Enhancing Postoperative Recovery and Reducing Risk Events in Lung Cancer Patients through an ERAS-Based Nursing Strategy: A Meta-analysis.

Objective: This study aims to conduct a meta-analysis evaluating the impact of an enhanced recovery after cesarean delivery (ERAS)-based nursing approach in patients undergoing surgery for lung cancer (LC). Methods: A systematic search of online literature databases was conducted to identify studies focusing on the application of ERAS-based nursing after radical LC surgery. Selected literature underwent quality assessment and data extraction, with Meta-analysis performed using RevMan 5.3 software. Results: A total of 7 studies, encompassing a total of 1684 subjects, 925 in the ERAS-based nursing group (test group) and 759 in the control group (conventional nursing group), were included. Meta-analysis results revealed that the implementation of ERAS-based nursing significantly reduced postoperative complications, shortened hospital stays, and decreased Visual Analogue Scale (VAS) scores when compared to the control group (P < .05). Additionally, Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) scores in the ERAS-based nursing group were lower post-nursing than pre-nursing (P < .05). Conclusions: ERAS-based nursing demonstrates efficacy in facilitating the recovery of LC patients post-surgery, reducing the risk of complications, and improving psychological well-being.

A novel imatinib-upregulated long noncoding RNA plays a critical role in inhibition of tumor growth induced by Abl oncogenes.

BACKGROUND: Dysregulation of long noncoding RNAs (lncRNAs) has been linked to various human cancers. Bcr-Abl oncogene that results from a reciprocal translocation between human chromosome 9 and 22, is associated with several hematological malignancies. However, the role of lncRNAs in Bcr-Abl-induced leukemia remains largely unexplored. METHODS: LncRNA cDNA microarray was employed to identify key lncRNAs involved in Bcr-Abl-mediated cellular transformation. Abl-transformed cell survival and xenografted tumor growth in mice were evaluated to dissect the role of imatinib-upregulated lncRNA 1 (IUR1) in Abl-induced tumorigenesis. Primary bone marrow transformation and in vivo leukemia transplant using lncRNA-IUR1 knockout (KO) mice were further conducted to address the functional relevance of lncRNA-IUR1 in Abl-mediated leukemia. Transcriptome RNA-seq and Western blotting were performed to determine the mechanisms by which lncRNA-IUR1 regulates Bcr-Abl-induced tumorigenesis. RESULTS: We identified lncRNA-IUR1 as a critical negative regulator of Bcr-Abl-induced tumorigenesis. LncRNA-IUR1 expressed in a very low level in Bcr-Abl-positive cells from chronic myeloid leukemia patients. Interestingly, it was significantly induced in Abl-positive leukemic cells treated by imatinib. Depletion of lncRNA-IUR1 promoted survival of Abl-transformed human leukemic cells in experiments in vitro and xenografted tumor growth in mice, whereas ectopic expression of lncRNA-IUR1 sensitized the cells to apoptosis and suppressed tumor growth. In concert, silencing murine lncRNA-IUR1 in Abl-transformed cells accelerated cell survival and the development of leukemia in mice. Furthermore, lncRNA-IUR1 deficient mice were generated, and we observed that knockout of murine lncRNA-IUR1 facilitated Bcr-Abl-mediated primary bone marrow transformation. Moreover, animal leukemia model revealed that lncRNA-IUR1 deficiency promoted Abl-transformed cell survival and development of leukemia in mice. Mechanistically, we demonstrated that lncRNA-IUR1 suppressed Bcr-Abl-induced tumorigenesis through negatively regulating STAT5-mediated GATA3 expression. CONCLUSIONS: These findings unveil an inhibitory role of lncRNA-IUR1 in Abl-mediated cellular transformation, and provide new insights into molecular mechanisms underlying Abl-induced leukemogenesis.

Metabolic factors contribute to T-cell inhibition in the ovarian cancer ascites.

Malignant ascites is one of the major clinical features of ovarian cancer, which serves as a carrier for the peritoneal dissemination of tumor cells and predicts a poor prognosis in patients. In the microenvironment of ovarian cancer ascites, antitumor immunity is suppressed, which enables the tumor cells to escape from immune surveillance. The metabolic factors, including hypoxia, nutrient deprivation and accumulation of metabolic products, contribute to the immunosuppressive status of malignant ascites. The malignant ascites and ovarian solid tumors exhibit differential metabolic profiles. In this review, we have summarized the most recent findings on the interaction between immune cells and metabolic factors in the ovarian cancer ascites. The effects of metabolic factors on the antitumor functions of T-cells in the malignant ascites were analyzed. Finally, we have discussed the potential directions for future research in this field.

