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BackgroundThe incidence of early-onset colorectal cancer (EOCRC) is increasing globally. This study aims to describe the temporal trends of incidence and explore related risk exposures in early-life at the country level based on the GBD 2019.MethodsData on the incidence and attributable risk factors of EOCRC were obtained from the GBD 2019. Temporal trends of age-standardized incidence were evaluated by average annual percentage change (AAPC). Early-life exposures were indicated as summary exposure values (SEV) of selected factors, SDI and GDP per capita in previous decades and at ages 0–4, 5–9, 10–14 and 15–19 years. Weighted linear or non-linear regressions were applied to evaluate the ecological aggregate associations of the exposures with incidences of EOCRC.ResultsThe global age-standardized incidence of EOCRC increased from 3.05 (3.03, 3.07) to 3.85 (3.83, 3.86) per 100,000 during 1990 and 2019. The incidence was higher in countries with high socioeconomic levels, and increased drastically in countries in East Asia and Caribbean, particularly Jamaica, Saudi Arabia and Vietnam. The GDP per capita, SDI, and SEVs of iron deficiency, alcohol use, high body-mass index, and child growth failure in earlier years were more closely related with the incidences of EOCRC in 2019. Exposures at ages 0–4, 5–9, 10–14 and 15–19 years were also associated with the incidences, particularly for the exposures at ages 15–19 years.ConclusionThe global incidence of EOCRC increased during past three decades. The large variations at regional and national level may be related with the distribution of risk exposures in early life.

IntroductionColorectal cancer (CRC) presents a substantial challenge characterized by unacceptably high mortality and morbidity, primarily attributed to delayed diagnosis and reliance on palliative care. The immune response of the host plays a pivotal role in carcinogenesis, with IL-38 emerging as a potential protective factor in CRC. However, the precise involvement of IL-38 among various leucocytes, its interactions with PD-1/PD-L1, and its impact on metastasis require further elucidation.ResultsOur investigation revealed a significant correlation between IL-38 expression and metastasis, particularly concerning survival and interactions among diverse leucocytes within draining lymph nodes. In the mesentery lymph nodes, we observed an inverse correlation between IL-38 expression and stages of lymph node invasions (TNM), invasion depth, distance, and differentiation. This aligns with an overall survival advantage associated with higher IL-38 expression in CRC patients’ nodes compared to lower levels, as well as elevated IL-38 expression on CD4+ or CD8+ cells. Notably, a distinct subset of patients characterized by IL-38high/PD-1low expression exhibited superior survival outcomes compared to other combinations.DiscussionOur findings demonstrate that IL-38 expression in colorectal regional nodes from CRC patients is inversely correlated with PD-1/PD-L1 but positively correlated with infiltrating CD4+ or CD8+ lymphocytes. The combined assessment of IL-38 and PD-1 expression in colorectal regional nodes emerges as a promising biomarker for predicting the prognosis of CRC.

IntroductionWound healing poses a clinical challenge in diabetes mellitus (DM) due to compromised host immunity. CD64, an IgG-binding Fcgr1 receptor, acts as a pro-inflammatory mediator. While its presence has been identified in various inflammatory diseases, its specific role in wound healing, especially in DM, remains unclear.ObjectivesWe aimed to investigate the involvement of CD64 in diabetic wound healing using a DM animal model with CD64 KO mice.MethodsFirst, we compared CD64 expression in chronic skin ulcers from human DM and non-DM skin. Then, we monitored wound healing in a DM mouse model over 10 days, with or without CD64 KO, using macroscopic and microscopic observations, as well as immunohistochemistry.ResultsCD64 expression was significantly upregulated (1.25-fold) in chronic ulcerative skin from DM patients compared to non-DM individuals. Clinical observations were consistent with animal model findings, showing a significant delay in wound healing, particularly by day 7, in CD64 KO mice compared to WT mice. Additionally, infiltrating CD163+ M2 macrophages in the wounds of DM mice decreased significantly compared to non-DM mice over time. Delayed wound healing in DM CD64 KO mice correlated with the presence of inflammatory mediators.ConclusionCD64 seems to play a crucial role in wound healing, especially in DM conditions, where it is associated with CD163+ M2 macrophage infiltration. These data suggest that CD64 relies on host immunity during the wound healing process. Such data may provide useful information for both basic scientists and clinicians to deal with diabetic chronic wound healing.

