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Abstract Objective The objective of this study was to develop and evaluate the performance of machine learning models for predicting the possibility of systemic inflammatory response syndrome (SIRS) following percutaneous nephrolithotomy (PCNL). Methods We retrospectively reviewed the clinical data of 337 patients who received PCNL between May 2020 and June 2022. In our study, 80% of the data were used as the training set, and the remaining data were used as the testing set. Separate prediction models based on the six machine learning algorithms were created using the training set. The predictive performance of each machine learning model was determined by the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity and specificity using the testing set. We used coefficients to interpret the contribution of each variable to the predictive performance. Results Among the six machine learning algorithms, the support vector machine (SVM) delivered the best performance with accuracy of 0.868, AUC of 0.942 (95% CI 0.890–0.994) in the testing set. Further analysis using the SVM model showed that prealbumin contributed the most to the prediction of the outcome, followed by preoperative urine culture, systemic immune-inflammation (SII), neutrophil to lymphocyte ratio (NLR), staghorn stones, fibrinogen, operation time, preoperative urine white blood cell (WBC), preoperative urea nitrogen, hydronephrosis, stone burden, sex and preoperative lymphocyte count. Conclusion Machine learning-based prediction models can accurately predict the possibility of SIRS after PCNL in advance by learning patient clinical data, and should be used to guide surgeons in clinical decision-making.

Abstract Background Certain occupations may predispose individuals to urolithiasis, a multi-factorial disease. The study aimed to evaluate the prevalence and related factors of nephrolithiasis in medical staff in Qingdao, China. Methods Physical examination results of 5115 in-service medical staff aged 22–60 years old were retrospectively analyzed. Multivariable logistic regression analysis and stratified analyses by age and gender were applied to explore the related factors of nephrolithiasis in these medical staff. Results The overall nephrolithiasis prevalence in medical staff in Qingdao, China was 4.65%. Doctors were more prone to nephrolithiasis than nurses (5.63% vs. 3.96%, P = 0.013) and the peak prevalence (6.69%) was observed in medical staff working in the emergency department (ED). Male gender (OR = 1.615, 95% CI = 1.123–2.323, P = 0.010), overweight or obesity (OR = 1.674, 95% CI = 1.266–2.214, P

Abstract Background Endoscopic spine lumbar interbody fusion (Endo-LIF) is well-regarded within the academic community. However, it presents challenges such as intraoperative disorientation, high rates of nerve damage, a steep learning curve, and prolonged surgical times, often occurring during the creation of the operative channel. Furthermore, the undefined safe operational zones under endoscopy continue to pose risks to surgical safety. We aimed to analyse the anatomical data of Kambin’s triangle via CT imaging to define the parameters of the safe operating area for transforaminal posterior lumbar interbody fusion (TPLIF), providing crucial insights for clinical practice. Methods We selected the L4–L5 intervertebral space. Using three-dimensional (3D), we identified Kambin’s triangle and the endocircle within it, and recorded the position of point ‘J’ on the adjacent facet joint as the centre ‘O’ of the circle shifts by angle ‘β.’ The diameter of the inscribed circle ‘d,’ the abduction angle ‘β,’ and the distances ‘L1’ and ‘L2’ were measured from the trephine’s edge to the exiting and traversing nerve roots, respectively. Results Using a trephine with a diameter of 8 mm in TPLIF has a significant safety distance. The safe operating area under the TPLIF microscope was also clarified. Conclusions Through CT imaging research, combined with 3D simulation, we identified the anatomical data of the L4–L5 segment Kambin’s triangle, to clarify the safe operation area under TPLIF. We propose a simple and easy positioning method and provide a novel surgical technique to establish working channels faster and reduce nerve damage rates. At the same time, according to this method, the Kambin’s triangle anatomical data of the patient’s lumbar spine diseased segments can be measured through CT 3D reconstruction of the lumbar spine, and individualised preoperative design can be conducted to select the appropriate specifications of visible trephine and supporting tools. This may effectively reduce the learning curve, shorten the time operation time, and improve surgical safety.

