Application research on the diagnosis of classic trigeminal neuralgia based on VB-Net technology and radiomics.

BACKGROUND: This study aims to utilize the deep learning method of VB-Net to locate and segment the trigeminal nerve, and employ radiomics methods to distinguish between CTN patients and healthy individuals. METHODS: A total of 165 CTN patients and 175 healthy controls, matched for gender and age, were recruited. All subjects underwent magnetic resonance scans. VB-Net was used to locate and segment the bilateral trigeminal nerve of all subjects, followed by the application of radiomics methods for feature extraction, dimensionality reduction, feature selection, model construction, and model evaluation. RESULTS: On the test set for trigeminal nerve segmentation, our segmentation parameters are as follows: the mean Dice Similarity Coefficient (mDCS) is 0.74, the Average Symmetric Surface Distance (ASSD) is 0.64 mm, and the Hausdorff Distance (HD) is 3.34 mm, which are within the acceptable range. Analysis of CTN patients and healthy controls identified 12 features with larger weights, and there was a statistically significant difference in Rad_score between the two groups (p < 0.05). The Area Under the Curve (AUC) values for the three models (Gradient Boosting Decision Tree, Gaussian Process, and Random Forest) are 0.90, 0.87, and 0.86, respectively. After testing with DeLong and McNemar methods, these three models all exhibit good performance in distinguishing CTN from normal individuals. CONCLUSIONS: Radiomics can aid in the clinical diagnosis of CTN, and it is a more objective approach. It serves as a reliable neurobiological indicator for the clinical diagnosis of CTN and the assessment of changes in the trigeminal nerve in patients with CTN.

A prediction model of dementia conversion for mild cognitive impairment by combining plasma pTau181 and structural imaging features.

AIMS: The early stages of Alzheimer's disease (AD) are no longer insurmountable. Therefore, identifying at-risk individuals is of great importance for precise treatment. We developed a model to predict cognitive deterioration in patients with mild cognitive impairment (MCI). METHODS: Based on the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, we constructed models in a derivation cohort of 761 participants with MCI (138 of whom developed dementia at the 36th month) and verified them in a validation cohort of 353 cognitively normal controls (54 developed MCI and 19 developed dementia at the 36th month). In addition, 1303 participants with available AD cerebrospinal fluid core biomarkers were selected to clarify the ability of the model to predict AD core features. We assessed 32 parameters as candidate predictors, including clinical information, blood biomarkers, and structural imaging features, and used multivariable logistic regression analysis to develop our prediction model. RESULTS: Six independent variables of MCI deterioration were identified: apolipoprotein E ε4 allele status, lower Mini-Mental State Examination scores, higher levels of plasma pTau181, smaller volumes of the left hippocampus and right amygdala, and a thinner right inferior temporal cortex. We established an easy-to-use risk heat map and risk score based on these risk factors. The area under the curve (AUC) for both internal and external validations was close to 0.850. Furthermore, the AUC was above 0.800 in identifying participants with high brain amyloid-ß loads. Calibration plots demonstrated good agreement between the predicted probability and actual observations in the internal and external validations. CONCLUSION: We developed and validated an accurate prediction model for dementia conversion in patients with MCI. Simultaneously, the model predicts AD-specific pathological changes. We hope that this model will contribute to more precise clinical treatment and better healthcare resource allocation.

Post-transplant lymphoproliferative disorders after allogeneic hematopoietic stem cell transplantation: a case report, meta-analysis, and systematic review.

