Repeatability of Pentacam-derived intraocular lens decentration measurements and the level of agreement with OPD-Scan III: A prospective observational case series.

PURPOSE: This study aimed to assess the repeatability of intraocular lens (IOL) decentration measurements obtained through Pentacam, based on corneal topographic axis (CTA) and pupillary axis (PA), and to evaluate the level of agreement between Pentacam and OPD-Scan III devices in measuring IOL decentration. METHODS: In this prospective observational case series, three measurements were performed with Pentacam to evaluate the repeatability of the measurements. The analysis included the calculation of the mean and standard deviations (SD), conducting a repeated measures analysis of variance (rANOVA), and determining an intraclass correlation coefficient (ICC) to assess the repeatability of the measurements. Moreover, Bland-Altman analysis was employed to assess the agreement between Pentacam and OPD-Scan III devices in measuring IOL decentration. IOL decentration measurements were obtained with respect to both CTA and PA. RESULTS: A total of 40 eyes from 40 patients were analyzed. The rANOVA revealed no significant difference among three consecutive measurements of IOL decentration obtained with Pentacam. The mean SD of all parameters ranged from 0.04 mm to 0.07 mm. With CTA as the reference axis, the ICC values for Pentacam measurements of IOL decentration were 0.82 mm for the X-axis, 0.76 mm for the Y-axis, and 0.82 mm for spatial distance. When using PA as the reference axis, the corresponding ICC values were 0.87, 0.89, and 0.77, respectively. The 95% limits of agreement for all IOL decentration measurements were wide when comparing Pentacam and OPD-Scan III. CONCLUSIONS: Pentacam demonstrated high repeatability in measuring IOL decentration with respect to both CTA and PA. However, due to poor agreement between Pentacam and OPD-Scan III measurements, caution should be exercised when using data interchangeably between the two devices.

Periplogenin inhibits pathologic synovial proliferation and infiltration in rheumatoid arthritis by regulating the JAK2/3-STAT3 pathway.

Rheumatoid arthritis (RA) is an autoimmune disease that affects joints, causing inflammation, synovitis, and erosion of cartilage and bone. Periplogenin is an active ingredient in the anti-rheumatic and anti-inflammatory herb, cortex periplocae. We conducted a study using a CIA model and an in vitro model of fibroblast-like synoviocytes (FLS) induced by Tumor Necrosis Factor-alpha (TNF-α) stimulation. We evaluated cell activity, proliferation, and migration using the CCK8 test, EDU kit, and transwell assays, as well as network pharmacokinetic analysis of periplogenin targets and RA-related effects. Furthermore, we measured inflammatory factors and matrix metalloproteinases (MMPs) expression using ELISA and qRT-PCR assays. We also evaluated joint destruction using HE and Safranin O-Fast Green Staining and examined the changes in the JAK2/3-STAT3 pathway using western blot. The results indicated that periplogenin can effectively inhibit the secretion of inflammatory factors, suppress the JAK2/3-STAT3 pathway, and impede the proliferation and migration of RA FLS. Thus, periplogenin alleviated the Synovial inflammatory infiltration of RA.

Super-Resolution Reconstruction of CT Images Based on Multi-scale Information Fused Generative Adversarial Networks.

