A multifunctional CaCO3 bioreactor coated with coordination polymers enhances cancer immunotherapy.

Designing effective nanomedicines to induce durable anti-tumor immunity represents a promising strategy for improving moderate immune stimulation. In this study, we engineered a multifunctional nanoreactor (named SCGFP NPs) for remodeling the tumor microenvironment (TME) to improve the therapeutic efficacy of immunotherapy. The core of SCGFP NPs consists of CaCO3 loaded with SN38, prepared by the gas diffusion method, and coated with a significant amount of gallic acid-Fe3+-PEG coordination polymer on the surface. In the acidic TME, SCGFP NPs explosively release exogenous Ca2+ and SN38. The SN38-induced intracellular Ca2+ accumulation and exogenous Ca2+ synergistically trigger immunogenic cell death (ICD) through sustained Ca2+ overload. The ablation of tumors with high-intensity photothermal therapy (PTT) by near-infrared (NIR) irradiation of GA-Fe3+ induces tumor cell necrosis, further enhancing ICD activation. Additionally, SN38 upregulates PD-L1, amplifying tumor responsiveness to immune checkpoint inhibitors (ICIs). This study indicates that SCGFP NPs, through the integration of a trimodal therapeutic strategy, hold enormous potential for various types of tumor immunotherapy through distinct mechanisms or synergistic effects.

The histone methyltransferase ASH1L protects against bone loss by inhibiting osteoclastogenesis.

Absent, small, or homeotic1-like (ASH1L) is a histone lysine methyltransferase that generally functions as a transcriptional activator in controlling cell fate. So far, its physiological relevance in bone homeostasis and osteoclast differentiation remains elusive. Here, by conditional deleting Ash1l in osteoclast progenitors of mice, we found ASH1L deficiency resulted in osteoporosis and potentiation of osteoclastogenesis in vivo and in vitro. Mechanistically, ASH1L binds the promoter of the Src homology 3 and cysteine-rich domain 2 (Stac2) and increases the gene's transcription via histone 3 lysine 4 (H3K4) trimethylation modification, thus augmenting the STAC2's protection against receptor activator of nuclear factor kB ligand (RANKL)-initiated inflammation during osteoclast formation. Collectively, we demonstrate the first piece of evidence to prove ASH1L as a critical checkpoint during osteoclastogenesis. The work sheds new light on our understanding about the biological function of ASH1L in bone homeostasis, therefore providing a valuable therapeutic target for the treatment of osteoporosis or inflammatory bone diseases.

Perioperative outcomes of bilateral axillo-breast approach robotic thyroidectomy (BABART) versus minimally invasive thyroidectomy (MIT): a systematic review and meta-analysis.

Minimally invasive thyroidectomy (MIT) is increasingly being used for the thyroid tumors. The comparison of bilateral axillo-breast approach robotic thyroidectomy (BABART) with other MIT has not yet led to a unified conclusion with regard to surgical outcomes. To conduct a systematic review and meta-analysis of the literature on the surgical outcomes of BABART compared with MIT. We performed a systematic search in PubMed, Web of Science, Embase and Cochrane Library database for randomized control trials (RCTs) and non-RCTs that compare BABART to MIT. The primary outcomes included perioperative, postoperative complications. The odds ratio (OR) and mean difference (MD) were applied for the comparison of dichotomous and continuous variables with 95% confidence intervals (CIs). Nine studies, comprising 3645 patients, were included in the meta-analysis. Our findings indicated that there were no significant differences in hospital stay, number of retrieved lymph nodes, recurrent laryngeal nerve (RLN) injury, and vocal cord dysfunction between BABRT and MIT. However, BABART was associated with a shorter operation time (MD = - 21.45 min, 95% CI [- 47.27, 4.38], p = 0.1) and lower rate of permanent hypoparathyroidism (OR = 0.42, 95% CI [0.20, 0.88], p = 0.02). Additionally, the MIT group had reduced postoperative pain score (MD = 0.45, 95% CI [0.02, 0.88], p = 0.04) and lower rate of hypocalcemia (OR = 2.31, 95% CI [1.04, 5.13], p = 0.04) than the BABART group. In comparison with MIT, BABART exhibits better results in terms of operative time and the rate of permanent hypoparathyroidism, with no significant difference in hospital stay, number of retrieved lymph nodes, RLN injury, and vocal cord dysfunction. However, the postoperative pain score and the rate of hypocalcemia of MIT are slightly better that of BABART.

