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1.
Retina ; 44(4): 680-688, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38011844

ABSTRACT

PURPOSE: To investigate the effectiveness of two regimens of ranibizumab-assisted pars plana vitrectomy in the treatment of patients with proliferative diabetic retinopathy. METHODS: This is a prospective, 6-month, randomized controlled trial. Eighty patients with 87 eyes requiring pars plana vitrectomy treatment for proliferative diabetic retinopathy were included and randomly divided into a 1.0-mg injection group and a 0.5-mg injection group. The ranibizumab was delivered intraoperatively, at the close of surgery. The vitreous hemorrhage grade, best-corrected visual acuity, central macular thickness, and safety data were assessed to Month 6. RESULTS: The 1.0-mg injection group had a milder grade and a lower reoccurrence rate of early postoperatively vitreous hemorrhage than the 0.5-mg injection group (35.0% and 63.4%, respectively, P = 0.0195). The mean best-corrected visual acuity of two groups was significantly improved from baseline to 6 months after surgery, 1.60 ± 0.72 Logarithm of the Minimum Angle of Resolution (LogMAR) (<20/200) to 0.47 ± 0.49 LogMAR (20/59) for the 1.0-mg injection group and 1.51 ± 0.69 LogMAR (<20/200) to 0.50 ± 0.31 LogMAR (20/63) for the 0.5-mg injection group, but there was no significant difference between the two groups ( P = 0.74). There was no significant difference in the mean decrease in central macular thickness and probability of postoperative adverse events between the two groups. CONCLUSION: Intravitreal injection of 1.0 mg of ranibizumab after pars plana vitrectomy compared with the recommended dose of 0.5 mg significantly reduced the recurrence and severity of early postoperative vitreous hemorrhage in patients with proliferative diabetic retinopathy. It also contributed to the early recovery of visual acuity after surgery and did not increase postoperative adverse events.


Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Humans , Diabetic Retinopathy/drug therapy , Intravitreal Injections , Prospective Studies , Ranibizumab/adverse effects , Ranibizumab/therapeutic use , Treatment Outcome , Vitrectomy/adverse effects , Vitreous Hemorrhage/surgery
2.
Pharmacol Res ; 187: 106559, 2023 01.
Article in English | MEDLINE | ID: mdl-36403720

ABSTRACT

Retinal Müller glial dysfunction and intracellular edema are important mechanisms leading to diabetic macular edema (DME). Aquaporin 11 (AQP11) is primarily expressed in Müller glia with unclear functions. This study aims to explore the role of AQP11 in the pathogenesis of intracellular edema of Müller glia in diabetic retinopathy (DR). Here, we found that AQP11 expression, primarily located at the endfeet of Müller glia, was down-regulated with diabetes progression, accompanied by intracellular edema, which was alleviated by intravitreal injection of lentivirus-mediated AQP11 overexpression. Similarly, intracellular edema of hypoxia-treated rat Müller cell line (rMC-1) was aggravated by AQP11 inhibition, while attenuated by AQP11 overexpression, accompanied by enhanced function in glutamate metabolism and reduced cell death. The down-regulation of AQP11 was also verified in the Müller glia from the epiretinal membranes (ERMs) of proliferative DR (PDR) patients. Mechanistically, down-regulation of AQP11 in DR was mediated by the HIF-1α-dependent and independent miRNA-AQP11 axis. Overall, we deciphered the AQP11 down-regulation, mediated by miRNA-AQP11 axis, resulted in Müller drainage dysfunction and subsequent intracellular edema in DR, which was partially reversed by AQP11 overexpression. Our findings propose a novel mechanism for the pathogenesis of DME, thus targeting AQP11 regulation provides a new therapeutic strategy for DME.


Subject(s)
Aquaporins , Diabetes Mellitus , Diabetic Retinopathy , Macular Edema , MicroRNAs , Rats , Animals , Diabetic Retinopathy/pathology , MicroRNAs/genetics , Down-Regulation , Aquaporins/metabolism
3.
Inorg Chem ; 62(20): 7617-7621, 2023 May 22.
Article in English | MEDLINE | ID: mdl-37171080

ABSTRACT

Luminescent metal-organic frameworks (MOFs) are emerging as one of several promising materials to study light-harvesting and energy-transfer processes. However, it is still a big challenge to tune and direct energy transfer in luminescent MOFs-based light-harvesting system. Herein, a series of new light-harvesting zinc-based luminescent MOFs with seh underlying topology were reported by successfully integrating 2,1,3-benzothiadiazole and its derivative-based carboxylic acids and pyridine-contained linkers into one structure. The strong spectra overlap between the emission and absorption spectra of carboxylic acids and pyridine-type linkers afforded an ideal platform to realize efficient energy transfer from the blue to near-infrared range. This work provides a novel approach to the rational design and synthesis of MOFs-based multicomponent light-harvesting materials with tunable energy transfer to mimic natural photosynthetic processes.