BACKGROUND: Post-transplant lymphoproliferative disorders (PTLD) are rare but severe complications that occur after solid organ or allogeneic hematopoietic stem cell transplantations (allo-HSCT), with rapid progression and high mortality. Primary central nervous system (CNS)-PTLD are rarely recognized histo-pathologically. In addition, the diagnostic value of the Epstein-Barr virus (EBV) DNA copies in CNS-PTLD remains poorly understood. OBJECTIVES: We herein report a case of monomorphic EBV-associated CNS-PTLD (diffuse large B-cell lymphoma, DLBCL) after allo-HSCT and perform a meta-analysis to assess the efficacy of PTLD treatment strategies in recent years. METHODS: We present the case report covering clinical manifestations, diagnosis, treatment, and outcomes of a patient with primary CNS-PTLD. Additionally, we include a systematic review and meta-analysis of the clinical characteristics of 431 patients with PTLD after allo-HSCT. We evaluate the main treatment options and outcomes of PTLD management, including rituximab, chemotherapies, and autologous or human leukocyte antigen (HLA)-matched EBV-specific cytotoxic T lymphocyte infusion (EBV-CTLs)/donor lymphocyte infusion (DLI). RESULTS: The meta-analysis revealed an overall response rate of 69.0% for rituximab alone (95% CI: 0.47-0.84), 45.0% for rituximab plus chemotherapies (95% CI: 0.15-0.80), and 91.0% for rituximab plus EBV-CTLs/DLI (95% CI: 0.83-0.96). The complete response (CR) rate after treatments for PTLD was 67.0% (95% CI: 0.56-0.77). Moreover, the 6-month and 1-year overall survival (OS) rate was 64.0% (95% CI: 0.31-0.87) and 49.0% (95% CI: 0.31-0.68), respectively. CONCLUSIONS: This case highlighted the urgent need for effective, low-toxic treatment regimens for CNS-PTLD. Our meta-analysis suggested that rituximab combined with EBV-CTLs/DLI could be a favorable strategy for the management of PTLD after allo-HSCT.

Vision Improvement in Keratoconus Patients Trained with Perceptual Learning: A Randomized Controlled Trial.

BACKGROUND: Keratoconus (KC) is a corneal ectasia disease in which the vision of some patients cannot achieve satisfaction by spectacle corrections. However, not everyone can embrace contact lenses to achieve better vision. Perceptual learning (PL) is a potential treatment for vision improvement in such patients. PURPOSE: To investigate the effectiveness and maintenance of PL on vision improvement in KC patients corrected with spectacles. DESIGN: Randomized, double-blind clinical trial. PARTICIPANTS: Thirty-five non-progressive KC patients aged 9 years or older with unsatisfied spectacle-corrected vision were enrolled. METHODS: Non-progressive KC patients with best spectacle-corrected distance visual acuity (CDVA) of 0 to 1.0 logMAR (Snellen equivalent range 20/20 to 20/200) and contact lenses intolerant were enrolled. Eligible subjects were randomized into PL and control groups to receive PL and placebo training for 3 months, respectively. Spectacle-corrected visual acuity, contrast sensitivity function (CSF), stereoacuity, and visual functioning and quality of life questionnaires were measured at baseline, 3 months, and 6 months of follow-up. Statistics were analyzed following the intention-to-treat (ITT) principle. RESULTS: After 3 months of training, the CDVA of patients in the PL group improved as compared to the placebo group (0.17 ± 0.15 logMAR vs. 0.02 ± 0.06 logMAR; P = 0.0006). Eight out of seventeen (47.06 %) patients in the PL group reached CDVA improvement ≥ 2 lines (P=0.0010). This improvement persisted for at least 6 months (from baseline) as compared to the placebo group (0.17 ± 0.17 logMAR vs. 0.01 ± 0.07 logMAR; P = 0.0011). The increase of CSF in the PL group mainly was found for moderate spatial frequency (0.11 ± 0.17 log units at 3 cpd; 0.12 ± 0.19 log units at 6 cpd). Linear regression indicated that patients with worse initial CDVA achieved better gains in CDVA after PL (P = 0.009). No side effects were observed and no subjects quit because of training difficulties. CONCLUSION: Three-month perceptual learning improved vision in KC patients and the improvement maintained after 3 months of treatment cessation. The results indicate that perceptual learning may be a promising therapy for KC patients with unsatisfied spectacle-corrected visual acuity.

Efficacy and safety of Tongxin formula in the treatment of coronary microvascular disease: A randomized, double-blind, placebo-controlled clinical trial study.