The popularization and widespread use of computed tomography (CT) in the field of medicine evocated public attention to the potential radiation exposure endured by patients. Reducing the radiation dose may lead to scattering noise and low resolution, which can adversely affect the radiologists' judgment. Hence, this paper introduces a new network called PANet-UP-ESRGAN (PAUP-ESRGAN), specifically designed to obtain low-dose CT (LDCT) images with high peak signal-to-noise ratio (PSNR) and high resolution (HR). The model was trained on synthetic medical image data based on a Generative Adversarial Network (GAN). A degradation modeling process was introduced to accurately represent realistic degradation complexities. To reconstruct image edge textures, a pyramidal attention model call PANet was added before the middle of the multiple residual dense blocks (MRDB) in the generator to focus on high-frequency image information. The U-Net discriminator with spectral normalization was also designed to improve its efficiency and stabilize the training dynamics. The proposed PAUP-ESRGAN model was evaluated on the abdomen and lung image datasets, which demonstrated a significant improvement in terms of robustness of model and LDCT image detail reconstruction, compared to the latest real-esrgan network. Results showed that the mean PSNR increated by 19.1%, 25.05%, and 21.25%, the mean SSIM increated by 0.4%, 0.4%, and 0.4%, and the mean NRMSE decreated by 0.25%, 0.25%, and 0.35% at 2[Formula: see text], 4[Formula: see text], and 8[Formula: see text] super-resolution scales, respectively. Experimental results demonstrate that our method outperforms the state-of-the-art super-resolution methods on restoring CT images with respect to peak signal-to-noise ratio (PSNR), structural similarity (SSIM) and normalized root-mean-square error (NRMSE) indices.

Postoperative intraocular lens stability following cataract surgery with or without primary posterior continuous curvilinear capsulorrhexis: an intra-individual randomized controlled trial.

PURPOSE: To evaluate the effect of primary posterior continuous curvilinear capsulorrhexis (PPCCC) on the positional stability of IOLs. METHODS: This study is a prospective intra-individual comparative randomized controlled trial including 31 patients (62 eyes). Eyes of the same patient were randomly assigned to the PPCCC group (18 right eyes and 13 left eyes) or group without PPCCC (NPCCC group). Eyes in both groups were implanted with a one-piece foldable hydrophobic acrylic IOL via routine cataract surgery. Patients in the PPCCC group underwent additional manual PPCCC before IOL implantation. Examinations were performed 1 day, 1 week, 1 month and 3 months postoperatively. IOL tilt (x, y), decentration (x, y), anterior chamber depth (z) and refractive prediction error data were collected and analyzed with Pentacam. RESULTS: Postoperatively, the range of IOL position change over 3 months in PPCCC group was comparable to NPCCC group, which indicated smaller value in every tilt and decentration index. PPCCC eyes showed comparable tilt and decentration with NPCCC eyes in this study endpoint: mean tilt (x, y), decentration (x, y) and anterior chamber depth (ACD) were 1.04 ± 0.56°, 0.90 ± 0.64°, 0.239 ± 0.140 mm, 0.233 ± 0.133 mm and 4.01 ± 0.32 mm, respectively, in the PPCCC group vs. 1.09 ± 0.76°, 1.10 ± 0.82°, 0.252 ± 0.153 mm, 0.244 ± 0.155 mm and 4.01 ± 0.38 mm, respectively, in the NPCCC group. Refractive prediction error in the PPCCC group demonstrated a mild hyperopic shift vs. the NPCCC group (0.13 ± 0.50 vs. 0.05 ± 0.39; p = 0.208), and corrected distance visual acuity (CDVA) did not differ between the two groups (0.027 ± 0.014 vs. 0.059 ± 0.185; p = 0.377). CONCLUSIONS: Comparable IOL tilt, decentration, ACD and refractive prediction error were observed in PPCCC eyes with that underwent routine cataract surgery. Little IOL position fluctuation and good visual acuity were shown in PPCCC group over time. TRAIL REGISTRATION: The study was registered at the Chinese Clinical Trial Register Center on May 27th, 2020 (protocol code ChiCTR2000033304, 27/05/2020).

Efficacy and safety of primary customized phacoemulsification combined with goniosynechialysis for refractory acute primary angle closure.