4.
Arch Orthop Trauma Surg ; 143(7): 3975-3984, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36348086

ABSTRACT

INTRODUCTION: Surgery is still an effective treatment option for adult degenerative scoliosis (ADS), but how to predict patients' significant amount of the improvement in quality of life remains unclear. The previous studies included an inhomogeneous population. This study aimed to report the results about concentrating on the amount of immediate changes in spinopelvic radiographic parameters to predict the amount of mid-term improvement in quality of life in ADS patients. MATERIALS AND METHODS: Pre-operative and immediately post-operative radiographic parameters included Cobb angle, coronal vertical axis (CVA), sagittal vertical axis (SVA), lumbar lordosis (LL), thoracic kyphosis (TK), pelvic tilt (PT), sacral slope (SS), pelvic incidence (PI) and LL/PI matching (PI-LL). Quality of life scores were evaluated pre-operatively and at the final follow-up using Oswestry Disability Index (ODI) and visual analogue scale (VAS). The amount of immediate changes in spinopelvic radiographic parameters (Δ) and the amount of mid-term improvement in quality of life (Δ) were defined, respectively. RESULTS: Patients showed significant change in radiographic parameters, ODI and VAS pre- and post-surgery, except CVA and PI. Univariate analysis showed a significant correlation between ΔTK, ΔLL, ΔCVA and the amount of mid-term improvement in quality of life, but multivariate analysis did not get a significant result. Univariate and multivariate analyses showed that ΔSVA was still a significant predictor of ΔVAS and ΔODI. The changes in the other radiographic parameters were not significant. The equations were developed by linear regression: ΔODI = 0.162 × ΔSVA - 21.592, ΔVAS = 0.034 × ΔSVA - 2.828. In the ROC curve for ΔSVA in the detection of a strong ΔODI or ΔVAS, the cut-off value of ΔSVA was - 19.855 mm and - 15.405 mm, respectively. CONCLUSIONS: This study shows that ΔSVA can predict the amount of mid-term improvement in quality of life in ADS patients. The changes in the other radiographic parameters were not significant. Two equations were yielded to estimate ΔODI and ΔVAS. ΔSVA has respective cut-off value to predict ΔODI and ΔVAS.


Subject(s)
Lordosis , Scoliosis , Animals , Humans , Adult , Scoliosis/diagnostic imaging , Scoliosis/surgery , Quality of Life , Retrospective Studies , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery
5.
Cell Biol Int ; 46(1): 129-138, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34647397

ABSTRACT

Microglial activation has been studied extensively in diabetic retinopathy. We have previously detected activation and migration of microglia in 8-week-old diabetic rat retinas. It is widely acknowledged that microglia-mediated inflammation contributes to the progression of diabetic retinopathy. However, existing cell models do not explore the role of activated microglia in vitro. In this study, microglia were subject to various conditions mimicking diabetic retinopathy, including high glucose, glyoxal, and hypoxia. Under high glucose or glyoxal treatment, microglia demonstrated only partially functional changes, while under hypoxia, microglia became fully activated showing enlarged cell bodies, enhanced migration and phagocytosis as well as increased production of pro-inflammatory factors such as cyclooxygenase-2 (COX-2), interleukin-1ß (IL-1ß), and inducible nitric oxide synthase (iNOS). The data indicate that hypoxia-treated microglia is an optimal in vitro model for exploration of microglia activation in diabetic retinopathy.


Subject(s)
Cell Movement , Diabetic Retinopathy/pathology , Microglia/pathology , Phagocytosis , Retina/pathology , Animals , Cell Hypoxia , Cell Line , Cell Movement/drug effects , Cyclooxygenase 2/genetics , Cyclooxygenase 2/metabolism , Diabetic Retinopathy/metabolism , Disease Models, Animal , Glucose/toxicity , Glyoxal/toxicity , Inflammation Mediators/metabolism , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Male , Mice , Microglia/drug effects , Microglia/metabolism , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type II/metabolism , Phagocytosis/drug effects , Rats, Sprague-Dawley , Retina/drug effects , Retina/metabolism
6.
J Pept Sci ; 28(9): e3408, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35128758