Effects of atorvastatin on pharmacokinetics of amlodipine in rats and its potential mechanism.

Atorvastatin combined with amlodipine (ALDP) can efficiently treat the hypertension with coronary heart disease. However, the drug-drug interaction between atorvastatin and ALDP are still unknown.This study investigates the effects of atorvastatin on the pharmacokinetics of ALDP in rats and clarifies its main mechanism.The pharmacokinetic profiles of oral administration of ALDP (1 mg/kg) in Sprague-Dawley rats, with or without pretreatment of atorvastatin (1.5 mg/kg/d for 7 d) were investigated. The effects of atorvastatin on the metabolism of ALDP were also investigated using rat liver microsomes.The results showed that atorvastatin could significantly increase the peak plasma concentration (from 18.28 ± 2.65 to 24.13 ± 1.96 ng/mL) and decrease the oral clearance (from 4.57 ± 1.15 to 1.79 ± 0.28 L/h/kg) of ALDP. In the rat liver microsome systems, the intrinsic clearance rate of ALDP was decreased by the pretreatment with atorvastatin (39.26 ± 2.1 vs. 33.24 ± 3.3 µL/min/mg protein).Those results indicated that atorvastatin could significantly affect the pharmacokinetic of ALDP, via inhibiting the metabolism of ALDP in rats.

Detecting glaucoma based on spectral domain optical coherence tomography imaging of peripapillary retinal nerve fiber layer: a comparison study between hand-crafted features and deep learning model.

PURPOSE: To develop a deep learning (DL) model for automated detection of glaucoma and to compare diagnostic capability against hand-craft features (HCFs) based on spectral domain optical coherence tomography (SD-OCT) peripapillary retinal nerve fiber layer (pRNFL) images. METHODS: A DL model with pre-trained convolutional neural network (CNN) based was trained using a retrospective training set of 1501 pRNFL OCT images, which included 690 images from 153 glaucoma patients and 811 images from 394 normal subjects. The DL model was further tested in an independent test set of 50 images from 50 glaucoma patients and 52 images from 52 normal subjects. A customized software was used to extract and measure HCFs including pRNFL thickness in average and four different sectors. Area under the receiver operator characteristics (AROC) curves was calculated to compare the diagnostic capability between DL model and hand-crafted pRNFL parameters. RESULTS: In this study, the DL model achieved an AROC of 0.99 [CI: 0.97 to 1.00] which was significantly larger than the AROC values of all other HCFs (AROCs 0.661 with 95% CI 0.549 to 0.772 for temporal sector, AROCs 0.696 with 95% CI 0.549 to 0.799 for nasal sector, AROCs 0.913 with 95% CI 0.855 to 0.970 for superior sector, AROCs 0.938 with 95% CI 0.894 to 0.982 for inferior sector, and AROCs 0.895 with 95% CI 0.832 to 0.957 for average). CONCLUSION: Our study demonstrated that DL models based on pre-trained CNN are capable of identifying glaucoma with high sensitivity and specificity based on SD-OCT pRNFL images.

Drainage relieves pain without increasing post-operative blood loss in high tibial osteotomy: a prospective randomized controlled study.

PURPOSE: Drainage is a common procedure in high tibial osteotomy (HTO), but the benefits of drainage during HTO remain poorly investigated. This study was designed to investigate the effect of drainage on blood loss and early functional recovery in HTO. METHODS: Altogether, 80 patients undergoing HTO were analyzed from August 2018 to September 2019. Patients were randomized into two groups: group A (drainage, n = 40) and group B (no drainage, n = 40). There were no intergroup differences in baseline parameters between the two groups, and the same surgical techniques and haemostatic methods were used. The mean follow-up time was 3.2 months. Blood loss and early functional recovery of the knee were examined post-operatively in both groups. RESULTS: The total post-operative blood loss was 253.34 ± 104.18 ml in group A and 222.51 ± 106.89 ml in group B. This difference was non-significant (p > 0.05). The post-operative haemoglobin and haematocrit differences between groups were also non-significant (p > 0.05). Post-operative visual analogue scale (VAS) pain scores and lower leg swelling were lower in group A than those in group B (p < 0.05), and the early range of motion of the knee joint was higher in group A than that in group B (p < 0.05). Group A had lower incidence rates of dressing seepage and incision complications than group B (p < 0.05). The differences in three month post-operative VAS and knee function scores were non-significant (p > 0.05). CONCLUSION: Drainage in HTO does not increase patients' total blood loss, but it can promote early knee function recovery by reducing post-operative pain, lower leg swelling, and the incidence of incision complications. TRIAL REGISTRATION: NCT-03954860.

