Search

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China. Most HCC patients have the complication of chronic liver disease and need overall consideration and whole-course management, including diagnosis, treatment and follow-up. To develop a reasonable, long-term, and complete management plan, multiple factors need to be considered, including the patient's general condition, basic liver diseases, tumor stage, tumor biological characteristics, treatment requirements and economic cost. Summary: To better guide the whole-course management of HCC patients, the Chinese Association of Liver Cancer and the Chinese Medical Doctor Association has gathered multidisciplinary experts and scholars in relevant fields to formulate the “Chinese Expert Consensus on The Whole-Course Management of Hepatocellular Carcinoma (2023).” Key Messages: This expert consensus, based on the current clinical evidence and experience, proposes surgical and nonsurgical HCC management pathways and involves 18 recommendations, including perioperative treatment, systematic treatment combined with local treatment, conversion treatment, special population management, symptomatic support treatment, and follow-up management.

Abstract Studies have shown that the cachexia index (CXI) is a useful predictor of cachexia in patients with colorectal cancer. However, the application of the CXI is limited stemming from the intricacy and additional cost of radiographic examinations. This study aimed to develop an easy-to-use and practical CXI based on fat-free mass index (FFMI-CXI) to evaluate the prognostic value of FFMI-CXI in CRC. A total of 656 patients with CRC were enrolled in the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) study. The FFMI-CXI was calculated as [FFMI (kg)/height (m)2 × serum albumin (g/L)]/neutrophil-lymphocyte ratio. The cutoff value for FFMI-CXI was determined through the analysis of ROC curves and Youden’s index for both male and female cohorts. Kaplan–Meier survival curves with log-rank tests were conducted to compare time–event relationships between different groups. Cox proportional hazards regression models incorporating both univariate and multivariate variables were employed to explore the independent prognostic factors associated with OS. Logistic regression analysis was performed to assess the association of the FFMI-CXI with secondary outcomes. The major outcome was 5-year overall survival (OS). Based on the cutoff values, 331 patients had low FFMI-CXI, and 325 patients had high FFMI-CXI. Patients in the low FFMI-CXI subgroup were significantly older and had advanced TNM stage, malnutrition, high systemic inflammation, long hospitalizations, high hospitalization costs, adverse short-term outcomes, and all-cause mortality. Multivariate Cox regression analyses revealed that FFMI-CXI (HR 0.47, 95% CI 0.33–0.66; p

Abstract This study aimed to identify predictive factors for the prognosis of acute-on-chronic liver disease (AoCLD) due to both hepatitis B virus (HBV) and alcohol and to develop prognostic models to improve treatment management. AoCLD patients with HBV and alcohol as etiological factors were selected from two multicenter prospective cohorts (NCT02457637,NCT03641872) and included in separate training and validation cohorts (n = 180 and n = 148). In the training cohort, the CATCH-LIFE A nomogram (based on age, bilirubin, international normalized ratio, serum sodium, and hepatic encephalopathy score) and CATCH-LIFE B nomogram (based on age, bilirubin, international normalized ratio, serum albumin, white blood cell, platelet count, and hepatic encephalopathy score) had discriminatory ability for predicting 28-day (c-indexes of 0.910 and 0.899) and 90-day mortality (c-indexes of 0.878 and 0.887, respectively). The area under the curve values for 28-day and 90-day mortality prediction by the CATCH-LIFE A nomogram were 0.922 (95% CI : 0.874, 0.971) and 0.905 (0.856, 0.956), respectively, while those for the CATCH-LIFE B nomogram were 0.916(0.861,0.972) and 0.915 (0.866,0.964), respectively. Similar performance results were observed in the validation cohort. Optimal cut-off scores for each nomogram could be used for patient stratification in high- and low-risk groups, and the high-risk groups showed shorter survival times than the low-risk groups in both the training and validation cohorts. Two nomograms constructed from the first short-term follow-up data from patients with AoCLD due to combined HBV infection and alcohol exposure showed good predictive performance for 28-day and 90-day mortality and might be used to guide clinical management.

Abstract Aiming at the problem of limited transmission energy of liquid crystal tunable filter (LCTF), a dual-wavelength transmission system with high signal-to-noise ratio (SNR) is proposed in this paper. The proposed transmission factor Qp is the main influence on the number and location of transmission wavelengths as well as the bandwidth of each transmission wavelength for dual-wavelength systems. Dual-wavelength LCTF can improve the effective transmission energy of the system by increasing the number of filtering channels, and the transmission energy can be increased by about 1.8 times and 70% at short and long wavelengths, respectively, which improves the signal-to-noise ratio (SNR) of the system. Moreover, the dual-wavelength LCTF system is even possible to increase the transmission energy by about 7% at a 33% increase in spectral resolution. Therefore, the dual-wavelength LCTF transmission method not only can improve the SNR of target detection with dual-wavelength response features, but also can effectively solve the problem of contradiction between spectral resolution and spectral transmission energy.

Abstract Background The Asian Working Group for Cachexia (AWGC) proposed the first consensus report on diagnostic criteria for cachexia in Asians in 2023. However, the current consensus lacks cohort evidence to validate its effectiveness and practicality. We aimed to explore the value of the AWGC2023 criteria for predicting the prognosis and medical burden of patients with cancer through a retrospective post hoc cross‐sectional analysis of the Investigation on Nutrition Status and its Clinical Outcome of Common Cancers (INSCOC) project in China. Methods Cox regression analyses were performed to assess the independent association between cachexia and long‐term survival. We utilized C‐reactive protein (CRP), neutrophil‐to‐lymphocyte ratio (NLR), inflammatory burden index (IBI), albumin (ALB) and Glasgow prognostic score (GPS) as diagnostic markers for cachexia, designating them as CRP‐based cachexia, NLR‐based cachexia, IBI‐based cachexia, ALB‐based cachexia and GPS‐based cachexia, respectively. Additionally, we diagnosed cachexia using body mass index (BMI) cutoff values of 18.5, 20, 21 and 22 kg/m2, respectively, and subsequently compared their prognostic predictive value through Harrell's concordance index (C‐index). Logistic regression models were used to assess the association between cachexia and medical burden. Results A total of 5426 patients with cancer were enrolled in this study. Cox regression analysis confirmed that cachexia based on the AWGC2023 criteria was an independent predictor of long‐term survival in patients with cancer. Patients with cachexia had significantly poorer long‐term survival than patients without cachexia (66.4% vs. 49.7%, P

Social organizations, which exist outside of governmental and market systems, are vital actors in social governance. Investigating the pathways through which social organizations participate in vaccination and immunization efforts can significantly contribute to the advancement of immunization programs. This paper elaborates on the practical need, theoretical basis, and policy support for social organizations′ involvement in vaccination and immunization activities. It identifies various challenges faced by these organizations, including incomplete collaborative mechanisms, limited societal recognition, and intrinsic organizational shortcomings. Furthermore, the paper explores strategies for enhancing social organizations′ participation in vaccination and immunization work, such as strengthening public education, providing consultation and advice, supporting grassroots immunization efforts, offering psychological assistance, linking social resources, and aiding in quality assurance. Recommendations are proposed with the aim of providing a reference for the efficient involvement of social organizations in vaccination and immunization activities.

Abstract Background Depression affects the oral health of older adults; however, little is known about its impact on oral health among rural older adults in developing countries, which warrants further research. Taking China as an example, there is a large population base of rural older adults suffering from depression, and many rural older people also have long-term oral health problems, which have seriously affected their quality of life in later life. Therefore, this study aimed to explore linear and non-linear associations of depressive symptoms with oral health knowledge, attitudes, and practices among rural older adults in China. Methods From November 2020 to December 2020, 1,902 rural community-dwelling older people aged 60 years and older were investigated, via a cross-sectional survey. The general information, depressive status, oral health knowledge, attitudes, and practices of the participants were obtained through face-to-face structured questionnaires. Among them, the Zung Depression Self-Rating Scale was used to investigate the depressive symptoms of the participants in this survey. The generalized linear model and classification and regression tree model were used, separately. Results Based on linear analysis results, we found that minimal to mild depressive symptoms [regression coefficient (β) = -0.345; 95% confidence interval (CI): -0.582 to -0.109, P = 0.004] and depressive symptoms (β = -1.064; 95% CI: -1.982 to -0.146, P = 0.023) were significantly correlated with oral health knowledge. A negative correlation was observed between minimal to mild depressive symptoms (β = -0.385; 95% CI: -0.600 to -0.170, P

