Medrysone promotes corneal injury repair by promoting M2-like polarization of macrophages.

BACKGROUND: Accumulated evidence suggests that M2-like polarized macrophages plays an important role in reducing inflammation, promoting and accelerating wound healing process and tissue repair. Thus, M2-like TAMs (Tumour-associated macrophages) was an appealing target for therapy intervention. METHOD: Flow cytometry and RT-PCR assay were used to detect the polarization of macrophages induced by Medrysone, and the rat corneal mechanical injury model was established to evaluate the efficacy of Medrysone in cornel repair. RESULTS: Here we found that Medrysone enhanced IL-4 induced M2 polarization of macrophages, as illustrated by increased expression of CD206, up-regulation of M2 marker mRNAs. Medrysone promoted VEGF and CCL2 secretion in IL-4 induced M2-like polarization. IL-4 triggered STAT6 activation was further enhanced by Medrysone and silencing of STAT6 partially abrogated the stimulatory effect of Medrysone. Medrysone improved migration-promoting feature of M2-like macrophages, as indicated by increased migration of endothelial cells. Further, Medrysone promoted corneal injury repair by inducing M2 polarization of macrophages in vivo. CONCLUSION: Our study suggest that Medrysone promotes corneal injury repair by inducing the M2 polarization of macrophages, providing a theoretical basis for the application of Medrysone in the treatment of corneal injury.

Platelet-lymphocyte ratio is a prognostic marker in small cell lung cancer-A systemic review and meta-analysis.

Aim: The aim of this study was to evaluate the relationship between platelet-lymphocyte ratio (PLR) and prognosis in small cell lung cancer (SCLC) patients. Method: A comprehensive search was carried out to collect related studies. Two independent investigators extracted the data of hazard ratio (HR) and 95% confidence interval (CI) for overall survival (OS) or progression-free survival (PFS). A random-effect model was applied to analyze the effect of different PLR levels on OS and PFS in SCLC patients. Moreover, subgroup analysis was conducted to seek out the source of heterogeneity. Results: A total of 26 articles containing 5,592 SCLC patients were included for this meta-analysis. SCLC patients with a high PLR level had a shorter OS compared with patients with a low PLR level, in both univariate (HR = 1.56, 95% CI 1.28-1.90, p < 0.0001) and multivariate (HR = 1.31, 95% CI 1.08-1.59, p = 0.007) models. SCLC patients with a high PLR level had a shorter PFS compared with patients with a low PLR level, in the univariate model (HR = 1.71, 95% CI 1.35-2.16, p < 0.0001), but not in the multivariate model (HR = 1.17, 95% CI 0.95-1.45, p = 0.14). Subgroup analysis showed that a high level of PLR shortened OS in some subgroups, including the Asian subgroup, the younger subgroup, the mixed-stage subgroup, the chemotherapy-dominant subgroup, the high-cutoff-point subgroup, and the retrospective subgroup. PLR level did not affect OS in other subgroups. Conclusion: PLR was a good predictor for prognosis of SCLC patients, especially in patients received chemotherapy dominant treatments and predicting OS. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022383069.

Nitric oxide in occurrence, progress and therapy of lung Cancer: a systemic review and meta-analysis.

