A novel strategy for spinal cord reconstruction via vascularized allogeneic spinal cord transplantation combine spinal cord fusion.

AIMS: Spinal cord injuries (SCI) pose persistent challenges in clinical practice due to the secondary injury. Drawing from our experience in spinal cord fusion (SCF), we propose vascularized allogeneic spinal cord transplantation (vASCT) as a novel approach for SCI, much like organ transplantation has revolutionized organ failure treatment and vascularized composite-tissue allotransplantation has addressed limb defects. MATERIALS AND METHODS: In this study, 24 dogs were paired and underwent vASCT, with donor spinal cord grafts and polyethylene glycol (PEG) application for SCF. The experimental group (n = 8) received tacrolimus and methylprednisolone, while the control group (n = 4) received only methylprednisolone. Safety and efficacy of vASCT were evaluated through electrophysiology, imaging, and 6-month follow-up. RESULTS: The experimental group showed substantial recovery in hind limb motor function. Imaging revealed robust survival of spinal cord grafts and restoration of spinal cord continuity. In contrast, the control group maintained hind limb paralysis, with imaging confirming spinal cord graft necrosis and extensive defects. Electrophysiologically, the experimental group exhibited restored motor evoked potential signal conduction postoperatively, unlike the control group. Notably, PEG application during vASCT led to signal conduction recovery in intraoperative spinal cord evoked potential examinations for all dogs. CONCLUSION: In the vASCT surgical model, the combination of PEG with tacrolimus has demonstrated the ability to reconstruct spinal cord continuity and restore hind limb motor function in beagles. Notably, a low dose of tacrolimus has also exhibited an excellent anti-immune rejection effect. These findings highlight vASCT's potential promise as a therapeutic strategy for addressing irreversible SCI.

Simultaneous EEG-fNIRS Data Classification Through Selective Channel Representation and Spectrogram Imaging.

The integration of electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) can facilitate the advancement of brain-computer interfaces (BCIs). However, existing research in this domain has grappled with the challenge of the efficient selection of features, resulting in the underutilization of the temporal richness of EEG and the spatial specificity of fNIRS data.To effectively address this challenge, this study proposed a deep learning architecture called the multimodal DenseNet fusion (MDNF) model that was trained on two-dimensional (2D) EEG data images, leveraging advanced feature extraction techniques. The model transformed EEG data into 2D images using a short-time Fourier transform, applied transfer learning to extract discriminative features, and consequently integrated them with fNIRS-derived spectral entropy features. This approach aimed to bridge existing gaps in EEG-fNIRS-based BCI research by enhancing classification accuracy and versatility across various cognitive and motor imagery tasks.Experimental results on two public datasets demonstrated the superiority of our model over existing state-of-the-art methods.Thus, the high accuracy and precise feature utilization of the MDNF model demonstrates the potential in clinical applications for neurodiagnostics and rehabilitation, thereby paving the method for patient-specific therapeutic strategies.

Botch improves cognitive impairment after cerebral ischemia associated with microglia-induced A1-type astrocyte activation.

Vascular cognitive impairment (VCI) is a clinical syndrome that arises from cerebrovascular issues and associated risk factors, resulting in difficulties in at least one area of cognitive function. VCI has emerged as the second most prevalent type of dementia following Alzheimer's disease, yet there is no effective clinical treatment. Botch, an endogenous Notch1 antagonist, demonstrates neuroprotective effects by inhibiting neuroinflammatory responses mediated through the Notch pathway. While its role in stroke-induced neuroinflammation is well-established, its involvement in VCI remains largely unexplored. This study investigates the role and potential mechanisms of Botch in a rat model of cognitive impairment caused by bilateral common carotid artery occlusion (BCCAO). Firstly, we observed that Botch levels were down-regulated in BCCAO rats, which correlated with increased release of inflammatory cytokines and neuronal damage. Microglia in BCCAO rats released interleukin-1α (IL-1α), tumor necrosis factor-α (TNF-α), and complement component 1q (C1q), leading to the activation of neurotoxic C3+ A1 reactive astrocytes. Then, the down-regulation of Botch exacerbated microglia-mediated inflammation, activated C3+ A1 astrocytes, worsened neuronal damage, and led to a decline in cognitive function. Conversely, the re-expression of Botch alleviated C3+ astrocyte activation, inhibited neuronal damage, and improved mental function. In conclusion, Botch plays a crucial role in inhibiting neuroinflammation induced by type A1 reactive astrocytes. It achieves this by blocking the activation of microglia triggered by the Notch pathway. Ultimately, it inhibits neuronal damage to play a neuroprotective role. These findings suggest that Botch may represent a novel potential target for treating VCI.

