Alternative polyadenylation regulates the translation of metabolic and inflammation-related proteins in adipose tissue of gestational diabetes mellitus.

In gestational diabetes mellitus (GDM), adipose tissue undergoes metabolic disturbances and chronic low-grade inflammation. Alternative polyadenylation (APA) is a post-transcriptional modification mechanism that generates mRNA with variable lengths of 3' untranslated regions (3'UTR), and it is associated with inflammation and metabolism. However, the role of APA in GDM adipose tissue has not been well characterized. In this study, we conducted transcriptomic and proteomic sequencing on subcutaneous and omental adipose tissues from both control and GDM patients. Using Dapars, a novel APA quantitative algorithm, we delineated the APA landscape of adipose tissue, revealing significant 3'UTR elongation of mRNAs in the GDM group. Omental adipose tissue exhibited a significant correlation between elongated 3'UTRs and reduced translation levels of genes related to metabolism and inflammation. Validation experiments in THP-1 derived macrophages (TDMs) demonstrated the impact of APA on translation levels by overexpressing long and short 3'UTR isoforms of a representative gene LRRC25. Additionally, LRRC25 was validated to suppress proinflammatory polarization in TDMs. Further exploration revealed two underexpressed APA trans-acting factors, CSTF3 and PPP1CB, in GDM omental adipose tissue. In conclusion, this study provides preliminary insights into the APA landscape of GDM adipose tissue. Reduced APA regulation in GDM omental adipose tissue may contribute to metabolic disorders and inflammation by downregulating gene translation levels. These findings advance our understanding of the molecular mechanisms underlying GDM-associated adipose tissue changes.

Single-cell Landscape of Malignant Transition: Unraveling Cancer Cell-of-Origin and Heterogeneous Tissue Microenvironment.

Understanding disease progression and sophisticated tumor ecosystems is imperative for investigating tumorigenesis mechanisms and developing novel prevention strategies. Here, we dissected heterogeneous microenvironments during malignant transitions by leveraging data from 1396 samples spanning 13 major tissues. Within transitional stem-like subpopulations highly enriched in precancers and cancers, we identified 30 recurring cellular states strongly linked to malignancy, including hypoxia and epithelial senescence, revealing a high degree of plasticity in epithelial stem cells. By characterizing dynamics in stem-cell crosstalk with the microenvironment along the pseudotime axis, we found differential roles of ANXA1 at different stages of tumor development. In precancerous stages, reduced ANXA1 levels promoted monocyte differentiation toward M1 macrophages and inflammatory responses, whereas during malignant progression, upregulated ANXA1 fostered M2 macrophage polarization and cancer-associated fibroblast transformation by increasing TGF-ß production. Our spatiotemporal analysis further provided insights into mechanisms responsible for immunosuppression and a potential target to control evolution of precancer and mitigate the risk for cancer development.

Impacts of gene variants on drug effects-the foundation of genotype-guided pharmacologic therapy for long QT syndrome and short QT syndrome.

The clinical significance of optimal pharmacotherapy for inherited arrhythmias such as short QT syndrome (SQTS) and long QT syndrome (LQTS) has been increasingly recognised. The advancement of gene technology has opened up new possibilities for identifying genetic variations and investigating the pathophysiological roles and mechanisms of genetic arrhythmias. Numerous variants in various genes have been proven to be causative in genetic arrhythmias. Studies have demonstrated that the effectiveness of certain drugs is specific to the patient or genotype, indicating the important role of gene-variants in drug response. This review aims to summarize the reported data on the impact of different gene-variants on drug response in SQTS and LQTS, as well as discuss the potential mechanisms by which gene-variants alter drug response. These findings may provide valuable information for future studies on the influence of gene variants on drug efficacy and the development of genotype-guided or precision treatment for these diseases.