Objective: The objective of this study was to evaluate the efficacy and safety of Tongxin Formula in the treatment of coronary microvascular disease. Methods: We conducted a randomized, double-blind, placebo-controlled study simultaneously in two hospitals, consisting of 80 participants. Using a random number table, we assigned patients to the treatment and control groups. Patients in both groups received conventional Western medicine for coronary microvascular disease. In addition, those in the treatment group received Tongxin formula granules, while those in the control group received a placebo. The treatment course for both groups was three months, and the follow-up duration was six months. The primary efficacy indicators were coronary blood flow reserve and cardiovascular adverse events; the secondary efficacy indicators were the traditional Chinese medicine (TCM) syndrome score, the angina symptom score, the Seattle Angina Questionnaire (SAQ) score, left ventricular function, and adverse reactions. Results: After treatment, patients in the treatment group showed significantly higher variation in the coronary flow reserve (CFR) levels (CFR >2) and improvement of diastolic function (peak filling rate, or PFR >2.5) than those in the control group (P < 0.05). After 6 months of follow-up, the incidence of cardiovascular events in the treatment group was significantly lower than that in the control group (P < 0.05). After 3 months of treatment and 6 months of follow-up, the total effective rates of TCM symptoms and angina symptoms, as well as the total SAQ standard scores, in the treatment group were higher than those in the control group (P < 0.05). There were no serious adverse reactions in either group before or after treatment, and there was no significant change (P > 0.05). Conclusion: We found that Tongxin Formula combined with conventional Western medicine can significantly improved the level of coronary blood flow reserve, reduced the occurrence of cardiovascular adverse events, improved the clinical symptoms of patients, and enhanced the quality of life of patients with coronary microvascular disease with favorable safety.

The effects of complement-independent, autoantibody-induced apoptosis of platelets in immune thrombocytopenia (ITP).

Autoantibodies that cause platelet apoptosis may play a role in the development of immune thrombocytopenia (ITP), specifically antibodies that target GPIIbIIIa and GPIbα. Our research aims to compare the impact of the antigen specificity of antiplatelet antibodies on normal platelets under conditions that do not rely on complement. Using a modified monoclonal antibody-specific immobilization of platelet antigen (MAIPA) assay, we detected the levels of autoantibodies against specific platelet membrane glycoproteins (GPIIb/IIIa, GPIb/IX) in the plasma of 36 patients diagnosed with chronic ITP. IgG was isolated and purified using a protein A agarose affinity chromatography column, and their concentrations were measured using spectrophotometry. We obtained normal platelets and treated them with the purified IgG anti-GPIIb/IIIa and/or anti-GPIb/IX antibodies, as well as an IgG-free buffer and healthy control IgG. Flow cytometry was used to analyze markers of apoptosis, including phosphatidylserine (PS) exposure, mitochondrial inner membrane potential (ΔΨm), and platelet particle formation. Our results indicate that ITP patients with GPIb/IX-specific autoantibodies can induce platelet apoptosis and platelet particle formation through complement-independent pathways, which are not associated with platelet activation, while GPIIb/IIIa-specific autoantibodies did not have this effect. This suggests that specific autoantibodies may serve as a valuable predictive tool to identify patients who could potentially benefit from complement-inhibiting therapy in the future.

Corrigendum: Characterizing the neutrophilic inflammation in chronic rhinosinusitis with nasal polyps.

[This corrects the article DOI: 10.3389/fcell.2021.793073.].

The role of metabolic memory in diabetic kidney disease: identification of key genes and therapeutic targets.

Diabetic kidney disease (DKD) is characterized by complex pathogenesis and poor prognosis; therefore, an exploration of novel etiological factors may be beneficial. Despite glycemic control, the persistence of transient hyperglycemia still induces vascular complications due to metabolic memory. However, its contribution to DKD remains unclear. Using single-cell RNA sequencing data from the Gene Expression Omnibus (GEO) database, we clustered 12 cell types and employed enrichment analysis and a cell‒cell communication network. Fibrosis, a characteristic of DKD, was found to be associated with metabolic memory. To further identify genes related to metabolic memory and fibrosis in DKD, we combined the above datasets from humans with a rat renal fibrosis model and mouse models of metabolic memory. After overlapping, NDRG1, NR4A1, KCNC4 and ZFP36 were selected. Pharmacology analysis and molecular docking revealed that pioglitazone and resveratrol were possible agents affecting these hub genes. Based on the ex vivo results, NDRG1 was selected for further study. Knockdown of NDRG1 reduced TGF-ß expression in human kidney-2 cells (HK-2 cells). Compared to that in patients who had diabetes for more than 10 years but not DKD, NDRG1 expression in blood samples was upregulated in DKD patients. In summary, NDRG1 is a key gene involved in regulating fibrosis in DKD from a metabolic memory perspective. Bioinformatics analysis combined with experimental validation provided reliable evidence for identifying metabolic memory in DKD patients.