Nutrition and continuous nursing intervention following radical resection of esophageal cancer in a patient after liver transplantation: a case report.

Background: Reasonable nutritional intervention is very important to promote wound healing and rehabilitation in patients with radical esophagectomy for esophageal cancer. This report aims to summarize the experience of nutritional and continuous nursing intervention in a patient who underwent radical resection of esophageal cancer after liver transplantation, by testing a comprehensive approach to optimize nursing plans in similar clinical practice. We hope that the implementation of home enteral nutrition can improve the nutrition status and quality of life of postoperative patients. Case Description: A patient with liver transplantation was admitted to The Fourth Hospital of Hebei Medical University for postoperative care. The nursing intervention were subsequently summarized and analyzed. In July 2023, the patient successfully underwent radical resection for esophageal cancer. Following the operation, the patient received regular medication and on-site nutritional intervention with the consent of her family. At discharge, the prealbumin, albumin, total protein and hemoglobin values of the patient were low, and body weight was 91 kg. The patient's nutritional risk screening (NRS2022) score was 5 points, and the Patient-Generated Subjective Global Assessment (PG-SGA) score was 4 points. After discharge, the patient continued to receive family enteral nutrition treatment, dietary guidance and psychological nursing. A follow-up review conducted 4 weeks after discharge showed improvements in the patient's NRS2022, albumin, total protein, hemoglobin, and body weight. Conclusions: Strengthening postoperative nutritional intervention are vital for promoting rehabilitation in patients who undergo radical resection of esophageal cancer after liver transplantation.

Strategies for treating the cold tumors of cholangiocarcinoma: core concepts and future directions.

Cholangiocarcinoma (CCA) is a rare type of digestive tract cancer originating from the epithelial cells of the liver and biliary tract. Current treatment modalities for CCA, such as chemotherapy and radiation therapy, have demonstrated limited efficacy in enhancing survival rates. Despite the revolutionary potential of immunotherapy in cancer management, its application in CCA remains restricted due to the minimal infiltration of immune cells in these tumors, rendering them cold and unresponsive to immune checkpoint inhibitors (ICIs). Cancer cells within cold tumors deploy various mechanisms for evading immune attack, thus impeding clinical management. Recently, combination immunotherapy has become increasingly essential to comprehend the mechanisms underlying cold tumors to enhance a deficient antitumor immune response. Therefore, a thorough understanding of the knowledge on the combination immunotherapy of cold CCA is imperative to leverage the benefits of immunotherapy in treating patients. Moreover, gut microbiota plays an essential role in the immunotherapeutic responses in CCA. In this review, we summarize the current concepts of immunotherapy in CCA and clarify the intricate dynamics within the tumor immune microenvironment (TIME) of CCA. We also delve into the evasion mechanisms employed by CCA tumors against the anti-tumor immune responses. The context of combination immunotherapies in igniting cold tumors of CCA and the critical function of gut microbiota in prompting immune responses have also been annotated. Furthermore, we have proposed future directions in the realm of CCA immunotherapy, aiming to improve the clinical prognosis of CCA patients.

Protection of Parkin over-expression on lung in rats with exertional heat stroke by activating mitophagy.

