Application and progress of nanozymes in antitumor therapy.

Tumors remain one of the major threats to public health and there is an urgent need to design new pharmaceutical agents for their diagnosis and treatment. In recent years, due to the rapid development of nanotechnology, biotechnology, catalytic science, and theoretical computing, subtlety has gradually made great progress in research related to tumor diagnosis and treatment. Compared to conventional drugs, enzymes can improve drug distribution and enhance drug enrichment at the tumor site, thereby reducing drug side effects and enhancing drug efficacy. Nanozymes can also be used as tumor tracking imaging agents to reshape the tumor microenvironment, providing a versatile platform for the diagnosis and treatment of malignancies. In this paper, we review the current status of research on enzymes in oncology and analyze novel oncology therapeutic approaches and related mechanisms. To date, a large number of nanomaterials, such as noble metal nanomaterials, nonmetallic nanomaterials, and carbon-based nanomaterials, have been shown to be able to function like natural enzymes, particularly with significant advantages in tumor therapy. In light of this, the authors in this review have systematically summarized and evaluated the construction, enzymatic activity, and their characteristics of nanozymes with respect to current modalities of tumor treatment. In addition, the application and research progress of different types of nicknames and their features in recent years are summarized in detail. We conclude with a summary and outlook on the study of nanozymes in tumor diagnosis and treatment. It is hoped that this review will inspire researchers in the fields of nanotechnology, chemistry, biology, materials science and theoretical computing, and contribute to the development of nano-enzymology.

Long-term effects of compound passivator coupled with silicon fertilizer on the reduction of cadmium and arsenic accumulation in rice and health risk evaluation.

Cadmium (Cd) and arsenic (As) are precedence-controlled contaminants in paddy soils, that can easily accumulate in rice grains. Limestone and sepiolite (LS) compound passivator can obviously reduce Cd uptake in rice, whereas Si fertilizer can effectively decrease rice As uptake. Here, the synergistic effects of the LS compound passivator coupled with Si fertilizer (LSCS) on the soil pH and availability of Si, Cd, and As, as well as rice grain Cd and As accumulation and its health risk were studied based on a 3-year consecutive field experiment. The results showed that the LSCS performed the best in terms of synchronously decreasing soil Cd and As availability and rice Cd and As uptake. In the LSCS treatments, soil pH gradually decreased with the rice-planting season, while soil available Cd and As contents gradually increased, suggesting that the influence of LSCS on Cd and As availability gradually weakened with rice cultivation. Nonetheless, the contents of Cd and inorganic As (i-As) in rice grains treated with LSCS were slightly affected by cultivation but were significantly lower than the single treatments of LS compound passivator or Si fertilizer. According to the Cd and As limit standards in food (GB2762-2022), the Cd and i-As content in rice grains can be lowered below the standard by using the 4500 kg/hm2 LS compound passivator coupled with 90 kg/hm2 Si fertilizer in soil and spraying 0.4 g/L Si fertilizer on rice leaves for at least three years. Furthermore, health risk evaluation revealed that LSCS treatments significantly reduced the estimated daily intake, annual excess lifetime cancer risk, and hazard quotient of Cd and i-As in rice grains. These findings suggest that LSCS could be a viable approach for reducing Cd and As accumulation in rice grains and lowering the potential health risks associated with rice.

Fluorescence Imaging of Diabetic Cataract-Associated Lipid Droplets in Living Cells and Patient-Derived Tissues.

Diabetic cataract (DC) surgery carries risks such as slow wound healing, macular edema, and progression of retinopathy and is faced with a deficiency of effective drugs. In this context, we proposed a protocol to evaluate the drug's efficacy using lipid droplets (LDs) as the marker. For this purpose, a fluorescent probe PTZ-LD for LDs detection is developed based on the phenothiazine unit. The probe displays polarity-dependent emission variations, i.e., lower polarity leading to stronger intensity. Especially, the probe exhibits photostability superior to that of Nile Red, a commercial LDs staining dye. Using the probe, the formation of LDs in DC-modeled human lens epithelial (HLE) cells is validated, and the interplay of LDs-LDs and LDs-others are investigated. Unexpectedly, lipid transfer between LDs is visualized. Moreover, the therapeutic efficacy of various drugs in DC-modeled HLE cells is assessed. Ultimately, more LDs were found in lens epithelial tissues from DC patients than in cataract tissues for the first time. We anticipate that this work can attract more attention to the important roles of LDs during DC progression.

The association between unilateral high-riding vertebral artery and atlantoaxial joint morphology: a multi-slice spiral computed tomography study of 396 patients and a finite element analysis.

