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PURPOSE: This study aims to comprehensively assess the safety of Asenapine by conducting an comprehensive statistical analysis of adverse event reports in the FAERS database, with a particular focus on potential adverse reactions related to its use in the treatment of psychiatric disorders. METHODS: Event reports from the first quarter of 2009 to the third quarter of 2023 were collected and analyzed. Detailed examinations of gender, age, reporter identity, and other aspects were conducted to reveal the fundamental characteristics of Asenapine-related adverse events. Signal mining techniques were employed to systematically evaluate various adverse reactions associated with Asenapine. RESULTS: The study found that adverse event reports involving Asenapine were more common among female patients, with the age group mainly distributed between 18 and 45 years. Physicians were the primary reporters of adverse events, and psychiatric disorders, neurological disorders, and gastrointestinal disorders were the most common areas affected by adverse reactions. In addition to known adverse reactions, potential risks not mentioned in the drug label were identified, such as anosognosia, attentional drift, and psychogenic compensation disorder. CONCLUSION: Asenapine carries the risk of various adverse reactions alongside its therapeutic effects. In clinical practice, physicians should closely monitor the occurrence of neurological disorders, psychiatric disorders, and gastrointestinal system disorders.
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Sistemas de Registro de Reacción Adversa a Medicamentos , Antipsicóticos , Bases de Datos Factuales , Dibenzocicloheptenos , Trastornos Mentales , Humanos , Femenino , Masculino , Persona de Mediana Edad , Antipsicóticos/efectos adversos , Trastornos Mentales/tratamiento farmacológico , Trastornos Mentales/inducido químicamente , Adulto , Adolescente , Adulto Joven , Enfermedades del Sistema Nervioso/inducido químicamente , Anciano , Compuestos Heterocíclicos de 4 o más Anillos/efectos adversosRESUMEN
Background: A serious complication after knee arthroscopy is venous thromboembolism (VTE), which includes both deep vein thrombosis (DVT) and pulmonary embolism (PE). However, asymptomatic VTE is frequently undetected. Purpose: To (1) report the incidence of VTE after knee arthroscopy using ultrasound examination and computed tomography pulmonary angiography (CTPA) and (2) discover the independent risk factors of VTE after knee arthroscopy and determine the corresponding cutoff values of these indicators. Study Design: Case-control study; Level of evidence, 3. Methods: Included were 222 patients (115 male) who underwent arthroscopic knee procedures between October 2022 and January 2023. Baseline characteristics, blood test results, and VTE assessments were collected. During the 2-week follow-up, routine lower extremity vascular ultrasound was applied for DVT measurement, with CTPA evaluation for suspected PE. Patients were allocated into VTE and no-VTE groups, and descriptive statistics were used to analyze baseline data. Logistic regression analysis was used to determine the correlation between binary variables and the presence of postoperative VTE. Multivariate logistic regression analysis was further performed to determine the independent risk factors of VTE. Results: Of the 222 patients, 37 (16.7%) had DVT and 1 (0.5%) had both DVT and PE. Compared to the no-VTE group, the VTE group was significantly older, with more female patients; higher body mass index (BMI) and postoperative D-dimer level; and higher rates of hypertension, hyperlipidemia, varicose veins of the lower extremity, and abnormal postoperative fibrin degradation product level (P≤ .043 for all). Notably, operative time >20 minutes was not significantly associated with postoperative VTE (P = .513). The independent risk factors for VTE included age >32 years (odds ratio [OR], 20.71 [95% CI, 4.40-97.47]; P < .001), BMI >23 kg/m2 (OR, 3.52 [95% CI, 1.11-11.14]; P = .032), hyperlipidemia (OR, 6.81 [95% CI, 1.86-24.88]; P = .004), and postoperative D-dimer level >0.63 mg/L (OR, 34.01 [95% CI, 7.36-157.07]; P < .001). Conclusion: The incidence of VTE after knee arthroscopy was 16.7% at the 2-week follow-up. Age >32 years, BMI >23 kg/m2, hyperlipidemia, and postoperative D-dimer >0.63 mg/L were independent risk factors of postoperative VTE within 2 weeks after knee arthroscopy. For patients with knee arthroscopy, the cutoff value of postoperative D-dimer for VTE was found to be 0.63 mg/L for timely intervention.
