Search

BackgroundFall risk prediction is crucial for preventing falls in patients with cerebral small vessel disease (CSVD), especially for those with gait disturbances. However, research in this area is limited, particularly in the early, asymptomatic phase. Wearable sensors offer an objective method for gait assessment. This study integrating wearable sensors and machine learning, aimed to predict fall risk in patients with covert CSVD.MethodsWe employed soft robotic exoskeleton (SRE) to acquire gait characteristics and surface electromyography (sEMG) system to collect sEMG features, constructing three datasets: gait-only, sEMG-only, and their combination. Using Support Vector Machine (SVM), Random Forest (RF), Gradient Boosting Decision Tree (GBDT), and Neural Network (NN) algorithms, we developed twelve predictive models. Furthermore, we integrated the selected baseline data and imaging markers with the three original datasets to create three new integrated datasets, and constructed another twelve optimized predictive models using the same methods. A total of 117 participants were enrolled in the study.ResultsOf the 28 features, ANOVA identified 10 significant indicators. The Gait & sEMG integration dataset, analyzed using the SVM algorithm, demonstrated superior performance compared to other models. This model exhibited an area under the curve (AUC) of 0.986, along with a sensitivity of 0.909 and a specificity of0.923, reflecting its robust discriminatory capability.ConclusionThis study highlights the essential role of gait characteristics, electromyographic features, baseline data, and imaging markers in predicting fall risk. It also successfully developed an SVM-based model integrating these features. This model offers a valuable tool for early detection of fall risk in CSVD patients, potentially enhancing clinical decision-making and prognosis.

Abstract Posttraumatic osteoarthritis (PTOA) is closely related to the inflammatory response caused by mechanical injury and leads to joint degeneration. Herein, we aimed to evaluate the role and underlying mechanism of NUMB in PTOA progression. Anterior cruciate ligament transection (ACLT)-induced rats and interleukin (IL)-1β-treated chondrocytes were used as in vivo and in vitro models of PTOA, respectively. The NUMB overexpression plasmid (pcDNA-NUMB) was administered by intra-articular injection to PTOA model rats, and safranin O-fast green staining, the Osteoarthritis Research Society International (OARSI) scoring system, and HE staining were used to evaluate the severity of cartilage damage. The secretion of inflammatory cytokines (TNF-α, IL-1β, and IL-6) and chondrocyte-specific markers (MMP13 and COL2A1) was detected via ELISA. Cell viability and apoptosis were evaluated by MTT and TUNEL assays. NUMB was expressed at lower levels in ACLT-induced PTOA rats and in IL-1β-treated chondrocytes than in control rats and cells. NUMB overexpression enhanced cell viability and reduced cell apoptosis, inflammation and cartilage degradation in chondrocytes stimulated by IL-1β. NUMB bound to BTRC to promote p-IκBα expression, resulting in NF-κB pathway inactivation. BTRC overexpression reversed the promoting effect of NUMB overexpression on cell viability and the inhibitory effects of NUMB overexpression on apoptosis, inflammation and cartilage degradation in IL-1β-induced chondrocytes. In addition, overexpression of NUMB alleviated articular cartilage damage by repressing inflammation and cartilage degradation in ACLT-induced PTOA rats. Our data indicated that NUMB regulated PTOA progression through the BTRC/NF-κB pathway, which may be a viable therapeutic target in PTOA.