OBJECTIVE: To investigate the role of Parkin overexpression-induecd mitophagy in alleviating acute lung injury of exertional heat stroke(EHS) rats. METHODS: Eighty SD rats were divided into four groups: Control group (CON group), Control Parkin overexpression group (CON + Parkin group), exertional heat stroke group (EHS group), and exertional heat stroke Parkin overexpression group (EHS + Parkin group). Adeno-associated virus carrying the Parkin gene was intravenously injected into the rats to overexpress Parkin in the lung tissue. An exertional heat stroke rat model was established, and survival curves were plotted. Lung Micro-CT was performed, and lung coefficient and pulmonary microvascular permeability were measured. Enzyme-linked immunosorbent assays(ELISA) were used to determine the levels of interleukin-6(IL-6), interleukin-1ß(IL-1ß), Tumor necrosis factor-α(TNF-α), and reactive oxygen species(ROS). The morphology of mitochondria in type II epithelial cells of lung tissue was observed using transmission electron microscopy. The apoptosis of lung tissue, the level of mitophagy, and the co-localization of Pink1 and Parkin were determined using immunofluorescence. The expression of Pink1, Parkin, MFN2, PTEN-L, PTEN, p62, and microtubule associated protein 1 light chain 3 (LC3) in rat lung tissue was measured by western blot. RESULTS: Compared with the CON group, there were more severe lung injury and more higher levels of IL-6, IL-1ß, TNF-α in EHS rats. Both of the LC3-II/LC3-I ratio and the co-localization of LC3 and Tom20 in the lung tissue of EHS rats decreased. Compared with the EHS group, the survival rate of rats in the EHS + Parkin overexpression group was significantly increased, lung coefficient and pulmonary microvascular permeability were reduced, and pathological changes such as exudation and consolidation were significantly alleviated. The levels of IL-6, IL-1ß, TNF-α, and ROS were significantly decreased; the degree of mitochondrial swelling in type II alveolar epithelial cells was reduced, and no vacuolization was observed. Lung tissue apoptosis was reduced, and the colocalization fluorescence of Pink1 and Parkin, as well as LC3 and Tom20, were increased. The expression of Parkin and LC3-II/LC3-I ratio in lung tissue were both increased, while the expression of P62, Pink1, MFN2, and PTEN-L was decreased. CONCLUSION: Pink1/Parkin-mediated mitophagy dysfunction is one of the mechanisms underlying acute lung injury in rats with EHS, and activation of Parkin overexpression induced-mitophagy can alleviate acute lung injury caused by EHS.

Functional elucidation of the EIF4A3-circR-4225-miR-507-TNFSF11 regulatory axis in LUAD and its role in tumor progression.

Lung adenocarcinoma (LUAD) is the most common subtypes of NSCLC. However, the therapeutic effects for LUAD are unsatisfactory at current stage, so it is important to find new molecular targets and therapeutic strategies. circRNAs can regulate the expression of target genes by binding to microRNAs (miRNAs) to form competitive endogenous RNAs (ceRNAs). Therefore, we investigated the functions of circR-4225 in the tumor progression of LUAD and its molecular mechanism in this paper. circR-4225 is up-regulated in LUAD tissues. EIF4A3, a member of the eukaryotic translation initiation factor 4A (EIF4A) family, promotes the expression of circR-4225. circR-4225 acts as a molecular sponge to down-regulate miR-507, which promotes the up-regulation of the expression of its target gene-tumor necrosis factor superfamily member 11 (TNFSF11). Knockdown of circR-4225 in the LUAD cell lines can inhibit cell proliferation and viability, and promote apoptosis of the LUAD cell lines, which can be reverted by inhibiting miR-507 or overexpressing TNFSF11. To sum it up, this study demonstrated that circR-4225 was significantly up-regulated in LUAD tissues, and circR-4225 promoted LUAD progression by sponging miR-507 and up-regulating TNFSF11. This study can provide new molecular targets for early diagnosis and treatment of LUAD.

Recent advances in Alzheimer's disease: Mechanisms, clinical trials and new drug development strategies.