Abstract Chimeric antigen receptor T (CAR-T) cell therapy has greatly improved the prognosis of relapsed and refractory patients with large B-cell lymphoma (LBCL). Early identification and intervention of patients who may respond poorly to CAR-T cell therapy will help to improve the efficacy. Ninety patients from a Chinese cohort who received CAR-T cell therapy and underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scans at the screening stage (median time to infusion 53.5 days, range 27–176 days), 1 month and 3 months after CAR-T cell infusion were analyzed, with RNA-sequencing conducted on 47 patients at the screening stage. Patients with maximum diameter of the largest lesion (Dmax)

Ovarian cancer ranks among the deadliest gynecological malignancies, with high-grade serous adenocarcinoma (HGSA) constituting 75 % of ovarian cancer cases and accounting for 80 %–90 % of ovarian cancer-related fatalities. Accurate prognosis prediction for ovarian HGSA is of critical clinical significance. However, existing prognostic analysis methods exhibit suboptimal performance in identifying prognostically relevant pathological markers, making it challenging, even for experienced pathologists, to forecast the prognosis of ovarian HGSA patients accurately. Deep learning holds promise in enhancing prognostic prediction accuracy. However, a significant challenge in this field arises from the impracticality of directly inputting histopathology whole-slide images with millions to billions of pixels into existing deep learning networks for training and inference. To address this issue, we propose a prognostic analysis network for ovarian cancer based on hierarchical sampling and fine-grained recognition. This network comprises a two-stage hierarchical sampling sub-network, a fine-grained image recognition sub-network, and a prognostic analysis sub-network. We assess the system's performance using a pathological dataset of 450 cases of ovarian HGSA diagnosed and treated at the Pathology Department of the West China Second University Hospital of Sichuan University. Results indicate that: (1) The proposed prognostic analysis network based on two-stage hierarchical sampling sub-network can effectively analyze the histopathology whole-slide image; (2) the use of fine-grained image recognition and the introduction of clinical information can improve the performance of HGSA prognosis analysis method, with an improvement range of 4.77–10.66%; and (3) the proposed method can be used for the model analysis of pathological datasets of HGSA. Moreover, this method can be used to explore effective characteristics from the multi-modal dataset through automatic learning with prediction recall, accuracy, and precision rates of 80.0%, 81.1%, and 81.8%, respectively, underscoring its clinical potential. This study reveals the reliability and effectiveness of the proposed prognosis evaluation method of HGCA. Conclusions can help clinicians precisely evaluate the recurrence risk of patients, take the initiative to master the diagnosis and treatment, and increase the long-term survival rate of patients.

To explore the effect of polycarboxylate superplasticizers on the strength and hydration performance of alkali slag building materials, this study prepared cross-linked polycarboxylate superplasticizers with different ratios of hydrogen peroxide, methyl allyl alcohol polyoxyethylene ether, acrylic acid, polyethylene glycol diacrylate, monomer aqueous solution, reducing agent, chain transfer agent, etc. according to certain ratios, and tested their effects on the hydration performance and strength of alkali slag building materials. Through experimental analysis, it was found that the higher the proportion of cross-linked polycarboxylate based high-efficiency water-reducing agents, the lower the initial flowability of building material slurry; The addition of cross-linked polycarboxylate water-reducing agent will prolong the initial and final setting time of alkali slag building materials, delaying the hydration time of building materials; Cross linked polycarboxylate superplasticizers can reduce the electrical conductivity of alkali slag building material slurry, delaying its hydration rate; Different ratios of water-reducing agents have a significant impact on the water reduction rate of alkali slag building materials, with V2 water-reducing agent having the highest water-reduction rate of 28.6%; Cross linked polycarboxylate superplasticizers can increase the flexural and compressive strength of alkali slag building materials. Therefore, cross-linked polycarboxylate water-reducing agents have shown great potential in regulating the properties of alkali slag building materials.

Background/Aims: As a very common malignancy of the digestive system, the incidence and mortality rates of gastric cancer (GC) are increasing year by year. The critical role of ferroptosis in cancer development has been well-documented. The polyphenol compound curcumin shows prominent anti-tumor effects in multiple cancer types, including GC. However, whether curcumin participates in GC tumorigenesis by regulating ferroptosis remains unknown. Materials and Methods: Gastric cancer cells AGS and HGC-27 were treated with curcumin (0, 10, and 20 μM). Cell viability and death were evaluated through CCK-8 and LDH release assays. LC3B expression in cells was estimated through immunofluorescence staining. Intracellular ferrous iron (Fe2+), GSH, MDA, and lipid ROS levels were assessed by corresponding assay kits. The cellular levels of autophagy markers (ATG5, ATG7, Beclin 1, and LC3B), ferroptosis markers (ACSL4, SLC7A11, and GPX4), and phosphorylated (p)-PI3K, p-AKT, and p-mTOR were determined through western blotting. Results: Curcumin attenuated cell viability but stimulated cell death in GC cells. Curcumin enhanced autophagy in GC cells, as demonstrated by the increased levels of ATG5, ATG7, Beclin 1, and LC3B. Besides, curcumin upregulated iron, MDA, GSH, and ACSL4 levels while downregulated lipid ROS, SLC7A11, and GPX4 levels, suggesting its stimulation on ferroptosis in GC cells. Curcumin decreased p-PI3K, p-AKT, and p-mTOR levels in cells. Importantly, the ferroptosis inhibitor ferrostatin-1 overturned the impacts of curcumin on GC cell viability, death, and ferroptosis. Conclusion: Curcumin suppresses GC development by inducing autophagy-mediated ferroptosis by inactivating the PI3K/AKT/mTOR signaling.

Abstract Background Aging is an inevitable biological process. Accelerated aging renders adults more susceptible to chronic diseases and increases their mortality rates. Previous studies have reported the relationship between lifestyle factors and phenotypic aging. However, the relationship between intrinsic factors, such as reproductive factors, and phenotypic aging remains unclear. Methods This study utilized data from the National Health and Nutrition Examination Survey (NHANES), spanning from 1999 to 2010 and 2015–2018, with 14,736 adult women. Random forest imputation was used to handle missing covariate values in the final cohort. Weighted linear regression was utilized to analyze the relationship between women-specific reproductive factors and PhenoAgeAccel. Considering the potential impact of menopausal status on the results, additional analyses were conducted on premenopausal and postmenopausal participants. Additionally, the Life’s Essential 8 (LE8) was used to investigate the impact of healthy lifestyle and other factors on the relationship between women-specific reproductive factors and PhenoAgeAccel. Stratified analyses were conducted based on significant interaction p-values. Results In the fully adjusted models, delayed menarche and gynecological surgery were associated with increased PhenoAgeAccel, whereas pregnancy history were associated with a decrease. Additionally, early or late ages of menopause, first live birth, and last live birth can all negatively impact PhenoAgeAccel. The relationship between women-specific reproductive factors and PhenoAgeAccel differs between premenopausal and postmenopausal women. High LE8 scores positively impacted the relationship between certain reproductive factors (age at menarche, age at menopause, age at first live birth, and age at last live birth) and phenotypic age acceleration. Stratified analysis showed significant interactions for the following variables: BMI with age at menarche, pregnancy history, and age at menopause; ethnicity with age at menopause, age at first live birth, and parity; smoking status with use of contraceptive pills and gynecologic surgery; hypertension with use of contraceptive pills, pregnancy history, and age at menopause. Conclusion Delayed menarche, gynecological surgery, and early or late ages of menopause, first live birth, and last live birth are associated with accelerated phenotypic aging. High LE8 score may alleviate the adverse effects of reproductive factors on phenotypic aging.

Abstract Background Periodontitis is the sixth-most common disease worldwide. The oral microbiome composition and its association with Periodontal disease (PD) have been largely explored; however, limited studies have explored the microbial profiles of both oral and toothbrushes in patients with PD. Thus, this study aimed to ascertain the oral and toothbrushes microbial composition in high-altitude populations, hypothesizing that their correlation with periodontal health would differ from those at lower altitudes, potentially indicating links between environmental factors, microbial colonization patterns, and periodontal health in distinct geographic contexts. Methods In the present study, we enrolled 35 individuals including 21 healthy and 14 diagnosed with PD from the Lhasa region of Tibet, China. Saliva and toothbrush samples were collected from each participant to assess the association between toothbrush usage and oral microbiome with PD using 16 S rRNA gene-specific V3-V4 regions sequencing. To assess the oral and toothbrush microbiome composition and diversity and its possible link to PD. Results Significantly higher Alpha diversity (Shannon index) was observed between the PD group and PD toothbrushes (p = 0.00021) and between the PD group and Healthy toothbrushes (p = 0.00041). The predominant species were Proteobacteria, Bacteroidota, Firmicutes, Actinobacteria, and Fusobacteria, with genera Pseudomonas, Veillonella, Neisseria, Acinetobacter, and Haemophilus. In addition, PICRUST2 analysis unveiled 44 significant pathways differentiating the disease and healthy groups, along with 29 pathways showing significant differences between their respective toothbrush microbial profiles. The distinct oral and toothbrush microbial composition among high-altitude populations suggests potential adaptations to the challenges of high-altitude environments. Conclusion This study emphasizes the importance of tailored dental care strategies, accounting for altitude and racial factors, to effectively manage periodontal health in these communities. Further research is warranted to investigate the specific microbial mechanisms and develop targeted interventions for optimizing oral health in populations across varying altitudes.

