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Abstract Background This retrospective study aimed to evaluate the precision and safety outcomes of image‐guided lung percutaneous thermal ablation (LPTA) methods, focusing on radiofrequency ablation (RFA) and microwave ablation (MWA). The study utilized an innovative angle reference guide to facilitate these techniques in the treatment of lung tumors. Methods This study included individuals undergoing LPTA with the assistance of laser angle guide assembly (LAGA) at our hospital between April 2011 and March 2021. We analyzed patient demographics, tumor characteristics, procedure details, and complications. Logistic regressions were employed to assess risk factors associated with complications. Results A total of 202 patients underwent ablation for 375 lung tumors across 275 sessions involving 495 ablations. Most procedures used RFA, especially in the right upper lobe, and the majority of ablations were performed in the prone position (49.7%). Target lesions were at a median depth of 39.3 mm from the pleura surface, and remarkably, 91.9% required only a single puncture. Complications occurred in 31.0% of ablations, with pneumothorax being the most prevalent (18.3%), followed by pain (12.5%), sweating (6.5%), fever (5.0%), cough (4.8%), hemothorax (1.6%), hemoptysis (1.2%), pleural effusion (2.0%), skin burn (0.6%), and air emboli (0.2%). The median procedure time was 21 min. Notably, smoking/chronic obstructive pulmonary disease emerged as a significant risk factor for complications. Conclusion The LAGA‐assisted LPTA enhanced safety by improving accuracy and reducing risks. Overall, this investigation contributes to the ongoing efforts to refine and improve the clinical application of these thermal ablation techniques in the treatment of lung tumors.

Abstract Purpose Investigating the effect of Muller’s muscle-conjunctival resection (MMCR) on the eyelid crease position. Methods This retrospective study included patients with unilateral acquired blepharoptosis who underwent MMCR during October 2018–December 2021. The following factors were recorded: preoperative, after phenylephrine, postoperative marginal reflex distance1 (MRD1) and tarsal platform show (TPS) of bilateral eyelids. The primary outcome was to measure the change in TPS and evaluate the factors associated with post-operative TPS. The secondary outcomes included exploring the rate of MRD1 and TPS symmetry after the operation. Results Forty patients were included in the final analysis. The mean MRD1 of the ptotic eye was 1.28 ± 0.78 mm, 2.79 ± 0.66 mm and 3.20 ± 0.67 mm before, after phenylephrine and after the operation, respectively. The mean TPS of the ptotic eye was 5.90 ± 1.86 mm, 3.96 ± 1.49 mm and 2.79 ± 1.63 mm before, after phenylephrine and after the operation, respectively. Changes in mean TPS after the phenylephrine test and post-operation were statistically significant (p

Summary: The accumulation of misfolded proteins in the endoplasmic reticulum (ER) induces the unfolded protein response (UPR), which acts through various mechanisms to reduce ER stress. While the UPR has been well studied for its effects on the ER, its impact on the Golgi is less understood. The Golgi complex receives transport vesicles from the endosome through two types of tethering factors: long coiled-coil golgin and the multisubunit Golgi-associated retrograde protein (GARP) complex. Here, we report that ER stress increases the phosphorylation of golgin Imh1 to maintain the GARP-mediated recycling of the SNAREs Snc1 and Tlg1. We also identify a specific function of the Golgi affected by ER stress and elucidate a homeostatic response to restore this function, which involves both an Ire1-dependent and a MAP kinase Slt2/ERK2-dependent mechanism. Furthermore, our findings advance a general understanding of how two different types of tethers act cooperatively to mediate a transport pathway.

