Vitamin D receptor gene polymorphisms and multiple myeloma: a meta-analysis.

Vitamin D acts through the vitamin D receptor (VDR), and vitamin D level decreases in multiple myeloma (MM) patients. Single nucleotide polymorphisms in VDR alter its functions to affect the vitamin D status. This raises the question of whether VDR gene polymorphisms are associated with MM risk, which has been investigated in case‒control studies, but the results have been inconsistent. This meta-analysis aimed to investigate the relationship between VDR gene polymorphisms and MM risk. The PubMed, Web of Science, Medline, Embase, Chinese National Knowledge Infrastructure (CNKI), Chinese Scientific Journal (VIP), Wanfang Databases (WANFANG) were searched from inception to June 1, 2023, without language restriction or publication preference. Pooled odds ratio (OR) and 95% confidence interval (CI) for each variable were calculated. Leave-one-out sensitivity analysis was performed to determine the source of heterogeneity. Publication bias was assessed using Begg' and Egger's tests, and the trim-and-fill method was used to compensate for publication bias. The correlation meta-analysis was conducted using Comprehensive Meta-Analysis 3.0 and STATA 12.0 software. All the included studies were based on Asian populations and involved four VDR gene polymorphisms, TaqI (rs731236), ApaI (rs7975232), BsmI (rs1544410) and FokI (rs2228570). The results showed that TaqI (C vs. T: OR = 1.487, 95% CI 1.052, 2.104, P = 0.025; CC + CT vs. TT: OR = 1.830, 95% CI 1.138, 2.944, P = 0.013), ApaI (T vs. G: OR = 1.292, 95% CI 1.101, 1.517, P = 0.002; TT vs. GG: OR = 1.600, 95% CI 1.106, 2.314, P = 0.013; TG vs. GG: OR 1.305, 95% CI 1.050, 1.622; P = 0.016; TT + TG vs. GG: OR = 1.353, 95% CI 1.103, 1.662, P = 0.004), BsmI (GG vs. AA: OR = 1.918, 95% CI 1.293, 2.844, P = 0.001; GA vs. AA: OR = 1.333, 95% CI 1.058, 1.679, P = 0.015; G vs. A: OR = 1.398, 95% CI 1.180, 1.657, P = 0.000; GG vs. AA + GA: OR = 1.686, 95% CI 1.174, 2.423, P = 0.005), and FokI (T vs. C: OR = 1.687, 95% CI 1.474, 1.931, P = 0.000; TT vs. CC: OR = 2.829, 95% CI 2.066, 3.872, P = 0.000; TC vs. CC: OR = 1.579, 95% CI 1.304, 1.913, P = 0.000, TT + TC vs. CC: OR = 1.771, 95% CI 1.477, 2.125, P = 0.000; TT vs. CC + TC: OR = 2.409, 95% CI 1.814, 3.200, P = 0.000) are associated with MM risk. VDR gene polymorphisms including ApaI, BsmI, TaqI, and FokI are associated with MM risk in Asian populations. Additional studies with large sample sizes and different ethnicities are needed.

Acupuncture in Multiple Myeloma Peripheral Neuropathy: A Systematic Review.

Background: Peripheral neuropathy (PN) is a prevalent complication of multiple myeloma (MM), due to the disease itself or its treatment. Despite extensive research, the optimal treatment for multiple myeloma peripheral neuropathy (MMPN) remains unclear. Clinical practice has shown the potential efficacy of acupuncture in managing MMPN. This study aimed to conduct a comprehensive analysis of the literature to assess the effectiveness and safety of acupuncture as a treatment for MMPN. Methods: The PubMed, Web of Science, MEDLINE, Cochrane Library, and Embase databases were comprehensively searched from inception to November 1, 2023 to identify relevant studies pertaining to the use of acupuncture to treat MMPN. Results: A total of five studies, encompassing 97 patients diagnosed with drug-related PN, were ultimately included in this analysis. The literature lacks any reports pertaining to the utilization of acupuncture for disease-related PN. ST36, LI4, SP6, and EX-LE-10 were found to be the most frequently chosen acupoints. Following acupuncture treatment, there was a consistent reduction in scores on the Visual Analogue Scale (VAS), Neuropathic Pain Scale (NPS), Brief Pain Inventory-Short Form (BPI-SF), and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) among MMPN patients. The results of Nerve Conduction Velocity (NCV) tests yielded conflicting results. No severe adverse effects were reported. Conclusion: The use of acupuncture for disease-related PN has not been studied to date. Acupuncture is safe for drug-related PN and is helpful for relieving pain. But uncertainty exists regarding the efficacy of this approach because there is substantial heterogeneity with respect to acupuncture treatment regimens, and more high-quality studies on this topic are warranted.

