Rhegmatogenous retinal detachment in highly myopic eyes with implantable collamer lens.

AIM: To investigate the clinical characteristics, treatment methods and outcomes of rhegmatogenous retinal detachment (RRD) in highly myopic eyes with implantable collamer lens (ICL). METHODS: High myopia patients who received treatment for nontraumatic RRD after ICL implantation surgery at the Retinal Department of Zhongshan Ophthalmic Center from Jan 2018 to Dec 2022 were reviewed. Comprehensive ophthalmologic examinations including visual acuity measurement and digital fundus photography were performed in each patient. RESULTS: A total of nine RRD eyes from nine patients who received V4c-ICL implantation were included. The mean time from ICL implantation surgery to the diagnosis of RRD was 32.44±22.56mo (range, 1-60mo). At the initial visit for RRD, giant retinal tear (GRT), horseshoe tear, simple round hole, and horseshoe tear combined with round hole were detected in 3, 3, 2, and 1 eye(s), respectively, with macula-off in eyes. Eight patients received surgical treatment, and one patient was treated by retinal laser photocoagulation alone. The ICL was preserved in 7 eyes. At the last follow-up, the mean best corrected visual acuity (BCVA) improved significantly from 1.76±1.06 logMAR at presentation to 0.81±1.01 logMAR (P=0.035), and no case of recurrent retinal detachment was found. CONCLUSION: The morphological presentation of retinal breaks is diverse in this study. The ICL can be preserved in most cases during the course of retinal detachment repair surgery in our data, companied with acceptable visual and anatomical outcomes.

Histone deacetylase inhibitor pracinostat suppresses colorectal cancer by inducing CDK5-Drp1 signaling-mediated peripheral mitofission.

Divisions at the periphery and midzone of mitochondria are two fission signatures that determine the fate of mitochondria and cells. Pharmacological induction of excessively asymmetric mitofission-associated cell death (MFAD) by switching the scission position from the mitochondrial midzone to the periphery represents a promising strategy for anticancer therapy. By screening a series of pan-inhibitors, we identified pracinostat, a pan-histone deacetylase (HDAC) inhibitor, as a novel MFAD inducer, that exhibited a significant anticancer effect on colorectal cancer (CRC) in vivo and in vitro. Pracinostat increased the expression of cyclin-dependent kinase 5 (CDK5) and induced its acetylation at residue lysine 33, accelerating the formation of complex CDK5/CDK5 regulatory subunit 1 and dynamin-related protein 1 (Drp1)-mediated mitochondrial peripheral fission. CRC cells with high level of CDK5 (CDK5-high) displayed midzone mitochondrial division that was associated with oncogenic phenotype, but treatment with pracinostat led to a lethal increase in the already-elevated level of CDK5 in the CRC cells. Mechanistically, pracinostat switched the scission position from the mitochondrial midzone to the periphery by improving the binding of Drp1 from mitochondrial fission factor (MFF) to mitochondrial fission 1 protein (FIS1). Thus, our results revealed the anticancer mechanism of HDACi pracinostat in CRC via activating CDK5-Drp1 signaling to cause selective MFAD of those CDK5-high tumor cells, which implicates a new paradigm to develop potential therapeutic strategies for CRC treatment.

Management of deep sacral and ischial pressure injuries with free-style local perforator flaps: A D+P+DPD model.

BACKGROUND: Previous reports on the treatment of sacral and ischial pressure injuries have not provided clear algorithms for surgical therapies. The objective of this study was to establish a reconstruction algorithm to guide the selection of an ideal free-style perforator flap that can be tailored to the defect in question. METHODS: We used 23 perforator flaps to reconstruct 14 sacral and 8 ischial defects in 22 patients over 5 years. A reconstruction algorithm system was developed based on the anatomical features of the perforator vessels (diameter, D; pulsatility [++∼+++], P) and their position in the skin island (DPD) (ie, D+P+DPD). A perforator-based propeller flap was applied as the first-line choice; if this plan was not feasible, we applied an altered V-Y advancement model or another second-choice technique. RESULTS: All flaps survived, and only 1 patient experienced partial wound dehiscence, which healed by secondary intention. After an average follow-up period of 11.2 months, no patient experienced recurrence or infection. CONCLUSIONS: Free-style perforator flap selection is determined by pressure injury and the desired advantage of a specific approach. The use of free-style perforator-based propeller flaps allows a surgeon to transfer healthy tissue into the defect, shifts the suture line away from the bony prominence, and preserves additional future donor sites. In cases where unexpected variations are encountered, the V-Y advancement model or another technique can be used. The simplified surgical algorithm (D+P+DPD) can provide versatility and reliability, achieve a durable, natural esthetic outcome, and minimize injuries to future donor sites.

