Unraveling host-pathogen dynamics in a murine Model of septic peritonitis induced by vancomycin-resistant Enterococcus faecium.

Vancomycin-resistant Enterococcus faecium (E. faecium) infection is associated with higher mortality rates. Previous studies have emphasized the importance of innate immune cells and signalling pathways in clearing E. faecium, but a comprehensive analysis of host-pathogen interactions is lacking. Here, we investigated the interplay of host and E. faecium in a murine model of septic peritonitis. Following injection with a sublethal dose, we observed significantly increased murine sepsis score and histological score, decreased weight and bacterial burden, neutrophils and macrophages infiltration, and comprehensive activation of cytokine-mediated signalling pathway. In mice receiving a lethal dose, hypothermia significantly improved survival, reduced bacterial burden, cytokines, and CD86 expression of MHC-II+ recruited macrophages compared to the normothermia group. A mathematical model constructed by observational data from 80 animals, recapitulated the host-pathogen interplay, and further verified the benefits of hypothermia. These findings indicate that E. faecium triggers a severe activation of cytokine-mediated signalling pathway, and hypothermia can improve outcomes by reducing bacterial burden and inflammation.

Salvage of Iatrogenic Sciatic Nerve Injury Caused by Operatively Treated Acetabular Fractures: Two Cases and Literature Review.

BACKGROUND: While sciatic nerve injury has been described as a complication of acetabular fractures, iatrogenic nerve injury remains sparsely reported. This study aims to assess iatrogenic sciatic nerve injuries occurring during acetabular fracture surgery, tracking their neurological recovery and clinical outcomes, and investigating any correlation between recovery and the severity of neurologic injury to facilitate physicians in providing prediction of prognosis. CASE PRESENTATION: We present two cases of male patients, aged 56 and 22, who developed sciatic palsy due to iatrogenic nerve injury during acetabular fracture surgery. Iatrogenic sciatic nerve injury resulted from operatively treated acetabular fractures. Surgical exploration, involving internal fixation removal and nerve decompression, successfully alleviated symptoms in both cases postoperatively. At the latest follow-up, one patient achieved full recovery with excellent function, while the other exhibited residual deficits at the L5/S1 root level along with minimal pain. CONCLUSION: Sciatic nerve injury likely stemmed from reduction techniques and internal fixation procedures for the posterior column, particularly when performed with the hip flexed, thereby placing tension on the sciatic nerve. Our case reports underscore the significance of liberal utilization of electrophysiologic examinations and intraoperative monitoring for the prediction of prognosis. Surgical exploration, encompassing internal fixation removal and nerve decompression, represents an effective intervention for resolving sciatic palsy, encompassing both sensory neuropathy and motor symptoms.

Coxiella burnetii effector CvpE maintains biogenesis of Coxiella-containing vacuoles by suppressing lysosome tubulation through binding PI(3)P and perturbing PIKfyve activity on lysosomes.

Coxiella burnetii (C. burnetii) is the causative agent of Q fever, a zoonotic disease. Intracellular replication of C. burnetii requires the maturation of a phagolysosome-like compartment known as the replication permissive Coxiella-containing vacuole (CCV). Effector proteins secreted by the Dot/Icm secretion system are indispensable for maturation of a single large CCV by facilitating the fusion of promiscuous vesicles. However, the mechanisms of CCV maintenance and evasion of host cell clearance remain to be defined. Here, we show that C. burnetii secreted Coxiella vacuolar protein E (CvpE) contributes to CCV biogenesis by inducing lysosome-like vacuole (LLV) enlargement. LLV fission by tubulation and autolysosome degradation is impaired in CvpE-expressing cells. Subsequently, we found that CvpE suppresses lysosomal Ca2+ channel transient receptor potential channel mucolipin 1 (TRPML1) activity in an indirect manner, in which CvpE binds phosphatidylinositol 3-phosphate [PI(3)P] and perturbs PIKfyve activity in lysosomes. Finally, the agonist of TRPML1, ML-SA5, inhibits CCV biogenesis and C. burnetii replication. These results provide insight into the mechanisms of CCV maintenance by CvpE and suggest that the agonist of TRPML1 can be a novel potential treatment that does not rely on antibiotics for Q fever by enhancing Coxiella-containing vacuoles (CCVs) fission.

Dual modality prompt learning for visual question-grounded answering in robotic surgery.