Novel lncRNA-IUR suppresses Bcr-Abl-induced tumorigenesis through regulation of STAT5-CD71 pathway.

BACKGROUND: Long noncoding RNAs (lncRNAs), defined as the transcripts longer than 200 nt without protein-coding capacity, have been found to be aberrantly expressed in diverse human diseases including cancer. A reciprocal translocation between chromosome 9 and 22 generates the chimeric Bcr-Abl oncogene, which is associated with several hematological malignancies. However, the functional relevance between aberrantly expressed lncRNAs and Bcr-Abl-mediated leukemia remains obscure. METHODS: LncRNA cDNA microarray was used to identify novel lncRNAs involved in Bcr-Abl-mediated cellular transformation. To study the functional relevance of novel imatinib-upregulated lncRNA (IUR) family in Abl-induced tumorigenesis, Abl-transformed cell survival and xenografted tumor growth in mice was evaluated. Primary bone marrow transformation and in vivo leukemia transplant using lncRNA-IUR knockdown (KD) transgenic mice were further conducted to corroborate the role of lncRNA-IUR in Abl-induced tumorigenesis. Transcriptome RNA-seq, Western blot, RNA pull down and RNA Immunoprecipitation (RIP) were employed to determine the mechanisms by which lncRNA-IUR-5 regulates Bcr-Abl-mediated tumorigenesis. RESULTS: We identified a conserved lncRNA-IUR family as a key negative regulator of Bcr-Abl-induced tumorigenesis. Increased expression of lncRNA-IUR was detected in both human and mouse Abl-transformed cells upon imatinib treatment. In contrast, reduced expression of lncRNA-IUR was observed in the peripheral blood lymphocytes derived from Bcr-Abl-positive acute lymphoblastic leukemia (ALL) patients compared to normal subjects. Knockdown of lncRNA-IUR remarkably promoted Abl-transformed leukemic cell survival and xenografted tumor growth in mice, whereas overexpression of lncRNA-IUR had opposite effects. Also, silencing murine lncRNA-IUR promoted Bcr-Abl-mediated primary bone marrow transformation and Abl-transformed leukemia cell survival in vivo. Besides, knockdown of murine lncRNA-IUR in transgenic mice provided a favorable microenvironment for development of Abl-mediated leukemia. Finally, we demonstrated that lncRNA-IUR-5 suppressed Bcr-Abl-mediated tumorigenesis by negatively regulating STAT5-mediated expression of CD71. CONCLUSIONS: The results suggest that lncRNA-IUR may act as a critical tumor suppressor in Bcr-Abl-mediated tumorigenesis by suppressing the STAT5-CD71 pathway. This study provides new insights into functional involvement of lncRNAs in leukemogenesis.

Respiratory Syncytial Virus Replication Is Promoted by Autophagy-Mediated Inhibition of Apoptosis.