BACKGROUND: Nitric oxide (NO) plays an important role in lung cancer. However, the results of previous studies about NO in the occurrence, progress and therapy were not consistent. Therefore, we conducted a meta-analysis to evaluate the relationship between NO and lung cancer. METHOD: We carried out comprehensive search in the databases, and collected related studies. The data of fraction of exhaled nitric oxide (FeNO) or blood NO in different populations (lung cancer patients and control subjects) and different time points (before therapy and after therapy) were extracted by two investigators. A random effect model was applied to analyze the differences of FeNO and blood NO in different populations and different time points. To further compare NO level of each subgroup with different pathological types and different stages, a network meta-analysis (NMA) was performed. RESULTS: Fifty studies including 2551 cases and 1691 controls were adopted in this meta-analysis. The FeNO (SMD 3.01, 95% CI 1.89-4.13, p < 0.00001) and blood NO (SMD 1.34, 95% CI 0.84-1.85, p < 0.00001) level in lung cancer patients was much higher than that in control subjects. NMA model indicated blood NO level in each cancer type except SCLC was higher than that in control patients. There was no significant difference of blood NO level among four kinds of lung cancer patients. Blood NO level in LCC patients (SUCRA = 83.5%) was the highest. Blood NO level in advanced stage but not early stage was higher than that in control subjects. Patients in advanced stage (SUCRA = 95.5%) had the highest blood NO level. No significant difference of FeNO (SMD -0.04, 95% CI -0.46-0.38, p > 0.05) and blood NO level (SMD -0.36, 95% CI -1.08-0.36, p > 0.05) was observed between pretreatment and posttreatment in all patients. However, FeNO level elevated (SMD 0.28, 95% CI 0.04-0.51, p = 0.02) and blood NO level decreased in NSCLC patients (SMD -0.95, 95% CI -1.89-0.00, p = 0.05) after therapy. CONCLUSION: FeNO and blood NO level would contribute to diagnosis of lung cancer and evaluation of therapy effect, especially for NSCLC patients.

Effect of berberine on lipopolysaccharide-induced monocyte chemotactic protein-1 and interleukin-8 expression in a human retinal pigment epithelial cell line.

PURPOSE: In this study, we elucidated the effects of berberine, a major alkaloid component contained in medicinal herbs, such as Phellodendri Cortex and Coptidis Rhizoma, on expression of monocyte chemotactic protein-1 (MCP-1) and interleukin-8 (IL-8) in a human retinal pigment epithelial cell line (ARPE-19) caused by lipopolysaccharide (LPS) stimulation. METHODS: ARPE-19 cells were cultured to confluence. Berberine and LPS were added to the medium. MCP-1 and IL-8 mRNA were measured by real-time polymerase chain reaction. MCP-1 and IL-8 protein concentrations in the media were measured using enzyme-linked immunosorbent assay. RESULTS: After stimulation with LPS, MCP-1 and IL-8 mRNA in ARPE-19 cells reached maximum levels at 3 h, and MCP-1 and IL-8 protein in the culture media reached maximum levels at 24 h. Berberine dose-dependently inhibited MCP-1 and IL-8 mRNA expression of the cells and protein levels in the media stimulated with LPS. CONCLUSIONS: These findings indicate that berberine inhibited the expression of MCP-1 and IL-8 induced by LPS.

First identification of Gordonia sputi in a post-traumatic endophthalmitis patient - a case report and literatures review.

BACKGROUND: We present a case of post-traumatic endophthalmitis with relatively good prognosis caused by Gordonia sputi, which, to our knowledge is the first case in the literature. CASE PRESENTATION: A 24 year old man, who underwent an intraocular foreign body extraction half a month before presentation in the left eye, was referred to us complaining of blurred vision and slight pain for 5 days. His first presentation showed moderate intracameral and intravitreous purulent inflammation with a best corrected vision of counting fingers. After gram staining of the intravitreous samples revealed a gram-positive bacilli infection, a combination of amikacin and vancomycin was initially injected intravitreously. The left eye kept stable for three days but deteriorated on the 4th day. On the 5th day after presentation conventional culture characterized the bacterium as an Actinomyces sp. while 16S ribosomal RNA gene sequencing confirmed it as Gordonia sputi. Thereby a complete pars plana vitrectomy combined with lensectomy and silicone oil tamponade was performed. During the surgery an intraocular irrigation with penicillin G was adopted, followed by administration of intravenous penicillin G twice one day for a week. A relatively normal fundus with slight intracameral inflammation was observed a week after the operation, and the best corrected vision recovered to 0.15. One year later his vision remained 0.1. CONCLUSION: Gordonia sputi should be taken into consideration in patients with post-traumatic endophthalmitis especially due to foreign body penetration. Compared to conventional laboratories, molecular methods are recommended for an accurate diagnosis. A comprehensive strategy of antimicrobial agents and vitrectomy may render a satisfactory result.