PURPOSE: To assess the safety, efficacy, and long-term clinical outcomes of primary customized phacoemulsification (phaco) combined with goniosynechialysis (GSL; phaco-GSL) in refractory acute primary angle closure (APAC) eyes with uncontrolled high intraocular pressure (IOP). METHODS: This retrospective case series comprised 51 eyes of 42 consecutive patients with refractory APAC and high IOP who were treated using primary customized phaco-GSL at 3 hospitals in China, from 2014 to 2021. Preoperative and postoperative IOP, corrected distant visual acuity (CDVA), corneal endothelial cell density (CECD), intraoperative and postoperative complications were recorded. The safety, efficacy and subsequent long-term clinical outcomes were analyzed. RESULTS: The mean CDVA (LogMAR) was improved from 1.67 ± 0.94 preoperatively to 0.23 ± 0.26 postoperatively (P < 0.001). Preoperative CECD was 2309.39 ± 541.03 cells/mm2 in 33 eyes and inaccessible in 18 eyes due to severe corneal edema; at the final follow-up, the mean CECD of all patients was 1823.50 ± 533.40 cells/mm2 (P < 0.001). The mean IOP decreased from 48.51 ± 6.25 mmHg preoperatively to 15.66 ± 2.27 mmHg at the final follow-up (P < 0.001). Among 51 eyes, additional customized procedures performed were corneal indentation in 42 eyes, epithelial debridement in 9 eyes, giant epithelial bullae view in 4 eyes, pars-plana fluid aspiration in 3 eyes, and secondary intraocular lens implantation in 7 eyes. The IOP of all eyes was well controlled eventually and 47 eyes (92.16%) were successfully treated by phaco-GSL alone. No significant intraoperative or postoperative complications were observed. CONCLUSIONS: Primary customized phaco-GSL is a safe and effective surgical management strategy for patients with refractory APAC and high IOP.

Urban scene segmentation model based on multi-scale shuffle features.

The monitoring of urban land categories is crucial for effective land resource management and urban planning. To address challenges such as uneven parcel distribution, difficulty in feature extraction and loss of image information in urban remote sensing images, this study proposes a multi-scale feature shuffle urban scene segmentation model. The model utilizes a deep convolutional encoder-decoder network with BlurPool instead of MaxPool to compensate for missing translation invariance. GSSConv and SE module are introduced to enhance information interaction and filter redundant information, minimizing category misclassification caused by similar feature distributions. To address unclear boundary information during feature extraction, the model applies multi-scale attention to aggregate context information for better integration of boundary and global information. Experiments conducted on the BDCI2017 public dataset show that the proposed model outperforms several established segmentation networks in OA, mIoU, mRecall, P and Dice with scores of 83.1%, 71.0%, 82.7%, 82.7% and 82.5%, respectively. By effectively improving the completeness and accuracy of urban scene segmentation, this study provides a better understanding of urban development and offers suggestions for future planning.

The Underlying Mechanism of Duanteng Yimu Decoction in Inhibiting Synovial Hyperplasia in Rheumatoid Arthritis.

Dysregulation of microRNAs (miRNAs) is associated with the pathogenesis of rheumatoid arthritis (RA). Our previous studies confirmed that Duanteng Yimu decoction (DTYMT) effectively inhibits RA fibroblast-like synoviocyte (FLS) proliferation. In this study, we investigated the influence of DTYMT on miR-221 in RA individuals. Hematoxylin-eosin (HE) staining was performed to assess histopathological alterations in collagen-induced arthritis (CIA) mice. The expression of miR-221-3p and TLR4 in PBMC, FLS, and cartilage was measured by RT-qPCR. In the in vitro experiments, DTYMT-containing serum was incubated with FLS-transfected miR-221 mimic or inhibitor. CCK-8 was performed to determine FLS proliferation, and the secretion of IL-1ß, IL-6, IL-18, and TNF-α was quantified by ELISA assay. In addition, the regulation of miR-221 expression on FLS apoptosis was assessed using flow cytometry. Finally, western blot was employed to reflect TLR4/MyD88 protein levels. HE results showed that DTYMT effectively reduced synovial hyperplasia in the joints of CIA mice. RT-qPCR assay of FLS and cartilage of the model group showed that miR-221-3p and TLR4 significantly increased compared with those in the normal group. All outcomes were improved by DTYMT. The miR-221 mimic reversed the inhibitory effect of DTYMT-containing serum on FLS proliferation, the release of IL-1ß, IL-18, IL-6, and TNF-α, and FLS apoptosis, as well as TLR4/MyD88 protein levels. The results showed that miR-221 promotes the activity of RA-FLS by activating TLR4/MyD88 signaling, and DTYMT treats RA by reducing miR-221 in CIA mice.