Combining Pre- and Postoperative Lymphocyte-C-Reactive Protein Ratios Can Better Predict Hepatocellular Carcinoma Prognosis After Partial Hepatectomy.

Background: Various preoperative inflammatory indicators have been identified as potential predictors of poor prognosis in patients with hepatocellular carcinoma (HCC), but the role of postoperative inflammatory indicators remains unclear. This study aimed to explore the prognostic value of the postoperative lymphocyte-C-reactive protein ratio (PostLCR) on its own and combined with preoperative LCR (PreLCR). Methods: A total of 290 patients with primary HCC were retrospectively enrolled in the study. Univariate analysis was used to identify factors significantly associated with poor disease-free survival (DFS) and overall survival (OS), then multivariate analysis was performed to identify independent prognostic indicators of poor survival. Prognostic models based on preoperative, postoperative, and both types of indicators were then constructed, and their predictive performance were evaluated using time-dependent receiver operating characteristic curves and the concordance index (C-index). Results: PreLCR and PostLCR levels correlated with DFS and OS more strongly than other pre- and postoperative inflammatory indicators, respectively. Decreased PreLCR and PostLCR were independent prognostic factors for both DFS and OS, while HCC patients with decreased PreLCR and PostLCR had worse prognosis than patients with increased PreLCR and PostLCR. Patients into three groups based on their cut-off values of PreLCR and PostLCR, Kaplan-Meier survival analysis indicated that HCC patients with low PreLCR and PostLCR had the worst DFS and OS. The combined model showed better predictive performance at 1 and 3 years post-surgery than individual pre- and postoperative models, the American Joint Committee on Cancer/Tumor-Node-Metastasis (8th edition) staging system and the Barcelona Clinic Liver Cancer system. The combine model demonstrated a markedly superior C-index compared with the other models in DFS and OS. Conclusion: Our study showed PreLCR and PostLCR are independent predictors of DFS and OS in HCC patients after partial hepatectomy. Models that include both PreLCR and PostLCR can predict prognosis better than well-established clinical staging systems.

Association between Systolic Blood Pressure and Diabetic Retinopathy in Both Hypertensive and Normotensive Patients with Type 2 Diabetes: Risk Factors and Healthcare Implications.

A common diabetes-related microvascular complication is diabetic retinopathy (DR), yet associations between blood pressure (BP) and risks for DR in diabetic patients with normal BP received inadequate attention. This may lead to 'clinical inertia' in early DR prevention. We aimed to assess whether the extent to which systolic BP levels were associated with DR in patients with type 2 diabetes (T2DM) and normal BP were similar to that in those with concurrent hypertension. Data were collected from patients with T2DM attending ophthalmic check-up with primary care referral (n = 2510). BP measurements, clinical laboratory tests, and dilated fundus examination were conducted according to gold standard of diagnosis and routine clinical procedure. Of all subjects, over 40% were normotensive and one fifth were clinically diagnosed with DR. Systolic BP levels increased across DR categories of escalated severity irrespective of the coexistence of hypertension. Ordinal logistic regression analysis showed that an increased systolic BP was independently and significantly associated with DR (adjusted odds ratio [aOR] = 1.020, p < 0.001 for hypertensives; aOR = 1.019, p = 0.018 for normotensives), after adjusting for diabetes duration, sex, lifestyles, and haemoglobin A1c levels. Regular monitoring of systolic BP should not be neglected in routine diabetes management even when BP falls within the normal range. (200 words).