BackgroundThe effectiveness of triage screening for colorectal cancer (CRC) is not fully achieved in Chinese populations, mainly due to low compliance to colonoscopy follow-up. This study aimed to collect viewpoints of experts in China on ongoing screening programs and emerging screening tests for CRC, which may help to improve effectiveness of CRC screening in the country.MethodsWe conducted 15 semi-structured interviews with experts involving CRC screening in China during October to November of 2020. Interview topics included personal characteristics, work context, opinions on ongoing screening programs, challenges and opportunities in optimization of screening strategies, and prospects for CRC screening in near future. To analyze the data, we used a generic qualitative research approach inspired by grounded theory, including open, axial, and selective coding.ResultsThis analysis revealed a total of 83 initial categories, 37 subcategories and 10 main categories, which included 4 core categories of current modality for CRC screening, factors influencing screening effectiveness, optimization of CRC screening modality, and prospects for development of CRC screening. The results provide insight into the factors underlying the challenges of the ongoing CRC screening programs in China: the most important concern is the low compliance to colonoscopy, followed by the low specificity of the currently-used initial tests. The experts proposed to use quantitative instead of qualitative fecal immunochemical test (FIT), and optimize risk assessment tools to improve specificity of initial tests. Regarding the emerging screening tests, 9 of 15 experts did not think that the novel techniques are good enough to replace the current tests, but can be used complementarily in opportunistic screening for CRC.ConclusionThe viewpoints of Chinese experts suggested that use quantitative FIT or optimize risk assessment tools may help to identify high-risk individuals of CRC more accurately, improve adherence to colonoscopy, and thus fully achieve the effectiveness of screening.

Background: Recent reports have suggested that antihypertensive drugs may play an oncogenic role in common cancers, but it is still uncertain whether this could influence the risk of oral cancer. Through two-sample Mendelian randomization (MR), we sought to assess the causal effect of antihypertensive drugs on oral cancer outcomes.Methods: To proxy the exposure of antihypertensive drugs, we utilized two genetic instruments, including expression quantitative trait loci of drug target genes and genetic variants within or around drug target genes related to blood pressure from genome-wide association studies. Inverse-variance-weighted MR (IVW-MR) and summary-data-based MR (SMR) were employed to compute the instrument effect estimates.Results: It was observed through IVW-MR analysis that there is a positive relationship between KCNH2 (target of beta-adrenoceptor blockers)–mediated blood pressure and oral cancer (odds ratio [OR] = 1.197, 95% confidence interval [CI] = 1.028–1.394). Similarly, SMR analysis demonstrated that a higher expression of KCNH2 (target of beta-adrenoceptor blockers) was linked to a greater risk of oral cancer (OR = 2.223, 95% CI = 1.094–4.516). Both analyses yielded no consistent evidence of other associations.Conclusion: This two-sample MR study proposed a latent causal association between KCNH2 (target of beta-adrenoceptor blockers) inhibition and diminished risk of oral cancer.