Abstract Dual inhibition of vascular endothelial growth factor and epidermal growth factor receptor (EGFR) signaling pathways offers the prospect of improving the effectiveness of EFGR-targeted therapy. In this phase 3 study (ClinicalTrial.gov: NCT04028778), 315 patients with treatment-naïve, EGFR-mutated, advanced non-small cell lung cancer (NSCLC) were randomized (1:1) to receive anlotinib or placebo plus gefitinib once daily on days 1–14 per a 3-week cycle. At the prespecified final analysis of progression-free survival (PFS), a significant improvement in PFS was observed for the anlotinib arm over the placebo arm (hazards ratio [HR] = 0.64, 95% CI, 0.48–0.80, P = 0.003). Particularly, patients with brain metastasis and those harboring EGFR amplification or high tumor mutation load gained significant more benefits in PFS from gefitinib plus anlotinib. The incidence of grade 3 or higher treatment-emergent adverse events was 49.7% of the patients receiving gefitinib plus anlotinib versus 31.0% of the patients receiving gefitinib plus placebo. Anlotinib plus gefitinib significantly improves PFS in patients with treatment-naïve, EGFR-mutated, advanced NSCLC, with a manageable safety profile.

Abstract Organic molecules with dynamic covalent-bonding characteristics have attracted much attention for their important role in constructing stimulus-responsive smart materials. However, it is difficult to realize sensitive and reversible covalent bond cleavage/formation through external stimuli in the aggregated state of molecules. Herein, a series of 2,3-diphenylmaleonitriles (DPMNs) with photoinduced π-bond cleavage properties have been designed and synthesized to construct the dynamic covalent bond materials. The cis-form 2,3-diphenylmaleonitriles (Z-DPMNs) exhibit significant photochromism in both solid and solution states under ultraviolet light and visible light. The photochromism stems from the photoinduced π-bond splitting of Z-DPMNs, resulting in a transition from the closed-shell to open-shell structure. Moreover, the twisted structure and molecular stacking of Z-DPMNs, the push-pull electron effect of substituents, and the external factors including temperature and solvent polarity have important effects on the dynamic conversion of π-bonds. Based on the sensitive and reversible optical performance transformation, Z-DPMNs can be applied as safety ink in anti-counterfeiting, information encryption and storage systems. This work not only provides an approach for constructing dynamic covalent bonds but also greatly enriches stimulus-responsive materials.

Abstract Our previous research found that fecal microbiota transplantation (FMT) and inulin synergistically affected the intestinal barrier and immune system function in chicks. However, does it promote the early immunity of the poultry gut-associated lymphoid tissue (GALT)? How does it regulate the immunity? We evaluated immune-related indicators in the serum, cecal tonsil, and intestine to determine whether FMT synergistic inulin had a stronger impact on gut health and which gene expression regulation was affected. The results showed that FMT synergistic inulin increased TGF-β secretion and intestinal goblet cell number and MUC2 expression on day 14. Expression of BAFFR, PAX5, CXCL12, and IL-2 on day 7 and expression of CXCR4 and IL-2 on day 14 in the cecal tonsils significantly increased. The transcriptome indicated that CD28 and CTLA4 were important regulatory factors in intestinal immunity. Correlation analysis showed that differential genes were related to the immunity and development of the gut and cecal tonsil. FMT synergistic inulin promoted the development of GALT, which improved the early-stage immunity of the intestine by regulating CD28 and CTLA4. This provided new measures for replacing antibiotic use and reducing the use of therapeutic drugs while laying a technical foundation for achieving anti-antibiotic production of poultry products.

Abstract Electrocatalytic alkynes semi-hydrogenation to produce alkenes with high yield and Faradaic efficiency remains technically challenging because of kinetically favorable hydrogen evolution reaction and over-hydrogenation. Here, we propose a hierarchically nanoporous Cu50Au50 alloy to improve electrocatalytic performance toward semi-hydrogenation of alkynes. Using Operando X-ray absorption spectroscopy and density functional theory calculations, we find that Au modulate the electronic structure of Cu, which could intrinsically inhibit the combination of H* to form H2 and weaken alkene adsorption, thus promoting alkyne semi-hydrogenation and hampering alkene over-hydrogenation. Finite element method simulations and experimental results unveil that hierarchically nanoporous catalysts induce a local microenvironment with abundant K+ cations by enhancing the electric field within the nanopore, accelerating water electrolysis to form more H*, thereby promoting the conversion of alkynes. As a result, the nanoporous Cu50Au50 electrocatalyst achieves highly efficient electrocatalytic semi-hydrogenation of alkynes with 94% conversion, 100% selectivity, and a 92% Faradaic efficiency over wide potential window. This work provides a general guidance of the rational design for high-performance electrocatalytic transfer semi-hydrogenation catalysts.

Abstract The overall health condition of patients significantly affects the diagnosis, treatment, and prognosis of endodontic diseases. A systemic consideration of the patient’s overall health along with oral conditions holds the utmost importance in determining the necessity and feasibility of endodontic therapy, as well as selecting appropriate therapeutic approaches. This expert consensus is a collaborative effort by specialists from endodontics and clinical physicians across the nation based on the current clinical evidence, aiming to provide general guidance on clinical procedures, improve patient safety and enhance clinical outcomes of endodontic therapy in patients with compromised overall health.

The escalating global demand for protein and the imperative to meet sustainable development goals have driven the emergence of biotransformation platforms, with methanotrophs showing significant potential in this field. In this paper, the metabolism, nutritional requirements, cultivation strategies, and bioreactors of methanotrophs are reviewed. Integrating upstream and downstream technologies is also advocated to advance the development of methanotroph biotransformation platforms toward a circular economy model. The advancements in utilizing biogas as a viable carbon source and wastewater as a nitrogen source are discussed, emphasizing the need for detailed quality control and safety assessments to ensure the suitability of single-cell protein as animal feed. In general, by integrating advanced nutrient recovery technologies to define new process routes, methanotroph biotransformation platforms can bring better environmental benefits by reducing carbon emissions and saving resources. Shifting to renewable energy is crucial for achieving environmental sustainability. By using renewable energy to power microbial fermentation, biomass dehydration, and waste recycling, the platform can offset high energy consumption and attain significant market competitiveness with traditional protein sources.

As China advances its green economy, innovative methods are being employed to enhance energy optimization and conservation within energy-intensive industries. Among these methods, microwave heating stands out due to its superior heating efficiency and lack of pollution. Nonetheless, uniform heating remains a challenge because the microwave absorption capacity of the heated medium varies with changes in heating time and temperature. To address this issue, an Adaptive Particle Swarm Optimization (APSO) neural network microwave system based on the Back Propagation Neural Network (BPNN) is proposed. This system leverages the fundamental principles of Particle Swarm Optimization (PSO), categorizing particle swarms into three types and iterating them through distinct processes to achieve optimal results. An APSO controller is designed based on system identification, adjusting the controller parameters according to the error between the real-time system output and the identification model. The feedback error is used as the fitness function in the PSO algorithm, continuously adjusting the weights and thresholds of the neural network. This intelligent control approach optimizes the microwave oven's input power to minimize the error between the actual temperature output and the identified temperature. The APSO controller is designed based on system identification, with the intelligently controlled microwave heating system adjusting its input power to minimize the error between the identified and actual temperature outputs. Unlike traditional Proportional Integral Differential (PID) and BPNN controllers, this approach calculates the output of the identified model and the error of the actual model, feeding this information back to the controller. The feedback error serves as the fitness function in the PSO algorithm, enabling continuous adjustment of the network's weights and thresholds to regulate the microwave equipment's output power, thereby ensuring the output temperature closely follows the preset temperature curve. Experimental results demonstrate that the actual output value of the system closely aligns with the original preset temperature curve, with a root mean square error of only 0.74. This designed identification and control system effectively achieves the desired outcome.