ABSTRACT

Cell-penetrating peptides (CPPs) can aid in intracellular and in vivo drug delivery. However, the mechanisms of CPP-mediated penetration remain unclear, limiting the development and further application of CPPs. Flow cytometry and laser confocal fluorescence microscopy were performed to detect the effects of different endocytosis inhibitors on the internalization of CC12 and penetratin in ARPE-19 cells. The co-localization of CPPs with the lysosome and macropinosome was detected via an endocytosis tracing experiment. The flow cytometry results showed that chlorpromazine, wortmannin, cytochalasin D, and the ATP inhibitor oligomycin had dose-dependent endocytosis-inhibitory effects on CC12. The laser confocal fluorescence results showed that oligomycin had the most significant inhibitory effect on CC12 uptake; CC12 was co-located with the lysosome, but not with the macropinosome. For penetratin, cytochalasin D and oligomycin had obvious inhibitory effects. The laser confocal fluorescence results indicated that oligomycin had the most significant inhibitory effect on penetratin uptake; the co-localization of penetratin with the lysosome was higher than that with the macropinosome. Cation-independent CC12 and cationic penetratin may be internalized into cells primarily through caveolae and clathrin-mediated endocytosis, and they are typically dependent on ATP. The transport of penetratin could be partly achieved through the direct transmembrane pathway, as the positive charge of penetratin interacts with the negative charge of the cell membrane, and partly through the endocytic pathway.


Subject(s)
Cell-Penetrating Peptides , Adenosine Triphosphate/metabolism , Carrier Proteins/metabolism , Cations/pharmacology , Cell-Penetrating Peptides/metabolism , Cell-Penetrating Peptides/pharmacology , Cytochalasin D/metabolism , Cytochalasin D/pharmacology , Endocytosis , Oligomycins/pharmacology , Transcytosis
7.
Exp Cell Res ; 407(2): 112800, 2021 10 15.
Article in English | MEDLINE | ID: mdl-34487731

ABSTRACT

PURPOSE: Increased permeability of retinal capillary endothelial cells is a key feature in the progression of diabetic retinopathy (DR). Precisely why and how diabetes causes dysfunction in retinal capillary endothelial cells is not well understood, making it challenging to explore more advanced therapeutics. METHODS: Cell proliferation was assessed by the Cell Counting Kit-8 assay. Ferroptosis was evaluated by measuring lipid reactive oxygen species levels by flow cytometry and determining malondialdehyde, superoxide dismutase, and glutathione peroxidase levels through biochemical assays. Western blot analysis and quantitative PCR were respectively used to check the expression of proteins and RNAs. Co-immunoprecipitation assays were used to confirm the interaction between TRIM46 and GPX4. RESULTS: High glucose (HG, 25 mM glucose) significantly suppressed cell growth, which could be reversed by the ferroptosis inhibitor, ferrostatin-1. HG treatment time-dependently induced ferroptosis in human retinal capillary endothelial cells (HRCECs) and induced TRIM46 expression. Lentiviral-mediated overexpression of TRIM46 decreased cell resistance against HG-induced ferroptosis, whereas knockdown showed the opposite effect. Administration of RSL3, a ferroptosis agonist, was able to reverse the protective effects of TRIM46 silencing. TRIM46 interacted with GPX4, an important enzyme that suppresses ferroptosis, and promoted GPX4 ubiquitination. Furthermore, lentiviral-mediated overexpression ofGPX4 ameliorated the effects of TRIM46 overexpression and conferred protection to cells against HG-induced ferroptosis. CONCLUSION: TRIM46 and GPX4 form a regulatory pathway that controls HG-induced ferroptosis of HRCECs. Inhibiting this pathway or sustaining the expression of GPX4 enables cells to resist damage caused by HG. We provide new mechanistic insight into the pathology of DR and identified TRIM46 and GPX4 as two molecular targets for the development of effective drugs for DR treatment.


Subject(s)
Endothelium, Vascular/pathology , Ferroptosis , Glucose/adverse effects , Growth Inhibitors/adverse effects , Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism , Retina/pathology , Tripartite Motif Proteins/metabolism , Ubiquitination , Cell Death , Cell Proliferation , Endothelium, Vascular/drug effects , Endothelium, Vascular/metabolism , Humans , Phospholipid Hydroperoxide Glutathione Peroxidase/genetics , Reactive Oxygen Species , Retina/drug effects , Retina/metabolism , Sweetening Agents/adverse effects
8.
Ophthalmic Res ; 2022 Jun 13.
Article in English | MEDLINE | ID: mdl-35697006

