Case report: Advanced modified pneumatic retinopexy for treating simultaneous bilateral rhegmatogenous retinal detachment.

Background: Simultaneous bilateral rhegmatogenous retinal detachment (RRD) is a rare and challenging condition in ophthalmology. This case report focuses on a modified pneumatic retinopexy technique, designed to improve treatment outcomes for this difficult condition. Case presentation: A 59-year-old male presented with decreased visual acuity in his right eye for one week. Examination revealed extensive retinal detachment in the right eye with multiple superior breaks and macula off, separated by approximately 3 clock hours. The left eye exhibited one quartile of retinal detachment with superior breaks and macula on. Bilateral simultaneous PR was performed for retinal repair. In the modified PR procedure, 0.7 ml of low-concentration perfluoropropane and 0.7 ml of filtered pure air were intravitreally injected into the right and left eyes, respectively. A head position maneuver was then employed to sequentially close retinal breaks, followed by laser photocoagulation once the surrounding retina reattached. Two days after gas injection, both retinas were completely reattached. Best corrected visual acuity improved to 0.6 in the right eye and 0.9 in the left eye at the 8-month follow-up. Conclusion: The innovative modified pneumatic retinopexy technique presented in this case report offers a promising new approach for effectively treating simultaneous bilateral rhegmatogenous retinal detachment.

The molecular subtyping and precision medicine in triple-negative breast cancer---based on Fudan TNBC classification.

Triple-negative breast cancer (TNBC) is widely recognized as the most aggressive form of breast cancer, occurring more frequently in younger patients and characterized by high heterogeneity, early distant metastases and poor prognosis. Multiple treatment options have failed to achieve the expected therapeutic effects due to the lack of clear molecular targets. Based on genomics, transcriptomics and metabolomics, the multi-omics analysis further clarifies TNBC subtyping, which provides a greater understanding of tumour heterogeneity and targeted therapy sensitivity. For instance, the luminal androgen receptor subtype (LAR) exhibits responsiveness to anti-AR therapy, and the basal-like immune-suppressed subtype (BLIS) tends to benefit from poly (ADP-ribose) polymerase inhibitors (PARPis) and anti-angiogenic therapy. The efficacy of multi-dimensional combination therapy holds immense importance in guiding personalized and precision medicine for TNBC. This review offers a systematic overview of recent FuDan TNBC molecular subtyping and its role in the instruction of clinical precision therapy.

A deep-learning-based clinical risk stratification for overall survival in adolescent and young adult women with breast cancer.

OBJECTIVE: The objective of this study is to construct a novel clinical risk stratification for overall survival (OS) prediction in adolescent and young adult (AYA) women with breast cancer. METHOD: From the Surveillance, Epidemiology, and End Results (SEER) database, AYA women with primary breast cancer diagnosed from 2010 to 2018 were included in our study. A deep learning algorithm, referred to as DeepSurv, was used to construct a prognostic predictive model based on 19 variables, including demographic and clinical information. Harrell's C-index, the receiver operating characteristic (ROC) curve, and calibration plots were adopted to comprehensively assess the predictive performance of the prognostic predictive model. Then, a novel clinical risk stratification was constructed based on the total risk score derived from the prognostic predictive model. The Kaplan-Meier method was used to plot survival curves for patients with different death risks, using the log-rank test to compared the survival disparities. Decision curve analyses (DCAs) were adopted to evaluate the clinical utility of the prognostic predictive model. RESULTS: Among 14,243 AYA women with breast cancer finally included in this study, 10,213 (71.7%) were White and the median (interquartile range, IQR) age was 36 (32-38) years. The prognostic predictive model based on DeepSurv presented high C-indices in both the training cohort [0.831 (95% CI 0.819-0.843)] and the test cohort [0.791 (95% CI 0.764-0.818)]. Similar results were observed in ROC curves. The excellent agreement between the predicted and actual OS at 3 and 5 years were both achieved in the calibration plots. The obvious survival disparities were observed according to the clinical risk stratification based on the total risk score derived from the prognostic predictive model. DCAs also showed that the risk stratification possessed a significant positive net benefit in the practical ranges of threshold probabilities. Lastly, a user-friendly Web-based calculator was generated to visualize the prognostic predictive model. CONCLUSION: A prognostic predictive model with sufficient prediction accuracy was construct for predicting OS of AYA women with breast cancer. Given its public accessibility and easy-to-use operation, the clinical risk stratification based on the total risk score derived from the prognostic predictive model may help clinicians to make better-individualized management.