IntroductionThis study investigates the mutual influence between online medical search and online medical consultation. It focuses on understanding the health information needs that drive these health information-seeking behaviors by utilizing insights from behavioral big data.MethodsWe used actual behavioral data from Chinese internet users on Baidu platform’s “Epidemic Index” from November 26, 2022, to January 25, 2023. Data modeling was conducted to ensure the reliability of the model. Drawing on the logistic model, we constructed a foundational model to quantify the evolutionary patterns of online medical search and online medical consultation. An impact function was defined to measure their mutual influence. Additionally, a pattern detection experiment was conducted to determine the structure of the impact function with maximum commonality through data fitting.ResultsThe analysis allowed us to build a mathematical model that quantifies the nonlinear correlation between online medical search and online medical consultation. Numerical analysis revealed a predation mechanism between online medical consultation and online medical search, highlighting the role of health information needs in this dynamic.DiscussionThis study offers a novel practical approach to better meet the public’s health information needs by understanding the interplay between online medical search and consultation. Additionally, the modeling method used here is broadly applicable, providing a framework for quantifying nonlinear correlations among different behaviors when appropriate data is available.

Abstract Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer (mCRC), but the prognosis remains poor. This phase 3 trial (ClinicalTrials.gov: NCT03950154) assessed the efficacy and adverse events (AEs) of the combination of PD-1 blockade-activated DC-CIK (PD1-T) cells with XELOX plus bevacizumab as a first-line therapy in patients with mCRC. A total of 202 participants were enrolled and randomly assigned in a 1:1 ratio to receive either first-line XELOX plus bevacizumab (the control group, n = 102) or the same regimen plus autologous PD1-T cell immunotherapy (the immunotherapy group, n = 100) every 21 days for up to 6 cycles, followed by maintenance treatment with capecitabine and bevacizumab. The main endpoint of the trial was progression-free survival (PFS). The median follow-up was 19.5 months. Median PFS was 14.8 months (95% CI, 11.6–18.0) for the immunotherapy group compared with 9.9 months (8.0–11.8) for the control group (hazard ratio [HR], 0.60 [95% CI, 0.40–0.88]; p = 0.009). Median overall survival (OS) was not reached for the immunotherapy group and 25.6 months (95% CI, 18.3–32.8) for the control group (HR, 0.57 [95% CI, 0.33–0.98]; p = 0.043). Grade 3 or higher AEs occurred in 20.0% of patients in the immunotherapy group and 23.5% in the control groups, with no toxicity-associated deaths reported. The addition of PD1-T cells to first-line XELOX plus bevacizumab demonstrates significant clinical improvement of PFS and OS with well tolerability in patients with previously untreated mCRC.

Abstract Anaplastic thyroid carcinoma (ATC) has a 100% disease-specific mortality rate. The JAK1/2-STAT3 pathway presents a promising target for treating hematologic and solid tumors. However, it is unknown whether the JAK1/2-STAT3 pathway is activated in ATC, and the anti-cancer effects and the mechanism of action of its inhibitor, ruxolitinib (Ruxo, a clinical JAK1/2 inhibitor), remain elusive. Our data indicated that the JAK1/2-STAT3 signaling pathway is significantly upregulated in ATC tumor tissues than in normal thyroid and papillary thyroid cancer tissues. Apoptosis and GSDME-pyroptosis were observed in ATC cells following the in vitro and in vivo administration of Ruxo. Mechanistically, Ruxo suppresses the phosphorylation of STAT3, resulting in the repression of DRP1 transactivation and causing mitochondrial fission deficiency. This deficiency is essential for activating caspase 9/3-dependent apoptosis and GSDME-mediated pyroptosis within ATC cells. In conclusion, our findings indicate DRP1 is directly regulated and transactivated by STAT3; this exhibits a novel and crucial aspect of JAK1/2-STAT3 on the regulation of mitochondrial dynamics. In ATC, the transcriptional inhibition of DRP1 by Ruxo hampered mitochondrial division and triggered apoptosis and GSDME-pyroptosis through caspase 9/3-dependent mechanisms. These results provide compelling evidence for the potential therapeutic effectiveness of Ruxo in treating ATC.

The through-thickness compressive mechanism of 3D needled nonwoven fiber preforms is complicated due to the complex fiber structure and enormous fiber-to-fiber contacts. This work developed a microscale modeling method to predict compressive behavior of carbon fiber nonwoven preforms. A newly-developed virtual fiber is proposed based on the generalized beam elements, for which the low bending stiffness of the fiber is calibrated by experimental data and decoupled from the high tensile stiffness. The feasibility of the proposed virtual fiber method is demonstrated through a simulation example of three-point bending of 6 k carbon fiber yarn. Influence of modeling parameters including amount of virtual fibers in the yarn and the element length of virtual fibers on the simulations is analyzed. High precision model of 3D needled preform is then generated using the proposed virtual fiber method. Through-thickness and axial compressive deformations of the preform are simulated. The predicted load–displacement curves agreed well with the experimental results.