Construction and Validation of a Nomogram Predicting the Overall Survival Benefit of Unilateral Breast Cancer Patients Undergoing Contralateral Prophylactic Mastectomy.

BACKGROUND: Currently, research on the prognostic factors of unilateral breast cancer (UBC) patients receiving contralateral prophylactic mastectomy (CPM) is limited. This study aimed to construct a new nomogram to predict these patients' overall survival (OS). METHODS: In this retrospective study, 88,477 patients who underwent CPM or unilateral mastectomy (UM) were selected from the Surveillance, Epidemiology, and End Results database. Kaplan-Meier curves and Cox regression analyses were used to determine the difference in the impact of the 2 surgical methods on the prognosis. Multivariate Cox analysis was used to determine the best prognostic variable and construct a nomogram. The concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve, decision curve analysis (DCA), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to evaluate the discrimination capability and clinical effectiveness of the nomogram. RESULTS: The prognosis of patients receiving CPM and UM was significantly different. The DCA curves indicated that the nomogram could provide more excellent clinical net benefits for these patients. The NRI and IDI of the nomogram demonstrated that its performance was better than that of the classical tumor-node-metastasis (TNM) staging system. CONCLUSION: This study developed and validated a practical nomogram to predict the OS of UBC patients undergoing CPM, which provided a beneficial tool for clinical decision-making management.

Exosomal lncCRLA is predictive for the evolvement and development of lung adenocarcinoma.

Lung adenocarcinoma, the most common histological subtype of non-small cell lung cancer, exhibits heterogeneity that enables adaptability, limits therapeutic success, and remains incompletely understood. Our team uncovers that lncRNA related to chemotherapy resistance in lung adenocarcinoma (lncCRLA) is preferentially expressed in lung adenocarcinoma cells with the mesenchymal phenotype. lncCRLA can not enhance chemotherapy resistance in lung adenocarcinoma due to its binding to RIPK1 in exosomes, which is released into intercellular media and transferred by exosomes from mesenchymal-like to epithelial-like cells. However, plasmatic lncCRLA corresponding to tissue lncCRLA functions as a preferred biomarker to reflect the response to chemotherapy and disease progression of lung adenocarcinoma. Through single-cell sequencing, RNA-Mutect technique and spatial transcriptomics, a handful of hybrid EMT cells with elevated lncCRLA are characterized as the origin of lung adenocarcinoma, which are indiscriminated from hybrid EMT cells by the in-depth sequencing. Plasmatic lncCRLA is properly predictive for the preinvasive lesion of lung adenocarcinoma that would evolve to invasive lesion. That notion is confirmed by a brand-new transgenic mouse model in which EMT is tracked by Cre and Dre system. Dasatinib is potential to hinder the spontaneous progression from preinvasive to invasive lesion of lung adenocarcinoma. Together, plasmatic lncCRLA is defined as a brand-new circulating biomarker to predict the occurrence and evolvement of lung adenocarcinoma, a light for early detection of lung adenocarcinoma.

The value of CT-based radiomics in predicting the prognosis of acute pancreatitis.