BACKGROUND CONTEXT: A high-riding vertebral artery (HRVA) can deviate too medially, too posteriorly, or too superiorly to allow the safe insertion of screws. However, it is unknown whether the presence of a HRVA is associated with morphological changes of the atlantoaxial joint. PURPOSE: To investigate the association between HRVA and atlantoaxial joint morphology in patients with and without HRVA. STUDY DESIGN: A retrospective case-control study and finite element (FE) analysis. PATIENT SAMPLE: A total of 396 patients with cervical spondylosis underwent multi-slice spiral computed tomography (MSCT) of cervical spine at our institutions from 2020 to 2022. OUTCOME MEASURES: A series of atlantoaxial joint morphological parameters, including C2 lateral mass settlement (C2 LMS), C1-2 sagittal joint inclination (C1-2 SI), C1-2 coronal joint inclination (C1-2 CI), atlanto-dental interval (ADI), lateral atlanto-dental interval (LADI), and C1-2 relative rotation angle (C1-2 RRA) were measured, and lateral atlantoaxial joints osteoarthritis (LAJs-OA) was recorded. The stress distribution on the C2 facet surface under different torques of flexion-extension, lateral bending, and axial rotation was analyzed by FE models. A 2-Nm moment was applied to all models to determine the range of motion (ROM). METHODS: A total of 132 consecutive cervical spondylosis patients with unilateral HRVA were enrolled in the HRVA group, and 264 patients without HRVA matched for age and sex were enrolled in the normal (NL) group. Atlantoaxial joint morphological parameters were compared between two sides of C2 lateral mass within HRVA or NL group, and between HRVA and NL groups. A 48-year-old woman with cervical spondylosis without HRVA was selected for cervical MSCT. A three-dimensional (3D) FE intact model of the normal upper cervical spine (C0-C2) was created. We established the HRVA model by simulating atlantoaxial morphological changes of unilateral HRVA with FE method. RESULTS: The C2 LMS was significantly smaller on the HRVA side than that on the non-HRVA side in the HRVA group, but C1-2 SI, C1-2 CI, and LADI on HRVA side were significantly larger than those on non-HRVA side. There was no significant difference between left and right sides in the NL group. The difference in C2 LMS (d-C2 LMS) between HRVA side and non-HRVA side in the HRVA group was larger than that in the NL group (P < 0.05). Meanwhile, the differences in C1-2 SI (d-C1/2 SI), C1-2 CI (d-C1/2 CI), and LADI (d-LADI) in the HRVA group were significantly larger than those in the NL group. The C1-2 RRA in the HRVA group was significantly larger than that in the NL group. Pearson correlations showed that d-C1/2 SI, d-C1/2 CI, and d-LADI were positively associated with d-C2 LMS (r=0.428, 0.649, 0.498, respectively, p<.05 for all). The incidence of LAJs-OA in the HRVA group (27.3%) was significantly larger than that in the NL group (11.7%). Compared with the normal model, the ROM of C1-2 segment declined in all postures of the HRVA FE model. We found a larger distribution of stress on the C2 lateral mass surface of the HRVA side under different moment conditions. CONCLUSIONS: We suggest that HRVA affects the integrity of the C2 lateral mass. This change in patients with unilateral HRVA is associated with the nonuniform settlement of the lateral mass and an increase in the lateral mass inclination, which may further affect the degeneration of the atlantoaxial joint because of the stress concentration on the C2 lateral mass surface.

Co-application of combined amendment (limestone and sepiolite) and Si fertilizer reduces rice Cd uptake and transport through Cd immobilization and Si-Cd antagonism.

Limestone and sepiolite combined amendment (LS) and silicon (Si) fertilizers are commonly applied for the remediation of Cd-polluted paddy soil. However, it is difficult to further decrease cadmium (Cd) accumulation in rice grains by the individual application of LS or Si fertilizer to heavily Cd-polluted paddy fields. Two seasons of continuous field experiments were conducted in heavily Cd-polluted soil to study how the co-application of LS and Si fertilizer (namely soil-applied Si and foliar-sprayed Si) influences Cd and Si bioavailability in soil and Cd uptake and transport in rice. The results indicated that LS co-applied with soil-applied Si fertilizer treatments can enhance pH, cation exchange capacity (CEC), and available Si content in soil by 0.56-1.26 units, 19.3%-57.2%, and 14.7%-58.9% (p < 0.05), respectively, and reduce the toxicity characteristic leaching procedure (TCLP) extractable Cd content in soil by 26.5%-49.8% (p < 0.05) relative to the control. Furthermore, the co-application of LS and soil and foliar-sprayed Si fertilizer treatments reduced the Cd content in brown rice by 18.8%-70.6% (p < 0.05) compared with the control. Particularly, the brown rice Cd content under the co-application treatment (4500 kg/ha of soil applied LS, 90 kg/ha of Si fertilizer, and 0.4 g/L of foliar-sprayed Si fertilizer) was below 0.20 mg/kg in both seasons. Meanwhile, the Si content in rice was considerably enhanced by LS co-applied with Si fertilizer and negatively (p < 0.05) correlated with the rice Cd content. Therefore, the reduction of Cd bioavailability in soil and the antagonistic effect between Cd and Si in rice might be the key factors regulating Cd accumulation in rice via the co-application of LS and Si fertilizer.