BackgroundYishen-Tongbi Decoction (YSTB), a traditional Chinese prescription, has been used to improve syndromes of rheumatoid arthritis (RA) for many years. Previous research has shown that YSTB has anti-inflammatory and analgesic properties. However, the underlying molecular mechanism of the anti-RA effects of YSTB remains unclear.Purpose and study designThe purpose of this research was to investigate how YSTB affected mice with collagen-induced arthritis (CIA) and RAW264.7 cells induced with lipopolysaccharide (LPS).ResultsThe findings show that YSTB could significantly improve the clinical arthritic symptoms of CIA mice (mitigate paw swelling, arthritis score, thymus and spleen indices, augment body weight), downregulated expression of pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), IL-6 and IL-17, while upregulated the level of anti-inflammatory like IL-10 and transforming growth factor-β (TGF-β). Meanwhile, YSTB inhibits bone erosion and reduces inflammatory cell infiltration, synovial proliferation, and joint destruction in CIA mice. In addition, we found that YSTB was able to suppress the LPS-induced inflammation of RAW264.7 cells, which was ascribed to the suppression of nitric oxide (NO) production and reactive oxygen species formation (ROS). YSTB also inhibited the production of inducible nitric oxide synthase and reduced the releases of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 in LPS-induced RAW264.7 cells. Furthermore, the phosphorylation expression of JAK2, JAK3, STAT3, p38, ERK and p65 protein could be suppressed by YSTB, while the expression of SOCS3 could be activated.ConclusionTaken together, YSTB possesses anti-inflammatory and prevention bone destruction effects in RA disease by regulating the JAK/STAT3/SOCS3 signaling pathway.

Summary: The decline of motor ability is a hallmark feature of aging and is accompanied by degeneration of motor synaptic terminals. Consistent with this, Drosophila motor synapses undergo characteristic age-dependent structural fragmentation co-incident with diminishing motor ability. Here, we show that motor synapse levels of Trio, an evolutionarily conserved guanine nucleotide exchange factor (GEF), decline with age. We demonstrate that increasing Trio expression in adult Drosophila can abrogate age-dependent synaptic structural fragmentation, postpone the decline of motor ability, and maintain the capacity of motor synapses to sustain high-intensity neurotransmitter release. This preservative activity is conserved in transgenic human Trio, requires Trio Rac GEF function, and can also ameliorate synapse degeneration induced by depletion of miniature neurotransmission. Our results support a paradigm where the structural dissolution of motor synapses precedes and promotes motor behavioral diminishment and where intervening in this process can postpone the decline of motor function during aging.

Abstract Cardiac remodeling is manifested by hypertrophy and apoptosis of cardiomyocytes, resulting in the progression of cardiovascular diseases. Long noncoding RNAs (lncRNAs) serve as modifiers of cardiac remodeling. In this study, we aimed to explore the molecular mechanism of H19 shuttled by mesenchymal stem cells (MSC)‐derived extracellular vesicles (EV) in cardiac remodeling upon heart failure (HF). Using the GEO database, H19, microRNA (miR)‐29b‐3p, and CDC42 were screened out as differentially expressed biomolecules in HF. H19 and CDC42 were elevated, and miR‐29b‐3p was decreased after MSC‐EV treatment in rats subjected to ligation of the coronary artery. MSC‐EV alleviated myocardial injury in rats with HF. H19 downregulation exacerbated myocardial injury, while miR‐29b‐3p inhibitor alleviated myocardial injury. By contrast, CDC42 downregulation aggravated the myocardial injury again. PI3K/AKT pathway was activated by MSC‐EV. These findings provide insights into how H19 shuttled by EV mitigates cardiac remodeling through a competitive endogenous RNA network regarding miR‐29b‐3p and CDC42.

Abstract Background The multifactorial aetiology of scoliosis is well known. Physical activity is considered both a treatment and causative factor for idiopathic scoliosis; however, evidence for a causal relationship between physical activity levels and idiopathic scoliosis in adolescents is conflicting. Therefore, we aimed to summarise the current evidence regarding the association between adolescent idiopathic scoliosis and physical activity and further to assess whether the relationship is dose dependent. Methods PubMed, Cochrane, Scopus, and Web of Science databases were searched from 1991 to July 2022 using the following main keywords: adolescent idiopathic scoliosis, physical activity, and risk factors, supplemented with manual searches, secondary citations, and reference searches. The quality of the included literature was evaluated using the Scale for Reporting Observational Studies in Enhanced Epidemiology guidelines. Results Eight studies were included in this review, of which six reported an association between adolescent idiopathic scoliosis and physical activity levels and two reported no association. One British study reported reduced physical function early in life as a new risk factor for scoliosis onset. Conclusions Physical activity is strongly associated with adolescent idiopathic scoliosis. Physical activity should be encouraged as it plays an important role in the prevention of adolescent idiopathic scoliosis. Further research is needed to determine the dose-dependent relationship between physical activity and prevention of adolescent idiopathic scoliosis.