With recent advancements in robotic surgery, notable strides have been made in visual question answering (VQA). Existing VQA systems typically generate textual answers to questions but fail to indicate the location of the relevant content within the image. This limitation restricts the interpretative capacity of the VQA models and their ability to explore specific image regions. To address this issue, this study proposes a grounded VQA model for robotic surgery, capable of localizing a specific region during answer prediction. Drawing inspiration from prompt learning in language models, a dual-modality prompt model was developed to enhance precise multimodal information interactions. Specifically, two complementary prompters were introduced to effectively integrate visual and textual prompts into the encoding process of the model. A visual complementary prompter merges visual prompt knowledge with visual information features to guide accurate localization. The textual complementary prompter aligns visual information with textual prompt knowledge and textual information, guiding textual information towards a more accurate inference of the answer. Additionally, a multiple iterative fusion strategy was adopted for comprehensive answer reasoning, to ensure high-quality generation of textual and grounded answers. The experimental results validate the effectiveness of the model, demonstrating its superiority over existing methods on the EndoVis-18 and EndoVis-17 datasets.

Prediction of Ki-67 expression in bladder cancer based on CT radiomics nomogram.

Objectives: This study aimed to create and validate a radiomics nomogram for non-invasive preoperative Ki-67 expression level prediction in patients with bladder cancer (BCa) using contrast-enhanced CT radiomics features. Methods: A retrospective analysis of 135 patients was conducted, 79 of whom had high levels of Ki-67 expression and 56 of whom had low levels. For the dimensionality reduction analysis, the best features were chosen using the least absolute shrinkage selection operator and one-way analysis of variance. Then, a radiomics nomogram was created using multiple logistic regression analysis based on radiomics features and clinical independent risk factors. The performance of the model was assessed using the Akaike information criterion (AIC) value, the area under the curve (AUC) value, accuracy, sensitivity, and specificity. The clinical usefulness of the model was assessed using decision curve analysis (DCA). Results: Finally, to establish a radiomics nomogram, the best 5 features were chosen and integrated with the independent clinical risk factors (T stage) and Rad-score. This radiomics nomogram demonstrated significant correction and discriminating performance in both the training and validation sets, with an AUC of 0.836 and 0.887, respectively. This radiomics nomogram had the lowest AIC value (AIC = 103.16), which was considered to be the best model. When compared to clinical factor model and radiomics signature, DCA demonstrated the more value of the radiomics nomogram. Conclusion: Enhanced CT-based radiomics nomogram can better predict Ki-67 expression in BCa patients and can be used for prognosis assessment and clinical decision making.

Three-dimensional printing versus traditional surgery for inveterate pelvic and acetabular fractures: A retrospective study of 37 patients.

Treatment of deformed pelvic and acetabular fractures is a considerable challenge for orthopedic surgeons. The aim of this study was to assess the availability of a three-dimensional (3D) printing model used in patients with inveterate pelvic and acetabular fractures by comparing 3D printing technology with conventional surgery. We conducted a retrospective review of patients with inveterate pelvic and acetabular fractures treated in our department between January 2008 and June 2020. The patients were divided into 2 groups according to their willingness. Perioperative data and clinical outcomes were compared to evaluate clinical efficacy. The t-test, Fisher exact test, and multivariable logistic regression analysis were conducted. A P value of .05 or less was considered to be statistically significant (two-tailed). Thirty-seven patients were enrolled in our study. Seventeen patients were divided into the case group treated by 3D printing model-assisted preoperative planning, and 20 patients were divided into the control group treated by conventional surgery. Patients treated with the 3D printing model had significantly shorter operation times, less blood loss, and shorter fluoroscopy times. Patients in the case group also showed better pain relief according to visual analog scale scores. However, the elevations in pelvis and hip joint functional outcomes were similar between the 2 groups, and no significant difference was shown in the radiological result. The usage of 3D printing techniques in patients with inveterate pelvic and acetabular fractures is of great importance in preoperative preparation and optimization of surgery but cannot improve postoperative function compared with conventional treatment.

Correlation Analysis of the TP53 Mutation With Clinical Characteristics in the Prognosis of Non-Small Cell Lung Cancer.

Background: Non-small cell lung cancer (NSCLC) with TP53 mutations has a worse prognosis. It was generally more resistant to chemotherapy and radiation. Our aim was to investigate the correlation between the TP53 co-mutated gene and clinical features, and prognostic value in patients with NSCLC. Methods: Seventy-three patients with a diagnosis of NSCLC at our hospital were recruited. They were divided into the TP53 mutation status (minor) (TP53 MU) and TP53 wild-type (major) (TP53 WT) groups according to their clinical characteristics after their mutation data and clinical information were collected. Serum markers were compared between groups using Mann-Whitney U test. Other clinical factors were compared between groups using χ2 test and Fisher exact test. The log-rank test was used to compare survival curves. Results: Of the 73 patients with NSCLC, 37 (50.68%) were found to carry TP53 mutation. TP53 MU and TP53 WT groups (n = 36) showed a significant difference in the number of smokers, incidence of squamous cell carcinoma, EGFR mutation, and number of advanced patients (P < .05), while gender, age, lymph node metastasis, and KRAS mutation did not differ significantly between the 2 groups. The survival curves in the TP53/KRAS and the TP53/EGFR co-mutation groups suggest that patients with NSCLC may have a shorter progression-free survival (PFS) if they carry one of the 2 types of co-mutation. Conclusions: TP53 gene mutations are more common in patients with NSCLC and squamous cell carcinoma. New predictive markers for NSCLC prognosis may be TP53/KRAS and TP53/EGFR co-mutations.