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MicroRNA (miRNA) and apurinic/apyrimidinic endonuclease 1 (APE1) have been reported to be closely associated with cancers, making them potential crucial biomarkers and therapeutic targets. However, focusing on the detection of a single target is not conducive to the diagnosis and prognosis assessment of diseases. In this study, an AND logic-gate-based dual-locking hairpin-mediated catalytic hairpin assembly (DL-CHA) was developed for sensitive and specific detection of microRNA and APE1. By addition of a lock to each of the hairpins, with APE1 and microRNA serving as keys, fluorescence signals could only be detected in the presence of simultaneous stimulation by APE1 and miRNA-224. This indicated that the biosensor could operate as an AND logic gate. DL-CHA exhibited advantages such as a low background, rapid response, and high logic capability. Therefore, the biosensor serves as a novel approach to cancer diagnosis with significant potential applications.
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Técnicas Biosensibles , ADN-(Sitio Apurínico o Apirimidínico) Liasa , MicroARNs , MicroARNs/análisis , ADN-(Sitio Apurínico o Apirimidínico) Liasa/metabolismo , Humanos , Técnicas Biosensibles/métodos , Lógica , Límite de DetecciónRESUMEN
Importance: Platelet-rich plasma (PRP) has been considered a promising treatment for musculoskeletal disorders. The effects of PRP on clinical outcomes of anterior cruciate ligament reconstruction (ACLR) are controversial. Objective: To compare subjective outcomes and graft maturity in patients undergoing ACLR with and without postoperative intra-articular PRP injection. Design, Setting, and Participants: This surgeon- and investigator-masked randomized clinical trial included patients treated at a national medical center in China who were aged 16 to 45 years and scheduled to undergo ACLR. Participants were enrolled between March 21, 2021, and August 18, 2022, and followed up for 12 months, with the last participant completing follow-up on August 28, 2023. Interventions: Participants were randomized 1:1 to the PRP group (n = 60), which received 3 doses of postoperative intra-articular PRP injection at monthly intervals, or to the control group (n = 60), which did not receive postoperative PRP injection. Both groups had the same follow-up schedule. Main Outcomes and Measures: The primary outcome was the mean score for 4 subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS4) (range, 0-100, with higher scores indicating better knee function and fewer symptoms) at 12 months postoperatively. Secondary outcomes were patient-reported outcomes, graft maturity (on magnetic resonance imaging), and physical examinations at 3, 6, and 12 months. Results: Among the 120 randomized participants (mean [SD] age, 29.0 [8.0] years; 84 males [70%]), 114 (95%) were available for the primary outcome analysis. The mean KOOS4 scores at 12 months were 78.3 (SD, 12.0; 95% CI, 75.2-81.4) in the PRP group and 76.8 (SD, 11.9; 95% CI, 73.7-79.9) in the control group (adjusted mean between-group difference, 2.0; 95% CI, -2.3 to 6.3; P = .36). Secondary outcomes were not statistically significantly different between the 2 groups except for sports and recreation level and graft maturity at 6 months. Intervention-related adverse events included pain at the injection site and knee swelling after injection. Conclusions and Relevance: In this randomized clinical trial among patients undergoing ACLR, the addition of postoperative intra-articular PRP injection did not result in superior improvement of knee symptoms and function at 12 months compared with no postoperative injection. Further studies are required to determine appropriate indications for PRP in musculoskeletal disorders. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2000040262.
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Reconstrucción del Ligamento Cruzado Anterior , Plasma Rico en Plaquetas , Humanos , Reconstrucción del Ligamento Cruzado Anterior/métodos , Adulto , Masculino , Femenino , Inyecciones Intraarticulares , Adulto Joven , Adolescente , Persona de Mediana Edad , China , Resultado del Tratamiento , Lesiones del Ligamento Cruzado Anterior/cirugía , Lesiones del Ligamento Cruzado Anterior/terapiaRESUMEN
Autism is a complex neurodevelopmental disorder with no effective treatment available currently. Repetitive transcranial magnetic stimulation (rTMS) is emerging as a promising neuromodulation technique to treat autism. However, the mechanism how rTMS works remains unclear, which restrict the clinical application of magnetic stimulation in the autism treatment. In this study, we investigated the effect of low-frequency rTMS on the autistic-like symptoms and explored if this neuroprotective effect was associated with synaptic plasticity and neuroinflammation in the hippocampus. A rat model of autism was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats and male offspring were treated with 1 Hz rTMS daily for two weeks continuously. Behavior tests were performed to identify behavioral abnormality. Synaptic plasticity was measured by in vivo electrophysiological recording and Golgi-Cox staining. Synapse and inflammation associated proteins were detected by immunofluorescence and Western blot analyses. Results showed prenatal VPA-exposed rats exhibited autistic-like and anxiety-like behaviors, and cognitive impairment. Synaptic plasticity deficits and the abnormality expression of synapse-associated proteins were found in the hippocampus of prenatal VPA-exposed rats. Prenatal VPA exposure increased the level of inflammation cytokines and promoted the excessive activation of microglia. rTMS significantly alleviated the prenatal VPA-induced abnormalities including behavioral and synaptic plasticity deficits, and excessive neuroinflammation. TMS maybe a potential strategy for autism therapy via rescuing synaptic plasticity and inhibiting neuroinflammation.