Alzheimer's disease (AD) stands as the predominant form of dementia, presenting significant and escalating global challenges. Its etiology is intricate and diverse, stemming from a combination of factors such as aging, genetics, and environment. Our current understanding of AD pathologies involves various hypotheses, such as the cholinergic, amyloid, tau protein, inflammatory, oxidative stress, metal ion, glutamate excitotoxicity, microbiota-gut-brain axis, and abnormal autophagy. Nonetheless, unraveling the interplay among these pathological aspects and pinpointing the primary initiators of AD require further elucidation and validation. In the past decades, most clinical drugs have been discontinued due to limited effectiveness or adverse effects. Presently, available drugs primarily offer symptomatic relief and often accompanied by undesirable side effects. However, recent approvals of aducanumab (1) and lecanemab (2) by the Food and Drug Administration (FDA) present the potential in disrease-modifying effects. Nevertheless, the long-term efficacy and safety of these drugs need further validation. Consequently, the quest for safer and more effective AD drugs persists as a formidable and pressing task. This review discusses the current understanding of AD pathogenesis, advances in diagnostic biomarkers, the latest updates of clinical trials, and emerging technologies for AD drug development. We highlight recent progress in the discovery of selective inhibitors, dual-target inhibitors, allosteric modulators, covalent inhibitors, proteolysis-targeting chimeras (PROTACs), and protein-protein interaction (PPI) modulators. Our goal is to provide insights into the prospective development and clinical application of novel AD drugs.

Proprioception enhancement for robot assisted neural rehabilitation: a dynamic electrical stimulation based method and preliminary results from EEG analysis.

Objective.In recent years, the robot assisted (RA) rehabilitation training has been widely used to counteract defects of the manual one provided by physiotherapists. However, since the proprioception feedback provided by the robotic assistance or the manual methods is relatively weak for the paralyzed patients, their rehabilitation efficiency is still limited. In this study, a dynamic electrical stimulation (DES) based proprioception enhancement and the associated quantitative analysis methods have been proposed to overcome the limitation mentioned above.Approach.Firstly, the DES based proprioception enhancement method was proposed for the RA neural rehabilitation. In the method, the relationship between the surface electromyogram (sEMG) envelope of the specified muscle and the associated joint angles was constructed, and the electrical stimulation (ES) pulses for the certain joint angles were designed by consideration of the corresponding sEMG envelope, based on which the ES can be dynamically regulated during the rehabilitation training. Secondly, power spectral density, source estimation, and event-related desynchronization of electroencephalogram, were combinedly used to quantitatively analyze the proprioception from multiple perspectives, based on which more comprehensive and reliable analysis results can be obtained. Thirdly, four modes of rehabilitation training tasks, namely active, RA, DES-RA, and ES-only training, were designed for the comparison experiment and validation of the proposed DES based proprioception enhancement method.Main results.The results indicated that the activation of the sensorimotor cortex was significantly enhanced when the DES was added, and the cortex activation for the DES-RA training was similar to that for the active training. Meanwhile, relatively consistent results from the multiple perspectives were obtained, which validates the effectiveness and robustness of the proposed proprioception analysis method.Significance.The proposed methods have the potential to be applied in the practical rehabilitation training to improve the rehabilitation efficiency.

An Adaptive Hybrid Brain-Computer Interface for Hand Function Rehabilitation of Stroke Patients.

Motor imagery (MI) based brain computer interface (BCI) has been extensively studied to improve motor recovery for stroke patients by inducing neuroplasticity. However, due to the lower spatial resolution and signal-to-noise ratio (SNR) of electroencephalograph (EEG), MI based BCI system that involves decoding hand movements within the same limb remains lower classification accuracy and poorer practicality. To overcome the limitations, an adaptive hybrid BCI system combining MI and steady-state visually evoked potential (SSVEP) is developed to improve decoding accuracy while enhancing neural engagement. On the one hand, the SSVEP evoked by visual stimuli based on action-state flickering coding approach significantly improves the recognition accuracy compared to the pure MI based BCI. On the other hand, to reduce the impact of SSVEP on MI due to the dual-task interference effect, the event-related desynchronization (ERD) based neural engagement is monitored and employed for feedback in real-time to ensure the effective execution of MI tasks. Eight healthy subjects and six post-stroke patients were recruited to verify the effectiveness of the system. The results showed that the four-class gesture recognition accuracies of healthy individuals and patients could be improved to 94.37 ± 4.77 % and 79.38 ± 6.26 %, respectively. Moreover, the designed hybrid BCI could maintain the same degree of neural engagement as observed when subjects solely performed MI tasks. These phenomena demonstrated the interactivity and clinical utility of the developed system for the rehabilitation of hand function in stroke patients.

Injectable Hydrogel of Chitosan-Octyl Itaconate Conjugate Modulates Inflammatory Response.