HHIP protein interactions in lung cells provide insight into COPD pathogenesis.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. The primary causes of COPD are environmental, including cigarette smoking; however, genetic susceptibility also contributes to COPD risk. Genome-Wide Association Studies (GWASes) have revealed more than 80 genetic loci associated with COPD, leading to the identification of multiple COPD GWAS genes. However, the biological relationships between the identified COPD susceptibility genes are largely unknown. Genes associated with a complex disease are often in close network proximity, i.e. their protein products often interact directly with each other and/or similar proteins. In this study, we use affinity purification mass spectrometry (AP-MS) to identify protein interactions with HHIP , a well-established COPD GWAS gene which is part of the sonic hedgehog pathway, in two disease-relevant lung cell lines (IMR90 and 16HBE). To better understand the network neighborhood of HHIP , its proximity to the protein products of other COPD GWAS genes, and its functional role in COPD pathogenesis, we create HUBRIS, a protein-protein interaction network compiled from 8 publicly available databases. We identified both common and cell type-specific protein-protein interactors of HHIP. We find that our newly identified interactions shorten the network distance between HHIP and the protein products of several COPD GWAS genes, including DSP, MFAP2, TET2 , and FBLN5 . These new shorter paths include proteins that are encoded by genes involved in extracellular matrix and tissue organization. We found and validated interactions to proteins that provide new insights into COPD pathobiology, including CAVIN1 (IMR90) and TP53 (16HBE). The newly discovered HHIP interactions with CAVIN1 and TP53 implicate HHIP in response to oxidative stress.

Non-invasive diagnosis of bacterial and non-bacterial inflammations using a dual-enzyme-responsive fluorescent indicator.

Bacterial infections, as the second leading cause of global death, are commonly treated with antibiotics. However, the improper use of antibiotics contributes to the development of bacterial resistance. Therefore, the accurate differentiation between bacterial and non-bacterial inflammations is of utmost importance in the judicious administration of clinical antibiotics and the prevention of bacterial resistance. However, as of now, no fluorescent probes have yet been designed for the relevant assessments. To this end, the present study reports the development of a novel fluorescence probe (CyQ) that exhibits dual-enzyme responsiveness. The designed probe demonstrated excellent sensitivity in detecting NTR and NAD(P)H, which served as critical indicators for bacterial and non-bacterial inflammations. The utilization of CyQ enabled the efficient detection of NTR and NAD(P)H in distinct channels, exhibiting impressive detection limits of 0.26 µg mL-1 for NTR and 5.54 µM for NAD(P)H, respectively. Experimental trials conducted on living cells demonstrated CyQ's ability to differentiate the variations in NTR and NAD(P)H levels between A. baumannii, S. aureus, E. faecium, and P. aeruginosa-infected as well as LPS-stimulated HUVEC cells. Furthermore, in vivo zebrafish experiments demonstrated the efficacy of CyQ in accurately discerning variations in NTR and NAD(P)H levels resulting from bacterial infection or LPS stimulation, thereby facilitating non-invasive detection of both bacterial and non-bacterial inflammations. The outstanding discriminatory ability of CyQ between bacterial and non-bacterial inflammation positions it as a promising clinical diagnostic tool for acute inflammations.

Study of prognostic splicing factors in cancer using machine learning approaches.

Splicing factors (SFs) are the major RNA-binding proteins (RBPs) and key molecules that regulate the splicing of mRNA molecules through binding to mRNAs. The expression of splicing factors is frequently deregulated in different cancer types, causing the generation of oncogenic proteins involved in cancer hallmarks. In this study, we investigated the genes that encode RNA-binding proteins and identified potential splicing factors that contribute to the aberrant splicing applying a random forest classification model. The result suggested 56 splicing factors were related to the prognosis of 13 cancers, two SF complexes in liver hepatocellular carcinoma, and one SF complex in esophageal carcinoma. Further systematic bioinformatics studies on these cancer prognostic splicing factors and their related alternative splicing events revealed the potential regulations in a cancer-specific manner. Our analysis found high ILF2-ILF3 expression correlates with poor prognosis in LIHC through alternative splicing. These findings emphasize the importance of SFs as potential indicators for prognosis or targets for therapeutic interventions. Their roles in cancer exhibit complexity and are contingent upon the specific context in which they operate. This recognition further underscores the need for a comprehensive understanding and exploration of the role of SFs in different types of cancer, paving the way for their potential utilization in prognostic assessments and the development of targeted therapies.

Myotubularin-related-protein-7 inhibits mutant (G12V) K-RAS by direct interaction.