Respiratory syncytial virus (RSV) is the main cause of acute lower respiratory tract infection (ALRI) in children worldwide. Virus-host interactions affect the progression and prognosis of the infection. Autophagy plays important roles in virus-host interactions. Respiratory epithelial cells serve as the front line of host defense during RSV infection, However, it is still unclear how they interact with RSV. In this study, we found that RSV induced autophagy that favored RSV replication and exacerbated lung pathology in vivo Mechanistically, RSV induced complete autophagy flux through reactive oxygen species (ROS) generation and activation of the AMP-activated protein kinase/mammalian target of rapamycin (AMPK-MTOR) signaling pathway in HEp-2 cells. Furthermore, we evaluated the functions of autophagy in RSV replication and found that RSV replication was increased in HEp-2 cells treated with rapamycin but decreased remarkably in cells treated with 3-methylademine (3-MA) or wortmannin. Knockdown key molecules in the autophagy pathway with short hairpinp RNA (shRNA) against autophagy-related gene 5 (ATG5), autophagy-related gene 7 (ATG7), or BECN1/Beclin 1 or treatment with ROS scavenger N-acetyl-l-cysteine (NAC) and AMPK inhibitor (compound C) suppressed RSV replication. 3-MA or shATG5/BECN1 significantly decreased cell viability and increased cell apoptosis at 48 hours postinfection (hpi). Blocking apoptosis with Z-VAD-FMK partially restored virus replication at 48 hpi. Those results provide strong evidence that autophagy may function as a proviral mechanism in a cell-intrinsic manner during RSV infection.IMPORTANCE An understanding of the mechanisms that respiratory syncytial virus utilizes to interact with respiratory epithelial cells is critical to the development of novel antiviral strategies. In this study, we found that RSV induces autophagy through a ROS-AMPK signaling axis, which in turn promotes viral infection. Autophagy favors RSV replication through blocking cell apoptosis at 48 hpi. Mechanistically, RSV induces mitophagy, which maintains mitochondrial homeostasis and therefore decreases cytochrome c release and apoptosis induction. This study provides a novel insight into this virus-host interaction, which may help to exploit new antiviral treatments targeting autophagy processes.

EFFECT OF OPTIC DISK-FOVEA DISTANCE ON MEASUREMENTS OF INDIVIDUAL MACULAR INTRARETINAL LAYERS IN NORMAL SUBJECTS.

PURPOSE: To investigate the effect of optic disk-fovea distance (DFD) on measurements of macular intraretinal layers using spectral domain optical coherence tomography in normal subjects. METHODS: One hundred and eighty-two eyes from 182 normal subjects were imaged using spectral domain optical coherence tomography. The average thicknesses of eight macular intraretinal layers were measured using an automatic segmentation algorithm. Partial correlation test and multiple regression analysis were used to determine the effect of DFD on thicknesses of intraretinal layers. RESULTS: Disk-fovea distance correlated negatively with the overall average thickness in all the intraretinal layers (r ≤ -0.17, all P ≤ 0.025) except the ganglion cell layer and photoreceptor. In multiple regression analysis, greater DFD was associated with thinner nerve fiber layer (6.78 µm decrease per each millimeter increase in DFD, P < 0.001), thinner ganglion cell-inner plexiform layer (2.16 µm decrease per each millimeter increase in DFD, P = 0.039), thinner ganglion cell complex (8.94 µm decrease per each millimeter increase in DFD, P < 0.001), thinner central macular thickness (18.16 µm decrease per each millimeter increase in DFD, P < 0.001), and thinner total macular thickness (15.94 µm decrease per each millimeter increase in DFD, P < 0.001). CONCLUSION: Thinner measurements of macular intraretinal layers were significantly associated with greater DFD. A clinical assessment of macular intraretinal layers in the evaluation of various macular diseases should always be interpreted in the context of DFD.

Assessment of Peripapillary Retinal Nerve Fiber Layer Optical Density Ratios in Healthy Eyes Using Optical Coherence Tomography with Different Analytical Radii.

PURPOSE: To explore the characteristics and determinants of peripapillary retinal nerve fiber layer (RNFL) optical density (OD) by optical coherence tomography (OCT) in healthy eyes with varied analytical radii. METHODS: Peripapillary OCT scans centered at the optic disc of 150 eyes from 150 healthy subjects (64 males and 86 females) were included. Under 5 analytical circles with different radii (1.45 mm, 1.7 mm, 1.95 mm, 2.2 mm and 2.45 mm), the circumpapillary circular cross-sectional images were exported for further analysis using Image J. Peripapillary RNFL and retinal pigment epithelium (RPE) OD in different quadrants and clock-hours were obtained. RNFL optical density ratio (ODR) was then calculated as RNFL OD divided by RPE OD. A linear mixed-effects model analysis was performed to assess the relationship between RNFL ODR and analytical radius, accounting for axial length, age, spherical equivalent, thickness and image score. RESULTS: The RNFL ODRs had a double-hump pattern with peaks in the superior and inferior quadrants and troughs in the temporal and nasal areas. In the linear mixed-effects model analysis, a trend of decreasing mean RNFL ODR with increasing analytical radius was found (0.9227 ± 0.0689, 0.9063 ± 0.0620, 0.8916 ± 0.0552, 0.8729 ± 0.0553 and 0.8575 ± 0.0564 respectively, p = 0.034). RNFL ODR values was negatively correlated with age (p < 0.001), positively correlated with corresponding RNFL thickness (p < 0.001). No significant correlation was found between RFNL ODR and image score, axial length and spherical equivalent. CONCLUSIONS: RNFL ODR profile showed a comparable double-hump configuration with RNFL thickness. RNFL ODR values tended to decrease with larger analytical circles and older age, and increase with corresponding RNFL thickness. These factors should be considered when interpreting RNFL ODR in glaucoma assessment.