Itaconic acid and its derivative 4-octyl itaconate (OI) represent a novel anti-inflammatory medication that has demonstrated efficacy in multiple inflammation models because of its minimal side effects. Recently, natural polymers conjugated with small molecule drugs, known as polymer-drug conjugates (PDCs), have emerged as a promising approach to sustained drug release. In this work, we reported an approach to prepare a PDC containing an OI and make it into an injectable hydrogel. Chitosan (CS) was selected for PDC synthesis because of its abundant free amino groups that can be conjugated with molecules containing carboxyl groups by carbodiimide chemistry. We used an ethanol/water cosolvent system to synthesize a CS-OI conjugate via EDC/NHS catalysis. The CS-OI conjugate had improved water solubility and unique anti-inflammatory activity and did not show compromised antibacterial activity compared with unmodified CS. Beta-glycerophosphate (ß-GP) cross-linked CS-OI hydrogel exhibited good injectability with sustainable OI release and effectively modulated inflammatory response in a rat model. Therefore, this study provides valuable insights into the design of PDC hydrogels with inflammatory modulatory properties.

Comparison of Predictive Performance for Pedicle Screw Loosening Between Computed Tomography-Based Hounsfield Units and Magnetic Resonance Imaging-Based Vertebral Bone Quality Score After Lumbar Surgery.

OBJECTIVE: To compare predictive performance for pedicle screw loosening between computed tomography (CT)-based Hounsfield units (HU) and magnetic resonance imaging (MRI)-based vertebral bone quality score (VBQ) after lumbar surgery. METHODS: A retrospective study was conducted on patients who received transforaminal lumbar interbody fusion continuously at our institution from May 2018 to September 2020. On the basis of 12 months' follow-up lumbar radiographs, screw loosening was defined as a clear zone of minimal thickness of ≥1 mm around the pedicle screw on radiography. VBQ score and HU value were measured using preoperative MRI and CT, respectively. Then, we evaluated the predictive performance of these 2 parameters by comparing the receiver operating characteristic curve. RESULTS: In all patients, area under the curve (AUC) of the VBQ score (AUC = 0.752; 95% confidence interval [CI] 0.663-0.841; P < 0.001) was larger than those of the CT HU value (AUC = 0.652; 95% CI 0.558-0.746; P = 0.005), but there was no significant difference between them (PAUC = 0.076). In patients with lumbar spinal stenosis, AUC of VBQ score (AUC = 0.863; 95% CI 0.764-0.961; P < 0.001) was larger than those of the CT HU value (AUC = 0.673; 95% CI 0.513-0.833; P = 0.043), with significant difference (PAUC = 0.003). CONCLUSIONS: MRI-based VBQ score and CT-based HU value have similar performance in predicting pedicle screw loosening after lumbar surgery. Furthermore, in patients with lumbar spinal stenosis, VBQ score demonstrated better predictive ability than HU value.

Investigating the potential mechanism and therapeutic effects of SLXG for cholesterol gallstone treatment.

BACKGROUND: Shugan Lidan Xiaoshi Granules (SLXG) is a traditional Chinese medicine (TCM) formulation frequently employed to prevent and treat cholesterol gallstones. SLXG is formulated based on the Chaihu Shugan Formula found in an ancient Chinese medical book, a traditional remedy in China for centuries, and has demonstrated successful treatment of numerous patients with gallbladder stones. PURPOSE: This research sought to clarify the therapeutic impact and molecular mechanisms of SLXG and its active components in the treatment of cholesterol gallbladder stones. METHODS: The study employed network pharmacology, UPLC-HRMS transcriptome sequencing, animal model experiments, molecular docking, and Surface Plasmon Resonance (SPR) to explore the molecular mechanisms of SLXG and its relationship with Traditional Chinese Medicines (TCMs) and potential targets. Furthermore, PPI network analysis, along with GO and KEGG enrichment analyses, were performed to explore the potential mechanisms through which SLXG and its active ingredient, naringenin, prevent and treat cholesterol gallstones. The mechanism of action was further elucidated using an animal model for gallbladder stone formation. RESULTS: The study employed a network pharmacology and UPLC-HRMS to investigate the active compounds of SLXG for the treatment of cholesterol gallbladder stones, and subsequently constructed a network of therapeutic targets of SLXG. The results from gene enrichment analyses indicated that SLXG targets the metabolic pathway of bile secretion and the cholesterol metabolism pathway in addressing cholesterol gallbladder stones. The molecular docking results confirmed the interaction between the genes enriched in the pathways and the active ingredients in SLXG. Transcriptome sequencing results demonstrated that SLXG exerts its therapeutic effect on gallstones by regulating cholesterol and bile acid synthesis and metabolism. Furthermore, animal model experiments and SPR provided evidence that SLXG and its active ingredient, naringenin, exert therapeutic effects on cholesterol gallbladder stones by targeting the genes HMGCR, SOAT2, and UGT1A1, and influencing substances associated with cholesterol synthesis and metabolism. CONCLUSIONS: Using systematic network pharmacology methods combined with in vivo validation experiments, we uncovered the fundamental pharmacological effects and potential mechanisms of SLXG and its active ingredient, naringenin, in the treatment of cholesterol gallstones. This research underscores the valuable role that traditional remedies can play in addressing medical challenges and suggests a promising direction for further exploration of natural treatments for the disease.

