Appendicitis is usually diagnosed based on a reliable set of signs and symptoms, and can be effectively treated with surgery, with low morbidity and mortality rates. However, appendicitis is often overlooked in vulnerable populations, including people with disabilities. This study compared 10-year trends of complicated appendicitis between South Koreans with a disability, according to disability severity and type, and those without disabilitiesTo identify cases of appendicitis, we used the DRG codes in the National Health Information Database of South Korea. Patients with appendicitis were classified in terms of severity based on the DRG codes. Age-standardized incidence rates were calculated for each year during 2008–2017 according to the presence, type, and severity of the disability. Factors associated with complicated appendicitis were examined by multivariate logistic regression using the most recent data .The incidence of complicated appendicitis was higher in people with disabilities, especially those with severe disabilities (26.9 vs. 11.6%). This difference was particularly marked when considering those with a severe disability , internal organ problems  or a mental disability .The incidence of complicated appendicitis was higher in people with disability than in those without disability in all years. There was a substantial difference in the incidence of complicated appendicitis between the severe disability and non-disabled groups. Among the various disability types, the incidence of complicated appendicitis was highest for major internal organ problems, followed by intellectual or psychological disabilities. Our findings may be explained by barriers to healthcare access among people with disabilities, particularly those with a severe disability, internal organ problem, or mental disability. Appendectomy is one of the most common operations performed worldwide, including in South Korea . AppendiA delay in the diagnosis and treatment of some conditions can result in serious adverse outcomes; delayed diagnosis and treatment of appendicitis can result in appendiceal rupture, peritonitis, and death . The risIt has been suggested that rupture rate of appendicitis could serve as an indicator of access to healthcare . In the Timely and appropriate healthcare plays a key role in wellness, illness prevention, and optimal recovery when illness occurs . SeveralAlthough numerous epidemiological studies on complicated appendicitis have been conducted, most focused on children or older adults; relatively few focused on people with disabilities, especially with a long observation period. Previous studies were mainly concerned with the incidence of complicated appendicitis –17, diffn = 84,981), as well as those who had missing data  or an appendectomy of unknown severity   database of the National Health Insurance Sharing Service. The Korean NHIS covers 97% of the Korean population; only Medical Aid beneficiaries in the lowest income bracket are not covered. The NHIS contains information about age, sex, residential area, monthly insurance contributions (a proxy for income status), disability type and severity, and vital statistics. The NHIS claims database enables easy retrieval and analysis of population-based epidemiological data. For this study, population-based medical data for patients of all ages with appendicitis were retrospectively extracted from the NHI claims database from January 2008 to December 2017. We collected information on disability severity and type from Using a disability registry. The database covered 93.8% of the total disabled population as of 2011 . Using K 11,834) . During The primary study outcome of the rate of complicated appendicitis. Patients with complicated appendicitis were classified based on KDRG codes according to severity. Cases of appendicitis treated with appendectomy were identified using diagnosis-related group (DRG) codes G081–G084. The DRG-based payment system in South Korea is a case-based prospective payment system under which payments are made according to physician-determined diagnoses . The Korp-value < 0.05 was considered significant. This study was approved by the Institutional Review Board of Chungbuk National University (CBNU-202010-HRHR-0717).Descriptive statistics were generated on disability status (present or absent) and the type and severity of disability. Age-standardized incidence rates were calculated using 2005 Korean census data as the reference. To examine the association between disability and the incidence of complicated appendicitis, we conducted a series of multivariate logistic regression analyses adjusted for age, income level, place of residence, smoking status, the CCI score, diabetes, hypertension, chronic obstructive pulmonary disease, coronary artery disease, obesity, and malignancies , 22, 23 n = 3,10,833) were male and 49.1%  were female, compared to 61.0%  and 39.0%  among the patients with a disability, respectively (<0.0001). Patients with appendicitis and a disability were slightly older than the control subjects . The economic status of the cohort with disabilities was lower than that of those without a disability. The proportion of patients with medical aid was higher in the disabled group, but the number in the fifth (highest) quartile was larger in the non-disabled group (<0.0001). People with versus without disabilities had more comorbidities and a higher mean CCI score , and were more likely to live in a rural area (<0.0001). In total, 12.2 and 11.0% of patients without a disability (<0.0001), and 27.3 and 26.2% of those with a disability (p = 0.0209), had been diagnosed with complicated appendicitis  = 1.204 and 1.389 for males and females, respectively]. This difference was greater in those with a severe disability . The risk was