Early Clinical Diagnosis Research Articles

A case series of melioidosis: An underdiagnosed entity in Kerala

Abstract Melioidosis is an emerging infection in India and is caused by a Gram-negative oxidase-positive bacilli, Burkholderia pseudomallei which is present in soil and surface water in the endemic region. Clinical manifestations are protean varying from asymptomatic infection, multiple skin abscesses, chronic pneumonia mimicking tuberculosis, and fulminant septic shock with abscesses in multiple internal organs. Isolation of bacilli from aspirated fluids remains the gold standard of diagnosis. Lack of microbiological services in many parts of the state, protean nature of clinical manifestations, lack of awareness among clinicians, and misidentification of the organism as Pseudomonas spp leads to delay in diagnosis and treatment. We have, retrospectively, analyzed 14 cases with culture-proven melioidosis diagnosed during 10 years. Case records of culture-positive patients were retrospectively analyzed for demographic data, clinical characteristics, management, complications, and clinical outcomes. Out of these, 13 cases were male. The most common age group affected was 50–59 years. The major occupation affected was manual laborer. Nonbacteremic melioidosis accounted for 12 cases. Concerning clinical presentations, intra-abdominal abscesses mainly in the liver and spleen accounted for seven cases. All the isolates were susceptible to ceftazidime, meropenem, and doxycycline, whereas 12 isolates were susceptible to chloramphenicol, 11 isolates were susceptible to trimethoprim–sulfamethoxazole combination, and 10 cases were susceptible to amoxicillin–clavulanic acid and ciprofloxacin. Ten cases recovered with ceftazidime administration along with surgical drainage of abscess and three cases recovered with meropenem administration and surgical drainage. One patient expired and was on piperacillin–tazobactam. Melioidosis is a disease of public health importance and early clinical and laboratory diagnosis is crucial in the effective management of melioidosis.

Novel “Signal-On” photoelectrochemical assay by regulating the release of cationic dyes with the utilization of target-specific enzymolysis hydrogels

Targeted response-based controlled release strategy exhibits high specificity and sensitivity in many biomedical applications. In this paper, we report a novel and simple “signal-on” photoelectrochemical (PEC) assay strategy, which regulates the release of cationic dyes through the utilization of target-specific enzymolysis hydrogel. The cationic dye crystal violet (CV) embedded in the hyaluronic acid (HA) hydrogel was released in the presence of hyaluronidase (HAase) and increased the cathodic photocurrent of BiOBr nanoflowers. The cathodic photocurrent response is linear with the logarithm of HAase activity in the range of 0.10–120 U/mL, with an ultralow detection limit of 0.034 U/mL detected. Our work provides a simple and efficient strategy to detect HAase activity by monitoring the enzyme response of hydrogel-controlled release photosensitizer, which is expected to be able to provide an efficient strategy for early clinical diagnosis of some other diseases and meet the ever-increasing needs in pharmaceutical and medical fields.

Copper(II)-Tannic Acid@Cu with In Situ Grown Gold Nanoparticles as a Bifunctional Matrix for Facile Construction of Label-Free and Ultrasensitive Electrochemical cTnI Immunosensor.

Sensitive detection of cardiac troponin I (cTnI) is of great significance in the diagnosis of a fatal acute myocardial infarction. A redox-active nanocomposite of copper(II)-tannic acid@Cu (CuTA@Cu) was herein prepared on the surface of a glassy carbon electrode by electrochemical deposition of metallic copper combined with a metal stripping strategy. Then, HAuCl4 was in situ reduced to gold nanoparticles (AuNPs) by strong reductive catechol groups in the TA ligand. The AuNPs/CuTA@Cu composite was further utilized as a bifunctional matrix for the immobilization of the cTnI antibody (anti-cTnI), producing an electrochemical immunosensor. Electrochemical tests show that the immunoreaction between anti-cTnI and target cTnI can cause a significant reduction of the electrochemical signal of CuTA@Cu. It can be attributed to the insulating characteristic of the immunocomplex and its barrier effect to the electrolyte ion diffusion. From the signal changes of CuTA@Cu, cTnI can be analyzed in a wide range from 10 fg mL-1 to 10 ng mL-1, with an ultralow detection limit of 0.65 fg mL-1. The spiked recovery assays show that the immunosensor is reliable for cTnI determination in human serum samples, demonstrating its promising application in the early clinical diagnosis of myocardial infarction.