ABSTRACT

INTRODUCTION: To describe the hyperreflective foci (HRF) on optical coherence tomography angiography (OCTA) in diabetic macular edema (DME) with subretinal fluid (SRF) and explore the association of HRF in the outer retina with photoreceptor integrity and visual outcomes after anti-vascular endothelial growth factor (anti-VEGF) treatment. METHODS: We retrospectively reviewed 46 eyes (36 patients) with DME treated with anti-VEGF drugs. The following parameters, including best-corrected visual acuity (BCVA), central macular thickness (CMT), the height of subretinal fluid (SRF), the number of HRF in the superficial capillary plexus (SCP), deep capillary plexus (DCP), and the outer retina, as well as the integrity of external limiting membrane (ELM) and ellipsoid zone (EZ), were evaluated and compared between the baseline and after 2 monthly injections of anti-VEGF drugs. The relationship between the HRF in the outer retina and the integrity of ELM and EZ, as well as BCVA was analyzed. RESULTS: BCVA was significantly improved in DME after anti-VEGF treatment, however, for the subgroup of DME patients with SRF, visual acuity remained unchanged after anti-VEGF treatment (p < 0.05 vs. p = 0.375). The number of HRF (p < 0.05), CMT (p < 0.001), and SRF height (p < 0.001) were significantly reduced, accompanied with partial restoration of ELM and EZ integrity after anti-VEGF injection. The HRF in the outer retina was correlated with the final ELM (p = 0.036) and EZ (p = 0.004) status. The final BCVA was significantly better in eyes with intact ELM (p = 0.002) and EZ at final visit (p< 0.001). CONCLUSION: The number of HRF in outer retina was negatively associated with the microstructural restoration of ELM and EZ, as well as the visual outcome in DME patients with SRF after anti-VEGF treatment.

9.
Spinal Cord ; 60(7): 635-640, 2022 07.
Article in English | MEDLINE | ID: mdl-34588624

ABSTRACT

STUDY DESIGN: Hospital-based retrospective review. OBJECTIVE: To describe the epidemiological characteristics of traumatic spinal cord injury (TSCI) in Liaocheng, China. SETTING: Liaocheng People's Hospital. METHODS: Medical records of 338 persons with TSCI admitted to Liaocheng People's Hospital from 2013 to 2017 were reviewed. The detailed information included gender, age, marital status, occupation, time, etiology, level of injury, ASIA grade, spinal stenosis, concomitant injury, treatment, length of stay. RESULTS: Over this period, the mean age (SD) of persons with TSCI was 50.1 (14.1) years, and the male/female ratio was 3.1:1. 96.4% of all were married. The leading cause was fall, followed by motor vehicle accident (MVA). The most common level of injury was the cervical cord. ASIA grade D and A injuries were the most common, accounting for 48.5 and 29.3% respectively. Among the concomitant injuries, spinal fractures were the most common. Within 24 h, 91.1% of individuals with TSCI arrived hospital, 63.3% of all accepted surgery. CONCLUSION: The results showed that fall and MVA were the two main causes, so we should focused on preventing fall and reducing MVA. Cervical spinal stenosis can increase the risk of TSCI, so education should be provided to this population to raise their risk awareness. In addition, timely treatment was critical for TSCI, but the data showed that rescue process was not standard, so it was necessary for medical staff to popularize professional knowledge.


Subject(s)
Spinal Cord Injuries , Spinal Fractures , Spinal Stenosis , Accidents, Traffic , China/epidemiology , Female , Humans , Incidence , Male , Middle Aged , Retrospective Studies , Spinal Cord Injuries/epidemiology , Spinal Cord Injuries/etiology , Spinal Cord Injuries/therapy
10.
J Cell Physiol ; 236(8): 5848-5864, 2021 08.
Article in English | MEDLINE | ID: mdl-33432588

ABSTRACT

The pathophysiology of diabetic retinopathy (DR) was complex. Under hyperglycemic conditions, the release of proinflammatory cytokines and the adhesion of leukocytes to retinal capillaries contribute to endothelial damage and the subsequent increase in vascular permeability resulting in macular edema. Melatonin, produced in the retina to regulate redox reactions and dopamine metabolism, plays protective roles against inflammation and oxidative stress. Considering its anti-inflammatory and antioxidative properties, melatonin was speculated to exert beneficial effects in DR. In this study, we characterized the protective effects of melatonin on the inner blood-retinal barrier (iBRB), as well as the possible mechanisms in experimental DR. Results showed that in diabetic rat retinas, the leakage of iBRB and the expression of inflammatory factors (VEGF, TNF-α, IL-1ß, ICAM-1, and MMP9) increased dramatically, while the expression of tight junction proteins (ZO-1, occludin, JAM-A, and claudin-5) decreased significantly. The above changes were largely ameliorated by melatonin. The in vivo data were confirmed in vitro. In addition, the protein expressions of p38 MAPK, NF-κB, and TXNIP were upregulated significantly in diabetes and were downregulated following melatonin treatment. Melatonin could maintain the iBRB integrity by upregulating the expression of tight junction proteins via inhibiting p38/TXNIP/NF-κB pathway, thus decreasing the production of inflammatory factors. This study may shed light on the development of melatonin-based DR therapy.


