Search

Abstract The objective of this study was to investigate the culture positivity and distribution of the conjunctival sac bacteria in the perioperative period of corneal refractive surgery. The selected time points of the perioperative period included before the use of antibiotic eye drops, before eye wash (after the use of antibiotic eye drops), after eye wash, and immediately after surgery. Conjunctival specimens obtained at the four time points were cultured to detect the positivity and distribution of bacteria. Before prophylactic antibiotic eye drops were administered, 49 eyes (50%) had positive bacterial culture results, with 45 isolates (91.8%) identified as Staphylococcus epidermidis. The culture positivity rates of the conjunctival sac specimens before eye wash, after eye wash, and immediately after surgery were 19.4%, 3.1%, and 4.1%, respectively. The difference was significant before and after the use of antibiotics and before and after eye wash (both P 0.05). The judicious preoperative use of antibiotic eye drops combined with the surgical sterile eye wash procedure maximised the removal of conjunctival sac bacteria. Skilled surgical manipulations generally did not increase the risk of infection.

ABSTRACT Purpose To compare the efficacy of first‐line regimens based on programmed cell death (or ligand) [PD‐(L)1] blockade in extensive‐stage small‐cell lung cancer (ES‐SCLC) patients with or without liver metastases (LM), and to identify optimal treatment strategies. Methods Network meta‐analysis of randomized controlled trials (RCTs) comparing chemo‐immunotherapy (CIT) and chemotherapy (CT) in ES‐SCLC patients stratified by LM. Overall survival (OS) and progression‐free survival (PFS) were evaluated using hazard ratios (HRs) and 95% confidence intervals (CIs). Results Seven RCTs involving 3658 ES‐SCLC patients (1243 with LM, 2415 without LM) were analyzed. For patients with LM, the combination therapies of anti‐PD‐1 + CT (HR, 0.67; 95% CI, 0.54%–0.82%; p

BackgroundChemotherapy (CT) remains the primary treatment for locally advanced unresectable pancreatic cancer (LAUPC) and metastatic pancreatic cancer (MPC). The role of radiotherapy (RT) in these conditions remains unclear. This study compares the outcomes of CT alone versus CT combined with RT (combined-modality therapy [CMT]) in LAUPC and MPC patients.Materials and methodsWe conducted a retrospective analysis of LAUPC and MPC patients treated with either CT or CMT from a single institution and Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier curves and Cox hazards models evaluated the association between treatment modalities and overall survival (OS). Propensity score matching (PSM) ensured balanced comparisons. Landmark analysis addressed immortal time bias. Subgroup analyses were based on clinical characteristics. eXtreme Gradient Boosting (XGBoost) and Shapley Additive Explanations (SHAP) assessed outcome prediction and influence of significant predictors.ResultsThe study included 102 patients receiving CMT and 155 receiving CT at single institution, along with 1733 CMT and 9310 CT patients from the SEER dataset. In the single-institution cohort, CMT showed superior survival compared to CT both before (median OS: 20.5 vs. 11.5 months, hazard ratio [HR]: 0.47, 95% CI: 0.34-0.65, P=0.001) and after PSM (median OS: 22.2 vs. 11.8 months, HR: 0.49, 95% CI: 0.30-0.79, P=0.003). Multivariate analyses confirmed that CMT was independently associated with improved OS both before (HR: 0.54, 95% CI: 0.38-0.77, P=0.001) and after PSM (HR: 0.45, 95% CI: 0.27-0.73, P=0.001). Landmark analysis indicated better OS for patients receiving CMT compared to CT alone. Subgroup analysis revealed an OS benefit for CMT across most subgroups. SHAP value analysis indicated that CMT was the most significant contributor to survival outcomes. SEER database validation confirmed these findings.ConclusionsThis study demonstrates that CMT significantly improves OS in LAUPC and MPC patients compared to CT alone. Integrating RT with CT could be beneficial for treating LAUPC and MPC.

Abstract Soil water-holding capacity decreases due to long-term mineral fertilizer application. The objective of this study was to determine how replacing mineral fertilizer with maize straw affected the soil water retention curve, soil water content, soil water availability, and soil equivalent pore size. Replacement treatments in which 25% (S25), 50% (S50), 75% (S75), and 100% (S100) of 225 kg ha−1 nitrogen from mineral fertilizer (CK) was replaced with equivalent nitrogen from maize straw were conducted for five years in the Loess Plateau of China. The Gardner model was used to fit the soil water retention curve and calculate the soil water constant and equivalent pore size distribution. The results indicated that the Gardner model fitted well. Replacing nitrogen from mineral fertilizer with nitrogen from straw increased soil specific water capacity, soil readily available water, soil delayed available water, soil available water, soil capillary porosity, and soil available water porosity over time. S25 increased field capacity and wilting point from the fourth fertilization year. S50 enhanced soil readily available water, soil delayed available water, soil available water, and soil available water porosity from the fifth fertilization year, whereas S25 and S75 increased these from the third fertilization year or earlier. Soil specific water capacity, soil readily available water, soil delayed available water, soil available water, soil capillary porosity, and soil available water porosity could better reflect soil water-holding capacity and soil water supply capacity compared with field capacity and wilting point.

Objectives: The aim of the study was to comprehensively analyze the effects of whey protein (WP)-enriched supplement intake with or without resistance training (RT) in older patients, either from the community or hospital, who were diagnosed with sarcopenia according to the EWGSOP or AWGS criteria. Methods: This meta-analysis study was registered in PROSPERO (CRD42023407885). We searched the PubMed, Embase, Web of Science, and Cochrane Library databases for RCTs up to June 1, 2023. Standardized mean differences (SMD) with 95% confidence intervals (CI) were used to estimate the pooled results. Results: Ten RCT studies, including 1154 participants, were included and analyzed. The primary outcomes were the changes in muscle mass, strength, and physical performance. In WP group versus (vs.) Isocaloric placebo (PLA)/Routine consultation (RC) group, WP significantly increased the appendicular skeletal muscle mass index (SMD: 0.47, 95%CI: 0.23, 0.71), appendicular skeletal muscle mass (SMD: 0.28, 95%CI: 0.11, 0.45) and gait speed (SMD: 1.13, 95%CI: 0.82, 1.44) in older patients with sarcopenia. In WP with RT group vs. PLA/ RC group, there was significant increase in handgrip strength (SMD: 0.67, 95%CI: 0.29, 1.04). In addition, in the secondary outcomes, WP significantly reduced interleukin-6, significantly increased insulin-like growth factor-1 and albumin, promoted participants' intake of total energy and protein, enhanced activities of daily living scores in patients, and had no significant effect on BMI, weight, or fat mass. Conclusion: This review confirms that WP can improve various aspects of older adult with sarcopenia, thereby enhancing their overall physical condition. More studies should be conducted to validate this result and further explore the effects of WP and RT in patients with sarcopenia.

Abstract Background Colorectal cancer (CRC) is one of the most common malignant tumors, influenced by several genetic loci in its clinical phenotypes. The aim of this study was to determine the relationship between the MMP8 gene polymorphism and CRC risk in the Chinese Han population. Method This study recruited 688 CRC patients and 690 healthy controls. The relationship between MMP8 polymorphism and CRC susceptibility was assessed by calculating the odds ratio (OR) and 95% confidence interval (CI) after stratifying by age, gender, body mass index (BMI), smoking, and alcohol consumption under a multi-genetic model. Results MMP8 rs3740938 was associated with increased CRC predisposition (p = 0.016, OR = 1.24, 95% CI: 1.04–1.48), and this association was detected particularly in subjects aged > 60 years, females, people with BMI > 24 kg/m2, smokers, and drinkers. Moreover, rs3740938 was found to be associated with the pathological type of rectal cancer. Conclusions Our results first displayed that rs3740938 in MMP8 was a risk factor for CRC predisposition. This finding may provide a new biological perspective for understanding the role of the MMP8 gene in CRC pathogenesis.