Pediatric mandibular malignancies: a comprehensive analysis of SEER data

Mandibular malignancies are rare in the pediatric population and subsequently not well characterized. SEER 18 registry data was collected, applying age 0–18 years and ICD-O-3 code C41.1 (‘mandible’). Univariate Cox regression analysis was conducted, and hazard ratios (HR) were calculated for overall survival (OS) and disease-specific survival (DSS) according to patient demographics, tumor characteristics, and treatment. Kaplan–Meier survival curves were generated for OS and DSS. Sixty-four patients met the inclusion criteria. The median age at diagnosis was 13.0 years, and median survival was 8.7 years. Osteosarcoma was the most common histological diagnosis (n = 22). Sex, race, age (<13 vs ≥13 years), histological type, odontogenic origin, and treatment modality were found not to be associated with OS or DSS. The SEER stage ‘distant’ was significantly associated with an elevated HR of 6.28 for DSS (P = 0.027) and 5.29 for OS (P = 0.025). Kaplan–Meier survival curves demonstrated significantly lower 5-year DSS (P < 0.001) and OS (P < 0.001) for SEER ‘distant’ stage. This study includes the analysis of a large number of pediatric mandibular malignancies when compared to previous studies. ‘Distant’ stage was associated with decreased survival. Early clinical suspicion and diagnosis are paramount for improved survival.

Causal effects of inflammatory cytokines on cardiovascular diseases: Insights from genetic evidence

BackgroundThe causal relationship between inflammatory cytokines and cardiovascular diseases (CVDs) has not been fully elucidated. Exploring this relationship between circulating inflammatory cytokines and CVDs is crucial for early clinical diagnosis and effective treatment. Methods and ResultsThis study investigated the causal relationships between 41 inflammatory cytokines and six CVDs: heart failure (HF), myocardial infarction (MI), unstable angina pectoris (UAP), stable angina pectoris (SAP), valvular heart disease (VHD), and aortic aneurysm (AA), using the Mendelian Randomization (MR) method. The primary analysis employed the inverse-variance weighted (IVW) method within MR. Heterogeneity and pleiotropy were assessed through MR-Egger regression and the Q statistic. Strong evidence supported the effect of macrophage inflammatory protein-1β (MIP-1β) on MI (OR = 1.062, P < 0.001, FDR <0.001). Suggestive evidence showed that the Beta nerve growth factor increased the risk of MI (OR = 1.145, P = 0.025), but the stem cell factor (SCF) demonstrated a potential protective effect against MI (OR = 0.910, P = 0.04). SCF and hepatocyte growth factor (HGF) exhibited potential protective effects against SAP. No inflammatory cytokine was associated with UAP. Monocyte chemotactic protein-1 was linked to an increased risk of VHD (OR = 1.056, P = 0.049). Higher levels of interleukin-13 (IL-13), interferon gamma-induced protein 10 (IP-10), and growth-regulated oncogene-alpha were associated with increased susceptibility to HF. Elevated basic fibroblast growth factor (bFGF) levels exhibited protective effects against AA (OR = 0.751, P = 0.038). Reverse MR analyses revealed that AA significantly decreased circulating TNF-related apoptosis-inducing ligand (TRAIL) levels (OR = 0.907, P < 0.001, FDR = 0.01). MI significantly increased circulating IL-12-p70 levels (OR = 1.146, P < 0.001, FDR = 0.014). Suggestive evidence indicated the Causal effects of six CVDs on 17 circulating inflammatory cytokines. ConclusionsThis study clarified the causal relationships between specific inflammatory cytokines and six CVDs, providing novel insights and evidence into the genetic involvement of inflammatory cytokines in CVDs. These inflammatory cytokines may be potential biomarkers for early disease diagnosis and treatment evaluation.

