbon and nitrogen resources on mycelial growth, conidia production, and conidia germination and the effects of humidity on conidia germination were studied. The optimum temperature for mycelial growth of representative strain D. segeticola C27 was 20°C. Increasing the light period significantly decreased conidia production and conidia germination. Maltose and beef extract were the best carbon and nitrogen sources, respectively, for the pathogen. Conidia germination was enhanced at 90% humidity. In vitro screening of effective fungicides was conducted. Among the 20 screened fungicides, difenoconazole showed the best inhibition rate, with an EC50 (concentration for 50% of the maximal effect) of 0.0007 µg/mL. Tetramycin also showed sufficient inhibitory effects against D. segeticola, with an EC50 value of 0.0009 µg/mL. Our study provides new insights into the causal agent of walnut leaf spot in Guizhou, China, as well as the first pathogen characteristics and promising candidate fungicides for its management.

Outer retina and choroid as potential imaging markers for evaluation of neural impairment in early type 2 diabetic patients.

PURPOSE: To quantify the presence of early structural alterations in the outer retinal layer and choroid among healthy subjects and diabetic patients with no or mild diabetic retinopathy, and to establish the correlation between the measured structural parameters and retinal sensitivity. METHODS: In total, 31 eyes from subjects with type 2 diabetes and 29 eyes from healthy subjects were enrolled. Optical coherence tomography was used to measure outer retina layers and choroid, while microperimetry was used to characterize the changes of visual function in a 6-mm diameter area at macula. Quantitative analysis of structural and functional changes was performed between groups and the structure-function correlations were determined. RESULTS: The thickness of myoid and ellipsoid zone, choroid and the mean retinal sensitivity were significantly smaller in diabetic group than that in controls (all P values < 0.05). Besides, thinner choroid and outer retina was associated with the decreased retinal sensitivity，especially in diabetic patients (r = 0.377, P = 0.048; r = 0.401, P = 0.034; respectively). Final multiple regression models showed the outer retinal thickness (ORT) (P = 0.033), choroidal thickness (P = 0.003) and the interaction between ORT and choroidal thickness (P = 0.001) were significant predictors to retinal sensitivity. CONCLUSIONS: Thinning of choroid and outer retina were significantly correlated with reduced retinal sensitivity, which indicate outer retina and choroid might be potential imaging markers for evaluation of visual function related to neural impairment in type 2 diabetic patients without or in the early stage of diabetic retinopathy.

Can XunTian Tai Chi intervention improve the level of emotional regulation of crew members in the Controlled Ecological Life Support System?

To explore the appropriate exercise methods and means for astronauts in confined and small isolation conditions, a set of XunTian Tai Chi suitable for the spaceflight workforce was created, with the aim of discovering the practical effects of XunTian Tai Chi and providing a scientific basis for the subsequent development of new astronaut health maintenance techniques with Chinese characteristics. Using the Controlled Ecological Life Support System (CELSS) as a research platform, we observed the changes in a crew member's emotion regulation-related indexes during 180 days of working and living in a confined isolation chamber through periodic interventions of the XunTian Tai Chi and conducted statistical analyses. During the 180-day cabin mission, expression suppression, cognitive reappraisal, attention index, and relaxation index were all lower than those before entering the cabin, suggesting that the crew member's emotion regulation ability decreased during the in-cabin mission. A single Tai Chi exercise could cause favorable changes in the indicators, positively affecting the crew member's emotional regulation. The attention and relaxation indices of the occupants were improved significantly by both single and periodic Tai Chi exercises. After the Tai Chi exercise cycle, the results of each index showed a certain degree of effect. The 180-day ground-based simulation of Tai Chi in the confinement of a space capsule positively affects the occupant's emotional regulation.

Effects of nitric acid rain stress on soil nitrogen fractions and fungal communities in a northern subtropical forest, China.