Impacts of cryopreservation on phenotype and functionality of mononuclear cells in peripheral blood and ascites.

Background: Mononuclear cells in peripheral blood and ascites are important clinical resources commonly used in translational and basic research. However, the impact of different cryopreservation durations and extra freeze-thaw cycles on the number and function of mononuclear cells is unknown. Methods: Peripheral blood samples (n = 21) and ascites samples (n = 8) were collected from healthy volunteers and ovarian cancer patients. Mononuclear cells were isolated, frozen, and thawed at 6 and 12 months. The impact of cryopreservation on cell viability, the phenotype, and the activation and proliferation of T cells were analyzed by flow cytometry. Single-cell sequencing was applied to investigate the underlying mechanism. Results: The cell number and viability of mononuclear cells in peripheral blood and ascites were significantly decreased after cryopreservation. The T lymphocytes, especially CD4+ T cells, were affected the most significantly. By contrast, monocytes, natural killer (NK) cells, natural killer T (NKT) cells, and B cells were more tolerant. Meanwhile, T cell proliferation and IL-2 secretion are significantly affected after long-term cryopreservation. Mechanistically, the cell death induced by elevated reactive oxygen species (ROS) was involved in the reduction of CD4+ T cells after cryopreservation. Conclusions: Our data indicates that different subtypes of mononuclear cells exhibit different tolerance capacities upon cryopreservation. Thus, our research can provide evidence and support for individuals who are conducting experiments using frozen clinical patient-derived mononuclear cells, for basic research or clinical trials. In addition, extra caution is worthwhile when researchers compare immune cell functionality from peripheral blood or ascites across datasets obtained in different cryopreservation conditions.

Targeting LTA4H facilitates the reshaping of the immune microenvironment mediated by CCL5 and sensitizes ovarian cancer to Cisplatin.

Ovarian cancer is the most lethal and aggressive gynecological cancer with a high recurrence rate and is often diagnosed late. In ovarian cancer, multiple metabolic enzymes of lipid metabolism are abnormally expressed, resulting in metabolism disorder. As a characteristic pathway in polyunsaturated fatty acid (PUFA) metabolism, arachidonic acid (AA) metabolism is disturbed in ovarian cancer. Therefore, we established a 10-gene signature model to evaluate the prognostic risk of PUFA-related genes. This 10-gene signature has strong robustness and can play a stable predictive role in datasets of various platforms (TCGA, ICGC, and GSE17260). The high association between the risk subgroups and clinical characteristics indicated a good performance of the model. Our data further indicated that the high expression of LTA4H was positively correlated with poor prognosis in ovarian cancer. Deficiency of LTA4H enhanced sensitivity to Cisplatin and modified the characteristics of immune cell infiltration in ovarian cancer. Additionally, our results indicate that CCL5 was involved in the aberrant metabolism of the AA/LTA4H axis, which contributes to the reduction of tumor-infiltrating CD8+ T cells and immune escape in ovarian cancer. These findings provide new insights into the prognosis and potential target of LTA4H/CCL5 in treating ovarian cancer.

EZH2 Inhibition Enhances PD-L1 Protein Stability Through USP22-Mediated Deubiquitination in Colorectal Cancer.

