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OBJECTIVE: To establish a machine learning model based on radiomics and clinical features derived from non-contrast CT to predict futile recanalization (FR) in patients with anterior circulation acute ischemic stroke (AIS) undergoing endovascular treatment. METHODS: A retrospective analysis was conducted on 174 patients who underwent endovascular treatment for acute anterior circulation ischemic stroke between January 2020 and December 2023. FR was defined as successful recanalization but poor prognosis at 90 days (modified Rankin Scale, mRS 4-6). Radiomic features were extracted from non-contrast CT and selected using the least absolute shrinkage and selection operator (LASSO) regression method. Logistic regression (LR) model was used to build models based on radiomic and clinical features. A radiomics-clinical nomogram model was developed, and the predictive performance of the models was evaluated using area under the curve (AUC), accuracy, sensitivity, and specificity. RESULTS: A total of 174 patients were included. 2016 radiomic features were extracted from non-contrast CT, and 9 features were selected to build the radiomics model. Univariate and stepwise multivariate analyses identified admission NIHSS score, hemorrhagic transformation, NLR, and admission blood glucose as independent factors for building the clinical model. The AUC of the radiomics-clinical nomogram model in the training and testing cohorts were 0.860 (95%CI 0.801-0.919) and 0.775 (95%CI 0.605-0.945), respectively. CONCLUSION: The radiomics-clinical nomogram model based on non-contrast CT demonstrated satisfactory performance in predicting futile recanalization in patients with anterior circulation acute ischemic stroke.
Subject(s)
Endovascular Procedures , Ischemic Stroke , Machine Learning , Tomography, X-Ray Computed , Humans , Male , Female , Retrospective Studies , Aged , Middle Aged , Ischemic Stroke/diagnostic imaging , Ischemic Stroke/surgery , Ischemic Stroke/therapy , Tomography, X-Ray Computed/methods , Endovascular Procedures/methods , Nomograms , Medical Futility , Prognosis , RadiomicsABSTRACT
Objective: To determine the impacts to research the impacts of pain's Specialized Pain Management Nursing Care in the perioperative period on pain symptoms and life quality of patients experiencing minimally invasive surgery for spinal injury. Method: Eighty patients with a spinal injury who underwent minimally invasive surgery in the Department of Orthopedics of Baoding No.1 Hospital from January 2018 to December 2021 were retrospectively analyzed. They were split into two groups following different nursing methods (n=40 each group). Specialized Pain Management Nursing Care were given to patients in the observation group. Those in the control group were given treated with routine care. Their pain score and nursing effect were compared, after which their quality of life, daily living ability and complication rate compared and analyzed. Results: The pain degree in the control group was considerably more than that in the observation group in the 1st postoperative period. The pain degree, which decreased in both groups, slumped more significantly in the observation group on the 2nd and 3rd postoperative days. The postoperative hospital stays and pain duration in the observation group were shorter than those in the control group (P<0.05), and the nursing effect was significantly better than that in the control group (P<0.05). After postoperative nursing intervention. Conclusion: Minimally invasive surgery integrated with the Specialized Pain Management Nursing Care can remarkably ameliorate pain after spinal injury surgery, reducing complications' incidence, and improving the life quality for patients.
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The synthesis of metal macrocycle complexes holds paramount importance in coordination and supramolecular chemistry. Toward this end, we report a new, mild, and efficient protocol for the synthesis of cyclometalated macrocycle Ir(III) complexes: [Ir(L1)](PF6) (1), [Ir(L2)](PF6) (2), and [Ir(L3)](PF6) (3), where L1 presents 10,17-dioxa-3,6-diaza-2(2,8),7(8,2)-diquinolina-1,8(1,4)-dibenzenacyclooctadecaphane, L2 is 10,13,16,19,22,25-hexaoxa-3,6-diaza-2(2,8),7(8,2)-diquinolina-1,8(1,4)-dibenzenacyclohexacosaphane, and L3 is 4-methyl-10,13,16,19,22,25-hexaoxa-3,6-diaza-2(2,8),7(8,2)-diquinolina-1,8(1,4)-dibenzenacyclohexacosaphane. This synthesis involves the preassembly of two symmetric 2-phenylquinoline arms into C-shape complexes, followed by cyclization with diamine via in situ interligand C-N cross-coupling, employing a metal ion as a template. Moreover, the synthetic yield of these cyclometalated Ir(III) complexes, tethered by an 18-crown-6 ether-like chain, is significantly enhanced in the presence of K+ ion as a template. The resultant cyclometalated macrocycle Ir(III) complexes exhibit high stability, efficient singlet oxygen generation, and superior catalytic activity for the aerobic selective oxidation of sulfides into sulfoxides under visible light irradiation in aqueous media at room temperature. The photocatalyst 2 demonstrates recyclability and can be reused at least 10 times without a significant loss of catalytic activity. These results unveil a new and complementary approach to the design and in situ synthesis of cyclometalated macrocycle Ir(III) complexes via a mild interligand-coupling strategy.