Upregulation of BMP1 through ncRNAs correlates with adverse outcomes and immune infiltration in clear cell renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) accounts for approximately 2-3% of all adult malignancies. Clear cell renal cell carcinoma (ccRCC), which comprises 70-80% of all RCC cases, is the most common histological subtype. METHODS: ccRCC transcriptome data and clinical information were downloaded from the TCGA database. We used the TCGA and GEPIA databases to analyze relative expression of BMP1 in various types of human cancer. GEPIA was used to perform survival analysis for BMP1 in various cancer types. Upstream binding miRNAs of BMP1 were obtained through several important target gene prediction tools. StarBase was used to predict candidate miRNAs that may bind to BMP1 and candidate lncRNAs that may bind to hsa-miR-532-3p. We analyzed the association between expression of BMP1 and immune cell infiltration levels in ccRCC using the TIMER website. The relationship between BMP1 expression levels and immune checkpoint expression levels was also investigated. RESULTS: BMP1 was upregulated in GBM, HNSC, KIRC, KIRP and STAD and downregulated in KICH and PRAD. Combined with OS and DFS, BMP1 can be used as a biomarker for poor prognosis among patients with KIRC. Through expression analysis, survival analysis and correlation analysis, LINC00685, SLC16A1-AS1, PVT1, VPS9D1-AS1, SNHG15 and the CCDC18-AS1/hsa-miR-532-3p/BMP1 axis were established as the most potential upstream ncRNA-related pathways of BMP1 in ccRCC. Furthermore, we found that BMP1 levels correlated significantly positively with tumor immune cell infiltration, biomarkers of immune cells, and immune checkpoint expression. CONCLUSION: Our results demonstrate that ncRNA-mediated high expression of BMP1 is associated with poor prognosis and tumor immune infiltration in ccRCC.

Combined effects of dietary carbohydrate levels and ammonia stress on growth, antioxidant capacity and glucose metabolism in juvenile oriental river prawn (Macrobrachium nipponense).

Ammonia is a common environmental stress factor that constrains aquaculture industry development. This study evaluated the effect of carbohydrate levels and ammonia stress in oriental river prawn (Macrobrachium nipponense). The experiment had six treatments containing two water ammonia levels (0 and 5 mg/L) and three dietary carbohydrate levels (low carbohydrate diet (LCD, 10%), medium carbohydrate diet [MCD, 20%], and high carbohydrate diet [HCD, 30%]), and lasted six weeks. The results showed that the prawns fed on MCD had higher weight gain than those fed on LCD and HCD during ammonia stress. Moreover, the prawns fed on MCD had significantly lower acid phosphatase and alkaline phosphatase activities during ammonia stress. Feeding the prawns on the MCD increased B cells in the hepatopancreas during ammonia stress. Interestingly, the prawns fed on MCD had significantly lower superoxide dismutase activity compared to LCD and HCD during ammonia stress. Moreover, the prawns fed on MCD had significantly lower pyruvate kinase activity and pyruvate and lactic acid contents, while those fed on LCD had significantly higher succinic dehydrogenase, 6-phosphogluconic dehydrogenase, and phosphoenol pyruvate carboxykinase activities during ammonia stress. The prawns fed on the MCD increased significantly glutaminase activity and decreased the ammonia content in the serum during ammonia exposure. In addition, feeding the prawns on MCD decreased significantly the expression of apoptosis and inflammation-related genes. Taken together, the MCD supplied energy required to counteract ammonia stress, which increased growth, improved antioxidant capacity, facilitated ammonia excretion, and alleviated inflammation and apoptosis of the oriental river prawn.

Management and Outcome of Elderly Patients With Patellar Fracture Treated With Novel Modified Cerclage Wiring.