Mechanism underlying the action of Duanteng-Yimu Tang in regulating Treg/Th17 imbalance and anti-rheumatoid arthritis.

Background: Rheumatoid arthritis (RA) is a chronic immune disease characterised by synovitis and cartilage destruction. Currently, many patients experience poor remission after new antirheumatic drug treatments. Duanteng-Yimu Tang (DTYMT), a traditional Chinese medicine, is effective in the treatment of RA. In this research, we designed to investigate the anti-RA effects of DTYMT and explore its potential mechanisms. Methods: Network pharmacology was adopted to explore the main pathways of DTYMT in patients with RA. Collagen-induced arthritis models of male DBA/1 mice were established, and their histopathological changes were observed by hematoxylin-eosin staining and micro-CT. qRT-PCR was performed to detect the expression of Foxp3 and RORγt in the serum and synovial tissue and IL-17, IL-1ß, TNF-α, and IL-10 mRNA in vivo. The proliferation and invasion of synovial cells were analyzed using Cell Counting Kit-8 and transwell assays, respectively. The ratio of T helper 17 (Th17) to regulatory T (Treg) cells was analyzed by flow cytometry. Results: Network pharmacology analysis revealed that Th17 cell differentiation may be the key pathway of DTYMT in RA. DTYMT ameliorated joint damage, inhibited RORγt expression, and increased Foxp3 expression in CIA mice. DTYMT significantly decreased IL-1ß, IL-17, and TNF-α mRNA levels, and increased IL-10 mRNA levels in IL-6-induced cells. Additionally, DTYMT inhibited Th17 cell differentiation and promoted Treg cell production, thus improving the Treg/Th17 imbalance. DTYMT also inhibited the proliferation, migration, and invasion of RA fibroblast-like synovial cells. Conclusions: These results indicate that DTYMT could regulate the Treg/Th17 cell balance, which is a possible mechanism of DTYMT in treating RA.

Intraocular lens tilt and decentration after cataract surgery with and without primary posterior continuous curvilinear capsulorhexis.

PURPOSE: To evaluate intraocular lens (IOL) tilt and decentration and their effects on higher-order aberrations (HOAs) after cataract surgery with and without primary posterior continuous curvilinear capsulorhexis (PPCCC). SETTING: Fujian Provincial Hospital, Fujian, China. DESIGN: Prospective, intraindividual, randomized, comparative clinical trial. METHODS: 64 eyes of 32 patients with age-related cataract who underwent bilateral cataract surgery and IOL implantation were enrolled in this study. In randomized order, all patients had phacoemulsification cataract surgery with PPCCC in 1 eye (PPCCC group) and routine cataract surgery in the contralateral eye (NPCCC group). IOL decentration, tilt, HOAs, modulation transfer function, and point spread function were measured at 1 day, 1 week, 1 month, and 3 months after surgery using OPD-Scan III. RESULTS: 52 eyes of 26 patients were available for analysis. The mean overall decentration in the NPCCC group was significantly higher than in the PPCCC group at 3 months (0.302 ± 0.157 mm vs 0.187 ± 0.099 mm, P < .001). Under 3 mm pupil, internal spherical aberration (SA) 1 day after surgery and coma 1 week after surgery were lower in the PPCCC group compared with the NPCCC group (0.15 ± 0.10 µm vs 0.30 ± 0.21 µm, P < .001, and 0.34 ± 0.18 µm vs 0.47 ± 0.31 µm, P = .03, respectively). IOL decentration was significantly correlated with ocular and internal coma, ocular and internal SA, and internal HOAs at 5 mm pupil ( R = 0.083 and R = 0.099, R = 0.650 and R = 0.613, and R = 0.418, respectively, all P < .01). CONCLUSIONS: Less IOL decentration was observed in the PPCCC group at 3 months after surgery, indicating that PPCCC may result in better IOL centrality.

Plant leaf veins coupling feature representation and measurement method based on DeepLabV3.