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Objective: This study aims to analyze the application effect of IMB (Information-Motivation-Behavioral skills) model rehabilitation nursing, which focuses on enhancing patient knowledge, motivation, and skills for disease management in patients with diabetes and end-stage renal disease receiving maintenance hemodialysis and its impact on the patient's nutritional status. Methods: Eighty-four patients with diabetes and end-stage renal disease undergoing maintenance hemodialysis were selected as study subjects at our hospital. All patients met the inclusion criteria and were divided into two groups based on the nursing interventions received. The control group (n=42) received routine rehabilitation nursing intervention, while the observation group (n=42) received IMB-guided rehabilitation nursing intervention. The effects of nursing intervention, psychological conditions, nutritional status, and quality of life were evaluated using standardized measurement tools. Psychological conditions were assessed using the Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS). Nutritional status was evaluated through measurements of albumin (ALB), body composition analysis (BBC), hemoglobin (Hb), triceps skinfold thickness (TSF), arm circumference (A.C.), and arm muscle circumference (AMC). Quality of life was assessed using the SF-36 Health Survey. Comparative analysis was conducted to examine the differences between the two groups in terms of the aforementioned outcomes. Results: The results of the study revealed compelling data showcasing the effectiveness of the nursing intervention. Notably, after the nursing intervention, ALB (albumin) levels in the observation group increased by 12%, indicating a significant improvement in nutritional status. This increase signifies enhanced protein synthesis and improved overall metabolic functioning among the patients. Additionally, the SF-36 scores, reflecting the quality of life, demonstrated a substantial improvement of 15 points in the observation group following the nursing intervention. This improvement indicates a significant enhancement in various aspects of health-related quality of life, such as physical functioning, mental health, social functioning, and overall well-being. Furthermore, the total nursing effective rate in the observation group was an impressive 97.62%, surpassing the 80.95% rate in the control group. This statistically significant difference (P < .05) emphasizes the superior outcomes achieved through the nursing intervention in the observation group. Moreover, when comparing psychological conditions, the SAS scores in the observation group after the nursing intervention were significantly lower than those in the control group by 8 points (P < .05). Similarly, the SDS scores in the observation group showed a significant decrease of 10 points compared to the control group (P < .05). These findings indicate a substantial reduction in anxiety and depression levels among patients in the observation group. Conclusion: The findings of this study have significant implications for patient care and highlight potential areas for future research. The results suggest that integrating IMB-guided approaches into hemodialysis care protocols could significantly enhance patient well-being. The notable improvements in nutritional status, as indicated by the increase in ALB levels, and the substantial enhancement in quality of life, as reflected by the improvement in SF-36 scores, underscore the effectiveness of the nursing intervention. These findings have important implications for clinical practice, emphasizing the need for broader implementation of IMB-guided approaches in diverse clinical settings. By incorporating these interventions into routine hemodialysis care, healthcare providers can potentially improve patient outcomes and enhance their overall quality of life. Furthermore, these results also highlight potential areas for future research. Additional studies could explore the long-term effects of the nursing intervention on patient health outcomes, sustainability of the improvements observed, and the cost-effectiveness of implementing IMB-guided approaches in hemodialysis settings. Moreover, investigating the feasibility and efficacy of these interventions in different patient populations could further expand our understanding and inform tailored approaches for specific subgroups.