Polycarboxylate superplasticizers BMC-L and BMC-S were utilized as modifiers in the formulation of novel cement-based grouting materials. Indoor tests were conducted on 32 groups of cement slurries, varying by water–cement ratio (0.5:1 and 0.6:1) and modifier content (0, 2‰, 4‰, 6‰, 8‰, 10‰, 12‰, and 14‰), to test their density, funnel viscosity, water separation rate, and stone rate. Four groups of slurry modified with BMC-L were selected as the preferred slurry, and the apparent viscosity test, uniaxial, and triaxial compression test of the slurry stone body were conducted. The study investigated the influence of BMC-L on various properties of the slurry, including its apparent viscosity, uniaxial compressive strength, stress–strain relationships, shear strength parameters, and elastic modulus. Ultimately, the pore structure and phase composition of the slurry stone body were detected by Nuclear Magnetic Resonance (NMR) and X-ray Diffraction (XRD), and the impact of BMC-L on slurry performance was examined from a microstructural perspective. Results indicate that the two polycarboxylate superplasticizers exert minimal influence on the density and water separation rate of the slurry. Within the effective incorporation range of the polycarboxylate superplasticizer, increasing the dosage correlates with a decrease in both the stone rate and viscosity of the slurry. BMC-L significantly enhances the mechanical properties of the slurry stone body by promoting more complete cement hydration and reducing porosity. The uniaxial compressive strength of slurry stone body with a 6 ‰ BMC-L dosage reached 29.7 MPa after 7 days and 38.5 MPa after 28 days of curing, representing increases of 118.4% and 64%, respectively, compared to masonry with 0 BMC-L dosage. The shear strength parameters and elastic modulus of the slurry stone body also showed corresponding increases.

Abstract Purpose To determine the role and rational application of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) adjuvant therapy in patients with completely resected stage IB-IIIA EGFR-mutant non-small-cell lung cancer (NSCLC). Method Randomized controlled trials (RCTs) that compared the survival outcomes between adjuvant EGFR-TKIs and adjuvant chemotherapy or a placebo, or between different EGFR-TKI treatment durations for resected NSCLC, were eligible for inclusion. Disease-free survival (DFS) and overall survival (OS) with hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated as effective measures using random-effect or fixed-effect models. Subgroup analysis was also performed. Results Eleven RCTs involving 2102 EGFR-mutant NSCLC patients with or without EGFR-TKI adjuvant therapy were included. For all stage IB-IIIA NSCLC patients, EGFR-TKIs adjuvant therapy could not only significantly improve DFS (HR 0.43, 95% CI 0.30–0.63, P

Abstract Purpose Colorectal cancer (CRC) is the third most common cancer in the world. The purpose of this study was to investigate the role of TNNT2 in the proliferation, migration and invasion of CRC cells and its expression in CRC tissues to better understand the regulatory role of TNNT2 in CRC. Methods Western blotting (WB) and qPCR were used to detect the expression of TNNT2 in colorectal cancer tissues and paracancerous tissues. CCK-8, colony formation, Transwell and other experiments were used to clarify the role of TNNT2 in the proliferation, migration and invasion of colorectal cancer cells. Changes in TNNT2, EGFR and HER2 mRNA transcription levels were detected by SYBR Real-Time PCR assay, and the effects of TNNT2 overexpression or knockdown on the expression of EGFR, HER2 and EMT-related proteins in CRC cells were determined by WB. TNNT2 and EGFR intreaction was carried out in HCT116 cells by coimmunoprecipitation experiments. Results The protein and mRNA expression level of TNNT2 in CRC tissues were higher than those in paracancerous tissues. The CCK-8 results suggested that overexpression of TNNT2 significantly promoted the proliferation of HCT116 and RKO cells, and TNNT2 konckdown gets the opposite result; and the colony formation results were the same as tthose of CCK-8 assay. Transwell invasion and migration experiments showed that overexpression of TNNT2 promoted the migration and invasion of HCT116 and PKO cells, and TNNT2 konckdown suppressed the migration and invasion of the these cells. The SYBR Green I real-time PCR method revealed that them RNA levels of TNNT2, EGFR and HER2 in the TNNT2 overexpression group were higher than those in RKO cells. WB showed that overexpressing TNNT2 increased the expression of EGFR and HER2 in HCT16 and RKO cells,decreased the expression of EMT marker E-cadherin, and increased the expression of Vimentin and N-cadherin. Konckdown of TNNT2 decreased the expression of EGFR and HER2, increased the expression of E-cadherin, and decreased the expression of Vimentin and N-cadherin in HCT16 and RKO cells. The immunocoprecipitation experiment showed that there was an interaction between EGFR and TNNT2. Conclusion TNNT2 can promote the proliferation, invasion and metastasis of colorectal cancer cells. There is an interaction between TNNT2 and EGFR protein. TNNT2 can upregulate EGFR and HER2-related proteins in colorectal cancer cells and promote the occurrence of EMT. Therefore, TNNT2 can promote the invasion and metastasis of CRC cells through the EGFR/HER2/EMT signal axis, suggesting that TNNT2 is a potential target of CRC treatment.

Polymorphic networks support diverse network requirements and can coexist, evolve, and change on a unified physical or logical infrastructure in the form of network modality.They can maximize the innovation vitality of network technology driven by new applications.The evolution and development of modality require the incremental deployment of modality to meet the needs of convenience and privacy protection in the multi-user deployment process.However, the deployment of current network functions still uses the one-by-one deployment method, resulting in high complexity of the deployment of new modality, and mutual exposure of processing logic between different users.To address these issues, an incremental deployment mechanism for polymorphic network environments was proposed.Firstly, an incremental deployment mechanism for network modality was designed.Then, the incremental deployment of modality was abstracted as a graph merging problem based on this mechanism, and an adjacency list-based merge parsing graph algorithm was designed.The simulation results indicate that the proposed mechanism can achieve fast and correct merging of network modality, support incremental modality deployment, and greatly reduce the application deployment and service provision threshold of new network systems.

Roadside barriers have proven effective in preventing run-off-road accidents that occurred in mountainous areas. Nonetheless, the influence of variables impacting the severity of injuries resulting from collisions involving distinct types of roadside barriers may diverge. This study delves into the factors that influence the severity of driver’s injuries in crashes encompassing three specific varieties of roadside barriers in mountainous regions, namely, W-beam barriers, flexible barriers, and roadside trees. The evolution of these factors over time is examined through the application of a random parameters logit modeling approach with heterogeneity in means and variances (RPLHMVs). By employing injury-severity data from 2016 to 2019 for the mountainous regions of a city in Southwest China, various potential influencing factors encompassing driver-, vehicle-, road-, and environment-specific characteristics are subjected to statistical analysis. The extent of the impact of identified statistically significant factors on driver’s injury severity is assessed through the computation of pseudoelasticities. The findings reveal distinctions in the outcomes of driver’s injury severity contingent upon the type of roadside barrier encountered during vehicle impacts. To illustrate, collisions involving W-beam barriers are more prone to result in severe injuries. Moreover, the influence of variables determining driver’s injury severity displays noteworthy temporal shifts. Notably, the pseudoelasticities of numerous explanatory variables remain temporally consistent for incidents involving flexible or roadside barriers. In contrast, crashes involving W-beam barriers highlight that solely the speeding indicator demonstrates temporally stable pseudoelasticities. The insights garnered from this investigation offer the potential to contribute to the formulation of fresh guidelines for the design and selection of roadside barriers aimed at mitigating the severity of injuries incurred in crashes within mountainous regions.