Lactiplantibacillus plantarum Regulated Intestinal Microbial Community and Cytokines to Inhibit Salmonella typhimurium Infection.

Lactic acid bacteria (LAB) are recognized as food-grade safe microorganisms and have many beneficial effects. LAB could maintain the host intestinal homeostasis and regulate intestinal microbial community to exert antibacterial effects. In this study, Lactiplantibacillus plantarum (L. plantarum, Lp01) strain isolated from pig intestine was orally administered to C57BL/6 mice, and mice were then infected with Salmonella typhimurium (ATCC14028). The protective effects of L. plantarum were evaluated by monitoring body weight loss, survival rates, bacterial loads in tissue, colon histopathology analysis, and cytokine secretion. 16S rRNA gene sequencing was also utilized to detect the dynamics of the blind gut microbial community in mice. We found that L. plantarum could significantly reduce the body weight loss and improve the survival rates. The survival rate in the L. P-Sty group was up to 67.5%, which was much higher than that in the STY group (25%). Counting of bacterial loads displayed that the colony-forming unit (CFU) of S. typhimurium in the spleen (p < 0.05) and the liver (p < 0.05) from L. P-Sty group both decreased, compared with STY group. Intestinal histopathology showed that it alleviated the intestinal injury caused by Salmonella, inhibited the secretion of pro-inflammatory cytokines, and promoted anti-inflammatory cytokines (p < 0. 01). In addition, L. plantarum also significantly ameliorated the intestinal gut microbiome disturbance caused by Salmonella. It displayed an obvious increase of beneficial bacteria including Lactobacillus and Bacteroidetes and reduction of pathogenic bacteria like Proteobacteria. In conclusion, L. plantarum could regulate microbial community to inhibit Salmonella typhimurium infection.

Low-Intensity Focused Ultrasound Alleviates Chronic Neuropathic Pain-Induced Allodynia by Inhibiting Neuroplasticity in the Anterior Cingulate Cortex.

Low-intensity focused ultrasound (LIFU) is a potential noninvasive method to alleviate allodynia by modulating the central nervous system. However, the underlying analgesic mechanisms remain unexplored. Here, we assessed how LIFU at the anterior cingulate cortex (ACC) affects behavior response and central plasticity resulting from chronic constrictive injury (CCI). The safety of LIFU stimulation was assessed by hematoxylin and eosin (H&E) and Fluoro-Jade C (FJC) staining. A 21-day ultrasound exposure therapy was conducted from day 91 after CCI surgery in mice. We assessed the 50% mechanical withdrawal threshold (MWT50) using Von Frey filaments (VFFs). The expression levels of microtubule-associated protein 2 (MAP2), growth-associated protein 43 (GAP43), and tau were determined via western blotting (WB) and immunofluorescence (IF) staining to evaluate the central plasticity in ACC. The regions of ACC were activated effectively and safely by LIFU stimulation, which significantly increased the number of c-fos-positive cells (P < 0.05) with no bleeding, coagulative necrosis, and neuronal loss. Under chronic neuropathic pain- (CNP-) induced allodynia, MWT50 decreased significantly (P < 0.05), and overexpression of MAP2, GAP43, and tau was also observed. After 3 weeks of treatment, significant increases in MWT50 were found in the CCI+LIFU group compared with the CCI group (P < 0.05). WB and IF staining both demonstrated a significant reduction in the expression levels of MAP2, GAP43, and tau (P < 0.05). LIFU treatment on ACC can effectively attenuate CNP-evoked mechanical sensitivity to pain and reverse aberrant central plasticity.

CT-based radiomics nomogram may predict local recurrence-free survival in esophageal cancer patients receiving definitive chemoradiation or radiotherapy: A multicenter study.