IntroductionNon-communicable diseases (NCDs) represent the leading cause of mortality and disability worldwide. Robust evidence has demonstrated that modifiable lifestyle factors such as unhealthy diet, smoking, alcohol consumption and physical inactivity are the primary causes of NCDs. Although a series of guidelines for the management of NCDs have been published in China, these guidelines mainly focus on clinical practice targeting clinicians rather than the general population, and the evidence for NCD prevention based on modifiable lifestyle factors has been disorganized. Therefore, comprehensive and evidence-based guidance for the risk management of major NCDs for the general Chinese population is urgently needed. To achieve this overarching aim, we plan to develop a series of expert consensuses covering 15 major NCDs on health risk management for the general Chinese population. The objectives of these consensuses are (1) to identify and recommend suitable risk assessment methods for the Chinese population; and (2) to make recommendations for the prevention of major NCDs by integrating the current best evidence and experts’ opinions.Methods and analysisFor each expert consensus, we will establish a consensus working group comprising 40–50 members. Consensus questions will be formulated by integrating literature reviews, expert opinions, and an online survey. Systematic reviews will be considered as the primary evidence sources. We will conduct new systematic reviews if there are no eligible systematic reviews, the methodological quality is low, or the existing systematic reviews have been published for more than 3 years. We will evaluate the quality of evidence and make recommendations according to the GRADE approach. The consensuses will be reported according to the Reporting Items for Practice Guidelines in Healthcare (RIGHT).

With the increasing integration of renewable energy into the power grid, the traditional roles of the transmission and distribution networks have become less distinct at the operational level. The integration between distribution network planning (DNP) and the transmission and distribution networks operation is crucial to ensure grid stability. Existing research has primarily focused on collaborative operation control between transmission and distribution networks, leaving a gap in integrated DNP, since few works can handle the integer variables. This study proposes a distribution network planning method based on the integration of operation and planning and coordinated with the transmission network. It aims to minimize investment and operational costs while considering local generation units, distributed renewables, and network constraints. Using a heterogeneous decomposition algorithm (HGD), the optimization model alternates between the two networks, assisted by injected parameters for global optimality. A convolutional neural network (CNN) surrogate model is then used to rapidly optimize precise distribution network plans that coordinate with the transmission network. Experimental results on IEEE 30 and IEEE 69 cases demonstrate that the proposed approach offers valuable engineering benefits, reducing iteration counts by up to 20% and improving accuracy compared to other distributed algorithms.

Three-dimensional (3D) bioprinting is an advanced tissue engineering technique that has received a lot of interest in the past years. We aimed to highlight the characteristics of articles on 3D bioprinting, especially in terms of research hotspots and focus. Publications related to 3D bioprinting from 2007 to 2022 were acquired from the Web of Science Core Collection database. We have used VOSviewer, CiteSpace, and R-bibliometrix to perform various analyses on 3,327 published articles. The number of annual publications is increasing globally, a trend expected to continue. The United States and China were the most productive countries with the closest cooperation and the most research and development investment funds in this field. Harvard Medical School and Tsinghua University are the top-ranked institutions in the United States and China, respectively. Dr. Anthony Atala and Dr. Ali Khademhosseini, the most productive researchers in 3D bioprinting, may provide cooperation opportunities for interested researchers. Tissue Engineering Part A contributed the largest publication number, while Frontiers in Bioengineering and Biotechnology was the most attractive journal with the most potential. As for the keywords in 3D bioprinting, Bio-ink, Hydrogels (especially GelMA and Gelatin), Scaffold (especially decellularized extracellular matrix), extrusion-based bioprinting, tissue engineering, and in vitro models (organoids particularly) are research hotspots analyzed in the current study. Specifically, the research topics “new bio-ink investigation,” “modification of extrusion-based bioprinting for cell viability and vascularization,” “application of 3D bioprinting in organoids and in vitro model” and “research in personalized and regenerative medicine” were predicted to be hotspots for future research.

Quantitative and mechanistic understanding of learning and long-term memory at the level of single neurons in living brains require highly demanding techniques. A specific need is to precisely label one cell whose firing output property is pinpointed amidst a functionally characterized large population of neurons through the learning process and then investigate the distribution and properties of dendritic inputs. Here, we disseminate an integrated method of daily two-photon neuronal population Ca2+ imaging through an auditory associative learning course, followed by targeted single-cell loose-patch recording and electroporation of plasmid for enhanced chronic Ca2+ imaging of dendritic spines in the targeted cell. Our method provides a unique solution to the demand, opening a solid path toward the hard-cores of how learning and long-term memory are physiologically carried out at the level of single neurons and synapses.