Objective Gastrointestinal dysfunction seriously affects the prognosis and quality of life of patients with multiple fractures. However, experimental evidence of this relationship is lacking. Here we describe a newly developed mouse model of postoperative gastrointestinal dysfunction after multiple fractures. Methods Trauma severity was assessed using the injury severity score (ISS). Based on the ISS, a multiple fracture model was established in mice as follows: limb fractures with pelvic fractures and multiple rib fractures; limb fractures with multiple rib fractures; closed fracture of both forelegs with pelvic fracture and rib fractures; closed limb fractures; limb fracture with pelvic fracture; spinal fractures; hind leg fractures with pelvic fractures; pelvic fracture with multiple rib fractures; closed fracture of both fore legs with pelvic fracture; and closed fracture of both fore legs with multiple rib fractures. In each model group, gastrointestinal motility was assayed and the histopathology of the small intestine was examined. Western blot and immunohistochemical analyses of jejunal tissue were performed to detect c‐kit protein expression, the level of which was compared with that of a control group. The results of ANOVA are expressed as mean ± standard deviation. Results In mice with multiple fractures, food intake was greatly reduced, consistent with histopathological evidence of an injured intestinal epithelium. The jejunal tissue of mice in groups a, c, f, and h was characterized by extensively necrotic and exfoliated intestinal mucosal epithelium and inflammatory cell infiltration in the lamina propria. In the gastrointestinal function assay, gastrointestinal motility was significantly reduced in groups a, b, c, f, and g; these group also had a higher ISS (p

Abstract Background With fast rising incidence, papillary thyroid carcinoma (PTC) is the most common head and neck cancer. Parthenolide, isolated from traditional Chinese medicine, inhibits various cancer cells, including PTC cells. The aim was to investigate the lipid profile and lipid changes of PTC cells when treated with parthenolide. Methods Comprehensive lipidomic analysis of parthenolide treated PTC cells was conducted using a UHPLC/Q-TOF–MS platform, and the changed lipid profile and specific altered lipid species were explored. Network pharmacology and molecular docking were performed to show the associations among parthenolide, changed lipid species, and potential target genes. Results With high stability and reproducibility, a total of 34 lipid classes and 1736 lipid species were identified. Lipid class analysis indicated that parthenolide treated PTC cells contained higher levels of fatty acid (FA), cholesterol ester (ChE), simple glc series 3 (CerG3) and lysophosphatidylglycerol (LPG), lower levels of zymosterol (ZyE) and Monogalactosyldiacylglycerol (MGDG) than controlled ones, but with no significant differences. Several specific lipid species were changed significantly in PTC cells treated by parthenolide, including the increasing of phosphatidylcholine (PC) (12:0e/16:0), PC (18:0/20:4), CerG3 (d18:1/24:1), lysophosphatidylethanolamine (LPE) (18:0), phosphatidylinositol (PI) (19:0/20:4), lysophosphatidylcholine (LPC) (28:0), ChE (22:6), and the decreasing of phosphatidylethanolamine (PE) (16:1/17:0), PC (34:1) and PC (16:0p/18:0). Four key targets (PLA2G4A, LCAT, LRAT, and PLA2G2A) were discovered when combining network pharmacology and lipidomics. Among them, PLA2G2A and PLA2G4A were able to bind with parthenolide confirmed by molecular docking. Conclusions The changed lipid profile and several significantly altered lipid species of parthenolide treated PTC cells were observed. These altered lipid species, such as PC (34:1), and PC (16:0p/18:0), may be involved in the antitumor mechanisms of parthenolide. PLA2G2A and PLA2G4A may play key roles when parthenolide treated PTC cells.

Animals use cognitive behavior, by integrating information from multiple senses, to cope with the complex and changing environment. However, it is not yet understood how single sensory cognitive processes get modified and combined by multisensory cognition in these environments. To address this question, we exposed mouse to positive (tactile experience enrichment (TEE)) and negative (chronic restraint stress (CRS)) environments, and then studied how the dependence of their behavior on unimodal sensory (tactile or visual) processing was influenced by different environments. We found that TEE promoted object recognition behavior that depended on vision or tactile participation alone, whereas CRS impaired this dependence of behavior on single sensory channels. These results suggest that a positive environment promotes unimodal cognitive behavior, while the behavioral effect of negative environments is the opposite.

IntroductionSurgical treatment is increasingly the treatment of choice in cancer patients with epidural spinal cord compression and spinal instability. There has also been an evolution in surgical treatment with the advent of minimally invasive surgical (MIS) techniques and separation surgery. This paper aims to investigate the changes in epidemiology, surgical technique, outcomes and complications in the last 17 years in a tertiary referral center in Singapore.MethodsThis is a retrospective study of 383 patients with surgically treated spinal metastases treated between January 2005 to January 2022. Patients were divided into 3 groups, patients treated between 2005 – 2010, 2011-2016, and 2017- 2021. Demographic, oncological, surgical, patient outcome and survival data were collected. Statistical analysis with univariate analysis was performed to compare the groups.ResultsThere was an increase in surgical treatment (87 vs 105 vs 191). Lung, Breast and prostate cancer were the most common tumor types respectively. There was a significant increase in MIS(p

Primary headache is a very common and burdensome functional headache worldwide, which can be classified as migraine, tension-type headache (TTH), trigeminal autonomic cephalalgia (TAC), and other primary headaches. Managing and treating these different categories require distinct approaches, and accurate diagnosis is crucial. Functional magnetic resonance imaging (fMRI) has become a research hotspot to explore primary headache. By examining the interrelationships between activated brain regions and improving temporal and spatial resolution, fMRI can distinguish between primary headaches and their subtypes. Currently the most commonly used is the cortical brain mapping technique, which is based on blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI). This review sheds light on the state-of-the-art advancements in data analysis based on fMRI technology for primary headaches along with their subtypes. It encompasses not only the conventional analysis methodologies employed to unravel pathophysiological mechanisms, but also deep-learning approaches that integrate these techniques with advanced statistical modeling and machine learning. The aim is to highlight cutting-edge fMRI technologies and provide new insights into the diagnosis of primary headaches.

The penis is a vital organ of perception that transmits perceived signals to ejaculation-related centers. The penis consists of the glans penis and penile shaft, which differ considerably in both histology and innervation. This paper aims to investigate whether the glans penis or the penile shaft is the main source of sensory signals from the penis and whether penile hypersensitivity affects the whole organ or only part of it. The thresholds, latencies, and amplitudes of somatosensory evoked potentials (SSEPs) were recorded in 290 individuals with primary premature ejaculation using the glans penis and penile shaft as the sensory areas. The thresholds, latencies, and amplitudes of SSEPs from the glans penis and penile shaft in patients were significantly different (all P < 0.0001). The latency of the glans penis or penile shaft was shorter than average (indicating hypersensitivity) in 141 (48.6%) cases, of which 50 (35.5%) cases were sensitive in both the glans penis and penile shaft, 14 (9.9%) cases were sensitive in the glans penis only, and 77 (54.6%) cases were sensitive in the penile shaft only (P < 0.0001). There are statistical differences in the signals perceived through the glans penis and the penile shaft. Penile hypersensitivity does not necessarily mean that the whole penis is hypersensitive. We classify penile hypersensitivity into three categories, namely, glans penis, penile shaft, and whole-penis hypersensitivity, and we propose the new concept of penile hypersensitive zone.

This paper studies the factors affecting injury severities involving motorcyclists of different age groups (under 25, 25-55, 55 and above) based on the random parameter logit model. Data collected from motorcycle crashes in the UK between 2017 and 2020 are utilized. The motorcyclist injury severity outcomes are categorized as follows: minor injury, severe injury, and fatal injury. The results of the likelihood ratio tests showed that transferability in multi-vehicle motorcycle crash injury severity involving motorcyclists of different age groups. The results of the modeling revealed significant variations in the factors that impact motorcycle crashes among three different age groups, including rider characteristics (such as male riders), motorcycle and non-motorcycle characteristics (such as vehicle running status preceding collision, age of the vehicle, and non-motorcycle vehicle type), roadway and environmental conditions (such as weather condition, speed limit, and road type), temporal-related characteristics (such as day of the week), and crash-related characteristics (such as crash types). The models demonstrate the existence of unobserved heterogeneity for three statistically significant variables, including the truck-involved, rear-end collision, and morning off-peak hours indicator in the under 25 age group crash model, and vehicle straight movement in the 25–55 age group crash model, and passenger car and sideswipe in the 55 and above age group crash model. Further, there are substantial differences in injury severity probabilities involving motorcyclists of different age groups by comparing prediction results based on out-of-sample prediction simulation. This paper emphasized the importance of revealing different age groups’ crash transferability and heterogeneity. The statistically significant differences involving age group crash injury severity models highlight the importance of age-targeted policies for motorcycle safety.