Potentiated effects of lactate receptor GPR81 on immune microenvironment in breast cancer.

G protein-coupled receptor (GPR81), as lactate receptor, is an upstart in immune regulation, however, its mechanisms involved in tumor escape have not been fully elucidated. In this study, we explored the effects of GPR81 activation on triple-negative breast cancer (TNBC) cells and macrophages. The expression and relationship with immune infiltration of GPR81 were analyzed with TCGA database. Checkpoints and cytokines were evaluated with flow cytometry or ELISA. The TCGA-based data showed a marked decrease of GPR81 in breast cancer (BRCA) compared with normal breast, especially in the basal-like subtype. In normal mammary tissues, GPR81 had negative correlation with various immune checkpoints, nevertheless, this trend weakened accompanied with the reduction of GPR81. GPR81 stimulation had a significantly inhibitory influence on PD-L1 exposure in BT-549 and MDA-MB-231 cell lines, but not in MDA-MB-453 cell line. The pretreatment of siGPR81 to knockdown GPR81 expression resulted in a remitting of PD-L1 reduction when MDA-MB-231 cells were treated with GPR81 agonist 1. However, little effect of GPR81 activation was observed on the expression of PD-L1 on phorbol-12-myristate-13-acetate (PMA)-induced THP-1 cells. Furthermore, GPR81 agonist 1 exerted no significant impact on the secretion of cytokines in THP-1 cells. In general, it is suggested that GPR81 may facilitate immune monitoring via the reduction of PD-L1 in TNBC with glycolytic phenotype. Our results not only provide a novel insight into the effects of GPR81 on immune evasion but a potential therapy targeting GPR81 in BRCA.

Pneumatic Retinopexy Involving the Use of Intravitreal Air Injection and Laser Photocoagulation for Rhegmatogenous Retinal Detachment in Phakic Eyes.

The clinical efficacy of pneumatic retinopexy (PR) using intravitreal pure air injection and laser photocoagulation for rhegmatogenous retinal detachment (RRD) remains unknown. Thirty-nine consecutive patients with RRD (39 eyes) were included in this prospective case series. All patients underwent two-step PR surgery containing pure air intravitreal injection and laser photocoagulation retinopexy during hospitalization. The main outcomes were best-corrected visual acuity (BCVA) and primary anatomic success rates after PR treatment. The mean follow-up was 18.3 ± 9.7 months, ranging from 6 to 37 months. The primary anatomic success rate was 89.7% (35/39) after PR treatment. Final reattachment of the retina was achieved in 100% of cases. Macular epiretinal membrane was developed in two patients (5.7%) among successful PR cases during the follow-up. The mean logMAR BCVA value was significantly improved from 0.94 ± 0.69 before surgery to 0.39 ± 0.41 after surgery. The average central retinal thickness was significantly thinner in the RRD eyes of macula-off patients (206.8 ± 56.13 µm) when compared with the fellow eyes (234.6 ± 48.4 µm) at the last follow-up (p = 0.005). This study concluded that an inpatient PR procedure with pure air injection and laser photocoagulation is a safe and effective approach to treating patients with RRD, who may achieve a high single-operation success rate and good visual acuity recovery.

The Undervalued Acute Leukopenia Induced By Radiotherapy In Cervical Cancer.