Subject(s)
Blood-Retinal Barrier/drug effects , Diabetic Retinopathy/drug therapy , Melatonin/pharmacology , NF-kappa B/drug effects , Animals , Antioxidants/pharmacology , Capillary Permeability/drug effects , Diabetic Retinopathy/metabolism , Endothelial Cells/metabolism , Male , NF-kappa B/metabolism , Rats, Sprague-Dawley , Retina/drug effects , Retina/metabolism , Retinal Vessels/drug effects
11.
Biochem Biophys Res Commun ; 581: 96-102, 2021 12 03.
Article in English | MEDLINE | ID: mdl-34662809

ABSTRACT

OBJECTIVE: To examine the mechanisms of Nogo-B (RTN4B) in the protection of blood-retinal barrier in experimental diabetic retinopathy. METHODS: The level of Nogo-B in vitreous and plasma samples was detected with ELISA. Diabetes was induced in Sprague-Dawley rats with intraperitoneal injection of streptozotocin. The rats were injected intravitreally with adeno-associated virus (AAV) for knockdown the expression of Nogo-B in retina or/and as AAV negative control. The permeability of blood-retinal barrier was detected with Rhodamine-B-dextran leakage assay. The expressions of Nogo-B, junctional proteins, inflammatory factors and signaling pathways were examined with Western blot and quantitative real-time PCR. RESULTS: Nogo-B expression was significantly upregulated in clinical samples and experimental diabetic rat models. Under normal condition, Nogo-B knockdown resulted in the increased permeability of retinal blood vessels. In diabetic rat retinas, the vascular leakage was increased significantly, which was partially decreased by Nogo-B knockdown through increasing p/t-Src (Tyr529) and p/t-Akt (Ser473), and decreasing p/t-ERK1/2. CONCLUSION: Nogo-B was increased in diabetic retinopathy and silencing Nogo-B is a promising therapy for diabetic retinopathy.


Subject(s)
Diabetes Mellitus, Experimental/genetics , Diabetic Retinopathy/genetics , Phosphatidylinositol 3-Kinases/genetics , Proto-Oncogene Proteins c-akt/genetics , Receptors, Cell Surface/genetics , src-Family Kinases/genetics , Animals , Blood-Retinal Barrier/metabolism , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/metabolism , Diabetic Retinopathy/metabolism , Diabetic Retinopathy/pathology , Diabetic Retinopathy/therapy , Gene Expression Regulation , Male , Mitogen-Activated Protein Kinase 1/genetics , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/genetics , Mitogen-Activated Protein Kinase 3/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Rats , Rats, Sprague-Dawley , Receptors, Cell Surface/antagonists & inhibitors , Receptors, Cell Surface/metabolism , Retina/metabolism , Retina/pathology , Retinal Vessels/metabolism , Retinal Vessels/pathology , Signal Transduction , Streptozocin/administration & dosage , src-Family Kinases/metabolism
12.
Opt Lett ; 46(5): 1073-1076, 2021 Mar 01.
Article in English | MEDLINE | ID: mdl-33649660

ABSTRACT

We investigate dynamical generation of macroscopic nonlocal entanglements between two remote massive magnon-superconducting-circuit hybrid systems. Two fiber-coupled microwave cavities are employed to serve as an interaction channel connecting two sets of macroscopic hybrid units, each containing a magnon (hosted by an yttrium-iron-garnet sphere) and a superconducting-circuit qubit. Surprisingly, it is found that stronger coupling does not necessarily mean faster entanglement generation. The proposed hybrid system allows the existence of an optimal fiber coupling strength that requires the shortest amount of time to generate a systematic maximal entanglement. Our theoretical results are shown to be within the scope of specific parameters that can be achieved with current technology. The noise effects on the implementation of systems are also treated in a general environment, suggesting the robustness of entanglement generation. Our discrete-variable qubit-like entanglement theory of magnons may lead to direct applications in various quantum information tasks.