Abstract Background Previous case reports have demonstrated the occurrence of ischemic optic neuropathy (ION) following intravitreal injections of antivascular endothelial growth factor (anti-VEGF). However, no previous studies have investigated the impact of injection numbers on the risk of ION. The aim of our study was to investigate whether repeated intravitreal injections of anti-VEGF would increase the risk of subsequent ION in patients with neovascular age-related macular degeneration (AMD). Methods A population-based, retrospective cohort study using the Taiwan National Health Insurance Research Database was conducted from 2007 to 2013. Neovascular AMD patients receiving intravitreal injections of anti-VEGF during the study period were enrolled in the study cohort. Enrollees were divided into three groups according to the categorized levels of injection number (first level: 15 times). Kaplan-Meier curves were generated to compare the cumulative hazard of subsequent ION among the three groups. Cox regression analyses were used to estimate crude and adjusted hazard ratios (HRs) for ION development with respect to the different levels of injection numbers. The confounders included for adjustment were age, sex, and comorbidities (diabetes, hypertension, hyperlipidemia, ischemic heart disease, and glaucoma). Results In total, the study cohort included 77,210 patients. Of these, 26,520, 38,010, and 12,680 were in the first-, second-, and third-level groups, respectively. The Kaplan-Meier method revealed that the cumulative hazards of ION were significantly higher in those who had a higher injection number. After adjusting for confounders, the adjusted HRs for ION in the second- and third-level groups were 1.91 (95% confidence interval [CI], 1.32–2.76) and 2.20 (95% CI, 1.42–3.43), respectively, compared with those in the first-level group. Conclusions Among patients with neovascular AMD, those who receive a higher number of anti-VEGF injections have a significantly higher risk of developing ION compared with individuals who receive a lower number of injections.

Postoperative hearing improvement is one of the main expectations for patients receiving tympanoplasty. The capacity to predict postoperative hearing may help to counsel a patient properly and avoid untoward expectations. It is difficult to predict postoperative hearing without knowing the disease process in the middle ear, which can only be assessed intraoperatively. However, the duration and extent of the underlying pathologies may represent in bone-conduction threshold and air-bone gap. Here in patients undergoing tympanoplasty without ossiculoplasty, we sorted and separated the surgery dates into the first group to build the predicting models and the second group to test the predictions. There were 87 and 30 ears, respectively. No specific enrollment or exclusion criteria were based on underlying pathologies such as the perforation size of the tympanic membrane or the middle ear conditions. The results show that bone-conduction threshold and air-bone gap together predicted air-conduction threshold after the surgery, including each frequency of 0.5k, 1k, 2k, and 4k Hz. The discrepancies between the predictions and recordings did not differ among these four frequencies. Of the variance in mean postoperative air-conduction threshold, 56.7% was linearly accounted for by these two preoperative predictors in this sample. The results suggest a trend that, the higher the frequency, the larger the part was accounted for by these two preoperative predictors. These together may help a surgeon to estimate frequency-specific hearing outcome after the surgery, answer patients' questions with quantitative statistics, and counsel patients with proper expectations.

The shift from postauricular to transcanal microscopic tympanoplasty brings potential advantages of minimal morbidity, less postoperative pain, patient comfort, and surgical ease and speed, but also uncertainties of unfamiliar grafting material, an inadequate operation view, and an uncertain learning curve. These challenges might affect the successful repair rate and the frequency-specific hearing outcome, which is important for hearing perception. Rare studies reported frequency-specific hearing outcome with the learning curve for shifting from postauricular to transcanal microscopic tympanoplasty. Here, from Jul. 2013 to Nov. 2018, we compared patients in a shift from postauricular approach (35 ears) to transcanal approach (35 ears) of microscopic type-1 tympanoplasty. The results show that both of postauricular and transcanal microscopic tympanoplasties reduced the mean air-bone gap, 0.5k Hz gap, and 1k Hz gap after the surgery. The further analyses on gap change as a function of frequency (0.5, 1, 2, and 4k Hz) show that both of postauricular and transcanal tympanoplasties improved postoperative air-bone gap among the levels of frequency. The post hoc comparisons display a common gap reduction difference between 0.5k and 4k Hz. The successful repair rate did not differ between the 2 groups. There was no correlation between the postoperative mean gap change and the surgery date, suggesting a minimal learning-curve effect. The results of similar frequency-specific improvements and a minimal learning-curve effect may help to ease the concerns of those uncertainties before the shift.

Abstract Background Global cerebral ischemia triggers neurodegeneration in the hippocampal CA1 region, but the mechanism of neuronal death remains elusive. The epsilon isoform of protein kinase C (PKCε) has recently been identified as a master switch that controls the nucleocytoplasmic trafficking of ATF2 and the survival of melanoma cells. It is of interest to assess the role of PKCε–ATF2 signaling in neurodegeneration. Results Phosphorylation of ATF2 at Thr-52 was reduced in the hippocampus of PKCε null mice, suggesting that ATF2 is a phosphorylation substrate of PKCε. PKCε protein concentrations were significantly reduced 4, 24, 48 and 72 h after transient global cerebral ischemia, resulting in translocation of nuclear ATF2 to the mitochondria. Degenerating neurons staining positively with Fluoro-Jade C exhibited cytoplasmic ATF2. Conclusions Our results support the hypothesis that PKCε regulates phosphorylation and nuclear sequestration of ATF2 in hippocampal neurons during ischemia-induced neurodegeneration.