Characterization of a Robust and pH-Stable Tannase from Mangrove-Derived Yeast Rhodosporidium diobovatum Q95.

Tannase plays a crucial role in many fields, such as the pharmaceutical industry, beverage processing, and brewing. Although many tannases derived from bacteria and fungi have been thoroughly studied, those with good pH stabilities are still less reported. In this work, a mangrove-derived yeast strain Rhodosporidium diobovatum Q95, capable of efficiently degrading tannin, was screened to induce tannase, which exhibited an activity of up to 26.4 U/mL after 48 h cultivation in the presence of 15 g/L tannic acid. The tannase coding gene TANRD was cloned and expressed in Yarrowia lipolytica. The activity of recombinant tannase (named TanRd) was as high as 27.3 U/mL. TanRd was purified by chromatography and analysed by SDS-PAGE, showing a molecular weight of 75.1 kDa. The specific activity of TanRd towards tannic acid was 676.4 U/mg. Its highest activity was obtained at 40 °C, with more than 70% of the activity observed at 25-60 °C. Furthermore, it possessed at least 60% of the activity in a broad pH range of 2.5-6.5. Notably, TanRd was excellently stable at a pH range from 3.0 to 8.0; over 65% of its maximum activity remained after incubation. Besides, the broad substrate specificity of TanRd to esters of gallic acid has attracted wide attention. In view of the above, tannase resources were developed from mangrove-derived yeasts for the first time in this study. This tannase can become a promising material in tannin biodegradation and gallic acid production.

Comparative Proteome Identifies Complement Component 3-Mediated Immune Response as Key Difference of Colon Adenocarcinoma and Rectal Adenocarcinoma.

Colorectal cancer (CRC) is one of the most lethal diseases with high morbidity and mortality worldwide. Clinically, tumors located in colon and rectum have diverse prognosis and therapeutic outcome. Here, we performed data mining derived from 20 CRC patient samples to compare proteomic difference between colon adenocarcinoma (COAD) and rectal adenocarcinoma (READ). We found that differential expressed proteins (DEPs) upregulated in COAD were mainly enriched in immune response, moreover, higher immune scores were found in COAD than READ, as calculated by The Cancer Genome Atlas (TCGA) data. To identify the core protein of DEPs with high prognostic value for COAD, we performed topological overlap matrix (TOM) to investigate the hub proteins using 77 immune-relevant DEPs, and identified complement component 3 (C3) as the core protein in the immune-relevant DEPs matrix between the COAD and READ. Moreover, we found that C3 was up-regulated in COAD, and its expression was negatively associated with overall survival of COAD patients but not READ. In conclusion, we identified C3-mediated immune response as key feature to distinguish COAD and READ, and highlighted C3 as potential biomarker with high prognostic value for clinical application, which provided new clue for precise treatment of COAD.

Correlations between the optic nerve head morphology and ocular biometrics in highly myopic eyes.

AIM: To analyze peripapillary atrophy ß/γ zone (PPA-ß/γ) and the optic disc ovality index, and to assess their associations with the axial length (AL), refractive error, best corrected visual acuity (BCVA), choroidal thickness (CT), and age in highly myopic eyes. METHODS: This was a retrospective observational case series. The study included 667 patients consecutively examined for highly myopic eyes [spherical equivalent ≤-6.0 diopters (D) and AL≥26 mm] with or without myopic retinopathy. Each patient went through a comprehensive ophthalmological examination that included spectral domain optical coherence tomography (SD-OCT) of the macula, A-mode ultrasonography, and a cycloplegic refraction test. The ovality index and PPA-ß/γ area were measured from optic disc photographs. RESULTS: A significant association was seen between PPA-ß/γ area and the ovality index (P=0.000, r=-0.232). The PPA-ß/γ area increased significantly with a longer AL, older age, worse BCVA, higher refractive error, and thinner choroid (P<0.01). The oval disc was significantly correlated with a longer AL, older age, worse BCVA, higher refractive error, larger PPA-ß/γ area, and thinner choroid (P<0.01). CONCLUSION: The PPA-ß/γ zone and ovality index in highly myopic eyes show distinct associations with the AL, refractive error, BCVA, age, and CT.