Purpose: Early judgment of the progress of acute pancreatitis (AP) and timely intervention are crucial to the prognosis of patients. The purpose of this study was to investigate the application value of CT-based radiomics of pancreatic parenchyma in predicting the prognosis of early AP. Materials and methods: This retrospective study enrolled 137 patients diagnosed with AP (95 cases in the progressive group and 42 cases in the non-progressive group) who underwent CT scans. Patients were randomly divided into a training set (n = 95) and a validation set (n = 42) in a ratio of 7: 3. The region of interest (ROI) was outlined along the inner edge of the pancreatic parenchyma manually, and the Modified CT Severity Index (MCTSI) was assessed. After resampling and normalizing the CT image, a total of 2,264 radiomics features were extracted from the ROI. The radiomics features were downscaled and filtered using minimum redundancy maximum correlation (mRMR) and the least absolute shrinkage and selection operator algorithm (LASSO) regression, in turn, and the more optimal subset of radiomics features was selected. In addition, the radiomics score (rad-score) was calculated for each patient by the LASSO method. Clinical data were also analyzed to predict the prognosis of AP. Three prediction models, including clinical model, radiomics model, and combined clinical-radiomics model, are constructed. The effectiveness of each model was evaluated using receiver operating characteristic (ROC) curve analysis. The DeLong test was employed to compare the differences between the ROC curves. The decision curve analysis (DCA) is used to assess the net benefit of the model. Results: The mRMR algorithm and LASSO regression were used to select 13 radiomics features with high values. The rad-score of each texture feature was calculated to fuse MCTSI to establish the radiomics model, and both the clinical model and clinical-radiomics model were established. The clinical-radiomics model showed the best performance, the AUC and 95% confidence interval, accuracy, sensitivity, and specificity of the clinical-radiomics model in the training set were 0.984 (0.964-1.000), 0.947, 0.955, and 0.931, respectively. In the validation set, they were 0.942 (0.870-1.000), 0.929, 0.966, and 0.846, respectively. The Delong test showed that the predictive efficacy of the clinical-radiomics model was higher than that of the clinical model (Z = 2.767, p = 0.005) and the radiomics model (Z = 2.033, p = 0.042) in the validation set. Decision curve analysis demonstrated higher net clinical benefit for the clinical-radiomics model. Conclusion: The pancreatic parenchymal CT clinical-radiomics model has high diagnostic efficacy in predicting the progression of early AP patients, which is significantly better than the clinical or radiomics model. The combined model can help identify and determine the progression trend of patients with AP and improve the prognosis and survival of patients as early as possible.

Ultrawide and unidirectional enhancements of a photonic spin Hall effect in a tilted uniaxial crystal.

Since the enhancement of the photonic spin Hall effect (PSHE) is limited around the Brewster's angle, the scientific problem of how to extend the range of incident angles and to keep them unidirectional for the enhanced PSHE remains open. Here, we propose an effective method to achieve the ultrawide angle and unidirectional enhancement of PSHE via the omnidirectional Brewster's effect in a tilted uniaxial crystal. By properly setting the permittivity and the optical axial angle of the uniaxial crystal, the omnidirectional Brewster's effect can be obtained to realize an ultrawide angle enhancement of the PSHE. Then, by appropriately deviating the optical axial angle, the ultrawide enhancement of the PSHE can be achieved within the maximum incident angle range of 60° with unchanged direction. These findings inspire an unprecedented route to facilitate the applications in precision measurement and spin-dependent devices.

Neoadjuvant immunotherapy combined with chemotherapy in the treatment of stage III lung squamous cell carcinoma: a retrospective cohort study.

Background: Neoadjuvant immunochemotherapy has been proven to be a successful therapeutic strategy for patients with locally advanced non-small cell lung cancer (NSCLC). Nevertheless, there is a paucity of information regarding surgical feasibility and safety as well as tumor response. The present study aimed to investigate the therapeutic and surgical outcomes for patients with stage III lung squamous cell carcinoma (LSCC). Methods: Patients with stage III potentially resectable LSCC treated with neoadjuvant immunochemotherapy at The First Affiliated Hospital of Ningbo University between March 2020 and June 2022 were retrospectively included. Oncologic outcomes and intraoperative and postoperative variables were assessed. Results: A total of 17 locally advanced LSCC patients were included in the study. Patients in stages IIIA and IIIB were represented by 10 (58.8%) and 7 (41.2%) cases, respectively. A minimally invasive procedure was successfully completed in 12 out of 17 cases (70.6%). A total of 10 patients (58.8%) had standard lobectomies performed, 1 (5.9%) had a bilobectomy, 3 (17.6%) had pneumonectomies, and 1 (5.9%) had a wedge resection. A total of 7 patients (41.2%) experienced postoperative complications, and there were no 30- or 90-day mortalities. The 2-year disease-free survival (DFS) and overall survival (OS) rates were 76.6% and 82.5%, respectively. The rate of major pathological response (MPR) was 70.6%. Conclusions: Lung resection after immunochemotherapy for potentially resectable stage III LSCC is feasible and safe. This treatment strategy results in a significant pathologic response and promising rates of OS at 2 years.

Two Birds with One Stone: V4 C3 MXene Synergistically Promoted VS2 Cathode and Zinc Anode for High-Performance Aqueous Zinc-Ion Batteries.