The Efficacy and Risk Profile of c-Met inhibitors in Non-small Cell Lung Cancer: a Meta-analysis.

c-MET inhibitors are considered as a kind of novel drugs in non-small cell lung cancer (NSCLC) treatment. However, the results of different clinical studies involving c-MET inhibitors were not consistent. In this report, we performed Meta-analysis to investigate the beneficial and harmful effects of these drugs from 9 studies including 1611 patients in target drug groups and 1605 patients in control groups. As a result, patients in target drugs group had longer progression free survival (PFS) (HR 0.80, 95% CI 0.66-0.99, p = 0.04) but not overall survival (OS) than those in control group, especially in Asian (HR 0.57, 95% CI 0.42-0.76, p < 0.001), Non-squamous (HR 0.79, 95% CI 0.64-0.97, p = 0.03), Phase III (HR 0.66, 95% CI 0.50-0.86, p = 0.002), previous treated (HR 0.77, 95% CI 0.63-0.95, p = 0.01) and small molecular compounds subgroups (HR 0.62, 95% CI 0.50-0.78, p < 0.001). In addition, target drugs did not affect the objective response rate (ORR) but improved disease control rate (DCR) (RR 1.22, 95% CI 1.02-1.46, p = 0.03) of NSCLC patients. Our study first indicated that targeting c-MET therapies improved PFS and DCR in advanced or metastatic NSCLC patients, especially in previous treated Asian patients with adenocarcinoma.

Predictive factors for postoperative visual function of primary chronic rhegmatogenous retinal detachment after scleral buckling.

AIM: To evaluate predictive factors for postoperative visual function of primary chronic rhegmatgenous retinal detachment (RRD) after sclera buckling (SB). METHODS: Totally 48 patients (51 eyes) with primary chronic RRD were included in this prospective interventional clinical cases study, which underwent SB alone from June 2008 to December 2014. Age, sex, symptoms duration, detached extension, retinal hole position, size, type, fovea on/off, proliferative vitreoretinopathy (PVR), posterior vitreous detachment (PVD), baseline best corrected visual acuity (BCVA), operative duration, follow up duration, final BCVA were measured. Pearson correlation analysis, Spearman correlation analysis and multivariate linear stepwise regression were used to confirm predictive factors for better final visual acuity. Student's t-test, Wilcoxon two-sample test, Chi-square test and logistic stepwise regression were used to confirm predictive factors for better vision improvement. RESULTS: Baseline BCVA was 0.8313±0.6911 logMAR and final BCVA was 0.4761±0.4956 logMAR. Primary surgical success rate was 92.16% (47/51). Correlation analyses revealed shorter symptoms duration (r=0.3850, P=0.0053), less detached area (r=0.5489, P<0.0001), fovea (r=0.4605, P=0.0007), no PVR (r=0.3138, P=0.0250), better baseline BCVA (r=0.7291, P<0.0001), shorter operative duration (r=0.3233, P=0.0207) and longer follow up (r=-0.3358, P=0.0160) were related with better final BCVA, while independent predictive factors were better baseline BCVA [partial R-square (PR(2))=0.5316, P<0.0001], shorter symptoms duration (PR(2)=0.0609, P=0.0101), longer follow up duration (PR(2)=0.0278, P=0.0477) and shorter operative duration (PR(2)=0.0338, P=0.0350). Patients with vision improvement took up 49.02% (25/51). Univariate and multivariate analyses both revealed predictive factors for better vision improvement were better baseline vision [odds ratio (OR) =50.369, P=0.0041] and longer follow up duration (OR=1.144, P=0.0067). CONCLUSION: Independent predictive factors for better visual outcome of primary chronic RRD after SB are better baseline BCVA, shorter symptoms duration, shorter operative duration and longer follow up duration, while independent predictive factors for better vision improvement after operation are better baseline vision and longer follow up duration.