Specnuezhenide ameliorates hepatic fibrosis via regulating SIRT6-Mediated inflammatory signaling cascades.

ETHNOPHARMACOLOGICAL RELEVANCE: Ligustrum lucidum W.T. Aiton is a traditional Chinese medicine that has long been used with high hepatoprotective therapeutic and condition value. Specnuezhenide (SP), the standard prominent secoiridoid compound of Fructus Ligustri Lucidi may ameliorate hepatic inflammation in chronic liver diseases. AIM OF THE STUDY: Regulating inflammation through SIRT6-P2X7R axis has caused the emergence of novel molecular mechanism strategies for reversing hepatic fibrosis. This study focused on the mechanism of SP in modulating the liver inflammatory microenvironment in hepatic fibrosis. MATERIALS AND METHODS: C57BL/6 mice with hepatic fibrosis were stimulated with thioacetamide (TAA) prior to administration of SP. Hepatic stellate cells (HSCs) or normal mouse primary hepatocytes were exposed to transforming growth factor-ß (TGF-ß) treatment. Meanwhile, normal mouse bone marrow-derived macrophages (BMDMs) were treated with lipopolysaccharide/adenosine triphosphate (LPS/ATP), aiming to obtain the conditioned medium. HSCs and hepatocytes were transfected with SIRT6 knockdown vector (siRNA-SIRT6) to estimate the impact of SP on the SIRT6-P2X7R/NLRP3 signaling pathway. RESULTS: SP suppressed the HSCs extracellular matrix (ECM) deposition as well as pro-inflammatory cytokine levels induced by the medium of BMDMs or TGF-ß. In addition, SP also significantly up-regulated SIRT6, inhibited P2X7R-NLRP3 inflammasome in HSCs and hepatocytes, and functioned as MDL-800 (a SIRT6 agonist). SP reduced the hepatocytes pyroptosis and further prevented the occurrence of inflammatory response in the liver. SP could inhibit the activation of BMDMs and impede IL-1ß and IL-18 from entering extracellular regions. Moreover, deficiency of SIRT6 in HSCs or hepatocytes reduced SP's regulation of P2X7R suppression. For TAA-treated mice, SP mitigated histopathological changes, ECM accumulation, EMT process, and NETs formation in hepatic fibrosis. CONCLUSIONS: Therefore, SP decreased inflammatory response via SIRT6-P2X7R/NLRP3 pathway and suppressed fibrillogenesis. These findings supported SP as the novel candidate to treat hepatic fibrosis.

The impact of a lung-protective ventilation mode using transpulmonary driving pressure titrated positive end-expiratory pressure on the prognosis of patients with acute respiratory distress syndrome.