[Nitrogen removal and N2O emission characteristics during the shortcut simultaneous nitrification and denitrification process].

Complete simultaneous nitrification and denitrification (SND) was achieved in an air lift circulation bioreactor. Based on this condition, the system could be switched to shortcut SND as the free ammonia (FA) concentration was increased with higher influent pH. The nitrogen removal and N2O emission characteristics of the shortcut SND process were investigated and those of the complete SND process were also observed as control. In the shortcut SND process, the average total nitrogen removal and average SND efficiency reached 71.9% and 80.9%, which was 18.0 and 16.8 percents higher than those in the complete SND process, respectively. In addition, the total nitrogen removal rate in the shortcut SND process was 0.11 mg x (L x min)(-1), 1.4 times as high as that in the complete SND process. Although higher nitrogen removal efficiency was obtained in the shortcut SND process, the mean N2O conversion rate reached 57.1% and the average N2O accumulated emission amount was approximately 4 times higher than that in the complete SND process. The results also indicated that the increase of NO2- -N concentration in the reactor should be responsible for the remarkable enhancement of N2O emission.

A comparing study of quantitative staining techniques for retinal neovascularization in a mouse model of oxygen-induced retinopathy.

AIM: To explore an efficient, practical and objective quantitative method to evaluate the retinal neovascularization in mouse model of oxygen induced retinopathy (OIR). METHODS: Thirty C57BL/6J mice were explored in OIR model procedure. Eyes were removed for different staining methods including: (1) HE staining; (2) immunohistochemistry with Griffonia Simplicifolia Lectin(GSL); (3) Immunofluorescence with FITC labeled CD31 antibody; (4) Two-step immunofluorescence with purified-CD31 antibody; (5) FITC-Dextran perfusion combined with two-step purified-CD31immunofluorescence. Images of the retinal vasculature were analyzed by imaging software. RESULTS: GSL immunohistochemistry could clearly demonstrate the deep and superficial capillary beds. FITC labeled CD31 Immunofluorescence was blurring with high fluorescence background which was hard to distinguish retinal neovascularization in some area. Excellent detail of neovascularization and preexistent retinal vessels was provided in two-step Purified-CD31 immunofluorescence group. CONCLUSION: GSL immunohistochemistry can clearly demonstrate neovascularization tufts in deep and superficial capillary beds. Immunofluorescence of specific antigen CD31 on vascular endothelium can selectively label the neovascularization of mouse retina. When combined with computer analysis software, it is an effective and objective quantitative method to evaluate the retinal neovascularization in OIR mouse model.

[The effect of rAAV2-PEDF on proliferation of human retinal capillary endothelium cells].