The plant leaf veins coupling feature representation and measurement method based on DeepLabV3+ is proposed to solve problems of slow segmentation, partial occlusion of leaf veins, and low measurement accuracy of leaf veins parameters. Firstly, to solve the problem of slow segmentation, the lightweight MobileNetV2 is selected as the extraction network for DeepLabV3+. On this basis, the Convex Hull-Scan method is applied to repair leaf veins. Subsequently, a refinement algorithm, Floodfill MorphologyEx Medianblur Morphological Skeleton (F-3MS), is proposed, reducing the burr phenomenon of leaf veins' skeleton lines. Finally, leaf veins' related parameters are measured. In this study, mean intersection over union (MIoU) and mean pixel accuracy (mPA) reach 81.50% and 92.89%, respectively, and the average segmentation speed reaches 9.81 frames per second. Furthermore, the network model parameters are compressed by 89.375%, down to 5.813M. Meanwhile, leaf veins' length and width are measured, yielding an accuracy of 96.3642% and 96.1358%, respectively.

Study on the effect and mechanism of quercetin in treating gout arthritis.

Quercetin is widely found in natural plants, especially Chinese herbal plants. It has been used to treat arthritis in China for thousands of years. However, the effects and mechanisms of quercetin in the treatment of gout arthritis (GA) remain unclear. We aimed to verify the treatment of GA with quercetin and investigate the underlying mechanism. A combination of network pharmacology and experiments was used to reveal the mechanism of quercetin in the treatment of GA. Potential targets of quercetin and gout were identified. Then, the protein-protein interaction network for the common targets between quercetin and gout was constructed and the core targets were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses for the common targets were performed to elucidate the pharmacological functions and mechanisms associated with quercetin treatment in GA. Finally, a monosodium urate-induced GA rat model was used to validate the predicted mechanisms in network pharmacology. Seventy-two common targets were identified. KEGG analysis revealed that treatment of GA with quercetin predominantly involved the interleukin (IL)-17, tumor necrosis factor (TNF), mitogen-activated protein kinase, and phosphoinositide 3-kinase-Akt signaling pathways. In an experimental validation, quercetin attenuated ankle joint inflammation-induced bone destruction and histological lesions. It also diminished the expression of IL-6, IL-17A, and IL-17F in the IL-17 pathway, and regulated the release of RAR-related orphan receptor gamma t,IL-17E, IL-1ß, IL-6, TNF-α, Foxp3, and transforming growth factor-beta 1. The collective findings implicate quercetin as a valuable alternative drug for the treatment of GA.

Quantum coherence of a circularly accelerated atom in a spacetime with a reflecting boundary.

We investigate, in the paradigm of open quantum systems, the dynamics of quantum coherence of a circularly accelerated atom coupled to a bath of vacuum fluctuating massless scalar field in a spacetime with a reflecting boundary. The master equation that governs the system evolution is derived. Our results show that in the case without a boundary, the vacuum fluctuations and centripetal acceleration will always cause the quantum coherence to decrease. However, with the presence of a boundary, the quantum fluctuations of the scalar field are modified, which makes that quantum coherence could be enhanced as compared to that in the case without a boundary. Particularly, when the atom is very close to the boundary, although the atom still interacts with the environment, it behaves as if it were a closed system and quantum coherence can be shielded from the effect of the vacuum fluctuating scalar field.

Effects of salinity and particle size on radium desorption from river sediments in the Qinghai-Tibet Plateau.