RBPJ Knockdown Promotes M2 Macrophage Polarization Through Mitochondrial ROS-mediated Notch1-Jagged1-Hes1 Signaling Pathway in Uveitis.

Uveitis is an autoimmune eye disease that can be involved in the entire body and is one of the leading causes of blindness. Therefore, comprehending the mechanisms underlying the development and regulation of ocular immune responses in uveitis is crucial for designing effective therapeutic interventions. In this study, we investigated how RBPJ regulates macrophage polarization in uveitis. We demonstrated that targeted RBPJ knockdown (RBPJKD) promotes M2 macrophage polarization and ameliorates uveitis through the mtROS-mediated Notch1-Jagged1-Hes1 signaling pathway. Real-time quantitative (Q-PCR) analysis revealed that the Notch1-Jagged1-Hes1 signaling pathway was active in the eye tissues of experimental autoimmune uveitis (EAU) rats. Immunofluorescence double staining confirmed enhanced signaling primarily occurring in macrophages, establishing a correlation between the Notch1 signaling pathway and macrophages. Transmission electron microscopy evaluated the morphological and functional changes of mitochondria in each group's eye tissues. It demonstrated significant swelling and disorganization in the EAU group, which were effectively restored upon RBPJ knockdown intervention. Finally, by employing an antioxidant N-acetyl-L-cysteine (NAC) to eliminate mtROS in vivo, we observed a decrease in the M2 macrophage polarization level, which prevented the cytoprotective effect conferred by RBPJKD. These findings underscore the relevance of the Notch signaling pathway to the immune system while highlighting the potential role of mtROS as a therapeutic target for inflammation and other related diseases.

Zinc Oxide Nanoparticles Trigger Autophagy in the Human Multiple Myeloma Cell Line RPMI8226: an In Vitro Study.

Multiple myeloma (MM) is a malignant clonal proliferative plasma cell tumor. Zinc oxide nanoparticles (ZnO NPs) are used for antibacterial and antitumor applications in the biomedical field. This study investigated the autophagy-induced effects of ZnO NPs on the MM cell line RPMI8226 and the underlying mechanism. After RPMI8226 cells were exposed to various concentrations of ZnO NPs, the cell survival rate, morphological changes, lactate dehydrogenase (LDH) levels, cell cycle arrest, and autophagic vacuoles were monitored. Moreover, we investigated the expression of Beclin 1 (Becn1), autophagy-related gene 5 (Atg5), and Atg12 at the mRNA and protein levels, as well as the level of light chain 3 (LC3). The results showed that ZnO NPs could effectively inhibit the proliferation and promote the death of RPMI8226 cells in vitro in a dose- and time-dependent manner. ZnO NPs increased LDH levels, enhanced monodansylcadaverine (MDC) fluorescence intensity, and induced cell cycle arrest at the G2/M phases in RPMI8226 cells. Moreover, ZnO NPs significantly increased the expression of Becn1, Atg5, and Atg12 at the mRNA and protein levels and stimulated the production of LC3. We further validated the results using the autophagy inhibitor 3-methyladenine (3­MA). Overall, we observed that ZnO NPs can trigger autophagy signaling in RPMI8226 cells, which may be a potential therapeutic approach for MM.

MiR-223-3p attenuates M1 macrophage polarization via suppressing the Notch signaling pathway and NLRP3-mediated pyroptosis in experimental autoimmune uveitis.

