Chemoenzymatic Dynamic Kinetic Resolution Protocol with an Immobilized Oxovanadium as a Racemization Catalyst.

An excellent compatible and cost-effective dynamic kinetic resolution (DKR) protocol has been developed by combining a novel immobilized oxovanadium racemization catalyst onto cheap diatomite (V-D) with an immobilized lipase LA resolution catalyst onto a macroporous resin (LA-MR). V-D was prepared via grinding immobilization, which may become a promising alternative for the immobilization of metals, especially precious metals due to its low cost, high efficiency, easy separation, and large reaction interface. The DKR afforded high yield (96.1%), e.e. (98.67%), and Sel (98.28%) under optimal conditions established using response surface methodology as follows: the amount of V-D 10.83 mg, reaction time 51.2 h, and temperature 48.1 °C, respectively, indicating that all the reactions in the DKR were coordinated very well. The DKR protocol was also found to have high stability up to six reuses. V-D exhibited excellent compatibility with LA-MR because the lipase immobilized onto MR did not physically contact with the vanadium species immobilized onto diatomite, thus avoiding inactivation. Considering that lipase, oxovanadium, diatomite, and MR used are relatively inexpensive, and the adsorption or grinding immobilization is simple, the LA-V-MD DKR by coupling LA-MR with V-D is a cost-effective and promising protocol for chiral secondary alcohols.

Prognostic Significance of the Highest Mediastinal Lymph Node Involvement in Patients with Stage III-N2 Non-small Cell Lung Cancer.

BACKGROUND: Highest mediastinal lymph node (HMLN) involvement is a category of uncertain resection, yet the prognostic significance of HMLN involvement remains controversial. METHODS: A total of 486 patients with pathological stage III-N2 disease who underwent radical resection were enrolled from January 2015 to December 2018. Patients were allocated into two groups-HMLN involvement (219 cases) and HMLN-negative (249 cases) groups. Kaplan-Meier analysis and Cox proportional hazard regression models were used to evaluate the impact of HMLN involvement on 5-year recurrence-free survival (RFS) and overall survival (OS). RESULTS: The proportion of patients with multiple N2 diseases (72.1% vs. 23.7%; p < 0.001) and stage IIIA (87.2% vs. 77.5%; p < 0.009) were greater in the HMLN-involvement group than in the HMLN-negative group, and the survival rates of the HMLN-involvement group were significantly lower than those of the HMLN-negative group (RFS: 27.2% vs. 49.8%, p < 0.001; OS: 42.1% vs. 59.2%, p = 0.001). HMLN status was an independent factor for OS only (RFS: adjusted hazard ratio [aHR] 1.26, 95% confidence interval CI 0.94-1.68; OS: aHR 1.45, 95% CI 1.07-1.99) in the entire stage III cohort. After stratification of patients according to stage, the involvement of HMLN decreased both RFS and OS in the stage IIIA group (RFS: aHR 1.46, 95% CI 1.06-2.02; OS: aHR 1.70, 95% CI 1.19-2.42); however, no such difference was observed within the stage IIIB group. CONCLUSIONS: HMLN involvement is a prognostic factor of deteriorating survival in highly advanced N2 disease only in patients with stage IIIA.

Establishment and validation of nomograms to predict the overall survival and cancer-specific survival for non-metastatic bladder cancer patients: A large population-based cohort study and external validation.

This study aimed to develop nomograms to accurately predict the overall survival (OS) and cancer-specific survival (CSS) of non-metastatic bladder cancer (BC) patients. Clinicopathological information of 260,412 non-metastatic BC patients was downloaded from the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2020. LASSO method and Cox proportional hazard regression analysis were utilized to discover the independent risk factors, which were used to develop nomograms. The accuracy and discrimination of models were tested by the consistency index (C-index), the area under the subject operating characteristic curve (AUC) and the calibration curve. Decision curve analysis (DCA) was used to test the clinical value of nomograms compared with the TNM staging system. Nomograms predicting OS and CSS were constructed after identifying independent prognostic factors. The C-index of the training, internal validation and external validation cohort for OS was 0.722 (95%CI: 0.720-0.724), 0.723 (95%CI: 0.721-0.725) and 0.744 (95%CI: 0.677-0.811). The C-index of the training, internal validation and external validation cohort for CSS was 0.794 (95%CI: 0.792-0.796), 0.793 (95%CI: 0.789-0.797) and 0.879 (95%CI: 0.814-0.944). The AUC and the calibration curves showed good accuracy and discriminability. The DCA showed favorable clinical potential value of nomograms. Kaplan-Meier curve and log-rank test uncovered statistically significance survival difference between high- and low-risk groups. We developed nomograms to predict OS and CSS for non-metastatic BC patients. The models have been internally and externally validated with accuracy and discrimination and can assist clinicians to make better clinical decisions.