OBJECTIVE: This study aimed to assess the impact of a lung-protective ventilation strategy utilizing transpulmonary driving pressure titrated positive end-expiratory pressure (PEEP) on the prognosis [mechanical ventilation duration, hospital stay, 28-day mortality rate and incidence of ventilator-associated pneumonia (VAP), survival outcome] of patients with Acute Respiratory Distress Syndrome (ARDS). METHODS: A total of 105 ARDS patients were randomly assigned to either the control group (n = 51) or the study group (n = 53). The control group received PEEP titration based on tidal volume [A tidal volume of 6 mL/kg, flow rate of 30-60 L/min, frequency of 16-20 breaths/min, constant flow rate, inspiratory-to-expiratory ratio of 1:1 to 1:1.5, and a plateau pressure ≤ 30-35 cmH2O. PEEP was adjusted to maintain oxygen saturation (SaO2) at or above 90%, taking into account blood pressure], while the study group received PEEP titration based on transpulmonary driving pressure (Esophageal pressure was measured as a surrogate for pleural pressure using an esophageal pressure measurement catheter connected to the ventilator. Tidal volume and PEEP were adjusted based on the observed end-inspiratory and end-expiratory transpulmonary pressures, aiming to maintain a transpulmonary driving pressure below 15 cmH2O during mechanical ventilation. Adjustments were made 2-4 times per day). Statistical analysis and comparison were conducted on lung function indicators [oxygenation index (OI), arterial oxygen tension (PaO2), arterial carbon dioxide tension (PaCO2)] as well as other measures such as heart rate, mean arterial pressure, and central venous pressure in two groups of patients after 48 h of mechanical ventilation. The 28-day mortality rate, duration of mechanical ventilation, length of hospital stay, and ventilator-associated pneumonia (VAP) incidence were compared between the two groups. A 60-day follow-up was performed to record the survival status of the patients. RESULTS: In the control group, the mean age was (55.55 ± 10.51) years, with 33 females and 18 males. The pre-ICU hospital stay was (32.56 ± 9.89) hours. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was (19.08 ± 4.67), and the mean Murray Acute Lung Injury score was (4.31 ± 0.94). In the study group, the mean age was (57.33 ± 12.21) years, with 29 females and 25 males. The pre-ICU hospital stay was (33.42 ± 10.75) hours. The mean APACHE II score was (20.23 ± 5.00), and the mean Murray Acute Lung Injury score was (4.45 ± 0.88). They presented a homogeneous profile (all P > 0.05). Following intervention, significant improvements were observed in PaO2 and OI compared to pre-intervention values. The study group exhibited significantly higher PaO2 and OI compared to the control group, with statistically significant differences (all P < 0.05). After intervention, the study group exhibited a significant increase in PaCO2 (43.69 ± 6.71 mmHg) compared to pre-intervention levels (34.19 ± 5.39 mmHg). The study group's PaCO2 was higher than the control group (42.15 ± 7.25 mmHg), but the difference was not statistically significant (P > 0.05). There were no significant differences in hemodynamic indicators between the two groups post-intervention (all P > 0.05). The study group demonstrated significantly shorter mechanical ventilation duration and hospital stay, while 28-day mortality rate and incidence of ventilator-associated pneumonia (VAP) showed no significant differences. Kaplan-Meier survival analysis revealed a significantly better survival outcome in the study group at the 60-day follow-up (HR = 0.565, 95% CI: 0.320-0.999). CONCLUSION: Lung-protective mechanical ventilation using transpulmonary driving pressure titrated PEEP effectively improves lung function, reduces mechanical ventilation duration and hospital stay, and enhances survival outcomes in patients with ARDS. However, further study is needed to facilitate the wider adoption of this approach.

Clinical features and genetic analysis of 5 cases of infantile-type glycogen storage disease type II: Case reports.

OBJECTIVE: Clinical and genetic mutation analysis was performed on 5 infantile glycogen storage disease type II children in Chinese mainland. METHODS: Clinical data of 5 children with infantile-type glycogen storage disease type II due to the acidic α-glucosidase (GAA) gene variants diagnosed and treated at Hebei Provincial Children's Hospital from January 2018 to April 2020 were retrospectively analyzed. RESULTS: Among the 5 cases, 1 was female and 4 were male, and the age at first diagnosis was from 2 months to 7 months. The first symptoms of all 5 cases showed progressive muscle weakness, hypotonia, and motor developmental backwardness, and all of them had abnormally elevated creatine kinase, and the echocardiograms suggested different degrees of myocardial hypertrophy, with ejection fractions ranging from 44% to 67%. Analysis of GAA gene variations: all 5 cases were compound heterozygous, and a total of 12 variant loci were detected, of which c.2024_2026delACA, c.2853G > A, c.1124G > T, c.574G > A, c.2509C > T, and c.2013G > A were new mutations that had not been reported. FOLLOWUP: All 5 children died before 1 year of age, and the age of death ranged from 7 months to 11.5 months, with a mean survival time of 9.8 months. CONCLUSION: Peripheral blood GAA gene testing and alpha-glucosidase enzyme activity testing is an effective method for diagnosing this disease.

