Role of microRNA-4739 in enhancing cisplatin chemosensitivity by negative regulation of RHBDD2 in human cervical cancer cells.

BACKGROUND: Cisplatin (DDP) is a widely used chemotherapy drug for advanced cervical cancer (CC), but resistance poses a significant challenge. While miR-4739 has been implicated in tumor development, its specific role in regulating DDP resistance in CC remains unclear. METHODS: We analyzed the expression levels of miR-4739 and RHBDD2 in DDP-resistant and DDP-sensitive CC tissues using quantitative real-time polymerase chain reaction (PCR) and assessed their correlation through Spearman's correlation analysis. DDP-resistant CC cell lines (HeLa/DDP and SiHa/DDP) were established by gradually increasing DDP concentrations, followed by transfection with miR-4739 mimics, si-RHBDD2, or a RHBDD2 overexpression vector. A series of functional assays, including CCK-8 assay, colony formation, flow cytometry, and transwell assay were performed. The interaction between miR-4739 and RHBDD2 was confirmed by luciferase reporter assay. We examined the protein levels of RHBDD2, P-gP, MRP1, cleaved caspase-3, and E-cadherin through western blot analysis. Moreover, we generated xenograft tumors by injecting stably transfected HeLa/DDP cells into mice to compare their tumorigenesis capacity. RESULTS: We observed downregulation of miR-4739 and upregulation of RHBDD2 in DDP-resistant CC tissues and cell lines. MiR-4739 was shown to directly bind to RHBDD2 gene sequences to repress RHBDD2 expression in HeLa/DDP and SiHa/DDP cells. Our in vitro and in vivo experiments demonstrated that overexpressing miR-4739 overcame DDP resistance in CC cells by targeting RHBDD2. Furthermore, RHBDD2 overexpression reversed the effects of miR-4739 mimics on drug-resistance-related proteins (P-gP and MRP1) and the expression of cleaved caspase-3 and E-cadherin in HeLa/DDP cells. CONCLUSIONS: In summary, our study revealed that miR-4739 can reverse DDP resistance by modulating RHBDD2 in CC cells.

Identification of potential inhibitors against Staphylococcus aureus shikimate dehydrogenase through virtual screening and susceptibility test.

Staphylococcus aureus shikimate dehydrogenase (SaSDH) plays a crucial role in the growth of Staphylococcus aureus (S. aureus), but absent in mammals and therefore a potential target for antibacterial drugs to treat drug-resistant S. aureus infection. In this study, a 3D model of SaSDH was constructed by homology modelling and inhibitors of SaSDH were screened through virtual screening. (-)-Gallocatechin gallate and rhodiosin were identified as inhibitors with Kis of 2.47 µM and 73.38 µM, respectively. Molecular docking and isothermal titration calorimetry showed that both inhibitors interact with SaSDH with a KD of 44.65 µM for (-)-gallocatechin gallate and 16.45 µM for rhodiosin. Both inhibitors had antibacterial activity, showing MICs of 50 µg/mL for (-)-gallocatechin gallate and 250 µg/mL for rhodiosin against S. aureus. The current findings have the potential for identification of drugs to treat S. aureus infections by targeting SaSDH.

Optical coherence tomography angiography-guided vs indocyanine green angiography-guided half-dose photodynamic therapy for acute central serous chorioretinopathy: 6-month randomized trial results.

PURPOSE: This study aimed to compare the anatomic and functional results of optical coherence tomography angiography (OCTA)-guided half-dose photodynamic therapy (PDT) versus indocyanine green angiography (ICGA)-guided PDT in eyes with acute central serous chorioretinopathy (CSC). METHODS: One hundred and thirty-one eyes of 131 patients with acute central serous chorioretinopathy (CSC) were recruited, and randomly assigned to the OCTA-guided group and ICGA-guided group. The primary outcome measures were the rates of complete subretinal fluid (SRF) resolution at 1 month, 3 months, and 6 months. The secondary outcomes included best-corrected visual acuity (BCVA), central retinal thickness (CRT), choroidal capillary flow deficit density at each scheduled visit, and recurrence rate of SRF at 3 months and 6 months. RESULTS: There were 110 eyes that finished the follow-up, with 56 eyes in the OCTA-guided group and 54 eyes in the ICGA guided group. OCTA-guided PDT was demonstrated to be noninferior to ICGA-guided PDT for SRF resolution rate at 1 months and 6 months (P = 0.021 and P = 0.037), but not at 3 months for acute CSC (P = 0.247). The average CRT of the ICGA-guided group was significantly lower than that of the OCTA-guided group at 3-month visit (P = 0.046), but no significant difference was found between them at the 1-month and 6-month visits (P = 0.891 and 0.527). There was no significant difference between the two groups for BCVA (P = 0.359, 0.700, and 0.143, respectively) and the deficit area on CC (P = 0.537, 0.744,and 0.604, respectively) at 1, 3, and 6 months. CONCLUSION: OCTA may replace ICGA to guide PDT for the treatment of acute CSC and their follow-up.