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C-reactive protein (CRP) is an acute-phase protein produced by the liver in response to infection and during chronic inflammatory disorders. Systemic inflammation is a major driver of cirrhosis progression from the compensated to the decompensated stage. Previous studies have shown that pentameric CRP (pCRP) to be a weak predictor of disease severity and prognosis in patients with decompensated hepatitis B cirrhosis, with it being only helpful for identifying patients with a higher short-term risk of death under certain conditions. Accumulating evidence indicates that pCRP dissociates to and acts primarily as the monomeric conformation (mCRP) at inflammatory loci, suggesting that mCRP may be a potentially superior disease marker with higher specificity and relevance to pathogenesis. However, it is unknown whether mCRP and anti-mCRP autoantibodies are associated with disease severity, or progression in decompensated hepatitis B cirrhosis. In this study, we evaluated the serum levels of mCRP and anti-mCRP autoantibodies in patients with decompensated cirrhosis of hepatitis B and their association with disease severity and theoretical prognosis. The results showed that patients with high mCRP and anti-mCRP autoantibody levels had more severe liver damage and that coagulation function was worse in patients with high anti-mCRP autoantibodies. Analysis of the correlation between pCRP, mCRP and anti-mCRP autoantibody levels with Model for End-Stage Liver Disease (MELD), Albumin-Bilirubin (ALBI), and Child-Turcotte-Pugh (CTP) prognostic scores showed that mCRP was the most strongly correlated with MELD score, followed by anti-mCRP autoantibodies; conversely, pCRP was not significantly correlated with prognostic score. Therefore, mCRP and anti-mCRP autoantibodies may be more advantageous clinical indicators than pCRP for evaluating the pathological state of decompensated hepatitis B cirrhosis.
Subject(s)
Autoantibodies , Biomarkers , C-Reactive Protein , Liver Cirrhosis , Severity of Illness Index , Humans , C-Reactive Protein/analysis , C-Reactive Protein/metabolism , Female , Prognosis , Male , Liver Cirrhosis/immunology , Liver Cirrhosis/diagnosis , Liver Cirrhosis/blood , Liver Cirrhosis/etiology , Autoantibodies/blood , Autoantibodies/immunology , Middle Aged , Biomarkers/blood , Adult , Disease Progression , Hepatitis B/immunology , Hepatitis B/bloodABSTRACT
Objective: Through meta-analysis, this study aims to comprehensively evaluate the efficacy of single-plating and double-plating in the treatment of comminuted fractures of the distal femur. Methods: Computer searches of PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), VIP, and Wanfang digital journals were performed, and the timeframe for the searches was from the establishment of each database to July 2023 for each of the databases. Meta-analysis was performed using RevMan 5.4 software provided by the Cochrane Library, and the review process was registered in the PROSPERO database. Results: A total of ten studies were included for statistical analysis. One randomised controlled study and nine retrospective cohort studies with a total of 563 patients were included. The double-plate group was superior to the single-plate group in terms of knee mobility at 6 months postoperatively, overall postoperative complications, and the rate of healing of knee deformity. However, it increased the operation time and intraoperative bleeding, and the difference between the two groups was statistically significant (P < 0.05). There was no significant difference between the two groups in terms of excellent knee function rate, fracture healing time, plate fracture, postoperative infection, delayed fracture healing, and non-union (P ≥ 0.05). Conclusion: Double plate fixation for comminuted fractures of the distal femur can improve knee mobility at 6 months postoperatively, reduce overall postoperative complications, and decrease the incidence of malunion healing. However, it increases operative time and bleeding. Randomised studies are needed to provide strong evidence in the future.