Context AMD3100, a CXCR4 antagonist, has beneficial effects immaculate in the treatment of acute lung injury (ALI). Objective ALI is a severe inflammatory condition associated with poor prognosis and limited treatment options. AMD3100, has therapeutic effects that reduce ALI. Our study explored the regulatory mechanisms of AMD3100 in alleviating the injury of lipopolysaccharide (LPS)-induced ALI in mice. Materials and Methods Male ICR mice were randomly divided into control, LPS-treated, AMD3100-treated, and LPS + AMD3100-treatment groups. The histological changes of lung tissues from different groups were evaluated using hematoxylin and eosin staining. Lung injury was measured by ELISA and lung wet/dry ratio. Moreover, lung tissues from the four groups were subjected to transcriptome sequencing followed by differential expression, functional enrichment, protein-protein interaction (PPI) networks, and transcription factor analyses. The validation of mRNAs and protein levels were conducted with qRT-PCR and ELISA. Results Hematoxylin and eosin staining combined with the concentration of IL-1 and IL1-β and lung wet/dry ratios revealed that AMD3100 reduced the level of LPS-induced lung injury. Analysis of the transcriptome sequencing data identified 294 differentially expressed genes in the LPS-induced ALI mouse model. Based on the PPI network and module analysis, hub targets of AMD3100, such as Cxcl10 and Cxcl9, were identified in module 1, and hub targets, such as Cxcl12 and Cxcl1, were identified in module 2. Cxcl10 and Cxcl9 are involved in the Toll-like receptor signaling pathway, and Cxcl12 and Cxcl1 arae enriched in the nuclear factor-kappa B signaling pathway. Cxcl19, Cxcl10, and Cxcl1 are targeted by transcription factors like NF-κB. The validation of mRNAs and protein levels conducted by PCR and ELISA supported our transcriptome data. Conclusions Our findings indicate that AMD3100 may exhibit a therapeutic effect on LPS-induced ALI in mice by modulating multiple chemokines to inhibit the Toll-like receptor/nuclear factor-kappa B signaling pathway.

Background Sepsis is a significant contributor to both intensive care unit (ICU) admissions and mortality among patients in ICU, with a rising prevalence of obesity. There is a lack of extensive research on the correlation between TyGI and findings in patients with sepsis, especially in obese patients.Methods This study used a retrospective cohort design and included patients with sepsis (≥18 years) from the Medical Information Mart for Intensive Care IV database. The association between TyGI and outcome was examined using multivariable logistic regression analysis.Results 8,840 patients with sepsis were included in the analysis. The in-ICU mortality rate was 9.7%. Non-survivors exhibited significantly greater TyGI levels than survivors [9.19(8.76–9.71) vs. 9.10(8.67–9.54), p

ABSTRACT: Objectives: Several linezolid population pharmacokinetic (popPK) models have been established to facilitate optimal therapy; however, their extrapolated predictive performance to other clinical sites is unknown. This study aimed to externally evaluate the predictive performance of published pharmacokinetic models of linezolid in adult patients. Methods: For the evaluation dataset, 150 samples were collected from 70 adult patients (72.9% of which were critically ill) treated with linezolid at our center. Twenty-five published popPK models were identified from PubMed and Embase. Model predictability was evaluated using prediction-based, simulation-based, and Bayesian forecasting-based approaches to assess model predictability. Results: Prediction-based diagnostics found that the prediction error within ±30% (F30) was less than 40% in all models, indicating unsatisfactory predictability. The simulation-based prediction- and variability-corrected visual predictive check and normalized prediction distribution error test indicated large discrepancies between the observations and simulations in most of the models. Bayesian forecasting with one or two prior observations significantly improved the models’ predictive performance. Conclusion: The published linezolid popPK models showed insufficient predictive ability. Therefore, their sole use is not recommended, and incorporating therapeutic drug monitoring of linezolid in clinical applications is necessary.

BackgroundThe choice of postoperative weight bearing protocol after uncemented total hip arthroplasty (THA) remains controversial. The aim of this study was to assess the efficacy and safety of immediate unrestricted weight bearing (UWB) compared with partial weight bearing (PWB) in patients undergoing uncemented THA.MethodsRelevant articles were retrieved from electronic databases. Both randomized controlled trials (RCTs) and non-RCTs were included but analyzed separately. All functional and clinical outcomes with at least 2 independent study outcomes were meta-analyzed.ResultsA total of 17 studies were investigated. No adverse effect was found regarding micromotion of the femoral stem with immediate UWB following uncemented THA. There was also no correlation between immediate UWB and failure of ingrowth fixation and higher risks of femoral stem subsidence and surgical revision in RCTs. Harris hip score was better in patients with immediate UWB than those with PWB at 1 year post surgery, but the difference was not statistically significant.ConclusionsImmediate UWB did not have extra harm compared with PWB in patients undergoing uncemented THA. UWB was not superior to PWB. Considering the improvement of Harris score and the compliance of patients, UWB can be encouraged in THA rehabilitation.