Natural radium isotopes have been widely used to study groundwater discharge in different systems. Therefore, it is of great significance to understand the desorption behavior of radium isotopes on sediments to trace water-land exchange processes. However, there is very limited studies observing the desorption Ra isotopes to lake water of the brine lake. 224Ra desorption experiments with different salinities and particle sizes were carried out by collecting samples of brackish water from Qinghai Lake, brine from Dabuxun Lake and river sediments entering the lakes. The results show that the desorption activity of 224Ra from the river sediments to lake water of Qinghai Lake is 0.2 dpm/g when the salinity is 10.07‰. The maximum desorption activity of 224Ra from river sediments to lake water of Dabuxun Lake is 0.195 dpm/g at a salinity of 40.81‰. A salinity of 41.81‰ and particle size of 16.28 µm are the threshold points affecting the desorption behavior of Ra. When the salinity is less than 40.81‰, the desorption activity of Ra increases linearly with increasing salinity. When the salinity is greater than 40.81‰, the desorption activity of Ra decreases nonlinearly with increasing salinity and tends toward a stable low value. When the particle size is larger than 16.28 µm, the small particle size promotes desorption. The smaller the particle size is, the greater the desorption activity is. When the particle size is less than 16.28 µm, the small particle size inhibits desorption. The smaller the particle size is, the smaller the desorption activity. The co-precipitation of Ra2+ with supersaturated Ca2+, SO42- and other ions may be the main reason for the threshold point of salinity and particle size in Ra desorption process in salt lake system.

Long non-coding RNA LUCAT1 promotes the progression of clear cell renal cell carcinoma via the microRNA-375/YAP1 axis.

Clear cell renal cell carcinoma (ccRCC) is a common renal cell carcinoma with a high mortality rate. Lung cancer-associated transcript 1 (LUCAT1) has been reported to be a potential biomarker of prognosis in human ccRCC. However, the underlying mechanism of the function of LUCAT1 in ccRCC remains poorly understood. The present study aimed to investigate the role and underlying mechanism of LUCAT1 in ccRCC. The expression level of LUCAT1, microRNA-375 (miR-375) and yes-associated protein 1 (YAP1) in ccRCC tissues and cells was detected by reverse transcription-quantitative PCR, and the protein level of YAP1 was detected by western blotting. The effects of LUCAT1 on cell proliferation, migration and invasion were analyzed using Cell Counting Kit-8 and Transwell assays. The association between miR-375 and LUCAT1 or miR-375 and YAP1 was predicted by lncBase Predicted v.2 or TargetScan and verified using dual-luciferase reporter assay. The effect of LUCAT1 on ccRCC progression in vivo was evaluated using a xenograft tumor model. The results revealed that LUCAT1 and YAP1 were upregulated and miR-375 was downregulated in ccRCC tissues and cells. LUCAT1 knockdown suppressed cell proliferation, migration and invasion, which were reversed by the inhibition of miR-375. In addition, YAP1 overexpression attenuated the inhibitory effects of miR-375 overexpression on cell proliferation, migration and invasion. Subsequent experiments suggested that LUCAT1 regulated YAP1 expression by sponging miR-375. Therefore, LUCAT1 exerted its role by regulating the miR-375/YAP1 axis in vitro. Moreover, LUCAT1 knockdown suppressed the growth of ccRCC xenograft tumors in vivo. These results collectively revealed that LUCAT1 promoted the proliferation, migration and invasion of ccRCC by the upregulation of YAP1 via sponging miR-375, which may be used as a potential therapeutic target for ccRCC.

Evaluation of the pharmacokinetic effects of itraconazole on alflutinib (AST2818): an open-label, single-center, single-sequence, two-period randomized study in healthy volunteers.

Alflutinib (AST2818) is a newly developed third-generation EGFR tyrosine kinase inhibitor for the treatment of lung cancer patients with T790M-resistant mutations. It is metabolized mainly by the CYP3A4 enzyme. At the same time, it has the potential to induce CYP3A4. In this study, we aimed to estimate the effect of itraconazole (a strong inhibitor of CYP3A4) on the pharmacokinetics of alflutinib. For this aim, a single-center, open-label, single-sequence, two-period trial was designed. The pharmacokinetic parameters of AST2818 and its active metabolite AST5902 were established from blood concentration measurements, and adverse events (AEs) of two periods of treatment were documented. For AST2818, the Cmax, AUC0-t, and AUC0-∞ in period II (coadministration of itraconazole) increased by 6.5 ng/mL, 1263.0 h*ng/mL, and 1067.0 h*ng/mL, respectively. And the corresponding 90% CIs were 1.23 (1.14-1.32), 2.41 (2.29-2.54), and 2.22 (2.11-2.34), respectively. The Cmax, AUC0-t, and AUC0-∞ of AST5902 in period II decreased by 4.849 ng/mL, 415.60 h*ng/mL, and 391.4 h*ng/mL, respectively. Moreover, the corresponding 90% CIs were 0.09 (0.08-0.10), 0.18 (0.17-0.19), and 0.14 (0.13-0.15), respectively. Nonetheless, in period II, plasma concentrations of total active components (AST2818 and AST5902) changed marginally. The AUC0-∞ of total active components increased 60%, and the corresponding Cmax increased 8%. Possible treatment-related AEs assessed by investigators were fewer in period II (23.3% vs 36.7%). In conclusion, the total exposure of AST2818 and active metabolite AST5902 increased following the coadministration of itraconazole, but it was still safe and well-tolerated.