The regulation of PD-L1 is the key question, which largely determines the outcome of the immune checkpoint inhibitors (ICIs) based therapy. However, besides the transcription level, the protein stability of PD-L1 is closely correlated with its function and has drawn increasing attention. In this study, EZH2 inhibition enhances PD-L1 expression and protein stability, and the deubiquitinase ubiquitin-specific peptidase 22 (USP22) is identified as a key mediator in this process. EZH2 inhibition transcriptionally upregulates USP22 expression, and upregulated USP22 further stabilizes PD-L1. Importantly, a combination of EZH2 inhibitors with anti-PD-1 immune checkpoint blockade therapy improves the tumor microenvironment, enhances sensitivity to immunotherapy, and exerts synergistic anticancer effects. In addition, knocking down USP22 can potentially enhance the therapeutic efficacy of EZH2 inhibitors on colon cancer. These findings unveil the novel role of EZH2 inhibitors in tumor immune evasion by upregulating PD-L1, and this drawback can be compensated by combining ICI immunotherapy. Therefore, these findings provide valuable insights into the EZH2-USP22-PD-L1 regulatory axis, shedding light on the optimization of combining both immune checkpoint blockade and EZH2 inhibitor-based epigenetic therapies to achieve more efficacies and accuracy in cancer treatment.

Elevated CD4+ T Cell Senescence Associates with Impaired Immune Responsiveness in Severe COVID-19.

Aging is a critical risk factor for unfavorable clinical outcomes among COVID-19 patients and may impact vaccine efficacy. However, whether the senescence of T cells is associated with severe COVID-19 outcome in elderly individuals is unclear. Using flow cytometry, we analyzed the frequency of senescent T cells (Tsens) in peripheral blood from 100 hospitalized elderly COVID-19 patients and compared differences between those with mild/moderate and severe/critical illness. We also assessed correlations between the percentage of Tsens and the quantity and quality of spike-specific antibodies by ELISA, neutralizing antibody test kit, and ELISPOT assay respectively, the cytokine production profile of COVID-19 reactive T cells, and plasma soluble factors by cytometric bead array (CBA). Our study found a significantly elevated level of CD4+ Tsens in patients with severe/critical disease compared to those with mild/moderate illness. Patients with a higher level of CD4+ Tsens (>19.78%) showed a decreased survival rate compared to those with a lower level (≤19.78%). This is more pronounced among patients with breakthrough infections. The percentage of CD4+ Tsens was negatively correlated with spike-specific antibody titers, neutralization ability, and COVID-19 reactive IL-2+CD4+ T cells. In addition, spike-specific antibody levels were positively correlated with IL-2 producing T cells and plasma IL-2 amount. Mechanistically, with defective CD40L, T cells from patients with CD4+ Tsens >19.78% were unable to support B cell proliferation and differentiation. Our data demonstrate that the percentage of CD4+ Tsens in peripheral blood may serve as a reliable biomarker for the prognosis of severe COVID-19 patients, especially in breakthrough infections. Therefore, restoring the immune response of CD4+ Tsens may be key to preventing severe illness and improving vaccine efficacy in older adults.

3-Anhydro-6-hydroxy-ophiobolin A, a new sesterterpene inhibiting the growth of methicillin-resistant Staphylococcus aureus and inducing the cell death by apoptosis on K562, from the phytopathogenic fungus Bipolaris oryzae.

A new ophiobolin derivative, 3-anhydro-6-hydroxy-ophiobolin A (1), as well as two known ophiobolin derivatives 3-anhydro-ophiobolin A (2) and 3-anhydro-6-epi-ophiobolin A (3) were isolated from the PDB culture of a phytopathogenic fungus Bipolaris oryzae. The structure of 1 was elucidated through 2D NMR and other spectroscopic techniques. Compound 1 exhibited strong antimicrobial activity against Bacille Calmette-Guerin, Bacillus subtilis, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus with MIC value of 12.5 µg/mL, and potent antiproliferative activity against cell lines HepG2 and K562 with IC50 of 6.49 µM and 4.06 µM, respectively. Further studies on the cytotoxicity of compound 1 against K562 cells demonstrated that it induced apoptosis, observed by flow cytometric method. Preliminary structure-activity relationships of these ophiobolins and the mechanism of apoptosis induced by 1 were analyzed.

Comparison of Digital Camera Real-Time Display with Conventional Teaching Tube for Slit Lamp Microscopy Teaching.