Tropical cyclone FANTALA's three turnbacks in the northeast of Madagascar Island.

The unique Tropical cyclone (TC) Fantala appeared in the central Indian Ocean (12.4°S, 73.5°E) at 00Z on April 11 in 2016 and moved northwestward along the northeast of Madagascar at 18 Z on April 15. Then, two incomprehensible turnbacks formed a unique TC track. The dynamic mechanisms of the three turnbacks were first studied based on remote sensing and multisource reanalysis data. The results reveal that the wind field with upper divergence and lower convergence promotes the development of Fantala. The anticyclone high pressure on the middle level atmosphere is an important factor for TC turnbacks. On 15 April, the TC made the first turnback to turn northwest due to the southward anticyclone weakened to moving northwest. On 18 April, the TC made the second turnback along the anticyclone edge due to the northern high-pressure and southern low-pressure trough. On 22 April, the TC made the third turnback because the anticyclonic high press center broke into two small independent anticyclonic centers in the southwest and northeast, which created a barrier band and pushed the northern TC to move to the northwest. Meanwhile, the vertical wind shear (VWS) also provides favorable conditions for TC turnbacks. On April 18, the middle atmosphere of the TC was affected by strong easterly shear and weak southerly shear, and the second turnback was completed. On April 22, the middle level environment was affected by strong westerly shear and weak north shear, and the third turnback was completed. Additionally, heat transport from the ocean to the atmosphere provides favorable conditions for TC development. On April 18, The maximum mean latent heat flux over northeastern Madagascar was 112.94 W/m2, Tropical Cyclone Heat Potential was 39.05 kJ/cm2, and the maximum wind speed at the center of the TC was 155 kts. On April 22, The heat transfer from the equator increased by 18.08 W/m2 compared with the latent heat on 21 April, the Tropical Cyclone Heat Potential was 33.30 kJ/cm2, the maximum wind speed in the TC center was 90 kts, the high PV centerspread down from 850 mb to 900 mb. This study deepens the understanding of track forecasting during the development of a TC.

An injectable and degradable heterogeneous microgel assembly capable of forming a "micro-nest group" for cell condensation and cartilage regeneration.

Cell condensation, linking the migration and chondrogenic differentiation of MSCs, plays a crucial role in cartilage development. Current cartilage repair strategies are inadequately concerned with this process, leading to a suboptimal quality of regenerated cartilage. Inspired by the "nest flocks" structure of Social Weavers, a degradable heterogeneous microgel assembly (F/S-MA) is developed, which can release SDF-1, to form a "micro-nest group" structure and bond with HAV peptides to promote cell recruitment, condensation and chondrogenic differentiation. First, slow-degrading microgels (S-microgels) grafted with HAV peptides and fast-degrading microgels (F-microgels) loaded with SDF-1 are fabricated by an amidation reaction and Schiff base reaction, respectively. They employ sulfhydryl-modified gelatin as assembling agents to form F/S-MA through a thiol-ene reaction, exhibiting injectability, tissue adhesion, and microporosity. F-microgels undergo rapid degradation, leading to the release of SDF-1 and the formation of a "micro-nest group" in F/S-MA. Consequently, F/S-MA exhibits cell recruitment ability, meanwhile facilitating BMSC condensation through the synergistic effects of the "micro-nest group" and HAV peptides. In vitro experiments prove that F/S-MA enhances the expression of cell-condensation-related markers, ultimately upregulating the secretion of cartilage matrix. Animal experiments show that F/S-MA optimizes the quality of regenerated cartilage by improving cell recruitment and condensation. F/S-MA enhances cell condensation through structural and component design, which will provide new insights for cartilage regeneration.

Balance chiropractic therapy for cervical spondylotic radiculopathy: A randomized controlled trial.