When metro systems need to be temporarily closed due to an unexpected disruption, the metro operators have to arrange shuttle buses as alternative transport for trains, while passengers have to find new routes to complete their journeys. However, the additional shuttle bus lines might be redundant if the well-known phenomenon of the “Braesss Paradox” exists. To address this issue, this paper proposes a bi-level programming model in which the objective of the upper-level model is to minimize the number of shuttle bus lines, while the lower-level model is a UE (User Equilibrium) model that simulates the route choice of passengers. To solve this bi-level programming model, the Overload Arc-oriented Heuristics (OAH) algorithm is developed to find an initial solution, and then we develop a BS (Bi-direction Search) algorithm to obtain the optimal solution to our model. Numerical cases of the partial Beijing Metro network have proved the efficiency and effectiveness of our method, and the result shows that: (1) compared with the standard bus bridging routes, the additional shuttle bus lines can significantly reduce the number of stranded passengers; (2) the number of stranded passengers at each station can be controlled by two strategies: adjust the departure frequency of each shuttle bus line and control the passenger flow at each station.

Abstract Aiming at the efficiency and implementation of in‐network cache in Named Data Network, an in‐network cache method based on the programmable data plane was proposed. Set the cache port on the programmable data plane, when the cache policy determined that the content needs to be cached, set the output port as the cache port and forward it to the cache unit for caching. According to the different requirements of different contents on Quality of Service, the request contents were classified. And the cache probability of classified contents was calculated based on the content popularity and the cache cooperation information between nodes. The cache threshold was dynamically set according to the state of cache space occupancy and compared with the cache probability to determine whether to cache the contents. Experimental results show that the proposed cache placement strategy can effectively improve the cache hit ratio and reduce the average transmission latency compared with the traditional cache placement strategy.

To solve the problem of uncertain end-to-end transmission delay caused by the separation of time-sensitive traffic scheduling and routing in time-sensitive network, a multi-constrained traffic scheduling method with joint routing planning was proposed.The inter-flow conflict degree of time-sensitive traffic was introduced to flexibly allocated traffic routing.On that basis, a scheduling constraint model of time-aware shaping and joint conflict-free routing was established to strictly guarantee the time-sensitive traffic scheduling with bounded low latency in both spatial and temporal dimensions.Experimental results show that the proposed method has good delay performance in different topological scenarios, and effectively reduces the delay caused by congestion conflicts under different time-sensitive traffic scales while ensuring link load balancing.

Pancreatic lipase (PL) is a well-known key target for the prevention and treatment of obesity. Human carboxylesterase 1A (hCES1A) has become an important target for the treatment of hyperlipidaemia. Thus, the discovery of potent dual-target inhibitors based on PL and hCES1A hold great potential for the development of remedies for treating related metabolic diseases. In this study, a series of natural triterpenoids were collected and the inhibitory effects of these triterpenoids on PL and hCES1A were determined using fluorescence-based biochemical assays. It was found that oleanolic acid (OA) and ursolic acid (UA) have the excellent inhibitory effects against PL and hCES1A, and highly selectivity over hCES2A. Subsequently, a number of compounds based on the OA and UA skeletons were synthesised and evaluated. Structure–activity relationship (SAR) analysis of these compounds revealed that the acetyl group at the C-3 site of UA (compound 41) was very essential for both PL and hCES1A inhibition, with IC50 of 0.75 µM and 0.014 µM, respectively. In addition, compound 39 with 2-enol and 3-ketal moiety of OA also has strong inhibitory effects against both PL and hCES1A, with IC50 of 2.13 µM and 0.055 µM, respectively. Furthermore, compound 39 and 41 exhibited good selectivity over other human serine hydrolases including hCES2A, butyrylcholinesterase (BChE) and dipeptidyl peptidase IV (DPP-IV). Inhibitory kinetics and molecular docking studies demonstrated that both compounds 39 and 41 were effective mixed inhibitors of PL, while competitive inhibitors of hCES1A. Further investigations demonstrated that both compounds 39 and 41 could inhibit adipocyte adipogenesis induced by mouse preadipocytes. Collectively, we found two triterpenoid derivatives with strong inhibitory ability on both PL and hCES1A, which can be served as promising lead compounds for the development of more potent dual-target inhibitors targeting on PL and hCES1A.

Poly (ADP-ribose)-polymerases (PARPs) play an essential role in the maintenance of genome integrity, DNA repair, and apoptosis. PARP inhibitors (PARPi) exert antitumor effects via synthetic lethality and PARP trapping. PARPi impact the antitumor immune response by modulating the tumor microenvironment, and their effect has dual properties of promoting and inhibiting the antitumor immune response. PARPi promote M1 macrophage polarization, antigen presentation by dendritic cells, infiltration of B and T cells and their killing capacity and inhibit tumor angiogenesis. PARPi can also inhibit the activation and function of immune cells by upregulating PD-L1. In this review, we summarize the dual immunomodulatory effects and possible underlying mechanisms of PARPi, providing a basis for the design of combination regimens for clinical treatment and the identification of populations who may benefit from these therapies.

As an excellent fluorescent nanomaterial, carbon quantum dots (CQDs) have the properties of small molecular weight, small particle size, high fluorescence stability, no optical flicker, wide excitation spectrum, continuous, long adjustable emission wavelength, good biocompatibility and low toxicity. At present, it has been widely used in biological detection, in vivo and in vitro imaging, drug delivery and diagnostic drugs. This review presents a broad overview of recent progress in synthesis, optical properties, and biomedical applications of CQDs. The synthesis methods of CQDs are first introduced, followed by an extensive discussion of its purification, surface functionalization methods and stability. Furthermore, the optical properties of CQDs are presented, with an emphasis on photoluminescence mechanism and the relationship between synthesis conditions and optical properties. This review's much focus is given to the biomedical applications of CQDs, including detection, imaging (in vivo and in vitro imaging) and drug delivery (targeted therapy, photodynamic and photothermal therapy, and immunological and gene therapy). Finally, we cover the key issues and future prospects/advances that CQDs still have to deal with in the biomedical sector as well as possible solutions.

The focus on female moral education issues allows us to reexamine the contributions of John Dewey, an American educational philosopher. Dewey’s ethics are built upon a rebellion against the universalism and rationalism that were predominant in the traditional ethics based on intrinsic manifestation and external rules. This ethical approach is primarily characterized by Dewey’s pursuit of a democratic society, as well as the emphasis he places on emotional and moral imagination. Dewey’s ethics can be seen as a means to address postmodern problems, integrating the traditional emphasis on “knowledge” with the postmodern focus on “discourse,” based on experience. However, it is worth contemplating whether this solution is effective or if it overly magnifies the power of “understanding” in its ethical system. In the dialogue with postmodern theory, perhaps what is more crucial for the myriad of postmodern issues, exemplified by female morality, is inclusion rather than understanding, as well as questioning knowledge and reconstructing its elements.

How to use nitrogen fertilizer is crucial for farmers in boosting crop yield and fostering sustainable agricultural development. We hypothesized that replacing the nitrogen (N) provided by mineral fertilizer with manure would enhance the soil water storage, increase water use efficiency (WUE), maintain maize yield, and improve economic benefits. We performed the experiment by replacing 0% (CK), 25% (M25), 50% (M50), 75% (M75), and 100% (M100) of mineral N fertilizer (225 kg ha–1) with an equivalent amount of N from manure during 2016–2019. M25 and M50 increased the soil water storage at 0–2 m depth after maize harvest, while M25 significantly decreased the evapotranspiration by 5.27–22.14% compared with CK. The replacement treatments significantly increased maize yield and WUE by 6.58–13.62% and 5.68–18.00%, respectively, during the fourth fertilization year. Meanwhile, the net benefits of the replacement treatments were significantly higher than that of CK in the year of higher precipitation and irrigation water. M75 significantly increased net benefits by 8.47–35.51% compared with CK. M75 had the highest comprehensive evaluation score. Thus, the study proposes a combination of 75% N from manure with 25% N from mineral fertilizer to achieve a high maize yield and benefits.