Inhibition of K-RAS effectors like B-RAF or MEK1/2 is accompanied by treatment resistance in cancer patients via re-activation of PI3K and Wnt signaling. We hypothesized that myotubularin-related-protein-7 (MTMR7), which inhibits PI3K and ERK1/2 signaling downstream of RAS, directly targets RAS and thereby prevents resistance. Using cell and structural biology combined with animal studies, we show that MTMR7 binds and inhibits RAS at cellular membranes. Overexpression of MTMR7 reduced RAS GTPase activities and protein levels, ERK1/2 phosphorylation, c-FOS transcription and cancer cell proliferation in vitro. We located the RAS-inhibitory activity of MTMR7 to its charged coiled coil (CC) region and demonstrate direct interaction with the gastrointestinal cancer-relevant K-RASG12V mutant, favouring its GDP-bound state. In mouse models of gastric and intestinal cancer, a cell-permeable MTMR7-CC mimicry peptide decreased tumour growth, Ki67 proliferation index and ERK1/2 nuclear positivity. Thus, MTMR7 mimicry peptide(s) could provide a novel strategy for targeting mutant K-RAS in cancers.

Gasdermin B, an asthma-susceptibility gene, promotes MAVS-TBK1 signaling and airway inflammation.

RATIONALE: Respiratory virus-induced inflammation is the leading cause of asthma exacerbation, frequently accompanied by induction of IFN-stimulated genes (ISGs). How asthma genetic susceptible genes modulate cellular response upon viral infection through fine-tuning ISGs induction and subsequent airway inflammation in genetically susceptible asthmatics remains largely unknown. OBJECTIVES: To decipher the functions of GSDMB in respiratory virus-induced lung inflammation. METHODS: In two independent cohorts, we analyzed expression correlation between GSDMB and ISGs. In human bronchial epithelial cell line or primary cells, we generated GSDMB-overexpressing and -deficient cells. A series of qPCR, ELISA and co-immunoprecipitation assays were performed to determine the function and mechanism of GSDMB for ISGs induction. We also generated a novel transgenic mouse line with inducible expression of human unique GSDMB gene in airway epithelial cells and applied respiratory syncytial virus (RSV) infection to determine the role of GSDMB on RSV-induced lung inflammation in vivo. MEASUREMENTS AND MAIN RESULTS: Gasdermin B encoded by GSDMB, one of the most significant asthma-susceptible genes at 17q21, acts as a novel RNA sensor, promoting MAVS-TBK1 signaling and subsequent inflammation. In airway epithelium, GSDMB is induced by respiratory viral infections. Expression of GSDMB and ISGs significantly correlated in respiratory epithelium from two independent asthma cohorts. Notably, inducible expression of human GSDMB gene in mouse airway epithelium leads to enhanced ISGs induction, increased airway inflammation with mucus hyper-secretion upon RSV infection. CONCLUSIONS: GSDMB promotes ISGs expression and airway inflammation upon respiratory virus infection, thereby conferring asthma risk in risk allele carriers.

Near-infrared electrochemiluminescence biosensors facilitated by thermally activated delayed fluorescence (TADF) emitters for ctDNA analysis.

The near-infrared electrochemiluminescence technique (NIR ECL) has gained significant attention as a powerful analytical tool in biomedicine and clinical diagnosis due to its inherent advantages. In this work, we successfully synthesized a novel NIR ECL emitter of TPA-DCPP nanoparticles (NPs) with a D-π-A-π-D configuration. By utilizing the thermally activated delayed fluorescence (TADF) property, we achieved enhanced electrochemiluminescence (ECL) emission through complete exciton harvesting for radiative decay. Specifically, when BDEA was used as a co-reactant, the TPA-DCPP NPs exhibited strong bandgap ECL emission. Additionally, they demonstrated an exceptionally higher ECL efficiency compared to conventional near-infrared fluorescence organic nanomaterials (BSeT-BT NPs). By integrating the efficient anodic ECL performance of TPA-DCPP NPs with Exo III-assisted polymerase enzyme reaction cascade amplification, a highly efficient ECL resonance energy transfer (ECL-RET) platform was developed for ultrasensitive detection of circulating tumor DNA (ctDNA). The established biosensor demonstrated an exceptional linear dynamic range and achieved attomolar-level detection limit. This study highlights the immense potential of TADF emitters in enhancing ECL efficiency and extends the emission wavelength of organic nanomaterials to the NIR region, thereby expanding their applications in biological analysis.

Identification of a distal enhancer regulating hedgehog interacting protein gene in human lung epithelial cells.