IntroductionClassical Muscovy duck reovirus (C-MDRV) and goose-origin Muscovy duck reovirus (Go-MDRV) infections cause “Liver white-spots disease” in Muscovy duckling and gosling. It is difficult to differentiate the infections caused by C-MDRV and Go-MDRV using conventional serological methods.MethodsSpecific primers were designed and synthesized according to σNS and λA nucleotide sequences of C-MDRV and Go-MDRV, respectively. The PCR amplified products were cloned into the pMD-18-T vector. The recombinant plasmid DNA was used to establish an SYBR Green І based duplex real-time PCR assay for the simultaneous detection and differentiation of C-MDRV and Go-MDRV using high-resolution melting (HRM) analysis. The specificity, sensitivity, and repeatability of the methodology were examined based on the optimization of the reaction system and amplification conditions.ResultsC-MDRV and Go-MDRV were identified by their distinctive melting temperatures with 84.50 ± 0.25°C for C-MDRV and 87.50 ± 0.20°C for Go-MDRV, respectively. The amplifications were specific, and other non-targeted waterfowl viruses employed in this study did not show normalized melting peaks. The intra- and inter-assay coefficients of variations were between 0.05 and 1.83%, demonstrating good repeatability. The detection limits of this assay were 51.4 copies·μl−1 for C-MDRV and 61.8 copies·μl−1 for Go-MDRV, respectively. A total of 45 clinical samples were tested by RT-qPCR, with positive rates of 15.56% for C-MDRV and 22.22% for Go-MDRV, without co-infections.DiscussionThese results suggest that this duplex RT-qPCR method is highly sensitive, specific, and reproducible. The HRM assay established in this study provides a powerful tool for the differential detection and epidemiological investigation of C-MDRV and Go-MDRV.

Random flaps are frequently employed in treating substantial skin abnormalities and in surgical tissue-rebuilding interventions. The random flap technique provides flaps of specific dimensions and contours to fit the surgical incision. However, blood supply deficiency and subsequent ischemia-reperfusion injury can cause severe oxidative stress and apoptosis, eventually leading to distal necrosis, which limits the clinical application of the flap. Quercetin (QUE) is primarily found in the glycoside form in many plant parts, such as stem bark, flowers, leaves, buds, seeds, and fruits. Cellular, animal, and clinical studies have demonstrated the antioxidant, anti-apoptosis, anti-inflammatory, and activation of autophagy properties of QUE. In previous studies, high doses of QUE effectively suppressed the survival of human umbilical vein endothelial cells (HUVECs) stimulated by hydrogen peroxide. However, different concentration gradients of QUE on HUVECs revealed a significant protective effect at a concentration of 10 mM. The protective impact of QUE on HUVECs was evaluated using scratch tests, CCK-8 assays, and EDU assays. Simultaneously, a mouse model of random skin flap was created, and the impact of QUE on skin flap survival was examined by intragastric injection. The QUE group showed a significantly larger survival area of the random flap and higher blood flow intensity compared to the control group. Furthermore, the beneficial effects of QUE were reversed by the autophagy inhibitor 3-MA. Therefore, autophagy plays a significant role in the therapeutic benefits of QUE on flap survival.

BackgroundObesity is as an important risk factor for chronic diseases. Metabolically healthy obesity (MHO) is considered a benign state. The association between metabolic health and obesity categories and cancer risk remains unclear. This study aimed to investigate the relationship between metabolic health status combined with obesity phenotypes and the risk of cancer.MethodsData from 91,834 participants in the Kailuan cohort were analyzed, excluding individuals with a body mass index (BMI) < 18.5 kg/m² and those with a history of cancer. Obesity phenotypes were classified based on BMI and waist circumference (WC) combined with metabolic health status, resulting in six phenotypes. Cox proportional hazard regression models were used to assess the association between metabolic health and obesity phenotypes with cancer risk and all-cause mortality.ResultsThe prevalence of metabolically healthy obesity and metabolically unhealthy obesity defined by BMI was 6.86% and 12.18%, while that defined by WC was 20.79% and 25.76%, respectively. Compared to metabolically healthy participants, individuals with an unhealthy metabolic status had a significantly higher risk of cancer (HR, 1.09; 95% CI, 1.03–1.15; p=0.004). The hazard ratios for cancer were 1.19, 1.23, 1.20, and 1.55 for individuals with one, two, three, and four metabolic disorders, respectively. Among those classified as metabolically unhealthy, both overweight and obesity were associated with a protective effect on cancer risk (HR, 0.88; 95% CI, 0.80–0.96; p=0.006 for overweight; HR, 0.87; 95% CI, 0.78–0.97; p=0.010 for obesity). However, abdominal obesity significantly increased cancer risk in both metabolically healthy and unhealthy participants. In subgroup analysis, simple obesity showed a protective trend against cancer in those with respiratory cancers, while abdominal obesity consistently posed a risk for various cancer types.ConclusionMetabolically unhealthy status and abdominal obesity are risk factors for cancer and all-cause mortality, whereas simple obesity offers protective effects against cancer and all-cause mortality in metabolically unhealthy individuals. These findings suggest that maintaining metabolic health and reducing the metabolic risks associated with abdominal obesity should be key targets for cancer prevention.

Background The model for end-stage liver disease (MELD) score is widely used for the prognostication in end-stage liver disease but has limited performance in acute-on-chronic liver failure (ACLF). In this study, we identified additional predictive parameters and reformed the MELD score to predict ACLF more accurately.Methods A meta-analysis was performed on relevant studies to identify the predictive factors of 28-day/90-day outcomes of ACLF, which were validated in two large prospective cohorts. A prognostic score was developed by incorporating predictive parameters into the MELD score. The model was evaluated with a focus on discrimination and calibration.Results The meta-analysis incorporated 32 cohort studies with a total of 13 939 patients, of which 13 risk factors were identified, and 3 risk factors (age, neutrophil count and hepatic encephalopathy (HE) grade) besides MELD score were validated in 751 patients with ACLF derived from two prospective cohorts. A new model (Chinese Acute-on-Chronic Liver Failure Consortium (CATCH-LIFE)-MELD score) was developed as follows: 0.028×age+0.3×HE grade+0.039×neutrophil count+0.079×MELD score. CATCH-LIFE-MELD score achieved a concordance index of 0.791/0.788 for 28-day/90-day outcomes, which is superior to other traditional scores. Other discrimination indices, including net reclassification improvement, integrated discrimination improvement and probability density function, and calibration including Nagelkerke’s R2 and Brier scores confirmed its superiority. Moreover, the accuracy of CATCH-LIFE-MELD score remained stable. It was highest in patients with or without hepatitis B virus infection, cirrhosis, liver failure or under the Chinese Group on the Study of Severe Hepatitis B (COSSH) criteria or European Association for the Study of the Liver (EASL) criteria. All results were substantiated by an evaluation using an external cohort.Conclusions CATCH-LIFE-MELD score, a modified MELD score exhibited improved accuracy in predicting the short-term prognosis of ACLF than other traditional scores.

Corn gluten meal-corn husk mixes (CCM) are an inexpensive and readily available agricultural by-product. This study explores a novel technique by converting CCM into high-value livestock feed protein sources through fermentation with Aspergillus niger AAX and Lactobacillus fermentum LLS, aiming to sustainably meet future global protein needs. The process of fermentation significantly altered the structural composition of high molecular weight proteins, zein, and dietary fibers. This transformation resulted in a marked elevation in the concentrations of peptides, free amino acids, and polyphenols. The acidic environment produced during fermentation prevented lipid oxidation in CCM, thereby extending its storability. After fermentation, the content of anti-nutritional factors decreased, while its antioxidant capacity increased. In vitro simulated digestion suggested that fermentation improved the digestibility of CCM protein. In vivo animal experiments showed that fermented CCM (FCCM) promoted growth and gut health in chicks. This study provides new insights into the utilization of CCM.