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Trastorno Autístico , Modelos Animales de Enfermedad , Hipocampo , Plasticidad Neuronal , Efectos Tardíos de la Exposición Prenatal , Estimulación Magnética Transcraneal , Ácido Valproico , Animales , Ácido Valproico/farmacología , Plasticidad Neuronal/efectos de los fármacos , Ratas , Trastorno Autístico/terapia , Trastorno Autístico/inducido químicamente , Femenino , Masculino , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Ratas Sprague-Dawley , Enfermedades Neuroinflamatorias/terapia , Conducta Animal/efectos de los fármacosRESUMEN
Accurate identification of single nucleotide variants (SNVs) in key driver genes holds a significant value for disease diagnosis and treatment. Fluorescent probes exhibit tremendous potential in specific, high-resolution, and rapid detection of SNVs. However, additional steps are required in most post-PCR assays to convert double-stranded DNA (dsDNA) products into single-stranded DNA (ssDNA), enabling them to possess hybridization activity to trigger subsequent reactions. This process not only prolongs the complexity of the experiment but also introduces the risk of losing target information. In this study, we proposed two strategies for enriching active double-stranded DNA, involving PCR based on obstructive groups and cleavable units. Building upon this, we explored the impact of modified units on the strand displacement reaction (SDR) and assessed their discriminatory efficacy for mutations. The results showed that detection of low variant allele frequencies (VAF) as low as 0.1% can be achieved. The proposed strategy allowed orthogonal identification of 45 clinical colorectal cancer tissue samples with 100% specificity, and the results were generally consistent with sequencing results. Compared to existing methods for enriching active targets, our approach offers a more diverse set of enrichment strategies, characterized by the advantage of being simple and fast and preserving original information to the maximum extent. The objective of this study is to offer an effective solution for the swift and facile acquisition of active double-stranded DNA. We anticipate that our work will facilitate the practical applications of SDR based on dsDNA.
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ADN , Polimorfismo de Nucleótido Simple , Polimorfismo de Nucleótido Simple/genética , Humanos , ADN/genética , ADN/química , Neoplasias Colorrectales/genética , Reacción en Cadena de la Polimerasa , Colorantes Fluorescentes/química , ADN de Cadena Simple/genética , ADN de Cadena Simple/químicaRESUMEN
Although gene expression signatures offer tremendous potential in diseases diagnostic and prognostic, but massive gene expression signatures caused challenges for experimental detection and computational analysis in clinical setting. Here, we introduce a universal DNA-based molecular classifier for profiling gene expression signatures and generating immediate diagnostic outcomes. The molecular classifier begins with feature transformation, a modular and programmable strategy was used to capture relative relationships of low-concentration RNAs and convert them to general coding inputs. Then, competitive inhibition of the DNA catalytic reaction enables strict weight assignment for different inputs according to their importance, followed by summation, annihilation and reporting to accurately implement the mathematical model of the classifier. We validated the entire workflow by utilizing miRNA expression levels for the diagnosis of hepatocellular carcinoma (HCC) in clinical samples with an accuracy 85.7%. The results demonstrate the molecular classifier provides a universal solution to explore the correlation between gene expression patterns and disease diagnostics, monitoring, and prognosis, and supports personalized healthcare in primary care.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Transcriptoma , Perfilación de la Expresión Génica , Neoplasias Hepáticas/genética , ADN , Biomarcadores de Tumor/metabolismo , Regulación Neoplásica de la Expresión GénicaRESUMEN
Accurate microRNA (miRNA) detection is pivotal in the diagnosis and monitoring of cancer. Entropy-driven catalysis (EDC) has attracted widespread attention as an enzyme-free, isothermal technique for miRNA detection owing to its inherent simplicity and reliability. However, conventional EDC is a single-output mode, limiting the efficiency of signal amplification. In this study, a novel EDC dual-output mode was employed in conjunction with DNAzyme, resulting in the development of an EDC dual-end DNAzyme (EDC-DED) approach for highly sensitive miRNA detection. In this system, miRNA-21 initiated the EDC reaction, producing a large amount of catalytically active dual-end Mg2+-dependent DNAzyme. The DNAzyme further cleaved the reporter cyclically, generating a notably amplified fluorescence signal. The proposed method achieved a low detection limit of 2 pM. Compared with the traditional EDC single-end DNAzyme (EDC-SED) strategy, the present method exhibited superior amplification efficiency, enhancing detection sensitivity by approximately 46.5-fold. Furthermore, this platform demonstrated ideal specificity, satisfactory reproducibility and acceptable detection capabilities in clinical serum samples. Therefore, the straightforward and convenient strategy is a potential tool for miRNA analysis, which may provide a new perspective for biological analysis and clinical application.