13.
Pharmacol Res ; 174: 105871, 2021 12.
Article in English | MEDLINE | ID: mdl-34619345

ABSTRACT

Microvascular dysfunction is the primary aetiology of visual impairment caused by diabetic retinopathy (DR). Dihydroartemisinin (DHA), the active metabolite of the antimalarials artemisinins, exhibits antiangiogenic properties in numerous diseases. Here, we investigated the function and mechanisms of DHA as a vasculoprotective agent in DR. DHA exerted its protective effect on vascular injuries in diabetic mice and inhibited cell proliferation and tube formation in human retinal microvascular endothelial cells by decreasing the level of fatty acid synthase (FASN), enhancing the malonylation of mechanistic target of rapamycin (mTOR) at lysine 1218 (K1218) and attenuating the activation of mTOR complex 1 (mTORC1). Impressively, a chemosynthetic small interfering RNA against FASN and mutagenesis of K1218 of mTOR showed therapeutic potential in suppressing cell proliferation and tube formation induced by high glucose. Notably, suppression of mTORC1 kinase activity further inhibited FASN by reducing p70S6K phosphorylation to subsequently reduce the expression of sterol regulatory element binding protein 1, which interacted directly with the FASN promoter at nucleotide positions -64 and -55. In conclusion, our study elucidated the promising effects of FASN and malonylation on vascular injuries of DR and indicated the great potential of DHA as a therapeutic approach.


Subject(s)
Artemisinins/pharmacology , Diabetes Mellitus/drug therapy , Fatty Acid Synthases/metabolism , Sterol Regulatory Element Binding Protein 1/metabolism , TOR Serine-Threonine Kinases/metabolism , Amino Acid Sequence , Animals , Cell Proliferation/drug effects , Diabetes Mellitus, Experimental , Endothelial Cells , Humans , Male , Mice, Inbred C57BL , Phosphorylation , Protein Binding , Ribosomal Protein S6 Kinases, 70-kDa/metabolism , Signal Transduction , Sirolimus/metabolism , Sterol Regulatory Element Binding Protein 1/genetics
14.
Gene Ther ; 27(9): 417-426, 2020 09.
Article in English | MEDLINE | ID: mdl-31896759

ABSTRACT

Accumulating evidence demonstrates that estrogen receptor α (ERα) and microRNAs (miRNAs) play crucial roles in intervertebral disc degeneration (IDD). However, the specific miRNA that related with ERα during IDD development remains unknown. Therefore, we aimed to explore the role of ERα-related miRNA in the IDD model. Nucleus pulposus (NP) cells were isolated from IDD patients. ERα-related miRNAs were selected and verified in NP tissues from IDD patients using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Also, the related cytokine mRNA levels were detected by qRT-PCR. Protein levels were determined by Western blot. The concentrations of inflammatory cytokines in culture supernatants were detected by enzyme-linked immunosorbent assay. MiR-203-3p was found to be upregulated in NP tissues of high-grade IDD patients compared with low-grade IDD patients, and negatively associated with ERα expression. MiR-203-3p directly targeted ERα in NP cells of IDD patients. After lipopolysaccharides (LPS) stimulation, miR-203-3p expression increased, while ERα expression decreased in NP cells. MiR-203-3p inhibition suppressed the effect of LPS on ERα expression and IDD related genes, while ERα downregulation rescued the effect of LPS. In conclusion, suppression the expression of miR-203-3p could inhibit LPS-induced human intervertebral disc inflammation and degeneration through upregulating ERα.


Subject(s)
Intervertebral Disc , MicroRNAs , Estrogen Receptor alpha , Humans , Inflammation/genetics , Lipopolysaccharides , MicroRNAs/genetics , Receptors, Estrogen
15.
Crit Care ; 24(1): 197, 2020 05 06.
Article in English | MEDLINE | ID: mdl-32375841

ABSTRACT

BACKGROUND: The use of an ultrasound-guided technique for radial arterial catheterization has not been well established in pediatric patients. We conducted a systematic review and meta-analysis to evaluate the efficacy of the ultrasound-guided technique for radial artery catheterization in pediatric populations. METHOD: A systematic review of PubMed, Medline, Embase, and the Cochrane library was performed from their date of inception to December 2019. In this meta-analysis, we conducted online searches using the search terms "ultrasonography," "ultrasonics," "ultrasound-guided," "ultrasound," "radial artery," "radial arterial," "catheter," "cannula," and "catheterization." The rate of the first-attempt and total success, mean attempts to success, mean time to success, and incidence of complications (hematomas) were extracted. Data analysis was performed with RevMan 5.3.5. RESULTS: From 7 relevant studies, 558 radial artery catheterizations were enrolled, including 274 ultrasound-guided and 284 palpation catheterizations. The ultrasound-guided technique could significantly improve the rate of first-attempt and total success (RR 1.78, 95% CI 1.46 to 2.18, P < 0.00001; RR 1.33; 95% CI 1.20 to 1.48; P < 0.00001). However, there was significant heterogeneity for the total success rate among the included studies (I2 = 67%). The ultrasound-guided radial artery catheterization was also associated with less mean attempts and mean time to success (WMD - 1.13, 95% CI - 1.58 to - 0.69; WMD - 72.97 s, 95% CI - 134.41 to - 11.52) and lower incidence of the hematomas (RR 0.17, 95% CI 0.07 to 0.41). CONCLUSIONS: The use of the ultrasound-guided technique could improve the success rate of radial arterial catheterization and reduce the incidence of hematomas in pediatric patients. However, the results should be interpreted cautiously due to the heterogeneity among the studies.