Background: Real-world data on C-MET protein overexpression in non-small cell lung cancer (NSCLC) patients, particularly among the Asian Chinese population, are limited. Objectives: This study aimed to evaluate the clinicomolecular characteristics and prognosis of C-MET overexpression in Chinese NSCLC patients, focusing on those with positive C-MET overexpression (immunohistochemistry (IHC) 3+). Design: A retrospective and observational study. Methods: Data were collected from NSCLC patients diagnosed at the First Affiliated Hospital of Guangzhou Medical University between November 2006 and April 2021. We identified C-MET overexpression using IHC and C-MET overexpression positivity was defined as IHC 3+ with ⩾50% tumor cells. Additionally, patient genotypes were collected for subgroup analysis. Results: Data from 9785 NSCLC patients were collected. C-MET (−) accounted for 5% (503/9785), C-MET (+) for 27% (2654/9785), C-MET (++) for 36% (3464/9785), and C-MET (+++) for 32% (3164/9785). Genetic testing was available for 4326 patients. Wild-type was observed in 37% (1591 cases), with epidermal growth factor receptor ( EGFR ) abnormalities being the most common at 49% (2127 cases). Positive C-MET overexpression correlated significantly with women ( p

The arable land abandonment caused by the large-scale non-agricultural transfer of labour has attracted substantial attention from all walks of life in China. Promoting improvement in human settlement environment can accelerate the construction of infrastructure, ameliorate grassroots organization and enhance management capacities while simultaneously decelerating agricultural production costs. High level of human settlement environment can also attract the labour force to return, stimulate the vitality of rural elements and endogenous powers. Then, can improving rural human settlement environment alleviate the phenomenon of arable land abandonment caused by non-agricultural labour transfer? In order to answer this question, based on the micro-survey data of 1325 households in 5 provinces of China, this paper uses the Tobit model to empirically test the effects of rural human settlement environment and non-agricultural transfer of labour on arable land abandoned. The results revealed that rural human settlement can alleviate the arable land abandonment caused by non-agricultural transfer of labour to a certain extent. In particular, the improvement of rural human settlement environment that mainly based on the infrastructure construction and organizational management level, has significantly alleviated the arable land abandonment caused by the non-agricultural transfer of labour. Heterogeneity analysis disclosed that, compared with mountainous and hilly areas, the improvement of rural human settlement environment had a more obvious mitigation effect on arable land abandonment in plain areas. Promoting infrastructure construction and strengthening organizational management ability were effective ways to alleviate arable land abandonment in plain areas. Farmer households with high place attachment level were more likely to be attracted by the improvement of rural human settlement environment to return to their hometown, so as to make use of arable land resources. Improving infrastructure, strengthening organizational management level, and promoting cultural and community development were the main measures for farmer households with high place attachment level to reduce arable land abandonment. In addition, there were significant differences in arable land abandonment and its driving factors in different regions. In the central and eastern regions or major grain-producing areas, improving human settlement environment had a significant mitigation effect on arable land abandonment. Therefore, improving the rural human settlement environment according to local conditions, promoting the supportive policy will be inclined to mountainous and hilly areas, enhancing the attractiveness of rural areas, encouraging farmers with high place attachment level to return to their hometowns for employment and entrepreneurship, and accelerating the cultivation of new types of agricultural operators, which will help alleviate the arable land abandonment caused by non-agricultural transfer of labour.

ObjectiveDevelop a predictive model utilizing weakly supervised deep learning techniques to accurately forecast major pathological response (MPR) in patients with resectable non-small cell lung cancer (NSCLC) undergoing neoadjuvant chemoimmunotherapy (NICT), by leveraging whole slide images (WSIs).MethodsThis retrospective study examined pre-treatment WSIs from 186 patients with non-small cell lung cancer (NSCLC), using a weakly supervised learning framework. We employed advanced deep learning architectures, including DenseNet121, ResNet50, and Inception V3, to analyze WSIs on both micro (patch) and macro (slide) levels. The training process incorporated innovative data augmentation and normalization techniques to bolster the robustness of the models. We evaluated the performance of these models against traditional clinical predictors and integrated them with a novel pathomics signature, which was developed using multi-instance learning algorithms that facilitate feature aggregation from patch-level probability distributions.ResultsUnivariate and multivariable analyses confirmed histology as a statistically significant prognostic factor for MPR (P-value< 0.05). In patch model evaluations, DenseNet121 led in the validation set with an area under the curve (AUC) of 0.656, surpassing ResNet50 (AUC = 0.626) and Inception V3 (AUC = 0.654), and showed strong generalization in external testing (AUC = 0.611). Further evaluation through visual inspection of patch-level data integration into WSIs revealed XGBoost’s superior class differentiation and generalization, achieving the highest AUCs of 0.998 in training and robust scores of 0.818 in validation and 0.805 in testing. Integrating pathomics features with clinical data into a nomogram yielded AUC of 0.819 in validation and 0.820 in testing, enhancing discriminative accuracy. Gradient-weighted Class Activation Mapping (Grad-CAM) and feature aggregation methods notably boosted the model’s interpretability and feature modeling.ConclusionThe application of weakly supervised deep learning to WSIs offers a powerful tool for predicting MPR in NSCLC patients treated with NICT.

Background: An association between increased aortic root dimensions (ARD) and elevated risk of cardiovascular mortality has been reported in the general population. However, evidence regarding the association between ARD and mortality in patients with acute heart failure (AHF) is limited. Methods: In a nationwide prospective cohort of the China Patient-Centered Evaluative Assessment of Cardiac Events Prospective Heart Failure Study, ARD was measured during diastole using echocardiography and indexed to body mass index (BMI). Cox proportional hazard models were used to validate the association between BMI-indexed ARD and mortality. Additionally, the relationship between BMI-indexed ARD and mortality was presented using restricted cubic spline in all populations, and both sexes. Results: A total of 2125 participants with ARD were included in the final analysis, among of 38.4 % were women, with a median age of 67 years. Over a median follow-up period of 54.4 (interquartile range: 30.1 to 59.7) months, 895 deaths occurred, with 750 attributed to cardiovascular causes and 145 to non-cardiovascular causes. Compared to the highest tertile group of BMI-indexed ARD, the lowest tertile group had a lower risk of cardiovascular mortality (hazard ratio [HR], 0.71; 95 % confidence interval [CI], 0.58 to 0.87; P

Abstract While smoking is widely acknowledged as a risk factor for rheumatoid arthritis (RA), the connection between secondhand smoke (SHS) exposure and RA in never-smoking adults remains limited and inconsistent. This study aims to explore and quantify this association using serum cotinine levels. We conducted a cross-sectional study with 14,940 adults who self-report as never smokers, using National Health and Nutrition Examination Survey data from 1999 to 2018. Based on previous literature, SHS exposure was categorized into four groups according to serum cotinine levels. Compared to individuals in the unexposed group (serum cotinine

Abstract Background Breast cancer is the most common malignancy in women worldwide. The relationship between remnant cholesterol (RC) and the prognosis of patients with breast cancer has not been clearly reported. This study investigated the prognostic value of RC in predicting mortality in patients with breast cancer. Methods This study prospectively analysed 709 women patients with breast cancer from the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) project. Restricted cubic splines were used to analyse the dose-response relationship between RC and breast cancer mortality. The Kaplan–Meier method was used to evaluate the overall survival of patients with breast cancer. A Cox regression analyses was performed to assess the independent association between RC and breast cancer mortality. Inverse probability of treatment weighting (IPTW) using the propensity score was used to reduce confounding. Sensitivity analysis was performed after excluding patients with underlying diseases and survival times shorter than one year. Results A linear dose-response relationship was identified between RC and the risk of all-cause mortality in patients with breast cancer (p = 0.036). Kaplan–Meier survival analysis and log-rank test showed that patients with high RC levels had poorer survival than those with low RC levels (p = 0.007). Univariate and multivariate Cox regression analyses showed that RC was an independent risk factor for mortality in women patients with breast cancer. IPTW-adjusted analyses and sensitivity analyses showed that CR remained a prognostic factor. Conclusions RC is an independent risk factor for the prognosis of patients with breast cancer, and patients with higher RC levels have poorer survival.

Abstract Background Lenvatinib is widely used in treatment of unresectable hepatocellular carcinoma (uHCC), but the benefit of its combination with immunotherapy needs to be verified. This study evaluated the efficacy and safety of tislelizumab plus lenvatinib in systemic treatment-naïve patients with uHCC. Methods In this multicenter, single-arm, phase 2 study, systemic treatment-naïve patients with uHCC received tislelizumab 200 mg every three weeks plus lenvatinib (bodyweight ≥ 60 kg: 12 mg; 6 responders were needed in stage 1 (n = 30) to continue the study, and ≥ 18 responders were needed by the end of stage 2 (n = 60) to demonstrate statistical superiority to a historical control of lenvatinib monotherapy. Results Sixty-four patients were enrolled. No DLTs were reported. The study achieved statistical superiority (p = 0.0003) with 23 responders assessed by IRC per RECIST v1.1 in the first 60 patients of the efficacy evaluable analysis set (n = 62). After a median follow-up of 15.7 months, confirmed ORR and disease control rate were 38.7% (24/62, 95% confidence interval [CI], 26.6–51.9) and 90.3% (56/62, 95% CI, 80.1–96.4), respectively. Median progression-free survival was 8.2 months (95% CI, 6.8–not evaluable). Overall survival rate at 12 months was 88.6% (95% CI, 77.7–94.4). Grade ≥ 3 treatment-related adverse events occurred in 18 (28.1%) patients. Conclusions Tislelizumab plus lenvatinib demonstrated promising antitumor activity with favourable tolerability as first-line therapy for patients with uHCC. Trial registration ClinicalTrials.gov (NCT 04401800).

