Effect of navigation endoscopy combined with three-dimensional printing technology in the treatment of orbital blowout fractures.

AIM: To explore the combined application of surgical navigation nasal endoscopy (NNE) and three-dimensional printing technology (3DPT) for the adjunctive treatment of orbital blowout fractures (OBF). METHODS: Retrospective analysis was conducted on the data of patients with OBF who underwent surgical treatment at the Affiliated Eye Hospital of Nanchang University between July 2012 and November 2022. The control group consisted of patients who received traditional surgical treatment (n=43), while the new surgical group (n=52) consisted of patients who received NNE with 3DPT. The difference in therapeutic effects between the two groups was evaluated by comparing the duration of the operation, best corrected visual acuity (BCVA), enophthalmos difference, recovery rate of eye movement disorder, recovery rate of diplopia, and incidence of postoperative complications. RESULTS: The study included 95 cases (95 eyes), with 63 men and 32 women. The patients' age ranged from 5 to 67y (35.21±15.75y). The new surgical group and the control group exhibited no statistically significant differences in the duration of the operation, BCVA and enophthalmos difference. The recovery rates of diplopia in the new surgical group were significantly higher than those in the control group at 1mo [OR=0.03, 95%CI (0.01-0.15), P<0.0000] and 3mo [OR=0.11, 95%CI (0.03-0.36), P<0.0000] post-operation. Additionally, the recovery rates of eye movement disorders at 1 and 3mo after surgery were OR=0.08, 95%CI (0.03-0.24), P<0.0000; and OR=0.01, 95%CI (0.00-0.18), P<0.0000. The incidence of postoperative complications was lower in the new surgical group compared to the control group [OR=4.86, 95%CI (0.95-24.78), P<0.05]. CONCLUSION: The combination of NNE and 3DPT can shorten the recovery time of diplopia and eye movement disorder in patients with OBF.

Utilizing network pharmacology and experimental validation to investigate the underlying mechanism of Denglao Qingguan decoction against HCoV-229E.

Background: Denglao Qingguan decoction (DLQGD) has been extensively utilized for the treatment of colds, demonstrating significant therapeutic efficacy. Human Coronavirus 229E (HCoV-229E) is considered a crucial etiological agent of influenza. However, the specific impact and underlying mechanisms of DLQGD on HCoV-229E remain poorly understood. Methods: Active ingredients and targets information of DLQGD were collected from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), literature search, and Swiss ADEM database. The Genecard database was used to collect HCoV-229E related targets. We built an "ingredient-target network" through Cytoscape. Protein - Protein interaction (PPI) networks were mapped using the String database. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) were enriched using the DAVID database. Then, we used molecular docking techniques to verify the binding activity between the core compounds and the core gene targets. Finally, in vitro experiments were conducted to validate DLQGD's antiviral activity against HCoV-229E and assess its anti-inflammatory effects. Results: In total, we identified 227 active components in DLQGD. 18 key targets involved in its activity against HCoV-229E. Notably, the core active ingredients including quercetin, luteolin, kaempferol, ß-sitosterol, and apigenin, and the core therapeutic targets were CXCL8, RELA, MAPK14, NFKB1, and CXCL10, all associated with HCoV-229E. KEGG enrichment results included IL-17 signaling pathway, Toll-like receptor signaling pathway, RIG-I-like receptor signaling pathway and so on. The core active ingredients and the core therapeutic targets and Human Aminopeptidase N (ANPEP) all showed good binding activity by molecular docking verification. In vitro, DLQGD exhibited anti-HCoV-229E activity and anti-inflammatory effects. Conclusion: Our study suggests that DLQGD has both effects of anti-HCoV-229E and anti-inflammatory. The core active ingredients (quercetin, luteolin, kaempferol, ß-sitosterol, apigenin) and the core therapeutic targets (CXCL8, RELA, MAPK14, NFKB1, CXCL10) may play key roles in the pharmacological action of DLQGD against HCoV-229E.

Initial implementation of surgical guide design utilizing digital medicine for lateral orbital decompression surgery.