Background and aimsThe disease burden attributable to metabolic risk factors is rapidly increasing in China, especially in older people. The objective of this study was to (i) estimate the pattern and trend of six metabolic risk factors and attributable causes in China from 1990 to 2019, (ii) ascertain its association with societal development, and (iii) compare the disease burden among the Group of 20 (G20) countries.MethodsThe main outcome measures were disability-adjusted life-years (DALYs) and mortality (deaths) attributable to high fasting plasma glucose (HFPG), high systolic blood pressure (HSBP), high low-density lipoprotein (HLDL) cholesterol, high body-mass index (HBMI), kidney dysfunction (KDF), and low bone mineral density (LBMD). The average annual percent change (AAPC) between 1990 and 2019 was analyzed using Joinpoint regression.ResultsFor all six metabolic risk factors, the rate of DALYs and death increased with age, accelerating for individuals older than 60 and 70 for DALYs and death, respectively. The AAPC value in rate of DALYs and death were higher in male patients than in female patients across 20 age groups. A double-peak pattern was observed for AAPC in the rate of DALYs and death, peaking at age 20–49 and at age 70–95 plus. The age-standardized rate of DALYs increased for HBMI and LBMD, decreased for HFPG, HSBP, KDF, and remained stable for HLDL from 1990 to 2019. In terms of age-standardized rate of DALYs, there was an increasing trend of neoplasms and neurological disorders attributable to HFPG; diabetes and kidney diseases, neurological disorders, sense organ diseases, musculoskeletal disorders, neoplasms, cardiovascular diseases, digestive diseases to HBMI; unintentional injuries to LBMD; and musculoskeletal disorders to KDF. Among 19 countries of Group 20, in 2019, the age-standardized rate of DALYs and death were ranked fourth to sixth for HFPG, HSBP, and HLDL, but ranked 10th to 15th for LBMD, KDF, and HBMI, despite the number of DALYs and death ranked first to second for six metabolic risk factors.ConclusionsPopulation aging continuously accelerates the metabolic risk factor driven disease burden in China. Comprehensive and tight control of metabolic risk factors before 20 and 70 may help to mitigate the increasing disease burden and achieve healthy aging, respectively.

BackgroundMacrophage is a central regulator of innate immunity. Its M2 subsets, such as interstitial synovial macrophages, have been found to play critical roles in suppressing chronic inflammation and maintaining homeostasis within the joint. These macrophages have great potential as a disease-modifying cell therapy for osteoarthritis (OA). However, this has not yet been studied.MethodsMacrophages were isolated from the bone marrow of rats. We constructed a stable macrophage that “locked” in anti-inflammatory and pro-regenerative M2a polarity (L-M2a) by simultaneously knocking out tumor necrosis factor receptor 1 (TNFR1) and overexpressing IL-4 using Cas9-ribonuclear proteins (Cas9-RNP) and electroporation. In vitro, these L-M2a macrophages were treated with OA synovial fluid or co-cultured with OA chondrocytes or fibroblast-like synoviocytes (FLS). In vivo, L-M2a macrophages were injected intra-articularly to evaluate their homing and engrafting abilities and therapeutic effects on OA progression using a rat model.ResultsL-M2a macrophages displayed a typical anti-inflammatory phenotype similar to that of M2 macrophages in vitro. In OA microenvironment, L-M2a macrophages maintained a stable anti-inflammatory phenotype, whereas unmodified M2 macrophages lost their phenotype and switched to M1 polarity. L-M2a macrophages demonstrated a potent anti-inflammatory effect in crosstalk with OA-FLSs and an anti-degenerative effect in crosstalk with senescent OA chondrocytes. In vivo, compared with M2 macrophages and exosomes, L-M2a macrophages exhibited significantly superior therapeutic effects in OA by successfully resolving inflammation, restoring tissue homeostasis, and promoting cartilage regeneration.ConclusionThe engineered L-M2a macrophages maintained a superior anti-inflammatory and pro-regenerative capacity in the inflammatory OA microenvironment and represents an ideal new strategy for the disease-modifying therapy of OA.