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ADN Catalítico , Entropía , MicroARNs , ADN Catalítico/química , ADN Catalítico/metabolismo , MicroARNs/análisis , MicroARNs/sangre , Humanos , Límite de Detección , Técnicas Biosensibles/métodosRESUMEN
BACKGROUND: The emergence of DNA nanotechnology has enabled the systematic design of diverse bionic dissipative behaviors under the precise control of nucleic acid nanodevices. Nevertheless, when compared to the dissipation observed in robust living systems, it is highly desirable to enhance the anti-interference for artificial DNA dissipation to withstand perturbations and facilitate repairs within the complex biological environments. RESULTS: In this study, we introduce strategically designed "trash cans" to facilitate kinetic control over interferences, transforming the stochastic binding of individual components within a homogeneous solution into a competitive binding process. This approach effectively eliminates incorrect binding and the accumulation of systemic interferences while ensuring a consistent pattern of energy fluctuation from response to silence. Remarkably, even in the presence of numerous interferences differing by only one base, we successfully achieve complete system reset through multiple cycles, effectively restoring the energy level to a minimum. SIGNIFICANCE: The system was able to operate stably without any adverse effect under conditions of irregular interference, high-abundance interference, and even multiplex interferences including DNA and RNA crosstalk. This work not only provides an effective paradigm for constructing robust DNA dissipation systems but also greatly broadens the potential of DNA dissipation for applications in high-precision molecular recognition and complex biological reaction networks.
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ADN , Nanotecnología , ADN/química , ARN , CinéticaRESUMEN
PURPOSE: Numerous methods have been proposed to characterise tubercle lateralisation. However, their normal values and related changes remain unclear. Accordingly, it was aimed to determine the potential sex and age effects and determined the optimal individualised method of diagnosing lateralisation of the tibial tubercle in patients with recurrent patellar dislocation (RPD). METHODS: Measurements included the tibial tubercle-trochlear groove (TT-TG) distance, tibial tubercle-posterior cruciate ligament (TT-PCL) distance and tibial tubercle lateralisation (TTL); and the proximal tibial width (PTW), trochlear width (TW) and trochlear dysplasia index (TDI), for adjustment. A two-way analysis of variance was used to determine the effect of age, sex and their interaction within the normal group. When the age effect was statistically significant, a nonlinear regression was created. Areas under the receiver-operating characteristic curve (AUCs) were calculated to assess diagnostic accuracy. RESULTS: A total of 277 normal participants (mean [SD] age, 13.5 [2.6] years; 125 [45.1%] female) and 227 patients with RPD (mean [SD] age, 13.5 [2.6] years; 161 [58.1%] female) were analysed. It was found that in the normal group, in patients aged 7-10, TT-PCL distance (p = 0.006), TTL (p = 0.007) and TT-PCL/PTW (p < 0.001) were significantly larger in females than in males. A significant sex effect was also detected on TT-TG/TW (p = 0.014). TT-TG distance, TT-PCL distance, TTL and TT-PCL/PTW (in male patients) approached an established normal adult value of 12.3 mm, 20.9 mm, 0.64 and 0.28, respectively, with increasing age (p < 0.001). The AUC was greater for TT-TG/TDI and TT-TG/TW (p ≤ 0.01) and TT-TG/TDI outperformed TT-TG/TW in patients aged 15-18 (p = 0.004). CONCLUSIONS: Tubercle lateralisation increased with age and was affected by sex, with the exception of TT-TG distance and TT-TG/TDI. TT-TG/TDI is the optimal method of diagnosing a lateralized tibial tubercle in patients with RPD. These findings assist with the evaluation of tubercle lateralisation in that they provide a proper protocol for paediatric and adolescent populations with RPD; and thus, will help determine whether medial tubercle transfer should be included among the tailored surgical procedures considered for the treatment of patients with RPD. LEVEL OF EVIDENCE: Level III.