Autoimmune uveitis is an intraocular inflammatory disease with a high blindness rate in developed countries such as the United States. It is pressing to comprehend the pathogenesis of autoimmune uveitis and develop novel schemes for its treatment. In the present research, we demonstrated that the Notch signaling pathway was activated, and the level of miR-223-3p was significantly reduced in rats with experimental autoimmune uveitis (EAU) compared with the level of normal rats. To investigate the relationship between miR-223-3p and Notch signaling, EAU rats received miR-223-3p-carrying lentivirus, miR-223-3p vector-carrying lentivirus (miR-223-3p-N), and γ-secretase inhibitor (DAPT), respectively. The results of Q-PCR, immunological experiments, and flow cytometry analysis all support the hypothesis that both miR-223-3p and DAPT, a Notch signaling pathway inhibitor, had similar inhibitory effects on the EAU pathological process. That is to say, they could both inhibit the activation of the Notch signaling pathway via modulating recombination signal binding protein-Jκ (RBPJ) to restore the polarization imbalance of M/M2 macrophages in EAU rats. In addition, miR-223-3p could also inhibit NLRP3 inflammasome activation and inflammasome-induced pyroptosis in ocular tissues. Taken together, our findings indicate that miR-223-3p serves as an important regulator in M1 macrophage polarization and pyroptosis, thereby alleviating the inflammatory response in uveitis.

[Research Progress of Mitochondrial Dynamics in Leukemia --Review].

Mitochondria is one of the most important organelles of eukaryotic cells, which is closely related to cell proliferation, apoptosis, autophagy and other life processes. Mitochondrias in biological cells are actually in a highly dynamic state. The fusion and division of mitochondria and their secondary effects play an important role in the regulation of cell life. As a malignant disease of hematopoietic system, leukemia is characterized by excessive proliferation, limited apoptosis, abnormal autophagy and other abnormal cell regulation. Therefore, abnormal mitochondrial dynamics regulation may play a key role in the pathogenesis of leukemia, refractory and drug resistance of leukemia. The article reviews the role of mitochondrial dynamics and abnormal regulation in the pathogenesis and development of leukemia, and provides a theoretical basis for the research on the regulation of mitochondrial dynamics in leukemia.

Zinc oxide nanoparticles induce toxicity in diffuse large B-cell lymphoma cell line U2932 via activating PINK1/Parkin-mediated mitophagy.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma. Zinc oxide (ZnO) nanoparticles have excellent anti-tumor properties in the biomedical field. The present study aimed to explore the underlying mechanism by which ZnO nanoparticles induce toxicity in DLBCL cells (U2932) via the PINK1/Parkin-mediated mitophagy pathway. After U2932 cells were exposed to various concentrations of ZnO nanoparticles, the cell survival rate, reactive oxygen species (ROS) generation, cell cycle arrest, and changes in the expression of PINK1, Parkin, P62, and LC3 were monitored. Moreover, we investigated monodansylcadaverine (MDC) fluorescence intensity and autophagosome and further validated the results using the autophagy inhibitor 3-methyladenine (3-MA). The results showed that ZnO nanoparticles could effectively inhibit the proliferation of U2932 cells and induce cell cycle arrest at the G0/G1 phases. Moreover, ZnO nanoparticles significantly increased ROS production, MDC fluorescence intensity, autophagosome formation, and the expression of PINK1, Parkin, and LC3, and decreased the expression of P62 in U2932 cells. In contrast, the autophagy level was reduced after the intervention of the 3-MA. Overall, ZnO nanoparticles can trigger PINK1/Parkin-mediated mitophagy signaling in U2932 cells, which may be a potential therapeutic approach for DLBCL.

Glucocorticoids improve the balance of M1/M2 macrophage polarization in experimental autoimmune uveitis through the P38MAPK-MEF2C axis.

Uveitis is a common ocular disease that can induce serious complications and sequelae. It is one of the major causes of blindness. Currently, mounting evidence suggests that glucocorticoids (GCs) can suppress ocular inflammation and promote the healing of damaged ocular tissues, but the underlying mechanism remains unclear. The present study aimed to elucidate the mechanism by which GCs modulate the homeostasis of M1/M2 macrophage polarization in experimental autoimmune uveitis (EAU) through the p38MAPK-MEF2C axis. Female Lewis rats were randomly divided into four groups: a normal control (NC) group, an EAU group, an EAU + glucocorticoid (EAU + GC) group, and an EAU + p38MAPK inhibitor (EAU + SB) group. The EAU model was induced in EAU, EAU + GC, and EAU + SB groups, followed by the treatments of normal saline, GC (predisione), and SB203580, respectively. The findings demonstrated that the rats in GC and SB groups had much less ocular inflammation, and the clinical and pathological scores decreased. Further research revealed that GC and SB treatment could inhibit iNOS and CD86 expression while promoting Arg-1 and CD206 secretion in IRBP-induced uveitis rats. Moreover, we found that the role of GC was similar to the results of SB203580, but the role of GC was masked by the C16-PAF (a p38MAPK activator) treatment. Molecular docking and western blot results confirmed that GC's therapeutic action against EAU is mediated via the p38MAPK-MEF2C axis. It regulates macrophage polarization by encouraging M1 to M2 transition and releasing anti-inflammatory factors.

