RNA M6A modification shaping cutaneous melanoma tumor microenvironment and predicting immunotherapy response.

Recent years have seen rising mortality rates linked to cutaneous melanoma (SKCM), despite advances in immunotherapy. Understanding RNA N6-methyladenosine (M6A) significance in SKCM is crucial for prognosis, tumor microenvironment (TME), immune cell presence, and immunotherapy efficacy. We analyzed 23 M6A regulators using SKCM samples from TCGA and GEO databases, identifying three M6A modification patterns linked to TME cell infiltration. Principal component analysis (PCA) yielded an M6A score for individual tumors, utilizing patient gene expression profiles and CNV data from TCGA. M6A modification patterns play a crucial role in SKCM development and progression, influencing tumor attributes such as inflammatory stage, subtype, TME interstitial activity, and genetic mutations. The M6A score independently predicts patient outcomes and correlates with improved response to immunotherapy, validated across anti-PD-1 and anti-PD-L1 therapy cohorts. M6A modifications significantly impact the TME landscape, with the M6A score serving as a predictive marker for immunotherapy response. Integrating M6A-related information into clinical practice could revolutionize SKCM management and treatment strategies.

The Chinese patent medicine Tongfengding capsule for gout in adults: a systematic review of safety and effectiveness.

BACKGROUND: Gout is a common inflammatory arthritis caused by increased serum uric acid levels. Untreated or insufficiently treated gout can lead to deposition of monosodium urate crystals in joints, cartilage, and kidneys. Although Tongfengding capsules, a Chinese patent medicine, have long been used to treat gout, their effects and safety have not been reviewed systematically. This study evaluated its efficacy and safety for gout in adults. METHODS: Randomized controlled trials involving Tongfengding capsule for gout in adults were searched from PubMed, EMBASE, Cochrane Central Register of Controlled Trials, CBM, CNKI, and VIP databases, and analyzed using the Cochrane Handbook criteria. The primary outcome measures were the total effective rate. The secondary outcome measures including the blood uric acid (BUA), 24-h urinary total protein (24-h UTP), blood urea nitrogen (BUN), interleukin (IL)-6, IL-8, tumor necrosis factor-alpha (TNF-α) and adverse effects. The risk of bias was evaluated in all included studies. RevMan ver. 5.3.5 and GRADE profiler was used for data analysis and assessing the quality of evidence, respectively. RESULTS: Six studies (n = 607 Chinese participants) were included. Tongfengding capsules plus conventional treatment significantly increased the total effective rate (RR 1.21, 95% CI 1.11-1.33), while reducing the BUA (MD - 66.05 µmol/L, 95% CI - 81.26 to - 50.84), 24-h UTP (MD - 0.83 g/24 h, 95% CI - 0.96 to - 0.70), BUN (MD - 0.90 mmol/L, 95% CI - 1.60 to - 0.20), IL-6 (MD - 6.99 ng/L, 95% CI - 13.22 to - 0.75), IL-8 (MD - 12.17 ng/L, 95% CI - 18.07 to - 6.27), TNF-α (MD - 8.50 ng/L, 95% CI - 15.50 to - 1.51), and adverse effects (RR 0.21, 95% CI 0.04-0.95). CONCLUSION: Tongfengding capsules plus conventional treatment is safe and beneficial for adults with gout compared with conventional treatment.

The Chinese patent medicine Tongfengding capsule for gout in adults: a systematic review of safety and effectiveness

Abstract Background Gout is a common inflammatory arthritis caused by increased serum uric acid levels. Untreated or insufficiently treated gout can lead to deposition of monosodium urate crystals in joints, cartilage, and kidneys. Although Tongfengding capsules, a Chinese patent medicine, have long been used to treat gout, their effects and safety have not been reviewed systematically. This study evaluated its efficacy and safety for gout in adults. Methods Randomized controlled trials involving Tongfengding capsule for gout in adults were searched from PubMed, EMBASE, Cochrane Central Register of Controlled Trials, CBM, CNKI, and VIP databases, and analyzed using the Cochrane Handbook criteria. The primary outcome measures were the total effective rate. The secondary outcome measures including the blood uric acid (BUA), 24-h urinary total protein (24-h UTP), blood urea nitrogen (BUN), interleukin (IL)-6, IL-8, tumor necrosis factor-alpha (TNF-α) and adverse effects. The risk of bias was evaluated in all included studies. RevMan ver. 5.3.5 and GRADE profiler was used for data analysis and assessing the quality of evidence, respectively. Results Six studies (n = 607 Chinese participants) were included. Tongfengding capsules plus conventional treatment significantly increased the total effective rate (RR 1.21, 95% CI 1.11-1.33), while reducing the BUA (MD − 66.05 μmol/L, 95% CI − 81.26 to − 50.84), 24-h UTP (MD − 0.83 g/24 h, 95% CI − 0.96 to − 0.70), BUN (MD − 0.90 mmol/L, 95% CI − 1.60 to − 0.20), IL-6 (MD − 6.99 ng/L, 95% CI − 13.22 to − 0.75), IL-8 (MD − 12.17 ng/L, 95% CI − 18.07 to − 6.27), TNF-α (MD − 8.50 ng/L, 95% CI − 15.50 to − 1.51), and adverse effects (RR 0.21, 95% CI 0.04-0.95). Conclusion Tongfengding capsules plus conventional treatment is safe and beneficial for adults with gout compared with conventional treatment.