BACKGROUND: An intergenic region at chromosome 4q31 is one of the most significant regions associated with COPD susceptibility and lung function in GWAS. In this region, the implicated causal gene HHIP has a unique epithelial expression pattern in adult human lungs, in contrast to dominant expression in fibroblasts in murine lungs. However, the mechanism underlying the species-dependent cell type-specific regulation of HHIP remains largely unknown. METHODS: We employed snATAC-seq analysis to identify open chromatin regions within the COPD GWAS region in various human lung cell types. ChIP-quantitative PCR, reporter assays, chromatin conformation capture assays and Hi-C assays were conducted to characterize the regulatory element in this region. CRISPR/Cas9-editing was performed in BEAS-2B cells to generate single colonies with stable knockout of the regulatory element. RT-PCR and Western blot assays were used to evaluate expression of HHIP and epithelial-mesenchymal transition (EMT)-related marker genes. FINDINGS: We identified a distal enhancer within the COPD 4q31 GWAS locus that regulates HHIP transcription at baseline and after TGFß treatment in a SMAD3-dependent, but Hedgehog-independent manner in human bronchial epithelial cells. The distal enhancer also maintains chromatin topological domains near 4q31 locus and HHIP gene. Reduced HHIP expression led to increased EMT induced by TGFß in human bronchial epithelial cells. INTERPRETATION: A distal enhancer regulates HHIP expression both under homeostatic condition and upon TGFß treatment in human bronchial epithelial cells. The interaction between HHIP and TGFß signalling possibly contributes to COPD pathogenesis. FUNDING: Supported by NIH grants R01HL127200, R01HL148667 and R01HL162783 (to X. Z).

A Cell Cycle-aware Network for Data Integration and Label Transferring of Single-cell RNA-seq and ATAC-seq.

In recent years, the integration of single-cell multi-omics data has provided a more comprehensive understanding of cell functions and internal regulatory mechanisms from a non-single omics perspective, but it still suffers many challenges, such as omics-variance, sparsity, cell heterogeneity and confounding factors. As we know, cell cycle is regarded as a confounder when analyzing other factors in single-cell RNA-seq data, but it's not clear how it will work on the integrated single-cell multi-omics data. Here, we developed a Cell Cycle-Aware Network (CCAN) to remove cell cycle effects from the integrated single-cell multi-omics data while keeping the cell type-specific variations. This is the first computational model to study the cell-cycle effects in the integration of single-cell multi-omics data. Validations on several benchmark datasets show the out-standing performance of CCAN in a variety of downstream analyses and applications, including removing cell cycle effects and batch effects of scRNA-seq datasets from different protocols, integrating paired and unpaired scRNA-seq and scATAC-seq data, accurately transferring cell type labels from scRNA-seq to scATAC-seq data, and characterizing the differentiation process from hematopoietic stem cells to different lineages in the integration of differentiation data.

Stroke Related Brain-Heart Crosstalk: Pathophysiology, Clinical Implications, and Underlying Mechanisms.

The emergence of acute ischemic stroke (AIS) induced cardiovascular dysfunctions as a bidirectional interaction has gained paramount importance in understanding the intricate relationship between the brain and heart. Post AIS, the ensuing cardiovascular dysfunctions encompass a spectrum of complications, including heart attack, congestive heart failure, systolic or diastolic dysfunction, arrhythmias, electrocardiographic anomalies, hemodynamic instability, cardiac arrest, among others, all of which are correlated with adverse outcomes and mortality. Mounting evidence underscores the intimate crosstalk between the heart and the brain, facilitated by intricate physiological and neurohumoral complex networks. The primary pathophysiological mechanisms contributing to these severe cardiac complications involve the hypothalamic-pituitary-adrenal (HPA) axis, sympathetic and parasympathetic hyperactivity, immune and inflammatory responses, and gut dysbiosis, collectively shaping the stroke-related brain-heart axis. Ongoing research endeavors are concentrated on devising strategies to prevent AIS-induced cardiovascular dysfunctions. Notably, labetalol, nicardipine, and nitroprusside are recommended for hypertension control, while ß-blockers are employed to avert chronic remodeling and address arrhythmias. However, despite these therapeutic interventions, therapeutic targets remain elusive, necessitating further investigations into this complex challenge. This review aims to delineate the state-of-the-art pathophysiological mechanisms in AIS through preclinical and clinical research, unraveling their intricate interplay within the brain-heart axis, and offering pragmatic suggestions for managing AIS-induced cardiovascular dysfunctions.

Research on Pig Sound Recognition Based on Deep Neural Network and Hidden Markov Models.