This study aimed to assess the feasibility of utilizing a surgical guide, designed through digital medical technology, in lateral orbital decompression surgery. METHODS: In total, 18 patients with thyroid-associated ophthalmopathy (TAO), who underwent orbital balance decompression surgery at the Affiliated Eye Hospital of Nanchang University between September 2018 and August 2022, were included. Orbital CT scanning was performed on all patients with TAO, and Mimics 21.0 software was used to reconstruct a three-dimensional model of the orbit based on the CT data. The osteotomy guide plate for lateral orbital decompression surgery was designed using 3-matic 13.0 software, adhering to the criteria of surgical effectiveness and safety. The surgical positioning guide was designed using Geomagic Wrap 21.0. Once printed, the surgical guide was sterilized with low-temperature plasma and applied during surgery. Of the nine patients treated using a surgical navigation system, three cases experienced cerebrospinal fluid leakage complications during the procedure, and two exhibited inadequate bone removal along the lateral wall. In contrast, among the nine patients treated with surgical guides, no intraoperative cerebrospinal fluid leakage or evidence of insufficient lateral wall bone removal was observed, highlighting a statistically significant distinction between the two cohorts (p = 0.046). Postoperative improvements were notable in best-corrected visual acuity (BCVA) and exophthalmos for patients afflicted with extremely severe TAO. The surgical guide, designed with digital medical technology, has been shown to be an effective and secure auxiliary tool in lateral orbital decompression surgery. It not only aids in reducing the incidence of intraoperative complications, but also enhances the accuracy and safety of surgery. These improvements offer robust support for continued exploration in this field within clinical practice.

MMP10 alleviates non-alcoholic steatohepatitis by regulating macrophage M2 polarization.

BACKGROUND: Non-alcoholic steatohepatitis (NASH), the most severe form of non-alcoholic fatty liver disease (NAFLD), is currently untreatable with a clinically validated treatment. Matrix Metallopeptidase 10 (MMP10) is a common host-response-gene involved in the immune response. However, it remains unknown whether and how MMP10 influences NASH development by modulating macrophage function. METHODS: In vitro, MMP10 overexpression (MMP10-OE), MMP10 knockout (MMP10-KO), proliferator-activated receptor γ (PPARγ)-OE, and control plasmids were transfected into primary Kupffer cells, which were then cultured with or without Interleukin (IL)-4 stimulation. MMP10-OE mice and MMP10-KO mice were fed a normal chow diet (NCD) or a high-fat diet (HFD) for 30 weeks to study the role of MMP10 in NASH model. Hepa1-6 cells were cultured with or without free fatty acid (FFA) treatment for 24 h. RESULTS: MMP10 is downregulated in NASH, and M1/M2 indicators are significantly imbalanced. MMP10 is triggered in response to M2 macrophages polarization. MMP10 overexpression diminishes hepatic steatosis and inflammation in HFD-induced NASH. Mechanistically, PPARγ can bind to the MMP10 promoter and then up-regulates MMP10 expression, which is engaged when IL-4 stimulates M2 macrophage polarization. The downstream STAT3 signaling pathway is further activated to induce M2 polarization, which results in a decreased expression of the pro-inflammatory IL-1ß and tumor necrosis factor (TNF)-a and an increased expression of the anti-inflammatory IL-10, ultimately alleviating NASH progression. CONCLUSIONS: We demonstrate that IL-4 effectively promotes MMP10 expression via PPARγ, and MMP10 overexpression modulates macrophage polarization, hepatic steatosis, and fibrosis, offering prospective targets for NASH treatment.

Eicosapentaenoic acid metabolites promotes the trans-differentiation of pancreatic α cells to ß cells.