BACKGROUND: Myelosuppression is common and threatening during tumor treatment. However, the effect of radiation on bone marrow activity, especially leukocyte count, has been underestimated in cervical cancer. The aim of this study was to evaluate the severity of radiotherapy- induced acute leukopenia and its relationship with intestinal toxicity. METHODS: The clinical data of 59 patients who underwent conventional radiation alone for cervical cancer were retrospectively analyzed. The patients had normal leukocyte count on admission, and the blood cell count, gross tumor volume (GTV) dose, and intestinal toxicity were evaluated. RESULTS: During radiotherapy (RT), 47 patients (79.7%) developed into leukopenia, with 38.3% mild and 61.7% moderate. The mean time for leukopenia was 9 days. Compared with leukopenianegative patients, leukopenia-positive ones had lower baseline leukocyte count, while neutrophil/ lymphocyte (NLR) and monocyte/lymphocyte (MLR) showed no significance. Logistic regression analysis indicated that excluding the factors for age, body mass index (BMI), TNM stage, surgery and GTV dose, baseline leukocyte count was an important independent predictor of leukopenia (OR=0.383). During RT, a significant reduction was found in leukocyte, neutrophil and lymphocyte count at week 2 while monocyte count after 2 weeks. Furthermore, NLR and MLR showed a significant and sustained upward trend. About 54.2% of patients had gastrointestinal symptoms. However, no significant relevance was noted between leukocyte count as well as NLR/MLR and intestinal toxicity, indicating leukopenia may not be the main factor causing and aggravating gastrointestinal reaction in cervical cancer. CONCLUSION: Our results suggest the underrated high prevalence and severity of leukopenia in cervical cancer patients receiving RT, and those with low baseline leukocyte count are more likely for leukopenia, for whom early prevention of infection may be needed during RT.

Prognostic value of lactate transporter SLC16A1 and SLC16A3 as oncoimmunological biomarkers associating tumor metabolism and immune evasion in glioma.

Background: Hypoxic microenvironment is immunosuppressive and protumorigenic, and elevated lactate is an intermediary in the modulation of immune responses. However, as critical lactate transporters, the role of SLC16A1 and SLC16A3 in immune infiltration and evasion of glioma is not fully elucidated. Methods: Gene expression in low- and high-grade glioma (LGG and GBM) was evaluated with TCGA database. The TISIDB, TIMER and CIBERSORT databases were utilized for the analysis of the correlation between SLC16A1 or SLC16A3 and immunocyte infiltration as well as immune checkpoints. Results: Compared with normal tissues, a significant increase of both SLC16A1 and SLC16A3 was found in LGG and GBM, and closely related to the poor prognosis only in LGG. Cancer SEA indicated that SLC16A1 was involved in hypoxia while SLC16A3 contributed to metastasis and inflammation in glioma. The SLC16A3 expression was significantly correlated with neutrophil activation by GO analysis. TISCH showed the distribution of SLC16A1 on glioma cells and SLC16A3 on immune cells, which was correlated to tumor-associated macrophages and neutrophils that are immunosuppressive. SLC16A1 and SLC16A3 were identified to tightly interacted with diverse immune checkpoints (especially PD1, PD-L1, PD-L2, Tim-3) and immunosuppressive factors (TGF-ß and IL-10) in glioma. Furthermore, SLC16A3 had a positive correlation to activation markers of tumor-associated neutrophils and chemokines such as CCL2, CCL22, CXCR2, CXCR4 in LGG and CCL7, CCL20 CXCL8 in GBM, which could enhance infiltration of immunosuppressive cells to the tumor microenvironment. Conclusion: In general, our results suggest that SLC16A1 and SLC16A3 act as a bridge between tumor metabolism and immunity by promoting immunosuppressive cell infiltration, which contributes to immune evasion and a worse prognosis in glioma. Targeting SLC16A1 and SLC16A3 may provide novel therapeutic strategy for immunotherapy in glioma.

Cytokine profiling reveals increased serum inflammatory cytokines in idiopathic choroidal neovascularization.

