Deficiency of tumor-expressed B7-H3 augments anti-tumor efficacy of anti-PD-L1 monotherapy rather than the combined chemoimmunotherapy in ovarian cancer.

As a high mortality gynecological malignancy, most ovarian cancer patients experience refractory to standard chemotherapy, current immunotherapy or chemoimmunotherapy in clinic and clinical trials. The underlying mechanisms and biomarkers predictive of response for patient selection is quite urgent. In this study, we found that the level of tumor-expressed B7-H3 is positively correlated with the poorer prognosis in ovarian cancer patients. Therapeutically, in syngeneic mouse model of ovarian cancer, deficiency of tumor-expressed B7-H3 significantly potentiates the anti-tumor efficacy of paclitaxel or PD-L1 blockade monotherapy. However, combination of paclitaxel plus anti-PD-L1 has no synergistic effects than PD-L1 blockade monotherapy. Mechanistically, deficiency of tumor-expressed B7-H3 attenuates inflammatory cytokine IL-6 production, upregulates type I interferon (IFN) expression and increases paclitaxel-induced tumor cells apoptosis via caspase 3 activation pathway, resulting in reprogramming the tumor microenvironment including increasing the infiltration of effector T lymphocytes and decreasing the recruitment of Ly6G+CD11b+ myeloid-derived suppressor cells (MDSCs) in vivo. Collectively, these results demonstrate that deficiency of tumor-expressed B7-H3 enhances the anti-tumor efficacy of paclitaxel or PD-L1 blockade monotherapy rather than their combined chemoimmunotherapy in ovarian cancer, suggesting that B7-H3 may be a potential predictive biomarker for beneficial patient stratification and a candidate therapeutic target in ovarian cancer.

Comparison of Three-Dimensional Surgical System Versus Binocular Microscope for Clear Corneal Incision in Cataract Surgery.

INTRODUCTION: To compare surgical outcomes of 2.2 mm clear corneal incision (CCI) between a three-dimensional (3D) visualization system and traditional binocular microscope (BM) for phacoemulsification and intraocular lens implantation surgery. METHODS: In this randomized controlled clinical study, 60 eyes with age-related cataracts were divided into two groups receiving cataract surgery using either a 3D vision system (n = 30 eyes) (3D group) or a binocular microscope (n = 30 eyes) (BM group). We recorded and statistically analyzed surgical parameters and pre- and postoperative ocular parameters. Primary outcomes included the change in endothelial cell density (ECD) and CCI architecture, and secondary outcomes comprised other ocular parameters and surgical parameters. All procedures complied with the tenets of the Declaration of Helsinki. RESULTS: Of the 60 eyes randomly assigned between January 5, 2021, and May 9, 2021, 55 (26 eyes in the 3D group and 29 eyes in the BM group) were analyzed. The ECD loss rate was 8.1% in the 3D group and 12.3% in the BM group, but the difference was not statistically significant. Local detachment of Descemet's membrane was seen in 50% (13 eyes, 3D group) and 51.6% (15 eyes, BM group), wound gaping at the endothelial side in 15.4% (four eyes, 3D group) and 10.3% (four eyes, BM group), gaping at the epithelial side in 11.5% (three eyes, 3D group) and 6.9% (two eyes, BM group), and misalignment of the incision in 3.4% (one eye, BM group) 1 day after surgery. These abnormalities improved with time. There was no difference between the 3D group and BM group in terms of other ocular parameters or surgical parameters before and after surgery. CONCLUSIONS: Using the 3D surgical system for phacoemulsification and IOL implantation surgery seems to result in similar ECD and CCI conditions as using a conventional binocular microscope. TRIAL REGISTRATION: The protocol was registered on ClinicalTrials.gov (NCT04839250).

A responsive fluorescent probe for detecting and imaging pyruvate kinase M2 in live cells.

In this study, we designed and tested fluorescent probe zy-2 for specific and responsive imaging of pyruvate kinase M2 (PKM2), which can be excited by 419 nm light. A 17-fold enhancement in the responsive emission upon zy-2's binding to PKM2 was observed, imaging of which was successfully recorded in a time- and concentration-dependent manner in PKM2-positive cells. Thus, we obtained a responsive fluorescent probe for the specific and sensitive detection of PKM2, which is innovative in design and applicable to the detection of cancer cells.