Type 1 diabetes mellitus (T1DM) is characterized by life-threatening absolute insulin deficiency. Although ω-3 polyunsaturated fatty acids (PUFAs) displayed significant anti-hyperglycemic activity, the insulinotropic effects of their metabolites remain unknown. In this study, we took advantage of a transgenic model, mfat-1, that overexpresses an ω-3 desaturase and can convert ω-6 PUFAs to ω-3 PUFAs. Eicosapentaenoic acid (EPA) was sharply elevated in the pancreatic tissues of mfat-1 transgenic mice compared with wild-type (WT) mice. In contrast to the WT mice, the mfat-1 transgenics did not develop overt diabetes and still maintained normal blood glucose levels and insulin secretion following streptozotocin-treatment. Furthermore, under the condition of pancreatic ß-cell damage, co-incubation of the metabolites of EPA produced from the CYP 450 pathway with isolated islets promoted the overexpression of insulin as well as ß-cell specific markers, pdx1 and Nkx6.1 in pancreatic α-cells. Addition of EPA metabolites to the cultured glucagon-positive α-cell lines, a series of pancreatic ß-cell markers were also found significantly elevated. Combined together, these results demonstrated the effects of ω-3 PUFAs and their metabolites on the trans-differentiation from α-cells to ß-cells and its potential usage in the intervention of T1DM.

Endogenous production of ω-3 polyunsaturated fatty acids mitigates cisplatin-induced myelosuppression by regulating NRF2-MDM2-p53 signaling pathway.

Cisplatin is a chemotherapy medication used to treat a wide range of cancers. A common side effect of cisplatin is myelosuppression. Research suggests that oxidative damages are strongly and consistently related to myelosuppression during cisplatin treatment. ω-3 polyunsaturated fatty acids (PUFAs) can enhance the antioxidant capacity of cells. Herein, we investigated the protective benefit of endogenous ω-3 PUFAs on cisplatin-induced myelosuppression and the underlying signaling pathways using a transgenic mfat-1 mouse model. The expression of mfat-1 gene can increase endogenous levels of ω-3 PUFAs by enzymatically converting ω-6 PUFAs. Cisplatin treatment reduced peripheral blood cells and bone marrow nucleated cells, induced DNA damage, increased the production of reactive oxygen species, and activated p53-mediated apoptosis in bone marrow (BM) cells of wild-type mice. In the transgenics, the elevated tissue ω-3 PUFAs rendered a robust preventative effect on these cisplatin-induced damages. Importantly, we identified that the activation of NRF2 by ω-3 PUFAs could trigger an antioxidant response and inhibit p53-mediated apoptosis by increasing the expression of MDM2 in BM cells. Thus, endogenous ω-3 PUFAs enrichment can strongly prevent cisplatin-induced myelosuppression by inhibiting oxidative damage and regulating the NRF2-MDM2-p53 signaling pathway. Elevation of tissue ω-3 PUFAs may represent a promising treatment strategy to prevent the side effects of cisplatin.

Circ-CCS regulates oxaliplatin resistance via targeting miR-874-3p/HK2 axis in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a malignancy that threatens the patient's life. Previous reports showed that circular RNAs (circRNAs) can affect CRC development. Herein, we demonstrated the characters of circular RNA copper chaperone for superoxide dismutase (circ-CCS) in CRC tissues and cells. METHODS: Circ-CCS, CCS mRNA, microRNA-874-3p (miR-874-3p) and hexokinase 2 (HK2) were indicated by qRT-PCR and western blot in CRC. The cell roles were examined. Additionally, the interaction between miR-874-3p and circ-CCS or HK2 was forecasted by the bioinformatics method and assessed by dual-luciferase reporter assay. Finally, the mouse test was implemented to demonstrate the effect of circ-CCS in vivo. RESULTS: Circ-CCS and HK2 were increased, whereas miR-874-3p was diminished in CRC. Circ-CCS lack subdued the IC50 value of oxaliplatin, cell proliferation, migration, invasion and glycolysis metabolism in CRC cells, while it endorsed cell apoptosis. Furthermore, miR-874-3p was validated as having a tumor repressive effect in CRC cells by restraining HK2. The results also showed that HK2 could regulate the development of CRC. In mechanism, circ-CCS targeted miR-874-3p to control HK2. In addition, circ-CCS knock-down also attenuated tumor growth in mice. CONCLUSION: Circ-CCS expedited CRC through miR-874-3p/HK2.