Silk fibroin/methacrylated gelatine/hydroxyapatite biomimetic nanofibrous membranes for guided bone regeneration.

By mimicking in vivo bionic microenvironment and promoting osteogenic differentiation, the hybrid organic-inorganic nanofibrous membranes provide promising potential for guided bone regeneration (GBR) in the treatment of clinical bone defects. To develop a degradable and osteogenic membrane for GBR by combining the natural biomacromolecule silk fibroin (SF) and gelatine with the bioactive nano hydroxyapatite (nHA), the anhydride-modified gelatine-nano hydroxyapatite (GelMA-nHA) composites were synthesized in situ and introduced into silk fibroin to prepare nanofibrous membranes with different ratios using electrospinning and photocrosslinking. The nanofibrous membranes, particularly those with a mass ratio of 7:2:1, were found to exhibit satisfactory elongation at break up to 110 %, maintain the nanofibrous structure for up to 28 days, and rapidly form bone-like apatite within 3 days, thus offering advantages when it comes to guided bone regeneration. In vitro cell results showed that the SF/GelMA/nHA membranes had excellent biocompatibility and enhanced osteogenic differentiation of hBMSCs. In vivo studies revealed that the hybrid composite membranes can improve bone regeneration of critical-sized calvarial defects in rat model. Therefore, the novel hybrid nanofibrous membrane is proposed to be a alternative candidate for creating a bionic microenvironment that promotes bone regeneration, indicating their potential application to bone injury treatment.

Machine Learning Supported the Modified Gustafson's Criteria for Dental Age Estimation in Southwest China.

Adult age estimation is one of the most challenging problems in forensic science and physical anthropology. In this study, we aimed to develop and evaluate machine learning (ML) methods based on the modified Gustafson's criteria for dental age estimation. In this retrospective study, a total of 851 orthopantomograms were collected from patients aged 15 to 40 years old. The secondary dentin formation (SE), periodontal recession (PE), and attrition (AT) of four mandibular premolars were analyzed according to the modified Gustafson's criteria. Ten ML models were generated and compared for age estimation. The partial least squares regressor outperformed other models in males with a mean absolute error (MAE) of 4.151 years. The support vector regressor (MAE = 3.806 years) showed good performance in females. The accuracy of ML models is better than the single-tooth model provided in the previous studies (MAE = 4.747 years in males and MAE = 4.957 years in females). The Shapley additive explanations method was used to reveal the importance of the 12 features in ML models and found that AT and PE are the most influential in age estimation. The findings suggest that the modified Gustafson method can be effectively employed for adult age estimation in the southwest Chinese population. Furthermore, this study highlights the potential of machine learning models to assist experts in achieving accurate and interpretable age estimation.