Introduction: The purpose of this study is to assess the efficacy and security of a fixation method for fixing patellar fractures in elderly patients utilizing modified cerclage wire. Methods: From January 2015 to December 2020, 31 cases (age≥65 years old) of closed patellar fracture were treated by modified cerclage wiring. Patients in these instances ranged in age from 65 to 87 (73.7 ± 7.2 years), with 15 men and 16 women. 4 instances were type 34-C1 (transverse fracture) according to the AO/OTA classification, 27 cases (87%) were comminuted fractures, including 11 cases that were type 34-C2 (3 fragments), and 16 cases that were type 34-C3 (more than 3 fragments). Postoperative problems such as fragment re-displacement, nonunion, internal fixation loosening, infection, and internal fixation rupture were evaluated. The clinical grading systems of Böstman were used to assess the postoperative clinical outcomes. Results: Thirty one patients in all were monitored for 14 to 31 months (22.2 ± 4.5 months). After the procedure, the fracture took 2.5-3.5 months (2.92 ± .25 months) to heal. There were no postoperative issues like infection, dislocation, implant breakage, uncomfortable hardware, or post-traumatic osteoarthritis. According to the clinical grading scales of Böstman, the average score of the final follow-up was 28.6 ± 1.1 (range 26-30). 29 (94%) of the patients had excellent results, whereas just 2 (6%) had good results. The patient's knee flexion activity ranged from 110 to 140°, making for a favorable prognosis. Conclusion: Most patella fractures in the elderly are comminuted. Elderly patients with patellar fractures may be successfully treated with modified cerclage wire, with good results and no noticeable side effects.

Trans-olecranon fracture posterior dislocation: a novel type of elbow injury.

BACKGROUND: Based on our experiences, we found that a kind of elbow injury is characterized by an olecranon fracture accompanied by elbow joint posterior dislocation with the proximal radioulnar joint intact. The aim of this study was to better define this kind of severe elbow instability, which has not been previously reported. METHODS: We retrospectively analyzed all patients with olecranon fractures who were treated at our institution from January 2013 to April 2021. Data on these patient demographics, injury characteristics, preoperative and postoperative imaging, surgical management, and outcomes were recorded and analyzed. We also made the inclusion criteria and exclusion criteria. RESULTS: A total of 309 patients were diagnosed olecranon fractures in our institution, and ten patients met the inclusion criteria, 9 males and 1 female, with an average age of 40.6 ± 12.7 years (26-68 years). Eight patients (80%) were comminuted, and two were oblique olecranon fracture. Nine patients (90%) suffered coronoid process fractures, eight fractures were type III, and one was type II. Eight patients (80%) suffered radial head fractures, seven fractures were type II, and one was type III. All patients suffered lateral collateral ligament complex injury. All patients underwent surgical management and were followed up on average for 15.8 ± 3.2 months (12-20 months). The motion of the elbow and functional outcome were evaluated with several methods. The mean arc of the elbow movement was 131.6° ± 6.0° (124°-140°), and the mean arc of the forearm rotation was 158.5° ± 17.8° (128°-180°). Nine patients' functional results according to the Mayo Elbow Performance Score (MEPS) were excellent with a mean score of 96.5 ± 5.3 points (85-100 points), and another was good. The mean score according to the Broberg and Morrey functional rating index was 98.8 ± 2.5 points (92-100 points), nine patients were excellent, and another was good. The mean Disabilities of the Arm, Shoulder, and Hand (DASH) score was 0.75 ± 1.2 points (0-3.3 points). CONCLUSIONS: Trans-olecranon fracture posterior dislocation is a rare injury and has unique characteristics, and it is a kind of complex elbow instability involving the coronoid process and radial head fractures. After bony structure is restored, the repairment of lateral collateral ligament complex is also important to the stability of the elbow joint. Correct understanding of this kind of injury and reasonable treatment plan can achieve good function.

A CT-based radiomics nomogram for differentiation of benign and malignant small renal masses (≤4 cm).