high for males in the internal organ problems  and intellectual/psychological disabilities  groups, particularly in those with severe internal organ problems  and intellectual/psychological disorders . Similarly, the risk of complicated appendicitis was particularly high in females with severe internal organ problems  .This is the first study to comprehensively analyze potential disparities in the incidence of complicated appendicitis according to disability status. The strengths of this study included the large number of participants, who were representative of the entire population of South Korea, and the accurate disability diagnoses.The incidence of complicated appendicitis has been continuously decreasing in both disabled and non-disabled patient groups since 2011. The incidence fell particularly sharply from 2014 to 2015, as also reported in previous studies based on KDRG codes. According to Shin, the ratio of the 1–3 to 0 severity classes decreased 0.49-fold during 2014–2015 among health insurance and medical aid patients. This obviously suggests a decrease in the proportion of high-severity patients, but may also reflect more accurate claims and KDRG code data in association with the introduction of a new payment system in 2013 . FurtherIn this study, the incidence rates of complicated appendicitis were higher in disabled people compared to those without disabilities. The main drivers of complicated appendicitis are considered to be delayed diagnosis and treatment. Although we could not establish the reasons for late diagnosis and treatment in our disabled group, barriers to healthcare have been suggested in previous studies, including access to facilities, equipment, and transportation , 28, 29.p < 0.05) was shown to be an independent predictor of mortality due to acute appendicitis . We believe that adjusting for other covariates in the multivariate model would be sufficient to address the confounding effect of differences in patient characteristics between people with and without disabilities, in terms of risk factor identification. Matching the subjects could prevent such confounding. Second, we could not ascertain why some patients were more at risk of complicated appendicitis, where potential reasons include patient or family refusal to undergo treatment, economic/transportation problems, or clinical decision-making. Further studies using other research methods and statistical analyses , including patient surveys and interviews, are required to precisely determine how these factors affect the incidence of complicated appendicitis. Third, although we included subjects with the DRG code for appendectomy, whether they were actually diagnosed with appendicitis was unclear, and patients who did not undergo surgery  were not included . However, the main treatment for appendicitis is appendectomy; previous studies reported that more than 96% of appendicitis patients underwent this surgery . TherefoOur findings indicate disparities in access to healthcare between non-disabled and disabled populations, particularly for those with severe or mental disabilities, or internal organ problems. Although the disparity might in part be due to clinical decision-making, unequal access to healthcare for people with disabilities is unjustifiable. Public health policies should focus on people with disabilities to reduce disparities in health outcomes. Healthcare professionals, as well as people with disabilities and their families, should be educated to improve attitudes, and regarding the need for equal access to diagnosis and treatment.The original contributions presented in the study are included in the article/KEY, SYK, JEP, and JHP: conceptualization. JEP and JHP: data curation. JEP: formal analysis. KEY, SYK, and JHP: funding acquisition. JEP and KEY: investigation and methodology. SYK: project administration. JHP: resources. KEY and SYK: software, supervision, validation, visualization, roles/writing—original draft, and writing—review and editing. All authors contributed to the article and approved the submitted version.This work was supported by National Research Foundation of Korea (NRF) grants funded by the Ministry of Education (Nos. 2020R1I1A1A01054268 and 2019R1D1A3A03103862) and by the Korean Government (MSIT) (No. 2019R1A2C1087507).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Prognostic nutritional index (PNI) is an independent predictor of the prognosis of various diseases. However, the prognosis value of PNI in patients with decompensated liver cirrhosis (DLC) remains unknown. The study aimed to investigate the prognostic significance of PNI in patients with DLC.A total of 214 eligible patients were enrolled in the study’s development cohort between January 2018 and March 2021. The clinical primary study endpoints were mortality at 3 and 6 months. Receiver operating characteristic (ROC) curve analysis was used to assess the PNI’s prediction accuracy, and Youden’s index was utilized to determine the PNI’s optimal cut-off value. Moreover, based on the optimal cut-off value, patients were categorized into high and low PNI groups. Multivariate logistic regression analysis was used to determine independent risk factors for mortality, while the relationship between PNI and the risk of death was identified and demonstrated using restricted cubic splines (RCS). A validation cohort of 139 patients was to verify the predictive power of the PNI.In the development cohort, the mortality rate at 3 and 6 months were 10.3% (22) and 14.0% (30), respectively. The PNI had comparable predictive power with the MELD score at all follow-up endpoints. Decreased PNI was an independent predictor of adverse prognosis at all follow-up endpoints. The RCS revealed a linear correlation between PNI and the risk of death. We confirmed