The role of IL-36 and 37 in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has garnered considerable attention due to its morbidity and mortality. Although the precise mechanisms underlying HCC tumorigenesis remain to be elucidated, evidence suggests that host immunity plays a pivotal role in its development. IL-36 and IL-37 are important immunoregulatory cytokines classified as pro-inflammatory and anti-inflammatory respectively. In the context of HCC, the downregulation of intrahepatic IL-36 is inversely correlated with cirrhosis, but positively correlated with 5-year survival rates, suggesting that IL-36 offers protection during HCC development. However, IL-36 may lose its hepatoprotective effects as the disease progresses to HCC in the context of dysregulated immunity in cirrhotic patients. Substantially increased circulating IL-36 in HCC patients is likely a systemic response to HCC stimulation, but is insufficient to suppress progression towards HCC. Intrahepatic IL-37 is suppressed in HCC patients, consistent with the inverse correlation between intrahepatic IL-37 and the level of AFP in HCC patients, suggesting IL-37 exerts hepatoprotection. There is no significant difference in IL-37 among differentiations of HCC or with respect to clinical BCLC stages or cirrhosis status in HCC patients. However, IL-37 protection is demonstrated in an IL-37 transfected HCC animal model, showing significantly reduced tumour size. IL-36/37 may inhibit HCC by enhancing M1 tumour-associated macrophages while not affecting M2 macrophages. The interplay between IL-36 (pro-inflammatory) and IL-37 (anti-inflammatory) is emerging as a crucial factor in host protection against the development of HCC. Further research is needed to investigate the complex mechanisms involved and the therapeutic potential of targeting these cytokines in HCC management.

Adult age estimation from the sternum using maximum intensity projection images of CT and data mining in a Chinese population.

This study aimed to explore and develop data mining models for adult age estimation based on CT reconstruction images from the sternum. Maximum intensity projection (MIP) images of chest CT were retrospectively collected from a modern Chinese population, and data from 2700 patients (1349 males and 1351 females) aged 20 to 70 years were obtained. A staging technique within four indicators was applied. Several data mining models were established, and mean absolute error (MAE) was the primary comparison parameter. The intraobserver and interobserver agreement levels were good. Within internal validation, the optimal data mining model obtained the lowest MAE of 9.08 in males and 10.41 in females. For the external validation (N = 200), MAEs were 7.09 in males and 7.15 in females. In conclusion, the accuracy of our model for adult age estimation was among similar studies. MIP images of the sternum could be a potential age indicator. However, it should be combined with other indicators since the accuracy level is still unsatisfactory.

Machine learning and deep learning enabled age estimation on medial clavicle CT images.

The medial clavicle epiphysis is a crucial indicator for bone age estimation (BAE) after hand maturation. This study aimed to develop machine learning (ML) and deep learning (DL) models for BAE based on medial clavicle CT images and evaluate the performance on normal and variant clavicles. This study retrospectively collected 1049 patients (mean± SD: 22.50±4.34 years) and split them into normal training and test sets, and variant training and test sets. An additional 53 variant clavicles were incorporated into the variant test set. The development stages of normal MCE were used to build a linear model and support vector machine (SVM) for BAE. The CT slices of MCE were automatically segmented and used to train DL models for automated BAE. Comparisons were performed by linear versus ML versus DL, and normal versus variant clavicles. Mean absolute error (MAE) and classification accuracy was the primary parameter of comparison. For BAE, the SVM had the best MAE of 1.73 years, followed by the commonly-used CNNs (1.77-1.93 years), the linear model (1.94 years), and the hybrid neural network CoAt Net (2.01 years). In DL models, SE Net 18 was the best-performing DL model with similar results to SVM in the normal test set and achieved an MAE of 2.08 years in the external variant test. For age classification, all the models exhibit superior performance in the classification of 18-, 20-, 21-, and 22-year thresholds with limited value in the 16-year threshold. Both ML and DL models produce desirable performance in BAE based on medial clavicle CT.

NR_103776.1 as a novel diagnostic biomarker for systemic lupus erythematosus.

BACKGROUND: With the development of sequencing technologies, there is increasing evidence that long noncoding RNAs (lncRNAs) are involved in systemic lupus erythematosus (SLE). The level of NR_103776.1 expression in SLE and its clinical associations are still not well defined. OBJECTIVE: To identify differentially expressed lncRNAs and explore their functional roles in SLE. METHODS: Transcriptome sequencing was used to screen differentially expressed lncRNAs and mRNAs. Expression validation of clinical samples was performed by QRT-PCR. Bioinformatics was used to analyze its prognostic value and potential function. RESULTS: Of the 231 significantly differentially expressed lncRNAs, NR_103776.1 could be used to distinguish not only SLE patients and rheumatoid arthritis patients but also active SLE patients, stable SLE patients, and healthy controls. NR_103776.1 was significantly and negatively correlated with inflammatory indexes (CRP and ESR). NR_103776.1 dysregulation might contribute to the metabolism of RNA and proteins in SLE patients. CONCLUSIONS: This study not only provided a transcriptome profile of lncRNAs aberrantly expressed in individual nucleated cells of SLE patients but also suggested NR_103776.1 as a novel potential diagnostic biomarker.