BackgroundOsteosarcoma remains to be the most devastating malignant tumor in children and teenagers. Mitochondria have also been proven to play critical roles in osteosarcoma. However, a mitochondria-related signature has been established in osteosarcoma to comprehensively evaluate the pathogenic roles and regulatory roles of mitochondria in osteosarcoma.MethodsIn this study, osteosarcoma samples' transcriptome data and clinical information were collected from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) databases. A comprehensive bioinformatics analysis was performed on the samples at the bulk RNA sequencing level and single-cell RNA sequencing (scRNA-seq) level. EdU, Transwell, and immunohistochemistry (IHC) were performed on PCCB.ResultsA mitochondria-related signature was constructed in osteosarcoma patients. The prognostic value of the mitochondria-related signature was explored. The predictive value of the mitochondria-related signature in the immune microenvironment and chemotherapy agents was explored. The association between mitochondria and immunity in the tumor microenvironment of osteosarcoma at the scRNA-seq level was investigated. The tumorigenic role of the critical mitochondria-related gene, PCCB, was verified by in vitro validation.ConclusionIn conclusion, a mitochondria-related signature was developed in osteosarcoma with solid predictive values in the immune microenvironment, chemotherapy agents, and prognosis.

BackgroundStudies show that lung ultrasound (LUS) can accurately diagnose community-acquired pneumonia (CAP) and keep children away from radiation, however, it takes a long time and requires experienced doctors. Therefore, a robust, automatic and computer-based diagnosis of LUS is essential.ObjectiveTo construct and analyze convolutional neural networks (CNNs) based on transfer learning (TL) to explore the feasibility of ultrasound image diagnosis and grading in CAP of children.Methods89 children expected to receive a diagnosis of CAP were prospectively enrolled. Clinical data were collected, a LUS images database was established comprising 916 LUS images, and the diagnostic values of LUS in CAP were analyzed. We employed pre-trained models (AlexNet, VGG 16, VGG 19, Inception v3, ResNet 18, ResNet 50, DenseNet 121 and DenseNet 201) to perform CAP diagnosis and grading on the LUS database and evaluated the performance of each model.ResultsAmong the 89 children, 24 were in the non-CAP group, and 65 were finally diagnosed with CAP, including 44 in the mild group and 21 in the severe group. LUS was highly consistent with clinical diagnosis, CXR and chest CT (kappa values = 0.943, 0.837, 0.835). Experimental results revealed that, after k-fold cross-validation, Inception v3 obtained the best diagnosis accuracy, PPV, sensitivity and AUC of 0.87 ± 0.02, 0.90 ± 0.03, 0.92 ± 0.04 and 0.82 ± 0.04, respectively, for our dataset out of all pre-trained models. As a result, best accuracy, PPV and specificity of 0.75 ± 0.03, 0.89 ± 0.05 and 0.80 ± 0.10 were achieved for severity classification in Inception v3.ConclusionsLUS is a reliable method for diagnosing CAP in children. Experiments showed that, after transfer learning, the CNN models successfully diagnosed and classified LUS of CAP in children; of these, the Inception v3 achieves the best performance and may serve as a tool for the further research and development of AI automatic diagnosis LUS system in clinical applications.Registrationwww.chictr.org.cn ChiCTR2200057328.