The present study was carried out to demonstrate novel use of pharmacokinetic approaches to characterize drug behaviors/movements in the vegetables with implications to food safety. The absorption, distribution, metabolism and most importantly, the elimination of tetracycline (TC) and sulfamethoxazole (SMX) in edible plants Brassica rapa chinensis and Ipomoea aquatica grown hydroponically were demonstrated and studied using non-compartmental pharmacokinetic analysis. The results revealed drug-dependent and vegetable-dependent pharmacokinetic differences and indicated that ephemeral vegetables could have high capacity accumulating antibiotics (up to 160 μg g-1 for TC and 38 μg g-1 for SMX) within hours. TC concentration in the root (Cmax) could reach 11 times higher than that in the cultivation fluid and 3-28 times higher than the petioles/stems. Based on the volume of distribution (Vss), SMX was 3-6 times more extensively distributed than TC. Both antibiotics showed evident, albeit slow elimination phase with elimination half-lives ranging from 22 to 88 hours. For the first time drug elimination through the roots of a plant was demonstrated, and by viewing the root as a central compartment and continuous infusion without a loading dose as drug administration mode, it is possible to pharmacokinetically monitor the movement of antibiotics and their fate in the vegetables with more detailed information not previously available. Phyto-pharmacokinetic could be a new area worth developing new models for the assessment of veterinary drugs in edible plants.

This paper is the first to investigate the effect of industrial penetration (geographic concentration of industries) and internet intensity (the proportion of enterprises that uses the internet) for Taiwan manufacturing firms, and analyses whether the relationships are substitutes or complements. The sample observations are based on a unique set of data, namely 153,081 manufacturing plants, and covers 26 two-digit industry categories and 358 geographical townships in Taiwan. The Heckman sample selection model is used to accommodate sample selectivity for unobservable data for firms that use the internet. The empirical results from Heckman’s two-stage estimation show that: (1) a higher degree of industrial penetration will not affect the probability that firms will use the internet, but it will affect the total expenditure on internet intensity; (2) for two-digit SIC (Standard Industrial Classification) industries, industrial penetration generally decreases the total expenditure on internet intensity; and, (3) industrial penetration and internet intensity are substitutes.

Type I insulin-like growth factor receptor (IGF-1R) and insulin receptor (INSR) are highly homologous molecules, which can heterodimerize to form an IGF-1R/INSR hybrid (Hybrid-R). The presence and biological significance of the Hybrid-R in human corneal epithelium has not yet been established. In addition, while nuclear localization of IGF-1R was recently reported in cancer cells and human corneal epithelial cells, the function and profile of nuclear IGF-1R is unknown. In this study, we characterized the nuclear localization and function of the Hybrid-R and the role of IGF-1/IGF-1R and Hybrid-R signaling in the human corneal epithelium.IGF-1-mediated signaling and cell growth were examined in a human telomerized corneal epithelial (hTCEpi) cell line using co-immunoprecipitation, immunoblotting and cell proliferation assays. The presence of Hybrid-R in hTCEpi and primary cultured human corneal epithelial cells was confirmed by immunofluorescence and reciprocal immunoprecipitation of whole cell lysates. We found that IGF-1 stimulated Akt and promoted cell growth through IGF-1R activation, which was independent of the Hybrid-R. The presence of Hybrid-R, but not IGF-1R/IGF-1R, was detected in nuclear extracts. Knockdown of INSR by small interfering RNA resulted in depletion of the INSR/INSR and preferential formation of Hybrid-R. Chromatin-immunoprecipitation sequencing assay with anti-IGF-1R or anti-INSR was subsequently performed to identify potential genomic targets responsible for critical homeostatic regulatory pathways.In contrast to previous reports on nuclear localized IGF-1R, this is the first report identifying the nuclear localization of Hybrid-R in an epithelial cell line. The identification of a nuclear Hybrid-R and novel genomic targets suggests that IGF-1R traffics to the nucleus as an IGF-1R/INSR heterotetrameric complex to regulate corneal epithelial homeostatic pathways. The development of novel therapeutic strategies designed to target the IGF-1/IGF-1R pathway must take into account the modulatory roles IGF-1R/INSR play in the epithelial cell nucleus.