OBJECTIVE: To culture human retinal capillary endothelium cells (HRCECs) in vitro and explore the effect of rAAV2-PEDF on proliferation of HRCEs. METHODS: Retinas were digested by 2.5% trypsin and 0.1% collagenase I in order. The isolated cells were cultured on fibronectin-coated dishes in media of human endothelial-sFM basal growth medium (HE-SFM BGM) with 10% fetal bovine serum, insulin-transferrin-selenium (ITS) and endothelial cell growth factor (ECGF). The cultured cells were identified by anti-factor VIII related antigen though immunohistochemistry stain. The effect of hypoxia induced by CoCl2 on proliferation of HRCECs was assessed by MTT assay. After rAAV2-PEDF were transfected into HRCECs, the EGPF positive cells were observed by laser confocal scanning microscopy, the protein expression of PEDF were detected by Western blot, and the proliferation of HRCECs were checked by MTT assay. Flow cytometry was used to analyze the apoptosis of HRCECs. RESULTS: Cultured HRCECs attached in the bottom of dishes in 48 h - 72 h and grew to confluence in 2 weeks after seeding. HRCECs were with a positive brown staining for factor VIII. EGPF positive cells were seen under laser confocal scanning microscopy after 48 h of rAAV2-EGFP transfection. The expression level of PEDF protein was higher in experimental group than in control group. The results of MTT assay showed the numeric value OA was 0.085 ± 0.021 in normal group and 0.166 ± 0.024 in hypoxia group (t = 3.938, P < 0.05). In normal oxygen condition, the numeric value OA was 0.171 ± 0.011 in normal control group, 0.178 ± 0.016 in rAAV2-EGFP treated group, and 0.169 ± 0.017 in rAAV2-PEDF treated group (F = 0.01, P > 0.05). In hypoxia condition, the numeric value OA was 0.166 ± 0.013 in CoCl(2) treated group, 0.155 ± 0.012 in CoCl(2) + rAAV2-EGFP treated group, and 0.116 ± 0.015 in CoCl(2) + rAAV2-PEDF treated group. In normal oxygen condition, the ratio of apoptosis was 2.3% in normal control group, and 3.3% in rAAV2-EGFP treated group, and 1.7% in rAAV2-PEDF treated group. In hypoxia condition, the ratio of apoptosis was 3.6% in CoCl(2) treated group, 6.7% in CoCl(2) + rAAV2-EGFP treated group, and 36.4% in CoCl(2) + rAAV2-PEDF treated group. CONCLUSIONS: PEDF gene can stably express in HRCECs after rAAV2-PEDF transfection and can obviously inhibit proliferation of HRCECs in hypoxia.

[Clinical study on childhood acute lymphoblastic leukemia diagnosed and treated with 04 Protocol in Chongqing, China].

OBJECTIVE: To analyze the clinical and laboratory data from acute lymphoblastic leukemia (ALL) patients and the results of treatment using 04 Protocol (suggested by the Pediatric Hematology Group of Chinese Medical Association in 2004). METHODS: This study included 88 children with ALL below the age of 18 years during the period from October 1, 2004 to June 30, 2007. Minimal inhibitory concentration (MIC) and clinical risk classification were done and the new chemotherapy regimen was used according to the protocol. Patients were stratified into low-risk (LR), medium-risk (MR), and high-risk (HR) groups. Life table method was used to estimate survival rate and statistical analysis was done by using software SPSS for Windows. RESULTS: From October 2004 to June 2007, 88 childhood ALL patients were treated with the 04 Protocol. Sixty-three (91.30%) patients attained complete remission (CR) and 17 patients lost to follow up. The overall 4-year-event-free survival (EFS) rate (+/- SE) was (59.73 +/- 7.22)%. EFS was (75.60 +/- 9.71)% in the LR (n = 30), (65.50 +/- 11.69)% in the MR (n = 20) and (44.03 +/- 12.36)% in the HR. Relapse occurred in 18.18% of patients. Seven (7.95%) of 88 patients with ALL died during he induction therapy. Infection was the most common cause of death. CONCLUSION: The outcome of patients treated with the 04 Protocol was favorable. Clinical risk classification and the leukemia cells of D19 are independent predictors of prognosis of ALL. High dose methotrexate played an important role in prevention and treatment of central nervous system leukemia. The mortality rate of this chemotherapeutic protocol during induction therapy was high.

[Changes of tight junction protein and GFAP in the retina of experimental diabetic rats and their relationship with blood aqueous barrier].

OBJECTIVE: To investigate the changes of vascular endothelial cell tight junction protein (occludin) and glial cell morphology as well as their relationship with blood-retinal barrier (BRB) in the retina of diabetic rats. METHODS: The distribution of occludin and GFAP were explored by immunofluorescence histochemical studies in the retina of streptozotocin (STZ)-diabetic rats and age-matched control rats. Evans blue was used to evaluate the impairment of BRB. RESULTS: GFAP immunoreactivity was limited to ganglion cell layer and nerve fiber layer in the control retina. GFAP immunoreactivity was significantly increased in ganglion cell layer and nerve fiber layer in one month diabetic rats. GFAP positive Müller cells were increased in three months and six months diabetic rats. Occludin immunoreactivity progressively decreased in three months and six months diabetic rats but not in the one month diabetic rats. Evans blue injection showed a progressive impairment of BRB. CONCLUSIONS: Astrocytes activation in the early stage of diabetes plays an important role in the maintaining of the BRB function. But the activation of Müller cells in the later stage destroyed the BRB eventually. These changes are consistent with the concept that BRB changes caused by altered glial-endothelial cell interactions contributes to the occurrence of diabetic retinopathy.