Objective: To assess the clinical effectiveness of the balance chiropractic therapy (BCT) compared with traction therapy (TT) for patients with cervical spondylotic radiculopathy. Methods: Subjects were enrolled from four hospitals. Eligible patients will be randomized to one of the two arms: the treatment group and the control group. In the treatment group, patients received the BCT for 20 days, while patients in the control group received TT. Patients visited the physician at 1- and 3-month follow-up. The primary outcome was pain severity measured with a Visual Analog Scale (VAS). Secondary outcomes included cervical curvature measured using the Borden method, a composite of functional status measured by the Neck Disability Index (NDI), patient health status (evaluated by the SF-36 health survey) and adverse events (AEs) as reported in the trial. Results: Of the 240 randomly assigned patients, 120 participants were assigned to the BCT and 120 to the TT. 231 (96.3 %) provided follow-up data at 1 and 3 months. There were no significant differences in baseline data between the two groups (P > 0.05), indicating good comparability. According to the results, after BCT and TT treatment, the pain VAS score, cervical curvature, NDI scores and SF-36 scores of two groups was significantly improved (P < 0.05). Furthermore, at 20 days of treatment and 1 and 3 months of follow-up, the participants in the BCT group showed superior treatment outcomes on both primary and secondary measures. Conclusion: The BCT may be a novel strategy for the treatment of the cervical spondylotic radiculopathy. Trial registration: Clinical Trials.gov Identifier: NCT02705131. Registered on March 10, 2016, https://clinicaltrials.gov/study/NCT02705131?cond=NCT02705131&rank=1&tab=table.

Liquiritigenin, an Active Ingredient of Liquorice, Alleviates Acute Kidney Injury by VKORC1-Mediated Ferroptosis Inhibition.

Acute kidney injury (AKI) is a major public health problem worldwide that still lacks effective treatments. Recent studies have suggested that ferroptosis is a key mediator of AKI due to its activation of lipid peroxidation. Therefore, we hypothesized that antiferroptosis agents might be a novel potential therapeutic strategy for AKI. Herein, we demonstrated that liquiritigenin (LG), an active ingredient of liquorice, improves renal function by inhibiting vitamin K epoxide reductase complex subunit 1 (VKORC1)-mediated ferroptosis, both in vivo and in vitro. In a folic acid-induced murine AKI model, after a single pre-treatment intravenous injection, LG markedly alleviated the loss of renal function through suppressing ferroptosis induced by iron accumulation. LG prevented mitochondrial morphological changes and upregulated glutathione and glutathione peroxidase 4 levels, while downregulating malonaldehyde and divalent iron levels. An in vitro RNA-sequence analysis suggested that the protective role of LG may involve upregulation of VKORC1. Moreover, knockdown of VKORC1 diminished the renal protective and antiferroptosis roles of LG. Collectively, our findings demonstrated that LG protected against AKI by inhibiting VKORC1-mediated ferroptosis. This suggests that inhibiting ferroptosis might be a novel therapeutic approach in the future.

Cytotoxicity evaluation of organophosphorus flame retardants using electrochemical biosensors and elucidation of associated toxic mechanisms.

In recent years, organophosphorus flame retardants (OPFRs) have been widely used as substitutes for brominated flame retardants with excellent properties, and their initial toxicological effects on the water ecosystem and human health have gradually emerged. However, to date, research on the cytotoxicity and health risks of OPFRs is still limited. Therefore, this study aims to systematically explore the cytotoxic effects and toxic mechanisms of OPFRs on cells. Human liver cancer (HepG2) cells were adopted as an ideal model for toxicity evaluation due to their rapid growth and metabolism. This study proposes a sensitive electrochemical cell-based sensor constructed on a graphitized multi-walled carbon nanotube/ionic liquid/gold nanoparticle-modified electrode. The sensor was used to detect the cytotoxicity of tri(2-butylxyethyl) phosphate (TBEP), tributyl phosphate (TnBP), triphenyl phosphate (TPhP), tri(1,3-dichloro-2-propyl) phosphate (TDCIPP), tri(2-chloropropyl) phosphate (TCPP) and tri(2-chloroethyl) phosphate (TCEP) in the liquid medium, providing insight into their toxicity in water environments. The half-maximal inhibitory concentration (IC50) of TBEP, TnBP, TPhP, TDCIPP, TCPP and TCEP on HepG2 cells were 179.4, 194.9, 219.8, 339.4, 511.8 and 859.0 µM, respectively. Additionally, the cytotoxic mechanism of six OPFRs was discussed from the perspective of oxidative stress and apoptosis, and four indexes were correlated with toxicity. Furthermore, transcriptome sequencing was conducted, followed by a thorough analysis of the obtained sequencing results. This analysis demonstrated a significant enrichment of the p53 and PPAR pathways, both of which are closely associated with oxidative stress and apoptosis. This study presents a simplified and efficient technique for conducting in vitro toxicity studies on organophosphorus flame retardants in a water environment. Moreover, it establishes a scientific foundation for further investigation into the mechanisms of cytotoxicity associated with these compounds.