Electrophysiological functional connectivity and complexity reflecting cognitive processing speed heterogeneity in young children with ADHD

Early intervention is imperative for young children with attention-deficit/hyperactivity disorder (ADHD) who manifest heterogeneous neurocognitive deficits. The study investigated the functional connectivity and complexity of brain activity among young children with ADHD exhibiting a fast cognitive processing speed (ADHD-F, n = 26), with ADHD exhibiting a slow cognitive processing speed (ADHD-S, n = 17), and typically developing children (n = 35) using wireless electroencephalography (EEG) during rest and task conditions. During rest, compared with the typically developing group, the ADHD-F group displayed lower long-range intra-hemispheric connectivity, while the ADHD-S group had lower frontal beta inter-hemispheric connectivity. During task performance, the ADHD-S group displayed lower frontal beta inter-hemispheric connectivity than the typically developing group. The ADHD-S group had lower frontal inter-hemispheric connectivity in broader frequency bands than the ADHD-F group, indicating ADHD heterogeneity in mental processing speed. Regarding complexity, the ADHD-S group tended to show lower frontal entropy estimators than the typically developing group during the task condition. These findings suggest that the EEG profile of brain connectivity and complexity can aid the early clinical diagnosis of ADHD, support subgrouping young children with ADHD based on cognitive processing speed heterogeneity, and may contain specific novel neural biomarkers for early intervention planning.

An efficient DNAzyme-locked leakless enzyme-free amplification system for alpha-foetoprotein detection in liver cancer and breast cancer.

Alpha-foetoprotein (AFP) is taken as a diagnostic tumor marker for the screening and diagnosis of cancer. Nucleic acid-based isothermal amplification strategies are emerging as a potential technology in early screening and clinical diagnosis of AFP. The leakages between hairpins dramatically increase the background and reduce the sensitivity. Thus, it is necessary to develop some strategies to reduce the leakage for isothermal amplification strategies. A DNAzyme-locked leakless enzyme-free amplification system was developed for AFP detection in liver cancer and breast cancer. AFP could open the apt-hairpin and initiate the catalytic hairpin assembly (CHA) reaction to produce a Y-shaped duplex. Two tails of a Y-shaped duplex cleaved the two kinds of leakless hairpins. Then, the third tail of the Y-shaped duplex catalyzed the second CHA between the cleaved leakless hairpins to recover the fluorescent intensity. The limit of detection reached 5fg/mL by the two levels of signal amplifications. Importantly, the leakless hairpin design effectively reduced leakage between hairpins and weakened the background. In addition, it also showed a great promising potential for AFP detection in early screening and clinical diagnosis.

Fluorometric determination of mecA gene in MRSA with a graphene-oxide based bioassay using flap endonuclease 1-assisted target recycling and Klenow fragment-triggered signal amplification

Methicillin-resistant Staphylococcus aureus (MRSA) is a multidrug-resistant bacterium that causes a wide range of illnesses, necessitating the development of new technologies for its detection. Herein, we propose a graphene oxide (GO)-based sensing platform for the detection of mecA gene in MRSA using flap endonuclease 1 (FEN1)-assisted target recycling and Klenow fragment (KF)-triggered signal amplification. Without the target, all the DNA probes were adsorbed onto GO, resulting in fluorescence quenching of the dye. Upon the addition of the target, a triple complex was formed that triggered FEN1-assisted target recycling and initiated two polymerization reactions with the assistance of KF polymerase, generating numerous dsDNA that were repelled by GO. These dsDNAs triggered fluorescence enhancement when SYBR Green I was added. Therefore, the target DNA was quantified by measuring the fluorescence at excitation and emission wavelengths of 480/526 nm. This mecA gene assay showed a good linear range from 1 to 50 nM with a lower limit of detection of 0.26 nM, and displayed good applicability to the analysis of real samples. Thus, a new method for monitoring MRSA has been developed that has great potential for early clinical diagnosis and treatment.