C5aR2 Deficiency Lessens C5aR1 Distribution and Expression in Neutrophils and Macrophages.

As another receptor for complement activation product C5a, C5aR2 has been paid much attention these years. Although controversial and complex, its specific signals or roles in modulating the classic receptor C5aR1 have been investigated and gradually revealed. The hypothesis of the heterodimer of C5aR1 and C5aR2 has also been suggested and observed under extremely high C5a concentrations. In this article, we tried to investigate whether C5aR2 would affect C5aR1 expression under normal or inflammatory conditions in WT and C5ar2 -/- mice of C57BL/6 background. We focused on the innate immune cells-neutrophils and macrophages. The mRNA levels of C5ar1 in normal kidney, liver, and the mRNA or protein levels of naïve-bone marrow and peripheral blood leukocytes and peritoneal Mφs were comparable between WT and C5ar2 -/- mice, indicating the technique of C5aR2 knockout did not affect the transcription of its neighboring gene C5aR1. However, the mean fluorescence intensity of surface C5aR1 on naïve circulating C5ar2 -/- neutrophils detected by FACS was reduced, which might be due to the reduced internalization of C5aR1 on C5ar2 -/- neutrophils. In the peritonitis model induced by i.p. injection of thioglycollate, more neutrophils were raised after 10 hr in C5ar2 -/- peritoneal cavity, indicating the antagonism of C5aR2 on C5aR1 signal in neutrophil chemotaxis. After 3 days of thioglycollate injection, the mainly infiltrating macrophages were comparable between WT and C5ar2 -/- mice, but the C5ar1 mRNA and surface or total C5aR1 protein expression were both reduced in C5ar2 -/- macrophages, combined with our previous study of reduced chemokines and cytokines expression in C5ar2 -/- peritoneal macrophages, indicating that C5aR2 in macrophages may cooperate with C5aR1 inflammatory signals. Our article found C5aR2 deficiency lessened C5aR1 distribution and expression in neutrophils and macrophages with different functions, indicating C5aR2 might function differently in different cells.

Exploring biomarkers for diagnosing and predicting organ dysfunction in patients with perioperative sepsis: a preliminary investigation.