Subject(s)
Catheterization, Peripheral/methods , Ultrasonography, Interventional/methods , Catheterization, Peripheral/instrumentation , Humans , Pediatrics/instrumentation , Pediatrics/methods , Radial Artery/diagnostic imaging , Randomized Controlled Trials as Topic/statistics & numerical data , Ultrasonography, Interventional/trends , Vascular Access Devices
16.
BMC Ophthalmol ; 20(1): 390, 2020 Oct 02.
Article in English | MEDLINE | ID: mdl-33008364

ABSTRACT

BACKGROUND: The causal effects of plasma lipid concentrations and the risk of primary open angle glaucoma (POAG) are still unclear. Thus, the purpose of this study was to identify, applying a two-sample Mendelian randomization (MR) analysis, whether plasma lipid concentrations are causally associated with the risk of POAG. METHODS: Two-sample MR analysis of data from a genome-wide association study (GWAS) was performed to investigate the causal role of plasma lipid levels and POAG. A total of 185 independent single-nucleotide polymorphisms (SNPs) associated with plasma lipid levels were selected as instrumental variables (IVs). The SNPs were obtained from a meta-analysis of GWAS based on 188,577 European-ancestry individuals for MR analyses. Association with POAG for the SNPs was obtained from a GWAS conducted among the United Kingdom (UK) Biobank study participants with a total of 463,010 European-ancestry individuals. Four MR methods (inverse variance weighted [IVW], weighted mode, weighted median, and MR-Egger regression) were applied to obtain the overall causal estimate for multiple, instrumental SNPs. RESULTS: Using the IVW analysis method, no evidence was found to support a causal association between plasma LDL-C level and POAG risk (ß = - 0.00026; 95% CI = -0.00062, 0.00011; P = 0.165) with no significant heterogeneity among SNPs. The overall causal estimate between plasma LDL-C level and POAG was consistent using the other three MR methods. Using the four MR methods, no evidence of an association between plasma HDL-C (ß = 0.00023; 95% CI = -0.00015, 0.00061; P = 0.238; IVW method) or TG levels (ß = - 0.00028; 95% CI = -0.00071, 0.00015; P = 0.206; IVW method) and POAG risk was found. Sensitivity analyses did not reveal any sign of directional pleiotropy. CONCLUSIONS: The present study did not find any evidence for a causal association between plasma lipid levels and POAG risk. Further research is needed to elucidate the potential biological mechanisms to provide a reasonable interpretation for these results.


Subject(s)
Glaucoma, Open-Angle , Mendelian Randomization Analysis , Genome-Wide Association Study , Glaucoma, Open-Angle/genetics , Humans , Lipids , Polymorphism, Single Nucleotide , United Kingdom
17.
BMC Anesthesiol ; 20(1): 288, 2020 11 18.
Article in English | MEDLINE | ID: mdl-33208089

ABSTRACT

BACKGROUND: Surgical procedure usually causes serious postoperative pain and poor postoperative pain management negatively affects quality of life, function and recovery time. We aimed to investigate the role of wound infiltration with ropivacaine as an adjuvant to patient controlled analgesia (PCA) in postoperative pain control for patients undergoing transforaminal lumbar interbody fusion. METHODS: One hundred twelve patients undergoing lumbar fusion were retrospectively reviewed and divided into two groups (ropivacaine and control groups) according to whether received wound infiltration with ropivacaine or not. Visual Analogue Scale (VAS) score, analgesics consumption, number of patients requiring rescue analgesic, hospital duration and incidence of complications were recorded. Surgical trauma was assessed using operation time, intraoperative blood loss and incision length. RESULTS: The amount of sufentanil consumption in ropivacaine group at 4 h postoperatively was lower than that of control group (24.5 ± 6.0 µg vs 32.1 ± 7.0 µg, P < 0.001) and similar results were observed at 8, 12, 24, 48 and 72 h postoperatively(P < 0.001). Fewer patients required rescue analgesia within 4 to 8 h postoperatively in ropivacaine group (10/60 vs 19/52, P = 0.017). Length of postoperative hospital durations were shorter in patients receiving ropivacaine infiltration compared to control cohorts (6.9 ± 0.9 days vs 7.4 ± 0.9 days, P = 0.015). The incidence of PONV in ropivacaine group was lower than that in control group (40.4% vs 18.3%, P = 0.01). However, VAS scores were similar in two groups at each follow-up points postoperatively, and no difference was observed(P > 0.05). CONCLUSION: Wound infiltration with ropivacaine effectively reduces postoperative opioid consumption and PONV and may be a useful adjuvant to PCA to improve recovery for patients undergoing lumbar spine surgery.