Predictive role of PAR and LAR in refractory suppurative meningitis in infants

BackgroundMeningitis can be caused by a variety of pathogenic microorganisms, which can lead to higher mortality and disability rates. However, the clinical manifestations of suppurative meningitis are often atypical in infants and young children, which makes early clinical diagnosis difficult.PAR and LAR are considered as a novel inflammatory biomarker and have been applied in tumors, IgA nephropathy, sepsis.ObjectiveTo investigate the application of platelet/albumin (PAR) and lactate dehydrogenase/albumin (LAR) in refractory suppurative meningitis in infants.MethodsThe relevant clinical data of 107 children with suppurative meningitis were retrospectively analyzed, and were divided into common group (82 cases) and refractory group (25 cases) according to the severity of the disease according to the relevant clinical consensus. The relevant clinical data and laboratory examination of the children in the two groups were compared. The diagnostic value of PAR and LAR in children with refractory suppurative meningitis was analyzed and multivariate Logistic regression analysis was performed.ResultThe PAR of children with suppurative meningitis in refractory group was lower than that in common group (P < 0.05), while LAR was higher than that in common group (P < 0.05). Meanwhile, multivariate Logistic regression analysis showed that LAR and cerebrospinal fluid glucose ≤ 1.5mmo/L were risk factors for poor prognosis (OR > 1, P < 0.05). PAR was a protective factor (OR < 1, P < 0.05).ConclusionPAR and LAR can be used for early diagnosis of refractory suppurative meningitis in children as protective and risk factors, respectively.

Label-free fluorescent aptasensor for myoglobin detection based on an aggregation-induced emission enhancement imidazole compound and a Fe3O4@4-VP platform

Acute myocardial infarction (AMI) is recognized as one of the deadliest cardiovascular diseases in the world, causing serious public health problems worldwide. Myoglobin (Mb) is an important biomarker for AMI. Therefore, the accurate detection of Mb is crucial for the early detection and clinical diagnosis of AMI. In this study, a novel imidazole Compound C and novel Fe3O4@4-VP microspheres were prepared and used to construct an unlabeled fluorescence aptasensor for Mb detection. Compound C can bind to the aptamer of Mb (Mb-Apt) through electrostatic attraction to form a C/Mb-Apt complex and produce the aggregation-induced emission enhancement effect. Then, Mb was added to the C/Mb-Apt solution. Mb could combine with C/Mb-Apt to form a C/Mb-Apt/Mb complex. Subsequently, Fe3O4@4-VP was added to the above mixture. The bases of Mb-Apt already combined with Mb, and thus, C/Mb-Apt/Mb would no longer interact with the pyridine rings on the surface of Fe3O4@4-VP through π-π stacking. After magnetic separation, the C/Mb-Apt/Mb complex remained in the supernate. The supernate exhibited strong fluorescence and its fluorescent intensity was proportional to the level of Mb. Experimental results showed an excellent linear relationship between the fluorescent intensity of the supernate and the level of Mb within the range of 0.167–20 ng/mL, with a detection limit reaching as low as 0.05 ng/mL (S/N = 3). In addition, the aptasensor exhibited high specificity and could be used for detecting Mb in human serum.

Automatic diagnosis of pediatric high myopia via Attention-based Patch Residual Shrinkage network

Fundus images can be obtained non-invasively and be adopted to monitor the follow-up on various fundus diseases, such as high myopia. Therefore, the use of fundus images for the early screening of eye diseases has principal clinical significance. However, AI-based medical research continues to face two main challenges, lack of prior-knowledge guidance and complex fundus information. In this paper, we propose a pediatric high myopia classification model, the Attention-based Patch Residual Shrinkage network (APRSnet), which facilitates early clinical diagnosis by evaluating the importance of different image features. A collection of 2492 high-resolution fundus images of children, including 768 images of high myopia and 1724 images of non-high myopia, is fed to APRSnet as the training dataset. To better understand how different features impact the classification, APRSnet is tested on multiple feature-enhanced fusion datasets. The result shows that, by removing irrelevant information in fundus images, APRSnet achieves an accuracy of 0.959 and an F1 score of 0.946 and outperforms all classic image classification networks we compared with. We also testify that, in fundus images, gradient information benefits severity classification the most since it helps with model convergence more than luminance and texture information.

Unpaired fundus image enhancement based on constrained generative adversarial networks.

Fundus photography (FP) is a crucial technique for diagnosing the progression of ocular and systemic diseases in clinical studies, with wide applications in early clinical screening and diagnosis. However, due to the nonuniform illumination and imbalanced intensity caused by various reasons, the quality of fundus images is often severely weakened, brings challenges for automated screening, analysis, and diagnosis of diseases. To resolve this problem, we developed strongly constrained generative adversarial networks (SCGAN). The results demonstrate that the quality of various datasets were more significantly enhanced based on SCGAN, simultaneously more effectively retaining tissue and vascular information under various experimental conditions. Furthermore, the clinical effectiveness and robustness of this model were validated by showing its improved ability in vascular segmentation as well as disease diagnosis. Our study provides a new comprehensive approach for FP and also possesses the potential capacity to advance artificial intelligence-assisted ophthalmic examination.