Aqueous zinc-ion batteries (AZIBs) are considered to be a rising star in the large-scale energy storage area because of their low cost and environmental friendliness properties. However, the limited electrochemical performance of the cathode and severe zinc dendrite of the anode severely hinder the practical application of AZIBs. Herein, a novel 3D interconnected VS2 ⊥V4 C3 Tx heterostructure material is prepared via one-step solvothermal method. Morphological and structural characterizations show that VS2 nanosheets are uniformly and dispersedly distributed on the surface of the V4 C3 MXene substrate, which can effectively suppress volume change of the VS2 . Owing to the open heterostructure along with the high conductivity of V4 C3 MXene, the VS2 ⊥V4 C3 Tx cathode shows a high specific capacity of 273.9 mAh g-1 at 1 A g-1 and an excellent rate capability of 143.2 mAh g-1 at 20 A g-1 . The V4 C3 MXene can also effectively suppress zinc dendrite growth when used as protective layer for the Zn anode, making the V4 C3 Tx @Zn symmetric cell with a stable voltage profile for ≈1700 h. Benefitting from the synergistic modification effect of V4 C3 MXene on both the cathode and anode, the VS2 ⊥V4 C3 Tx ||V4 C3 Tx @Zn battery exhibits a long cycling lifespan of 5000 cycles with a capacity of 157.1 mAh g-1 at 5A g-1 .

Genome-wide DNA methylation analysis identifies potent CpG signature for temzolomide response in non-G-CIMP glioblastomas with unmethylated MGMT promoter: MGMT-dependent roles of GPR81.

PURPOSES: To identify potent DNA methylation candidates that could predict response to temozolomide (TMZ) in glioblastomas (GBMs) that do not have glioma-CpGs island methylator phenotype (G-CIMP) but have an unmethylated promoter of O-6-methylguanine-DNA methyltransferase (unMGMT). METHODS: The discovery-validation approach was planned incorporating a series of G-CIMP-/unMGMT GBM cohorts with DNA methylation microarray data and clinical information, to construct multi-CpG prediction models. Different bioinformatic and experimental analyses were performed for biological exploration. RESULTS: By analyzing discovery sets with radiotherapy (RT) plus TMZ versus RT alone, we identified a panel of 64 TMZ efficacy-related CpGs, from which a 10-CpG risk signature was further constructed. Both the 64-CpG panel and the 10-CpG risk signature were validated showing significant correlations with overall survival of G-CIMP-/unMGMT GBMs when treated with RT/TMZ, rather than RT alone. The 10-CpG risk signature was further observed for aiding TMZ choice by distinguishing differential outcomes to RT/TMZ versus RT within each risk subgroup. Functional studies on GPR81, the gene harboring one of the 10 CpGs, indicated its distinct impacts on TMZ resistance in GBM cells, which may be dependent on the status of MGMT expression. CONCLUSIONS: The 64 TMZ efficacy-related CpGs and in particular the 10-CpG risk signature may serve as promising predictive biomarker candidates for guiding optimal usage of TMZ in G-CIMP-/unMGMT GBMs.

Harmonics elimination in phase-shifting fringe projection profilometry by use of a non-filtering algorithm in frequency domain.

In phase-shifting fringe projection profilometry, fringe harmonics caused by device nonlinearities as well as other factors may badly ruin the measurement results. Generally, the used phase-shifting algorithm enables restraint of effects of harmonics below a certain order depending on the number of phase shifts. When reducing the number of phase shifts for efficiency, high order harmonics will affect the phase-measuring results because of aliasing caused by insufficient sampling rate. To overcome this issue, this paper suggests a non-filtering technique operating in frequency domain, that enables improvement of measurement accuracy by eliminating effects of high order harmonics. With this technique, the phase-shifting algorithm is restated as a process of retrieving the fundamental complex fringes from the phase-shifted fringe patterns. Implementing a Fourier transform to this calculated complex fringe pattern, the actual fundamental signals and the aliased harmonics have their own lobes with separated peaks in the frequency domain. We reconstruct each order of the aliased harmonics by exploiting their relations with the fundamental signals and then estimate their magnitudes by using the spectral peaks. Instead of directly filtering the fringe spectrum, we subtract spectra of the harmonics from Fourier transform of the just calculated complex fringes, so that the Fourier spectrum of the fundamental fringes without harmonics is recovered through an iterative operation. Further, the phase map is measured accurately. Simulation and experimental results confirm that this proposed method can significantly suppress effects of fringe harmonics. Meanwhile, by taking advantage of non-filtering, it effectively preserves the edges and details of the measured surfaces from being blurred.

Paternal lipopolysaccharide exposure induced intrauterine growth restriction via the inactivation of placental MEST/PI3K/AKT pathway in mice.