Abstract With the continuous development of wireless communication and artificial intelligence technology, Internet of Things (IoT) technology has made great progress. Deep learning methods are currently used in IoT technology, but deep neural networks (DNNs) are notoriously susceptible to adversarial examples, and subtle pixel changes to images can result in incorrect recognition results from DNNs. In the real‐world application, the patches generated by the recent physical attack methods are larger or less realistic and easily detectable. To address this problem, a Generative Adversarial Network based on Visual attention model and Style transfer network (GAN‐VS) is proposed, which reduces the patch area and makes the patch more natural and less noticeable. A visual attention model combined with generative adversarial network is introduced to detect the critical regions of image recognition, and only generate patches within the critical regions to reduce patch area and improve attack efficiency. For any type of seed patch, an adversarial patch can be generated with a high degree of stylistic and content similarity to the attacked image by generative adversarial network and style transfer network. Experimental evaluation shows that the proposed GAN‐VS has good camouflage and outperforms state‐of‐the‐art adversarial patch attack methods.

Abstract Chemical cleaning and disinfection are crucial steps for eliminating infection in root canal treatment. However, irrigant selection or irrigation procedures are far from clear. The vapor lock effect in the apical region has yet to be solved, impeding irrigation efficacy and resulting in residual infections and compromised treatment outcomes. Additionally, ambiguous clinical indications for root canal medication and non-standardized dressing protocols must be clarified. Inappropriate intracanal medication may present side effects and jeopardize the therapeutic outcomes. Indeed, clinicians have been aware of these concerns for years. Based on the current evidence of studies, this article reviews the properties of various irrigants and intracanal medicaments and elucidates their effectiveness and interactions. The evolution of different kinetic irrigation methods, their effects, limitations, the paradigm shift, current indications, and effective operational procedures regarding intracanal medication are also discussed. This expert consensus aims to establish the clinical operation guidelines for root canal irrigation and a position statement on intracanal medication, thus facilitating a better understanding of infection control, standardizing clinical practice, and ultimately improving the success of endodontic therapy.

Study region: The watersheds of the four flux sites in the United States were selected as the study areas for this research. Study focus: This study validates the efficiency of Convolutional Long Short-Term Memory Network (ConvLSTM) models for site-scale ETa prediction. We enhanced the ConvLSTM model by adding a Spatial Pyramid Pooling module (SPPM) and a Multi-head Self-Attention Module (MSA-Module), creating the Multi-head Self-Attention ConvLSTM (MSA-ConvLSTM) model, which we applied to predicting regional-scale actual evapotranspiration (ETa). This study aims to investigate whether the MSA-ConvLSTM model can enhance the accuracy of predicting regional-scale ETa, considering multiple feature variables. Furthermore, we evaluated different performance indicators, discussed possible reasons for errors in regional ETa prediction, and conducted sensitivity analysis of the model characteristics. New hydrological insights for the region: The MSA-ConvLSTM model accurately predicts the future state of ETa. The average R2 was 0.81, which is 11.6 % and 5.5 % higher than those of the ConvLSTM and Self-Attention ConvLSTM (SA-ConvLSTM) models, respectively. The average RMSE is 11.94 mm/m, which is 21.5 % and 13.7 % lower than ConvLSTM and SA-ConvLSTM, respectively. The average MAE is 9.46 mm/m, which is 21.3 % and 13 % lower than ConvLSTM and SA-ConvLSTM, respectively. Incorporating of a multi-head self-attention module enhances the model’s capacity for comprehensive understanding of input data features. This improvement allows the model to better adapt to feature relationships at varying scales and angles, enhancing its representational capacity and enabling effective adaptation to complex environmental changes.

Interactions between International Organisations (IOs) within a regime complex often manifest themselves through competition and cooperation. Current research has examined the factors that promote inter-organisational competition and cooperation, yet the precise timing of when such competition or cooperation commences remains unclear. This paper focuses on two pivotal IOs in global health governance, the World Health Organization (WHO) and the World Bank, to explore the timing and onset of competition and cooperation within a regime complex, as well as the driving factors in the evolution of their inter-organisational relationships. By looking into the interactions between the WHO and the World Bank in norm-setting and resource mobilising, the paper sheds light on how their relationships have transitioned from competitors to cooperators. It systematically presents the mechanisms and processes of policy transformation in inter-organisational interactions. As a new agenda arises, IOs within a regime complex often compete for dominance, with ideational differences driving them to propose and implement distinct governance strategies. They will compete for resources and mainstream of their strategy. The negative spillover effects of competitive policies consequently undermine the effectiveness of IOs’ policy, thereby undercut their legitimacy. To surmount these challenges, the international community should promote inter-institutional coordination in global governance.

Accurately quantifying terrestrial gross primary productivity (GPP) can provide insights into the dynamics of global ecosystems. Light Use Efficiency (LUE) models with simple and effective structures have been widely used to estimate GPP. However, GPP estimation using LUE models was biased due to inaccurately representing the nonlinear effect of solar radiation on photosynthesis. To address this issue, we developed a hybrid LUE model, termed LUE-MLP, which integrates a multilayer perceptron (MLP) neural network simulating the relationship between GPP and solar radiation with a big-leaf LUE model. LUE-MLP was optimized and tested for GPP simulation on data from 166 flux sites from the FLUXNET2015 dataset, which covers 10 biome types. Results show that LUE-MLP exhibited a reliable performance (R2 = 0.76 and RMSE = 4.17 μmol m−2 s−1) in estimating (half-)hourly GPP on test data. Compared to the original big-leaf and two-leaf LUE models, LUE-MLP's R² (RMSE) for (half-)hourly GPP simulation across biomes rose (fell) by – 0.01-0.13 (−7.6%−16.8%) and 0.01-0.15 (0.39%−29.1%), respectively. Additionally, LUE-MLP well captured the seasonal variations in tower-based GPP. The proposed model can improve GPP estimation on a global scale, enhancing our understanding of global ecosystem dynamics.

Objective To determine the efficacy and safety of Astragalus combined with renin-angiotensin-aldosterone system (RAAS) blockers in treating stage III diabetic nephropathy (DN) by meta-analysis.Methods PubMed, Embase, Cochrane Library, Wiley, and Web of Science databases were searched for articles published between August 2007 and August 2022. Clinical studies on Astragalus combined with RAAS blockers for the treatment of stage III DN were included. Meta-analysis was performed by RevMan 5.1 and Stata 14.3 software.Results A total of 32 papers were included in this meta-analysis, containing 2462 patients from randomized controlled trials, with 1244 receiving the combination treatment and 1218 solely receiving RAAS blockers. Astragalus combined with RAAS blockers yielded a significantly higher total effective rate (TER) (mean difference [MD] 3.63, 95% confidence interval [CI] 2.59–5.09) and significantly reduced urinary protein excretion rate (UPER), serum creatinine (Scr), blood urine nitrogen (BUN) and glycosylated hemoglobin (HbAlc) levels. In subgroup analysis, combining astragalus and angiotensin receptor blocker significantly lowered fasting plasma glucose (FPG) and 24 h urinary protein (24hUTP) levels, compared with the combined astragalus and angiotensin-converting enzyme inhibitor treatment. Meanwhile, the latter significantly decreased the urinary microprotein (β2-MG). Importantly, the sensitivity analysis confirmed the study’s stability, and publication bias was not detected for UPER, BUN, HbAlc, FPG, or β2-MG. However, the TER, SCr, and 24hUTP results suggested possible publication bias.Conclusions The astragalus-RAAS blocker combination treatment is safe and improves outcomes; however, rigorous randomized, large-scale, multi-center, double-blind trials are needed to evaluate its efficacy and safety in stage III DN.

Introduction Non-attendance with scheduled postoperative follow-up visits remains a common issue in orthopaedic clinical research. The objective of this study was to identify the risk factors associated with loss to follow-up among elderly patients with hip-fracture postoperatively. Methods A retrospective analysis of 1-year post-surgery was performed on patients aged over 60 years who underwent hip-fracture surgery from January 2017 to March 2019. Based on their completion of the appointed follow-up schedule, the patients were classified into 2 groups: the Loss to Follow-up (LTFU) Group and the Follow-up (FU) Group. Clinical outcomes were evaluated by Functional Recovery Score (FRS) questionnaires. Telephone interviews were conducted with patients lost to follow-up to determine the reasons for non-attendance. A comparative analysis of baseline characteristics between the 2 groups was implemented, with further exploration of statistical differences through logistic regression. Results A total of 992 patients met the inclusion criteria were included in this study, of which 189 patients, accounting for 19.1%, were lost to follow-up 1 year postoperatively. The mean age of the patients in the LTFU Group was 82.0 years, significantly higher than the 76.0 years observed in the FU Group ( P < 0.001). The FRS for the LTFU Group was marginally higher than that of the FU group (84.0 vs 81.0), with no significant difference ( P = 0.060). Logistic regression analysis identified several significant predictors of noncompliance, including advanced age at surgery, femoral neck fracture, hip arthroplasty, long distance from residence to hospital, and the reliance on urban-rural public transportation for reaching the hospital. Conclusion Postoperative follow-up loss was prevalent among elderly patients with hip fractures. Our study indicated a constellation of risk factors contributing to noncompliance, including advanced age, transportation difficulties, long travel distance, femoral neck fracture and hip arthroplasty surgery.