Prednisone acetate modulates Th1/Th2 and Th17/Treg cell homeostasis in experimental autoimmune uveitis via orchestrating the Notch signaling pathway.

Uveitis is an immune eye disease that can seriously impair vision. Glucocorticoids (GCS) have been extensively used to treat uveitis, though the mechanisms have not been fully elucidated. In this study, we investigated the regulatory effects of prednisone acetate (PA) on the Th1/Th2 and Th17/Treg balance in experimental autoimmune uveitis (EAU) through modulating the Notch signaling pathway. Briefly, Lewis rats were randomly divided into the normal control (NC), EAU, and EAU + PA groups. Rats in EAU and EAU + PA groups were induced EAU, while those in the EAU + PA group were treated with PA. Clinical and histopathological scores were employed to assess the progression of EAU. The expression levels of Notch signaling-related molecules (Notch1, Notch2, Dll3, Dll4, and Rbpj) and Th-associated cytokines (IFN-γ, IL-4, IL-10, and IL-17) were assessed via quantitative PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA). In addition, the frequencies of Th1, Th2, Th17 and Treg cells were detected by flow cytometry. These experimental results indicated that activation of the Notch signaling pathway occurred in EAU rats and resulted in a severe imbalance of the Th17/Treg and Th1/Th2 ratios. PA treatment significantly alleviated ocular inflammation, inhibited activation of the Notch signaling pathway, and declined Th1, and Th17 cell differentiation, thereby restoring the Th1/Th2 and Th17/Treg balance. Collectively, PA can positively enhance the systemic immune response and improve the intraocular microenvironmental homeostasis by inhibiting activation of the Notch signaling pathway and by restoring Th1/Th2 and Th17/Treg balance, thus achieving the goal of treating uveitis.

High Expression of ACOT2 Predicts Worse Overall Survival and Abnormal Lipid Metabolism: A Potential Target for Acute Myeloid Leukemia.

Acyl-CoA thioesterase (ACOT) plays a considerable role in lipid metabolism, which is closely related to the occurrence and development of cancer, nevertheless, its role has not been fully elucidated in acute myeloid leukemia (AML). To explore the role of ACOT2 in AML and to provide a potential therapeutic target for AML, the expression pattern of ACOT was investigated based on the TNMplot, Gene Expression Profiling Interactive Analysis (GEPIA), and Cancer Cell Line Encyclopedia (CCLE) database, and diagnostic value, prognostic value, and clinical phenotype of ACOT were explored based on data from The Cancer Genome Atlas (TCGA). Functional annotation and enrichment analysis of the common targets between ACOT2 coexpressed and AML-related genes were further performed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) analyses. The protein-protein interaction (PPI) network of ACOT2 coexpressed genes and functional ACOT2-related metabolites association network were constructed based on GeneMANIA and Human Metabolome Database. Among ACOTs, ACOT2 was highly expressed in AML compared to normal control subjects according to TNMplot, GEPIA, and CCLE database, which was significantly associated with poor overall survival (OS) in AML (P=0.003). Moreover, ACOT2 exhibited excellent diagnostic efficiency for AML (AUC: 1.000) and related to French-American-British (FAB) classification and cytogenetics. GO, KEGG, and GSEA analyses of 71 common targets between ACOT2 coexpressed and AML-related genes revealed that ACOT2 is closely related to ACOT1, ACOT4, enoyl-acyl carrier protein reductase, mitochondrial (MECR), puromycin-sensitive aminopeptidase (NPEPPS), SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1), and long-chain fatty acid-CoA ligase 1 (ACSL1) in PPI network, and plays a significant role in lipid metabolism, that is, involved in fatty acid elongation and biosynthesis of unsaturated fatty acids. Collectively, the increase of ACOT2 may be an important characteristic of worse OS and abnormal lipid metabolism, suggesting that ACOT2 may become a potential therapeutic target for AML.