OBJECTIVE: Early diagnosis and prediction of organ dysfunction are critical for intervening and improving the outcomes of septic patients. The study aimed to find novel diagnostic and predictive biomarkers of organ dysfunction for perioperative septic patients. METHOD: This is a prospective, controlled, preliminary, and single-center study of emergency surgery patients. Mass spectrometry, Gene Ontology (GO) functional analysis, and the protein-protein interaction (PPI) network were performed to identify the differentially expressed proteins (DEPs) from sepsis patients, which were selected for further verification via enzyme-linked immunosorbent assay (ELISA). Logistic regression analysis was used to estimate the relative correlation of selected serum protein levels and clinical outcomes of septic patients. Calibration curves were plotted to assess the calibration of the models. RESULTS: Five randomized serum samples per group were analyzed via mass spectrometry, and 146 DEPs were identified. GO functional analysis and the PPI network were performed to evaluate the molecular mechanisms of the DEPs. Six DEPs were selected for further verification via ELISA. Cathepsin B (CatB), vascular cell adhesion protein 1 (VCAM-1), neutrophil gelatinase-associated lipocalin (NGAL), protein S100-A9, prosaposin, and thrombospondin-1 levels were significantly increased in the patients with sepsis compared with those of the controls (p < 0.001). Logistic regression analysis showed that CatB, S100-A9, VCAM-1, prosaposin, and NGAL could be used for preoperative diagnosis and postoperative prediction of organ dysfunction. CatB and S100-A9 were possible predictive factors for preoperative diagnosis of renal failure in septic patients. Internal validation was assessed using the bootstrapping validation. The preoperative diagnosis of renal failure model displayed good discrimination with a C-index of 0.898 (95% confidence interval 0.843-0.954) and good calibration. CONCLUSION: Serum CatB, S100-A9, VCAM-1, prosaposin, and NGAL may be novel markers for preoperative diagnosis and postoperative prediction of organ dysfunction. Specifically, S100-A9 and CatB were indicators of preoperative renal dysfunction in septic patients. Combining these two biomarkers may improve the accuracy of predicting preoperative septic renal dysfunction. TRIAL REGISTRATION: The study was registered at the Chinese Clinical Trials Registry (ChiCTR2200060418) on June 1, 2022.

Central Lean Mass Distribution and the Risks of All-Cause and Cause-Specific Mortality in 40,283 UK Biobank Participants.

INTRODUCTION: The purpose of this study was to investigate the association of central lean mass distribution with the risk of mortality. METHODS: This cohort study included 40,283 UK Biobank participants. Cox proportional hazards regression models were used to estimate the association of central lean mass distribution, i.e., trunk-to-leg lean mass ratio, assessed by dual-energy X-ray absorptiometry, with the risk of mortality. RESULTS: The median age of the participants was 65 years, and 52% were women. During a median follow-up of 4.18 years, 674 participants died, of whom 366 were due to cancer and 126 were due to cardiovascular causes. Compared with the lowest tertile of a trunk-to-leg lean mass ratio, the multivariable-adjusted (age, sex, ethnicity, lifestyle, comorbidities, body mass index, and appendicular muscle mass index) hazards ratios of the highest tertile of trunk-to-leg lean mass ratio were 1.55 (95% CI: 1.23-1.94), 1.69 (95% CI: 1.26-2.26), and 1.14 (95% CI: 0.72-1.80) for all-cause, cancer, and cardiovascular mortality, respectively. Neutrophil-to-lymphocyte ratio mediated 9.3% (95% CI: 3.3%-40.4%) of the association of trunk-to-leg lean mass ratio with all-cause mortality. There was evidence for additive interactions of trunk-to-leg lean mass ratio with older age and poor diet quality for all-cause mortality. CONCLUSION: Trunk-to-leg lean mass ratio, assessed by dual-energy X-ray absorptiometry, was positively associated with the risks of all-cause and cancer mortality, independent of general obesity and central obesity, in UK middle-aged and older adults. Central lean mass distribution may interact synergistically with aging and poor diet quality to further increase the risk of death.

Effect of Posterior Cruciate Ligament Resection on Gap Balancing in Robot-assisted Total Knee Arthroplasty.

OBJECTIVE: Retention or sacrifice of the posterior cruciate ligament (PCL) is one of the most controversial issues while performing total knee arthroplasty (TKA). This study aimed to evaluate the impact of PCL resection on flexion-extension gaps, femoral component rotation, and bone resection amounts during robot-assisted TKA. METHODS: This prospective study included 40 patients with knee osteoarthritis who underwent robot-assisted posterior-stabilized (PS) TKA between September 2021 and February 2022. Of the patients, 75% were women (30/40) with a mean age and BMI of 72.6 years and 27.4 kg/m2, respectively. The guidance module and camera stand assembly were used to capture gaps before and after PCL resection. Measurements of femoral component rotation and bone resection amounts were made in cruciate-retaining (CR) TKA mode and PS-TKA mode. RESULTS: After PCL resection, the mean change in the medial and lateral compartments of flexion gaps increased by 2.0 and 0.6 mm, respectively (p < 0.001). Compared with the CR-TKA mode group, the bone resection amounts of the medial posterior condyle and the lateral posterior condyle in the PS-TKA mode group decreased by 2.0 ± 1.1 and 1.1 ± 1.1 mm, respectively, and the external rotation of the femoral prosthesis relative to the posterior condylar axis and trans-epicondylar line was reduced by 1.0° ± 1.3° and 1.2° ± 1.6°, respectively (p < 0.001). CONCLUSION: The release of the PCL did not affect the extension gap, but significantly increased the flexion gap. Moreover, the increases in the medial flexion gap were greater than those of the lateral flexion gap. After PCL resection, less external rotation of the femoral prosthesis and fewer bone cuts of the posterior femur were needed in PS-TKA.