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Recent advances have revealed that the role of the immune system is prominent in the antitumor response. In the present study, it is aimed to provide an expression profile of tumor-infiltrating lymphocytes (TILs), including mature B cells, plasma cells, and their clinical relevance in neuroblastoma. The expression of CD20 and CD138 was analyzed in the Cangelosi786 dataset (n = 769) as a training dataset and in our cohort (n = 120) as a validation cohort. CD20 high expression was positively associated with favorable overall survival (OS) and event-free survival (EFS) (OS: P < 0.001; EFS: P < 0.001) in the training dataset, whereas CD138 high expression was associated with poor OS and EFS (OS: P < 0.001; EFS: P < 0.001) in both the training and validation datasets. Accordingly, a combined pattern of CD20 and CD138 expression was developed, whereby neuroblastoma patients with CD20highCD138low expression had a consistently favorable OS and EFS compared with those with CD20lowCD138high expression in both the training and validation cohorts (P < 0.0001 and P < 0.01, respectively). Examination of potential molecular functions revealed that signaling pathways, including cytokineâcytokine receptor interactions, chemokine, and the NF-kappa B signaling pathways, were involved. Differentially expressed genes, such as BMP7, IL7R, BIRC3, CCR7, CXCR5, CCL21, and CCL19, predominantly play important roles in predicting the survival of neuroblastoma patients. Our study proposes that a new combination of CD20 and CD138 signatures is associated with neuroblastoma patient survival. The related signaling pathways reflect the close associations among the number of TILs, cytokine abundance and patient outcomes and provide therapeutic insights into neuroblastoma.
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A 28-year-old man involved in a serious motorcycle accident was admitted to our hospital with comminuted fractures of the ipsilateral femoral shaft and tibial shaft, as well as multiple fractures of the right lower limb, including the proximal fibula, medial malleolus, and the third and fourth distal metatarsals. In addition, the patient suffered a skin contusion and laceration of the right foot. On the first day of admission, this patient suddenly developed tachycardia, pyrexia, and tachypnoea, and was immediately transferred to the ICU for further treatment due to a CT-diagnosed pulmonary fat embolism (FE). As a symptomatic treatment, he received a prophylactic dose of low-molecular-weight heparin for 10 days, after which his condition improved. A Doppler ultrasound of the lower leg and a follow-up chest CT angiography were performed, which excluded any remaining thrombus and verified that the pulmonary FE had improved without deterioration. Closed-reduction and retrograde intramedullary nailing were performed for the femoral shaft fractures, while antegrade intramedullary nailing was performed for the tibial shaft fractures under general anaesthesia. In the three-year follow-up, the patient had recovered with good function of the right limb, without any respiratory discomfort. Both the femoral and tibial shaft fractures finally resolved without any further treatment. Ipsilateral femoral and tibial shaft fractures should undergo surgical stabilisation as early as possible to avoid pulmonary FEs. It is still controversial whether intramedullary nailing is suitable for floating knee injuries complicated by pulmonary FEs. However, if patients with pulmonary FEs require intramedullary nailing, we suggest that surgery should be performed after at least one week of anticoagulant use, when patient vital signs are stable and there is no sign of dyspnoea. In addition, patients should try to avoid reaming during the operation to prevent and decrease "second hit" for the lung.
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The surface chemistry of colloidal semiconductor nanocrystals (QDs) profoundly influences their physical and chemical attributes. The insulating organic shell ensuring colloidal stability impedes charge transfer, thus limiting optoelectronic applications. Exchanging these ligands with shorter inorganic ones enhances charge mobility and stability, which is pivotal for using these materials as active layers for LEDs, photodetectors, and transistors. Among those, InP QDs also serve as a model for surface chemistry investigations. This study focuses on group III metal salts as inorganic ligands for InP QDs. We explored the ligand exchange mechanism when metal halide, nitrate, and perchlorate salts of group III (Al, In Ga), common Lewis acids, are used as ligands for the conductive inks. Moreover, we compared the exchange mechanism for two starting model systems: InP QDs capped with myristate and oleylamine as X- and L-type native organic ligands, respectively. We found that all metal halide, nitrate, and perchlorate salts dissolved in polar solvents (such as n-methylformamide, dimethylformamide, dimethyl sulfoxide, H2O) with various polarity formed metal-solvent complex cations [M(Solvent)6]3+ (e.g., [Al(MFA)6]3+, [Ga(MFA)6]3+, [In(MFA)6]3+), which passivated the surface of InP QDs after the removal of the initial organic ligand. All metal halide capped InP/[M(Solvent)6]3+ QDs show excellent colloidal stability in polar solvents with high dielectric constant even after 6 months in concentrations up to 74 mg/mL. Our findings demonstrate the dominance of dissociation-complexation mechanisms in polar solvents, ensuring colloidal stability. This comprehensive understanding of InP QD surface chemistry paves the way for exploring more complex QD systems such as InAs and InSb QDs.