Automated bone age assessment from knee joint by integrating deep learning and MRI-based radiomics.

Bone age assessment (BAA) is a crucial task in clinical, forensic, and athletic fields. Since traditional age estimation methods are suffered from potential radiation damage, this study aimed to develop and evaluate a deep learning radiomics method based on multiparametric knee MRI for noninvasive and automatic BAA. This retrospective study enrolled 598 patients (age range,10.00-29.99 years) who underwent MR examinations of the knee joint (T1/T2*/PD-weighted imaging). Three-dimensional convolutional neural networks (3D CNNs) were trained to extract and fuse multimodal and multiscale MRI radiomic features for age estimation and compared to traditional machine learning models based on hand-crafted features. The age estimation error was greater in individuals aged 25-30 years; thus, this method may not be suitable for individuals over 25 years old. In the test set aged 10-25 years (n = 95), the 3D CNN (a fusion of T1WI, T2*WI, and PDWI) demonstrated the lowest mean absolute error of 1.32 ± 1.01 years, which is higher than that of other MRI modalities and the hand-crafted models. In the classification for 12-, 14-, 16-, and 18- year thresholds, accuracies and the areas under the ROC curves were all over 0.91 and 0.96, which is similar to the manual methods. Visualization of important features showed that 3D CNN estimated age by focusing on the epiphyseal plates. The deep learning radiomics method enables non-invasive and automated BAA from multimodal knee MR images. The use of 3D CNN and MRI-based radiomics has the potential to assist radiologists or medicolegists in age estimation.

Predicting micropapillary or solid pattern of lung adenocarcinoma with CT-based radiomics, conventional radiographic and clinical features.

BACKGROUND: To build prediction models with radiomics features, clinical/conventional radiographic signs and combined scores for the discrimination of micropapillary or solid subtypes (high-risk subtypes) of lung adenocarcinoma. METHODS: This retrospective study enrolled 351 patients with and without high-risk subtypes. Least Absolute Shrinkage and Selection Operator (LASSO) regression with cross-validation was performed to determine the optimal features of radiomics model. Missing clinical data were imputed by Multiple Imputation with Chain Equations (MICE). Clinical model with radiographic signs was built and scores of both models were integrated to establish combined model. Receiver operating characteristics (ROC) curves, area under ROC curves and decision curve analysis (DCA) were plotted to evaluate the model performance and clinical application. RESULTS: Stratified splitting allocated 246 patients into training set. MICE for missing values obtained complete and unbiased data for the following analysis. Ninety radiomic features and four clinical/conventional radiographic signs were used to predict the high-risk subtypes. The radiomic model, clinical model and combined model achieved AUCs of 0.863 (95%CI: 0.817-0.909), 0.771 (95%CI: 0.713-0.713) and 0.872 (95%CI: 0.829-0.916) in the training set, and 0.849 (95%CI: 0.774-0.924), 0.778 (95%CI: 0.687-0.868) and 0.853 (95%CI: 0.782-0.925) in the test set. Decision curve showed that the radiomic and combined models were more clinically useful when the threshold reached 37.5%. CONCLUSIONS: Radiomics features could facilitate the prediction of subtypes of lung adenocarcinoma. A simple combination of radiomics and clinical scores generated a robust model with high performance for the discrimination of micropapillary or solid subtype of lung adenocarcinoma.

Colorimetric Sensor Based on the Oxidase-Mimic Supramolecular Catalyst for Selective and Sensitive Biomolecular Detection.