In order to solve the problem of low recognition accuracy of traditional pig sound recognition methods, deep neural network (DNN) and Hidden Markov Model (HMM) theory were used as the basis of pig sound signal recognition in this study. In this study, the sounds made by 10 landrace pigs during eating, estrus, howling, humming and panting were collected and preprocessed by Kalman filtering and an improved endpoint detection algorithm based on empirical mode decomposition-Teiger energy operator (EMD-TEO) cepstral distance. The extracted 39-dimensional mel-frequency cepstral coefficients (MFCCs) were then used as a dataset for network learning and recognition to build a DNN- and HMM-based sound recognition model for pig states. The results show that in the pig sound dataset, the recognition accuracy of DNN-HMM reaches 83%, which is 22% and 17% higher than that of the baseline models HMM and GMM-HMM, and possesses a better recognition effect. In a sub-dataset of the publicly available dataset AudioSet, DNN-HMM achieves a recognition accuracy of 79%, which is 8% and 4% higher than the classical models SVM and ResNet18, respectively, with better robustness.

The metabolic role of the CD73/adenosine signaling pathway in HTR-8/SVneo cells: A Double-Edged Sword?

The ecto-5'-nucleotidase (CD73)/adenosine signaling pathway has been reported to regulate tumor epithelial-mesenchymal transition (EMT), migration and proliferation. However, little is known about the metabolic mechanisms underlying its role in trophoblast proliferation and migration. In this study, we aimed to investigate the metabolic role of the CD73/adenosine signaling pathway on the proliferation and migration of trophoblast. We found that CD73 levels were upregulated in preeclamptic placentas compared with the placentas of normotensive pregnant women. EMT and migration of HTR-8/SVneo cells were enhanced when treated with a CD73 inhibitor (100 µM) in vitro. Conversely, excessive adenosine (25 or 50 µM) suppressed trophoblast cell EMT, migration and proliferation. RNA-seq, metabolomics and seahorse findings showed that adenosine treatment resulted in increased expression of PDK1, suppression of aerobic respiration, glycolysis and amino acids synthesis, as well as increased utilization of short-chain fatty acids (SCFAs). Furthermore, the 13C-adenosine isotope tracking experiment demonstrated that adenosine served as a carbon source for the tricarboxylic acid (TCA) cycle. Our results reveal the role of adenosine in regulating trophoblast energy metabolism is like a double-edged sword - either inhibiting aerobic respiration or supplementing carbon sources into metabolic flux. CD73/adenosine signaling regulated trophoblast EMT, migration, and proliferation by modulating energy metabolism. This study indicates that CD73/adenosine signaling potentially plays a role in the occurrence of placenta-derived diseases, including preeclampsia.

Exploring resting-state EEG oscillations in patients with Neuromyelitis Optica Spectrum Disorder.

BACKGROUND AND OBJECTIVE: Quantitative resting-state electroencephalography (rs-EEG) is a convenient method for characterizing the functional impairments and adaptations of the brain that has been shown to be valuable for assessing many neurological and psychiatric disorders, especially in monitoring disease status and assisting neuromodulation treatment. However, it has not yet been explored in patients with neuromyelitis optica spectrum disorder (NMOSD). This study aimed to investigate the rs-EEG features of NMOSD patients and explore the rs-EEG features related to disease characteristics and complications (such as anxiety, depression, and fatigue). METHODS: A total of 32 NMOSD patients and 20 healthy controls (HCs) were recruited; their demographic and disease information were collected, and their anxiety, depression, and fatigue symptoms were evaluated. The rs-EEG power spectra of all the participants were obtained. After excluding the participants with low-quality rs-EEG data during processing, statistical analysis was conducted based on the clinical information and rs-EEG data of 29 patients and 19 HCs. The rs-EEG power (the mean spectral energy (MSE) of absolute power and relative power in all frequency bands, as well as the specific power for all electrode sites) of NMOSD patients and HCs was compared. Furthermore, correlation analyses were performed between rs-EEG power and other variables for NMOSD patients (including the disease characteristics and complications). RESULTS: The distribution of the rs-EEG power spectra in NMOSD patients was similar to that in HCs. The dominant alpha-peaks shifted significantly towards a lower frequency for patients when compared to HCs. The delta and theta power was significantly increased in the NMOSD group compared to that in the HC group. The alpha oscillation power was found to be significantly negatively associated with the degree of anxiety (reflected by the anxiety subscore of hospital anxiety and depression scale (HADS)) and the degree of depression (reflected by the depression subscore of HADS). The gamma oscillation power was revealed to be significantly positively correlated with the fatigue severity scale (FSS) score, while further analysis indicated that the electrode sites of almost the whole brain region showing correlations with fatigue. Regarding the disease variables, no statistically significant rs-EEG features were related to the main disease features in NMOSD patients. CONCLUSION: The results of this study suggest that the rs-EEG power spectra of NMOSD patients show increased slow oscillations and are potential biomarkers of widespread white matter microstructural damage in NMOSD. Moreover, this study revealed the rs-EEG features associated with anxiety, depression, and fatigue in NMOSD patients, which might help in the evaluation of these complications and the development of neuromodulation treatment. Quantitative rs-EEG analysis may play an important role in the management of NMOSD patients, and future studies are warranted to more comprehensively understand its application value.