Resistin Promotes Nasopharyngeal Carcinoma Metastasis through TLR4-Mediated Activation of p38 MAPK/NF-κB Signaling Pathway.

NPC is a type of malignant tumor with a high risk of local invasion and early distant metastasis. Resistin is an inflammatory cytokine that is predominantly produced from the immunocytes in humans. Accumulating evidence has suggested a clinical association of circulating resistin with the risk of tumorigenesis and a relationship between blood resistin levels and the risk of cancer metastasis. In this study, we explored the blood levels and the role of resistin in NPC. High resistin levels in NPC patients were positively associated with lymph node metastasis, and resistin promoted the migration and invasion of NPC cells in vitro. These findings were also replicated in a mouse model of NPC tumor metastasis. We identified TLR4 as a functional receptor in mediating the pro-migratory effects of resistin in NPC cells. Furthermore, p38 MAPK and NF-κB were intracellular effectors that mediated resistin-induced EMT. Taken together, our results suggest that resistin promotes NPC metastasis by activating the TLR4/p38 MAPK/NF-κB signaling pathways.

Danlu tongdu tablets: Preclinical safety evaluation and mechanism of hepatotoxicity.

Danlu tongdu tablets (DLTD) is a listed Chinese patent medicine collected in the Pharmacopoeia of the People's Republic of China (version 2020). This prescription has been applied in clinics in China for lumbar spinal stenosis and lumbosacral disc herniations. The wide application of Danlu tongdu in therapy has raised some clinical adverse reactions, such as significant elevation of alanine transaminase (ALT) and aspartate transaminase (AST) in individual patients after use. The present study aimed to investigate the safety of Danlu tongdu and analyze its adverse effects on the liver. The maximum feasible dose (MFD) was used to carry out the acute toxicity tests. Mortality, adverse effects, body weight and food consumption were recorded for up to 14 days post treatment. In the 6-month chronic toxicity test, sprague-dawley rats were randomly divided into four groups according body weight, the experimental groups were administrated to rats at the concentrations of 1.67, 3.34 and 6.67 g/kg/day, whereas the control group was received the ultrapure water (vehicle) only, 10 ml/kg, once a day. The animal's body weight, food consumption was monitored weekly. In addition, their hematological and biochemical parameters, body and organ weights and histopathology, were all measured at specific observation time points. Additionally, we further explored the adverse effects mechanism of Danlu tongdu on the liver through transcriptome analysis. No deaths or substance-relative toxicity were observed in the acute toxicity study or the 6-month chronic toxicity study with doses of 1.67 g/kg and 3.34 g/kg, respectively. We found that mild hypertrophy and hyperplasia of hepatic interlobular bile ducts were detected in some rats with doses of 6.67 g/kg after repeated oral administration of Danlu tongdu for 13 and 26 weeks, but the above changes in liver were reversible. The results of transcriptome sequencing showed that Danlu tongdu had a significant effect on cytochrome P450 enzymes in rat liver, especially cytochrome P450 1 (CYP1) subtype. Therefore, the toxic target organ of Danlu tongdu is the liver and the mechanism of mild liver injury is closely related to the up-regulation of cytochrome P450 1A1 (CYP1A1) and cytochrome P450 1A2 (CYP1A2) expression.

Adiponectin Suppresses Metastasis of Nasopharyngeal Carcinoma through Blocking the Activation of NF-κB and STAT3 Signaling.

Adiponectin is an adipocytokine with anti-inflammatory and anticancer properties. Our previous study has shown that blood adiponectin levels were inversely correlated to the risk of nasopharyngeal carcinoma (NPC), and that adiponectin could directly suppress the proliferation of NPC cells. However, the effect of adiponectin on NPC metastasis remains unknown. Here, we revealed in clinical studies that serum adiponectin level was inversely correlated with tumor stage, recurrence, and metastasis in NPC patients, and that low serum adiponectin level also correlates with poor metastasis-free survival. Coculture with recombinant adiponectin suppressed the migration and invasion of NPC cells as well as epithelial-mesenchymal transition (EMT). In addition, recombinant adiponectin dampened the activation of NF-κB and STAT3 signaling pathways induced by adipocyte-derived proinflammatory factors such as leptin, IL-6, and TNF-α. Pharmacological activation of adiponectin receptor through its specific agonist, AdipoRon, largely stalled the metastasis of NPC cells. Taken together, these findings demonstrated that adiponectin could not only regulate metabolism and inhibit cancer growth, but also suppress the metastasis of NPC. Pharmacological activation of adiponectin receptor may be a promising therapeutic strategy to stall NPC metastasis and extend patients' survival.