that lower PNI was an independent predictor of poor prognosis in the validation cohort.The findings showed that lower PNI is an independent factor of poor outcomes and might be utilized as a potentially promising prognostic predictor in patients with DLC. Liver cirrhosis possesses a significant global morbidity and mortality rate, resulting in a million deaths annually, and is the 11th leading cause of death globally . As compPrognostic Nutritional Index (PNI) is a simple and objective index of inflammatory and nutrition status derived from serum albumin (ALB) and lymphocyte counts. Recently, PNI has been reported to be an independent prognostic predictor for patients with cancer, stroke, heart disease, chronic kidney disease, acute exacerbation of the chronic obstructive pulmonary disease, sepsis, COVID-19, and autoimmune disease –17. HoweBetween January 2018 and March 2021, we recruited patients with DLC who were admitted to the Department of Gastroenterology, Yijishan Hospital of Wannan Medical College as the development cohort of the study. We enrolled patients with DLC attending the Yijishan Hospital of Wannan Medical College between April 2021 and February 2022 as the validation cohort. DLC was defined as biochemical, clinical, endoscopic manifestations, imaging signs, and complications of ascites, gastrointestinal bleeding, hepatorenal syndrome, or hepatic encephalopathy . Reasons9/L)  . The Mod9/L) . The mort-test  or the Mann-Whitney U-test  were used to examine the differences in continuous variables. Categorical data were assessed by the chi-square test , R (version 4.0.2), and MedCalc (Version 15.2) were used to perform the statistical analyses in the study.Categorical data were reported as frequency and percentage, while continuous variables were expressed as means ± standard deviation or medians (25th–75th percentiles). The independent sample are test . Associaare test . Multivaare test . The diaare test , and theare test . The valare test . The patare test . The numare test . Two-sidA total of 353 patients with DLC who met the inclusion criteria were recruited for the study. In the development cohort, ascites (84.6%) were found to be the most common type of decompensation, followed by variceal bleeding (32.2%), hepatic encephalopathy (4.2%), and hepatorenal syndrome (2.3%). Cirrhosis was caused by chronic hepatitis B virus in most cases, and the patients’ average age was 61.4 ± 12.9 years. The mortality rate at 3 and 6 months were 10.3 and 14.0%, respectively. The baseline characteristics of patients in the development and validation cohort are shown in P < 0.05). At all follow-up endpoints, no significant differences were found between the two groups in lymphocyte (LYM), hemoglobin (HGB), total bilirubin (TBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ–glutamyl transpeptidase (GGT), blood urea nitrogen (BUN), creatinine (Cr), and gender. The clinical and laboratory characteristics between non-survivors and survivors in the development and validation cohort are shown in In the development cohort, the PNI and ALB of the survivor were significantly higher than the non-survivor, while the white blood cell (WBC), platelet (PLT), and MELD scores of the survivor were considerably lower than the non-survivor at any phase of the follow-up   . In addiP-value > 0.05)  .P for non-linearity > 0.05)  . PNI wasP-value > 0.05)  .The findings demonstrated that lower PNI was an independent predictor for adverse outcomes at all follow-up endpoints and PNI had a potential predictive value for mortality in patients with DLC. Furthermore, a linear correlation between PNI and the risk of death was observed, indicating that mortality increased with the decrease in PNI. Currently, the MELD score is the most extensively used scoring system for stratifying disease severity and predicting mortality in advanced liver disease but requires complicated calculations that are inconvenient for clinical practice . In contPNI is a simple index developed by Onodera et al., reflecting immune, inflammatory, and nutritional status . AccordiThere are specific explanations as to why PNI can predict the prognosis in patients with DLC. Firstly, albumin can reflect systemic inflammation and nutritional status , 41. SerThere are certain drawbacks in the current study. Firstly, it is a single-centered, retrospective, observational study, and selection bias cannot be avoided. Secondly, the predominant etiology of the patients in this study was hepatitis B virus infection, requiring caution to extrapolate these findings to other populations, especially in western cirrhosis populations where alcohol and NASH predominate. Third, this study did not compare the predictive ability of PNI with other nutritional indicators, such as skeletal muscle index or phase angle markers, for the prognosis of patients with DLC. Hence, prospective multicentered research with large sample numbers is required to further evaluate the clinical relevance of the PNI in patients with DLC.Prognostic nutritional index may be a potential and promising predictor of prognosis in patients with DLC. It is readily available and could be used to identify patients at high risk of death. This finding may be used to improve the prognosis in patients with DLC by adjusting the treatment strategies in clinical practice.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Scientific Research and New Technology Institutional Review Board of Yijishan Hospital of Wannan Medical College. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.WW designed the research. YX and CH collected the data. YX and WW analyzed the data and wrote the main manuscript text. YX prepared all tables and figures. WW and CH revised the manuscript. All authors have read and approved the final manuscript.