Molecular Engineering of Bright NIR-I/NIR-II Nanofluorophores for High-Resolution Bioimaging and Tumor Detection in Vivo.

A comprehensive approach for the construction of NIR-I/NIR-II nanofluorophores with exceptional brightness and excellent chemo- and photostability has been developed. This study first confirmed that the amphiphilic molecules with stronger hydrophobic moieties and weaker hydrophilic moieties are superior candidates for constructing brighter nanofluorophores, which are attributed to its higher efficiency in suppressing the intramolecular charge transfer/aggregation-caused fluorescence quenching of donor-acceptor-donor type fluorophores. The prepared nanofluorophore demonstrates a fluorescence quantum yield exceeding 4.5% in aqueous solution and exhibits a strong NIR-II tail emission up to 1300 nm. The superior performance of the nanofluorophore enabled the achievement of high-resolution whole-body vessel imaging and brain vessel imaging, as well as high-contrast fluorescence imaging of the lymphatic system in vivo. Furthermore, their potential for highly sensitive fluorescence detection of tiny tumors in vivo has been successfully confirmed, thus supporting their future applications in precise fluorescence imaging-guided surgery in the early stages of cancer.

Effectiveness of bone grafting versus cannulated screw fixation in the treatment of posterolateral tibial plateau compression fractures with concomitant ACL injury: a comparative study.

BACKGROUND: Posterolateral tibial plateau compression fractures (PTPCF) are one of the significant factors leading to knee instability and anterior cruciate ligament (ACL) reconstruction failure. The effectiveness of fixation for such cases without the use of metal implants remains inconclusive. The aim of this study is to investigate whether the fixation with isolated bone grafting is stable enough for the treatment of PTPCF with concomitant ACL injuries. METHODS: This retrospective study analyzed patients treated for concomitant ACL injuries and PTPCF in authors' institution. A total of 53 patients (21 males and 32 females) with an average age of 47.43 ± 14.71 years were included. Patient data were collected, including factors leading to injury, affected side, height, weight, and basic medical history. The posterior inclination angle and the lateral tibial plateau lateral inclination angle were measured to evaluate the fixation stability. Rasmussen functional score and HSS score were used to assess the knee functional recovery. RESULTS: The bone grafting group achieved satisfactory levels of Rasmussen score (28.22 ± 0.85) and HSS knee joint function scores (95.57 ± 1.97). The cannulated screw fixation group had a Rasmussen knee joint function score of 28.70 ± 0.92 and a HSS knee joint function score of 96.07 ± 1.93. No statistically significant difference was found (P > 0.05). The cannulated screw fixation group had a mean posterior inclination angle reduction loss of 0.20° ± 1.11°, while the bone grafting group had a reduction loss of 0.18° ± 1.01°, with no statistically significant difference (P > 0.05). The cannulated screw fixation group had a lateral inclination angle reduction loss of 0.01° ± 0.37°, and the bone grafting group had a reduction loss of 0.03° ± 0.43°, with no statistically significant difference (P > 0.05). CONCLUSION: The use of bone grafting for fixation of PTPCF with accompanying ACL injuries demonstrated no substantial disparities in knee joint function. In cases of simple PTPCF, filling and compacting the bone defect underneath the tibial plateau fracture fragment can yield satisfactory fixation, obviating the necessity for supplementary cannulate screw fixation.

Biomedical Big Data Technologies, Applications, and Challenges for Precision Medicine: A Review.