Novel dynamic light scattering immunosensor for prostate specific antigens based upon dual-tyramine signal amplification strategy

The sensitive detection of biomarkers is crucial for the early diagnosis, treatment, and improvement of the quality of life of patients. A novel dynamic light scattering-dual tyramine signal amplification strategy (DLS-dTSA) was constructed to detect prostate-specific antigen (PSA). The Oligo 1 was first immobilized in a 96-well plate for PSA capture. Afterwards, horseradish peroxidase (HRP) and Oligo 2 functionalized AuNPs (HRP-Au NPs-Oligo 2) bound to Oligo 1 through DNA hybridization. In the presence of hydrogen peroxide (H2O2), tyramine could be converted into a transient radical intermediate by HRP, leading to the aggregation of tyramine and HRP-labeled AuNPs (tyramine-AuNPs-HRP) near HRP-AuNPs-Oligo 2, triggering the first TSA process. Later, the PSA was added into the 96-well plate, to specifically recognize aptamer and thus depart the Au-aggregate from the 96-well plate. Then H2O2 was added to the Au-aggregate solution, triggering the free Au-aggregate to gather again, realizing the second TSA amplification. The average diameter of Au NPs increased linearly with the concentration of PSA during the range of 0.0001 – 1000 ng mL−1, and the limit of detection was 0.033 pg mL−1. Moreover, this strategy has been used to analyze PSA in human serum samples successfully, demonstrating the potential application of the proposed method for rapid clinical and early clinical diagnosis of prostate cancer in vitro.

O-150 Identification and validation of RPL7 and RCCD1 as potential biomarkers associated with immune infiltration in patients with thin endometrium

Abstract Study question For patients with thin endometrium (TE), what potential genes could be utilized for exploring the underlying mechanisms and clinical therapy? Summary answer Ribosomal protein L7 (RPL7) and RCC1 domain containing 1 (RCCD1) were suggested as specific biomarkers for TE. What is known already TE is an important contributor to embryo implantation failure and female infertility. However, the pathogenesis and mechanism of TE are not clear, and consequently, there is a paucity of data on effective targeted treatments for patients with TE. Study design, size, duration Endometrial cells were collected from 18 women with TE and 18 normal controls for transcriptional sequencing. Experimental validation was based on other 10 endometrium samples, consisting of 6 TE samples and 4 controls. Participants/materials, setting, methods After performing transcriptional sequencing, differentially expressed genes (DEGs) were extracted between the two groups via bioinformatic analysis. Based on DEGs, we applied functional enrichment and LASSO analysis to identify potential biomarkers, whose expressions were then validated by quantitative real-time PCR and western blot. Immune infiltration as well as the correlation with immune cells was also explored in the study. Main results and the role of chance RPL7 and RCC1 were identified and validated to be potential biomarkers, which exhibited an overexpression in TE at both mRNA and protein levels. An abnormal immune environment was found in TE, and correlation analysis showed that the two candidate genes correlated with atypical regulation of immune cells. Limitations, reasons for caution It might not be adequate to evaluate TE by only considering the immunologic aspects. Moreover, prospective studies are required to determine whether RPL7 and RCC1 may be used for early clinical diagnosis and prediction of pregnancy outcomes. Wider implications of the findings Further understanding and better knowledge of the functions of RPL7 and RCCD1 can promote the development of targeted therapeutics to improve clinical outcomes of patients with TE. Trial registration number not applicable

Necrotising fasciitis of the upper limb: a review of the literature.

Necrotising fasciitis is an uncommon life-threatening surgical emergency. While most commonly seen in the lower limb it can also affect the upper limb. This article reviews and summarises the current literature on necrotising fasciitis in the upper limb, covering common predisposing factors, clinical presentations, scoring systems, common organism types and the timing of surgical treatment. The key to managing this condition continues to be early clinical diagnosis and aggressive surgical debridement to attempt to reduce the morbidity and mortality of this condition.