We have engineered a colorimetric sensor capable of selective and sensitive detection of amino acids. This sensor employs a supramolecular copper-dependent oxidase mimic as the probe, stemming from our prior research. The oxidase mimic is constructed through the self-assembly of commercially available guanosine monophosphate (GMP), Fmoc-lysine, and Cu2+. It catalyzes the formation of a red product with a maximum absorbance at 510 nm. The changes in color and absorbance are responsive to both the concentrations and types of amino acids present. This effect is most pronounced in the presence of histidine, with a detection limit (LOD) of 6.4 nM. Furthermore, the catalytic probe can distinguish histidine from histamine and imidazole propionate, as well as 1-methyl-histidine from 3-methyl-histidine, based on their distinct coordination capacities with copper. This underscores the high selectivity of the sensing platform. Both theoretical simulations and experimental results (including UV-vis spectra, fluorescence, and EPR) indicate that the amino acids may engage in copper center coordination, thereby impeding O2 access to copper─a pivotal aspect of the oxidase catalysis. This sensing platform, characteristic of its swift response, simple fabrication, and exceptional sensitivity and selectivity, can also be applied to detect other biological analytes such as nucleotides. It holds potential for use in environmental and biochemical analyses.

Wavelength sensitivity reconfigurable SPR photodetector with a blazed grating profile.

Surface plasmonic detectors based on one-dimensional half-wavelength gratings have attracted attention due to their wavelength- or polarization-specific photodetection. Although the effect of a grating period and a grating depth on the photoelectric conversion of 1D half-wavelength grating-based surface plasmon resonance (SPR) detectors has been discussed thoroughly in recent years, the effect of different grating profiles on device performance is still limited to the rectangular shape. In this article, we proposed a wavelength sensitivity reconfigurable photodetector enhanced by SPR with a blazed grating profile. The gold layer was fabricated on a silicon-based blazed grating to form a Schottky barrier and act as an SPR coupler. By measuring the photocurrent in the range of -58° to -48°of an incident angle, the peak shifts of a photocurrent signal waveform are found to depend on the wavelength over 800-1000 nm.

Human Mesenchymal Stem Cells-Derived Exosome Mimetic Vesicles Regulation of the MAPK Pathway and ROS Levels Inhibits Glucocorticoid-Induced Apoptosis in Osteoblasts.

Background: Long-term extensive use of glucocorticoids will lead to hormonal necrosis of the femoral head, and osteoblasts play an important role in the prevention of osteonecrosis. However, there is no complete cure for necrosis of the femoral head. Mesenchymal stem cell- (MSCs-) derived exosomes are widely used for the repair of various tissue lesions. Therefore, the aim of this study was to investigate the mechanism of dexamethasone- (DEX-) induced osteoblast apoptosis and the therapeutic effect of human umbilical cord MSC- (hucMSC-) derived exosome mimetic vesicles (EMVs) on osteoblast-induced apoptosis by DEX. Methods: The viability and apoptosis of primary MC3T3-E1 cells were determined by the Cell Counting Kit-8 (CCK-8), FITC-Annexin V/PI staining and immunoblot. The intracellular levels of reactive oxygen species (ROS) after DEX treatment were measured by 2', 7' -dichlorodihydrofluorescein diacetate (DCFH-DA) staining. In this study, hucMSC-EMVs and N-acetyl-l-cysteine (NAC) were used as therapeutic measures. The expression of B-cell lymphoma 2-associated X, Bcl 2, HO-1, and nuclear factor erythroid-derived 2-like 2 and MAPK- signaling pathway in osteogenic cell MC3T3-E1 cells treated with Dex was analyzed by the immunoblotting. Results: DEX significantly induced osteoblasts MC3T3-E1 apoptosis and ROS accumulation. MAPK-signaling pathway was activated in MC3T3-E1 after DEX treatment. hucMSC-EMVs intervention significantly downregulated DEX-induced MAPK-signaling pathway activation and ROS accumulation. In addition, hucMSC-EMVs can reduce the apoptosis levels in osteoblast MC3T3-E1 cells induced by DEX. Conclusions: Our study confirmed that hucMSC-EMVs regulates MAPK-signaling pathway and ROS levels to inhibit DEX-induced osteoblast apoptosis.

Analysis of the Ability of a Distal Tibial Anatomical Locking Plate to Capture the Distal Tibial Fragments in Patients with Pilon Fractures.