Hsa_circ_0001550 facilitates colorectal cancer progression through mediating microRNA-4262/nuclear casein kinase and cyclin-dependent kinase substrate 1 cascade.

BACKGROUND: Circular RNAs (circRNAs) play important roles in various malignancies, such as colorectal cancer (CRC). However, the function of hsa_circ_0001550 in CRC remains to be elucidated. METHODS: The expression levels of hsa_circ_0001550, microRNA (miR)-4262, and nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) were determined by real-time qPCR. Cell biological behaviors were evaluated via colony formation assay, transwell assay, flow cytometry, and sphere formation assays. The target relationship was validated via dual-luciferase reporter and RNA pull-down assays. Protein expression was analyzed by western blot. Xenograft tumor model was adopted to evaluate hsa_circ_0001550 function in vivo. RESULTS: Hsa_circ_0001550 enrichment was enhanced in CRC tissue specimens and cell lines. Hsa_circ_0001550 absence hindered CRC cell proliferation, metastasis, stemness, and caused apoptosis. Hsa_circ_0001550 targeted miR-4262, and hsa_circ_0001550 absence-caused impacts were diminished by anti-miR-4262. MiR-4262 targeted NUCKS1. Hsa_circ_0001550 had positive regulation on NUCKS1 expression. NUCKS1 overexpression overturned the influences of hsa_circ_0001550 silencingon CRC cell progression. Hsa_circ_0001550 interference notably blocked in vivo xenograft tumor growth. CONCLUSION: Hsa_circ_0001550 facilitated CRC progression by binding to miR-4262 to positively regulate NUCKS1 abundance.

Effectiveness of a combined problem-based learning and flipped classroom teaching method in ophthalmic clinical skill training.

BACKGROUND: Previous studies have primarily implemented problem-based learning (PBL) or flipped classroom (FC) teaching models in different majors; however, research on the combined PBL-FC teaching method in clinical medicine is scarce. Therefore, we investigated the combined PBL-FC teaching method in teaching ocular trauma on students' competencies. METHOD: About 75 ophthalmology postgraduates were randomly divided into PBL-FC and traditional teaching groups. Students completed pre-and post-class theoretical examinations, skills evaluation, learning ability scales, and feedback questionnaires. RESULTS: Both groups showed significantly higher theoretical scores and improved learning ability. Feedback questionnaire scores of the PBL-FC group's postgraduates without clinical experience were significantly higher than the traditional group's for some items; there was no difference between groups in postgraduates with clinical experience. PBL-FC group's pre-class preparation time was significantly longer than the traditional group's, but the post-class review time was significantly shorter. PBL-FC group's post-class theoretical performance was significantly higher than the traditional group's. There was no statistical difference between the groups regarding skill operation. Among postgraduates without clinical experience, the PBL-FC group's skill operation performance was significantly higher than the traditional group's; for postgraduates with clinical experience, the traditional group's skill operation performance was significantly higher than the PBL-FC group's. CONCLUSIONS: PBL-FC teaching is better for students without clinical experience or knowledge of ophthalmic diseases. Meanwhile, traditional teaching is a good choice for students with clinical experience who need more relevant knowledge.

circ_0006089 promotes gastric cancer growth, metastasis, glycolysis, and angiogenesis by regulating miR-361-3p/TGFB1.