Ginsenoside Rg1 Regulates Immune Microenvironment and Neurological Recovery After Spinal Cord Injury Through MYCBP2 Delivery via Neuronal Cell-Derived Extracellular Vesicles.

Spinal cord injury (SCI) is a severe neurological condition that frequently leads to significant sensory, motor, and autonomic dysfunction. This study sought to delineate the potential mechanistic underpinnings of extracellular vesicles (EVs) derived from ginsenoside Rg1-pretreated neuronal cells (Rg1-EVs) in ameliorating SCI. These results demonstrated that treatment with Rg1-EVs substantially improved motor function in spinal cord-injured mice. Rg1-EVs enhance microglial polarization toward the M2 phenotype and repressed oxidative stress, thereby altering immune responses and decreasing inflammatory cytokine secretion. Moreover, Rg1-EVs substantially diminish reactive oxygen species accumulation and enhanced neural tissue repair by regulating mitochondrial function. Proteomic profiling highlighted a significant enrichment of MYCBP2 in Rg1-EVs, and functional assays confirmed that MYCBP2 knockdown counteracted the beneficial effects of Rg1-EVs in vitro and in vivo. Mechanistically, MYCBP2 is implicated in the ubiquitination and degradation of S100A9, thereby promoting microglial M2-phenotype polarization and reducing oxidative stress. Overall, these findings substantiated the pivotal role of Rg1-EVs in neuronal protection and functional recovery following SCI through MYCBP2-mediated ubiquitination of S100A9. This research offers novel mechanistic insights into therapeutic strategies against SCI and supports the clinical potential of Rg1-EVs.

A Review: Visuospatial Dysfunction in Patients with the Cerebral Small Vessel Disease.

Cerebral small vessel disease (CSVD) impairs visuospatial function, and this is one of the most obvious areas of cognitive impairment in CSVD. So, recognizing, monitoring, and treating visuospatial dysfunction are all important to the prognosis of CSVD. This review discussed the anatomical and pathological mechanisms, clinical recognition (scales, imaging, and biomarkers), and treatment of cognitive impairment especially visuospatial dysfunction in CSVD.

Antioxidative, Anti-Inflammatory, Antibacterial, Photo-Cross-Linkable Hydrogel of Gallic Acid-Chitosan Methacrylate: Synthesis, In Vitro, and In Vivo Assessments.

Chitosan (CS)-based photo-cross-linkable hydrogels have gained increasing attention in biomedical applications. In this study, we grafted CS with gallic acid (GA) by carbodiimide chemistry to prepare the GA-CS conjugate, which was subsequently modified with methacrylic anhydride (MA) modification to obtain the methacrylated GA-CS conjugate (GA-CS-MA). Our results demonstrated that the GA-CS-MA hydrogel not only exhibited improved physicochemical properties but also showed antibacterial, antioxidative, and anti-inflammatory capacity. It showed moderate antibacterial activity and especially showed a more powerful inhibitory effect against Gram-positive bacteria. It modulated macrophage polarization, downregulated pro-inflammatory gene expression, upregulated anti-inflammatory gene expression, and significantly reduced reactive oxygen species (ROS) and nitric oxide (NO) production under lipopolysaccharide (LPS) stimulation. Subcutaneously implanted GA-CS-MA hydrogels induced significantly lower inflammatory responses, as evidenced by less inflammatory cell infiltration, thinner fibrous capsule, and predominately promoted M2 polarization. This study provides a feasible strategy to prepare CS-based photo-cross-linkable hydrogels with improved physicochemical properties for biomedical applications.