Case Report: A Promising Treatment Strategy for Noninfectious Uveitis.

Background: Uveitis refers to inflammation in the uvea, retina, retinal blood vessels, and vitreous, which can lead to irreversible eye damage and permanent vision loss. Glucocorticoid drugs are the first-line treatment, but side effects, such as obesity and hyperglycemia, can occur. Therefore, biologics have become a new treatment choice. Case Presentation: A 18-year-old girl developed eye pain and was diagnosed with binocular uveitis. Prednisone 50 mg was administered once a day, and the redness and pain in both eyes improved. Later, the prednisone dose was gradually reduced, and treatment was discontinued 3 years ago. Two years ago, the patient's condition relapsed, with both eyes becoming red and painful. She was administered prednisone 20 mg once daily and adalimumab. Visual acuity in both eyes continued to progressively decrease, accompanied by cataracts. At the same time, the patient experienced complications, including obesity and hyperglycemia. Subsequently, a new treatment regimen, oral prednisone 20 mg once a day, tofacitinib 5 mg twice a day, and methotrexate 10 mg once a week, as well as the use of insulin to control blood sugar, was initiated. One month later, the patient's redness and eye pain eased, and her vision gradually improved. The dosage of prednisone was gradually reduced to 5 mg once daily. At the same time, her blood sugar returned to normal, and insulin was stopped. Outcomes: The patient was treated with tofacitinib for 10 months. Subsequently, her best-corrected visual acuity of the right eye rose from 0.06 to 0.075, and the best-corrected visual acuity of the left eye rose from CF/30 cm to CF/100 cm. Redness and eye pain were relieved, her glucocorticoid consumption reduced from 15 to 2.5 mg, and her blood sugar gradually normalized. Conclusion: This case study shows that tofacitinib relieves ocular inflammation in patients with uveitis and improves eyesight. We believe that JAK inhibitors could be another treatment option for noninfectious uveitis in patients who do not respond to conventional anti-TNF-α inhibitors (such as adalimumab).

ß-Sitosterol Inhibits Rheumatoid Synovial Angiogenesis Through Suppressing VEGF Signaling Pathway.