BACKGROUND AND PURPOSE: To establish and validate a contrast-enhanced computed tomography-based hybrid radiomics nomogram for prediction of local recurrence-free survival (LRFS) in esophageal squamous cell cancer (ESCC) patients receiving definitive (chemo)radiotherapy in a multicenter setting. MATERIALS AND METHODS: This retrospective study included 302 ESCC patients from Xijing Hospital receiving definitive (chemo)radiotherapy, which were randomly assigned to the training (n = 201) and internal validation sets (n = 101). And 74 and 21 ESCC patients from the other two centers were used as the external validation set (n = 95). A hybrid radiomics nomogram was established by integrating clinical factors, radiomic signature and deep-learning signature in training set and was tested in two validation sets. RESULTS: The deep-learning signature showed better prognostic performance than radiomic signature for predicting LRFS in training (C-index: 0.73 vs 0.70), internal (Cindex: 0.72 vs 0.64) and external validation sets (C-index: 0.72 vs 0.63), which could stratify patients into high and low-risk group with different prognosis (cut-off value: -0.06). Low-risk groups had better LRFS than high-risk groups in training (p < 0.0001; 2-y LRFS 71.1% vs 33.0%), internal (p < 0.01; 2-y LRFS 58.8% vs 34.8%) and external validation sets (p < 0.0001; 2-y LRFS 61.9% vs 22.4%), respectively. The hybrid radiomics nomogram established by integrating radiomic signature, deep-learning signature with clinical factors including T stage and concurrent chemotherapy outperformed any one or two combinations in training (C-index: 0.82), internal (Cindex: 0.78), and external validation sets (C-index: 0.76). Calibration curves showed good agreement. CONCLUSIONS: The hybrid radiomics based on pretreatment contrast-enhanced computed tomography provided a promising way to predict local recurrence of ESCC patients receiving definitive (chemo)radiotherapy.

Thrombo-Inflammatory Prognostic Scores Improve BISAP-Based Risk Stratification in Acute Pancreatitis Patients: A Retrospective Cohort Study.

Purpose: The thrombo-inflammatory prognostic score (TIPS) and the bedside index for severity in acute pancreatitis (BISAP) are both scoring systems that enable the rapid prognostic assessment of early-stage acute pancreatitis (AP) patients, but the overall prognostic utility of these individual systems is limited. This study was thus developed to explore whether a combination of TIPS and BISAP scores would offer better insight to facilitate the risk stratification of AP patients. Methods: This single-center retrospective cohort research evaluated AP cases referred to the emergency department from January 1, 2017 to September 30, 2017. The ability of TIPS scores to improve BISAP-based AP patient risk stratification was appraised employing the curves of receiver-operating characteristic (ROC) and decision curve analysis (DCA) approaches. The initial endpoint for this research was 28-day mortality, while secondary endpoints comprised intensive care unit admission (AICU) and mechanical ventilation (MV) over a 28-day follow-up period. Results: Totally, 440 cases enrolled in the current study were divided at a ratio of 1:1 to derivation and validation cohorts. When estimating 28-day mortality, the combination of TIPS and BISAP (T-BISAP) improved the area under the curve (AUC) value in the derivation group from 0.809 to 0.903 (P < 0.05), in addition to similarly improving this AUC value from 0.709 to 0.853 (P < 0.05) in the validation cohort. Moreover, T-BISAP significantly improved the AUC values for 28-day AICU from 0.751 to 0.824 (P < 0.05) and the AUC values for 28-day MV from 0.755 to 0.808 (P < 0.05). A DCA approach revealed T-BISAP to exhibit higher net benefit when used for patient risk stratification as compared to BISAP alone. Conclusion: The addition of TIPS scores to BISAP scores can enable prediction of 28-day adverse clinical outcomes with AP patients in the ED.

Analysis of the Value of the Blood Urea Nitrogen to Albumin Ratio as a Predictor of Mortality in Patients with Sepsis.

Purpose: At present, simple, accurate, and efficient prognostic tools for the evaluation of cases with early-stage sepsis in the emergency department (ED) are lacking. An increased blood urea nitrogen to albumin ratio (BAR) has previously been shown to be a valuable biomarker with predictive utility in several diseases. The relationship between BAR and sepsis patient outcomes, however, is not well-understood. This exploration was thus developed for the exploration of the link between BAR values and the short-term prognosis of cases with sepsis. Methods: This was a retrospective cohort research of sepsis cases admitted to the West China Hospital of Sichuan University ED from July 2015 to June 2016. Laboratory data were collected upon ED admission, and 7-day all-cause mortality was the primary study endpoint. Relationships between BAR values and APACE II and SOFA scores were generated assessed with correlation coefficient heatmaps. Independent risk factors were identified through multivariate analyses, with the curves of receiver operating characteristic (ROC) being employed to gauge the value of BAR as a predictor of the risk of mortality in sepsis cases. Results: In sum, 801 patients participated in the present investigation. BAR values were strongly correlated with APACHE II and SOFA scores. In a multivariate logistic regression assessment, BAR was identified as an independent predictor of mortality among patients with sepsis (HR=1.032, 95% CI: 1.010-1.055, P=0.004). BAR exhibited an AUC of 0.741 (95% CI: 0.688-0.793, P<0.001) when used to predict patient mortality risk, with 5.27 being the optimal BAR cut-off. Conclusion: We found that BAR can be used as a reliable biomarker to predict mortality in patients with sepsis.