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A broadband and narrowband switchable terahertz (THz) absorber based on a bulk Dirac semimetal (BDS) and strontium titanate (STO) is proposed. Narrowband and broadband absorption can be switched by adjusting the Fermi level of the BDS. When the Fermi level of the BDS is 100 meV, the device is an absorber with three narrowband absorption peaks. The frequencies are 0.44, 0.86, and 1.96 THz, respectively, when the temperature of STO is 250 K. By adjusting the temperature of STO from 250 to 500 K, the blue shifts of the frequencies are approximately 0.14, 0.32, and 0.60 THz, respectively. The sensitivities of the three absorption peaks are 0.56, 1.27, and 2.38 GHz/K, respectively. When the Fermi level of the BDS is adjusted from 100 to 30 meV, the device can be switched to a broadband absorber with a bandwidth of 0.70 THz. By adjusting the temperature of STO from 250 to 500 K, the central frequency shifts from 1.40 to 1.79 THz, and the bandwidth broadens from 0.70 to 0.96 THz. The sensitivity of the central frequency is 1.57 GHz/K. The absorber also has a wide range of potential applications in multifunctional tunable devices, such as temperature sensors, stealth equipment, and filters.
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Eupyrochroa Blair, 1914 is a small genus of fire-colored beetles (Coleoptera: Pyrochroidae) with two putative species recorded from limited historical distributions in China. The two species, E. insignita (Fairmaire, 1894) and E. limbaticollis (Pic, 1909), have been distinguished on the basis of color differences in the pronotum and scutellum, characters now known to exhibit significant variability. In the present study, adult morphology of the two species was compared, and partial fragments of cytochrome c oxidase subunit I (COI) from 36 samples representing 14 pyrochroid species were obtained by extraction and a GenBank search. Nucleotide composition, genetic distance, and phylogeny were analyzed. The results of morphological and molecular analyses indicate consistency, suggesting that the two species are indistinguishable by any significant measure. Therefore, Eupyrochroa limbaticollis (Pic, 1909) is proposed as a junior synonym of E. insignita (Fairmaire, 1894). The species is also redescribed and illustrated, including both adults and larvae.
Subject(s)
Coleoptera , Animals , Phylogeny , Larva , Databases, Nucleic AcidABSTRACT
AIM: To quantitatively measure ocular morphological parameters of guinea pig with Python technology. METHODS: Thirty-six eyeballs of eighteen 3-week-old guinea pigs were measured with keratometer and photographed to obtain the horizontal, coronal, and sagittal planes respectively. The corresponding photo pixels-actual length ratio was acquired by a proportional scale. The edge coordinates were identified artificially by ginput function. Circle and conic curve fitting were applied to fit the contour of the eyeball in the sagittal, coronal and horizontal view. The curvature, curvature radius, eccentricity, tilt angle, corneal diameter, and binocular separation angle were calculated according to the geometric principles. Next, the eyeballs were removed, canny edge detection was applied to identify the contour of eyeball in vitro. The results were compared between in vivo and in vitro. RESULTS: Regarding the corneal curvature and curvature radius on the horizontal and sagittal planes, no significant differences were observed among results in vivo, in vitro, and the keratometer. The horizontal and vertical binocular separation angles were 130.6°±6.39° and 129.8°±9.58° respectively. For the corneal curvature radius and eccentricity in vivo, significant differences were observed between horizontal and vertical planes. CONCLUSION: The Graphical interface window of Python makes up the deficiency of edge detection, which requires too much definition in Matlab. There are significant differences between guinea pig and human beings, such as exotropic eye position, oblique oval eyeball, and obvious discrepancy of binoculus. This study helps evaluate objectively the ocular morphological parameters of small experimental animals in emmetropization research.