Pars plana vitrectomy and internal limiting membrane peeling for macular oedema secondary to retinal vein occlusion: a pilot study.

INTRODUCTION: Macular oedema is the main cause of visual impairment following retinal vein occlusion. The purpose of this study was to evaluate the anatomical and functional outcome of pars plana vitrectomy and internal limited membrane (ILM) peeling for macular oedema secondary to retinal vein occlusion. CLINICAL PICTURE: This pilot study is a prospective nonrandomised series of 11 eyes of 11 patients with macular oedema secondary to retinal vein occlusion. The best-corrected visual acuity (BCVA), foveal thickness on optical coherence tomography, fundus fluorescein angiography (FFA) and multifocal electroretinography were evaluated. TREATMENT AND OUTCOME: All 11 patients underwent pars plana vitrectomy with ILM peeling. The mean postoperative follow-up was 13.5 months (range, 1.5 to 24). The mean thickness at the foveal centre decreased from 794 +/- 276 microm preoperatively to 373 +/- 150 microm, 302 +/- 119 microm, 249 +/- 203 microm and 185 +/- 66 microm at 1 week, 1 month, 3 months and the final visit postoperatively, respectively (all P <0.001, paired t- test, compared to preoperative thickness). Postoperative FFA demonstrated markedly reduced leakage in the macular region. At the final visit, BCVA improved 2 lines or more in 72.7% (8/11) of patients and was unchanged in 27.3% (3/11) patients. Complications included cataract in 7 patients and vitreous haemorrhage, recurrence of macular oedema and visual field defect in 1 case each. CONCLUSION: Pars plana vitrectomy and ILM peeling rapidly reduced the macular oedema caused by retinal vein occlusion, with improvement in BCVA.

[A preliminary study on intravitreal injection of bevacizumab for treatment of neovascular age-related macular degeneration].

OBJECTIVE: To evaluate the short-term safety of intravitreous bevacizumab (Avastin) and its effects on visual acuity (VA) and subfoveal choroidal neovascularization (CNV) in patients with neovascular age-related macular degeneration (ARMD). METHODS: Single-center, uncontrolled clinical study. Five ARMD patients (5 eyes) with subfoveal CNV and best-corrected VA (BCVA) less than 0.1 were participated. Patients were treated with an intravitreous injection of bevacizumab (1.5 mg, 0.06 ml). Ophthalmologic evaluations included BCVA test, ocular examination, intraocular pressure (IOP) measurement, optical coherence tomography (OCT) imaging and fluorescein angiography (FFA). RESULTS: There were no ocular or systemic adverse events observed, except a mild elevation of IOP [26 mm Hg (1 mm Hg = 0.133 kPa)] in 1 case on the 3rd day after injection, which was controlled by topical medication. One out of 5 eyes had a significant improvement of BCVA (from 0.1 improved to 0.4) in one week after injection. By 2 months, the BCVA increased in 4 cases (increased 1 to 6 lines) and 3 of them remained stable for 4 to 6 months and 1 decreased at the 4 th month post injection. The thickness of central retina reduced 5.9% to 41.4% and FFA revealed a remarkable reduction or an absence of leakage from CNV in 3 eyes by the 4th month. CONCLUSION: Our preliminary results are promising, showing that intravitreous bevacizumab therapy is well tolerated with an improvement in VA, OCT, and FFA outcomes. A multi-center randomized controlled clinical trial is needed to evaluate the long-term safety and effectiveness of intravitreous bevacizumab therapy on neovascular ARMD.