Vitrectomy with sulfur hexafluoride versus air tamponade for idiopathic macular hole: a retrospective study.

BACKGROUND: To evaluate the effect of room air and sulfur hexafluoride (SF6) gas in idiopathic macular hole(MH)surgery. METHODS: Retrospective, interventional, and comparative study. 238 eyes with the idiopathic macular hole that underwent pars plana vitrectomy, internal limiting membrane peeling, fluid-air exchange, and 20% SF6 (SF6 group:125 eyes) or room air tamponade (air group: 113 eyes) were reviewed. The primary outcome measure was the closure rate of primary surgery. RESULTS: The baseline characteristics of the SF6 group and air group were comparable except for the hole size (479.90 ± 204.48 vs. 429.38 ± 174.63 µm, P = 0.043). The anatomical closure rate was 92.8% (116 / 125) with the SF6 group and 76.1% (86 / 113) with the air group (P < 0.001). A cut-off value of MH size to predict primary anatomical closure was 520 µm, which is based on the lower limit of 95% confidential interval of the MH size among the unclosed patients in the air group. There was no significant difference in anatomical closure rates between SF6 and air group (98.7% vs. 91.9%, P = 0.051) for MH ≤ 520 µm, whereas a significantly lower anatomical closure rate was shown in the air group than SF6 group (46.2% vs. 84.0%, P < 0.001) for MH > 520 µm. CONCLUSION: SF6 exhibited more effectiveness than air to achieve a good anatomical outcome for its longer tamponade when MH > 520 µm.

Fucoxanthin prevents cell growth and induces apoptosis in endometrial cancer HEC-1A cells by the inhibition of the PI3K/Akt/mTOR pathway.

Endometrial cancer is the major type of gynecological cancer and ranks as the sixth most common cancer in women. Endometrial cancer usually is diagnosed in an advanced stage, complicating the treatments in many cases. The present research was focused on unveiling the in vitro anticancer role of fucoxanthin against the endometrial cancer HEC-1A cells by inhibiting the phosphatidylinositol-3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling axis. The cytotoxicity of fucoxanthin against the endometrial cancer HEC-1A cells was studied using the MTT test. The level of reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP) status, and apoptotic cell death in the 7.5 and 10 µM administered HEC-1A cells were assayed using fluorescent staining techniques. The messenger RNA expression was analyzed using RT-PCR for PI3K/Akt/mTOR signaling molecules, proapoptotic (Bax and caspase-3) antiapoptotic (cyclin D1 and Bcl-2) genes, and inflammatory markers like tumour necrosis factor α (TNFα), nuclear factor kappa B (NF-κB), Cox-2, and interleukin (IL)-6. The cell viability assay proved that fucoxanthin effectively prevented HEC-1A cell viability, where the IC50 was 7.5 µM. Fucoxanthin at 7.5 and 10 µM remarkably improved ROS production and apoptosis and decreased the MMP in HEC-1A cells. The fucoxanthin effectively inhibited the PI3K/Akt/mTOR cascade along with the expression of TNF-α, NF-κB, Cox-2, and IL-6 and antiapoptotic genes cyclin D1 and Bcl-2 in the HEC-1A cells. Fucoxanthin treatment also enhanced the Bax and caspase-3 expressions in the HEC-1A cells. Our results from this work unveiled that fucoxanthin triggered growth inhibition and apoptosis in endometrial cancer HEC-1A cells. Besides, fucoxanthin inhibited the PI3K/Akt/mTOR cascade and improved apoptotic marker expressions in the HEC-1A cells.

Risk factors of persistent subretinal fluid after half-dose photodynamic therapy for treatment-naïve central serous chorioretinopathy.

