Changes in posterior corneal elevation after small incision lenticule extraction for different myopic diopters.

AIM: To study the changes and effect factors of posterior corneal surface after small incision lenticule extraction (SMILE) with different myopic diopters. METHODS: Ninety eyes of 90 patients who underwent SMILE were included in this retrospective study. Patients were allocated into three groups based on the preoperative spherical equivalent (SE): low myopia (SE≥-3.00 D), moderate myopia (-3.00 D>SE>-6.00 D) and high myopia (SE≤-6.00 D). Posterior corneal surfaces were measured by a Scheimpflug camera preoperatively and different postoperative times (1wk, 1, 3, 6mo, and 1y). Posterior mean elevation (PME) at 25 predetermined points of 3 concentric circles (2-, 4-, and 6-mm diameter) above the best fit sphere was analyzed. RESULTS: All surgeries were completed uneventfully and no ectasia was found through the observation. The difference of myopia group was significant at the 2-mm ring at 1 and 3mo postoperatively (1mo: P=0.017; 3mo: P=0.018). The effect of time on ΔPME was statistically significant (2-mm ring: P=0.001; 4-mm ring: P<0.001; 6-mm ring: P<0.001). The effect of different corneal locations on ΔPME was significant except 1wk postoperatively (1mo: P=0.000; 3mo: P=0.000; 6mo: P=0.001; 1y: P=0.001). Posterior corneal stability was linearly correlated with SE, central corneal thickness, ablation depth, residual bed thickness, percent ablation depth and percent stromal bed thickness. CONCLUSION: The posterior corneal surface changes dynamically after SMILE. No protrusion is observed on the posterior corneal surface in patients with different degrees of myopia within one year after surgery. SMILE has good stability, accuracy, safety and predictability.

Combining protein arginine methyltransferase inhibitor and anti-programmed death-ligand-1 inhibits pancreatic cancer progression.

BACKGROUND: Immunotherapy targeting programmed death-1 (PD-1) or programmed death-ligand-1 (PD-L1) has been shown to be effective in a variety of malignancies but has poor efficacy in pancreatic ductal adenocarcinoma (PDAC). Studies have shown that PD-L1 expression in tumors is an important indicator of the efficacy of immunotherapy. Tumor cells usually evade chemotherapy and host immune surveillance by epigenetic changes. Protein arginine methylation is a common posttranslational modification. Protein arginine methyltransferase (PRMT) 1 is deregulated in a wide variety of cancer types, whose biological role in tumor immunity is undefined. AIM: To investigate the combined effects and underlying mechanisms of anti-PD-L1 and type I PRMT inhibitor in pancreatic cancer in vivo. METHODS: PT1001B is a novel type I PRMT inhibitor with strong activity and good selectivity. A mouse model of subcutaneous Panc02-derived tumors was used to evaluate drug efficacy, toxic and side effects, and tumor growth in vivo. By flow cytometry, we determined the expression of key immune checkpoint proteins, detected the apoptosis in tumor tissues, and analyzed the immune cells. Immunohistochemistry staining for cellular proliferation-associated nuclear protein Ki67, TUNEL assay, and PRMT1/PD-L1 immunofluorescence were used to elucidate the underlying molecular mechanism of the antitumor effect. RESULTS: Cultured Panc02 cells did not express PD-L1 in vitro, but tumor cells derived from Panc02 transplanted tumors expressed PD-L1. The therapeutic efficacy of anti-PD-L1 mAb was significantly enhanced by the addition of PT1001B as measured by tumor volume (1054.00 ± 61.37 mm3 vs 555.80 ± 74.42 mm3, P < 0.01) and tumor weight (0.83 ± 0.06 g vs 0.38 ± 0.02 g, P < 0.05). PT1001B improved antitumor immunity by inhibiting PD-L1 expression on tumor cells (32.74% ± 5.89% vs 17.95% ± 1.92%, P < 0.05). The combination therapy upregulated tumor-infiltrating CD8+ T lymphocytes (23.75% ± 3.20% vs 73.34% ± 4.35%, P < 0.01) and decreased PD-1+ leukocytes (35.77% ± 3.30% vs 6.48% ± 1.08%, P < 0.001) in tumor tissue compared to the control. In addition, PT1001B amplified the inhibitory effect of anti-PD-L1 on tumor cell proliferation and enhanced the induction of tumor cell apoptosis. PRMT1 downregulation was correlated with PD-L1 downregulation. CONCLUSION: PT1001B enhances antitumor immunity and combining it with anti-PD-L1 checkpoint inhibitors provides a potential strategy to overcome anti-PD-L1 resistance in PDAC.

Effect of photodynamic therapy with (17R,18R)-2-(1-hexyloxyethyl)-2-devinyl chlorine E6 trisodium salt on pancreatic cancer cells in vitro and in vivo.

AIM: To investigate the antitumor effects and underlying mechanisms of (17R,18R)-2-(1-hexyloxyethyl)-2-devinyl chlorine E6 trisodium salt (YLG-1)-induced photodynamic therapy (PDT) on pancreatic cancer in vitro and in vivo. METHODS: YLG-1 is a novel photosensitizer extracted from spirulina. Its phototoxicity, cellular uptake and localization, as well as its effect on reactive oxygen species (ROS) production, apoptosis, and expression of apoptosis-associated proteins were detected in vitro. An in vivo imaging system (IVIS), the Lumina K imaging system, and mouse models of subcutaneous Panc-1-bearing tumors were exploited to evaluate the drug delivery pathway and pancreatic cancer growth in vivo. RESULTS: YLG-1 was localized to the mitochondria, and the appropriate incubation time was 6 h. Under 650 nm light irradiation, YLG-1-PDT exerted a potent cytotoxic effect on pancreatic cancer cells in vitro, which could be abolished by the ROS scavenger N-acetyl-L-cysteine (NAC). The death mode caused by YLG-1-PDT was apoptosis, accompanied by upregulated Bax and cleaved Caspase-3 and decreased Bcl-2 expression. The results from the IVIS images suggested that the optimal administration route was intratumoral (IT) injection and that the best time to conduct YLG-1-PDT was 2 h post-IT injection. Consistent with the results in vitro, YLG-1-PDT showed great growth inhibition effects on pancreatic cancer cells in a mouse model. CONCLUSION: YLG-1 is a potential photosensitizer for pancreatic cancer PDT via IT injection, the mechanisms of which are associated with inducing ROS and promoting apoptosis.