It is critical to identify the stroke onset time of patients with acute ischemic stroke (AIS) for the treatment of endovascular thrombectomy (EVT). However, it is challenging to accurately ascertain this time for patients with wake-up stroke (WUS). The current study aimed to construct a deep learning approach based on computed tomography perfusion (CTP) or perfusion weighted imaging (PWI) to identify a 6-h window for patients with AIS for the treatment of EVT.We collected data from 377 patients with AIS, who were examined by CTP or PWI before making a treatment decision. Cerebral blood flow (CBF), time to maximum peak (Tmax), and a region of interest (ROI) mask were preprocessed from the CTP and PWI. We constructed the classifier based on a convolutional neural network (CNN), which was trained by CBF, Tmax, and ROI masks to identify patients with AIS within a 6-h window for the treatment of EVT. We compared the classification performance among a CNN, support vector machine (SVM), and random forest (RF) when trained by five different types of ROI masks. To assess the adaptability of the classifier of CNN for CTP and PWI, which were processed respectively from CTP and PWI groups.p = 0.001 and p = 0.001, respectively). For the CNN classifier trained by different ROI masks, the best performance was trained by CBF, Tmax, and ROI masks of Tmax > 6 s. No significant difference was detected in the classification performance of the CNN between CTP and PWI .Our results showed that the CNN classifier had a higher performance with an area under the curve (AUC) of 0.935, which was significantly higher than that of support vector machine (SVM) and random forest (RF) (The CNN classifier trained by CBF, Tmax, and ROI masks of Tmax > 6 s had good performance in identifying patients with AIS within a 6-h window for the treatment of EVT. The current study indicates that the CNN model has potential to be used to accurately estimate the stroke onset time of patients with WUS. In the guidelines for the early management of patients with acute ischemic stroke (AIS) published by the American Heart Association/American Stroke Association (AHA/ASA) in 2019, recombinant tissue-type plasminogen activator (rt-PA) thrombolysis and endovascular thrombectomy (EVT) are recommended to treat patients with AIS , which was processed from CTP or perfusion weighted imaging (PWI), to identify patients with AIS within a 6-h window for the treatment of EVT. We constructed a classifier based on a convolutional neural network (CNN), which was trained by CBF, Tmax, and a region of interest (ROI) mask. Compared to previous studies, to classify patients within a 4.5 h window for rt-PA thrombolysis treatment, our method is able to identify them within a 6-h window for the treatment of EVT. Meanwhile, our method has stable performance for both CTP and PWI. It means that our method enables compatible with both magnetic resonance (MR) and computed tomography (CT) devices, rather than only MR devices. Thus, our method has more potential to be used widely in hospitals, especially primary hospitals.The local institutional review board approved this retrospective analysis, and the patient had signed the informed consent form. Also, patient records and images (including the source or raw imaging data) were anonymized before image analysis. Anonymized data are available on reasonable request to the corresponding author, and the data collected in the repository will be made accessible to qualified researchers worldwide, based on the recommendations of a scientific committee that will evaluate proposed research projects. The confidentiality of patients' information will be rigorously protected.https://github.com/bianyueyan/CNN-EVT.We recruited patients with AIS between April 2020 and April 2021 from the eStroke China national thrombolytic and thrombectomy imaging platform. Thirteen subcenters are registered on the platform and upload CTP or PWI images examined from patients with AIS before treatment to the eStroke platform. In addition, clinical information, including age, sex, national institute of health stroke scale (NIHSS), and exact stroke onset time are recorded. In order to align the examination performance among subcenters, we adjusted imaging protocols based on different device types, which are summarized in According to previous works, the stroke onset time is correlated with CBF/ADC, Tmax, and changes in the benign hypoperfusion, ischemic, and infarct core regions. These regions can be estimated by different thresholds in CBF and Tmax , 15. TheIn order to compare the performance among the different classifiers , each classifier was trained by three channels of images, consisting of CBF, Tmax, and ROI masks of Tmax > 6 s. Meanwhile, for observing the differences from the ROI