Refractive shift of silicone oil tamponade in pseudophakic eye.

BACKGROUND: Refraction change of silicone oil (SO) tamponade in phakic and aphakic eye has been studied thoroughly; however, it is rarely studied in pseudophakic eye. In this paper we aimed to deduce a theoretical formula predicting refractive shift of silicone oil tamponade in pseudophakic eye and compared it with clinical findings. METHOD: A theoretical formula was deduced through strict geometric optical principles under the Helmholtz Schematic eye model. Pre/postoperative refractive status of patients who previously underwent phacoemulsification, intraocular lens (IOL) implant, vitrectomy, SO tamponade and required SO extraction was studied. RESULTS: Twenty-six patients (27 eyes, 13 males and 13 females) were studied. Refractive error of SO-off was -1.88 ± 2.73D, and of SO-in was 2.02 ± 3.90. Refractive shift of SO tamponade was -3.90 ± 1.74D. Refractive shift was significantly associated with refractive power of IOL (r = -0.7903, p < 0.0001, Pearson correlation test) and anterior chamber distance (ACD, r = 0.3840, p = 0.0480, Pearson correlation test). Theoretical refractive shift was -4.10 ± 1.51D, and there was no significant difference between the theoretical and the clinical refractive shift (p = 0.3329, Paired T test). CONCLUSIONS: Refractive shift of SO tamponade in pseudophakic eye correlates with refractive power of implanted IOL and ACD, and strong correlation between theoretical formula and clinical findings was detected.

Changes in vitreous VEGF, bFGF and fibrosis in proliferative diabetic retinopathy after intravitreal bevacizumab.

AIM: To evaluate the relationship between intravitreal bevacizumab (IVB) treatment and the levels of vitreous vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and vitreous-retina surface fibrosis in patients with proliferative diabetic retinopathy (PDR). METHODS: This study was a prospective, open-label, controlled, randomized clinical trial. Sixty-eight eyes of PDR patients (n=53) and macular hole patients (n=15) were enrolled in this study. Thirty-four eyes of the PDR patients received IVB before vitrectomy. Twenty-three of the 34 PDR patients received IVB treatment 5d before vitrectomy (subgroup a), and 11 of the 34 PDR patients received IVB treatment greater than 2wk prior to vitrectomy (subgroup b). Nineteen of the PDR patients did not receive IVB treatment at any time prior to vitrectomy. The levels of bFGF and VEGF in vitreous samples were measured using enzyme-linked immunosorbent assay (ELISA) and the degree of vitreoretinal fibrosis was characterized using clinical data and data obtained intra-operatively. RESULTS: In PDR patients, VEGF and bFGF levels were significantly increased compared to non-PDR (control) subject's eyes (P<0.01). In PDR patients, vitreous VEGF levels were significantly decreased following IVB treatment compared to PDR patients that did not receive IVB treatment (P<0.01). The degree of vitreoretinal fibrosis was significantly increased in subgroup b compared to subgroup a(P<0.05) and to patients that did not receive IVB (P<0.05). Vitreous bFGF levels were significantly greater in subgroup b than subgroup a (P<0.01) or in patients who did not receive IVB treatment (P<0.05). A Spearman's rank correlation test indicated that higher levels of vitreous bFGF, but not VEGF, correlated with the degree of vitreoretinal fibrosis. CONCLUSION: We found that bFGF levels increase in PDR patient's vitreous after IVB treatment longer than two weeks prior to vitrectomy and correlated with the degree of fibrosis after IVB treatment. These findings suggest vitreous fibrosis is increased in PDR patients after IVB treatment may be due to increased levels of bFGF.

[Preretinal hemorrhage and prognosis following vitrectomy and silicone oil tamponade for severe proliferative diabetic retinopathy].