Realgar (As4S4), a traditional Chinese medicine, induces acute promyelocytic leukemia cell death via the Bcl-2/Bax/Cyt-C/AIF signaling pathway in vitro.

Acute promyelocytic leukemia (APL) is a specific subtype of acute myelogenous leukemia (AML) characterized by the proliferation of abnormal promyelocytes. Realgar, a Chinese medicine containing arsenic, can be taken orally. Traditional Chinese medicine physicians have employed realgar to treat APL for over a thousand years. Therefore, realgar may be a promising candidate for the treatment of APL. Nevertheless, the underlying mechanism behind realgar therapy is largely unclear. The present study aimed to investigate the effect of realgar on cell death in the APL cell line (NB4) in vitro and to elucidate the underlying mechanism. In this study, after APL cells were treated with different concentrations of realgar, the cell survival rate, apoptotic assay, morphological changes, ATP levels and cell cycle arrest were assessed. The expression of Bcl-2, Bax, Cytochrome C (Cyt-C) and apoptosis-inducing factor (AIF) at the mRNA and protein levels were also measured by immunofluorescence, quantitative PCR (qPCR) and Western blotting. We found that realgar could significantly inhibit APL cell proliferation and cell death in a time- and dose-dependent manner. Realgar effectively decreased the ATP levels in APL cells. Realgar also induced APL cell cycle arrest at the S and G2/M phases. Following realgar treatment, the mRNA and protein levels of Bcl-2 were significantly downregulated, whereas the levels of Bax, Cyt-C, and AIF were significantly upregulated. In summary, realgar can induce APL cell death via the Bcl-2/Bax/Cyt-C/AIF signaling pathway, suggesting that realgar may be an effective therapeutic for APL.

Clinical significance and potential mechanism of heat shock factor 1 in acute myeloid leukemia.

BACKGROUND: Heat shock factor 1 (HSF1) is now considered to have the potential to be used as a prognostic biomarker in cancers. However, its clinical significance and potential function in acute myeloid leukemia (AML) remain underexplored. METHODS: In this study, the expression pattern and clinical significance of HSF1 in AML were examined by integrating data from databases including The Cancer Genome Atlas (TCGA), The Genotype-Tissue Expression (GTEx), Vizome, Cancer Cell Line Encyclopedia (CCLE) and Gene Expression Omnibus (GEO). Linkedomics was applied to collect HSF1-related genes in AML. GeneMANIA was applied to outline HSF1-related functional networks. CancerSEA analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene Set Enrichment Analysis (GSEA) were performed to mine the potential mechanism of HSF1 in leukemogenesis. Single-sample Gene Set Enrichment Analysis (ssGSEA) was applied to explore the correlation between HSF1 and infiltrating immune cells in AML. RESULTS: HSF1 expression was elevated in AML compared to healthy controls and indicate a poor overall survival. HSF1 expression was significantly correlated with patients age, associated with patient survival in subgroup of bone marrow blasts (%) >20. Functional analyses indicated that HSF1 plays a role in the metastatic status of AML, and is involved in inflammation-related pathways and biological processes. HSF1 expression was significantly correlated with the immune infiltration of nature killer cells and T cell population. CONCLUSION: HSF1 plays a vital role in the molecular network of AML pathogenesis, and has the potential to be a biomarker for prognosis prediction.

Induced effect of zinc oxide nanoparticles on human acute myeloid leukemia cell apoptosis by regulating mitochondrial division.