Low-Intensity Focused Ultrasound Alleviates Spasticity and Increases Expression of the Neuronal K-Cl Cotransporter in the L4-L5 Sections of Rats Following Spinal Cord Injury.

Low-intensity focused ultrasound (LIFU) has been shown to provide effective activation of the spinal cord neurocircuits. The aim of this study was to investigate the effects of LIFU in order to alleviate spasticity following spinal cord injury (SCI) by activating the spinal neurocircuits and increasing the expression of the neuronal K-Cl cotransporter KCC2. Adult male Sprague Dawley (SD) rats (220-300 g) were randomly divided into a sham control group, a LIFU- group, and a LIFU+ group. The mechanical threshold hold (g) was used to evaluate the behavioral characteristics of spasm. Electromyography (EMG) was used to assess activation of the spinal cord neurocircuits and muscle spontaneous contraction. Spasticity was assessed by frequency-dependent depression (FDD). The expression of KCC2 of the lumbar spinal cord was determined via western blot (WB) and immunofluorescence (IF) staining. The spinal cord neurocircuits were activated by LIFU simulation, which significantly reduced the mechanical threshold (g), FDD, and EMG recordings (s) after 4 weeks of treatment. WB and IF staining both demonstrated that the expression of KCC2 was reduced in the LIFU- group (P < 0.05). After 4 weeks of LIFU stimulation, expression of KCC2 had significantly increased (P < 0.05) in the LIFU+ group compared with the LIFU- group. Thus, we hypothesized that LIFU treatment can alleviate spasticity effectively and upregulate the expression of KCC2 in the L4-L5 section of SCI rats.

The ratio of red blood cell distribution width to serum calcium predicts severity of patients with acute pancreatitis.

BACKGROUND: Illness severity of patients with acute pancreatitis (AP) at early stage is crucial because the identified moderate and severe cases need early intensive care to reduce the risk of serious complications such as multi-organ failure. Although red blood cell distribution width(RDW)and serum calcium(Ca)alone can be used as predictors of the severity of AP, they have low sensitivity and specificity. Thus, this study is aimed at evaluating the value of the ratio of RDW to serum calcium, which can all be acquired on admission, in predicting the severity of AP. METHODS: This study was based on a retrospective cohort study on patients with AP at the emergency department (ED) of West China Hospital Hospital from January 2016 to June 2016. We divided the patients with AP into two groups, mild acute pancreatitis (MAP) and moderate severe acute pancreatitis (MSAP) + severe acute pancreatitis (SAP). A receiver-operating characteristic (ROC) curve analysis was used to valuate the predictive value of the ratio of RDW to serum calcium for the severity of AP patients and the cut-off value for the ratio of RDW to serum calcium was calculated with sensitivity and specificity. P < 0.05 was considered statistically significant. RESULTS: A total of 666 AP patients were enrolled in this study. These patients were divided into MAP (n = 518) and MSAP+SAP (n = 148) groups. The AUC of RDW/ Ca was 0.912 (95% CI 0.887 to 0.937, P < 0.001), larger than the AUCs of RDW (AUC = 0.768, 95% CI 0.723 to 0.812, P < 0.001) and Ca (AUC = 0.875, 95% CI 0.844 to 0.906, P < 0.001). The optimal cut-off value for RDW/ Ca to predict MSAP and SAP was 7.04 (sensitivity = 0.885, specificity = 0.834). CONCLUSION: The RDW/Ca might be a valuable predictor of the severity of patients with AP.