Intravitreal dexamethasone implant has better retinal perfusion than anti-vascular endothelial growth factor treatment for macular edema secondary to retinal vein occlusion: a five-year real-world study.

PURPOSE: To investigate the long-term effect of intravitreal dexamethasone (DEX) implant and anti-vascular endothelial growth factor (VEGF) injection on macular edema (ME) secondary to retinal vein occlusion (RVO) in a real-world setting. METHODS: The medical records of RVO-ME cases, with intravitreal injections and followed-up for at least 5 years, were retrospectively reviewed. Changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT) were primary outcomes. Images of fluorescence angiography (FA) and swept-source optical coherence tomography angiography (OCTA) were analyzed. Foveal avascular zone (FAZ) metrics and perfusion density at the last visit were also compared between the two treatments. RESULTS: A total of 16 patients were recruited, 8 in the anti-VEGF group and 8 in the DEX group. At the 5th year, the BCVA and the CMT in the DEX group were not different from those in the anti-VEGF group (0.69 ± 0.36 LogMAR vs 0.57 ± 0.30 LogMAR, P = 0.574; 183.25 ± 97.31 µm vs 195.38 ± 40.92 µm, P = 0.442). Compared with the anti-VEGF group, the DEX group had higher FAZ circularity index (0.57 ± 0.14 vs 0.68 ± 0.14, P = 0.130) and higher retinal perfusion density (0.45 ± 0.02 vs 0.39 ± 0.03, P = 0.001), especially in the deep capillary plexus. CONCLUSION: DEX implant and anti-VEGF injection had comparative long-term effects on RVO-ME. Compared with the anti-VEGF treatment, the DEX treatment had advantages in maintaining retinal perfusion in patients with RVO.

Prevalence and risk factors of diabetic retinopathy in patients with type 2 diabetes in Shanghai.

AIM: To investigate the prevalence of diabetic retinopathy (DR) in residents of Shanghai and analyze the risk factors of DR. METHODS: This study involved 7233 patients with diabetes in 2016. The demographic data of the participants were collected using a questionnaire survey. Physical examination, laboratory tests, and ophthalmological examinations were conducted. Two professional ophthalmologists diagnosed and graded DR by fundus examination and then combined the results with fundus images. The unconditional multivariate Logistic regression analysis was used to determine the risk factors. RESULTS: In total, 6978 patients with type 2 diabetes in Shanghai with a mean age of 68.33±8.40y were recruited, including 2975 males (42.6%) and 4003 females (57.4%). Overall, 1184 patients were diagnosed with DR, with a prevalence rate of 16.97%. Regression analysis showed that duration of diabetes (OR 1.061, 95%CI 1.049-1.073), high systolic blood pressure (SBP; OR 1.071, 95%CI 1.037-1.106), increased glycosylated hemoglobin level (OR 1.234, 95%CI 1.162-1.311), high blood glucose level (OR 1.061, 95%CI 1.023-1.099), increased neutrophil-to-lymphocyte ratio (NLR; OR 1.132, 95%CI 1.053-1.217) and mean platelet volume (MPV; OR 1.077, 95%CI 1.016-1.142) were risk factors of DR. Conversely, hematocrit (HCT; OR 0.971, 95%CI 0.954-0.988) and mean corpuscular volume (MCV; OR 0.980, 95%CI 0.965-0.994) were protective factors. CONCLUSION: The prevalence rate of DR in Shanghai is 16.97%. The duration of diabetes, high SBP, increased glycosylated hemoglobin, NLR, and MPV were determined as risk factors of DR.

OBSERVATION OF VITREOUS FEATURES USING ENHANCED VITREOUS IMAGING OPTICAL COHERENCE TOMOGRAPHY IN HIGHLY MYOPIC RETINOSCHISIS.