Zinc oxide nanoparticles (ZnO NPs) have exhibited excellent anti-tumor properties; the present study aimed to elucidate the underlying mechanism of ZnO NPs induced apoptosis in acute myeloid leukemia (AML) cells by regulating mitochondrial division. THP-1 cells, an AML cell line, were first incubated with different concentrations of ZnO NPs for 24 hr. Next, the expression of Drp-1, Bcl-2, Bax mRNA, and protein was detected, and the effects of ZnO NPs on the levels of reactive oxygen species (ROS), mitochondrial membrane potential (Δψm), apoptosis, and ATP generation in THP-1 cells were measured. Moreover, the effect of Drp-1 inhibitor Mdivi-1 and ZnO NPs on THP-1 cells was also detected. The results showed that the THP-1 cells survival rate decreased with the increment of ZnO NPs concentration and incubation time in a dose- and time-dependent manner. ZnO NPs can reduce the cell Δψm and ATP levels, induce ROS production, and increase the levels of mitochondrial division and apoptosis. In contrast, the apoptotic level was significantly reduced after intervention of Drp-1 inhibitor, suggesting that ZnO NPs can induce the apoptosis of THP-1 cells by regulating mitochondrial division. Overall, ZnO NPs may provide a new basis and idea for treating human acute myeloid leukemia in clinical practice.

Association between anti-fibrillin-2 protein induced retinal degeneration via intravitreous delivery and activated TGF-ß signalling in mice.

Fibrillin-2 (FBN2) is a major component of tissue microfibrils, and the decrease of FBN2 perturbs the signalling events mediated by transforming growth factor-ß (TGF-ß), thereby playing a role in macular degeneration. However, the association between the retinal degeneration resulting from the abnormality of FBN2 and the activation of TGF-ß signalling has not been fully addressed. In the present study, the mice were divided into a normal control group (NC group), a phosphate-buffered saline (PBS) injection group (PBS group), and an anti-FBN2 protein injection group (anti-FBN2 group), and the mice in PBS and anti-FBN2 groups received the relevant treatment via the intravitreal injection once a week for three consecutive weeks. One week later after injection, the retinal morphology and visual function of the fundus were detected. Further, the expression of FBN2, TGF-ß1, TGF-ß2 and TGF-ß3 in retina was measured using quantitative polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA), respectively. As a result, fundus examination suggests that after intravitreous injection of anti-FBN2 protein, there were a large patchy yellow white degeneration region and numerous pigmentations in the retina in anti-FBN2-treated mice; by contrast, there was no apparent change in mice from the NC and PBS groups. The retina suffered markedly damage, and the thickness of whole retina and outer nuclear layer markedly thinned. The expression of FBN2 was decreased whereas the levels of TGF-ß1, TGF-ß2 and TGF-ß3 were upregulated. Together, our findings indicate that the intravitreous delivery of anti-FBN2 protein could induce retina degeneration in mice, accompanied by the higher activated TGF-ß. The retinal degeneration mouse model established will provide a platform for the investigation of the retinal diseases.

Efficacy and safety of selinexor in the treatment of AML: A protocol for systematic review and meta-analysis.

BACKGROUND: Acute myeloid leukemia (AML) is the most common leukemia among the adult population and accounts for about 80% of all cases. Despite advancements in therapeutic regimens, the prognosis remains very poor, especially in the elderly population. Selinexor is a first-in-class, oral, small molecule Exportin-1 inhibitor that is being developed for the treatment of a variety of cancers, including AML. The efficacy and safety issues of selinexor in the treatment of AML are still the focus of attention. Therefore, we conducted a meta-analysis to evaluate the efficacy and safety of selinexor in the treatment of AML. METHODS: According to the search strategy, regardless of publication date or language, randomized controlled trials of selinexor for AML will be retrieved from 8 databases. First of all, the literature was screened according to the eligibility criteria, and use the Cochrane Collaboration's tool to assess the quality of the included literature. Then, using Rev Man 5.3 and STATA 14.2 software for traditional meta-analysis. Finally, the evaluation of the quality of the evidence and the strength of the recommendations will adopt the Grading of Recommendations, Assessment, Development, and Evaluation method. RESULTS: This study will evaluate the efficacy and safety of selinexor for AML, thereby providing more evidence support for clinical decision-making in AML. CONCLUSION: Our research will provide more references for the clinical medication of patients with AML.

Removal of a congenital corneal dermoid through tumor excision and lamellar keratoplasty in a young child: A case report.