PURPOSE: To investigate the prognostic factors on spectral domain optical coherence tomography (SD-OCT) associated with incomplete subretinal fluid (SRF) absorption in treated-naïve eyes with central serous chorioretinopathy (CSC) after the half-dose verteporfin photodynamic therapy (vPDT). METHODS: Patients with CSC who underwent half-dose vPDT with a follow-up period of more than 3 months were included in this retrospective study. Logistic regression was performed to determine the risk factors associated with the SRF persistence at 3 months after the treatment. RESULTS: A total of 143 patients with 150 eyes were enrolled in this study (102 male and 41 female patients). The rate of complete SRF resolution was 82.7% at 3 months for all cases. The duration of symptoms > 6 months (odds ratio [OR] = 3.135, 95% confidence interval [95% CI] (1.147-8.573), p = 0.026), larger SRF area with base diameter > 3 mm (odds ratio (OR) = 4.051, 95% CI: 1.336-12.284, p = 0.013), and larger flat irregular pigment epithelium detachment (FI-PED) area with base diameter > 1 mm (OR = 3.311, 95% CI: 1.249-8.780, p = 0.016) on OCT B-scans were risk factors for incomplete SRF absorption after half-dose vPDT, while outer nuclear layer (ONL) thickness was not significantly associated with the anatomical outcome (OR = 1.015, 95% CI: 0.995-1.036, p = 0.145). CONCLUSION: The duration of symptoms, baseline SRF, and FI-PED base diameter on SD-OCT were important predictors for the anatomical outcome at 3 months after half-dose vPDT. Further studies are needed to establish a better therapeutic strategy for patients with poor response to half-dose vPDT.

Comparison of swept-source OCTA and indocyanine green angiography in central serous chorioretinopathy.

BACKGROUND: To compare swept-source optical coherence tomography angiography (SS-OCTA) and indocyanine green angiography (ICGA) in patients with central serous chorioretinopathy (CSC). METHODS: SS-OCTA and ICGA images of 39 eyes with symptomatic CSC were collected and aligned. Spatial overlap of the annotations of the coarse granulated high reflective area on choriocapillary OCTA and the hyperfluorescence area on mid-phase ICGA was calculated according to the Jaccard index (JI). SS-OCTA findings of fellow eyes and changes in SS-OCTA abnormalities during the follow-up were also analyzed. RESULTS: Three main types of abnormalities in choriocapillaris SS-OCTA images were found: type A, coarse granulated high reflective area (39 eyes [100%]); type B, roundish dark halo around Type A (32 eyes [82.1%]); and type C, coarse granulated low reflective area (39 eyes [100%]). The mean JI of type A on SS-OCTA and the hyperfluorescence area on ICGA were 0.55 ± 0.15 for grader 1 and 0.49 ± 0.15 for grader 2. The mean area of type A abnormalities on SS-OCTA and hyperfluorescence on ICGA was 3.976 (IQR, 2.139-8.168) and 3.043 (IQR, 1.408-4.909) mm2 (P = 0.199). The areas of type A, B and C abnormalities on SS-OCTA after laser treatment or observation were 3.36mm2 (IQR, 2.399-9.312), 2.9mm2 (IQR, 2.15-3.7), and 0.19mm2 (IQR, 0.08-0.23), respectively, which was smaller than those in the baseline (7.311mm2 (IQR 3.788-11.209), P < 0.001; 4.3mm2 (IQR, 2.8-9.8), P = 0.002;0.33mm2 (IQR, 0.23-0.38), P < 0.001). The change in the type A, B or C area was not significantly different between the two groups (P = 0.679, 0.732, and 0.892). CONCLUSION: The coarse granulated high reflective area in SS-OCTA corresponded well with the hyperpermeability area in ICGA. SS-OCTA promotes noninvasive visualization and follow-up quantifications of the choroidal vasculature in CSC patients.

Case series: pachychoroid pigment epitheliopathy transformed to polypoidal choroidal vasculopathy after long-term follow-up.