BackgroundThe role of ferroptosis in tumor progression and immune microenvironment is extensively investigated. However, the potential value of ferroptosis regulators in predicting prognosis and therapeutic strategies for osteosarcoma (OS) patients remains to be elucidated.MethodsHere, we extracted transcriptomic and survival data from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) to investigate the expression and prognostic value of ferroptosis regulators in OS patients. After comprehensive analyses, including Gene set variation analysis (GSVA), single-sample gene-set enrichment analysis (ssGSEA), Estimated Stromal and Immune cells in Malignant Tumor tissues using Expression (ESTIMATE), single-cell RNA sequencing, and biological experiments, our constructed 8-ferroptosis-regulators prognostic signature effectively predicted the immune landscape, prognosis, and chemoradiotherapy strategies for OS patients.ResultsWe constructed an 8-ferroptosis-regulators signature that could predict the survival outcome of OS. The signature algorithm scored samples, and high-scoring patients were more prone to worse prognoses. The tumor immune landscape suggested the positive relevance between risk score and immunosuppression. Interfering HILPDA and MUC1 expression would inhibit tumor cell proliferation and migration, and MUC1 might improve the ferroptosis resistance of OS cells. Moreover, we predicted chemoradiotherapy strategies of cancer patients following ferroptosis-risk-score groups.ConclusionDysregulated ferroptosis gene expression can affect OS progression by affecting the tumor immune landscape and ferroptosis resistance. Our risk model can predict OS survival outcomes, and we propose that HILPDA and MUC1 are potential targets for cancer therapy.

The characteristic of ulcerative colitis (UC) is extensive colonic mucosal inflammation. Moringa oleifera (M. oleifera) is a medicine food homology plant, and the polysaccharide from M. oleifera leaves (MOLP) exhibits antioxidant and anti-inflammatory activity. The aim of this study to investigate the potential effect of MOLP on UC in a mouse model as well as the underlying mechanism. Dextran sulfate sodium (DSS) 4% in drinking water was given for 7 days to mice with UC, at the same time, MOLP (25, 50, and 100 mg/kg/day) was intragastric administered once daily during the experiment. Structural analysis revealed that MOLP had an average molecular weight (Mw) of 182,989 kDa and consisted of fucose, arabinose, rhamnose, galactose, glucose, xylose, mannose, galactose uronic acid, glucuronic acid, glucose uronic acid and mannose uronic acid, with a percentage ratio of 1.64, 18.81, 12.04, 25.90, 17.57, 12.01, 3.51, 5.28, 0.55, 1.27, and 1.43%, respectively. In addition, the features of MOLP were identified by Fourier-transform infrared (FT-IR) and spectra, X-ray diffraction (XRD). The results showed that MOLP exhibited protective efficacy against UC by alleviating colonic pathological alterations, decreasing goblet cells, crypt destruction, and infiltration of inflammatory cells caused by DSS. Furthermore, MOLP notably repressed the loss of zonula occludens-1 (ZO-1) and occludin proteins in mucosal layer, as well as up-regulating the mRNA expression of interleukin-10 (IL-10) and peroxisome proliferator-activated receptor-γ (PPAR-γ), whereas down-regulating the activation of Toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), nuclear factor-kappa B (NF-κB) signaling pathway and the production of pro-inflammatory cytokines. Therefore, these results will help understand the protective action procedure of MOLP against UC, thereby providing significance for the development of MOLP.

Leukaemia accounted for approximately 2.5% of all new cancer incidence and 3.1% of cancer-related mortality. The investigation of its risk factors and epidemiologic trends could help describe the geographical distribution and identify high-risk population groups. This study aimed to evaluate the global incidence, mortality, associated risk factors, and temporal trends of leukaemia by sex, age, and country. We extracted incidence and mortality of leukaemia from GLOBOCAN, CI5, WHO mortality database, NORDCAN, and SEER. We searched the WHO Global Health Observatory data repository for the age-standardised prevalence of lifestyle and metabolic risk factors. We tested the trends by calculating Average Annual Percentage Change (AAPC) from Joinpoint regression. The age-standardized rate of incidence and mortality were 5.4 and 3.3 per 100,000 globally. The incidence and mortality of leukaemia were associated with Human Development Index, Gross Domestics Products per capita, prevalence of smoking, physical activity, overweight, obesity, and hypercholesterolaemia at the country level. Overall, more countries were showing decreasing trends than increasing trends in incidence and mortality. However, an increasing trend of leukaemia incidence was found in Germany, Korea, Japan, Canada and the United Kingdom (AAPC, 2.32-0.98) while its mortality increased in the Philippines, Ecuador, Belarus, and Thailand (AAPC, 2.49-1.23). There was a decreasing trend of leukaemia for the past decade while an increase in incidence and mortality was observed in some populations. More intensive lifestyle modifications should be implemented to control the increasing trends of leukaemia in regions with these trends. Future studies may explore the reasons behind these epidemiological transitions.