Maternal lipopolysaccharide (LPS) exposure during pregnancy has been related to IUGR. Here, we explored whether paternal LPS exposure before mating impaired fetal development. All male mice except controls were intraperitoneally injected with LPS every other day for a total of five injections. The next day after the last LPS, male mice were mated with untreated female mice. Interestingly, fetal weight and crown-rump length were reduced, while the incidence of IUGR was increased in paternal LPS exposure group. Additionally, paternal LPS exposure leaded to poor placental development through causing cell proliferation inhibition and apoptosis. Additional experiment demonstrated that the inactivation of placental PI3K/AKT pathway might be involved in paternal LPS-induced cell proliferation inhibition and apoptosis of trophoblast cells. Furthermore, the mRNA and protein levels of mesoderm specific transcript (MEST), a maternally imprinted gene with paternal expression, were significantly decreased in mouse placentas from paternal LPS exposure. Further analysis showed that paternal LPS exposure caused the inactivation of placental PI3K/AKT pathway and then cell proliferation inhibition and apoptosis might be via down-regulating placental MEST. Overall, our results provide evidence that paternal LPS exposure causes poor placental development and subsequently IUGR may be via down-regulating MEST/PI3K/AKT pathway, and then inducing cell proliferation inhibition and apoptosis in placentas.

Defect-Free Few-Layer M4 C3 Tx (M = V, Nb, Ta) MXene Nanosheets: Synthesis, Characterization, and Physicochemical Properties.

High-quality few-layer M4 C3 Tx (M = V, Nb, Ta) MXenes are very important for applications and are necessary for clarifying their physicochemical properties. However, the difficulty in etching for themselves and the existence of MC/MC1-δ and M-Al alloy impurities in their M4 AlC3 precursors seriously hinder the achievement of defect-free few-layer M4 C3 Tx (M = V, Nb, Ta) MXenes nanosheets. Herein, three different defect-free few-layer M4 C3 Tx (M = V, Nb, Ta) nanosheets are obtained by using a universal synthesis strategy of calcination, selective etching, intercalation, and exfoliation. Comprehensive characterizations confirm their defect-free few-layer structure feature, large interlayer spacing (1.702-1.955 nm), types of functional groups (-OH, -F, -O), and abundant valance states (M5+ , M4+ , M3+ , M2+ , M0 ). M4 C3 Tx (M = V, Nb, Ta) free-standing films obtained by vacuum filtration of few-layer M4 C3 Tx inks show good hydrophilia, high thermostability, and conductivity. A roadmap on synthesis of defect-free few-layer M4 C3 Tx (M = V, Nb, Ta) nanosheets are proposed and three key points are summarized. This work provides detailed guidelines for the synthesis of other defect-free few-layer MXenes nanosheets, but also will stimulate extensive functional explorations for M4 C3 Tx (M = V, Nb, Ta) MXenes nanosheets in the future.

Broadband binary-reflection-phase metasurfaces with undistorted transmission wavefront via mirror symmetry.

In this work, we report the realization of broadband binary-reflection-phase metasurfaces that simultaneously exhibit undistorted transmission wavefront. Such a unique functionality is bestowed by leveraging mirror symmetry in the metasurface design. Under the normal incidence of waves polarized along the mirror surface, a broadband binary-phase pattern with π phase difference is induced in the cross-polarized reflection, while the co-polarized transmission and reflection are unaffected by the binary-phase pattern. Consequently, the cross-polarized reflection can be flexibly manipulated by designing the binary-phase pattern, without distorting the wavefront in transmission. The phenomena of reflected-beam splitting and undistorted transmission wavefront are hereby experimentally validated in a broad bandwidth from 8 GHz to 13 GHz. Our findings reveal a unique mechanism to realize independent manipulation of reflection with undistorted transmission wavefront in a broad spectrum, which has potential implications in meta-domes and reconfigurable intelligent surfaces.

Thickness-dependent in-plane shift of photonic spin Hall effect in an anisotropic medium.