PURPOSE: To compare slit-lamp microscopy teaching outcomes with digital camera real-time display and conventional teaching tube in undergraduate education of clinical ophthalmology. METHODS: Thirty-seven Year 4 medical students were assigned to two groups for slit lamp microscopy teaching with digital camera real-time display (n = 18) and teaching tube (n = 19). The outcome measures included a 5-item questionnaire on their experience and the quality of slit lamp photos taken by the students. RESULTS: The overall satisfaction score was significantly higher in the group of digital camera real-time display compared with the group of teaching tube (4.5 ± 0.5 vs. 4.2 ± 0.7, P = .013). The former group also achieved higher quality score of the slit-lamp photography (4.1 ± 0.3 vs. 3.6 ± 0.5, P = .002). CONCLUSIONS: The digital camera real-time display attachment is more effective in undergraduate ophthalmic education over conventional slit-lamp teaching tube. It is also more favored by students and is thus highly recommended for clinical ophthalmology education.

Integration of Massive Open Online Course (MOOC) in Ophthalmic Skills Training for Medical Students: Outcomes and Perspectives.

PURPOSE: To integrate a massive open online course (MOOC) into conventional clinical ophthalmology teaching and investigate its impact on the skills of medical students. METHODS: This was a nonrandomized, prospective, and comparative study. Seventy-six medical students were assigned to 2 groups before their clinical teaching. Some were asked to follow a MOOC for slitlamp microscope examination but used textbook for preview of visual acuity test (SLMM group, n=39), while others were required to take a MOOC for visual acuity test and previewed slitlamp microscopy using textbook (VATM group, n=37). All the students then underwent conventional clinical ophthalmology teaching on slitlamp microscopy and visual acuity test. Their performance was evaluated using Direct Observation of Procedural Skills (DOPS). Students were also asked to complete a 5-item questionnaire about their learning experience and comment on the MOOC. RESULTS: Students in the SLMM group obtained overall higher scores in the slitlamp practical skills (47.64±4.01 vs 44.68±5.99, P=0.013), while those in the VATM group performed better in the visual acuity test (46.45±4.90 vs 43.78±4.94, P=0.004). MOOC was deemed to increase learning interests (4.13 of 5 points) and motivation (4.01 of 5 points) but was more preferred as an additional tool to traditional teaching methods (4.34 of 5 points) rather than to replace them (2.92 of 5 points). CONCLUSIONS: MOOC offers an added benefit in improving clinical skills and is worth advocating as an additional tool for clinical ophthalmic education.

High GPER expression in triple-negative breast cancer is linked to pro-metastatic pathways and predicts poor patient outcomes.

Triple-negative breast cancer (TNBC) is a particularly aggressive and heterogeneous disease with few effective targeted therapies and precision therapeutic options over a long period. It is generally considered that TNBC is an estrogen-independent breast cancer, while a new estrogen receptor, namely G protein-coupled estrogen receptor (GPER), is demonstrated to mediate estrogenic actions in TNBC. Based on our transcriptomic analysis, expression of GPER was correlated with clinicopathological variables and survival of 360 TNBC patients. GPER expression at mRNA level was significantly correlated with immunohistochemistry scoring in 12 randomly chosen samples. According to the cutoff value, 26.4% (95/360) of patients showed high GPER expression and significant correlation with the mRNA subtype of TNBC (P = 0.001), total metastatic events (P = 0.019) and liver metastasis (P = 0.011). In quantitative comparison, GPER abundance is correlated with the high-risk subtype of TNBC. At a median follow-up interval of 67.1 months, a significant trend towards reduced distant metastasis-free survival (DMFS) (P = 0.014) was found by Kaplan-Meier analysis in patients with high GPER expression. Furthermore, univariate analysis confirmed that GPER was a significant prognostic factor for DMFS in TNBC patients. Besides, high GPER expression was significantly linked to the worse survival in patients with lymph node metastasis, TNM stage III as well as nuclear grade G3 tumors. Transcriptome-based bioinformatics analysis revealed that GPER was linked to pro-metastatic pathways in our cohort. These results may supply new insights into GPER-mediated estrogen carcinogenesis in TNBC, thus providing a potential strategy for endocrine therapy of TNBC.

Hydrogen sulfide alleviates particulate matter-induced emphysema and airway inflammation by suppressing ferroptosis.