BackgroundMeasuring quality of primary care has attracted much attention around the world. Our team has developed and validated an Assessment Survey of Primary Care (ASPC) for evaluating quality of primary care in China. To facilitate the daily use of ASPC, this study aimed to develop and validate a rapid assessment version of ASPC (RA-ASPC) in China.MethodsThis is a multi-phase study on 21 experts and 1,184 patients from 12 primary care facilities in 10 cities in China. Importance, representativeness, easy understanding, and general applicability of each item in ASPC scale were rated to select the top two ranked items for constituting RA-ASPC. Reliability of RA-ASPC was tested by calculating both Cronbach's alpha and McDonald's omega coefficients. Structural validity was assessed by exploratory and confirmatory factor analysis (EFA and CFA). Concurrent validity was performed by analyzing the relationship between RA-ASPC and patient satisfaction. Discriminant validity was tested by assessing the difference of RA-ASPC scores between patients with or without family doctors.ResultsTen items were selected for RA-ASPC. Both Cronbach's alpha (0.732) and McDonald's omega (0.729) suggested satisfactory internal consistency. In EFA, explained variance of RA-ASPC (72.6%) indicated its ability to measure quality of primary care in China. CFA indicators showed convincing goodness-of-fit (GFI = 0.996, AGFI = 0.992, CFI = 1.000, NFI = 0.980, RMR = 0.022, and the RMSEA = 0.000) for RA-ASPC. Positive association between RA-ASPC and patient satisfaction supported the concurrent validity of RA-ASPC. Patients with family doctors perceived higher quality of primary care than those without family doctors, indicating good discriminant validity of RA-ASPC.ConclusionThe theoretical framework of RA-ASPC was in line with internationally recognized core functions of primary care. Good psychometric properties of RA-ASPC proved its appropriateness in assessing quality of primary care from patients' perspectives in China.

The stability of wind turbine output is affected by multi-factor disturbances, which makes traditional proportion-integral-differential (PID) control strategy hardly achieve a satisfactory effect. Hence, a pitch control strategy based on fuzzy adaptive particle-swarm-optimization (PSO)-PID is proposed in this paper. Firstly, the models of wind turbine, pitch regulator, and permanent magnet synchronous generator (PMSG) are built. Then, the influence of various disturbances, such as blade deformation, installation errors, and external wind speed, on the wind wheel speed is analyzed. Furtherly, a wind turbine pitch control strategy is devised in detail, in which the PID parameters are initially optimized by PSO and adaptively adjusted by fuzzy controller. Simulations under gust wind and turbulent wind conditions are carried out, and the results show that compared with fuzzy PID and PID, the fuzzy adaptive PSO-PID could reduce errors of wind wheel speed and wind turbine output power effectively.