Background: Rheumatoid arthritis (RA) is a chronic disabling inflammatory disease that causes synovial angiogenesis in an invasive manner and leads to joint destruction. Currently available pharmacotherapy for RA has unwanted side effects and limitations. Although anti-angiogenic therapy is regarded as a new potential treatment for RA, only a few anti-angiogenic drugs are available. An increasing number of studies have shown that ß-sitosterol (BSS) may exert inhibitory effects against angiogenesis. However, the mechanisms involved are still unclear. Methods: Based on the results of the gene set enrichment analysis (GSEA) of the transcriptome data of endothelial cells from RA patients, we evaluated the pharmacological effects of BSS on the tube formation, cell proliferation, and migration of human umbilical vein endothelial cells (HUVECs). Furthermore, the effects of BSS treatment on vascular endothelial growth factor receptor 2 (VEGFR2) were determined using molecular docking and Western blotting. Additionally, in the presence or absence of BSS, synovial angiogenesis and joint destruction of the ankle were investigated in collagen-induced arthritis (CIA) mice. The effect of BSS treatment on VEGFR2/p-VEGFR2 expression was verified through immunohistochemical staining. Results: The immunohistochemistry results revealed that BSS treatment inhibited angiogenesis both in vitro and in vivo. In addition, the results of 5-ethynyl-2'-deoxyuridine and cell cycle analysis showed that BSS treatment suppressed the proliferation of HUVECs, while the Transwell migration and stress fiber assays demonstrated that BSS treatment inhibited the migration of HUVECs. Notably, the inhibitory effect of BSS treatment on VEGFR2/p-VEGFR2 was similar to that of axitinib. In CIA mice, BSS also exerted therapeutic effects on the ankles by reducing the degree of swelling, ameliorating bone and cartilage damage, preventing synovial angiogenesis, and inhibiting VEGFR2 and p-VEGFR2 expression. Conclusion: Therefore, our findings demonstrate that BSS exerts an inhibitory effect on synovial angiogenesis by suppressing the proliferation and migration of endothelial cells, thereby alleviating joint swelling and bone destruction in CIA mice. Furthermore, the underlying therapeutic mechanisms may involve the inhibition of VEGF signaling pathway activation.

Upregulation of cervical carcinoma expressed PCNA regulatory long non-coding RNA promotes esophageal squamous cell carcinoma progression.

Cervical carcinoma expressed PCNA regulatory long non-coding (lnc)RNA (CCEPR) has recently been reported to play oncogenic roles in some common types of human cancer. However, the clinical significance of CCEPR mRNA expression levels in esophageal squamous cell carcinoma (ESCC) and the exact function of CCEPR in regulating the malignant phenotypes of ESCC cells have not been previously investigated. In the present study, CCEPR mRNA expression level was upregulated in ESCC tissues and cell lines, and overexpression of CCEPR was associated with advanced TNM stage, lymph node metastasis, and poor prognosis in ESCC. In vitro experiments showed that silencing CCEPR mRNA expression levels significantly suppressed the proliferation, migration, and invasion of ESCC cells, while inducing ESCC cell apoptosis. Furthermore, inhibition of CCEPR decreased the protein expression levels of matrix metalloproteinase (MMP)2 and MMP9 and inhibited epithelial-mesenchymal transition in ESCC cells. In conclusion, the results showed that CCEPR plays an oncogenic role in ESCC and suggests that CCEPR could be used as a potential therapeutic target for ESCC treatment.

A Randomized, Open, Single-Centre, Crossed Study of the Effect of Food on the Pharmacokinetics of One Oral Dose of Alflutinib Mesylate Tablets (AST2818) in Healthy Male Subjects.

The aim of the study was to study the PK of AST2818 tablets after one oral dose in healthy male subjects on an empty stomach and in a postprandial state and to evaluate the effect of food on AST2818 bioavailability. Sixteen healthy Chinese male subjects were randomly divided into two groups: a fasting-postprandial group and a postprandial-fasting group. The drug was administered once per evaluation at a dose of 80 mg, with an interval of 22 days between the two treatments. The LC-MS/MS method was used to determine the concentrations of AST2818 and its metabolite AST5902. Plasma pharmacokinetic parameters were calculated by noncompartmental analysis (NCA). WinNonlin® version 7.0 was used to analyse PK parameters, and SAS version 9.4 was used for statistical analyses. After a meal, the peak concentration of alflutinib increased by approximately 53%, and the AUC increased by approximately 32%; The peak concentration of its metabolite AST5902 decreased by approximately 20%, and the AUC decreased by approximately 8%. There was no significant change in peak time. The peak AST5902 concentration and AUC0-∞ were 27.4% and 71.4%, respectively, of that of alflutinib. None of the subjects experienced serious AEs, and both fasting and high-fat meal administration were safe. There was no statistically significant difference between groups in AEs (P = 0.102, RR = 1.40) or adverse reactions (P = 0.180, RR = 1.30). The effects of food may not need to be considered for the clinical use of alflutinib. No serious AEs occurred, and drug administration was safe and tolerable after fasting or a high-fat meal.