Objective: Pregnancy has been identified as a risk factor for pelvic floor dysfunction (PFD). The aim of this study was to establish primary prevention measures for PFD during pregnancy and reduce the overall incidence of PFD. Methods: We assembled a panel of 36 experts, including gynecologists, obstetricians, and physiotherapists. Through surveys and expert meetings, the panel reviewed and assessed the safety and effectiveness of various clinical interventions. Based on expert comments from Round 1, a revised list of 8 clinical interventions was developed and submitted for a second round of expert review. Results: A consensus was reached on the importance of implementing prevention measures to protect pelvic floor function during pregnancy. Experts particularly emphasized the significance of health education, weight management, pelvic floor muscle training, respiratory training, overall exercise, physical activity, and perineal massage. Conclusion: The expert consensus provides comprehensive clinical measures to safeguard pelvic floor function during pregnancy. This paper represents the initial step toward developing scientific recommendations for pregnant women regarding the primary prevention of PFD. Future research should focus on the implementation of these recommendations in clinical practice.

The crude protein (CP) content is an important determining factor for the quality of alfalfa, and its accurate and rapid evaluation is a challenge for the industry. A model was developed by combining Fourier transform infrared spectroscopy (FTIS) and chemometric analysis. Fourier spectra were collected in the range of 4000~400 cm−1. Adaptive iteratively reweighted penalized least squares (airPLS) and Savitzky–Golay (SG) were used for preprocessing the spectral data; competitive adaptive reweighted sampling (CARS) and the characteristic peaks of CP functional groups and moieties were used for feature selection; partial least squares regression (PLSR) and random forest regression (RFR) were used for quantitative prediction modelling. By comparing the combined prediction results of CP content, the predictive performance of airPLST-cars-PLSR-CV was the best, with an RP2 of 0.99 and an RMSEP of 0.053, which is suitable for establishing a small-sample prediction model. The research results show that the combination of the PLSR model can achieve an accurate prediction of the crude protein content of alfalfa forage, which can provide a reliable and effective new detection method for the crude protein content of alfalfa forage.

Bound states in the continuum (BICs) based on metasurfaces have gained significant attention recently to enhance the strength of light-matter interaction. However, most BIC metasurfaces possess fixed optical properties once they have been fabricated. In this study, we introduce the concept of BICs to the phase-change metasurfaces composed of Ge2Sb2Te5 nanodisk dimers. The Ge2Sb2Te5 nanodisk dimers can support a low-Q transverse magnetic dipole resonance, a high-Q toroidal dipole resonance and a high-Q longitudinal magnetic dipole resonance. By adjusting geometric parameter, the high-Q longitudinal magnetic dipole resonance can be converted into a BIC mode. Notably, when Ge2Sb2Te5 is in the amorphous phase, high-Q electromagnetically induced transparency (EIT)-like resonances can be achieved due to the interaction between a low-Q transverse magnetic dipole mode and either a high-Q toroidal dipole mode or a high-Q longitudinal magnetic dipole mode. However, the EIT resonances are switched off when Ge2Sb2Te5 is transformed into the crystalline phase. Furthermore, the high-Q EIT resonances enable the realization of an ultrahigh group refractive index, and can be tuned through the phase transition of Ge2Sb2Te5. The switchable high-Q EIT resonances hold potential applications in slow-light devices, optical modulators, and biosensors.

With an increase in aging population, osteoporosis has become one of the major public health issues nowadays, affecting over 200 million people worldwide. Since current medications are associated with various side effects, there is a clear clinical need to develop alternative therapeutics for managing osteoporosis. Selenium is an essential trace mineral, which has been proved to play important role in bone health. However, the narrow therapeutic window of selenium has greatly hindered its further development. Recently, selenium nanoparticles (SeNPs) have become a new selenium source due to its promising bioactivity and low toxicity. Nevertheless, scientific research concerning their effects on bone health is still very limited. By using the mushroom polysaccharide-protein complex isolated from Cordyceps sinensis, we have successfully prepared novel SeNPs (“Cs4-SeNPs”) with well-characterized structure and high stability. Interestingly, Cs4-SeNPs (10 μM) were found to markedly induce proliferation, differentiation, and mineralization of the pre-osteoblast murine MC3T3-E1 cells. Further mechanistic study discovered that after cellular internalization via endocytosis, Cs4-SeNPs would trigger Nox4-derived intracellular ROS generation in the MC3T3-E1 cells followed by promoting downstream BMP-2 gene transcription and activating BMP signaling via both Smad dependent and Smad independent p38 MAPK pathways. More importantly, Cs4-SeNPs (25–500 μg/kg BW/d) exhibitedpromising in vivo bone protective efficacy against OVX-induced osteoporosis by promoting bone formation, inhibiting bone resorption, and improving bone microarchitecture after oral gavage for 6 weeks. Findings of this study collectively suggested that Cs4-SeNPs is of great potential to be further developed into a safe and evidence-based nano-mineral for managing postmenopausal osteoporosis.