Background Immune escape is an important feature of hepatocellular carcinoma (HCC). The overall response rate of immune checkpoint inhibitors (ICIs) in HCC is still limited. Revealing the immune regulation mechanisms and finding new immune targets are expected to further improve the efficacy of immunotherapy. Our study aims to use CRISPR screening mice models to identify potential targets that play a critical role in HCC immune evasion and further explore their value in improving immunotherapy.Methods We performed CRISPR screening in two mice models with different immune backgrounds (C57BL/6 and NPG mice) and identified the immunosuppressive gene Gsk3a as a candidate for further investigation. Flow cytometry was used to analyze the impact of Gsk3a on immune cell infiltration and T-cell function. RNA sequencing was used to identify the changes in neutrophil gene expression induced by Gsk3a and alterations in downstream molecules. The therapeutic value of the combination of Gsk3a inhibitors and anti-programmed cell death protein-1 (PD-1) antibody was also explored.Results Gsk3a, as an immune inhibitory target, significantly promoted tumor growth in immunocompetent mice rather than immune-deficient mice. Gsk3a inhibited cytotoxic T lymphocytes (CTLs) function by inducing neutrophil chemotaxis. Gsk3a promoted self-chemotaxis of neutrophil expression profiles and neutrophil extracellular traps (NETs) formation to block T-cell activity through leucine-rich α-2-glycoprotein 1 (LRG1). A significant synergistic effect was observed when Gsk3a inhibitor was in combination with anti-PD-1 antibody.Conclusions We identified a potential HCC immune evasion target, Gsk3a, through CRISPR screening. Gsk3a induces neutrophil recruitment and NETs formation through the intermediate molecule LRG1, leading to the inhibition of CTLs function. Targeting Gsk3a can enhance CTLs function and improve the efficacy of ICIs.

Severe fever with thrombocytopenia syndrome (SFTS) is a recently identified infectious ailment triggered by a new strain of bunyavirus. It is distinguished by elevated fatality rates, ranging from 12 % to 30 %. The mechanism underlying the development of severe illness caused by SFTS bunyavirus (SFTSV) is not yet fully understood. To evaluate the role of the TLR2 receptor pathway in regulating Treg function in the progression of SFTS disease and possible mechanisms, sequential serum samples from 29 patients with SFTS (15 mild, 14 severe cases) were examined. Flow cytometry was employed to scrutinize the phenotypic and functional characteristics of TLR2 expression on circulating CD4 T cells, CD8 T cells, and Tregs. In all admitted patients, the evaluation of correlations between the frequencies of the aforementioned cells and SFTS index (SFTSI) was conducted. For SFTS, the levels of TLR2 on CD4 T cells and Tregs were significantly heightened when compared to those in healthy subjects. Additionally, the expression of TLR2 on Tregs exhibited a positive correlation with Ki-67 expression in Tregs and the severity of disease. Additionally, compared with those in uninfected controls, the expression levels of NF-κB in Tregs were significantly increased. Collectively, Tregs may be activated and proliferate through the stimulation of the TLR2/NF-кB pathway in reaction to SFTSV infection.

Understanding the impact-induced ignition properties and energy release behavior of polymer-bonded explosives (PBXs) is critical for the safety of explosive systems. In this study, a new impact test component was designed using a light gas gun to quantify the ignition mechanism and chemical reaction of micro-damaged PBXs under different inertial loading conditions. A constitutive model was developed to describe the mechanical-thermal-chemical response of the PBXs. This model was employed to further investigate the correlation between microcracks, debonding, hot spots, and chemical reactions. The results show that the stress state of the material is not uniformly distributed due to the micro-inhomogeneities and structural defects of PBXs. The shear friction of the microcracks contributes to localized hot spots, thereby inducing ignition. The critical loading condition for ignition is the length of the steel pillar is 32 mm. The damage and hotspot temperatures of the anterior lateral and posterior lateral regions are greater than those of other locations. The ignition response is accentuated with longer steel pillars, resulting in a more violent release of energy.

Asthma is a heterogeneous airway inflammatory disease that can be classified according to the inflammatory phenotype. The pathogenesis, clinical features, response to hormone therapy, and prognosis of different inflammatory phenotypes differ significantly. This condition also refers to age-related chronic ailments. Here, we intend to identify the function of aging-related genes in different inflammatory phenotypes of asthma using bioinformatic analyses. Initially, the research adopted the GSEA analysis to understand the fundamental mechanisms that govern different inflammatory phenotypes of asthma pathogenesis and use the CIBERSORT algorithm to assess the immune cell composition. The differentially expressed genes (DEGs) of eosinophilic asthma (EA), neutrophilic asthma (NA), and paucigranulocytic asthma (PGA) were identified through the limma R package. Aging-related genes, screened from multiple databases, were intersected with DEGs of asthma to obtain the asthma-aging-related DEGs. Then, the GO and KEGG pathway enrichment analyses showed that the NA- and EA-aging-related DEGs are involved in the various cytokine-mediated signaling pathways. PPI network and correlation analysis were performed to identify and evaluate the correlation of the hub genes. Further, the clinical characteristics of asthma-aging-related DEGs were explored through ROC analysis. 3 and 12 aging-related DEGs in EA and NA patients show high diagnostic accuracy, respectively (AUC >0.7). This study provided valuable insights into aging-related gene therapy for phenotype-specific asthma. Moreover, the study suggests that effective interventions against asthma may operate by disrupting the detrimental cycle of “aging induces metabolic diseases, which exacerbate aging''.

Hexavalent chromium [Cr(VI)] exists widely in occupational environments. The mechanistic target of rapamycin (mTOR) has been well-documented to regulate autophagy negatively. However, we found that low concentration of Cr(VI) (0.2 μM) elevated both mTOR and autophagy and promote cell survival. Conversely, high concentration of Cr(VI) (6 μM) caused cell death by inhibiting mTOR and subsequently inducing autophagy. Tunicamycin (Tm), as an Endoplasmic reticulum (ER) stress activator was used to induce mild ER stress at 0.1 μg/ml and it activated both autophagy and mTOR, which also caused cell migration in a similar manner to that observed with low concentration of Cr(VI). Severe ER stress caused by Tm (2 μg/ml) decreased mTOR, increased autophagy and then inhibited cell migration, which was the same as 6 μM Cr(VI) treatment, although Cr(VI) in high concentration inhibited ER stress. Activating transcription factor 4 (ATF4), a downstream target of ER stress, only increased under mild ER stress but decreased under severe ER stress and 6 μM Cr(VI) treatment. Chromatin immunoprecipitation (ChIP) experiment indicated that ATF4 could bind to the promoter of ATG4B and AKT1. To sum up, our data revealed that mild ER stress induced by low concentration of Cr(VI) could enhance transcriptional regulation of ATG4B and AKT1 by ATF4, which induced both autophagy and mTOR to promote cell viability.

ABSTRACT: The late stage of embryo development is a crucial period of metabolic changes, with rapid organ development requiring a substantial supply of nutrients. During this phase, maternal nutritional levels play a vital role in the growth, development, and metabolism of the offspring. In this study, we added 2 doses of β-carotene (βc) (120 mg/kg and 240 mg/kg) to the daily diet of Hailan Brown laying hens to investigate the impact of maternal nutritional enrichment on embryo development. Maternal nutrition supplementation significantly increased the expression of chicken embryo liver index, growth hormone (GH), insulin-like growth factor-1 (IGF-1), and hepatocyte growth factor (HGF) in serum. At the same time, the expression of GH/growth hormone receptor (GHR), IGF-1 mRNA, and Proliferating Cell Nuclear Antigen (PCNA) protein in the liver was upregulated, indicating that maternal nutrition intervention may promote chicken embryo liver development through the GH-IGF-1 axis. Transcriptome sequencing results showed that differential genes in liver after maternal nutritional supplementation with β-carotene were enriched in pathways related to cell proliferation and metabolism. Consequently, we postulated that maternal β-carotene supplementation might operate via the GH-IGF-1 axis to regulate the expression of genes involved in growth and development, thereby promoting liver development. These results contribute to formulating more effective poultry feeding strategies to promote offspring growth and development.