RATIONALE AND OBJECTIVES: Based on radiomics signature and clinical data, to develop and verify a radiomics nomogram for preoperative distinguish between benign and malignant of small renal masses (SRM). MATERIALS AND METHODS: One hundred and fifty-six patients with malignant (n = 92) and benign (n = 64) SRM were divided into the following three categories: category A, typical angiomyolipoma (AML) with visible fat; category B, benign SRM without visible fat, including fat-poor angiomyolipoma (fp-AML), and other rare benign renal tumors; category C, malignant renal tumors. At the same time, one hundred and fifty-six patients included in the study were divided into the training set (n = 108) and test set (n = 48). Respectively from corticomedullary phase (CP), nephrogram phase (NP) and excretory phase (EP) CT images to extract the radiomics features, and the optimal features were screened to establish the logistic regression model and decision tree model, and computed the radiomics score (Rad-score). Demographics and CT findings were evaluated and statistically significant factors were selected to construct a clinical factors model. The radiomics nomogram was established by merging Rad-score and selected clinical factors. The Akaike information criterion (AIC) values and the area under the curve (AUC) were used to compare model discriminant performance, and decision curve analysis (DCA) was used to assess clinical usefulness. RESULTS: Seven, fifteen, nineteen, and seventeen distinguishing features were obtained in the CP, NP, EP, and three-phase joint, respectively, and the logistic regression and decision tree models were built based on this features. In the training set, the logistic regression model works better than the decision tree model for distinguishing categories A and B from category C, with the AUC of CP, NP, EP and three-phase joint were 0.868, 0.906, 0.937 and 0.975, respectively. The radiomics nomogram constructed based on the three-phase joint Rad-score and selected clinical factor performed well on the training set (AUC, 0.988; 95% CI, 0.974-1.000) for differentiation of categories A and B from category C. In the test set, the AUC of clinical factors model, radiomics signature and radiomics nomogram for discriminating categories A and B from category C were 0.814, 0.954 and 0.968, respectively; for the identification of category A from category C, the AUC of the three models were 0.789, 0.979, 0.985, respectively; for discriminating category B from category C, the AUC of the three models were 0.853, 0.915, 0.946, respectively. The radiomics nomogram had better discriminative than the clinical factors model in both training and test sets (P < 0.05). The radiomics nomogram (AIC = 40.222) with the lowest AIC value was considered the best model compared with that of the clinical factors model (AIC = 106.814) and the radiomics signature (AIC = 44.224). The DCA showed that the radiomics nomogram have better clinical utility than the clinical factors model and radiomics signature. CONCLUSIONS: The logistic regression model has better discriminative performance than the decision tree model, and the radiomics nomogram based on Rad-score of three-phase joint and clinical factors has a good predictive effect in differentiating benign from malignant of SRM, which may help clinicians develop accurate and individualized treatment strategies.

Incidence of traumatic sciatic nerve injury in patients with acetabular fractures and factors affecting recovery: a retrospective study.

BACKGROUND: Reports on traumatic sciatic nerve injury associated with acetabular fracture are rare. In this study, we investigated the demographics of these injuries, their clinical characteristics, management, and factors potentially influencing neurological recovery. METHODS: We retrospectively reviewed all patients diagnosed to have acetabular fracture at our trauma center between January 2014 and June 2021. Data on patient demographics, characteristics of sciatic nerve injury, neurological recovery, factors potentially influencing neurological recovery were analyzed. RESULTS: Eighteen patients (bilateral in one case) met the diagnostic criteria. All these injuries involved the posterior wall or posterior column, and most patients had posterior dislocation of the hip joint. Four of the 19 sides with traumatic sciatic nerve injury involved the common peroneal nerve division and 15 involved both the common peroneal and tibial nerve divisions. Seventeen patients (18 sides) underwent intraoperative nerve exploration, which revealed abnormalities in 7 sides and no obvious abnormality in 11 sides. At the last follow-up, 10 sides (52.6%) had complete recovery and 9 (47.4%) had partial recovery; the difference was statistically significant between those with or without abnormal nerve damage during exploration (P = 0.046). Linear regression analysis showed that a nerve abnormality detected intraoperatively was a predictor of nerve recovery (P = 0.009). The mean recovery time was significantly longer for partial recovery than for complete recovery (13.78 months vs. 6.70 months; P = 0.001). CONCLUSIONS: All the injuries in this series involved the posterior wall or posterior column, and most patients had posterior dislocation of the hip joint. Damage to the common peroneal nerve division was more severe than that to the tibial nerve division preoperatively. However, the degree of recovery of the common peroneal division was not worse than that of the tibial division. There was a relationship between the degree of neurological recovery and whether there was an abnormality at the time of intraoperative nerve exploration. Patients with partial recovery took longer to recover.

CT-based deep learning radiomics signature for the preoperative prediction of the muscle-invasive status of bladder cancer.

Objectives: Although the preoperative assessment of whether a bladder cancer (BCa) indicates muscular invasion is crucial for adequate treatment, there currently exist some challenges involved in preoperative diagnosis of BCa with muscular invasion. The aim of this study was to construct deep learning radiomic signature (DLRS) for preoperative predicting the muscle invasion status of BCa. Methods: A retrospective review covering 173 patients revealed 43 with pathologically proven muscle-invasive bladder cancer (MIBC) and 130 with non-muscle-invasive bladder cancer (non- MIBC). A total of 129 patients were randomly assigned to the training cohort and 44 to the test cohort. The Pearson correlation coefficient combined with the least absolute shrinkage and selection operator (LASSO) was utilized to reduce radiomic redundancy. To decrease the dimension of deep learning features, Principal Component Analysis (PCA) was adopted. Six machine learning classifiers were finally constructed based on deep learning radiomics features, which were adopted to predict the muscle invasion status of bladder cancer. The area under the curve (AUC), accuracy, sensitivity and specificity were used to evaluate the performance of the model. Results: According to the comparison, DLRS-based models performed the best in predicting muscle violation status, with MLP (Train AUC: 0.973260 (95% CI 0.9488-0.9978) and Test AUC: 0.884298 (95% CI 0.7831-0.9855)) outperforming the other models. In the test cohort, the sensitivity, specificity and accuracy of the MLP model were 0.91 (95% CI 0.551-0.873), 0.78 (95% CI 0.594-0.863) and 0.58 (95% CI 0.729-0.827), respectively. DCA indicated that the MLP model showed better clinical utility than Radiomics-only model, which was demonstrated by the decision curve analysis. Conclusions: A deep radiomics model constructed with CT images can accurately predict the muscle invasion status of bladder cancer.