Analysis of imaging features of rare tumors in nasal cavity and paranasal sinus

Objective:To explore the imaging features of rare tumors of nasal cavity and sinuses, and to improve the understanding of these diseases, thereby aiding clinical diagnosis and treatment. Methods:The CT and MRI findings of 79 cases of rare neoplasm of nasal cavity and sinuses confirmed by pathology were retrospectively analyzed, and the imaging features were summarized. Results:Among the 79 cases, there were 16 cases of neuroendocrine carcinoma, most showing expansive and infiltrative bone destruction without hyperosteogeny and sclerosis. The sphenoid sinus exhibited a "pigeon" shape. In 28 cases of malignant melanoma, MRI signals were diverse, typical signals were rare, but mixed signals were more common. In 12 cases of rhabdomyosarcoma, MRI enhancement mostly showed "grape-like" enhancement and partial ring enhancement; There were 10 cases of olfactory neuroblastoma, the lesions were consistent with the distribution area of olfactory mucosa, most of them were lobulated, marginal nodules, and "flower ring" enhancement, and 2 cases grew across intracranial and external, with multiple cystic lesions and surrounding flaky edema bands. In 5 cases of solitary fibrous tumor, Benign tumors had regular shape and uniform density, while malignant tumors had irregular shape and uneven density, The enhancement was obviously uneven and showed a "pattern" change. There were 2 cases of sarcomatoid carcinoma, both with lobed appearance, uneven density, lamellar low-density shadow, and osteolytic bone destruction. In 4 cases of schwannoma, the enhancement showed obvious inhomogeneous enhancement. One case showed cystic necrosis, one case showed calcification, and the surrounding structure was compressed without damage. There was 1 case of neurofibroma, with many cystic components, low signal separation and compartmentalized enhancement. One case of paraganglioma showed moderate enhancement in the arterial phase and progressive enhancement in the venous phase, accompanied by significant swelling bone destruction. Conclusion:Rare tumors of nasal cavity and paranasal sinuses have distinctive imaging features. CT and MRI can effectively show the extent of the lesions and the degree of infiltration into adjacent tissues and organs, which is helpful for early clinical diagnosis and staging. However, definitive diagnosis still depends on pathology and immunohistochemistry.

The Value of Serum Procalcitonin, Thromboelastography Combined with Platelet Count in Predicting the Short-Term Progression of Septic Shock in the Intensive Care Unit.

By evaluating the level of serum procalcitonin (PCT), thromboelastography (TEG) and platelet count (PLT) of patients with septic shock in intensive care unit (ICU), the predictive value of the combination of the three indicators on the short-term progression was discussed, which provided a new basis for early clinical diagnosis and disease evaluation. The clinical data of 130 patients with septic shock admitted to the IUC of our hospital from December 2021 to December 2023 were analyzed retrospectively. These subjects were divided into good prognosis group (n=78) and poor prognosis group (n=52) according to the 28 d deaths. The influencing factors were explored using the Multivariate logistic regression analysis. The value of single or combined PCT, PLT and TEG in predicting poor short-term prognosis was assessed using the receiver operating characteristic (ROC) curve. The patients in poor prognosis group had higher Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, serum PCT level, coagulation reaction time (R value) and coagulation formation time (K value), but lower PLT levels, final strength of coagulation (MA value) and coagulation formation rate (α angle) than those in good prognosis group (P<0.001). PCT, R value and K value were risk factors (P<0.001), while PLT, MA value and α angle were protective factors (P<0.001). The area under the curve (AUC) of PCT, PLT and TEG predicting poor short-term progression was 0.813, 0.658 and 0.752, respectively. The AUC of combined three indicators was 0.905, which had the highest predictive value. Serum levels of PCT, PLT and TEG had certain value in predicting poor short-term progression of septic shock patients, and their combined diagnostic value was higher. Therefore, regular monitoring of these three indicators could provide certain guiding significance for the prevention and treatment of poor short-term prognosis in patients with septic shock.

A cancer-targeted glutathione-gated probe for self-sufficient ST/CDT combination therapy and FRET-based miRNA imaging.