OBJECTIVE: Although pilon fractures are rare in clinical practice, they are difficult to treat because of their complexity. Effective fixation of the fracture fragment is the key to the treatment of pilon fractures. Plate osteosynthesis is common clinically, but there are many types of plates and the evaluation of the effect of fixation plates is not comprehensive. This study attempted to compare the capture effect of different fixation plates on the fracture fragments based on 3D modeling and fine distinctions of fracture fragments. METHODS: The computed tomography (CT) images before treatment of 127 patients with pilon fractures from January 2019 to December 2021 were retrospectively collected. The fracture lines were mapped and digitally displayed as 3D images using MIMICS 21 software. APLUS distal tibia anatomical locking plate (Plate A) and ZIMMER distal tibia anatomical plate (Plate B) were placed on a pseudo-bone model and CT scans were used to determine the number of screws in the major and minor fragments of pilon fractures. The frequency of the two plates capturing the fracture fragments was recorded. RESULTS: Under Assumption 1 or 2, Plate A performed significantly better than Plate B in capturing the major, Chaput, Volkmann, medial malleolus, and die-punch fracture fragments. Plate A captured markedly more minor fragments than Plate B under Assumption 2 but was not significantly different from Plate B under Assumption 1. Plate A or Plate B showed no obvious difference between major and minor capture rates under the same assumption, and A1 or B1 showed a markedly higher capture rate compared with A2 or B2. In addition, there was a significant positive correlation between the major capture rate and the major fragments in B1, and a significant negative correlation between the minor capture rate and the minor fragments in Plates A and B. However, there was no correlation between the major capture rate of Plate A and the major fragments. CONCLUSION: The APLUS distal tibial anatomical locking plate is superior to the ZIMMER distal tibia anatomical plate in the ability to capture distal tibial fragments in pilon fracture cases.

Misdiagnosis of Systemic Lupus Erythematosus Combined with Urinary Tuberculosis Leading to Tuberculous Meningitis: A Case Report and Literature Review.

Purpose: To explore the lessons learned from the misdiagnosis of systemic lupus erythematosus (SLE) combined with urinary tuberculosis leading to tuberculous meningitis (TBM) and the diagnosis and treatment of TBM through case reports and review of the literature. Methods: We report a case of an SLE patient presenting with urinary tuberculosis infection misdiagnosed as interstitial cystitis and complex urinary tract infection, who developed neurological infection after a cystocentesis biopsy and was eventually diagnosed with TBM. In addition, all cases of SLE combined with TBM from January 1975 to February 2022 were summarised and reviewed to compare current diagnostic and treatment strategies for the disease. Results: The patient suddenly developed neurological symptoms after cystocentesis biopsy, and we detected Mycobacterium tuberculosis in the macrogenomic next-generation sequence (mNGS) of the cerebrospinal fluid. We therefore excluded interstitial cystitis and neuropsychiatric lupus to confirm the diagnosis of Mycobacterium tuberculosis infection leading to urinary tract tuberculosis and TBM. Conclusion: SLE is complicated by urological tuberculosis, surgery triggering hematogenous dissemination leading to tuberculous meningitis. At the same time, the lack of specificity in the clinical presentation of patients makes it easy to misdiagnose neuropsychiatric lupus and delay treatment, so timely and accurate diagnosis and effective anti-tuberculosis treatment are essential.

Acute psilocybin increased cortical activities in rats.