Glaucoma and risk factors three years after congenital cataract surgery.

BACKGROUND: This study aimed to identify the incidence of and risk factors for postoperative glaucoma-related adverse events at various time points after congenital cataract surgery. METHODS: This retrospective cohort study enrolled 259 eyes from 174 patients (surgical age ≤ 7 years) who underwent congenital cataract surgery. All surgical procedures were conducted at the Eye Hospital of Wenzhou Medical University between May 2011 and March 2019. Patients were classified into group 1 [primary intraocular lens (IOL) implantation, N = 111 eyes], group 2 (secondary IOL implantation, N = 85 eyes), and group 3 (no IOL implantation, N = 63 eyes). We recorded demographic factors and incidence and risk factors for glaucoma-related adverse events. RESULTS: Glaucoma-related adverse events occurred in 21 (8.1%) eyes, whereas 27 (10.4%) eyes developed steroid-induced ocular hypertension. The percentage of glaucoma-related adverse events was 0%, 1.2%, 1.2%, 1.6%, 4.0%, and 8.9% at 1 month, 6 months, 1 year, 2 years, 3 years and 4 years after surgery, respectively. Sixteen (18.8%), five (7.9%), and zero eyes developed glaucoma-related adverse events in groups 2, 3, and 1, respectively. Family history of congenital cataract [hazard ratio (HR), 50.463; 95% confidence interval (CI), 7.051-361.139; P < 0.001], preoperative central corneal thickness (CCT) [HR, 1.021; 95% CI, 1.009-1.034; P = 0.001], preoperative horizontal corneal diameter (HCD) [HR, 3.922; 95% CI, 1.558-9.804; P = 0.004], and preoperative lens thickness (LT) [HR, 3.745; 95% CI, 1.344-10.417; P = 0.012] were identified as predictors of postoperative glaucoma-related adverse events. CONCLUSIONS: Family history of congenital cataract, thicker preoperative CCT, smaller preoperative HCD, and thinner preoperative LT are the main risk factors of postoperative glaucoma-related adverse events. Regular monitoring of children after cataract surgery with these risk factors may help ophthalmologists detect susceptible individuals and provide timely interventions in the clinic.

Deficiency of GFRα1 promotes hepatocellular carcinoma progression but enhances oxaliplatin-mediated anti-tumor efficacy.

Neurotrophic factors and their receptors have been identified to promote tumor progression. GFRα1, the receptor for glial cell line-derived neurotrophic factor (GDNF), has been demonstrated to be predominantly expressed in adult liver tissue. Our preliminary data showed that GFRα1 is significantly downregulated in hepatocellular carcinoma (HCC) tissue, compared to the matched non-neoplastic tissue. However, the role of GFRα1 in HCC progression remains unknown. Here we found that the expression of GFRα1 in HCC tissue is inversely correlated with the poorer prognosis of HCC patients. Silencing of GFRα1 expression markedly enhances HCC cell growth, tumor metastasis, as well as shortens the survival of HCC tumor-bearing mice. Forced expression of GFRα1 in HCC cells significantly reverses the tumor-promoting effects of GFRα1 silencing, and AAV8-mediated GFRα1 transfection in HCC tumor tissues significantly impedes tumor growth and prolongs the survival of HCC tumor-bearing mice. These results are also verified in vivo in GFRα1 knock-out mice model, with increased DEN-induced HCC carcinogenesis. Mechanistically, GFRα1 could inhibit epithelial-to-mesenchymal transition (EMT) of HCC cells, by upregulating expression of Claudin-1 and ZO-1. Of note, silencing of GFRα1 expression promotes oxaliplatin-mediated HCC cell apoptosis resulting in prolonged survival of HCC-bearing mice, and forced expression of GFRα1 markedly increased oxaliplatin resistance of HCC cells. These results demonstrate that deficiency of GFRα1 promotes HCC progression but enhances chemotherapeutic anti-tumor efficacy, suggesting that GFRα1 may be a candidate prognostic biomarker and a potential therapeutic target in HCC.