Astragaloside IV ameliorates spinal cord injury through controlling ferroptosis in H2O2-damaged PC12 cells in vitro.

Background: Spinal cord injury (SCI) is associated with significant paralysis and high fatality. Recent research has revealed that ferroptosis participates in the pathogenesis of SCI. Astragaloside IV (AS-IV), the main active ingredient of the plant Astragalus membranaceus, has been reported to promote motor function recovery in rats with SCI. This study explored the effects of AS-IV in H2O2-treated PC12 pheochromocytoma cells. Methods: The optimal concentration and duration of AS-IV treatment in PC12 cells was assessed using the cell counting kit 8 (CCK-8) assay. Subsequently, the SCI cell model was established in PC12 cells using H2O2. The effects of AS-IV, FIN56, and transcription factor EB (TFEB) small interfering (si)RNA on cell viability and apoptosis in the SCI model were determined using the CCK-8 assay and flow cytometry, respectively. Caspase­3 and lactate dehydrogenase (LDH) levels were measured by colorimetric assay and enzyme-linked immunosorbent assay (ELISA), respectively. Cellular reactive oxygen species (ROS) were detected by flow cytometry combined with dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay. The cellular ultrastructure was analyzed by transmission electron microscopy (TEM). The ferroptosis pathway-related proteins were confirmed using Western blot analysis. TFEB expression was confirmed by Western blot and immunofluorescence. Results: The optimal concentration and duration of AS-IV treatment in PC12 cells was determined to be 1.0 µM and 48 h, respectively. AS-IV markedly accelerated proliferation, suppressed apoptosis, and reduced ROS and LDH accumulation. Furthermore, AS-IV enhanced TFEB expression in H2O2-damaged PC12 cells. The effects of AS-IV on SCI were inhibited by si-TFEB, and this inhibition was further reinforced by the addition of FIN56. Conclusions: The results of this investigation using the SCI cell model suggested that AS-IV alleviated SCI by promoting TFEB expression and subsequently mediating ferroptosis. This may represent a potential clinical treatment for SCI.

Biomechanical tests and finite element analyses of pelvic stability using bilateral single iliac screws with different channels in lumbo-iliac fixation.

Background: In lumbo-iliac fixation, the iliac screw can be placed in several locations and directions. There is no uniform standard for the placement of a single iliac screw. Biomechanical tests and finite element analyses were used to compare the effect of bilateral single iliac screws with three channels on pelvic stability to determine the best channel. Methods: Five embalmed adult cadaver pelvic specimens were selected. An unstable Tile C1 pelvic injury model was established. Lumbo-iliac fixation for the treatment of left sacral Denis II fracture includes the following: three channels of bilateral, single iliac screws (channel A from posterior superior iliac spine (PSIS) to anterior inferior iliac spine (AIIS), channel B from 1 cm medial and 1 cm caudal of PSIS to AIIS, and channel C from 2 cm below PSIS to AIIS). Biomechanical testing was performed for stiffness evaluations. A finite element model was established to study the stress distribution of the model and the maximum von Mises stress of internal fixation. Results: Biomechanical tests revealed that under vertical compression loading. The compressive stiffness fixed by channel B (246.15 ± 27.85 N/mm) was better than that fixed by channel A and channel C. Under torsional load, the torsional stiffness fixed by channel B (2.234 ± 0.223 N·m/°) was stronger than that fixed by channel A and channel C. However, there was no significant difference in terms of compressive and torsional stiffness between channel B and channel A (P > 0.05). Finite element analyses conformed that the maximum von Mises stress of the internal fixator fixed in channel B under the conditions of vertical, forwards bending, backwards extension, left bending, left rotating, and right bending (213.98 MPa, 338.96 MPa, 100.63 MPa, 297.06 MPa, 200.95 MPa and 284.75 MPa, respectively) was significantly lower than those fixed in channel A and channel C. Conclusions: The construct stiffness of the channel from 1 cm medial and 1 cm caudal of PSIS to AIIS is better than that of the other two channels. This channel has the advantages of good biomechanical stability, small maximum von Mises stress of internal fixation.