Psilocybin, a naturally occurring hallucinogenic component of magic mushrooms, has significant psychoactive effects in both humans and rodents. But the underlying mechanisms are not fully understood. Blood-oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is a useful tool in many preclinical and clinical trials to investigate psilocybin-induced changes of brain activity and functional connectivity (FC) due to its noninvasive nature and widespread availability. However, fMRI effects of psilocybin on rats have not been carefully investigated. This study aimed to explore how psilocybin affects resting-state brain activity and FC, through a combination of BOLD fMRI and immunofluorescence (IF) of EGR1, an immediate early gene (IEG) closely related to depressive symptoms. Ten minutes after psilocybin hydrochloride injection (2.0 mg/kg, i.p.), positive brain activities were observed in the frontal, temporal, and parietal cortex (including the cingulate cortex and retrosplenial cortex), hippocampus, and striatum. And a region-of-interest (ROI) -wise FC analysis matrix suggested increased interconnectivity of several regions, such as the cingulate cortex, dorsal striatum, prelimbic, and limbic regions. Further seed-based analyses revealed increased FC of cingulate cortex within the cortical and striatal areas. Consistently, acute psilocybin increased the EGR1 level throughout the brain, indicating a consistent activation thought the cortical and striatal areas. In conclusion, the psilocybin-induced hyperactive state of rats is congruent to that of humans, and may be responsible for its pharmacological effects.

Verbenalin alleviates acute lung injury induced by sepsis and IgG immune complex through GPR18 receptor.

Acute lung injury is significantly associated with the aberrant activation and pyroptosis of alveolar macrophages. Targeting the GPR18 receptor presents a potential therapeutic approach to mitigate inflammation. Verbenalin, a prominent component of Verbena in Xuanfeibaidu (XFBD) granules, is recommended for treating COVID-19. In this study, we demonstrate the therapeutic effect of verbenalin on lung injury through direct binding to the GPR18 receptor. Verbenalin inhibits the activation of inflammatory signaling pathways induced by lipopolysaccharide (LPS) and IgG immune complex (IgG IC) via GPR18 receptor activation. The structural basis for verbenalin's effect on GPR18 activation is elucidated through molecular docking and molecular dynamics simulations. Furthermore, we establish that IgG IC induces macrophage pyroptosis by upregulating the expression of GSDME and GSDMD through CEBP-δ activation, while verbenalin inhibits this process. Additionally, we provide the first evidence that IgG IC promotes the formation of neutrophil extracellular traps (NETs), and verbenalin suppresses NETs formation. Collectively, our findings indicate that verbenalin functions as a "phytoresolvin" to promote inflammation regression and suggests that targeting the C/EBP-δ/GSDMD/GSDME axis to inhibit macrophage pyroptosis may represent a novel strategy for treating acute lung injury and sepsis.

A retrospective comparison of double-hooked locking plates versus non-locking plates in minimally invasive percutaneous plate osteosynthesis for the treatment of comminuted distal fibular fractures accompanied by tibial Pilon fractures.

BACKGROUND: Surgical approach and fixation material are crucial in the treatment of comminuted distal fibular fractures accompanied by tibial Pilon fractures. This study compared the efficacy of double-hooked locking plates and anatomic plates in minimally invasive percutaneous plate osteosynthesis (MIPPO) for the treatment of comminuted distal fibular fractures accompanied by tibial Pilon fractures. METHODS: Clinical data were collected from 96 patients diagnosed with comminuted distal fibular fractures accompanied by tibial Pilon fractures who had undergone MIPPO. Patients in the study group (n = 48) received double-hooked locking plate fixations and the control group (n = 48) received anatomical plate fixations. The operating time, intraoperative bleeding, length of hospital stays, full weight-bearing time, fracture healing time and complication rates in the two groups were compared. The quality of fracture reduction was evaluated using the Burwell-Chamley imaging scoring system; the ankle function was assessed based on the American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Score. RESULTS: Patients in the study group had shorter operating time, less bleeding, significantly shorter hospital stays, and shorter time to full weight-bearing as well as fracture healing compared to the control group (P < 0.05). Additionally, the post-operative complication rates were significantly lower in the study group (6.16% vs. 22.92%) (P < 0.05), but there was no significant difference in the fracture reduction rate between the two groups (P > 0.05). Patients in the study group experienced better ankle recovery than those in the control group (93.75% vs. 75.00%) (P < 0.05). CONCLUSION: Double-hooked locking plates have advantages in the treatment of comminuted distal fibular fractures accompanied by tibial Pilon fractures during MIPPO due to their shorter operating time and less intraoperative bleeding, as well as shorter hospital stays, full weight-bearing time and fracture healing time, fewer complications and better ankle recovery. Therefore, double-hooked locking plates are worthy of clinical application.