Circular RNA (circRNA) participates in a variety of pathophysiological processes, including the development of gastric cancer (GC). However, the role of circ_0006089 in GC progression and its underlying molecular mechanism need to be further revealed. Quantitative real-time PCR was utilized for detecting circ_0006089, microRNA (miR)-361-3p and transforming growth factor-ß1 (TGFB1) expression. The interaction between miR-361-3p and circ_0006089 or TGFB1 was confirmed using a dual-luciferase reporter assay and an RNA immunoprecipitation (RIP) assay. Cell proliferation, metastasis, apoptosis, and angiogenesis were determined using colony formation assay, EdU assay, transwell assay, flow cytometry, and tube formation assay. Cell glycolysis was evaluated by detecting glucose consumption, lactate production, and ATP levels. In addition, western blot (WB) analysis was used to measure protein expression. Xenograft tumor models were used to assess the effect of circ_0006089 knockdown on GC tumorigenesis. circ_0006089 had been found to be upregulated in GC tissues and cells, and it could act as an miR-361-3p sponge. circ_0006089 knockdown suppressed GC proliferation, metastasis, glycolysis, angiogenesis, and increased apoptosis, while this effect could be revoked by miR-361-3p inhibitor. TGFB1 was targeted by miR-361-3p, and its overexpression reversed the effects of miR-361-3p on GC cell function. Also, circ_0006089 promoted TGFB1 expression via sponging miR-361-3p. Animal experiments showed that silenced circ_0006089 inhibited GC tumorigenesis through the miR-361-3p/TGFB1 pathway. Our results revealed that the circ_0006089/miR-361-3p/TGFB1 axis contributed to GC progression, confirming that circ_0006089 might be a potential therapeutic target for GC.

Artesunate inhibits proliferation and migration of RPE cells and TGF-ß2 mediated epithelial mesenchymal transition by suppressing PI3K/AKT pathway.

AIM: To study the braking effectiveness of artesunate on transforming growth factor (TGF)-ß2 mediated epithelial-mesenchymal transition (EMT) in retinal pigment epithelium (RPE) in vitro. METHODS: The fostered ARPE-19 cells were processed with artesunate alone or combined with the TGF-ß2. The CCK-8 examination was utilized to test the cell propagation. Cell migration was detected by scratch as well as the Transwell examination. The EMT characters and activation of PI3K/Akt signal channel were estimated by Western blotting and immunofluorescence. The Western blotting was utilized in order to confirm the vitreous of controls as well as patients with proliferative vitreoretinopathy (PVR) were collected and the levels of PI3K, phospho-PI3K, Akt. RESULTS: Disposal of ARPE-19 cells with artesunate (50-150 µmol/L) obviously suppressed their propagation and immigration, which dependent on the concentration and time. Artesunate suppressed the EMT which was induced by TGF-ß2 in ARPE-19 cells through sustaining the expression of vimentin and α-SMA through the suppression of PI3K, phospho-PI3K, phospho-Akt and Akt. Levels of PI3K, phospho-PI3K, AKT and phospho-Akt was increased in the vitreous in PVR (P<0.05). CONCLUSION: Such findings indicate that PI3K/Akt signal channel is highly activated in vitreous of PVR. Artesuante is an operative depressor of the propagation, immigration and TGF-ß2-mediated EMT of ARPE-19 cells by reduced the expression of PI3K/Akt channel.

Adiponectin suppresses tumor growth of nasopharyngeal carcinoma through activating AMPK signaling pathway.