Subject(s)
Analgesia, Patient-Controlled/methods , Anesthetics, Local/pharmacokinetics , Lumbar Vertebrae/surgery , Pain, Postoperative/drug therapy , Ropivacaine/pharmacokinetics , Spinal Fusion/methods , Adult , Aged , Female , Humans , Male , Middle Aged , Retrospective Studies
19.
Int Orthop ; 40(6): 1103-10, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26983411

ABSTRACT

PURPOSE: The purpose of this study was to evaluate the efficacy and safety of percutaneous pedicle screw fixation at the fractured vertebra in the treatment of thoracolumbar fractures. METHODS: Thirty-two consecutive patients were enrolled in the study. All patients received percutaneous pedicle screw fixation, and they were randomly divided into two groups to undergo either the placement of pedicle screws into the fractured vertebra (fractured group) or not (control group). The operation time and intra-operative blood loss were recorded. Oswestry disability index (ODI) questionnaire and visual analogue scale (VAS) as clinical assessments were quantified. Radiographic follow-up was defined by the vertebral body index (VBI), anterior vertebral body height (AVBH), and Cobb angle (CA). RESULTS: No significant difference was observed in the operation time and intra-operative blood loss between the two groups. Clinical results (VAS and ODI scores) showed no significant difference during all the follow-up periods. In the fractured group, there were better correction and less loss of AVBH and VBI compared with the control group. However, post-operative correction of the CA immediately after surgery and the correction loss at the final follow-up showed no significant difference between the two groups. CONCLUSION: Percutaneous screw fixation combined with intermediate screws at the fractured vertebra could more effectively restore and maintain fractured vertebral height, and is an acceptable, minimally invasive surgical choice for patients with type A thoracolumbar fractures.


Subject(s)
Fracture Fixation, Internal/methods , Minimally Invasive Surgical Procedures/methods , Pedicle Screws/adverse effects , Spinal Fractures/surgery , Adult , Female , Fracture Fixation, Internal/adverse effects , Humans , Lumbar Vertebrae/surgery , Male , Middle Aged , Minimally Invasive Surgical Procedures/adverse effects , Pain Measurement , Postoperative Complications , Prospective Studies , Thoracic Vertebrae/surgery , Visual Analog Scale
20.
Zhonghua Yi Xue Za Zhi ; 94(35): 2731-5, 2014 Sep 23.
Article in Zh | MEDLINE | ID: mdl-25533977

ABSTRACT

OBJECTIVE: To compare the clinical efficacies of single segment transforaminal lumbar interbody fusion (TLIF) with cage versus autogenous morselized bone for degenerative lumbar spinal stenosis. METHODS: A total of 87 patients undergoing single segment TLIF were randomly divided into 2 groups. A cage was implanted into intervertebral space in group A patients while autogenous morselized bone in group B patients. Operative duration, blood loss, length of stay and cost of hospitalization of two groups were recorded. They were followed up at 1 week, 12, 24 months post-operation. Oswestry disability index (ODI), visual analogue scale (VAS) fusion rates, intervertebral space and foramen height restoration, lumbar lordosis and postoperative complications were compared between two groups. RESULTS: No significant inter-group difference existed in operative duration, blood loss or length of stay. However, the average hospitalization cost in group A were 18% higher than that of group B (P < 0.05). Both groups achieved excellent clinical outcomes within 2 years. ODI, VAS score improvement rates and postoperative complication rates were not statistically different. Lumbar fusion rate was 86.7% in group A versus 85.7% in group B after 2 years. And there was no significant difference (P > 0.05). The heights of intervertebral space and foramen in group A achieved a better recovery than those of group B. Both groups had similar improvements of lumbar lordosis. CONCLUSION: For degenerative lumbar spinal stenosis, usage of interbody cage is more effective in terms of recovery of intervertebral space and foraminal height compared with usage of bone graft. However it brings no better clinical efficacy while the usage of autogenous morselized bone is more cost-effective. Two grafting methods yield similar overall clinical outcomes.


Subject(s)
Intervertebral Disc Degeneration , Spinal Stenosis , Bone Transplantation , Humans , Lumbar Vertebrae , Lumbosacral Region , Minimally Invasive Surgical Procedures , Nervous System Diseases , Pain Measurement , Postoperative Complications , Postoperative Period , Prospective Studies , Spinal Fusion , Treatment Outcome
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