PURPOSE: To observe features of the posterior vitreous and vitreoretinal interface in highly myopic eyes with retinoschisis using enhanced vitreous imaging optical coherence tomography. METHODS: Comprehensive ophthalmologic examination and enhanced vitreous imaging optical coherence tomography were performed in 77 eyes of 63 patients with highly myopic retinoschisis. Two different modes of spectral domain optical coherence tomography were employed to estimate retinoschisis and the posterior vitreous features in optical coherence tomography images, respectively. The types and distribution of vitreoretinal interface abnormalities were also analyzed. RESULTS: Complete posterior vitreous detachment (PVD) was identified in 55 eyes (71.4%) with a Weiss ring. Residual cortex was found in 39 eyes (70.9%) with complete PVD. Vitreoretinal interface changes, including vitreoretinal adhesion and epiretinal membrane (ERM), most frequently appeared in the macular area (47.3%), followed by the inferior arched vessels region (34.5%). In partial PVD eyes, vitreoretinal traction, vitreoretinal adhesion, and epiretinal membrane tended to be observed in the inferior and superior arched vessels regions (54.5 and 40.9%, respectively). Among all types of vitreoretinal interface abnormalities, epiretinal membrane comprised the largest proportion (46.8%) despite the status of PVD. The presence of inner layers of retinoschisis connoted a relatively high possibility of vitreoretinal interface abnormalities occurring. CONCLUSION: Enhanced vitreous imaging optical coherence tomography reveals a high prevalence of vitreoretinal interface abnormalities in highly myopic eyes with retinoschisis. Vitreous cortex tends to remain on the macular area in eyes with complete PVD. Our findings may lead to better guidance for the surgical treatment of highly myopic retinoschisis.

Identification of novel PROM1 mutations responsible for autosomal recessive maculopathy with rod-cone dystrophy.

PURPOSE: To characterize two patients with macular and rod-cone dystrophy and identify the genetic basis for disease. METHOD: Ophthalmic examinations were performed for the family and the peripheral blood samples were collected for whole exome sequencing. The mutated sequences of PROM1 gene were cloned and expressed in cultured cell lines after transient transfection followed by analysis with confocal microscopy and bridge-PCR. RESULT: We reported that two patients, brothers in a family, were diagnosed with macular and rod-cone dystrophy. Phenotypically, both patients experience progressive visual impairment and nyctalopia. The fundus examination showed macular and choroid dystrophy with pigment deposits in the macular region. Functionally, photoreceptor response to electrophysiological stimulation was significantly compromised with more severe decline in rods. Genetic analysis by whole exome sequencing revealed two novel compound heterogeneous point mutations in PROM1 gene that co-segregate with patients in an autosomal recessive manner. Specifically, the c.C1902G(p.Y634X) nonsense mutation results in a truncated, labile, and mislocalized protein, while the c.C1682+3A>G intronic mutation disrupts messenger RNA splicing. CONCLUSION: Our findings have identified two novel deleterious mutations in PROM1 gene that are associated with hereditary macular and rod-cone dystrophy in human.

Pro-apoptotic effects of micro-ribonucleic acid-365 on retinal neurons by targeting insulin-like growth factor-1 in diabetic rats: An in vivo and in vitro study.

AIMS/OBJECTIVE: The present study aimed to explore the effects of micro-ribonucleic acid-365 (miR-365) on apoptosis of retinal neurons by targeting insulin-like growth factor-1 (IGF-1) in diabetes mellitus rats. MATERIALS AND METHODS: High glucose-induced retinal neurons were assigned into the blank (with no plasmid transfection), negative control (with plasmid transfection), anti-miR-365 (transfected miR-365 antagomir), transfected IGF-1 short hairpin RNA plasmid (sh-IGF-1) and transfected miR-365 antagomir and IGF-1 shRNA plasmid (anti-miR-365 + sh-IGF-1) groups. Proliferation and apoptosis of retinal neurons were detected by 5-ethynyl-2'-deoxyuridine assay and Hoechst 33342 staining, respectively. Expressions of miR-365, IGF-1, Bcl-2-associated X protein (Bax) and Bcl-2 were determined by reverse transcription quantitative polymerase chain reaction and western blotting. A control group contained 10 healthy rats. Terminal deoxynucleotidyl transferase dUTP nick-end labeling staining was used to evaluate apoptosis of retinal neurons in rats. RESULTS: In the anti-miR-365 group, the apoptosis rate and Bax expression were reduced in comparison with the negative control and blank groups, whereas the sh-IGF-1 and anti-miR-365 + sh-IGF-1 groups presented an opposite trend. Compared with the normal group, expressions of miR-365 and Bax were increased, and expressions of IGF-1 and Bcl-2 were decreased, with more apoptotic cells in diabetes mellitus rat models. The sh-IGF-1 group had lower Bax expression, and higher expressions of IGF-1 and Bcl-2 with fewer apoptotic cells. Additionally, Bax expression was upregulated, expressions of IGF-1 and Bcl-2 were downregulated, and apoptotic cells were higher in the anti-miR-365 + sh-IGF-1 groups than the anti-miR-365 group. CONCLUSION: The results of the present study suggest that suppressed miR-365 increases the IGF-1 expression, leading to anti-apoptotic effects on retinal neurons in diabetic rats.