masks , the CNN classifier was trained by CBF, Tmax, and each ROI mask. Through the above process, the classifier with the best performance was selected. Finally, we trained the best classifier using CBF, Tmax, and ROI mask, respectively, from CTP and PWI to compare their agreement.x, y, and z directions to reduce the impact of image resolutions. The resampled images were chosen as the analytical basis of feature extraction, training, and testing datasets.The CTP and PWI of patients with AIS were examined before the treatment, and then intra-phase rigid registration was performed to correct motion artifacts. After this, the images were smoothed using a Gaussian filter with a kernel with a width of 2.5 mm. In order to reduce disturbance of skull and cerebrospinal fluid (CSF), the images were segmented using BET2  and the According to previous studies, ROI masks segmented by different thresholds based on CBF and Tmax express the progression of AIS, which are strongly related to the stroke onset time –8. In orFeatures for training machine learning methods, including SVM and RF, were generated based on CBF, Tmax images, and ROI masks, which mainly included first-order descriptive statistics, features of shape, gray level co-occurrence matrix (GLCM) features, gray level dependance matrix (GLDM) features, and gray level size zone matrix (GLSZM) features. All of the features are shown in We compared the performance of three types of classifiers, namely, SVM, RF, and CNN in identifying a 6-h window for the treatment of EVT. Briefly, SVM is a supervised machine learning algorithm, mainly used to process classification and regression tasks. The objective of SVM is to find a hyperplane in a N-dimensional space that is defined by the number of features in order to classify the dataset . RF is aIn this study, a CNN was constructed based on VGGNet with 2 convolutional blocks , which cp < 0.05.We computed the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC), which can compare the ability of all classifiers to identify patients with AIS within a 6-h window. To determine the significance of differences among classifiers in the task of identification, we used the DeLong test to compare the AUCs of the classifiers . We alsoWe recruited 2,500 patients from the eStroke platform; 426 were excluded due to loss of original data, and 922 were excluded because of poor image quality, such as motion artifacts during scanning. Additionally, 775 with an onset time exceeding 24 h were excluded. Finally, a total of 377 patients  were included in this study. The stroke onset time was 6.7 ± 5.7 h (range = 0–24 h). All patients had ACA occlusion. The patients' baseline and NIHSS are listed in p-values for each patient characteristic between the training and testing datasets were estimated. We observed that all p-values were higher than 0.05, which means that there were no significant differences in each patient characteristic between the training and testing datasets.Training and testing datasets were selected randomly, which were grouped by the onset time of stroke. p = 0.001) and RF (p = 0.001). The AUCs of the classifiers compared with the previous work are depicted in p = 0.017 and p = 0.002, respectively). Although the AUC of Tmax > 6 s was higher than that of Tmax > 4 s, there was no significant difference between them (p = 0.285). Comparing the ROI masks segmented by Tmax, the AUC of CBF < 30% was only 0.796 (0.723–0.867).The CNN classifier was trained by CBF, Tmax, and each ROI mask , each ROC curve of which is shown in p = 0.557).We separated the training dataset into two groups (CTP and PWI), and the CNN classifier was trained by CBF, Tmax, and ROI mask of Tmax > 6 s in each group. In this study, we proposed to use a CNN framework based on a perfusion map (CBF and Tmax) to identify patients with AIS within a 6-h window for the treatment of EVT. We compared the performance of each classifier  and differences from each ROI mask . Our results showed that the CNN classifier trained by CBF, Tmax, and ROI masks of Tmax > 6 s had a higher performance in terms of identification within a 6-h window. Apart from this, our method had stable performance for both CTP and PWI, which means that the proposed method has higher potential to be used widely in stroke centers.In a previous study, the progression of AIS could be directly expressed by changes in the infarct core and ischemic region –14. Thomp = 0.285). According to a previous work (In identifying patients with AIS within a 4.5 h window for rt-PA thrombolysis treatment, the AUC of the best classifier was 0.780 –11. For ous work , the regThis study has some methodological limitations that need to be addressed. First, the sample size was relatively lower than that of other studies based on deep learning