Abstract Forming of various customized bending parts, small batches, as well as numerous types of materials is a new challenges for Industry 4.0, the current control strategies can not meet the precision and flexibility requirement, expected control strategy of bending processes need to not only resist unknown interferences of process condition and models, but also produce various new parts automatically and efficiently. In this paper, a precision and flexible bending control strategy based on analytical models and data models is proposed to build adaptive bending systems. New analytical prediction models for loading and unloading are established and suitable for various materials, a sequential identification strategy is proposed to search nominal properties using the four sub-optimization models. A data-based feedback model is established to prevent over-bending and eliminate online deviation. Above models are merged into a precision and flexible control strategy. The system firstly uses sub-optimization models to search the nominal point which is near to target point, secondly the system further uses feedback model to eliminate residual error between the nominal point and target point. Compared with four kinds sheet metals, the allowable ranges for variables are determined for a good convergence. The target bending angles were set to 20°, 40°, and 60°. Forty parts were tracked for each kind material, the adaptive bending system converged after one iteration, and exhibited better performances.

It is of great economic significance to optimize the total cost and improve the performance of the supply chain. In this paper, we assume that the market demand is random, and the seller and the buyer share information and make decisions together. We analyze the optimal joint order quantity under probabilistic demand and design the quantity discount model and profit distribution mechanism. Under a certain quantity discount mechanism and profit distribution strategy, both the seller and the buyer can reduce costs. The quantity discount model and profit distribution mechanism designed require supply chain members to share information. In order to protect the privacy of members and improve the willingness of supply chain members to share information, we designed a privacy protection joint ordering policy protocol and privacy protection quantity discount policy based on Secure multiparty computation technology. Then, the joint ordering strategy, the privacy-preserving joint ordering strategy, and quantity discount protocol are numerically simulated. The numerical simulation results show that the privacy-preserving quantity discount coordination mechanism designed by us can reduce the cost of supply chain members to varying degrees and effectively protect the shared information of supply chain members. This work is helpful to the research of cost optimization of the system in complex supply chain systems.

Abstract Background Parthenolide has anti-inflammatory, immunomodulatory and anti-cancer activities. But its effect on thyroid cancer cells is still largely unknown. Methods Label-free quantitative proteomics and bioinformatics analysis were used to investigate the differentially expressed proteins and their functions in thyroid cancer treated with parthenolide and control pair. Hoechst 33258 fluorescent staining and Annexin V-FITC/PI double staining flow cytometry were used to detected BCPAP cells apoptosis. Parallel reaction monitoring (PRM) and quantitative real-time PCR were used to verify the expression of apoptosis-related differential proteins and their mRNA. Results Sixty up-regulated and 96 down-regulated differentially expressed proteins were identified in parthenolide treated thyroid cancer cells BCPAP compared with control thyroid cancer cells. The proteins were mainly relevant to various biological processes that included metabolic processes, response to extracellular stimulus and interaction with host. The molecular functions of most differentially expressed proteins were associated with binding functions and nucleotidyltransferase activity. According to the Kyoto Encyclopedia of Genes and Genomes, the differentially expressed proteins identified are primarily related to various types of metabolic pathways and DNA replication. In cell experiments in vitro, with the increase of the dose of parthenolide, the number of cells gradually decreased, the apoptosis rate gradually increased. PRM verified that the apoptosis-related proteins HMOX1 and GCLM were up-regulated and IL1B was down-regulated in BCPAP cells treated with parthenolide. The mRNA expressions of HMOX1, GCLM, ITGA6 and CASP8 were up-regulated and HSPA1A was down-regulated by PCR. Conclusions Parthenolide may influence the biological behavior of human thyroid cancer cells by affecting the expression of proteins related to cell metabolism and DNA replication. Parthenolide induced significant cellular morphological changes and apoptosis in human thyroid cancer cells, leading to an anti-proliferative effect.

Abstract Background Cryptosporidium andersoni initiates infection by releasing sporozoites from oocysts through excystation. However, the proteins involved in excystation are unknown. Determining the proteins that participate in the excystation of C. andersoni oocysts will increase our understanding of the excystation process. Methods Cryptosporidium andersoni oocysts were collected and purified from the feces of naturally infected adult cows. Tandem mass tags (TMT), coupled with liquid chromatography–tandem mass spectrometry (LC–MS/MS) proteomic analysis, were used to investigate the proteomic expression profiles of C. andersoni oocysts before and after excystation. Results Proteomic analysis identified a total of 1586 proteins, of which 17 were differentially expressed proteins (DEPs) upon excystation. These included 10 upregulated and seven downregulated proteins. The 17 proteins had multiple biological functions associated with control of gene expression at the level of transcription and biosynthetic and metabolic processes. Quantitative real-time RT-PCR of eight selected genes validated the proteomic data. Conclusions This study provides information on the protein composition of C. andersoni oocysts as well as possible excystation factors. The data may be useful in identifying genes for diagnosis, vaccine development, and immunotherapy for Cryptosporidium. Graphical Abstract

When an inaudible sound covert channel (ISCC) attack is launched inside a computer system, sensitive data are converted to inaudible sound waves and then transmitted. The receiver at the other end picks up the sound signal, from which the original sensitive data can be recovered. As a forceful countermeasure against the ISCC attack, strong noise can be used to jam the channel and literally shut down any possible sound data transmission. In this paper, enhanced ISCC whose transmission frequency can be dynamically changed is proposed. Essentially, if the transmitter detects that the covert channel is being jammed, the transmitter and receiver both will switch to another available frequency and re-establish their communications, following the proposed communications protocol. Experimental results show that the proposed enhanced ISCC can remain connected even in the presence of a strong jamming noise source. Correspondingly, a detection method based on frequency scanning is proposed to help to combat such an anti-jamming sound channel. With the proposed countermeasure, the bit error rate (BER) of the data communications over enhanced ISCC soars to more than 48%, essentially shutting down the data transmission, and thus neutralizing the security threat.

IntroductionInvestigating the neuroimaging changes from mild cognitive impairment (MCI) to Alzheimer's disease (AD) is of great significance. However, the details about the distinct functional characteristics of AD and MCI remain unknown.MethodsIn this study, we investigated distinct profiles of functional connectivity density (FCD) differences between AD and MCI compared with the normal population, aiming to depict the progressive brain changes from MCI to AD. As a data-driven method, FCD measures the profiles of FC for the given voxel at different scales. Resting-state functional magnetic resonance imaging (fMRI) images were obtained from patients with AD and MCI and matched healthy controls (HCs). One-way ANCOVA was used to investigate (global, long-range, and local) FCD differences among the three groups followed by post-hoc analysis controlling age, sex, and head motion.ResultsThe three groups exhibited significant global FCD differences in the superior frontal gyrus. The post-hoc results further showed that patients with AD had a significant increase in global FCD values than those with MCI and HCs. Patients with MCI exhibited an increased trend compared with HCs. We further identified brain regions contributing to the observed global FCD differences by conducting seed-based FC analysis. We also identified that the observed global FCD differences were the additive effects of altered FC between the superior frontal gyrus and the posterior default model network.DiscussionThese results depicted the global information communication capability impairment in AD and MCI providing a new insight into the progressive brain changes from MCI to AD.