OBJECTIVE: To examine the prognosis of preretinal hemorrhage following vitrectomy and silicone oil tamponade for severe proliferative diabetic retinopathy. METHODS: Clinical data of 76 cases of proliferative diabetic retinopathy treated with vitrectomy and silicone oil infusion tamponade in Sir Run Run Shaw Hospital from October 2006 to September 2013 were retrospectively reviewed. Intraoperative bleeding,postoperative preretinal bleeding,blood reabsorption time, and preretinal fibrosis were assessed. RESULTS: All preretinal hemorrhage developed within 1 week after surgery, blood was distributed in thin and scattered patterns (32 cases), thick and localized patterns (25 cases) or thick and scattered patterns (19 cases). The preretinal hemorrhage was ceased in 1 day after operation in 35 cases, in 2 days after operation in 18 cases, in two weeks after operation in 23 case. Recurrent hemorrhage occurred within 1 week after operation in 15 cases. Thin blood was largely reabsorbed in about two weeks, and thick blood was largely reabsorbed in about five weeks. Fibrosis tissue was resulted in 15 cases(34.1%) with thick blood. CONCLUSION: Most of preretinal hemorrhage occurs within 1 week after surgery and is reabsorpted with 5 weeks in patients with proliferative diabetic retinopathy undergoing vitrectomy and silicone oil tamponade. The major complication of preretinal bleeding is the formation of preretinal fibrosis.

[Optical coherence tomography predictive factors for idiopathic macular hole surgery outcome].

OBJECTIVE: To evaluate the use of preoperative optical coherence tomography (OCT) image and some related indexes as predictive factors for the visual outcomes of the idiopathic macular hole (IMH) after pars plana vitrectomy and the internal limiting membrane (ILM) peeling surgery. METHODS: This was a case-series study. Twenty-five eyes of 23 IMH patients undergoing a successful vitrectomy and ILM peeling surgery and following up more than 6 months were included in this retrospective study. Of the 23 patients, 6 were male and 17 were female. The median patient age was 67-year old (range 63 to 71 years). The median duration of IMH was 6 months (range 3.5 to 12.0 months).In the patients, the macular hole was found in 9 eyes at stage II, 11 eyes at stage III, and 5 eyes at stage IV. Best corrected visual acuity (BCVA) were examined before and after the surgery. The minimum diameter (a) , the height (b) and the base diameter (c) of macular holes were measured by OCT. According to the indexes, macular hole index (MHI, b/c) , tractional hole index (THI, b/a) , diameter hole index (DHI, a/c) were calculated, respectively. Spearman rank correlation analysis was performed to understand the correlations between postoperative BCVA and the related indexes. Cut-off values were obtained for MHI and THI, respectively, from receiver operating characteristic (ROC) curve analysis. RESULTS: The median preoperative BCVA was 0.100(range 0.050 to 0.180). The median MHI, THI and DHI was 0.476(range 0.416 to 0.684), 1.048(range 0.761 to 1.346) and 0.536(range 0.431 to 0.645), respectively. The median 3-month postoperative BCVA was 0.150 (range 0.120 to 0.275), markedly improved after surgery (Mann-Whitney U test:P = 0.002) . The median latest postoperative BCVA was 0.250 (range 0.135 to 0.350), also markedly improved (Mann-Whitney U test, P = 0.002) . MHI, THI and preoperative BCVA correlated significantly with postoperative BCVA by Spearman rank correlation analysis (rMHI = 0.481, P = 0.015; rTHI= 0.516, P = 0.008; preoperative BCVA = 0.560, P = 0.004, respectively). Areas under the curve of 0.740 and 0.760 for MHI and THI were obtained respectively. Cut-off values of 0.475 and 0.973 were obtained for MHI and THI, respectively, from ROC curve analysis. Postoperative BCVAs in the MHI ≥ 0.475 group and in the THI ≥ 0.973 group was better than that in the MHI < 0.475 and in the THI < 0.973 group, respectively (Mann-Whitney U test:P MHI = 0.013, P THI = 0.008) . CONCLUSION: An MHI ≥ 0.475 or a THI ≥ 0.973 may be predictive factors for a good visual prognosis after IMH surgery.