BACKGROUND: Pachychoroid pigment epitheliopathy (PPE), a retinal disorder that falls into the pachychoroid spectrum, is characterized by retinal pigment epithelium changes in pachychoroid eyes without existing or previous subretinal fluid or soft drusen. Previous reports have indicated that PPE may share some pathophysiologic component with other pachychoroid spectrum diseases and could transform into central serous chorioretinopathy (CSC) during follow-up. CSC transformation to PNV and PCV has also been reported, but PPE transformation to PCV has not been reported.  CASE PRESENTATION: Seven eyes of seven patients (four male three female, aged 62.7 ± 8.4 years) who presented with PPE at baseline transformed to PCV during follow-up. All study eyes had baseline contralateral eye diagnoses of PCV. All PPE eyes reported no symptoms at baseline and were followed up regularly for the treatment of their contralateral eyes. All PPE presented as pigment epithelium detachment (PED) at baseline. The mean central macular thickness (CMT) was 217.6 ± 14.6 µm, the mean subfoveal choroidal thickness (SFCT) was 354.9 ± 94.9 µm, and the mean sub-PPE choroidal thickness was 332.3 ± 84.6 µm. The mean PPE width and height were 1326.4 ± 791.4 µm and 58.7 ± 23.6 µm, respectively, at baseline. Disruption of the ellipsoid zone (EZ) was noted in 3 eyes, while choroidal vascular hyperpermeability (CVH) was noted in 5 eyes at baseline. The follow-up period was 75.0 ± 41.1 months, and the mean transformation time was 49.6 ± 24.8 months. All study eyes received no intervention before transformation. CONCLUSIONS: PPE could transform to PCV after a long follow-up period. Regular follow-ups for a long time should be recommended for patients with PPE.

Efficient extracellular production of recombinant proteins in E. coli via enhancing expression of dacA on the genome.

D, D-carboxypeptidase DacA plays an important role in the synthesis and stabilization of Escherichia coli cell wall peptidoglycan. The production level of extracellular recombinant proteins in E. coli can be enhanced by high D, D-carboxypeptidase activity. Construction of expression systems under optimal promoters is one of the main strategies to realize high protein production in E. coli. In this study, the promoter PdacA-3 from DacA on the genome of E. coli BL21 (DE3) was verified to be efficient for recombinant green fluorescent protein using the plasmid mutant pET28a-PdacA with PdacA-3. Meanwhile, the promoter PdacA-3 was engineered to increase the production level of proteins via inserting one or two Shine-Dalgarno (SD) sequences between the promoter PdacA-3 and the target genes. The expression level of dacA on the genome was increased by the improved transcription of the engineered promoters (especially after inserting one additional SD sequence). The engineered promoters increased cell membrane permeabilities to significantly enhance the secretion production of extracellular recombinant proteins in E. coli. Among them, the extracellular recombinant amylase activities in E. coli BL21::1SD-pET28a-amyK and E. coli BL21::2SD-pET28a-amyK were increased by 2.0- and 1.6-fold that of the control (E. coli BL21-pET28a-amyK), respectively. Promoter engineering also affected the morphology and growth of the E. coli mutants. It was indicated that the engineered promoters enhanced the expression of dacA on the genome to disturb the synthesis and structural stability of cell wall peptidoglycans.

An overview and future prospects of recombinant protein production in Bacillus subtilis.

Bacillus subtilis is a well-characterized Gram-positive bacterium and a valuable host for recombinant protein production because of its efficient secretion ability, high yield, and non-toxicity. Here, we comprehensively review the recent studies on recombinant protein production in B. subtilis to update and supplement other previous reviews. We have focused on several aspects, including optimization of B. subtilis strains, enhancement and regulation of expression, improvement of secretion level, surface display of proteins, and fermentation optimization. Among them, optimization of B. subtilis strains mainly involves undirected chemical/physical mutagenesis and selection and genetic manipulation; enhancement and regulation of expression comprises autonomous plasmid and integrated expression, promoter regulation and engineering, and fine-tuning gene expression based on proteases and molecular chaperones; improvement of secretion level predominantly involves secretion pathway and signal peptide screening and optimization; surface display of proteins includes surface display of proteins on spores or vegetative cells; and fermentation optimization incorporates medium optimization, process condition optimization, and feeding strategy optimization. Furthermore, we propose some novel methods and future challenges for recombinant protein production in B. subtilis.Key points• A comprehensive review on recombinant protein production in Bacillus subtilis.• Novel techniques facilitate recombinant protein expression and secretion.• Surface display of proteins has significant potential for different applications.

One-year results of intravitreal conbercept in treatment-naïve subjects with polypoidal choroidal vasculopathy.