As the in-plane spin splitting (IPSS) has a broad application for the precision measurement and sensing, it is extremely important to explore its enhancement mechanism via the photonic spin Hall effect (PSHE). However, for a multilayer structure, the thickness in most of previous works is generally set as a fixed value, lacking the deeply exploration of the influence of thickness on the IPSS. By contrast, here we demonstrate the comprehensive understanding of thickness-dependent IPSS in a three layered anisotropic structure. As thickness increases, near the Brewster angle, the enhanced in-plane shift exhibits a thickness-dependently periodical modulation, besides with much wider incident angle than that in an isotropic medium. While near the critical angle, it becomes thickness-dependently periodical or linear modulation under different dielectric tensors of the anisotropic medium, no longer keeps almost constant in an isotropic medium. In addition, as exploring the asymmetric in-plane shift with arbitrary linear polarization incidence, the anisotropic medium could bring more obvious and wider range of thickness-dependently periodical asymmetric splitting. Our results deepen the understanding of enhanced IPSS, which is expected to promise a pathway in an anisotropic medium for the spin control and integrated device based on PSHE.

Generalized Brewster angle-enhanced photonic spin Hall effect in an all-dielectric metasurface.

The enhancement of the photonic spin Hall effect (PSHE) is usually limited at horizontally polarized incidence and around the nonadjustable Brewster angle. In this Letter, a flexible method for enhancing the reflective PSHE with tunable incident angle under both vertically (V) and horizontally (H) polarized light has been theoretically explored. By using the multipole decomposition method, the variable generalized Brewster angle (GBA) is proven to be obtained under both V- and H-polarized light at different wavelengths in the all-dielectric metasurface. Then, owing to the large ratio of Fresnel coefficients at the GBA, the enhancement of PSHE in this Letter can not only be available for both V- and H-polarization, but also achieved at widely tunable incident angle and different operating wavelengths in the same metasurface. This work provides a simple method to achieve the flexible enhancement of PSHE and offers a novel way for designing a functional spin-based photonic device.

Annexin A3 accelerates osteoclast differentiation by promoting the level of RANK and TRAF6.

Annexin A3 (ANXA3), a member of Annexin family, is reported to mediate membrane transport and cancer development. However, the effect of ANXA3 on osteoclast formation and bone metabolism is still unclear. In this study, we found that knockdown of ANXA3 can significantly inhibit receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation through NF-κB signaling. ANXA3 downregulation abrogated the expression of osteoclast-specific genes, including Acp5, Mmp9 and Ctsk in osteoclast precursors. Moreover, lentiviral of shRNA against ANXA3 reversed the bone loss in osteoporosis using ovariectomized mice model. Mechanistically, we found that ANXA3 directly bound to RANK and TRAF6 to accelerate osteoclast differentiation by promoting their transcription and limiting degradation. In conclusion, we propose a fundamentally novel RANK-ANXA3-TRAF6 complex to effectively modulate the formation and differentiation of osteoclast to manipulate bone metabolism. The ANXA3-targeted therapeutic strategy may provide new insight for bone degrading-related diseases prevention and treatment.

Characteristics of fibrotic-foci-like lung adenocarcinoma on 18 F-FDG PET/computed tomography and HRCT.

PURPOSE: To assess the characteristics of fibrotic-foci-like lung adenocarcinoma on 18 F-fluorodeoxyglucose PET/computed tomography ( 18 F-FDG PET/CT) and high-resolution computed tomography (HRCT). MATERIAL AND METHODS: This was a retrospective study with 20 cases in the fibrotic-foci-like lung adenocarcinoma group; the control group was old fibrotic-foci of the lung with 20 cases. The following 18 F-FDG PET/CT and HRCT features were evaluated: the maximum standardized uptake value (SUVmax); the tumor-to-background ratios of SUVmax (TBRmax); the long-to-short diameter ratio (L/S); anatomic location; location type; internal characteristics; marginal characteristics and surrounding structures. In the fibrotic-foci-like lung adenocarcinoma group, a comparison of 18 F-FDG uptake between the metastatic group ( n  = 10) and the non-metastatic group ( n  = 10) was performed. Finally, the comparison of diagnostic accuracy for fibrotic-foci-like lung adenocarcinoma between 18 F-FDG PET/CT and HRCT was performed. RESULTS: The SUVmax [2.6 (1.7-7.9) vs. 1.0 (0.7-1.4)], TBRmax [2.9 (2.1-9.9) vs. 1.3 (1.2- 1.7)], L/S [2.4 (1.7-3.8) vs. 4.0 (3.2-6.3)], ground-glass opacity (GGO) [13/20 (65.0%) vs. 4/20 (20.0%)], and vessel convergence [7/20 (35.0%) vs. 1/20 (5.0%)] were found to be statistically significant differences between the fibrotic-foci-like lung adenocarcinoma group and the old fibrotic-foci group ( P  < 0.05). SUVmax [7.9 (4.7-8.8) vs. 1.7 (1.2-2.2)] and TBRmax [9.9 (6.5-11.0) vs. 2.1 (1.6-2.9)] were found to be statistically significant differences between the metastatic group and the non-metastatic group ( P  < 0.05). 18 F-FDG PET/CT showed the higher diagnostic accuracy for fibrotic-foci-like lung adenocarcinoma than HRCT [95.0% (19/20) vs. 65.0% (13/20), P  < 0.05]. CONCLUSION: The specific characteristics of fibrotic-foci-like lung adenocarcinoma on 18 F-FDG PET/CT and HRCT were high 18 F-FDG uptake, GGO, and vessel convergence, which could be distinguished from old fibrotic-foci of the lung.