Growing research reveals that circular RNAs (circRNAs) play a major part in the progression and development of cancer. Here, we investigated the oncogenic function and regulatory mechanisms of the circRNA circACTN4 in hepatocellular carcinoma (HCC), particularly in the tumor epithelial-mesenchymal transition (EMT). In vitro functional assays (Cell Counting Kit 8, TUNEL, scratch wound healing, and invasion assays) of HCC cell lines, alongside in vivo analyses of subcutaneous tumors in nude model mice, were employed to assess the impact of circACTN4 on HCC proliferation. Interactions concerning circACTN4, microRNA (miR)-424-5p, and non-SMC condensing I complex subunit G (NCAPG) have been assessed deploying luciferase reporter assays and also quantitative reverse transcription PCR investigation of circACTN4 transcripts in HCC tissues. Findings indicated a high expression of circACTN4 in HCC, promoted proliferation, while inhibiting apoptosis of HCC cells, and correlated with poor prognosis. Mechanistically, circACTN4 served as a rival internal RNA for miR-424 5p, controlling NCAPG level and initiating the Wnt/β-catenin signaling routes, which in turn impacted the EMT machinery in HCC. According to our surveys, the circACTN4/miR-424 5p/NCAPG axis could be an intriguing candidate for therapy to address the treatment of HCC. [ABSTRACT FROM AUTHOR]

Abstract Voriconazole increases tacrolimus blood concentration significantly when coadministrated. The recommendation of reducing tacrolimus to 1/3 in voriconazole package insert seems not to be satisfactory in clinical practice. In vitro studies demonstrated that the magnitude of inhibition depends on the concentration of voriconazole, while voriconazole exposure is determined by the genotype status of CYP2C19. CYP2C19 gene polymorphism challenges the management of drug-drug interactions(DDIs) between voriconazole and tacrolimus. This work aimed to predict the impact of CYP2C19 polymorphism on the DDIs by using physiologically based pharmacokinetics (PBPK) models. The precision of the developed voriconazole and tacrolimus models was reasonable by evaluating the pharmacokinetic parameters fold error, such as AUC0-24, Cmax and tmax. Voriconazole increased tacrolimus concentration immediately in all population. The simulated duration of DDIs disappearance after voriconazole withdrawal were 146h, 90h and 66h in poor metabolizers (PMs), intermediate metabolizers (IMs) and extensive metabolizers(EMs), respectively. The developed and optimized PBPK models in this study can be applied to assit the dose adjustment for tacrolimus with and without voriconazole.

ObjectiveSex-specific thyroid cancer risk exists in patients diagnosed with diabetes mellitus (DM). However, thyroid cancer risk in different types of DM is still unclear. This meta-analysis aims to identify the real correlation between different types of DM and thyroid cancer risk in both sexes.MethodsStudies were identified by an electronic search of PubMed, EMBASE, and Cochrane Library on 16 January 2022. A random-effects model was used to estimate the relative risks (RRs). The Cochran’s Q and I2 statistics were computed to detect heterogeneity between studies.ResultsIn comparison with non-DM counterparts, patients with DM had a 1.32-fold higher risk of thyroid cancer (95% CI, 1.22–1.44) with 1.26-fold (95% CI, 1.12–1.41) in men and 1.36-fold (95% CI, 1.22–1.52) in women, respectively. Subgroup analysis by the type of DM showed that the RR of thyroid cancer in patients with type 2 diabetes was 1.34 (95% CI, 1.17–1.53) in the study population with 1.32 (95% CI, 1.12–1.54) in men and 1.37 (95% CI, 1.12–1.68) in women, respectively; the RR of thyroid cancer was 1.30 (95% CI, 1.17–1.43) in patients with gestational diabetes; the risk of thyroid cancer in patients with type 1 diabetes was 1.51-fold in women but not in men. Although there were some heterogeneities, it did not affect the above results of this study.ConclusionThis study indicates that, compared with non-DM individuals, patients with any type of DM have an elevated thyroid cancer risk. This positive correlation between type 2 diabetes and thyroid cancer risk exists in both men and women.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, CRD42022304028.