Abstract Background Macular corneal dystrophy (MCD) is a rare corneal stromal dystrophy with bilateral progressive vision loss. The pathogenic gene of MCD is carbohydrate sulfotransferase 6 (CHST6). Herein, we report a novel missense mutation and a rare exon deletion mutation in the CHST6 gene in a Chinese family with MCD. Methods Genomic DNA was extracted from the peripheral blood, and next generation sequencing was used to analyse the gene sequence. The pathogenic mutations were identified in all affected family members. The proband successively received binocular penetrating keratoplasty (PKP), and the corneas were examined by histopathology and colloidal iron staining to prove the diagnosis. A long-term follow-up was made to observe the changes after PKP. Results Genetic analysis demonstrated hemizygous mutations in the proband, including a novel c.520A>C (p.K174Q) missense mutation and a rarely reported exon 3 deletion mutation, which were co-segregated with the MCD phenotypes in the pedigree. The positive colloidal iron staining confirmed the diagnosis of MCD in the proband. However, the clinical phenotype and pathological manifestation of both eyes were different from each other because of complicated keratitis in the left eye. During the nine years of follow-up, visual acuity was improved significantly, and the cornea was transparent without rejection and postoperative recurrence in both eyes. Conclusions The novel hemizygous mutations were thought to contribute to the loss of CHST6 function, which induced typical clinical and pathological features of MCD. PKP was an effective treatment for MCD.

Elucidating distinct morphological atrophy patterns of Alzheimer’s disease (AD) and its prodromal stage, namely, mild cognitive impairment (MCI) helps to improve early diagnosis and medical intervention of AD. On that account, we aimed to obtain distinct patterns of voxel-wise morphological atrophy and its further perturbation on structural covariance network in AD and MCI compared with healthy controls (HCs). T1-weighted anatomical images of matched AD, MCI, and HCs were included in this study. Gray matter volume was obtained using voxel-based morphometry and compared among three groups. In addition, structural covariance network of identified brain regions exhibiting morphological difference was constructed and compared between pairs of three groups. Thus, patients with AD have a reduced hippocampal volume and an increased rate of atrophy compared with MCI and HCs. MCI exhibited a decreased trend in bilateral hippocampal volume compared with HCs and the accelerated right hippocampal atrophy rate than HCs. In AD, the hippocampus further exhibited increased structural covariance connected to reward related brain regions, including the anterior cingulate cortex, the putamen, the caudate, and the insula compared with HCs. In addition, the patients with AD exhibited increased structural covariance of left hippocampus with the bilateral insula, the inferior frontal gyrus, the superior temporal gyrus, and the cerebellum than MCI. These results reveal distinct patterns of morphological atrophy in AD and MCI, providing new insights into pathology of AD.

Accurate equipment operation trend prediction plays an important role in ensuring the safe operation of equipment and reducing maintenance costs. Therefore, monitoring the equipment vibration and predicting the time series of the vibration trend is one of the effective means to prevent equipment failures. In order to reduce the error of equipment operation trend prediction, this paper proposes a method for equipment operation trend prediction based on a combination of signal decomposition and an Informer prediction model. Aiming at the problem of high noise in vibration signals, which makes it difficult to obtain intrinsic characteristics when directly using raw data for prediction, the original signal is decomposed once using the variational mode decomposition (VMD) algorithm optimized by the improved sparrow search algorithm (ISSA) to obtain the intrinsic mode function (IMF) for different frequencies and calculate the fuzzy entropy. The improved adaptive white noise complete set empirical mode decomposition (ICEEMDAN) is used to decompose the components with the largest fuzzy entropy to obtain a series of intrinsic mode components, fully combining the advantages of the Informer model in processing long time series, and predict equipment operation trend data. Input all subsequences into the Informer model and reconstruct the results to obtain the predicted results. The experimental results indicate that the proposed method can effectively improve the accuracy of equipment operation trend prediction compared to other models.

Purpose: Immune checkpoint and antiangiogenic inhibitors have a potentially synergistic antitumor effect. We aimed to assess the efficacy and safety of immunotherapy in combination with antiangiogenesis therapy with or without chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC).Methods: PubMed, Embase, the Cochrane library, Google Scholar, Ovid, Scopus, and Web of Science were searched for eligible trials. ClinicalTrials.gov and meeting abstracts were also searched for qualified clinical studies. The inclusion criteria were as follows: prospective studies (including single-arm studies) that evaluated efficacy and/or toxicity of immunotherapy combined with antiangiogenic agents (A + I) with or without chemotherapy (A + I + chemo) in patients with advanced or metastatic NSCLC; and primary outcome of each study reported at least one of these endpoints: progression-free survival (PFS), overall survival, objective response rate (ORR), disease control rate (DCR), or adverse events (AEs).Results: Twenty three prospective studies comprising 1,856 patients with advanced NSCLC were included. The pooled ORR, median PFS and estimated overall survival were 39%, 6.8 months [95% confidence interval (CI), 5.53–8.13], and 18.6 months in the overall group. Similar ORR and median PFS with A + I + chemo versus A + I were observed in patients treated in first-line setting [59% and 9.47 months (95% CI, 6.45–12.49) versus 52% and 10.9 months (95% CI, 1.81–19.98), respectively]. We also observed improved ORR and mPFS with A + I + chemo versus A + I in subsequent-line setting [56% and 8.1 months (95% CI, 5.00–11.26) versus 22% and 5.1 months (95% CI, 4.01–6.15), respectively]. Efficacy of A + I + chemo therapy was evident across different PD-L1 subgroups, especially in patients with EGFR mutations [ORR: 59%; mPFS: 8.13 months (95% CI: 5.00–11.26)] or baseline liver metastases. The incidence of AEs with a major grade of ≥3 in the overall, A + I, and A + I + chemo groups were 4.1% vs. 5.5% vs. 3.4% for proteinuria, 13.7% vs. 16.2% vs. 9.7% for hypertension, and 1.9% vs. 1.2% vs. 2.8% for rash, respectively. No new safety signals were identified in this pooled analysis.Conclusion: Immunotherapy combined with antiangiogenic agents with or without chemotherapy showed encouraging antitumor activity and an acceptable toxicity profile in treatment-naïve or pretreated patients with advanced NSCLC. Doublet treatment with immunotherapy and antiangiogenic agents might be a new option for patients with advanced NSCLC, especially those who are treatment-naive or cannot tolerate chemotherapy.

Cancer is one of the most serious diseases threatening human health, so it is particularly important to develop effective tumor-targeting drugs. As the first CDK4/6 inhibitor, palbociclib effectively inhibits tumor proliferation by blocking the cell cycle to the G1 phase. 10-HCPT is a Topo I inhibitor; however, its clinical application has been greatly limited due to its high toxicity. Based on the successful development of double target inhibitors, three novel palbociclib derivatives (HP-1, HP-2, and HP-3) were designed and synthesized from Palbociclib and 10-HCPT, and their biological activities were investigated. At first, the possible binding sites of the three compounds to Topo I and CDK4/6 were predicted by molecular docking. Then, we evaluated the anti-proliferative effects of the three palbociclib derivatives. In general, human lung cancer cells were more sensitive to HP-1, HP-2, and HP-3, especially NCI-H460. In addition, cell cycle arrest and apoptosis induction were investigated by flow cytometry. The three palbociclib derivatives, especially HP-1, had obvious cell cycle arrest phenomenon on NCI-H460 cells and induced apoptosis of NCI-H460 cells significantly. In the end, it was proved that these three drugs had obvious cyclin-dependent kinase inhibitory activities. In short, all the data showed that HP-1, HP-2, and HP-3 could play anti-cancer roles by acting on dual targets and had the characteristics of high efficiencies and low toxicities, which opened up a new idea for the study of palbociclib derivatives.

Parkinson’s disease (PD), the second most common neurodegenerative disease after Alzheimer’s disease, commonly occurs in the elderly population, causing a significant medical and economic burden to the aging society worldwide. At present, there are few effective methods that achieve satisfactory clinical results in the treatment of PD. Platelet-derived growth factors (PDGFs) and platelet-derived growth factor receptors (PDGFRs) are important neurotrophic factors that are expressed in various cell types. Their unique structures allow for specific binding that can effectively regulate vital functions in the nervous system. In this review, we summarized the possible mechanisms by which PDGFs/PDGFRs regulate the occurrence and development of PD by affecting oxidative stress, mitochondrial function, protein folding and aggregation, Ca2+ homeostasis, and cell neuroinflammation. These modes of action mainly depend on the type and distribution of PDGFs in different nerve cells. We also summarized the possible clinical applications and prospects for PDGF in the treatment of PD, especially in genetic treatment. Recent advances have shown that PDGFs have contradictory roles within the central nervous system (CNS). Although they exert neuroprotective effects through multiple pathways, they are also associated with the disruption of the blood–brain barrier (BBB). Our recommendations based on our findings include further investigation of the contradictory neurotrophic and neurotoxic effects of the PDGFs acting on the CNS.