PURPOSE: To evaluate the functional and structural outcomes of intravitreal conbercept monotherapy using a "3 + pro re nata (PRN)" regimen in treatment-naïve subjects with polypoidal choroidal vasculopathy (PCV) up to 12 months. METHODS: Thirty subjects (30 eyes) with PCV participated in this interventional, retrospective study. All subjects received intravitreal injections of 0.5 mg (0.05 ml) conbercept using a "3 + PRN" regimen for 12 months. The changes in best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) parameters, polyp lesion area, and regression rate were evaluated at baseline, month 3, and month 12. RESULTS: At the study end-point, BCVA improved significantly from 52.80 ± 17.17 ETDRS letters at baseline to 62.20 ± 18.96 letters (P < 0.001), with a mean gain of 9.40 ± 14.97 letters. The central retinal thickness (CRT) significantly reduced from 454.93 ± 147.31 µm at baseline to 308.73 ± 106.80 µm (P < 0.001) at end-point, and the total macular volume (TMV) decreased from 9.51 ± 1.04 mm3 at baseline to 8.32 ± 0.84 mm3 at end-point (P < 0.001). The mean volume of pigment epithelial detachment (PED) decreased from 0.73 ± 0.97 mm3 at baseline to 0.48 ± 0.71 mm3 (P < 0.05) at month 3. At month 12, the mean volume of PED was 0.57 ± 0.80 mm3 (P > 0.05 compared to baseline). After the 3-monthly loading injections, 6 eyes (20.0%) showed complete polyp regression, whereas a total of 19 eyes (63.5%) showed complete regression at month 12. The average injections given per subject were 7.70 ± 1.81. CONCLUSION: Intravitreal conbercept using the "3 + PRN" regimen was effective in the treatment of PCV.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY-GUIDED PHOTODYNAMIC THERAPY FOR ACUTE CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To compare the anatomic results of optical coherence tomography angiography (OCTA)-guided half-dose photodynamic therapy (PDT) versus indocyanine green angiography (ICGA)-guided PDT in eyes with acute central serous chorioretinopathy. METHODS: This study is a prospective, single-center, noninferiority, double-masked, randomized, controlled clinical trial. Fifty-one eyes of 45 patients with acute central serous chorioretinopathy were recruited, and randomized to an ICGA-guided group and an OCTA-guided group. The primary outcome measures were the rates of complete subretinal fluid (SRF) resolution at 1 month and 3 months. RESULTS: Forty-six eyes of 40 patients finished the follow-up and were analyzed. In the OCTA-guided group, the SRF was completely resolved in 13 (56.5%) eyes within 1 month and in 21 (91.3%) eyes within 3 months. In the ICGA-guided group, the SRF was resolved in 16 (69.6%) of the eyes within 1 month and in 22 (95.7%) of the eyes by 3 months. Optical coherence tomography angiography-guided PDT was demonstrated noninferior to ICGA-guided PDT for SRF resolution rate at 3 months (P = 0.016), but not at 1 month (P = 0.311) for acute central serous chorioretinopathy patients. Subretinal fluid did not recur in any of the eyes in the OCTA-guided group, but did recur in 2 eyes (8.7%) of the ICGA-guided group during the 3-month follow-up period. CONCLUSION: Optical coherence tomography angiography-guided PDT seemed to be noninferior to ICGA-guided PDT for resolution of SRF at 3 months in eyes with acute central serous chorioretinopathy.

Anti-recoverin antibodies indicate fundus abnormalities in systemic lupus erythematosus.

OBJECTIVES: Lupus fundus abnormalities are a sight-threatening complication of systemic lupus erythematosus (SLE) and its pathogenesis remains to be studied. The aim of this study was to assess the clinical characteristics associated with the presence of anti-recoverin antibodies in patients with SLE, especially those with fundus abnormalities. METHODS: Seventy-six participants were enrolled, including 21 patients with fundus abnormalities (fundus group), 30 patients without fundus abnormalities (non-fundus group) and 25 healthy individuals. Serum anti-recoverin antibody levels were measured using enzyme-linked immunosorbent assay, and clinical and laboratory data were obtained from medical records. RESULTS: Compared with the non-fundus group, the fundus group had a higher incidence of hematuria (p < 0.05). The Systemic Erythematosus Disease Activity Index (SLEDAI) score in the fundus group was significantly higher than the non-fundus group (21.48 ± 8.06 versus 10.80 ± 5.74, p < 0.001). The levels of serum anti-recoverin antibodies in the fundus group were significantly higher than the non-fundus group (p = 0.029) or the healthy control group (p = 0.011). Anti-recoverin-negative and -positive patients differed on a number of clinical parameters, including incidence of fever, rash, antinuclear antibody, anti-dsDNA antibody, erythrocyte sedimentation rate, immunoglobulin G, complement C3 and complement C4. The average SLEDAI score of anti-recoverin-positive patients was significantly higher than anti-recoverin-negative patients (17.73 ± 8.11 versus 12.56 ± 8.37, p < 0.05). CONCLUSIONS: Anti-recoverin antibodies were related to higher disease activities in SLE, especially those with fundus abnormalities, suggesting that anti-recoverin antibodies may play an important role in the pathogenesis of fundus abnormalities in SLE.