BACKGROUND: The exact pathogenesis of idiopathic choroidal neovascularization (ICNV) remains unclear. Cytokine-mediated inflammation has been thought to be involved in the pathophysiology of ICNV. The purpose of this study was to investigate serum cytokine profiles in patients with ICNV and to explore the relationship between serum cytokine levels and ICNV severity. METHODS: This case-control study was conducted in 32 ICNV patients and 30 healthy volunteers. Clinical and demographic information was obtained from the medical data platform and the serum was analysed with a multiplex assay to determine the levels of seven cytokines: interleukin (IL)-2, IL-10, IL-15, IL-17, basic fibroblast growth factor (basic FGF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and vascular endothelial growth factor (VEGF). RESULTS: Serum levels of IL-2, IL-10, IL-17, basic FGF, and VEGF were elevated in ICNV patients compared to controls. Serum GM-CSF levels were positively related to central retinal thickness, and serum IL-17 levels were positively related to CNV lesion area. CONCLUSION: Serum inflammatory cytokines were significantly elevated in ICNV patients compared to controls. This suggests that systemic inflammation may play a critical role in the physiopathology of ICNV.

Idiopathic Choroidal Neovascularization: Intraocular Inflammatory Cytokines and the Effect of Intravitreal Ranibizumab Treatment.

Idiopathic choroidal neovascularization (ICNV) is a disorder that primarily affecting patients younger than 50 years and can cause severe loss of vision. Choroidal abnormalities, especially choroidal inflammation, have been thought to be involved in the pathophysiology of ICNV. However, the exact pathogenesis of ICNV remains unclear. The aim of our study was investigate the levels of 27 inflammatory cytokines in the aqueous humor of eyes with ICNV, and to determine the effect of intravitreal injection of ranibizumab (IVR) on cytokine levels. Significantly higher levels of IL-2, IL-10, IL-15, IL-17, basic FGF, and GM-CSF were observed in patients with ICNV compared with controls. However, only IL-17 levels were significantly higher in patients with ICNV compared with controls after adjusting for axial length. Furthermore, there were significant correlations between the levels of IL-10, IL-17, GM-CSF, and VEGF and the lesion area. Significant changes in visual acuity and central retinal thickness were observed after IVR. Besides VEGF, IVR also significantly reduced the levels of IL-2, IL-10, basic FGF, and IL-12, however, the IL-6 levels were significantly increased. Our results suggest that there may be an involvement of IL-17-related inflammatory processes in the etiology of ICNV.

Transcorneal electrical stimulation promotes survival of retinal ganglion cells after optic nerve transection in rats accompanied by reduced microglial activation and TNF-α expression.

Microglial activation plays a crucial role in the pathological processes of various retinal and optic nerve diseases. TNF-α is a pro-inflammatory cytokine that is rapidly upregulated and promotes retinal ganglion cells (RGCs) death after optic nerve injury. However, the cellular source of TNF-α after optic nerve injury remains unclear. Thus, we aimed to determine the changes of retinal microglial activation in a rat model of optic nerve transection (ONT) after transcorneal electrical stimulation (TES). Furthermore, we assessed TNF-α expression after ONT and evaluated the effects of TES on TNF-α production. Rats were divided into 2 control groups receiving a sham surgery procedure, 2 ONT+Sham TES groups, and 2 ONT+TES groups. The rats were sacrificed on day 7 or 14 after ONT. RGCs were retrogradely labelled by Fluorogold (FG) 7 days before ONT, one TES group and corresponding controls were stimulated on day 0, 4, and the second were stimulated on day 0, 4, 7, 10. Whole-mount immunohistofluorescence, quantification of RGCs and microglia, and western blot analysis were performed on day 7 and 14 after ONT. TES significantly increased RGCs survival on day 7 and 14 after ONT, which was accompanied by reduced microglia on day 7, but not 14. TNF-α was co-localized with ameboid microglia and significantly increased on day 7 and 14 after ONT. TES significantly reduced TNF-α production on day 7 and 14 after ONT. Our study demonstrated that TES promotes RGCs survival after ONT accompanied by reduced microglial activation and microglia-derived TNF-α production.