Prognostic factors for excellent response (ER) to initial therapy in patients with papillary thyroid cancer (PTC) have not been determined. In this study, we investigated the response to initial therapy in PTC patients and independent prognostic factors for ER in a prospective multicenter study in China. A total of 506 PTC patients from nine centers in China were enrolled in this study, all of whom underwent total or near total thyroidectomy with lymph node dissection and subsequent radioiodine therapy. Univariate and multivariable logistic regression analyses were carried out to determine the independent prognostic factors for ER. The optimal cutoff value of the number of metastatic lymph nodes for predicting ER was determined by the receiver operating characteristic curve. A total of 139 patients (27.5%) achieved ER after initial therapy. Extrathyroidal extension, the number of metastatic lymph nodes, and preablative-stimulated thyroglobulin (Ps-Tg) were independent risk factors for ER for the entire population. In a subgroup analysis, extrathyroidal extension and Ps-Tg were independent risk factors for ER in pathological N1a patients, while the number of metastatic lymph nodes and Ps-Tg were independent risk factors for ER in pathological N1b patients. The appropriate cutoff values of the number of metastatic lymph nodes in predicting ER were 5 and 13 for the entire population and pathological N1b PTC patients, respectively. PTC patients with more metastatic lymph nodes were more likely to fail to achieve ER. Extrathyroidal extension, the number of metastatic lymph nodes, and Ps-Tg were important prognostic factors for ER after initial therapy in PTC patients.

Context Salidroside, a compound extracted from Rhodiola rosea L. (Crassulaceae), possesses many beneficial pathological effects. Objective To explore the effect of salidroside on ventilator-induced lung endothelial dysfunction in vivo and in vitro. Materials and methods In vivo, male ICR mice were divided into sham, ventilation, salidroside, and ventilation plus salidroside groups. The mice were ventilated for 4 h, salidroside (50 mg/kg) was administrated intraperitoneally before ventilation, dexamethasone (Dex) (5 mg/kg) was used as a positive control. In vitro, mouse lung vascular endothelial cells (MLVECs) were treated with salidroside, MMP-9 siRNA, and BAY11-7082 (10 μM), and then exposed to cyclic stretch for 4 h. Afterward, lung tissues and MLVECs were collected for further analysis. Results Salidroside pre-treatment significantly reversed the expression of vascular endothelial cadherin (VE-cadherin) and zonula occluden-1 (ZO-1) proteins in cyclic stretch-treated MLVECs (0.46 ± 0.09 vs. 0.80 ± 0.14, 0.49 ± 0.05 vs. 0.88 ± 0.08) and ventilated lung tissues (0.56 ± 0.06 vs. 0.83 ± 0.46, 0.49 ± 0.08 vs. 0.80 ± 0.12). The results further indicated that salidroside inhibited the expression of matrix metalloproteinase-9 (MMP-9), whereas knockdown of its expression restored the expression levels of VE-cadherin (0.37 ± 0.08 vs. 0.85 ± 0.74) and ZO-1 (0.48 ± 0.08 vs. 0.81 ± 0.11) in stretched MLVECs. Meanwhile, salidroside inhibited the NF-κB signalling pathway and alleviated lung injury. Conclusions Salidroside protected against stretch-induced endothelial barrier function, improving lung injury after ventilation. Thus, salidroside may be a promising therapeutic agent for patients with MV-induced lung injury.

Aims: This study aimed to investigate an appropriate catheter manipulation approach for ventricular arrhythmias (VAs) originating from the left ventricular epicardium adjacent to the transitional area from the great cardiac vein to the anterior interventricular vein (DGCV-AIV).Methods: A total of 123 patients with DGCV-AIV VAs were retrospectively analyzed. All these patients underwent routine mapping and ablation by conventional approach [Non-Swartz sheath support (NS) approach] firstly. In the situation of the distal portion of the coronary venous system (CVS) not being accessed or a good target site not being obtained, the Swartz sheath support (SS) approach was attempted alternatively. If this still failed, the hydrophilic coated guidewire and left coronary angiographic catheter-guided deep engagement of Swartz sheath in GCV to support ablation catheter was performed.Results: A total of 103 VAs (103/123, 83.74%) were successfully eliminated in DGCV-AIV. By NS approach, the tip of the catheter reached DGCV in 39.84% VAs (49/123), reached target sites in 35.87% VAs (44/123), and achieved successful ablation in 30.89% VAs (38/123), which was significantly lower than by SS approach (88.61% (70/79), 84.81 % (67/79), and 75.95% (60/79), P < 0.05). There were no significant differences in complication occurrence between the NS approach and the SS approach (4/123, 3.25% vs. 7/79, 8.86%, p > 0.05). The angle between DGCV and AIV 0.69 more favored a SS approach with a predictive value of 87%.Conclusion: For radiofrequency catheter ablation (RFCA) of VAs arising from DGCV-AIV, the SS approach facilitates the catheter tip to achieve target sites and contributes to a successful ablation.