One-step fabrication and electromagnetic wave absorption of graphene/Ag@polyaniline ternary nanocomposites.

Based on in situ intercalation polymerization of aniline, a one-step synthesis of a graphene/Ag@PANI ternary composite is proposed. The results show that together with sunlight exposure, Ag+ induces the polymerization of aniline accompanied by self-reduction to form a Ag@PANI core-shell nanostructure, and consequently, exfoliates the graphite sheet into graphene. Through a PANI shell, Ag@PANI nanoparticles all anchor onto the surface of graphene, forming a stable ternary structure. The performance of graphene/Ag@PANI is closely related to its micro-morphology, which depends on the selected Ag+/aniline ratio during the synthesis. Double-layer absorbers with graphene/Ag@PANI as the absorbing layer present excellent absorption performance. The effective absorbing bandwidths of DB-10, DB-5, and DB-1 all exceed 3 GHz with a thickness of 1 mm and the reflection loss of 1.3 mm DB-10 reaches -44.5 dB at 10.5 GHz. The as-proposed facile and eco-friendly preparation of a graphene-based ternary composite is also of great significance for sensors, supercapacitor electronics, degradation of polymers, and other applications.

Photodynamic therapy for bullous retinal detachment: a single-center experience of case series with a 6-month follow-up study.

PURPOSE: To evaluate the efficacy of half-dose photodynamic therapy (PDT) for the treatment of bullous retinal detachment. METHODS: Interventional prospective case series in six eyes from six consecutive patients with bullous retinal detachment. The effected eyes were treated with indocyanine green angiography (ICGA)-guided half-dose PDT with multifocal and large laser spots. Clinical evaluations included best-corrected visual acuity (BCVA), ophthalmoscopy, ophthalmic B scan, fundus fluorescein angiography (FFA), optical coherence tomography (OCT), and ICGA at each scheduled visit at baseline; at 1, 3, and 6 months after PDT; and during follow-up after 6 months. RESULTS: All six eyes received half-dose verteporfin PDT with a mean number of therapeutic spots 2.83 ± 1.47 and a mean spot size of 4647 ± 996 µm in diameter. Three months after PDT, retinal reattachment was observed on B scans and resolution of sub-retinal fluid (SRF) was observed in OCT images for five eyes. There was no significant difference in the mean logMAR BCVA between the baseline and the value at 1 month after PDT (P = 0.477). At 3 months after PDT, the mean logMAR BCVA improved significantly from a baseline value of 1.02 to 0.54 (P = 0.044). At 6 months after PDT, the mean logMAR BCVA further improved to 0.46 (P = 0.025) and remained stable. One affected eye received a second half-dose PDT for SRF not reduced until the second month after PDT. Retinal reattachment and SRF resolution were observed at 1 and 3 months after the second therapy, respectively. BCVA improved from a baseline value of 20/63 to 20/20 at 1 month after the second PDT and remained stable until the sixth month after the second PDT. During follow-up after more than 6 months, recurrence occurred in no cases. CONCLUSIONS: This study demonstrated half-dose PDT with multifocal and large laser spots was an effective treatment for bullous retinal detachment contributing to the retinal reattachment, a resolution of SRF, and an improvement of BCVA. Thus, PDT for the treatment of bullous retinal detachment is considered to be a worthwhile endeavor.