Ultrasonography Assessments of Optic Nerve Sheath Diameter as a Noninvasive and Dynamic Method of Detecting Changes in Intracranial Pressure.

Importance: The crtierion standard method for monitoring intracranial pressure (ICP) can result in complications and pain. Hence, noninvasive, repeatable methods would be valuable. Objective: To examine how ultrasonographic optic nerve sheath diameter (ONSD) correlated with noninvasive and dynamically monitored ICP changes. Design, Setting, and Participants: The ONSD was measured before the lumbar puncture (LP) in 60 patients on admission. Patients with elevated ICP were divided into group 1 (200 < LP ≤ 300 mm H2O) and group 2 (LP > 300 mm H2O). Patients underwent follow-up ONSD and LP measurements within 1 month. We analyzed the correlations between the ONSD and ICP on admission and between the changes in ONSD and ICP, which were the respective changes in ONSD and ICP from admission to follow-up. Main Outcomes and Measures: The ultrasonographic ONSD and ICP were measured on admission and follow-up. The correlations between the ONSD and ICP on admission and between the changes in ONSD and ICP were analyzed using Pearson correlation analyses. Results: For 60 patients (Han nationality; mean [SD] age, 36.2 [12.04] years; 29 [48%] female) on admission, the ONSD and ICP values were strongly correlated, with an r of 0.798 (95% CI, 0.709-0.867; P < .001). Twenty-five patients with elevated ICP who completed the follow-up were included. The mean (SD) ONSD and ICP on admission were 4.50 (0.54) mm and 302.40 (54.26) mm H2O, respectively. The ONSD and ICP values obtained on admission were strongly correlated , with an r of 0.724 (95% CI, 0.470-0.876; P < .001). The mean (SD, range) changes in ICP and ONSD were 126.64 (52.51 mm H2O, 20-210 mm H2O) (95% CI, 106.24-146.07) and 1.00 (0.512 mm, 0.418-2.37 mm) (95% CI, 0.83-1.20), respectively. The change in ONSD was strongly correlated with the change in ICP, with an r of 0.702 (95% CI, 0.425-0.870; P < .001). The follow-up evaluations revealed that the elevated ICP and dilated ONSD had returned to normal, and no evidence of difference was found in the mean ONSDs between group 1 (3.49 mm; 95% CI, 3.34-3.62 mm) and group 2 (3.51 mm; 95% CI, 3.44-3.59 mm) (P = .778) at follow-up. Conclusions and Relevance: The dilated ONSDs decreased along with the elevated ICP reduction. Ultrasonographic ONSD measurements may be a useful, noninvasive tool for dynamically evaluating ICP.

Treatment for incarcerated indirect hernia with "Cross-Internal Ring" inguinal oblique incision in children.

BACKGROUND: This study aims to evaluate the utility of the "Cross-Internal Ring" inguinal oblique incision for the surgical treatment of incarcerated indirect hernia (IIH) complicated with severe abdominal distension. MATERIALS AND METHODS: Patients of IIH complicated with severe abdominal distension were reviewed retrospectively. All patients received operation through the "Cross-Internal Ring" inguinal oblique incision. RESULTS: There were totally 13 patients were included, male to female ratio was 9-4. The time for patients to resume oral feeding varying from 2 to 5 days after operation, no complications include delayed intestinal perforation, intra-abdominal abscess, and incision infection happened. Average postoperative hospital stay was 5.2 days. All cases were followed up for 6-18 months. No recurrence or iatrogenic cryptorchidism happened. CONCLUSION: "Cross-Internal Ring" inguinal oblique incision is a simple, safe, and reliable surgical method to treat pediatric IIH complicated with severe abdominal distension.

Noninvasive and quantitative intracranial pressure estimation using ultrasonographic measurement of optic nerve sheath diameter.

We aimed to quantitatively assess intracranial pressure (ICP) using optic nerve sheath diameter (ONSD) measurements. We recruited 316 neurology patients in whom ultrasonographic ONSD was measured before lumbar puncture. They were randomly divided into a modeling and a test group at a ratio of 7:3. In the modeling group, we conducted univariate and multivariate analyses to assess associations between ICP and ONSD, age, sex, BMI, mean arterial blood pressure, diastolic blood pressure. We derived the mathematical function "Xing &Wang" from the modelling group to predict ICP and evaluated the function in the test group. In the modeling group, ICP was strongly correlated with ONSD (r = 0.758, p < 0.001), and this association was independent of other factors. The mathematical function was ICP = -111.92 + 77.36 × ONSD (Durbin-Watson value = 1.94). In the test group, a significant correlation was found between the observed and predicted ICP (r = 0.76, p < 0.001). Bland-Altman analysis yielded a mean difference between measurements of -0.07 ± 41.55 mmH2O. The intraclass correlation coefficient and its 95%CIs for noninvasive ICP assessments using our prediction model was 0.86 (0.79-0.90). Ultrasonographic ONSD measurements provide a potential noninvasive method to quantify ICP that can be conducted at the bedside.