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Nicotinamide mononucleotide (NMN) has garnered substantial interest as a functional food product. Industrial NMN production relies on chemical methods, facing challenges in separation, purification, and regulatory complexities, leading to elevated prices. In contrast, NMN biosynthesis through fermentation or enzyme catalysis offers notable benefits like eco-friendliness, recyclability, and efficiency, positioning it as a primary avenue for future NMN synthesis. Enzymatic NMN synthesis encompasses the nicotinamide-initial route and nicotinamide ribose-initial routes. Key among these is nicotinamide riboside kinase (NRK), pivotal in the latter route. The NRK-mediated biosynthesis is emerging as a prominent trend due to its streamlined route, simplicity, and precise specificity. The essential aspect is to obtain an engineered NRK that exhibits elevated activity and robust stability. This review comprehensively assesses diverse NMN synthesis methods, offering valuable insights into efficient, sustainable, and economical production routes. It spotlights the emerging NRK-mediated biosynthesis pathway and its significance. The establishment of an adenosine triphosphate (ATP) regeneration system plays a pivotal role in enhancing NMN synthesis efficiency through NRK-catalyzed routes. The review aims to be a reference for researchers developing green and sustainable NMN synthesis, as well as those optimizing NMN production.
Subject(s)
Adenosine Triphosphate , Nicotinamide Mononucleotide , Nicotinamide Mononucleotide/metabolism , Adenosine Triphosphate/metabolism , Biocatalysis , NAD/metabolismABSTRACT
PURPOSE: Anti-gamma-aminobutyric acid B receptor (GABABR) encephalitis is an uncommon form of autoimmune encephalitis associated with a poor prognosis and a high fatality rate. We aim to find diagnostic markers for anti- GABABR encephalitis as well as the effects of immune cell infiltration on this pathology. METHODS: For quantitative proteomic analysis, isobaric tags for relative and absolute quantitation were used in conjunction with LC-MS/MS analysis. To conduct functional correlation analyses, differentially expressed proteins (DEPs) were identified. Following that, we used bioinformatics analysis to screen for and determine the diagnostic signatures of anti- GABABR encephalitis. ROC curves were used to evaluate the diagnostic values. To assess the inflammatory status of anti- GABABR encephalitis, we used cell-type identification by estimating relative subsets of the RNA transcript (CIBERSORT) and explored the link between diagnostic markers and infiltrating immune cells. RESULTS: Overall, 108 robust DEPs (47 upregulated and 61 downregulated) were identified, of which 11 were immune related. The most impressively enriched pathways were complemented and coagulation cascades, actin cytoskeleton regulation, and cholesterol metabolism; GSEA revealed that the enriched pathways were considerably differentially connected to immune modulation. Eleven immune-related DEPs were chosen for further investigation. We developed a novel diagnostic model based on CSF1R and AZGP1 serum levels using ROC analysis (area under the ROC curve = 1). M1 macrophages and activated natural killer cells are likely to play a role in course of anti- GABABR encephalitis. CONCLUSION: We identified CSF1R and AZGP1 are possible anti-GABABR encephalitis diagnostic indicators, and immune cell infiltration may have a significant impact on the development and occurrence of anti- GABABR encephalitis.
Subject(s)
Encephalitis , gamma-Aminobutyric Acid , Humans , Autoantibodies , Chromatography, Liquid , Proteomics , Receptors, GABA-B , Tandem Mass SpectrometryABSTRACT
BACKGROUND: The repair and reconstruction of medial meniscus posterior root tears (MMPRTs) is an important issue in the field of orthopedic sports medicine. This study reports the first application of arthroscopic linear chain fixation for the treatment of MMPRTs. CASE PRESENTATION: A 78-year-old female patient presented with a 1.5-month history of right knee pain accompanied by a locked facet joint. The patient underwent surgery with the new linear chain fixation method. In this method, the suture and the loop part of the buckle-strap titanium plate were combined into a linear chain mechanical complex, and the tension of the posterior root stump was gradually increased by pulling on the two attachment lines at the external mouth of the tibial tunnel. The postoperative Lysholm score was 89, and the visual analogue scale score was 0.9, indicating a significant improvement in knee joint function. At the 7-month and 1-year post-surgery follow-up, physical and MRI examinations confirmed satisfactory healing of the MMPRTs. CONCLUSION: This surgical approach offers several benefits, including a simplified instrumentation setup, preservation of natural anatomical structures, and reliable residual stump fixation. It has the potential for clinical implementation.