PurposeEpidermal growth factor receptor (EGFR) T790M-negative/unknown advanced non-small cell lung cancer (NSCLC) patients lack subsequent approved targeted therapies. This meta-analysis aimed to assess the efficacy of osimertinib in advanced NSCLC patients with different T790M status after resistance to prior first- or second-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs) and to predict the subgroups that may benefit beside T790M-positive disease.MethodsPubMed, Embase, Web of Science, and Cochrane Library databases were searched for relevant trials. Meeting abstracts were also reviewed to identify appropriate studies. Studies evaluating the efficacy and/or survival outcomes of osimertinib in patients with different T790M status (positive, negative, or unknown) after resistance to prior first- or second-generation EGFR-TKIs were enrolled, and data were pooled to assess hazard ratios (HRs) or relative risk ratios (RRs) in terms of overall survival (OS), progression-free survival (PFS), and objective response rate (ORR).ResultsA total of 1,313 EGFR-mutated NSCLC patients from 10 retrospective and one prospective studies treated with osimertinib after resistance to first- or second-generation EGFR-TKIs were included. In overall groups, T790M-positive patients showed an improved OS (HR=0.574, p=0.015), PFS (HR = 0.476, p = 0.017), and ORR (RR = 2.025, p = 0.000) compared with T790M-negative patients. In the brain metastases subgroup, no significant difference in OS was observed between T790M-positive and T790M-negative patients (HR = 0.75, p = 0.449) or between T790M-positive and T790M-unknown patients (HR = 0.90, p = 0.673). In the plasma genotyping subgroup, PFS was similar between T790M-positive and T790M-negative patients (HR = 1.033, p = 0.959).ConclusionPatients with progressive brain metastases on first- or second-generation EGFR-TKIs can benefit from subsequent osimertinib therapy regardless of T790M status. Patients with plasma T790M-negative status and lack of tissue genotyping should be allowed to receive osimertinib treatment.

Abstract Background In the era of immunotherapy, it is still unclear which is the best first-line therapy for patients with oncogenic driver negative advanced non-squamous non-small cell lung cancer (NS-NSCLC) who cannot tolerate immunotherapy, or subsequent therapy for patients with oncogenic driver positive NS-NSCLC whose disease progressed on prior targeted therapy. To assess the optimal choice of first-line and maintenance treatment regimens, we performed a meta-analysis of prospective randomized controlled clinical trials (RCTs) of patients with NS-NSCLC on bevacizumab combined with chemotherapy. Methods All eligible RCTs comparing pemetrexed-platinum with or without bevacizumab (PP ± B) and paclitaxel-carboplatin with bevacizumab (PC + B) as a first-line therapy, or comparing bevacizumab plus pemetrexed (Pem + B) and bevacizumab alone (B) as a maintenance treatment for advanced NS-NSCLC, were included after systematically searching web databases and meeting abstracts. The main research endpoints were comparisons of overall survival (OS) and progression-free survival (PFS). The other endpoints were objective response rate (ORR), 1-year PFS rate (PFSR1y) and major grade 3/4 treatment-related adverse events. Results Data of 3139 patients from six RCTs were incorporated into analyses. Three RCTs were included in an analysis that compared PP ± B and PC + B as a first-line therapy for advanced NS-NSCLC. Patients treated with first-line PP ± B showed similar OS and ORR, but significantly improved PFS (hazard ratio [HR], 0.88) and PFSR1y (risk ratio [RR], 0.83), as compared to patients treated with PC + B (all P

Abstract Background The outcomes of immediate autologous breast reconstruction (IABR) after partial mastectomy followed by postoperative radiotherapy (RT) in terms of aesthetics, treatment-related complications, and local control are unclear. In this study, we evaluated the efficacy of IABR after partial mastectomy with or without breast RT, and thus the impact of radiation on autologous flap transfer. Method A retrospective cohort study involving consecutive breast cancer patients who underwent IABR after partial mastectomy between July 2011 and December 2017 at Shengjing Hospital was performed. Patients were divided into two groups based on whether or not they received RT after IABR. We compared aesthetic outcomes and changes in the flap size over the three-dimensional coordinates at various timepoints (pre-RT, 1, 6, and 12 months post-RT), as well as postoperative complications, survival, and recurrence rates between the two groups. Results In total, 84 breast cancer patients were enrolled, with 32 patients in the RT group and 52 in the non-RT group. At a median follow-up time of 33.3 months, no significant difference was found in the rate of regional recurrence between the two groups (3.13% vs. 3.85%, P = 1.00), and no local recurrences occurred in either group. At the timepoints pre-RT, 1, and 6 months post-RT (approximately 4, 7, and 12 months after IABR, respectively), 77 (91.7%), 70 (83.3%), and 83 (98.8%) patients, respectively, had achieved very good or good cosmetic outcomes, and only changes in breast skin color at 1 month after RT significantly differed between the RT and non-RT groups, with very good or good cosmetic result rates of 62.5% vs. 96.2%, respectively (P 0.05). Additionally, no grade 3 or greater RT-associated adverse events occurred during or after RT. Conclusion RT following IABR provides aesthetically satisfactory results without intolerable adverse complications and may safely be performed in patients who underwent IABR after partial mastectomy.

In the existing medical knowledge graphs, there are problems concerning inadequate knowledge discovery strategies and the use of single sources of medical data. Therefore, this paper proposed a research method for multi-data-source medical knowledge graphs based on the data, information, knowledge, and wisdom (DIKW) system to address these issues. Firstly, a reliable data source selection strategy was used to assign priorities to the data sources. Secondly, a two-step data fusion strategy was developed to effectively fuse the processed medical data, which is conducive to improving the quality of medical knowledge graphs. The proposed research method is for the design of a multi-data-source medical knowledge graph based on the DIKW system. The method was used to design a set of DIK three-layer knowledge graph architectures according to the DIKW system in line with the medical knowledge discovery strategy, employing a scientific method for expanding and updating knowledge at each level of the knowledge graph. Finally, question and answer experiments were used to compare the two different ways of constructing knowledge graphs, validating the effectiveness of the two-step data fusion strategy and the DIK three-layer knowledge graph.

BackgroundInflammation and immune dysfunction play significant roles in the pathogenesis of Alzheimer's disease (AD)-related dementia. Changes in peripheral blood cell profiles are a common manifestation of inflammation and immune dysfunction and have been reported in patients with AD or mild cognitive impairment (MCI). We systematically evaluated the association of peripheral blood cell counts and indices with AD or MCI through a meta-analysis.MethodsWe electronically searched sources to identify all case–control trials comparing peripheral blood cell counts and/or lymphocyte subsets between patients with AD or MCI and healthy controls (HCs). Meta-analyses were used to estimate the between-group standardized mean difference (SMD) and 95% confidence interval (CI).ResultsA total of 36 studies involving 2,339 AD patients, 608 MCI patients, and 8,352 HCs were included. AD patients had significantly decreased lymphocyte counts (SMD −0.345, 95% CI [−0.545, −0.146], P = 0.001) and significantly increased leukocyte counts (0.140 [0.039, 0.241], P = 0.006), neutrophil counts (0.309 [0.185, 0.434], P = 0.01), and neutrophil–lymphocyte ratio (NLR) (0.644 [0.310, 0.978], P < 0.001) compared to HCs. Similarly, significantly increased leukocyte counts (0.392 [0.206, 0.579], P < 0.001), NLR (0.579 [0.310, 0.847], P < 0.001), and neutrophil counts (0.248 [0.121, 0.376], P < 0.001) were found in MCI patients compared with HCs. A significantly decreased percentage of B lymphocytes (−1.511 [−2.775, −0.248], P = 0.019) and CD8+ T cells (−0.760 [−1.460, −0.061], P = 0.033) and a significantly increased CD4/CD8 ratio (0.615 [0.074, 1.156], P = 0.026) were observed in AD patients compared to HCs. Furthermore, significant changes in hemoglobin level and platelet distribution width were found in patients with AD or MCI compared with HCs. However, no significant difference was found between AD or MCI patients and HCs in terms of platelet counts, mean corpuscular volume, red cell distribution width, mean platelet volume, and CD4+ T, CD3+ T, or natural killer cell counts.ConclusionChanges in peripheral blood cell profiles, particularly involving leukocyte, lymphocyte, neutrophil, and CD8+ T cell counts, as well as the NLR and the CD4/CD8 ratio, are closely associated with AD. The diagnostic relevance of these profiles should be investigated in future.