Viral disease management has been proven difficult, and there are no broadly licensed vaccines or therapeutics. Vesicular stomatitis virus (VSV) is an active pathogen of wild ungulates and livestock; its infection frequently caused irreversible vesicles on the tongue or other positions, leading to enormous economic loss. Tea tree oil (TTO) has been shown to be a popular remedy for many skin diseases owing to its antibacterial, antipruritic, and anti-inflammatory effects. However, the potential effect of TTO on VSV proliferation and the corresponding inflammatory response in cells remain unclear. In this study, methyl thiazolyl tetrazolium assay was used to evaluate the cell viability of TTO, and cytotoxic concentration 50 (CC50) was calculated. Then, fluorescence observation, reverse transcription–quantitative polymerase chain reaction, Western blot (WB), and flow cytometry (FCM) assay were used to evaluate the antiviral effect of TTO against VSV under three manners of pre-infection before medication, co-administration, pretreatment before infection at safe doses to Vero cells. Meanwhile, the mRNA expressions of interleukin 8, tumor necrosis factor α, and ISG56 in cells were also detected. The results showed that the maximum safe concentration of TTO to Vero cells was 0.063% and the CC50 is 0.32%. Most notably, TTO dose-dependently inhibited the VSV GFP fluorescence generation and restrained the replication of VSV in gene and protein levels regardless of the treatment modes. Based on the results of the FCM, effective concentration 50 of TTO against VSV is 0.019%. Similarly, the mRNA expression of the above cytokines induced by viral infection was also remarkably curbed. These findings suggest that TTO emerged blocking, prophylaxis, and treatment action against VSV replication and suppressed the related inflammation in Vero cells. This study provides a novel potential for TTO fighting against viral infection and anti-inflammatory activities in Vero cells.

Interleukin (IL)-33 belongs to a novel chromatin-associated cytokine newly recognized by the IL-1 family, and its specific receptor is the orphan IL-1 receptor (ST2). Cumulative evidence suggests that IL-33 plays a crucial effect on the pathological changes and pathogenesis of central nervous system (CNS) diseases and injuries, such as recurrent neonatal seizures (RNS). However, the specific roles of IL-33 and its related molecular mechanisms in RNS remain confused. In the present study, we investigated the protein expression changes and co-localized cell types of IL-33 or ST2, as well as the effect of IL-33 on RNS-induced neurobehavioral defects, weight loss, and apoptosis. Moreover, an inhibitor of IL-33, anti-IL-33 was performed to further exploited underlying mechanisms. We found that administration of IL-33 up-regulated the expression levels of IL-33 and ST2, and increased the number of its co-localization with Olig-2-positive oligodendrocytes and NeuN-positive neurons at 72 h post-RNS. Noteworthily, RNS-induced neurobehavioral deficits, bodyweight loss, and spatial learning and memory impairment, as well as cell apoptosis, were reversed by IL-33 pretreatment. Additionally, the increase in IL-1β and TNF-α levels, up-regulation of ER stress, as well as a decrease in anti-apoptotic protein Bcl-2 and an increase in pro-apoptotic protein CC-3 induced by RNS are prevented by administration of IL-33. Moreover, IL-33 in combination with Anti-IL-33 significantly inverted the effects of IL-33 or Anti-IL-33 alone on apoptosis, ER stress, and inflammation. Collectively, these data suggest that IL-33 attenuates RNS-induced neurobehavioral disorders, bodyweight loss, and spatial learning and memory deficits, at least in part through mechanisms involved in inhibition of apoptosis, ER stress, and neuro-inflammation.

Enterobacter cloacae is a well-characterized opportunistic pathogen that is closely associated with various nosocomial infections. The O-antigen, which is one of the most variable constituents on the cell surface, has been used widely and traditionally for serological classification of many gram-negative bacteria. E. cloacae is divided into 30 serotypes, based on its O-antigen diversity. In this study, by using genomic and comparative-genomic approaches, we analyzed the O-antigen gene clusters of 26 E. cloacae serotypes in depth. We also identified the sero-specific gene for each serotype and developed a multiplex polymerase chain reaction (PCR) method. The sensitivity of the assay was 0.1 ng for genomic DNA and 103 colony forming units for pure cultures. The assay reliability was evaluated by double-blinded testing with 81 clinical strains. Furthermore, we established a valid, genome-based tool for in silico serotyping of E. cloacae. By screening 431 E. cloacae genomes deposited in GenBank, 304 were classified into current antigenic scheme, and 112 were allocated into 55 putative novel serotypes. Our results represent the first genetic basis of the O-antigen diversity and variation of E. cloacae, providing a rationale for studying the O-antigen associated evolution and pathogenesis of this bacterium. In addition, we extended the current serotyping system for E. cloacae, which is important for detection and epidemiological surveillance purposes for this important pathogen.