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Luxación de la Rótula , Tibia , Humanos , Femenino , Masculino , Adolescente , Niño , Tibia/anatomía & histología , Factores Sexuales , Factores de Edad , Ligamento Cruzado Posterior/anatomía & histología , Valores de Referencia , Curva ROC , RecurrenciaRESUMEN
Dynamic biological structures involve the continual turnover of molecules within supramolecular assemblies such as tubulin. Inspired by dynamic biology self-organizing systems, we build an artificial dynamic structure based on DNA nanotechnology through a nonequilibrium chemical system. Herein, a metastable domain (MD), essentially a stem-loop structure, was introduced into DNA hairpins within hybridization chain reaction (HCR), thereby imparting dynamic activity to the DNA polymers. Hairpins with MD thermodynamically assemble to a high-energy polymer in the presence of trigger strands. The polymer can relax back to the stable unassembled state once the invader is added and finally relax to the activated hairpin by an anti-invader. Reversible assembly/disassembly of the HCR is achieved through invader/anti-invader cycles. We accomplished kinetic modulation, reversible conformational switching, cascading regulation, and enzyme activity control through the MD-HCR. We believe that the design of the MD-HCR could inspire the development of autonomous biological functions within artificial systems.
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ADN , Tubulina (Proteína) , Tubulina (Proteína)/genética , ADN/química , Hibridación de Ácido Nucleico , NanotecnologíaRESUMEN
BACKGROUND: An anterior cruciate ligament (ACL) injury accompanied by patellar instability (PI) is a topic that has gained orthopaedic surgeons' attention recently. Untreated PI is reportedly associated with worse clinical outcomes after isolated ACL reconstruction (ACLR) in patients after an ACL injury with PI. Nevertheless, the appropriate surgical approach and its long-term therapeutic effects in these patients remain unclear. PURPOSE: (1) To compare the clinical and radiological outcomes between isolated ACLR (iACLR) and combined ACLR and medial patellofemoral ligament reconstruction (cAMR) in patients after an ACL injury with PI and (2) to explore the correlations between these 2 procedures and clinical and radiological outcomes. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A total of 106 patients diagnosed with an ACL injury accompanied by PI between January 2016 and April 2021 were analyzed in this study. There were 34 patients excluded because of missing postoperative radiological data. Among the remaining 72 patients, 34 patients underwent iACLR, while 38 patients underwent cAMR. Demographic characteristics, intraoperative findings, and patient-reported outcomes (Lysholm score, subjective International Knee Documentation Committee score, and Tegner activity score) were prospectively collected. Patellar alignment parameters and worsening patellofemoral osteoarthritis (PFOA) features (evaluated with the modified Whole-Organ Magnetic Resonance Imaging Score) were analyzed longitudinally on magnetic resonance imaging. The Kujala score was used to evaluate the functional recovery of the patellofemoral joint, and redislocations of the patella were prospectively recorded. Finally, multivariate logistic regression analysis was used to explore the correlations between these 2 procedures and clinical (not achieving the minimal detectable change [MDC] for the Lysholm score) and radiological (worsening PFOA features) outcomes. RESULTS: The mean follow-up duration was 28.9 ± 6.2 and 27.1 ± 6.8 months for the iACLR and cAMR groups, respectively (P = .231). Significantly higher Lysholm scores (88.3 ± 9.9 vs 82.1 ± 11.1, respectively; P = .016) and subjective International Knee Documentation Committee scores (83.6 ± 11.9 vs 78.3 ± 10.2, respectively; P = .046) were detected in the cAMR group compared with the iACLR group postoperatively. The rates of return to preinjury sports were 20.6% and 44.7% in the iACLR and cAMR groups, respectively (difference, 24.1% [95% CI, 3.3%-45.0%]; P = .030). Moreover, the rates of worsening PFOA features were 44.1% and 18.4% in the iACLR and cAMR groups, respectively (difference, 25.7% [95% CI, 4.9%-46.4%]; P = .018). In addition, significantly higher Kujala scores (87.9 ± 11.3 vs 80.1 ± 12.0, respectively; P = .006), lower redislocation rates (0.0% vs 11.8%, respectively; difference, 11.8% [95% CI, 0.9%-22.6%]; P = .045), and significantly better patellar alignment were detected in the cAMR group compared with the iACLR group postoperatively. Furthermore, multivariate logistic regression analysis determined that iACLR and partial lateral meniscectomy were significantly correlated with not achieving the MDC for the Lysholm score and worsening PFOA features in our study population. CONCLUSION: In patients after an ACL injury with PI, cAMR yielded better clinical and radiological outcomes compared with iACLR, with better patellar stability and a lower proportion of worsening PFOA features. Furthermore, not achieving the MDC for the Lysholm score and worsening PFOA features were significantly correlated with iACLR and partial lateral meniscectomy. Our study suggests that cAMR may be a more appropriate procedure for patients after an ACL injury with PI, which warrants further high-level clinical evidence.
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Lesiones del Ligamento Cruzado Anterior , Inestabilidad de la Articulación , Osteoartritis de la Rodilla , Articulación Patelofemoral , Humanos , Lesiones del Ligamento Cruzado Anterior/diagnóstico por imagen , Lesiones del Ligamento Cruzado Anterior/cirugía , Estudios de Cohortes , Articulación Patelofemoral/diagnóstico por imagen , Articulación Patelofemoral/cirugía , Inestabilidad de la Articulación/diagnóstico por imagen , Inestabilidad de la Articulación/cirugía , Articulación de la Rodilla/cirugíaRESUMEN
OBJECTIVES: Underestimation of concomitant patellofemoral instability in patients with anterior cruciate ligament (ACL) injury has aroused extensive attention. However, the characteristics of the combined injury is not well recognized. Hence, we aimed to characterize the features of the combined injury, and determine the radiographic risk factors. METHODS: Fifteen radiological parameters were identified after discussion and pilot-tested. Radiographic measurements were compared using the analysis of variance model with Tukey post hoc analysis. A stepwise binomial logistic regression was performed and a nomogram model combining the significant risk factors was created. The model performance was validated by C-index, calibration plot, and decision curve. RESULTS: A total of 204 patients (mean [SD] age, 25.1 [6.7] years; 108 [52.9%] male) were included. The final model was updated through regression analysis using 4 parameters as significant risk factors: lateral femoral condyle ratio (OR (95% CI), 1.194 (1.023 to 1.409)), medial anterior tibial subluxation (mATS) (OR (95% CI), 1.234 (1.065 to 1.446)), medial posterior plateau tibial angle (mPPTA) (OR (95% CI), 1.266 (1.088 to 1.500)), and trochlear depth (OR (95% CI), 0.569 (0.397 to 0.784)). C-index for the nomogram was 0.802 (95% CI, 0.731 to 0.873) and was confirmed to be 0.784 through bootstrapping validation. Calibration plot established a good agreement between prediction and observation. Decision curve analysis showed that if threshold probability was over 10%, using the nomogram adds more benefit than either all or none scheme. CONCLUSIONS: Lateral femoral condyle ratio, mATS, mPPTA, and trochlear depth are strong adverse predictors of patellofemoral instability in patients with ACL injury. CLINICAL RELEVANCE: This study characterizes the radiological features of the combined injury. Patellofemoral instability should be noted when treating ACL injuries. KEY POINTS: ⢠The radiological characteristics of the combined ACL injury and patellofemoral instability is not well recognized. ⢠Lateral femoral condyle ratio, mATS, mPPTA, and trochlear depth are predominant risk factors for patellofemoral instability in patients with ACL injury. ⢠Patellofemoral instability should be noted when treating ACL injuries.