RATIONALE: Corneal dermoids are a rare cause of corneal opacification, consisting of abnormal mesoblastic tissue surrounded by epithelium. Here, we describe the case of a 1-year-old child who had a congenital corneal dermoid in the left eye since birth; thus, the patient underwent tumor excision followed by keratoplasty. PATIENT CONCERN: A 1-year-old girl was brought to the hospital by her parents, who had been noticing a mass on the surface of her left eyeball since birth. The patient had no other previous or concurrent disease nor family history for dermoids. CLINICAL FINDINGS: No abnormalities were present in the cornea and the anterior and posterior segments of the right eye. Eye movement, intraocular pressure, and the position of the upper eyelid of the left eye were normal. No signs of conjunctival hyperemia were present. The tumor presented as a yellowish-pink mass with hair and veins on the surface. DIAGNOSE: The patient was initially diagnosed with a keratoconjunctival tumor of the left eye by a clinical doctor. INTERVENTIONS: Corneal tumor resection combined with keratoplasty was performed in the patient. Eye drops with 1% cyclosporine were administered 3 times per day to prevent immune rejection. OUTCOMES: Based on postoperative pathological examinations, the final diagnosis was a corneal dermoid. The patient had an uneventful healing process and rapid corneal re-epithelization. The ocular surface was stable during the follow-up visits, and no complications emerged. LESSONS: We report a rare case of congenital corneal dermoid. We learned that close follow-up is needed after surgery in such cases.

Zinc oxide nanoparticle-triggered oxidative stress and autophagy activation in human tenon fibroblasts.

Glaucoma is a leading cause of irreversible blindness worldwide due to elevated intraocular pressure, and filtering surgery can efficiently control intraocular pressure of glaucoma patients. However, failure of filtering surgery commonly results from scarring formation at the surgical site, in which fibroblast proliferation plays an essential role in the scarring process. Our previous study has demonstrated that zinc oxide (ZnO) nanoparticles could efficiently inhibit human tenon fibroblasts (HTFs) proliferation. The present study aimed to explore the underlying mechanism involved in oxidative stress and autophagy signaling in zinc oxide (ZnO) nanoparticles-induced inhibition of HTFs proliferation. In this study, we investigated the effect of ZnO nanoparticles on HTFs proliferation, mitochondrial function, ATP production and nuclear morphology. Moreover, we also explored the interactions between ZnO nanoparticles and HTFs, investigated the influence of ZnO nanoparticles on the autophagosome formation, the expression of autophagy-related 5 (Atg5), Atg12 and Becn1 (Beclin 1), and the level of light chain 3 (LC3). The results suggested that ZnO nanoparticles can efficiently inhibit HTFs proliferation, disrupt the mitochondrial function, attenuate the adenosine triphosphate (ATP) generation, and damage the nuclear morphology of HTFs. Exposure of HTFs to ZnO nanoparticles can also induce the shifted peak, elevate the expression of Atg5, Atg12 and Becn1, enhance the autophagosome formation, and promote the LC3 expression, and thus activate autophagy signaling. Overall, ZnO nanoparticles can apparently trigger oxidative stress and activate autophagy signaling in HTFs, and thus inhibit HTFs proliferation and mediate HTFs apoptosis.

Efficacy and safety of chemotherapy combined with different doses of IL-2 maintenance therapies for acute myeloid leukemia: A protocol for a Bayesian network meta-analysis.

BACKGROUND: Acute myeloid leukemia (AML) is the most common malignant tumor of the hematopoietic system, which seriously threatens the lives of patients. Most AML patients have acute onset, severe condition, and poor prognosis. The present study aimed to comprehensively evaluate the effectiveness and safety of chemotherapy combined with different doses of interleukin-2 (IL-2) maintenance treatments in AML by Bayesian network meta-analysis (NMA). METHODS: From its inception until October 2021, we will search PubMed, Cochrane Library, CNKI, Embase, and other databases to comprehensively collect randomized controlled trials (RCTs) of chemotherapy combined with different doses of IL-2 maintenance therapies for AML. Two independent researchers will complete the literature screening and data extraction according to the inclusion and exclusion criteria, and then independently conduct a bias risk assessment of all the evidence. Bayesian NMA was used to evaluate all the evidence comprehensively. Use STATA16.0 and WinBUGS1.4.3 software to process and analyze all data, and classify the quality of evidence in NMA according to grading of recommendations assessment, development, and evaluation . RESULTS: The study will evaluate the efficacy and safety of chemotherapy combined with different doses of IL-2 maintenance therapies for AML. CONCLUSION: The study will provide a basis for the efficacy and safety of chemotherapy combined with different doses of IL-2 maintenance therapies for AML. We hope that this study can provide meaningful support for clinicians and patients. PROTOCOL REGISTRATION NUMBER: INPLASY202140106. ETHICAL APPROVAL: Since the study is based on published or registered RCTs, ethical approval and patient informed consent are abandoned.