Development and Validation of a Novel Prognostic Score Based on Thrombotic and Inflammatory Biomarkers for Predicting 28-Day Adverse Outcomes in Patients with Acute Pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a multifactorial disease that is associated with substantial morbidity and mortality. Thrombosis and inflammation are involved in the development and progression of AP. AIM: To develop and validate a novel and simple scoring system for predicting 28-day adverse outcomes in AP patients based on a thrombotic and an inflammatory biomarker. METHODS: A single-center, retrospective cohort study was used to establish the new scoring system (thrombo-inflammatory prognostic score; TIPS), and another study was used to verify it. The study end points were 28-day mortality, requirement for mechanical ventilation (MV), persistent organ failure (POF), and admission to the intensive care unit (AICU). Receiver operating characteristic (ROC) curves was drawn to validate the predictive value of the TIPS. The performance of the TIPS was compared with that of conventional predictive scoring systems. Logistic regression models were used to investigate the relationship between the TIPS and the different end points. RESULTS: Among 440 patients with AP in the derivation group, 27 patients died within the 28-day follow-up period. Prothrombin time (PT) and interleukin-6 (IL-6) were used to calculate the TIPS. The TIPS (AUC=0.843) showed a performance comparable to that of the more established APACHE II (AUC=0.841), SOFA (AUC=0.797), BISAP (AUC=0.762), and Balthazar CT (AUC=0.655) in predicting 28-day mortality in AP. The 28-day mortality and the incidence of MV, POF, and AICU were significantly higher among patients with a higher TIPS (P<0.001). The results of logistic regression analyses indicated that the TIPS was independently associated with the risks of 28-day mortality, AICU, MV and POF. CONCLUSION: The TIPS can enable prediction of 28-day adverse clinical outcomes with AP patients in the ED.

Effects of Noninvasive Low-Intensity Focus Ultrasound Neuromodulation on Spinal Cord Neurocircuits In Vivo.

Although neurocircuits can be activated by focused ultrasound stimulation, it is unclear whether this is also true for spinal cord neurocircuits. In this study, we used low-intensity focused ultrasound (LIFU) to stimulate lumbar 4-lumbar 5 (L4-L5) segments of the spinal cord of normal Sprague Dawley rats with a clapper. The activation of the spinal cord neurocircuits enhanced soleus muscle contraction as measured by electromyography (EMG). Neuronal activation and injury were assessed by EMG, western blotting (WB), immunofluorescence, hematoxylin and eosin (H&E) staining, Nissl staining, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC), somatosensory evoked potentials (SEPs), motor evoked potentials (MEPs), and the Basso-Beattie-Bresnahan locomotor rating scale. When the LIFU intensity was more than 0.5 MPa, LIFU stimulation induced soleus muscle contraction and increased the EMG amplitudes (P < 0.05) and the number of c-fos- and GAD65-positive cells (P < 0.05). When the LIFU intensity was 3.0 MPa, the LIFU stimulation led to spinal cord damage and decreased SEP amplitudes for electrophysiological assessment (P < 0.05); this resulted in coagulation necrosis, structural destruction, neuronal loss in the dorsal horn by H&E and Nissl staining, and increased expression of GFAP, IL-1ß, TNF-α, and caspase-3 by IHC, ELISA, and WB (P < 0.05). These results show that LIFU can activate spinal cord neurocircuits and that LIFU stimulation with an irradiation intensity ≤1.5 MPa is a safe neurostimulation method for the spinal cord.

Classification of unilateral cervical locked facet with or without lateral mass-facet fractures and a retrospective observational study of 55 cases.

This study describes a morphology-based unilateral cervical facet interlocking classification in an attempt to clarify the injury mechanism, instability, neurological deficits, radiological features, and determine optimum management strategies for these injuries. A total of 55 patients with unilateral cervical locked facet (UCLF) involving C3 to C7 were identified between January 1, 2012 and December 1, 2019. The injuries were classified into three types, and they were further divided into six subtypes using three-dimensional computed tomography. The injury mechanism, clinical features, neurological deficits, and imaging characteristics were analyzed, and the appropriate treatment strategies for UCLF were discussed. UCLFs were divided into the following six subtypes: UCLF without lateral mass-facet fracture (type I) in nine cases, with superior articular process fracture (type II A) in 22, with inferior articular process fracture (type II B) in seven, both superior and inferior articular process fractures (type II C) in four, with lateral mass splitting fracture (type III A) in three, and with lateral mass comminution fractures (type III B) in ten. A total of 22 (40.0%) of the 55 patients presented with radiculopathy, and 23 patients (41.8%) had spinal cord injuries. The subtype analyses showed high rates of radiculopathy in types II A (68.2%) and II C (75.0%), as well as significant spinal cord injury in types I (77.8%) and III (61.5%). Destruction of the facet capsule was observed in all patients, but the injury of disc, ligamentous complex, and vertebra had a significant difference among the types or subtypes. The instability parameters of the axial rotation angle, segmental kyphosis, and sagittal displacement showed significant differences in various types of UCLF. Closed reduction by preoperative and intraoperative general anesthesia traction was achieved in 27 patients (49.1%), and successful rate of closed reduction in type I (22.2%) was significantly lower than that in type II (51.5%) and type III (61.5%). A total of 35 of 55 patients underwent a single anterior fixation and fusion, 10 patients were treated with posterior pedicle and (or) lateral mass fixation, and combined surgery was performed in ten patients. Ten patients (18.2%) with a poor outcome were observed after first surgery. Among them, 3 patients treated with a single anterior surgery had persistent or aggravated radiculopathy and posterior approach surgery with ipsilateral facet resection, foramen enlargement, and pedicle and (or) lateral mass screw fixation was performed immediately, 5 patients treated with a short-segment posterior surgery showed mild late kyphosis deformity, and 2 patients with vertebral malalignment were encountered after anterior single-level fusion during the follow-up. This retrospective study indicated that UCLF is a rotationally unstable cervical spine injury. The classification proposed in this study will contribute to understanding the injury mechanism, radiological characteristics, and neurological deficits in various types of UCLF, which will help the surgeons to evaluate the preoperative closed reduction and guide the selection of surgical approach and fusion segment.