algorithms. However, data were collected from 13 centers, with eight types of CT and MR scanners, uniformly distributed between 0 and 24 h from the stroke onset time. Thus, the sample size was enough to support the training of the CNN model in this study. Second, data were collected retrospectively, and some inaccurate information was involved. In fact, a prospective study to evaluate the performance of our method in clinical use is a future avenue for investigation, but it does not enable to assume the clinical potential of this study. In the future, a larger, randomized, and prospective study will be designed to evaluate the performance of this method.In this study, a CNN classifier trained by CBF, Tmax, and ROI masks of Tmax > 6 s, has good performance to identify patients with AIS within a 6-h window for the treatment of EVT. Comparing with existing works to classify patients within a 4.5-h window for the treatment of rt-PA thrombolysis, to the best of our knowledge, this is the first work to assist the treatment of EVT. Meanwhile, our method performs the identifying task using CBF and Tmax, which can be acquired by CTP or PWI. It means that our method is compatible with both CT and MR devices, while previous works only support MR devices because their inputs rely on DWI and FLAIR images which are examined only by MR devices. Commonly, CT examination is faster than MR, which benefits to bring the patients out of danger. Therefore, it has the potential to be widely used to accurately estimate the stroke onset time of patients with WUS.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. Written informed consent from the [patients/ participants OR patients/participants legal guardian/next of kin] was not required to participate in this study in accordance with the national legislation and the institutional requirements.HG and YB designed the study. HG, YC, and JW collected the data. HG, YB, and HY were involved in the interpretation of data. YB, HZ, and GC analyzed and visualized the data. HG and YB drafted the manuscript. QY and LW revised the manuscript. All authors read and approved the final manuscript.


Solidago canadensis and its co-occurring native species, Artemisia argyi, when grown in culture racks in the greenhouse. The species were grown in monoculture and together in a mixed community, with and without warming, and with and without increased UV in a full factorial design. We found that growth in S. canadensis and A. argyi were inhibited and more affected by warming than UV-B radiation. Additionally, there were both antagonistic and synergistic interactions between warming and UV-B on growth and performance in both species. Overall, our results suggested that S. canadensis was more tolerant to elevated temperatures and high UV radiation compared to the native species. Therefore, substantial increases in temperature and UV-B may favour invasive S. canadensis over native A. argyi. Research focusing on the effects of a wider range of temperatures and UV levels is required to improve our understanding of the responses of these two species to greater environmental variability and the impacts of climate change.Changes in environmental factors, such as temperature and UV, have significant impacts on the growth and development of both native and invasive plant species. However, few studies examine the combined effects of warming and enhanced UV on plant growth and performance in invasive species. Here, we investigated single and combined effects of warming and UV radiation on growth, leaf functional and photosynthesis traits, and nutrient content  of invasive  Throughout the world, thousands of plant species have been moved from their native habitats and intentionally or accidentally introduced to new areas . Some ofIt is generally expected that, under current and future global environmental changes, biological invasions will increase ,10,11. T2 and other greenhouse gases are reduced in the next few decades, the global temperature is expected to increase by 1.5~2 °C by the end of this century [Over the past 200 years, human activities have warmed the climate at an unprecedented rate ,29. In t century . Plant g century , and glo century ,33. Many century ,35. Temp century , Gianoli century , Liu et  century ).While global temperatures are rising, several other environmental factors are also changing, including the amount of ultraviolet (UV) radiation reaching the earth’s surface, which is increasing mainly due to ozone depletion ,39,40. APicea asperata seedlings but also enhances their antioxidant capacity, improving their resistance to UV radiation stress. As such, warming may reduce some of the negative effects of UV (and thus the interaction has antagonistic effects) [Solidago canadensis, and its co-occurring native species, Artemisia