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Lesiones del Ligamento Cruzado Anterior , Reconstrucción del Ligamento Cruzado Anterior , Humanos , Masculino , Adulto , Femenino , Lesiones del Ligamento Cruzado Anterior/diagnóstico por imagen , Lesiones del Ligamento Cruzado Anterior/complicaciones , Estudios Retrospectivos , Articulación de la Rodilla/cirugía , Factores de Riesgo , Tomografía Computarizada por Rayos X , Imagen por Resonancia MagnéticaRESUMEN
DNA strand displacement reactions are vital for constructing intricate nucleic acid circuits, owing to their programmability and predictability. However, the scarcity of effective methods for eliminating circuit leakages has hampered the construction of circuits with increased complexity. Herein, a versatile strategy is developed that relies on a spatially controlled proximity split tweezer (PST) switch to transduce the biomolecular signals into the independent oligonucleotides. Leveraging the double-stranded rigidity of the tweezer works synergistically with the hindering effect of the hairpin lock, effectively minimizing circuit leakage compared with sequence-level methods. In addition, the freely designed output strand is independent of the target binding sequence, allowing the PST switch conformation to be modulated by nucleic acids, small molecules, and proteins, exhibiting remarkable adaptability to a wide range of targets. Using this platform, established logical operations between different types of targets for multifunctional transduction are successfully established. Most importantly, the platform can be directly coupled with DNA catalytic circuits to further enhance transduction performance. The uniqueness of this platform lies in its design straightforwardness, flexibility, scalable intricacy, and system compatibility. These attributes pave a broad path toward nucleic acid-based development of sophisticated transduction networks, making them widely applied in basic science research and biomedical applications.
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BACKGROUND: The powerful logic processing capability of DNA logic circuits over multiple input signals perfectly meets the demands of multi-biomarker-based clinical diagnostics. As important biomarkers for cancer diagnosis and treatment, the orthogonal differential expression of microRNAs (miRNAs) in different diseases and different cancer cells makes the precise logical detection of multiple miRNAs particularly critical. RESULTS: Therefore, we constructed two fundamental "AND" and "OR" logic gates and one "AND-OR" logic gate on the basis of our proposed multifunctional dumbbell probes. These logic gates allowed for the logical profiling of multiple cancer-associated miRNAs. In addition, by making simple adjustments to the functional modules of multifunctional dumbbell probes, the three logic gates we proposed could be easily transformed without the use of sophisticated probe design. Remarkably, these logic gates, in particular the "AND-OR" logic gate, were able to compute several miRNAs simultaneously, demonstrating excellent cell identification capabilities. SIGNIFICANCE: Overall, this work provided a new idea for accurately distinguishing multiple cell types and showed great application prospects.
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MicroARNs , MicroARNs/genética , ADN/genética , Lógica , Computadores MolecularesRESUMEN
As CRISPR technology is promoted to more fine-divided molecular biology applications, its inherent performance finds it increasingly difficult to cope with diverse needs in these different fields, and how to more accurately control the performance has become a key issue to develop CRISPR technology to a new stage. Herein, we propose a CRISPR/Cas12a regulation strategy based on the powerful programmability of nucleic acid nanotechnology. Unlike previous difficult and rigid regulation of core components Cas nuclease and crRNA, only a simple switch of different external RNA accessories is required to change the reaction kinetics or thermodynamics, thereby finely and almost steplessly regulating multi-performance of CRISPR/Cas12a including activity, speed, specificity, compatibility, programmability and sensitivity. In particular, the significantly improved specificity is expected to mark advance the accuracy of molecular detection and the safety of gene editing. In addition, this strategy was applied to regulate the delayed activation of Cas12a, overcoming the compatibility problem of the one-pot assay without any physical separation or external stimulation, and demonstrating great potential for fine-grained control of CRISPR. This simple but powerful CRISPR regulation strategy without any component modification has pioneering flexibility and versatility, and will unlock the potential for deeper applications of CRISPR technology in many finely divided fields.
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Sistemas CRISPR-Cas , Edición Génica , Sistemas CRISPR-Cas/genética , Endonucleasas/genética , ARN/genética , ARN Guía de Sistemas CRISPR-CasRESUMEN
Toehold-mediated strand displacement (TMSD) is widely employed in constructing a wide range of chemical reaction networks. In TMSD, single-stranded DNA or RNA can fold back upon itself to form a local short double-strand structure often hindering bimolecular hybridization. Here, based on series and parallel circuits, we introduce two mechanisms: series toehold-mediated strand displacement (STMSD) and parallel toehold-mediated strand displacement (PTMSD). These mechanisms can be highly effective when the target area is blocked by a secondary structure. In addition, these systems allow regulating the reaction rates spanning three to five orders of magnitude by adjusting the length of the two toeholds with the added advantage of multifunctional regulation and selectivity. To demonstrate the impressive function of this approach, a logic operation system based on STMSD was constructed to simulate the signal processing of a half-adder. We believe that the introduction of series and parallel toeholds will provide design flexibility contributing to the development of molecular computers, molecular robotics, and DNA-based biosensors.