BACKGROUND: Adiponectin is an adipocyte-secreted cytokine that enhances insulin sensitivity and attenuates inflammation. Although circulating adiponectin level is often inversely associated with several malignancies, its role in the development of nasopharyngeal carcinoma (NPC) remains unclear. Here, we investigated the clinical association between circulating adiponectin level and NPC, and examined the impact of adiponectin, as well as the underlying mechanisms, on NPC growth both in vitro and in vivo. METHODS: The association between circulating adiponectin level and the risk of developing NPC was assessed in two different cohorts, including a hospital-based case-control study with 152 cases and 132 controls, and a nested case-control study with 71 cases and 142 controls within a community-based NPC screening cohort. Tumor xenograft model, cell proliferation and cycle assays were applied to confirm the effects of adiponectin on NPC growth in cultured cells and in xenograft models. We also investigated the underlying signaling mechanisms with various specific pharmacological inhibitors and biochemistry analysis. RESULTS: High adiponectin levels were associated with a monotonic decreased trend of NPC risk among males in both the hospital-based case-control study and a nested case-control study. In vitro, recombinant human full-length adiponectin significantly inhibited NPC cell growth and arrested cell cycle, which were dependent on AMPK signaling pathway. The growth of xenograft of NPC tumor was sharply accelerated in the nude mice carrying genetic adiponectin deficiency. An adiponectin receptor agonist, AdipoRon, displayed strong anti-tumor activity in human xenograft models. CONCLUSIONS: These findings demonstrated for the first time that circulating adiponectin is not only inversely associated with NPC, but also controls the development of NPC via AMPK signaling pathway. Stimulation of adiponectin function may become a novel therapeutic modality for NPC.

Circular RNA circ_0006948 Promotes Esophageal Squamous Cell Carcinoma Progression by Regulating microRNA-3612/LASP1 Axis.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is the most prevalent malignancy worldwide. Circular RNAs (circRNAs) circ_0006948 is reported to be upregulated in ESCC cells. AIMS: This study is designed to explore the role and mechanism of circ_0006948 in ESCC progression. METHODS: Circ_0006948, linear FNDC3B, microRNA-3612 (miR-3612), and LIM and SH3 protein 1 (LASP1) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell viability, colony number, migration, invasion, and apoptosis were examined by Cell Counting Kit-8 (CCK-8), colony formation, transwell, and flow cytometry assays, severally. Glucose consumption, lactate production, and ATP level were measured by the corresponding kits. Protein levels of hexokinase 2 (HK2) and lactate dehydrogenase A (LDHA), and LASP1 were assessed by western blot assay. The cytoplasmic localization of circ_0006948 was identified by the subcellular fractionation assay. The binding relationship between miR-3612 and circ_0006948 or LASP1 was predicted by starBase or TargetScan and then verified by a dual-luciferase reporter assay. The biological role of circ_0006948 on ESCC tumor growth was examined by the xenograft tumor model in vivo. RESULTS: Circ_0006948 and LASP1 were increased, and miR-3612 was decreased in ESCC tissues and cells. Furthermore, circ_0006948 knockdown could suppress cell viability, colony number, migration, invasion, glycolysis, and boost apoptosis in ESCC cells. Mechanically, circ_0006948 could act as a sponge of miR-3612 to regulate LASP1 expression. In addition, circ_0006948 silencing inhibited ESCC tumor growth in vivo. CONCLUSION: Circ_0006948 boosted ESCC progression partly by regulating the miR-3612/LASP1 axis, providing an underlying therapeutic target for the ESCC treatment.

Effects of Artesunate Tablet on Immune Activation and Reconstitution Among Highly Active Antiretroviral Therapy-Treated Patients with Incomplete Immune Responses.

The level of T cell activation is a better predictor of CD4+ T cell depletion in highly active antiretroviral therapy (HAART) patients than viral load. Artesunate is an artemisinin derivative that has an immunomodulatory effect. This study investigated whether artesunate tablet reduces T cell activation and improves immune reconstitution among patients with suboptimal immune recovery despite receiving long-term effective HAART. This was a randomized prospective parallel open-label trial consisting of 45 participants whose plasma HIV load was effectively suppressed by HAART for >18 months and who had CD4+ T cell counts of <300 cells/µL or an increase of <20% from baseline. The patients were randomized 2:1 into the artesunate group or the control group and received artesunate tablets (orally, 50 mg two times daily) combined with HAART or HAART alone, respectively. T cell subsets, activation markers, clinical symptoms, viral load, and side effects were assessed. By 48 weeks, artesunate tablet did not improve CD4+ T cell recovery or reduce the activation of T cell subsets but induced in a smaller decline in the expression of T cell activation markers among HAART patients with incomplete immune responses. However, artesunate tablet did appear to reduce the level of T cell apoptosis. One subject developed moderate anemia. Long-term use of artesunate tablet is unlikely to produce substantial clinical benefits in patients receiving HAART who exhibit an incomplete immune response.