Acancer-targeted glutathione (GSH)-gated theranostic probe (CGT probe) for intracellular miRNA imaging and combined treatment of self-sufficient starvation therapy (ST) and chemodynamic therapy (CDT) was developed. TheCGT probe is constructed using MnO2 nanosheet (MS) as carrier material to adsorb the elaborately designed functional DNAs. It can be internalized by cancer cells via specific recognition between the AS1411 aptamer and nucleolin.After CGT probe entering the cancer cells, the overexpressed GSH, as gate-control, can degrade MS to Mn2+ which can be used for CDT by Fenton-like reaction. Simultaneously, Mn2+-mediated CDT can further cascade with the enzyme-like activities (catalase-like activity and glucose oxidase-like activity) of CGT probe, achieving self-sufficient ST/CDT synergistic therapy. Meanwhile, the anchored DNAs are released, achieving in situ signal amplification via disubstituted-catalytic hairpin assembly (DCHA) and FRET (fluorescence resonance energy transfer) imaging of miR-21. The in vitro and in vivo experiments demonstrated that accurate and sensitive miRNA detection can be achieved using the CGT probe. Overall, the ingenious CGT probe opens a new avenue for the development of early clinical diagnosis and cancer therapy.

Predicting renal damage in children with IgA vasculitis by machine learning.

Children with IgA Vasculitis (IgAV) may develop renal complications, which can impact their long-term prognosis. This study aimed to build a machine learning model to predict renal damage in children with IgAV and analyze risk factors for IgA Vasculitis with Nephritis (IgAVN). 50 clinical indicators were collected from 217 inpatients at our hospital. Six machine learning algorithms-Logistic Regression, Linear Discriminant Analysis, K-Nearest Neighbor, Support Vector Machine, Decision Trees, and Random Forest-were utilized to select the model with the highest predictive performance. A simplified model was developed through feature importance ranking and validated by an additional cohort with 46 patients. The random forest model had the highest accuracy, precision, recall, F1 score, and area under the curve, with values of 0.91, 0.98, 0.70, 0.79 and 0.94, respectively. The top 11 features according to the importance ranking were anti-streptolysin O, corticosteroids therapy, antihistamine therapy, absolute eosinophil count, immunoglobulin E, anticoagulant therapy, C-reactive protein, prothrombin time, age at onset, D-dimer, recurrence of rash ≥ 3 times. A simplified model using these features demonstrated optimal performance with an accuracy of 84.2%, a sensitivity of 89.4%, and a specificity of 82.5% in external validation. Finally, we provided a web tool based on the simplified model, whose code was published on https://github.com/mulanruo/IgAVN_Prediction . The model based on the random forest algorithm demonstrates good performance in predicting renal damage in children with IgAV, providing a basis for early clinical diagnosis and decision-making.

ATP citrate lyase promotes the progression of hepatocellular carcinoma by activating the REGγ-proteasome pathway.

The search for novel tumor biomarkers and targets is of significant importance for the early clinical diagnosis and treatment of Hepatocellular Carcinoma (HCC). The mechanisms by which ATP citrate lyase (ACLY) promotes HCC progression remain unclear, and the connection between ACLY and REGγ has not been reported in the literature. In vitro, we will perform overexpression/knockdown of ACLY or overexpression/knockdown of REGγ to investigate the impact of ACLY on HCC cells and its underlying mechanisms. In vivo, we will establish mouse tumor models with overexpression/knockdown of ACLY or overexpression/knockdown of REGγ to study the effect of ACLY on mouse tumors and its mechanisms. Firstly, ACLY overexpression upregulated REGγ expression and activated the REGγ-proteasome pathway, leading to changes in the expression of downstream signaling pathway proteins. This promoted HCC cell proliferation, invasion, and migration in vitro, as well as tumor growth and metastasis in vivo. Secondly, ACLY overexpression increased acetyl-CoA production, upregulated the acetylation level of the REGγ promoter region histone H3K27ac, and subsequently induced REGγ expression. Lastly, enhanced acetylation of the REGγ promoter region histone H3K27ac resulted in upregulated REGγ expression, activation of the REGγ-proteasome pathway, changes in downstream signaling pathway protein expression, and promotion of HCC cell proliferation, invasion, and migration in vitro, as well as tumor growth and metastasis in vivo. Conversely, REGγ knockdown reversed these effects. ACLY and REGγ may serve as potential biomarkers and clinical therapeutic targets for HCC.