BACKGROUND: Redox imbalance is an vital mechanism for COPD. At present, insufficient researches have been conducted on the protective effect of hydrogen sulfide (H2S) on PM-induced COPD. However, whether H2S exerts the anti-injury role by blocking ferroptosis and restoring redox equilibrium remain to be investigated. METHODS: Human lung tissue samples were collected for IHC staining, and the expressions of Nrf2, ferritinophagy- and ferroptosis-related proteins were observed. The WT C57BL/6 and Nrf2 knockout mice models were established with PM(200 µg per mouse). NaHS(Exogenous H2S) was injected intraperitoneally 30 min in advance. Twenty-nine days later, mice lung tissues were evaluated by HE's and PERLS-DAB's staining. Meanwhile, inflammation and oxidative stress indicators and iron levels were assessed by corresponding ELISA kit. Related protein expressions were detected through Western blot. BEAS-2B cells with or without H2S were exposed to PM2.5 for 36 h. Cell viability, mitochondrial morphology, inflammatory cytokines, antioxidant factors, iron levels, autophagic flux and the levels of ROS, LIP ROS, MitoROS, MMP, as well as related protein expressions were detected by specific methods, respectively. In addition, V5-Nrf2, Nrf2 siRNA, Nrf2 inhibitor ML385, PPAR-γ inhibitor GW9662, autophagy inhibitor CQ, iron chelator DFO and ferroptosis inhibitor Fer-1 were used to verify the target signaling pathways. RESULTS: We found that the expressions of LIP ROS, ROS, COX2, MDA and other oxidative factors increased, while the antioxidant markers GPX4, GSH and GSH-Px significantly decreased, as well as active iron accumulation in COPD patients, PM-exposured WT and Nrf2-KO mice models and PM2.5-mediated cell models. NaHS pretreatment markedly inhibited PM-induced emphysema and airway inflammation by alleviating ferroptotic changes in vivo and vitro. With the use of V5-Nrf2 overexpression plasmid, Nrf2 siRNA and pathway inhibitors, we found NaHS activates the expressions of Nrf2 and PPAR-γ, and inhibites ferritinophagy makers LC3B, NCOA4 and FTH1 in BEAS-2B cells. Moreover, the anti-ferroptotic effect of NaHS was further verified to be related to the activation of Nrf2 signal in MEF cells. CONCLUSION: This research suggested that H2S alleviated PM-induced emphysema and airway inflammation via restoring redox balance and inhibiting ferroptosis through regulating Nrf2-PPAR-ferritinophagy signaling pathway.

Determinants of peripapillary retinal nerve fiber layer's grayscale value in normal eyes by spectral domain optical coherence tomography.

To determine and evaluate the distribution, variation, and determinants of peripapillary retinal nerve fiber layer (pRNFL) grayscale value with spectral-domain optical coherence tomography (SD-OCT) in normal eyes. In this cross-sectional study, three hundred ninety-seven normal eyes from 397 healthy Chinese adults aged 18-80 were consecutively recruited from a tertiary eye care center. An SD-OCT instrument took pRNFL imaging. We used a customized software to measure pRNFL parameters, including thickness and grayscale value. Univariable and multiple linear regression analyses were performed to examine the relationship between pRNFL grayscale value with ocular (e.g., axial length [A.L.], spherical equivalent [S.E.], intraocular pressure [IOP]), and systemic (e.g., age, sex) factors. A total of 397 eyes from 397 healthy subjects were included in the final analysis with mean (± SD) age 44.63 ± 16.43 years (range 18-80 years) and 196 (49.4%) males. The mean average of pRNFL grayscale value and thickness 164.82 ± 5.69 and 106.68 ± 8.89 µm, respectively. pRNFL grayscale value in nasal sectors (163.26 ± 9.31) was significantly lower comparing those in all other five sectors (all with p < 0.001)]. In multivariable analysis, average pRNFL grayscale value was independently correlated to older age (ß = - 0.053, p = 0.002), longer axial length (ß = - 0.664, p = 0.003), lower RPE grayscale value (ß = 0.372, p < 0.001) and lower ImageQ (ß = 0.658, p < 0.001). In this study, we provided normative SD-OCT data on the pRNFL grayscale value profile in nonglaucomatous eyes. Lower average pRNFL grayscale value was independently correlated to older age, longer axial length, lower RPE grayscale value, and lower ImageQ. These determinants should be considered when interpreting pRNFL grayscale value in glaucoma assessment.