In this study, three novel jet-stabilized combustor geometries with cavity, vertical ring and vertical pipe are respectively proposed, the combustion and emission characteristics are numerically investigated and compared with the original geometry. The realizable k−ε model and presumed probability density functions (PDF) model are used for turbulent combustion, and the nitrogen oxide (NOx) formation model is used for nitric oxide (NO) emission. The results show that two vortex pairs formed in primary zone under four cases, but for the combustor with vertical ring, a vortex pair also appears downstream of air jet holes. For the combustor with vertical pipe geometry, the right-side vortex pair is the biggest, meanwhile the extrusion effect on the left vortexes is obvious. The high-temperature zone is mainly located in the primary zone and downstream of air jet holes for all cases, while the combustor with vertical ring have the smallest high temperature region, and it with a uniform temperature distribution. The outlet temperature distribution factor is lower than 0.036 for all combustors. Compared with the original combustor, the NO emission of combustors with cavity and vertical ring decrease respectively by 31% and 52%, while the NO emission of combustor with vertical pipe increases by 32%.

Background: The purpose of this study was to examine the dimensional change of IVC during acute hemorrhage through a volume-controlled acute hemorrhagic shock model in swine. Methods: Volume-controlled hemorrhage was performed in 10 adult Bama mini pigs. Enhanced CT scan and hemodynamic monitoring were performed when the cumulative blood loss volume reached 0%, 10%, 20%, 30%, and 40%. The transverse diameter (T) and anteroposterior diameter (AP) of IVC were measured in axial images. Hemodynamic parameters were obtained with Pulse Contour Cardiac Output (PiCCO) hemodynamic monitor device. Arterial blood samples were also collected for artery blood gas analysis at each time point. Results: As the blood loss volume increased, the collapsibility (T/AP) and cross section area (CSA) of IVC significantly changed first in hepatic level and pre-renal level. The significant decrease of the CSA of IVC (shrink) occurred early when the blood loss volume reached only 10%, but the collapse of IVC occurred until the blood loss volume reached 30%. Conclusions: IVC shrank early but collapsed late during the acute hemorrhage in swine. The finding of collapsed IVC on CT scans suggested severe hypovolemic shock. Evaluation of the IVC at the CT scans can be an adjunctive test of the hemodynamic status in trauma patients.

Abstract Background Pancreatic neuroendocrine neoplasms (p-NENs) are a group of highly heterogeneous tumors with distinct clinicopathological features and long-term prognosis. In 2017, in order to better stratify patients into prognostic groups and predicting their outcomes, World Health Organization (WHO) officially updated its grading system for p-NENs which distinguished these neoplasms among Grading 1 (G1) pancreatic neuroendocrine tumors (p-NETs), G2 p-NETs, G3 p-NETs and G3 pancreatic neuroendocrine carcinomas (p-NECs). However, this new grading classification for p-NENs has not yet been rigorously validated. Methods Data of patients who were surgically treated and histopathologically diagnosed as p-NENs at West China Hospital of Sichuan University from January 2002 to December 2018 were retrospectively collected and analyzed according the novel WHO 2017 grading classification. Results We eventually enrolled 480 eligible patients with p-NENs in our present study, in which 150 patients with WHO 2017 G1 p-NETs, 158 with G2 p-NETs, 64 with G3 p-NETs and 108 with G3 p-NECs were identified. The estimated 5-year overall survival for patients with G1 p-NETs, G2 p-NETs, G3 p-NETs and G3 p-NECs was 75.8, 58.4, 35.1 and 11.1%, with a median survival time of 85.3mons, 67.4mons, 51.3mons and 26.8mons, respectively. Patients with G2 p-NETs present notably worse survival than those with G1 p-NETs (P = 0.03). Survival of G3 p-NETs were significantly worse than that of G1 p-NETs or G2 p-NETs (P

Abstract Purpose To assess the efficacy and safety of recombinant human endostatin in combination with radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) in patients with locally advanced non-small cell lung cancer (LA-NSCLC). Methods We searched eligible literature in available databases using combinations of the following search terms: lung cancer, endostatin or endostar, radiotherapy or radiation therapy or chemoradiotherapy. The inclusion criteria were: prospective or retrospective (including single-arm) studies that evaluated the efficacy and safety of endostatin plus radiotherapy (ERT) or concurrent chemoradiotherapy (ECRT) in patients with LA-NSCLC. Primary outcomes included the following: objective response rate (ORR), local control rates (LCR), overall survival (OS), progression-free survival (PFS), and adverse events (AEs). Tests of heterogeneity, sensitivity, and publication bias were performed. Results A total of 271 patients with LA-NSCLC from 7 studies were enrolled, including six prospective trials and one retrospective study. The pooled median PFS was 11.3 months overall, 11.2 months in the ECRT group, and 11.8 months in the ERT group. Pooled median OS and ORR were 18.9 months and 77.2% overall, 18.4 months and 77.5% in the ECRT group, and 19.6 months and 76.1% in the ERT group, respectively. The incidences of major grade ≥ 3 AEs for all patients, subgroups of ECRT and ERT were 10.9% vs 11.9% vs 9.4% for radiation pneumonitis, 11.6% vs 12.2% vs 9.4% for radiation esophagitis, 35.5% vs 43.4% vs 0 for leukopenia, 27.8% vs 40.7% vs 2.1% for neutropenia, and 10.5% vs 12.3% vs 2.1% for anemia. Conclusions Combined endostatin with RT or CCRT is effective and well tolerated in treating LA-NSCLC, and less toxicities occur. Further validation through prospective randomized control trials is required.

Abstract Background Fatty liver is a high incidence of perinatal disease in dairy cows caused by negative energy balance, which seriously threatens the postpartum health and milk production. It has been reported that lysine acetylation plays an important role in substance and energy metabolism. Predictably, most metabolic processes in the liver, as a vital metabolic organ, are subjected to acetylation. Comparative acetylome study were used to quantify the hepatic tissues from the severe fatty liver group and normal group. Combined with bioinformatics analysis, this study provides new insights for the role of acetylation modification in fatty liver disease of dairy cows. Results We identified 1841 differential acetylation sites on 665 proteins. Among of them, 1072 sites on 393 proteins were quantified. Functional enrichment analysis shows that higher acetylated proteins are significantly enriched in energy metabolic pathways, while lower acetylated proteins are significantly enriched in pathways related to immune response, such as drug metabolism and cancer. Among significantly acetylated proteins, many mitochondrial proteins were identified to be interacting with multiple proteins and involving in lipid metabolism. Furthermore, this study identified potential important proteins, such as HADHA, ACAT1, and EHHADH, which may be important regulatory factors through modification of acetylation in the development of fatty liver disease in dairy cows and possible therapeutic targets for NAFLD in human beings. Conclusion This study provided a comprehensive acetylome profile of fatty liver of dairy cows, and revealed important biological pathways associated with protein acetylation occurred in mitochondria, which were involved in the regulation of the pathogenesis of fatty liver disease. Furthermore, potential important proteins, such as HADHA, ACAT1, EHHADH, were predicted to be essential regulators during the pathogenesis of fatty liver disease. The work would contribute to the understanding the pathogenesis of NAFLD, and inspire in the development of new therapeutic strategies for NAFLD.