Artesunate inhibits the development of PVR by suppressing the TGF-ß/Smad signaling pathway.

Proliferative vitreoretinopathy (PVR) is the main cause of retinal detachment surgery failure. The epithelial-mesenchymal transition (EMT) induced by transforming growth factor (TGF-ß2) plays an important role in the development of PVR. Artesunate has been widely studied as a treatment for ophthalmic diseases because of its antioxidant, anti-inflammatory, antiapoptotic and antiproliferative properties. The purpose of this study was to investigate the effects of artesunate on the TGF-ß2-induced EMT in ARPE-19 cells and PVR development. We found that artesunate inhibited the proliferation and contraction of ARPE-19 cells after the EMT and the autocrine effects of TGF-ß2 on ARPE-19 cells. Additionally, the levels of Smad3 and p-Smad3 were increased in clinical samples, and artesunate decreased the levels of Smad3 and p-Smad3 in ARPE-19 cells treated with TGF-ß2. Artesunate also inhibited the occurrence and development of PVR in vivo. In summary, artesunate inhibits the occurrence and development of PVR by inhibiting the EMT in ARPE-19 cells.

Biological role of postoperative low level laser therapy in preventing hydroxyapatite orbital implantation exposure: A case report.

Conjunctival sac stenosis is the contraction of the conjunctival sac as a result of trauma or disease. The aim of the present study was to observe the clinical effects of low-level laser therapy (LLLT) combined with hydroxyapatite (HA) orbital implantation as a treatment strategy for conjunctival sac stenosis. A total of 10 patients with conjunctival sac stenosis were treated with scleral graft transplantation in conjunction with HA implantation and postoperative LLLT. In addition, a rabbit model was used to investigate the biological mechanism underlying the effects of LLLT with the aim of preventing and treating orbital implantation exposure. The right eyeball was removed, orbital implantation performed and LLLT applied to experimental groups. 99mTc-Methyl diphosphonate scanning methods were performed at different timepoints to compare the average radioactivity count of the region of interest between surgical (right) and control (left) eyes (R/L). Histopathological examination was performed 8 weeks post-surgery, followed by analysis of fiber vascularization. Following LLLT, moderate conjunctival wounds were completely healed within 2 weeks and severe stenosis wounds healed within 3 weeks. Following prosthesis implantation in the rabbit model, a significantly elevated R/L ratio was observed after 4 weeks, whereas no significant difference was observed compared with the control group at 6 and 8 weeks postoperatively. Histopathological examination revealed that all implants were fibrotic. Overall, the present study demonstrated that LLLT promoted the survival of conjunctival grafts, stimulated conjunctival incision healing and promoted early vascularization of HA implants. Clinical trial registration no: ChiCTR-DDT-12002660 (www.chictr.org/cn/).

Circular RNA 0081146 facilitates the progression of gastric cancer by sponging miR-144 and up-regulating HMGB1.

OBJECTIVES: Recent studies have revealed that circular RNA (circRNA) plays a pivotal role in cancer development. The study aimed to investigate the role of circ_0081146 in gastric cancer (GC). RESULTS: Circ_0081146 was upregulated in GC tissues and cells. Patients with high expression of circ_0081146 had a significantly reduced 5-year overall survival rate. Circ_0081146 knockdown restrained the growth, migration and invasion of GC cells in vitro as well as tumorigenesis in vivo. Circ_0081146 targeted miR-144 and HMGB1 was targeted by miR-144. Circ_0081146 was negatively correlated with miR-144 expression, while positively correlated with HMGB1 expression in GC tissues. Moreover, the inhibitory effect of circ_0081146 knockdown on the progression of GC cells were reversed by silencing miR-144 or HMGB1 overexpression. Mechanically, circ_0081146 increased HMGB1 expression by targeting miR-144. CONCLUSION: Circ_0081146 functions as an oncogene in GC to promote cell growth, migration and invasion via modulating the miR-144/HMGB1 axis.