Since a scarcity of sufficient grafting materials, several complications can arise after urothelial defect reconstruction surgery, including severe hypospadias. Accordingly, developing alternative therapies, such as urethral restoration via tissue engineering are needed. In the present study, we developed a potent adhesive and repairing material using fibrinogen-poly(l-lactide-co-caprolactone) copolymer (Fib-PLCL) nanofiber scaffold to achieve effective urethral tissue regeneration after seeding with epithelial cells on the surface. The in vitro result found the Fib-PLCL scaffold promoted the attachment and viability of epithelial cells on their surface. The increased expression levels of cytokeratin and actin filaments were observed in Fib-PLCL scaffold than PLCL scaffold. The in vivo urethral injury repairing potential of Fib-PLCL scaffold was evaluated using a rabbit urethral replacement model. In this study, a urethral defect was surgically excised and replaced with the Fib-PLCL and PLCL scaffolds or autograft. As expected, the animals healed well after surgery in the Fib-PLCL scaffold group, and no significant strictures were identified. As expected, the cellularized Fib/PLCL grafts have induced the luminal epithelialization, urethral smooth muscle cell remodelling, and capillary development all at the same time. Histological analysis revealed that the urothelial integrity in the Fib-PLCL group had progressed to that of a normal urothelium, with enhanced urethral tissue development. Based on the results, the present study suggests that the prepared fibrinogen–PLCL scaffold is more appropriate for urethral defect reconstruction.

Abstract: The H-8 horizontal channel of CARR is an experimental channel to provide neutrons, which can provide a stable radiation field. For different neutron experiments, the required neutron energy spectrum shapes are often different, so accurate measurement of neutron energy spectrum is of great significance. A passive single sphere neutron spectrometer with gold foils as thermal neutron detector is developed to measure the neutron energy spectrum of H-8 horizontal channel. The neutron energy response in 10-11-15 MeV is calculated by MCNP and the rationality of the energy response is analyzed. The single sphere spectrometer was tested in the conduit hall of CARR, the activity of each gold foil was measured by high-purity germanium detector, and the experimental data were calculated by UGA (unfolding based on genetic algorithm). The results show that the neutron energy range emitted from the conduit hall is 10-9-10-6 MeV and the single sphere neutron spectrometer can give accurate neutron energy spectrum data, and can be applied to the measurement and research of neutron energy spectrum in H-8 horizontal channel of CARR.

Abstract Objective Recent studies found that exosomes (Exo) derived from mesenchymal stem cells (MSC) (MSC‐Exo) accelerated diabetic wound healing. However, the low yield during exosome extraction is still a major barrier to their clinical utility. Methods We constructed a method to produce umbilical cord MSC‐derived nanovesicles (UCMSC‐NV) by serial extrusion through filters and investigated the effects of UCMSC‐NV on wound healing in vivo and in vitro, as well as the potential mechanisms. Results We found that the characteristics of UCMSC‐NV were similar to those of exsome (UCMSC‐Exo) but with much higher production yields. Further analysis showed that UCMSC‐NV promoted the migration of fibroblasts and angiogenesis in vitro, and both UCMSC‐NV and UCMSC‐Exo showed similar therapeutic capacities for wound healing in vivo. Sequencing analysis revealed that UCMSC‐NV and UCMSC‐Exo had similar miRNA compositions, and the target genes of the differentially expressed miRNAs in UCMSC‐NV were enriched in pathways of inflammation and damage‐repair‐related functions. Mass spectrometry analysis showed that UCMSC‐NV encapsulated functional proteins that may achieve therapeutic effect equally as good as UCMSC‐Exo. Conclusions UCMSC‐NV are more efficacious and can be obtained at a higher yield than UCMSC‐Exo and are a promising therapeutic strategy to improve wound healing in diabetes patients.