ObjectiveTo investigate the feasibility of leg wound closure and reconstruction of maxillofacial soft defect by a fusiform-designed skin paddle in fibula free flap (FFF).MethodsFifty patients who underwent FFF for reconstruction of maxillofacial soft defect were divided into two groups. The fusiform group (20 patients) was treated using a fusiform-designed skin paddle in FFF (skin paddle width less than 2 cm), and leg wound was closed using primary suturing. Reconstruction of the maxillofacial soft defect or filling of dead space was achieved by folding the fusiform skin paddle. The conventional group (30 patients) was treated using the conventional-designed skin paddle (skin paddle width no less than 2.5 cm). The leg wound was closed using mattress suturing or skin graft, while reconstruction of the maxillofacial soft defect or filling of dead space by conventional way. The average postoperative length of hospital stay, healing time of leg wound, and post-surgical complications were recorded at least 6 months after the surgery.ResultsCompared with traditional method, the fusiform-designed skin paddle reduced the average healing time of the leg wound (fusiform group: 11.05 days, conventional group: 14.77 days, P < 0.05). The average length-to-width ratio in fusiform group was significantly greater than that of in conventional group (fusiform group: 5.85, conventional group: 2.93, P < 0.05), and no difference was observed on the graft size of skin paddle between two groups (fusiform group: 23.13, conventional group: 27.13, P > 0.05). The post-surgical early complications of the leg wound in the conventional group were higher than that of in the fusiform group (fusiform group: 0%, conventional group: 6.67%), while the post-surgical late complication of the donor site between the two groups showed no case. Healing disorders of maxillofacial soft reconstruction in the conventional group were higher than that of in the fusiform group (fusiform group: 5.26%, conventional group: 20.69%).ConclusionsFusiform-designed skin paddle for closure of the leg wound and maxillofacial soft defect is a feasible alternative to the conventional- designed skin paddle. The fusiform- designed skin paddle resulted in the less postoperative length of hospital stay, shorter healing time of leg wound and less complication.

Abstract Intrahepatic cholangiocarcinoma (iCCA) is a highly lethal biliary epithelial cancer in the liver. Here, Laminin subunit gamma‐2 (LAMC2) with important oncogenic roles in iCCA is discovered. In a total of 231 cholangiocarcinoma patients (82% of iCCA patients) across four independent cohorts, LAMC2 is significantly more abundant in iCCA tumor tissue compared to normal bile duct and non‐tumor liver. Among 26.3% of iCCA patients, LAMC2 gene is amplified, contributing to its over‐expression. Functionally, silencing LAMC2 significantly blocks tumor formation in orthotopic iCCA mouse models. Mechanistically, it promotes EGFR protein translation via interacting with nascent unglycosylated EGFR in the endoplasmic reticulum (ER), resulting in activated EGFR signaling. LAMC2‐mediated EGFR translation also depends on its interaction with the ER chaperone BiP via their C‐terminus. Together LAMC2 and BiP generate a binding “pocket” of nascent EGFR and facilitate EGFR translation. Consistently, LAMC2‐high iCCA patients have poor prognosis in two iCCA cohorts. LAMC2‐high iCCA cells are highly sensitive to EGFR tyrosine kinase inhibitors (TKIs) treatment both in vitro and in vivo. Together, these data demonstrate LAMC2 as an oncogenic player in iCCA by promoting EGFR translation and an indicator to identify iCCA patients who may benefit from available EGFR‐targeted TKIs therapies.

Background: collagen type I is a fundamental composition of extracellular matrix. Typically it exists in the form of a heterotrimer, consisting of two α1 chains encoded by COL1A1 and one α2 chain encoded by COL1A2. However, in cancer a homotrimeric form of collagen type I comprises three α1 chains encoded by COL1A1 was founded. There is still a lack of transcriptional and histologic methods for detecting homotrimeric collagen type I. Furthermore, a comprehensive analysis of the pan-cancer distribution pattern and clinical relevance of homotrimeric collagen type I is conspicuously absent. Method: Using transcriptional and immunoflourance method, we established homocol signature, which is able to transcriptionally and histologically detect homotrimeric collagen type I. We investigated the diagnostic and prognostic potential of homocol as a novel cancer biomarker in a pan-cancer cohort. Furthermore, we assessed its association with clinical manifestations in a liver cancer cohort undergoing treatment at our institute. Result: Homotrimer Collagen Type I is predominantly expressed by cancer cells and is linked to several critical cancer hallmarks, particularly inflammatory response and proliferation. Survival analyses have indicated that a high Homocol expression is correlated with poor outcomes in most types of cancer studied. In terms of cancer detection, Homocol demonstrated strong performance in Receiver Operating Characteristic (ROC) analysis, with an Area Under Curve (AUC) of 0.83 for pan-cancer detection and between 0.72 and 0.99 for individual cancers.In cohorts undergoing PD1 treatment, we noted a higher presence of Homocol in the response group. In a Hepatocellular Carcinoma (HCC) clinical set, high Homocol expression was associated with an increased formation of intra-tumor tertiary lymphoid structures (TLS), larger tumor sizes, more advanced Barcelona Clinic Liver Cancer (BCLC) stages, higher microvascular invasion (MVI) grades, absence of a capsule, and an enriched para-tumor collagen presence. Conclusion: our research has led to the development of a novel gene signature that facilitates the detection of Homotrimer Collagen Type I. This may greatly assist efforts in cancer detection, prognosis, treatment response prediction, and further research into Homotrimer Collagen Type I.

Background: Cervical cancer is one of the most common malignancies in women worldwide. As a RING type ubiquitin ligase, SIAH2 has been reported to promote the progression of a variety of tumors by interacting with and targeting multiple chaperones and substrates. The aim of this study was to further identify the role and the related molecular mechanisms involved of SIAH2 in cervical carcinogenesis. Methods and results: Cellular assays in vitro showed that knockdown of SIAH2 inhibited the proliferation, migration and invasion of human cervical cancer cells C33A and SiHa, induced apoptosis, and increased the sensitivity to cisplatin treatment. Knockdown of SIAH2 also inhibited the epithelial-mesenchymal transition and activation of the Akt/mTOR signaling pathway in cervical cancer cells, which were detected by Western blot. Mechanistically, SIAH2, as a ubiquitin ligase, induced the ubiquitination degradation of GSK3β degradation by using coIP. The results of complementation experiments further demonstrated that GSK3β overexpression rescued the increase of cell proliferation and invasion caused by SIAH2 overexpression. Specific expression of SIAH2 appeared in precancerous and cervical cancer tissues compared to inflammatory cervical lesions tissues using immunohistochemical staining. The more SIAH2 was expressed as the degree of cancer progressed. SIAH2 was significantly highly expressed in cervical cancer tissues (44/55, 80 %) compared with precancerous tissues (18/69, 26.1 %). Moreover, the expression level of SIAH2 in cervical cancer tissues was significantly correlated with the degree of cancer differentiation, and cervical cancer tissues with higher SIAH2 expression levels were less differentiated. Conclusion: Targeting SIAH2 may be beneficial to the treatment of cervical cancer.

Abstract Background Hepatocellular carcinoma (HCC) is closely associatedwith chronic liver diseases, particularly liver cirrhosis, which has an altered extracellular matrix (ECM) composition. The influence and its mechanism of the cirrhotic-ECM on the response of HCC to immune checkpoint inhibitor (ICI) remains less clarified. Methods In silico, proteomic and pathological assessment of alteration of cirrhotic-ECM were applied in clinical cohort. Multiple pre-clinical models with ECM manipulation were used to evaluate cirrhotic-ECM’s effect on ICI treatment. In silico, flow cytometry and IHC were applied to explore how cirrhotic-ECM affect HCC microenvironment. In vitro and in vivo experiments were carried out to identify the mechanism of how cirrhotic-ECM undermined ICI treatment. Results We defined “a pro-tumor cirrhotic-ECM” which was featured as the up-regulation of collagen type 1 (Col1). Cirrhotic-ECM/Col1 was closely related to impaired T cell function and limited anti PD-1 (aPD-1) response of HCC patients from the TCGA pan cancer cohort and the authors’ institution, as well as in multiple pre-clinical models. Mechanically, cirrhotic-ECM/Col1 orchestrated an immunosuppressive microenvironment (TME) by triggering Col1-DDR1-NFκB-CXCL8 axis, which initiated neutrophil extracellular traps (NETs) formation to shield HCC cells from attacking T cells and impede approaching T cells. Nilotinib, an inhibitor of DDR1, reversed the neutrophils/NETs dominant TME and efficiently enhanced the response of HCC to aPD-1. Conclusions Cirrhotic-ECM modulated a NETs enriched TME in HCC, produced an immune suppressive TME and weakened ICI efficiency. Col1 receptor DDR1 could be a potential target synergically used with ICI to overcome ECM mediated ICI resistance. These provide a mechanical insight and novel strategy to overcome the ICI resistance of HCC.