The evaluation of the retinal nerve fiber layer in multiple sclerosis with special-domain optical coherence tomography.

BACKGROUND/AIMS: Retinal nerve fiber layer (RNFL) thinning has been observed on histopathology and time-domain optical coherence tomography in many diseases of the central nervous system. In this study, with a higher resolution of spectral-domain optical coherence tomography (SDOCT), we detected RNFL changes in patients with multiple sclerosis (MS) in China, and compared RNFL thickness between eyes with and without optic neuritis (ON). METHODS: In this retrospective, nonrandom case study, the patients were recruited from the Affiliated Sir Run Run Shaw Hospital of Zhejiang University. RNFL thickness was measured for each eye using SDOCT. The controls were recruited from the healthy population. RESULTS: Peripapillary RNFL thickness of 24 eyes in 12 patients was detected by SDOCT. The average RNFL thickness of the MS patients was 81.9 ± 17.8 µm compared to the control value of 102.1 ± 8.1 µm (p = 0.00). The average RNFL of the patients with a history of ON was thinner than that of patients without ON (71.8 ± 19.2 µm vs. 92.0 ± 8.5 µm, p = 0.001). CONCLUSION: The RNFL thinning in Chinese patients with MS can be detected by SDOCT. The SDOCT scan represents a high-resolution, objective, noninvasive and easily quantifiable in vivo biomarker of MS.

Surgical management of retinal detachment resulting from macular hole in a setting of high myopia.

PURPOSE: To evaluate the anatomical and visual outcomes of pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling and use of retinal tamponade for retinal detachments resulting from macular hole (MHRD) in highly myopic eyes. METHODS: Twenty-nine highly myopic patients (29 eyes) underwent PPV with ILM peeling and retinal tamponade for MHRD were enrolled. Demographics and best-corrected visual acuity (BCVA) were measured preoperatively and at final follow-up. Anatomical success and macular hole closure were analyzed. RESULTS: Patients' mean age of patients was 58.7 ± 10.6 years, mean follow-up was 11.7 ± 7.4 months. Twenty three eyes (23/26, 88.5%) undergoing primary PPV combined with ILM peeling had successful initial retinal reattachment, including 19 eyes (19/19, 100%) with silicone oil tamponade and in 4 eyes (4/7, 57.1%) with sulfur hexafluoride (C3F8) tamponade. Overall anatomical success was achieved in 27 eyes (27/29, 93.1%). The macular hole closure was observed in 17 eyes (17/26, 65.4%) with final anatomical success. Compared to preoperative BCVA, the mean postoperative BCVA in the eyes with anatomical success was significantly improved (P = 0.007, Wilcoxon signed rank test). CONCLUSION: As a primary or secondary procedure, PPV combined with ILM peeling and usage of retinal tamponade serves as an effective method for MHRD in highly myopic eyes.

Risk factors related to chronic rhegmatogenous retinal detachment.

AIM: To evaluate the clinical factors related to chronic rhegmatogenous retinal detachment (RRD). METHODS: A retrospective case-control study. A total of 103 consecutive patients (103 eyes) with primary RRD were studied to evaluate the clinical factors related to chronic RRD. RESULTS: Chi-square test was used to sift out the following associated factors with chronic RRD: younger patients (P=0.0028), better preoperative best corrected visual acuity (BCVA, P=0.0316), atrophic retinal break (P<0.0001), inferior retinal break (P<0.0001), smaller break (P=0.0005); then the independent risk factors related to chronic RRD was determined by stepwise logistic regression analysis as following: atrophic retinal break (odds ratio (OR)=7.997, P=0.007), inferior retinal break (OR=14.127, P<0.0001) and better preoperative BCVA (OR=1.636 P<0.0722) . CONCLUSION: Atrophic retinal break, inferior retinal break and better preoperative BCVA are the independent risk factors related to chronic RRD.