The association between urinary sodium and the risk of dementia: Evidence from a population-based cohort study.

BACKGROUND: Sodium intake reduction is crucial for cardiovascular health, however, its lasting impact on dementia remains unclear. METHODS: We included 458,577 UK Biobank participants without dementia at baseline. We estimated 24-h urinary sodium (E24hUNa) using spot urinary parameters and obtained the incidence of all-cause dementia, Alzheimer's disease, and vascular dementia from multiple sources. RESULTS: The mean E24hUNa was 3.0 g (1st-99th percentile: 1.5 g-5.1 g). Over a mean follow-up of 13.6 years, 7886 (1.7 %) participants developed all-cause dementia, including 3763 (0.8 %) Alzheimer's disease and 1851 (0.4 %) vascular dementia. In the restricted cubic spline model, we identify a potential cutoff of 3.13 g for E24hUNa, below which each 1 g decrease in E24hUNa was associated with 21 % (95 % confidence interval [CI] 1.11-1.34) higher all-cause dementia risk and 35 % (95 % CI 1.11-1.63) higher vascular dementia risk (P-value <0.001 for non-linearity). The hazard ratios were 1.15 (95 % CI, 1.07-1.24) for all-cause dementia and 1.21 (95 % CI 1.04-1.40) for vascular dementia among individuals with E24hUNa below 3.13 g compared to those with E24hUNa higher than 3.13 g. LIMITATIONS: One of the major limitations is the estimation of 24-h urinary sodium with spot urine samples. CONCLUSIONS: An E24hUNa level below 3.13 g, equivalent to 3.37 g daily sodium intake, is associated with increased risks of all-cause and vascular dementia. This exploratory study suggests a potential lower limit below which the risk of dementia increases with a lower sodium level. Future studies are necessary to validate our findings.

Nano-vibration exciter: Hypoxia-inducible factor 1 signaling pathway-mediated extracellular vesicles as bioactive glass substitutes for bone regeneration.

Bioactive glasses (BG) play a vital role in angiogenesis and osteogenesis through releasing functional ions. However, the rapid ion release in the early stage will cause excessive accumulation of metal ions, which in turn leads to obvious cytotoxicity, long-term inflammation, and bone repair failure. Inspired by the vibration exciter, small extracellular vesicles (sEVs) obtained by treating mesenchymal stem cells with copper-doped bioactive glass (CuBG-sEVs), is prepared as a nano-vibration exciter. The nano-vibration exciter can convert the ion signals of CuBG into biochemical factor signals through hypoxia-inducible factor 1 (HIF-1) signaling pathway and its activated autophagy, so as to better exert the osteogenic activity of BG. The results showed that CuBG extracts could significantly improve the enrichment of key miRNAs and increase the yield of CuBG-sEVs by activating HIF-1 signaling pathway and its activated autophagy. Cell experiments showed that CuBG-sEVs are favor to cell recruitment, vascularization and osteogenesis as the enrichment of key miRNAs. The animal experiments results showed that CuBG-sEVs stimulated angiogenesis mediated by CD31 and promoted bone regeneration by activating signaling pathways related to osteogenesis. These findings underscored the significant potential of sEVs as alternative strategies to better roles of BG.