argyi, to increases in two global environmental change factors: temperature and UV radiation (under single and combined treatments). We tested the following hypotheses: (1) increasing temperature alone will inhibit growth performance of both invasive S. canadensis and native A. argyi; (2) only increasing UV will inhibit growth and photosynthetic traits of S. canadensis and A. argyi; (3) there will be an antagonistic effect on plants between temperature and UV radiation; and (4) S. canadensis will be less affected by changes in temperature and UV compared to A. argyi.The effects of changes in temperature and UV radiation on plants are often studied separately, with only a few studies focusing on their combined effects . Han et effects) . HoweverS. canadensis, while increased UV significantly affected leaf area, leaf mass, and root to shoot ratio in this species , as did the interaction between temperature, UV light, and plant community  and under warming and increased UV . Root:shoot ratio and leaf mass in S. canadensis in the mixed community were significantly reduced when exposed to both warming and increased UV compared to the control . In the mixed community, warming significantly reduced total biomass, leaf area, and leaf mass of A. argyi  and the interactions between plant community and temperature (p < 0.001) and between community and UV , while UV had a significant effect on stomatal conductance  and increased UV (decreased by 42.80% in U compared to the control) but was not significantly affected by high temperature and UV , and C:N was significantly affected by all interactions between temperature, UV, and plant community , and with increased temperature and UV  and warmed with increased UV , while plant community had a significant effect on C:P  compared to UV , in A. argyi stomatal conductance and chlorophyll decreased under higher temperatures  under higher temperatures, resulting in an overall decline in plant productivity and biomass [Temperature affects nearly all aspects of plant growth and development, from seed germination to growth and senescence . Our resA. argyi . As suchnadensis , as wellnadensis . In our  culture . Gas exceratures . Therefo biomass .A. argyi in the monoculture, net photosynthetic rate, and maximum photochemical efficiency (PSII) were not affected by high UV alone  and Zhenjiang in Jiangsu Province, China . Seeds were placed in square pots (15 × 15 × 12 cm) filled with soil collected from Zhenjiang, sand, and a nutrient mixture (in a ratio of 1:1:1). We allocated 20 pots to each of three cultures: native species monoculture (four seedlings of A. argyi were planted per pot), native and invasive mixed culture (two seedlings of A. argyi and two seedlings of S. canadensis were placed in each pot), and invasive species monoculture (four seedlings of S. canadensis were planted per pot). In our study, we used two types of temperature, ambient and warming: as well as two levels of UV, ambient and high. Six weeks after germination, each pot was assigned to one of four treatments in a full factorial design: ambient temperature and low UV , ambient temperature and high UV (U), warming and low UV (T), and high UV and warming (U × T). There were 5 pots  per culture and per treatment. Therefore, there were a total of 240 plants in 60 pots.The experiment was conducted in the greenhouse at Jiangsu University in the summer of 2021 (June to September). We collected seeds from a community of co-occurring 2 and CO2 levels inside the culture rack, minimizing the impact of uncontrolled microclimates on the pots. To better simulate the temperature changes in the natural environment, we did not set a fixed temperature but instead ensured that the ambient treatment in the experiment was as close to the natural local temperature (in Zhenjiang) as possible by ventilating the greenhouse. For the warming group, we set a treatment that would maintain a relative temperature difference of 2 degrees in real time as the environment changed , each with one of the four treatments described above. The periphery of each culture rack was covered with a black shading net, which allowed plants to receive UV light from the top with the temperature being increased from the bottom. This design ensured the stability of Onged see . To ensunged see .