Acid rain has severely negatively impacted terrestrial ecosystems and biogeochemical cycles. However, the potential impacts of nitric acid rain (NAR) on soil nitrogen (N) fractions and fungal community diversity in northern subtropical forest soils remain largely unevaluated. In this study, treatments of NAR at pH = 4.5 (AR4.5), pH = 3.5 (AR3.5), and pH = 2.5 (AR2.5) were randomly sprayed in a typical Quercus acutissima Carruth. stand in northern subtropical China. The soil N fractions and soil fungal communities were analyzed after a 12-month experimental period. The results revealed that compared to the control, the soil total N (TN), microbial biomass N (MBN), hydrolysable ammonium N (HAN), amino-sugar N (ASN) and amino-acid N (AAN) contents decreased significantly by 19.61-13.07 %, 20.10-9.04 %, 60.41-28.87 %, 74.10-62.25 %, and 65.69-45.64 % under stronger acidity inputs (i.e., AR2.5 and AR3.5), respectively. Besides, the AR2.5 and AR3.5 treatments increased the α-diversity indices of soil fungal communities and altered the soil fungal community structure. Moreover, the NAR treatments represented an increase in the relative abundance of Ascomycota and Mortierellomycota and a decrease in that of Basidiomycota. Mortierella, Penicillium, and Tomentella can be used as indicator genera for changes in soil fungal community structures under NAR stress. Furthermore, AAN was the main environmental factor affecting soil fungal community at the phylum and genus levels. Cumulatively, findings from this research provide valuable insight into NAR's effects on N cycling and microbial communities in forest soils.

Clinical and genetic analysis for two Chinese siblings with 17α-hydroxylase/17,20-lyase deficiency.

AIMS: 17α-hydroxylase/17,20-lyase deficiency (17OHD) is characterized by impaired productions of gonadal steroids and cortisol, a subsequent elevation of adrenocorticotropic hormone, and accumulation of steroid precusors, which are shunted into the mineralocorticoid synthesis pathway. This disease is caused by mutations in the CYP17 gene. In this paper, we will describe the clinical features and genetic alterations on two female siblings of 46,XY and 46,XX from a family with complete 17OHD. METHODS: This study employed a spectrum of methods, including clinical, hormonal, radiological and genetic analyses. Blood samples from the siblings and their family members were taken for genetic tests. Genomic DNA was extracted from peripheral blood leukocytes, and coding sequence abnormalities of the CYP17 gene were assessed by polymerase chain reaction and direct sequencing analysis. RESULTS: Genetic analysis of the CYP17 gene revealed a homozygous mutation in the two siblings. The mutation is a microdeletion, located in exon 8, Asp487-Ser488-Phe489 deletion. This deletion may be a prevalent CYP17 mutation in the Chinese population. CONCLUSION: Our study showed that a possible founder effect may account for the recurrent mutation Asp487-Ser488-Phe489 deletion in Chinese patients with 17OHD. And genetic testing could provide a useful method for a definitive diagnosis of 17OHD.

Real-time intraoperative computed tomography can accurize virtual surgical planning on the double-barrel fibular flap for mandibular reconstruction.

Real-time intraoperative computed tomography created the accuracy of less than 1 mm deviation in virtual surgical planning double barrel fibular flap for mandibular reconstruction-the symbiosis of intelligent technology in a digital OR. BACKGROUND: With the intelligent technology of virtual surgical planning, CAD/CAM, and intraoperative CT(iCT) in a digital OR, the secondary mandibular defect or primary amelobalstoma mandibulectomy can be restored using double barrel fibula and be achieved precision medicine purpose. MATERIAL AND METHOD: A series of 7 patients underwent free flap for oral cancers who sustained 5 osteoradionecrosis, 2 segmental mandibular defect, and 2 ameloblastoma. They received 9 double barrel fibula flap and 2 free skin flaptransfers. The fibula flap were reconstructed using a virtual surgical planning including CAD/CAM for simulation 3D model, cutting guides for recipient sites and fibulas osteotomy, and iCT for image fusion in a digital OR. RESULT: The mandibular defect was 5-16 cm (average: 9.56 cm), and 2-5 fibular struts for double barrel fibula (average: 3.67 struts) image fusion. One vein graft for artery was required and all 11 flaps were transferred successfully without reexploration. Six patients had intraoperative revision of the fibula and plate to improve the onlay image fusion volume from 74.71 to 82.57%. The postoperative inter-incisor midline deviation was less than 2 mm in 5 patients, and well reduction image in 4 edentulous patients. Five landmarks including bilateral condyles, bilateral gonions, and gnathion demonstrated deviation less than 1 mm in average. CONCLUSION: CAD/CAM can allow a practical virtual surgery to restore mandibular defect reconstruction using a double barrel fibula. The symbiosis of intelligent technology in a digital OR, the iCT can promote the accuracy of mandibular spatialframework and occlusion plain.