Csf2ra deletion attenuates acute lung injuries induced by intratracheal inoculation of aerosolized ricin in mice.

Specific therapeutics are not available for acute lung injury (ALI) induced by ricin toxin (RT). Inhibiting the host immune response in the course of pulmonary ricinosis is hypothesized to be of benefit and can be achieved by impairing granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling, thereby reducing the pro-inflammatory response to exogenous foreign body invasion. However, it is unknown whether mice with impaired GM-CSF signaling can survive after RT inhalation. To test this, colony stimulating factor 2 receptor alpha (Csf2ra) knockout (KO) mice that lack GM-CSF signaling and wild-type (WT) mice models of intratracheal exposure to a lethal dose (2× LD50) of RT were established. Survival was greater in Csf2ra KO mice 21 days after RT inhalation compared with WT mice. Highly co-expressed genes that probably attenuated the pro-inflammatory response in the lung of Csf2ra KO mice were identified. Bioinformatics analysis revealed that transcriptome changes involved mostly inflammation-related genes after RT exposure in both Csf2ra KO mice and WT mice. However, the activity levels of pro-inflammatory pathways, such as the TNF signaling pathway and NF-κB signaling pathway, in Csf2ra KO mice were significantly decreased and the degree of neutrophil chemotaxis and recruitment inhibited after RT-exposure relative to WT mice. RT-qPCR and flow cytometry validated results of RNA-Seq analysis. This work provides potential avenues for host-directed therapeutic applications that can mitigate the severity of ALI-induced by RT.

Dietary thiamine modulates carbohydrate metabolism, antioxidant status, and alleviates hypoxia stress in oriental river prawn Macrobrachium nipponense (de Haan).

Hypoxia is one of the challenges in prawns aquaculture. However, the role of thiamine, which is a coenzyme in carbohydrate metabolism with antioxidant properties, in reducing hypoxia in prawns aquaculture is currently unknown. We investigated the effects of thiamine on antioxidant status, carbohydrate metabolism and acute hypoxia in oriental river prawn, Macrobrachium nipponense. One thousand eight hundred prawns (0.123 ± 0.003 g) were fed five diets (60 prawns each tank, six replicates per diet) supplemented with graded thiamine levels (5.69, 70.70, 133.67, 268.33 and 532.00 mg/kg dry mater) for eight weeks and then exposed to hypoxia stress for 12 h followed by reoxyegnation for 12 h. The results showed that, under normoxia, prawns fed the 133.67 or 268.33 mg/kg thiamine diet had significantly lower glucose 6-phosphatedehydrogenase, succinate dehydrogenase and phosphoenolpyruvate carboxykinase activities than those fed the other diets. Moreover, total antioxidant capacity (T-AOC) increased significantly when prawns were fed the 133.67 mg/kg thiamine diet. Superoxide dismutase (SOD) activity and malonaldehyde (MDA) content also increased significantly when prawns were fed the 268.33 or 532.00 mg/kg thiamine diet under hypoxia. And the significantly increased SOD activity and MDA level also observed in prawns fed 532.00 mg/kg thiamine under reoxygenation. Under normoxia, prawns fed the 70.70 or 133.67 mg/kg thiamine diet decreased the mRNA expressions of AMP-activated protein kinase-alpha (AMPK-α), pyruvate dehydrogenase-E1-α subunit (PDH-E1-α) and hypoxia-inducible factor-1s (HIF-1α, HIF-1ß), but increased the mRNA expressions of phosphofructokinase (PFK) significantly. After 12 h of hypoxia, the energy metabolism related genes (AMPK-ß, AMPK-γ, PFK, PDH-E1-α), hypoxia-inducible factor related genes (HIF-1α, HIF-1ß) and thiamine transporter gene (SLC19A2) were up-regulated significantly in prawns fed the 133.67 or 268.33 mg/kg thiamine diets. After 12 h of reoxygenation, prawns fed the 133.67 or 268.33 mg/kg diet significantly decreased the SOD activity, MDA level and SLC19A2 mRNA expression compared with other diets. The optimum thiamine was 161.20 mg/kg for minimum MDA content and 143.17 mg/kg for maximum T-AOC activity based on cubic regression analysis. In summary, supplementing 143.17 to 161.20 mg/kg thiamine in the diets for M. nipponense improves the antioxidant capacity under normoxia and reduces the oxidative damage under hypoxia stress.