The explosive growth of biomedical Big Data presents both significant opportunities and challenges in the realm of knowledge discovery and translational applications within precision medicine. Efficient management, analysis, and interpretation of big data can pave the way for groundbreaking advancements in precision medicine. However, the unprecedented strides in the automated collection of large-scale molecular and clinical data have also introduced formidable challenges in terms of data analysis and interpretation, necessitating the development of novel computational approaches. Some potential challenges include the curse of dimensionality, data heterogeneity, missing data, class imbalance, and scalability issues. This overview article focuses on the recent progress and breakthroughs in the application of big data within precision medicine. Key aspects are summarized, including content, data sources, technologies, tools, challenges, and existing gaps. Nine fields-Datawarehouse and data management, electronic medical record, biomedical imaging informatics, Artificial intelligence-aided surgical design and surgery optimization, omics data, health monitoring data, knowledge graph, public health informatics, and security and privacy-are discussed.

A stable ratiometric fluorescent probe for hypochlorous acid detection and rheumatoid arthritis evaluation.

A ratiometric fluorescent probe (MeO-CNPPV Pdots) based on the principle of fluorescence resonance energy transfer (FRET) was designed for hypochlorous acid (HOCl) and rheumatoid arthritis (RA) detection. The presence of HOCl can block the energy transfer from CNPPV to MeOTPATBT, resulting in a ratio change in the fluorescence of Pdots (I600 nm/I680 nm). This strategy provides a valuable paradigm in early RA evaluation.

Robotic-assisted total knee arthroplasty improves implant position and early functional recovery for the knee with severe varus/valgus deformity.

PURPOSE: Robotic-assisted total knee arthroplasty (r-TKA) facilitates precise bone resection and lower limb alignment, yet accuracy and functional recovery for severe varus/valgus deformity is not well-documented. The aim of study was to investigate whether r-TKA improves implant alignment in the coronal and sagittal view and early functional recovery compared to conventional TKA(c-TKA). METHODS: This comparative study included 86 patients with symptomatic knee arthritis who underwent primary TKA at our institution between 1st May and 31th November 2021. Radiological parameters evaluated included hip-knee-ankle angle (HKAA), femoral varus-valgus angle (FVVA), tibial varus-valgus angle (TVVA), posterior tibial slope angle (PTSA), femoral sagittal angle (FSA), posterior condylar offset ratio, and Insall-Salvati index. Operative time, stay length, and complications were reviewed from patient records. The hospital for special surgery (HSS), Visual Analogue Scale (VAS) and knee joint motion range were evaluated at the six-month follow-up. RESULTS: The c-TKA and r-TKA groups had no significant differences in HKAA (179.73 ± 3.76°, range: 172.10-188.90° vs. 180.53 ± 2.91°, range: 173.30-188.32°, p = 0.277), FVVA (96.13 ± 2.61°, range: 90.27-101.52° vs. 96.38 ± 2.23°, range: 90.98-100.95°, p = 0.636), and TVVA (88.74 ± 2.03°, range: 83.75-92.74° vs. 89.43 ± 1.83°, range: 85.32-94.15°, p = 1.000). Outlier of mechanical alignment incidence (> 3°) was significantly lower in r-TKA compared with c-TKA, 17.50% (7/40) vs. 41.30% (19/46), (p = 0.017). PTSA of r-TKA remained significantly lower than c-TKA (p = 0.009) in mild-deformity patients. For severe varus/valgus deformity, r-TKA had a significantly lesser HKAA-outlier incidence (p = 0.025), PTSA-outlier incidence (p = 0.019), and lower PTSA (p < 0.001) compared with c-TKA. The r-TKA functional outcome was better than c-TKA regarding HSS (93.12 ± 1.97, range: 90-95, 95%CI:92.11-94.13 vs. 91.33 ± 2.50, range: 85-95, 95%CI:90.20-92.69, p = 0.036), and VAS (0.24 ± 0.44, range:0-1 vs. 0.72 ± 0.75, range:0-2, p = 0.026), knee joint flexion (118.53° ± 8.06, range: 105-130°, 95%CI:114.39-122.67° vs. 112.22 ± 8.09°, range: 100-130°, 95%CI:108.20-116.24° ,p = 0.027) for severe varus/valgus deformity. CONCLUSION: r-TKA improved lower-limb coronal alignment, sagittal implant position, and early functional recovery for patients with severe varus/valgus deformity of the knee. r-TKA did not confer substantial advantages over c-TKA in both radiological and clinical outcomes for the mild varus/valgus deformity.