Frequency and Etiologies of Visual Disturbance After Cataract Surgery Identified in Neuro-Ophthalmology Clinics.

BACKGROUND: To identify the frequency and etiologies of visual disturbances after cataract surgery in patients referred to Neuro-ophthalmology. METHODS: This study is a retrospective chart review. Records of patients 18 years and older referred to neuro-ophthalmology clinics for new-onset visual disturbances within 6 months of cataract surgery were reviewed. Those with pre-existing neuro-ophthalmic disorders, combined intraocular procedures with cataract surgery, or inadequate follow-up were excluded. The main outcome measures were frequency and etiologies of visual disturbances after cataract surgery. Secondary analyses of a cohort of patients who had cataract surgery at our institution were performed to determine the frequency and etiology of visual disturbances after uneventful cataract surgery. RESULTS: One hundred seventy-three patients met the inclusion criteria (internal referral: 36/173, from outside surgeons: 137/173). Sixty-one percent (106/173) were newly diagnosed with neuro-ophthalmic etiologies, including 21% (36/173) with afferent and 40% (70/173) with efferent disorders. Thirty-six percent (62/173) of patients had non neuro-ophthalmic causes and 3% (5/173) had systemic conditions responsible for visual disturbances postoperatively. Decompensated strabismus causing diplopia was the most common neuro-ophthalmic diagnosis after cataract surgery (50%, 53/106). Of the 13,715 patients who had cataract surgery performed at our institution over a 9-year period, 20 of 36 patients referred for visual disturbances were identified with neuro-ophthalmic etiologies of which 85% (17/20) had postoperative diplopia. CONCLUSIONS: In our study, decompensated strabismus causing diplopia was the most common neuro-ophthalmic visual disturbance after cataract surgery. Detailed history and ocular alignment should be assessed before cataract surgery to identify patients with the risk.

Cholic acid exposure during late pregnancy causes placental dysfunction and fetal growth restriction by reactive oxygen species-mediated activation of placental GCN2/eIF2α pathway.

Epidemiological studies suggest that fetal growth restriction (FGR) caused by gestational cholestasis is associated with elevated serum cholic acid (CA). Here, we explore the mechanism by which CA induces FGR. Pregnant mice except controls were orally administered with CA daily from gestational day 13 (GD13) to GD17. Results found that CA exposure decreased fetal weight and crown-rump length, and increased the incidence of FGR in a dose-dependent manner. Furthermore, CA caused placental glucocorticoid (GC) barrier dysfunction via down-regulating the protein but not the mRNA level of placental 11ß-Hydroxysteroid dehydrogenase-2 (11ß-HSD2). Additionally, CA activated placental GCN2/eIF2α pathway. GCN2iB, an inhibitor of GCN2, significantly inhibited CA-induced down-regulation of 11ß-HSD2 protein. We further found that CA caused excessive reactive oxygen species (ROS) production and oxidative stress in mouse placentas and human trophoblasts. NAC significantly rescued CA-induced placental barrier dysfunction by inhibiting activation of GCN2/eIF2α pathway and subsequent down-regulation of 11ß-HSD2 protein in placental trophoblasts. Importantly, NAC rescued CA-induced FGR in mice. Overall, our results suggest that CA exposure during late pregnancy induces placental GC barrier dysfunction and subsequent FGR may be via ROS-mediated placental GCN2/eIF2α activation. This study provides valuable insight for understanding the mechanism of cholestasis-induced placental dysfunction and subsequent FGR.