Effectiveness of Noninvasive Positive Pressure Ventilation Combined with Enteral Nutrition in the Treatment of Patients with Combined Respiratory Failure after Lung Cancer Surgery and Its Effect on Blood Gas Indexes.

Purpose: To investigate the effect of noninvasive positive pressure ventilation (NIPPV) combined with enteral nutrition support in the treatment of patients with combined respiratory failure after lung cancer surgery and its effect on blood gas indexes. Methods: A total of 82 patients with combined respiratory failure after lung cancer surgery who were treated in our hospital from March 2016∼September 2021 were selected as the research subjects, and according to the random number table method, they were equally divided into the parenteral nutrition group (n = 41) with NIPPV + parenteral nutrition support treatment and the enteral nutrition group (n = 41) with NIPPV + enteral nutrition support treatment. The curative effects of two groups after treatment were compared, and the pulmonary function indexes (maximum expiratory pressure (PEmax), maximum midexpiratory flow rate (MMF), and maximum ventilation volume (MVV)), blood gas indexes (blood oxygen partial pressure (PaO2) and partial pressure of carbon dioxide (PaCO2)), oxygen metabolism indicators [mixed venous oxygen tension (PvO2) and central venous oxygen saturation (ScvO2)], nutritional status indicators (hemoglobin (HGB), serum albumin (ALB), and total protein (TP)), and nutritional score before and after treatment in two groups were detected, and the 6-month follow-up of the two groups was recorded. Results: After treatment, the total effective rate of the enteral nutrition group 95.12% (39/41) was higher than that of the parenteral nutrition group 80.49% (33/41) (P < 0.05). At 3, 12, 24, and 48 hours after the operation, the levels of PEmax, MMF, and MVV in two groups were higher than those before treatment, and the enteral nutrition group was higher than the parenteral nutrition group at the same time point (P < 0.05). At 3, 12, 24, and 48 hours after the operation, the PaO2 levels in two groups were higher than those before treatment, and the PaCO2 levels were lower than those before treatment. The PaO2 levels in the enteral nutrition group were higher than those in the parenteral nutrition group at the same time point, and the PaCO2 levels were lower than those in the parenteral nutrition group at the same time point (P < 0.05). At 3, 12, 24, and 48 hours after the operation, the levels of PvO2 and ScvO2 in two groups were higher than those before treatment, and the enteral nutrition group was higher than the parenteral nutrition group at the same time point (P < 0.05). After treatment, the levels of HGB, ALB, and TP in two groups were higher than those before treatment, and the enteral nutrition group was higher than the parenteral nutrition group (P < 0.05). After treatment, the nutritional scores of the two groups were higher than those before treatment, and the enteral nutrition group was higher than the parenteral nutrition group (P < 0.05). At 6-month postoperative follow-up, the incidence of death in the enteral nutrition group 2.44% (1/41) was lower than that of the parenteral nutrition group 17.07% (7/41) (P < 0.05). Conclusions: The efficacy of NIPPV combined with enteral nutrition support in treating patients with combined respiratory failure after lung cancer surgery is remarkable. It can improve patients' pulmonary function and blood gas index, correct patients' hypoxia status and the patients' nutritional level was significantly improved, which helped to reduce the mortality rate and improve the prognosis.

Laminectomy for Penetrating Spinal Cord Injury with Retained Foreign Bodies.

BACKGROUND: Penetrating spinal cord injury (PSCI) with retained foreign bodies (RFB) is rarely observed in clinics and may result in a complete or incomplete neurological deficit. This study was performed to appraise the treatment effect of laminectomy for PSCI with RFB. CASE PRESENTATION: This study presented three patients referred to a tertiary hospital between August 2011 and October 2018 due to PSCI with RFB and receiving laminectomy. The first patient was a 25-year-old female with a butcher's knife piercing the T9 lamina and T10 vertebral body obliquely; the second was a 49-year-old male who suffered a perforating wound of the cervical spinal canal and injury of vertebral artery from foreign glass, while the third was a 60-year-old male with a wooden stick penetrating stomach and terminating in the L1 lamina. The first and second patients immediately underwent laminectomy for debridement and removal of RFB, while the third received two-staged operations to remove the retained stick thoroughly. Unfortunately cases 1 and 3 eventually resulted in total paralysis and case 2 revealed no improvement in myodynamia. Then, Medline/PubMed, Embase and the Cochrane Library were systematically searched, and 23 articles involving 25 additional cases with this kind of injury were included for analysis. CONCLUSIONS: The optimal treatment strategy for penetrating spinal cord injury with retained foreign bodies remains challenging and should be assessed case-by-case. If possible, surgical removal of foreign bodies by laminectomy is preferred immediately to prevent delayed presentation and persistent contamination. Meanwhile, a multidisciplinary team is needed to address concomitant injuries.