CLASSIFICATION AND QUANTITATIVE ANALYSIS OF GEOGRAPHIC ATROPHY JUNCTIONAL ZONE USING SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: The junctional zone at the border of areas of geographic atrophy (GA) in eyes with nonneovascular age-related macular degeneration is an important target region for future therapeutic strategies. The goal of this study was to perform a detailed classification and quantitative characterization of the junctional zone using spectral domain optical coherence tomography. METHODS: Spectral domain optical coherence tomography volume cube scans (Spectralis OCT, 1024 × 37, Automatic Real Time > 9) were obtained from 15 eyes of 11 patients with GA because of nonneovascular age-related macular degeneration. Volume optical coherence tomography data were imported into previously described validated grading software (3D-OCTOR), and manual segmentation of the retinal pigment epithelium (RPE) and photoreceptor layers was performed on all B-scans (total of 555). Retinal pigment epithelium and photoreceptor defect maps were produced for each case. The borders of the photoreceptor defect area and RPE defect area were delineated individually on separate annotation layers. The two outlines were then superimposed to compare the areas of overlap and nonoverlap. The perimeter of the RPE defect area was calculated by the software in pixels. The superimposed outline of the photoreceptor defect area and the RPE defect area was scrutinized to classify the overlap configuration of the junctional zone into one of three categories: Type 0, exact correspondence between the edge of the RPE defect and photoreceptor defect; Type 1, loss of photoreceptors outside and beyond the edge of the RPE defect; Type 2, preservation of photoreceptors beyond the edge of the RPE defect. The relative proportion of the various border configurations was expressed as a percentage of the perimeter of the RPE defect. Each configuration was then classified into four subgroups according to irregularity of the RPE band and the presence of debris. RESULTS: Fifteen eyes of 11 patients (mean age: 79.3 ± 4.3 years; range: 79-94 years) were included in this study. Seventeen GA lesions were analyzed. Two hundred and thirty-two B-scans were found to pass through the GA lesions, yielding 612 individual GA borders which were separately analyzed and classified. The mean area of the RPE defect was 4.0 ± 4.4 mm, which was significantly smaller than that of the photoreceptor defect which measured 4.4 ± 4.1 mm (paired t test, P = 0.037). On average, 18.0 ± 9.6% (range, 2.3-36.6%) of the junctional zone was of the Type 0 configuration, 57.3 ± 19.0% (range, 21.3-96.8%) was Type 1, and 24.7 ± 18.0% (range, 0.9-64.4%) was Type 2. Type 1 was more prevalent than Type 0 and 2 (analysis of variance, P = 0.000). Debris was present at the margin of the defect in 24.3% (149 of 612) of all assessed junctional zones; 20.0% (14 of 70) of Type 0 junctions, 28.7% (120 of 418) of Type 1, and 12.1% (15 of 124) of Type 2. Debris was more common in Type 1 than Type 2 junctions (P < 0.001). Retinal pigment epithelial irregularity was present at the margin of the defect in 34.8% (213 of 612) of all assessed junctional zones; 52.9% (37 of 70) of Type 0 junctions, 38.0% (159 of 418) of Type 1, and 13.7% (17 of 124) of Type 2. Retinal pigment epithelial irregularity was present more often at Type 0 and Type 1 than at Type 2 junctions (P < 0.001 for both). CONCLUSION: The size of the optical coherence tomography-visible RPE and photoreceptor defect in GA lesions differ significantly. There were significant areas where the photoreceptor outer segments were preserved despite the absence of visible RPE cells, and also areas of photoreceptor outer segment loss despite apparent RPE preservation. These findings have implications for development of therapeutic strategies, particularly cell-replacement approaches.

The repeatability of superficial retinal vessel density measurements in eyes with long axial length using optical coherence tomography angiography.

BACKGROUND: To investigate the repeatability of superficial retinal vessel density measurements in healthy eyes with long axial length (AL) using optical coherence tomography angiography (OCTA). METHODS: There were 60 eyes of 31 volunteers enrolled in this cross-sectional observational study. All subjects underwent OCTA, AL and refraction test. The enrolled eyes were divided into the long AL group (26 mm ≤ AL < 28 mm) and normal AL group (22 mm ≤ AL < 26 mm). The vessel length density (VLD), perfusion density (PD), and fovea avascular zone (FAZ) of the superficial retinal vessel were evaluated. Repeatability was assessed by intraclass correlation coefficients (ICCs) and Bland-Altman analysis. Pearson's r correlation was used to analyze the relation of AL and the absolute difference between two measurements. RESULTS: The 3 × 3 mm scan pattern showed good repeatability with all ICCs over 0.7. For all parameters of all scan patterns, the ICCs of the normal AL group were distinctly higher than those of the long AL group; this finding was also confirmed by Bland-Altman analysis. The correlation analysis of AL and repeatability of OCTA parameters showed significant negative correlations between the ALs and repeatability of VLD in 6 × 6 mm inner ring (r2 = 0.13, p = 0.01), VLD in 6 × 6 mm outer ring (r2 = 0.09, p = 0.02) and PD in 6 × 6 mm outer ring (r2 = 0.08, p = 0.03). CONCLUSIONS: The AL and the scanned area will both affect the repeatability of superficial retinal vessel density measurements in OCTA.

MiR-200a promotes epithelial-mesenchymal transition of endometrial cancer cells by negatively regulating FOXA2 expression.