Visual acuity is correlated with ischemia and neurodegeneration in patients with early stages of diabetic retinopathy.

PURPOSE: We investigated the effects of retinal ischemia, neurodegeneration, and subclinical edema on best-corrected visual acuity (BCVA) in the early stages of diabetic retinopathy (DR). METHODS: Ischemia was evaluated by the microvascular parameters measured by optical coherence tomography angiography. Neurodegeneration and subclinical edema were identified by the intraretinal layer thickness obtained by optical coherence tomography. Eyes with nonproliferative diabetic retinopathy (n = 132) from 89 patients were analyzed. Eyes were classified as having normal BCVA (n = 88 [66.7%], Snellen equivalent ≥ 20/20) or decreased BCVA (n = 44 [33.3%], Snellen equivalent < 20/20). The prevalence of ischemia, neurodegeneration, and subclinical edema was explored in patients with and without decreased BCVA, and correlations between BCVA and these pathological pathways were determined. RESULTS: Vessel density in the deep retinal capillary plexus (DRCP) and thickness of ganglion cell layer plus inner plexiform layer (GCL-IPL) were significantly lower in eyes with decreased BCVA compared with eyes with normal BCVA (both P < 0.05). In the final multiple regression predictive model, age, DRCP vessel density, and GCL-IPL thickness (all P ≤ 0.044) were predictors of BCVA. DRCP vessel density and GCL-IPL thickness have an interactive effect on visual acuity. The proportions of ischemia and neurodegeneration were significantly higher in eyes with decreased BCVA than in eyes with normal BCVA (P = 0.001 and P = 0.004, respectively). CONCLUSION: During the natural course of the early stages of DR, ischemia and neurodegeneration were the main disease pathways associated with visual acuity, and the mechanisms varied among patients.

Reduced Retinal Microvascular Density Related to Activity Status and Serum Antibodies in Patients with Graves' Ophthalmopathy.

Objective: To investigate changes in retinal capillary density (RCD) that occur in Graves' ophthalmopathy (GO) and explore their association with the clinical manifestations for GO.Material and Methods: A total of 125 participants (93 GO patients and 32 normal subjects) were enrolled. All participants underwent ophthalmology and endocrinology examinations. Retinal microvasculature was imaged by spectral domain optical coherence tomographic angiography (OCT-A). The RCDs in the superficial and deep retinal capillary plexuses (SRCP and DRCP) were quantified by the custom software from the OCT-A images, which were divided into total annular zones (TAZ) and four quadrants. Multiple linear regression analysis was used to explore the associations between RCD and the relevant factors.Results: Significant reduction was seen in the TAZ zone in SRCP and DRCP of GO group (P < .05) when compared to the healthy subjects; significant differences remained after adjustment of vascular relevant factors. According to the univariate analysis, the relevant factors of higher IOP, larger proptosis, higher clinical activity scoring (CAS), thyroid stimulating hormone-receptor autoantibodies (TRAb), and 131I therapy were significantly associated with decreased RCDs in GO patients (P < .05). Multivariate linear regression analysis showed that CAS and TRAb were the most important relevant factors for decreased RCDs.Conclusions: The RCD of GO patients was significantly decreased compared to the healthy controls. The activity status and serum antibodies associated with GO were the relevant factors for reduced RCD.

Stasis Leg Ulcers: Venous System Revises by Triggered Angiography Non-Contrast-Enhanced Sequence Magnetic Resonance Imaging.