Subject(s)
Menisci, Tibial , Tibial Meniscus Injuries , Female , Humans , Aged , Menisci, Tibial/diagnostic imaging , Menisci, Tibial/surgery , Arthroscopy/methods , Tibial Meniscus Injuries/diagnostic imaging , Tibial Meniscus Injuries/surgery , Knee Joint/surgery , Tibia , RuptureABSTRACT
AIM: To evaluate the efficacy and safety of perfluoro-n-octane (PFO) for ophthalmic surgery versus F-Octane as an intraoperative tamponade in pars plana vitrectomy (PPV) in management of retinal detachment. METHODS: This multicenter, prospective, randomized, double-masked, parallel-controlled, non-inferiority trial was conducted in three ophthalmology clinical centers in China. Patients with retinal detachment, who were eligible for PPV were consecutively enrolled. Participants were assigned to PFO for ophthalmic surgery or F-Octane for intraocular tamponade in a 1:1 ratio. Best-corrected visual acuity (BCVA), intraocular pressure (IOP) measurement, and dilated fundus examination were performed preoperatively and at 1, 7±1, 28±3d postoperatively. The primary outcome was complete retinal reattachment rate at postoperative day one. The non-inferiority margin was set at 9.8%. The secondary outcomes included intraoperative retinal reattachment rate, and mean changes in IOP and BCVA from baseline to 1, 7±1, 28±3d postoperatively, respectively. Safety analyses were presented for all randomly assigned participates in this study. RESULTS: Totally 124 eligible patients completed the study between Mar. 14, 2016 and Jun. 7, 2017. Sixty of them were randomly assigned to the PFO for ophthalmic surgery group, and 64 were assigned to the F-Octane group. Baseline characteristics were comparable between the two groups. Both groups achieved 100% retinal reattachment at postoperative day one (difference 0, 95%CI: -6.21% to 5.75%, P=1). The pre-defined noninferiority criterion was met. No significant difference was observed in intraoperative retinal reattachment rate (difference 1.77%, P=0.61), mean changes in IOP (difference 0.36, -0.09, 2.22 mm Hg at 1, 7±1, 28±3d postoperatively, with all P>0.05) and BCVA (difference 0.04, -0.02, 0.06 logMAR at 1, 7±1, 28±3d postoperatively, all P>0.05) between the two groups. No apparent adverse events related to the utilization of PFO were reported. CONCLUSION: In patients with retinal detachment undergoing PPV, PFO for ophthalmic surgery is non-inferior to F-Octane as an intraocular tamponade, and both are safe and well-tolerated.
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Bacoside A (gypenoside, Gyp) is a potent bioactive compound derived from Gynostemma pentaphyllum, known to exert inhibitory effects on various malignant tumors. However, the effects of Gyp on glioma as well as the underlying mechanisms remain unclear. In the present study, we first conducted a comprehensive investigation into the anti-glioma potential of gypenosides using network pharmacology to identify potential glioma-related targets. Protein-protein interaction networks were assembled, and GO and KEGG enrichment analyses were performed for shared targets. Experimental validation involved assessing the viability of U251 and U87 cell lines using the MTS method. Furthermore, trans-well and scratch migration assays evaluated the cell migration, while flow cytometry and Hoechst 33342 staining were utilized for apoptosis assessment. The study also monitored changes in autophagy flow through fluorescence microscopy. The expression levels of proteins pertinent to migration, apoptosis, and autophagy were tested using Western blotting. Findings revealed that Gyp upregulated apoptosis-related proteins (Bax and cleaved caspase-9), downregulated anti-apoptotic protein Bcl-2, and migration-associated matrix metalloproteinases (MMP-2 and MMP-9). Furthermore, autophagy-related proteins (Beclin1 and LC3 II) were upregulated, and p62 protein expression was downregulated. Gyp displayed considerable potential in suppressing glioma progression by inhibiting cell proliferation, invasion, and migration and promoting apoptosis and autophagy. Gyp may offer potential clinical therapeutic choices in glioma management.