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Loop-mediated isothermal amplification (LAMP) is a commonly used alternative to PCR for point-of-care detection of nucleic acids due to its rapidity, sensitivity, specificity, and simpler instrumentation. While dual-labeled TaqMan probes are widely used in PCR for single-nucleotide polymorphism (SNP) genotyping, real-time LAMP primarily relies on turbidimetry or intercalator fluorescence measurements, which can be non-specific and generate false-positive results. In this study, we propose a closed-tube, dual-labeled RNA-modified probes and RNase H II-assisted real-time LAMP (RART-LAMP) method for SNP genotyping. Our findings indicate that (1) fluorescence signals were predominantly derived from probe hydrolysis rather than hybridization, (2) temperature-controlled hybridization between the probe and template ensured the specificity of SNP analysis, and (3) RNase H II hydrolysis between the target containing SNP sites and probes did not exhibit sequence specificity. Our RART-LAMP approach demonstrated excellent performance in genotyping C677T clinical samples, including gDNA extracted from blood, saliva, and swabs. More importantly, saliva and swab samples could be directly analyzed without any pretreatment, indicating promising prospects for nucleic acid analysis at the point of care in resource-limited settings.
Asunto(s)
Técnicas de Amplificación de Ácido Nucleico , Polimorfismo de Nucleótido Simple , Genotipo , Sensibilidad y Especificidad , Técnicas de Amplificación de Ácido Nucleico/métodos , Reacción en Cadena de la Polimerasa , Hibridación de Ácido NucleicoRESUMEN
Detection of single nucleotide polymorphisms (SNPs) is critical for personalized clinical diagnosis, treatment, and medication. Current clinical detection methods suffer from primer dimerization and require the redesigning of reaction systems for different targets, resulting in a time-consuming and laborious process. Here, we present a robust and versatile method for SNP typing by using tailed primers and universal small molecule probes in combination with a visualized lateral flow assay (LFA). This approach enables not only rapid typing of different targets, but also eliminates the interference of primer dimers and enhances the accuracy and reliability of the results. Our proposed universal assay has been successfully applied to the typing of four SNP loci of clinical samples to verify the accuracy and universality, and the results are consistent with those obtained by Sanger sequencing. Therefore, our study establishes a new universal "typing formula" using nucleic acid tags and small molecule probes that provides a powerful genotyping platform for genetic analysis and molecular diagnostics.
Asunto(s)
Polimorfismo de Nucleótido Simple , Genotipo , Cartilla de ADN , Reproducibilidad de los ResultadosRESUMEN
Vancomycin is the first-line drug for infections of methicillin-resistant Staphylococcus aureus (MRSA) and multi-drug-resistant bacteria. The effective therapeutic concentration range of vancomycin is narrow, so it's essential to implement vancomycin therapeutic drug monitoring. However, conventional detection methods have disadvantages of expensive equipment, complicated operation, or poor reproducibility. Herein, a fluorescent sensing platform initiated by an allosteric probe was constructed for simple and sensitive monitoring of vancomycin at a low cost. The key point of this platform is the well-designed allosteric probe, which comprises an aptamer and a trigger sequence. When vancomycin exists, the combination of vancomycin and the aptamer will lead to a conformational change of the allosteric probe, thus exposing the trigger sequence. The trigger can react with the molecular beacon (MB) to generate fluorescent signals. In addition, the allosteric probe combined with hybridization chain reaction (HCR) was applied to develop an amplified platform, the linear range is from 0.5 µg mL-1 to 50 µg mL-1 with the limit of detection (LOD) of 0.26 µg mL-1. Most importantly, this allosteric probe-initiated sensing platform shows good detection ability in human serum samples, and it also indicates great correlation and accuracy compared with HPLC. The present simple and sensitive allosteric probe-initiated platform has the potential to support the therapeutic drug monitoring of vancomycin, which is of great significance to promote the rational use of antibiotics in clinics.