Efficacy and safety of dapagliflozin in the treatment of chronic heart failure: A protocol for systematic review and meta-analysis.

BACKGROUND: As the last link in the chain of cardiovascular events, chronic heart failure (CHF) has high morbidity, high mortality, and poor prognosis. It is one of the main causes of death and disability worldwide. As a new drug for the treatment of chronic cardiovascular disease, dapagliflozin, the efficacy, and safety issues are still the focus of attention. Therefore, we conducted a meta-analysis to evaluate the efficacy and safety of dapagliflozin in the treatment of CHF. METHODS: According to the search strategy, regardless of publication date or language, randomized controlled trials (RCTs) of dapagliflozin for CHF will be retrieved from 8 databases. First of all, the literature was screened according to the eligibility criteria, and use the Cochrane Collaboration's tool to assess the quality of the included literature. Then, using Rev Man 5.3 and STATA 14.2 software for traditional meta-analysis. Finally, the evaluation of the quality of the evidence and the strength of the recommendations will adopt the Grading of Recommendations, Assessment, Development and Evaluation method. RESULTS: This study will evaluate the efficacy and safety of dapagliflozin for CHF, thereby providing more evidence support for clinical decision-making in CHF. CONCLUSION: Our research will provide more references for the clinical medication of patients with CHF. PROTOCOL REGISTRATION NUMBER: INPLASY202150046.

Longdan Xiegan Decoction alleviates experimental autoimmune uveitis in rats by inhibiting Notch signaling pathway activation and Th17 cell differentiation.

This study aimed to investigate the dynamic effects of the traditional Chinese medicine compound Longdan Xiegan Decoction (LXD) on the inhibition of Notch signaling pathway activation and T helper (Th) cell differentiation in rats with experimental autoimmune uveitis (EAU). Based on a network pharmacology strategy, we conducted protein interaction network analysis to construct an active ingredient-disease treatment network. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were further used to screen out the possible signaling pathways regulated by LXD in the treatment of uveitis. In the subsequent functional studies, we established an EAU rat model and investigated the regulatory role of LXD in the Notch signaling pathway and Th cell differentiation in rats with EAU. Female Lewis rats were randomly divided into a normal control (NC) group, an EAU group, and an LXD group. After the induction of EAU, the ocular inflammation and pathological changes in the rats in each group were observed; for documentation, a scanning laser ophthalmoscope (SLO) was used to observe fundus inflammation on day 12 after immunization. Additionally, quantitative polymerase chain reaction (Q-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression of Notch1, DLL4, IL-10 and IL-17A in the spleen, lymph nodes and ocular tissues of each group at 0, 6, 9, 12, 15 and 18 days after immunization. In addition, the dynamic frequencies of the CD4+, CD8+, Th17 and Treg cell subsets in the spleen, lymph nodes and ocular tissues were measured by flow cytometry. We found that the Notch signaling pathway was activated and the Th17 frequency was elevated in rats with EAU, leading to disrupted CD4+/CD8+ and Th17/Treg balance. The expression of Notch1, DLL4 and IL-17 mRNA and proteins in the EAU and LXD groups reached a peak on day 12, and then gradually decreased (all P < 0.05), and the ratios of the CD4+/CD8+ and Th17/Treg also peaked on day 12. However, after treatment with LXD, the expression of Notch1, DLL4 and IL-17 mRNA and proteins was significantly decreased (all P < 0.05), and the CD4+/CD8+ and Th17/Treg ratios significantly gradually returns to balance. LXD can efficiently inhibit Th17 cell differentiation, decrease inflammatory cytokine expression, and restore the CD4+/CD8+ and Th17/Treg balance by inhibiting the activation of the Notch signaling pathway in rats with EAU, thus effectively alleviating eye inflammation, protecting eye tissue structures, and positively regulating the immune state of the whole body and the intraocular microenvironment.