Subject(s)
Apoptosis , Glioma , Saponins , Triterpenes , Humans , Glioma/drug therapy , Glioma/pathology , Apoptosis Regulatory Proteins/metabolism , Cell Proliferation , Autophagy , Cell Line, TumorABSTRACT
The lateral parabrachial nucleus (LPBN) is known to play a key role in relaying noxious information from the spinal cord to the brain. Different LPBN efferent mediate different aspects of the nocifensive response. However, the function of the LPBN â lateral hypothalamus (LH) circuit in response to noxious stimuli has remained unknown. Here, we show that LPBN â LH circuit is activated by noxious stimuli. Interestingly, either activation or inhibition of this circuit induced analgesia. Optogenetic activation of LPBN afferents in the LH elicited spontaneous jumping and induced place aversion. Optogenetic inhibition inhibited jumping behavior to noxious heat. Ablation of LH glutamatergic neurons could abolish light-evoked analgesia and jumping behavior. Our study revealed a role for the LPBN â LH pathway in nocifensive behaviors.
Subject(s)
Hypothalamic Area, Lateral , Parabrachial Nucleus , Humans , Parabrachial Nucleus/physiology , Pain/metabolism , Brain , Neurons/metabolismABSTRACT
BACKGROUND: Anti-IL-5 monoclonal antibodies (mAbs) targeting IL-5 or IL-5 R α (including mepolizumab, benralizumab, and reslizumab) are widely used for inflammatory diseases such as asthma, eosinophilia, and polyangiitis. However, real-world data regarding its safety in a large sample population are incomplete. So, we evaluated the safety of anti-IL-5 mAbs by pharmacovigilance analyzes based on related adverse events (AEs) from the FDA Adverse Event Reporting System (FAERS). METHODS: In disproportionality analysis, four algorithms were employed to detect the signals of anti-IL-5 mAbs from the FAERS between 2016 and 2022. In addition, we also used MYSQL 8.0, Navicat Premium 15, and Microsoft EXCEL 2019 to analyze the signals of anti-IL-5 mAbs systematically. RESULTS: There are 9,476,351 reports collected from the FAERS database, of which 22,174 reports listed anti-IL-5 mAbs as the 'primary suspected (PS)' drug. A total of 59 (20 new signals, mepolizumab) and 62 (19 new signals, benralizumab) significant disproportionality preferred terms (PTs) conforming to the four algorithms were retained synchronously. Finally, we detected that the anti-IL-5 mAbs-induced AEs occurred in 31 organ systems (mepolizumab) and 30 organ systems (benralizumab). For mepolizumab and reslizumab, unexpected and new significant PTs of AEs were found, such as asthmatic crisis, chronic obstructive pulmonary disease (COPD), pneumonia, COVID-19, pneumothorax, adrenal insufficiency and so on. Notably, the risk signal of asthmatic crisis for mepolizumab was stronger than benralizumab (ROR 108.04 [95%CI, 96.09-121.47] vs 26.83 [95%CI, 18.91-38.06]). Comparing with mepolizumab and benralizumab, we found the proportion of serious adverse events in mepolizumab was both greater than benralizumab in each age group (≤20, 20-65, and ≥ 65). The median onset time of mepolizumab was 280 days (interquartile range [IQR] 1-367 days). CONCLUSION: Analysis of FAERS data identified anti-IL-5 mAbs-associated AEs, and our findings supported continuous clinical monitoring, pharmacovigilance, and further studies of anti-IL-5 mAbs. In addition, clinicians may be more aware of the limitations of use in package inserts of anti-IL-5 mAbs: Not for relief of acute bronchospasm or status asthmaticus. Because of some limitations in the FAERS such as self-reports from patients and other confounding factors, the safety of anti-IL-5 mAbs needed more studies in different dimensions, especially the risk of cancer.