OBJECTIVES: The distribution of venous pathology in stasis leg ulcers is unclear. The main reason for this uncertainty is the lack of objective diagnostic tools. To fill this gap, we assessed the effectiveness of triggered angiography non-contrast-enhanced (TRANCE)-magnetic resonance imaging (MRI) in determining the venous status of patients with stasis leg ulcers. METHODS: This prospective observational study included the data of 23 patients with stasis leg ulcers who underwent TRANCE-MRI between April 2017 and May 2020; the data were retrospectively analyzed. TRANCE MRI utilizes differences in vascular signal intensity during the cardiac cycle for subsequent image subtraction, providing not only a venogram but also an arteriogram without the use of contrast agents or radiation. RESULTS: TRANCE MRI revealed that the stasis leg ulcers of nine of the 23 patients could be attributed to valvular insufficiency and venous occlusion (including deep venous thrombosis [DVT], May-Thurner syndrome, and other external compression). Moreover, TRANCE MRI demonstrated no venous pathology in five patients (21.7%). We analyzed TRANCE MRI hemodynamic parameters, namely stroke volume, forward flow volume, backward flow volume, regurgitant fraction, absolute volume, mean flux, stroke distance, and mean velocity, in the external iliac vein, femoral vein, popliteal vein, and great saphenous vein (GSV) in three of the patients with valvular insufficiency and three of those with venous occlusion. We found that the mean velocity and stroke volume in the GSV was higher than that in the popliteal vein in all patients with venous valvular insufficiency. CONCLUSIONS: Stasis leg ulcers may have no underlying venous disease and could be confirmed by TRANCE-MRI. TRANCE MRI has good Interrater reliability between Duplex study in greater saphenous venous insufficiency. It also potentially surpasses existing diagnostic modalities in terms of distinguishable hemodynamic figures. Accordingly, TRANCE-MRI is a safe and useful tool for examining stasis leg ulcers and is extensively applied currently.

Reduced macular inner retinal thickness and microvascular density in the early stage of patients with dysthyroid optic neuropathy.

BACKGROUND: The goal was to investigate changes of the inner intra-retinal layer thicknesses and retinal capillary density (RCD) around the macula in thyroid-associated ophthalmopathy (TAO) patients with or without dysthyroid optic neuropathy (DON). METHODS: Forty-four TAO patients including 23 non-DON and 21 DON patients, and 38 healthy participants were enrolled. Spectral domain optical coherence tomography equipped with Angiovue was used to obtain three-dimensional retinal thickness maps and microvascular images of the superficial and deep retinal capillary layers (SRCL and DRCL, respectively) around the macula. Quantitative analyses were performed using a custom automated algorithm. RESULTS: The thicknesses of the nerve fiber layer, ganglion cell layer + inner plexiform layer, and ganglion cell complex (GCC) as well as the RCDs in the SRCL and DRCL in both TAO groups were significantly decreased compared to the controls. In addition, the RCDs in DRCL of the DON group were further decreased compared to the non-DON group. GCC thickness in both TAO groups was positively correlated with the RCDs of the SRCL in the total annular zone and in the temporal, inferior, and nasal sectors. The areas under the receiver operating characteristic curves for the GCC thickness combined with the RCD were generally larger than those of each single indicator. CONCLUSIONS: Thinned inner intra-retinal layers and decreased RCDs in the TAO patients without DON revealed that morphological changes might precede visual dysfunction. The composite index of the retinal structure and the microvascular density might be valuable in the diagnosing, monitoring, and intervention for early DON.

Tumor-induced osteomalacia with the culprit lesion located in the palm: a case report.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome. We herein report a rare case of TIO in a 58-year-old Chinese man who presented with a large lump in the right palm. Clinical, biochemical, and radiological assessments were performed. Laboratory examination showed severe hypophosphatemia, phosphaturia, an elevated serum alkaline phosphatase level, and an elevated serum fibroblast growth factor 23 (FGF-23) level. Dual-energy X-ray absorptiometry showed low bone mineral density. Magnetic resonance imaging revealed an irregular mass located in the right palm and abnormal findings in several metacarpal bones. During the operation, the surgeons found that the tumor had penetrated the surrounding muscles. The tumor had unique characteristics of local tissue invasion. The patient's symptoms fully resolved and his serum phosphorus level normalized, although his serum FGF-23 level remained slightly high in the postoperative phase. Our findings suggest that in some patients with TIO, the serum phosphorus level might return to the normal range despite a relatively high postoperative serum FGF-23 level. These patients should be kept under close observation and regularly surveyed for any evidence of a residual tumor.