What is the difference in pedicle morphology of the fifth lumbar vertebra between isthmic and degenerative L5-S1 spondylolisthesis? An anatomic study of 328 patients via multi-slice spiral computed tomography.

PURPOSE: The purpose of this study was to investigate and determine whether there are differences in L5 pedicles morphology between isthmic and degenerative L5-S1 spondylolisthesis. METHODS: One hundred and nineteen patients with isthmic spondylolisthesis and 45 patients with degenerative spondylolisthesis at L5-S1 were enrolled in the IS group and DS group, respectively, and 164 lumbar disc herniation patients without spondylolysis or spondylolisthesis were classified into the normal (NL) group. A series of pedicle parameters of the fifth lumbar vertebra, including pedicle length (PL), pedicle width (PW), pedicle screw trajectory length (PSTL), pedicle height (PH), and the pedicle camber angle (PCA), were measured using multi-slice spiral computed tomography (MSCT). The slip distance of the L5 vertebra was measured on radiography, and the percentage of slip was also recorded. RESULTS: The pedicles of the fifth lumbar vertebra were shorter and wider, and the PCA was larger in the IS group compared to the DS group and NL group. On the contrary, the pedicles in the DS group were elongated and thinner, and the PCA was smaller. The pedicle parameters of PL were significantly positively correlated with the percentage of slip in the DS group, but PW and PCA were negatively correlated with the percentage of slip. There was no correlation between the percentage of slip and L5 pedicle parameters in the IS group. CONCLUSIONS: The L5 pedicles morphology in L5-S1 isthmic spondylolisthesis shows abduction, shortness, and width, while that in the degenerative spondylolisthesis shows adduction, lengthening, and thinning compared with the normal populations. The morphology changes may be the result of pedicle stress remodelling in the development of spondylolisthesis, which should be taken into consideration when placing at the insertion of pedicle screws.

Prognostic value of red blood cell distribution width in patients with acute pulmonary embolism: A protocol for systematic review and meta-analysis.

BACKGROUND: Prior reports have suggested that the red blood cell distribution width (RDW) parameter could be measured as a prognostic indicator in pulmonary embolism (PE) patients, thereby helping to guide their care. However, no systematic analyses on this topic have been completed to date, and the exact relationship between RDW and PE remains to be fully clarified. We will therefore conduct a systematic literature review with the goal of defining the correlation between RDW and mortality in acute PE cases. METHODS: The EMBASE, Web of Knowledge, PubMed, ClinicalTrials.gov, and Cochrane Library databases will be searched for all relevant studies published from inception through March 2021 using the following search strategy: ("red blood cell distribution width") AND ("pulmonary embolism"). Two authors will independently identify eligible studies and extract data. The Q and I2 statistics will be used to judge heterogeneity among studies. RESULTS: This study will establish the relative efficacy of RDW as a metric for predicting PE patient mortality. CONCLUSIONS: This study will offer a reliable, evidence-based foundation for the clinical utilization of RDW as a tool for gauging mortality risk in acute PE patients. ETHICS AND DISSEMINATION: As this is a protocol for a systematic review of previously published data, no ethical approval is required. Electronic dissemination of study results will be done through a peer-review publication or represented at a related conference.

LIFU Alleviates Neuropathic Pain by Improving the KCC2 Expression and Inhibiting the CaMKIV-KCC2 Pathway in the L4-L5 Section of the Spinal Cord.