Endometrial cancer is the most common gynecological cancer. Epithelial-mesenchymal transition (EMT) plays a critical role in tumor invasion and metastasis, which limits the success of treatment. Here, we investigated the roles of forkhead box A2 (FOXA2) and microRNA-200a (miR-200a) in regulating the EMT of endometrial cancer cells RL95-2. Empty vector or FOXA2 was stably transfected into RL95-2 cells. MTT assay measured cell proliferation, apoptosis assay measured apoptosis, Transwell invasion assay measured cell invasion, and Western blot measured the protein expression of FOXA2, E-cadherin, and vimentin. ChIP assay determined the binding of FOXA2 to E-cadherin promoter. For miR-200a analysis, the cells with stable FOXA2 expression were transfected with miR-negative control or miR-200a. Forced expression of FOXA2 decreased the proliferation and invasion, and increased the apoptosis of RL95-2 cells. FOXA2 also affected the EMT-associated proteins: FOXA2 increased the protein expression of E-cadherin and decreased the expression of vimentin. Moreover, FOXA2 positively regulated the promoter of E-cadherin in RL95-2 cells. Luciferase reporter assay identified FOXA2 as a target of miR-200a, which negatively regulated FOXA2. Western blot results showed that overexpression of miR-200a decreased the expression of E-cadherin but increased the expression of vimentin in the endometrial cancer cells by downregulating FOXA2 expression. FOXA2 may act as a tumor suppressor and inhibit EMT of endometrial cancer cells. FOXA2 expression is controlled by miR-200a, which promotes EMT of the endometrial cancer cells.

EFFICACY OF INTRAVITREAL INJECTION OF CONBERCEPT IN POLYPOIDAL CHOROIDAL VASCULOPATHY: Subgroup Analysis of the Aurora Study.

PURPOSE: To evaluate the efficacy of different doses of conbercept in patients with polypoidal choroidal vasculopathy in the AURORA study. METHODS: Retrospective subgroup analyses of 12-month data from the AURORA study. Fifty-three patients (32 in 0.5-mg group and 21 in 2.0-mg group) diagnosed with polypoidal choroidal vasculopathy in AURORA study were retrospectively evaluated. Efficacy outcomes were compared between the two dosage groups. RESULTS: At Month 12, mean changes in best-corrected visual acuity from baseline were 14.4 ± 14.1 letter scores for the 0.5-mg group and 14.2 ± 21.0 letter scores for the 2.0-mg group; mean central retinal thickness decreased by 104.5 ± 127.3 µm in the 0.5-mg group and 140.7 ± 127.9 µm in the 2.0-mg group; mean total macular volume decreased by 0.9 ± 2.3 mm and 1.0 ± 1.2 mm in the 0.5-mg and 2.0-mg groups, respectively. The mean subretinal fluid thickness decreased by 111.9 ± 122.5 µm and 76.3 ± 112.6 µm in the 0.5-mg and 2.0-mg groups, respectively. The mean pigment epithelial detachment height decreased by 79.3 ± 217.8 µm and 61.3 ± 161.5 µm in the 0.5-mg and 2.0-mg groups, respectively. The mean area of polyps decreased by 0.46 ± 0.76 mm and 0.55 ± 1.34 mm in the 0.5-mg and 2.0-mg groups, respectively. The mean total lesion area decreased by 2.51 ± 5.94 mm (P = 0.088) and 4.62 ± 5.51 mm in the 0.5-mg group and 2.0-mg groups, respectively. Complete regression of polyps was observed in 56.5% of patients in the 0.5-mg group and 52.9% of those in the 2.0-mg group, whereas partial regression was observed in 26.1% and 35.3% of patients in the 0.5-mg and 2.0-mg groups, respectively. CONCLUSION: Intravitreal injection of conbercept appears to significantly improve visual acuity and anatomical outcomes in patients with polypoidal choroidal vasculopathy.

A Wolfram-like syndrome family: Case report.

BACKGROUND: Wolfram-like syndrome (WFLS) is an autosomal dominant inherited disease characterized by a single heterozygous pathogenic variant in the WFS1 gene. Its clinical presentation is similar to autosomal recessive Wolfram syndrome. CASE PRESENTATION: We reported a case of a 10-year-old boy and his family members who initially experienced hearing impairment (HI), followed by optic atrophy. Genetic testing revealed the presence of a WFS1 variant (chr4-6302385 exon8 NM_006005.3: c.2590G > A, p. Glu864Lys). CONCLUSION: Wolfram-like syndrome, a rare neurodegenerative genetic disorder, manifested as deafness, optic atrophy, and diabetes mellitus. There hasn't been a definite treatment yet. Early identification of the variant in the WFS1 gene is beneficial for genetic counseling.