Effective treatment remains lacking for neuropathic pain (NP), a type of intractable pain. Low-intensity focused ultrasound (LIFU), a noninvasive, cutting-edge neuromodulation technique, can effectively enhance inhibition of the central nervous system (CNS) and reduce neuronal excitability. We investigated the effect of LIFU on NP and on the expression of potassium chloride cotransporter 2 (KCC2) in the spinal cords of rats with peripheral nerve injury (PNI) in the lumbar 4-lumbar 5 (L4-L5) section. In this study, rats received PNI surgery on their right lower legs followed by LIFU stimulation of the L4-L5 section of the spinal cord for 4 weeks, starting 3 days after surgery. We used the 50% paw withdraw threshold (PWT50) to evaluate mechanical allodynia. Western blotting (WB) and immunofluorescence (IF) were used to calculate the expression of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), calcium/calmodulin-dependent protein kinase type IV (CaMKIV), phosphorylated cyclic adenosine monophosphate response element-binding protein (p-CREB), and KCC2 in the L4-L5 portion of the spinal cord after the last behavioral tests. We found that PWT50 decreased (P < 0.05) 3 days post-PNI surgery in the LIFU- and LIFU+ groups and increased (P < 0.05) after 4 weeks of LIFU stimulation. The expression of p-CREB and CaMKIV decreased (P < 0.05) and that of KCC2 increased (P < 0.05) after 4 weeks of LIFU stimulation, but that of p-ERK1/2 (P > 0.05) was unaffected. Our study showed that LIFU could effectively alleviate NP behavior in rats with PNI by increasing the expression of KCC2 on spinal dorsal corner neurons. A possible explanation is that LIFU could inhibit the activation of the CaMKIV-KCC2 pathway.

Advances in The Diagnosis and Treatment of Achalasia of The Cardia: a Review.

Idiopathic achalasia is an esophageal motor disorder characterized by the loss of the lower esophageal sphincter ganglion, resulting in impaired lower esophageal relaxation and absence of esophageal peristalsis. Patients commonly present with progressive dysphagia accompanied by reflux, heartburn, retrosternal pain, and severe weight loss. Diagnosis is primarily based on the patient's chief complaints, barium esophagography, and the most recent high-resolution manometry. Endoscopic assessment and endoscopic ultrasonography also have significant value with regard to the exclusion of esophageal anatomical lesions, neoplastic diseases, and pseudoachalasia. However, as most patients with achalasia demonstrate a gradual onset, early diagnosis is difficult. Currently, treatment of idiopathic achalasia, including pneumatic dilation, stent placement, and surgical myotomy, is aimed at reducing lower esophageal sphincter pressure and relieving the symptoms of dysphagia. Peroral endoscopic myotomy has gradually become the mainstream treatment because it causes less trauma and has a rapid recovery rate. This article reviews the main methods of diagnosis and treatment of achalasia, with an emphasis on the potential of peroral endoscopic myotomy and the advancements of immunotherapy for achalasia.

Stent placement to prevent strictures after esophageal endoscopic submucosal dissection: a systematic review and meta-analysis.

Endoscopic submucosal dissection (ESD) is an important method for the treatment of early esophageal cancer. However, post-procedure stenosis is one of the most common long-term complications. This meta-analysis aimed to investigate whether stent placement is effective in the stenosis prevention, and which type of stent would be more effective. A systematic and electronic search of clinical trials and observational studies conducted before March 2020 on the efficacy of stent placement in preventing esophageal stricture after ESD was performed. Search terms included "ESD," "esophageal stenosis," "esophageal stricture," and "stents." We conducted a bias risk assessment of the eligible reports and a meta-analysis of the data using Revman 5.3 software. We included two randomized controlled trials (RCTs) and a prospective cohort study involving 163 patients with esophageal mucosal defects encompassing at least three-quarters of the esophagus circumference after ESD. The meta-analysis results showed that post-ESD stenosis rates (RR, 0.37; 95% CI, 0.22-0.64; P = 0.0003) and the number of endoscopic balloon dilations (EBDs) (MD, -1.74; 95% CI, -2.46 to -1.01; P < 0.00001) were reduced in the pooled analysis of three studies, indicating that stent placement was effective for stenosis prevention, especially a polyglycolic acid (PGA) sheet combined with stent placement can prevent stenosis (RR, 0.41; 95% CI, 0.23-0.74; P = 0.003) and reduce the number of EBDs (MD, -1.65; 95% CI, -2.40 to -0.90; P < 0.0001) significantly. Stent placement can reduce the rate of esophageal stenosis after ESD, especially when stents are covered with PGA sheets. However, more high-quality, low-bias RCTs with a sufficient sample size are needed to demonstrate its effectiveness.