−2, mean ± SE) that reached inside the greenhouse was used as the basis for the low or ambient UV treatment in our study. Two UV-B lamps  were installed in each culture shelf about 100 cm above the soil surface in the pots. The lamps in two UV high treatment culture shelves were turned on for 14 h (6:00–20:00) every day during the experiment. In the UV high treatment, the UV intensity was increased by 10.936 ± 0.186 µw cm−2 compared to the control treatment .For our experiment, we used the ambient natural UV-B light in the greenhouse as the control treatment. We measured the natural light in the greenhouse at 50 cm above the soil surface of the pots using a UV-B radiometer , and found that about 20% of the ambient UV-B was blocked. As such, the remaining UV-B light  methods, respectively. The carbon-nitrogen (C:N), carbon-phosphorus (C:P), and nitrogen-phosphorus (N:P) ratios of each plant were calculated . Finally, the total organic carbon, nitrogen, and phosphorus of each plant after drying and grinding were determined using Klculated .ARTool. The anova function  was then used to evaluate the significance of these effects, with plant number considered as a random effect. The contrast tests were implemented using the art.con function (ARTool package) [All statistical analyses were performed in R version 4.2.1 (R Core Team 2022). Plots of all measured traits were generated using the ggplot2 and ggsignif packages in R. Our preliminary exploration of the data using Levene’s and Shapiro-Wilks tests revealed that the normality and variance assumptions of the analysis of variance (ANOVA) were not met. Therefore, we used aligned rank transformation (ART) to implement the nonparametric factorial ANOVA. ART is a powerful and robust approach that is a nonparametric equivalent to the usual classical parameter analysis techniques and can be applied when the normality criterion is not met ,105,106.package) ,110,111.S. canadensis and a co-occurring native species, A. argyi, were inhibited under the influence of warming and increased UV-B, with both species being more affected by increased temperature. We found evidence of antagonistic interactions between temperature and UV on plant growth in both species, although more traits in A. argyi were affected by antagonism between the two factors than in S. canadensis. Although growth and performance traits in the two species were negatively impacted by single and combined effects of warming and UV, overall, S. canadensis was more tolerant than A. argyi in response to high temperature and UV-B irradiance. As such, under large increases in temperature and UV radiation, S. canadensis may be more resistant, and could gain an advantage over A. argyi in the wild. Future research should examine the growth performance of these two species when exposed to a wider range of temperature and UV radiation than explored in this study to assess the impacts of large-scale environmental changes.Our study showed that the growth of the invasive


Many observational studies imply elevated blood pressure (BP) as a leading risk factor for incident myocardial infarction (MI), but whether this relationship is causal remains unknown. In this study, we used bidirectional Mendelian randomization (MR) to investigate the potential causal association of BP levels with the risk of MI.N = 7,57,601) and UKB , obtaining 1,26,40,541 variants. We used two-sample MR (TSMR) analyses to examine the potential bidirectional causal association of systolic BP (SBP), diastolic BP (DBP) and pulse pressure (PP) with MI.Genetic variants associated with BP and MI traits were retrieved from the International Consortium of Blood Pressure pp: 1.0092, P = 0.179]. However, the reverse analysis suggested no causal relation . These findings were robust in sensitivity analyses such as the MR–Egger method, the maximum likelihood method and the MR pleiotropy residual sum and outlier test (MR-PRESSO). No horizontal pleiotropy  was observed.The forward MR analysis identified a potentially causal association between MI and BP except PP[odds ratio (OR) Elevated SBP or DBP levels increase the risk of MI, but there is no causal relationship between MI and changes in BP including PP. Independent of other risk factors, optimal BP control might represent an important therapeutic target for MI prevention in the general population. Hypertension (HT) and myocardial infarction (MI) are two interconnected global public health burdens. The estimated prevalence of hypertension is 31%, and coronary artery disease (CAD) affects 10% of adults –4.Myocardial infarction, a major reason of mortality and morbidity in older adults, is a term for a heart attack event that originates from the Latin: infarctus myocardii, or MI . When onAmong the risk factors, age has the strongest relationship with the development of CAD and myocardial infarction , 7. OtheIt is difficult to confirming a causality, as the effect between BP and MI might be confounded with several disparate factors. For instance, elevated BP is usually associated with advanced age, which is also an vital risk factor. This makes it challenging to clarify whether or not BP and MI are related to each other or simply mean comorbidities clustered in older subjects. Mendelian randomization (MR)  is an inN = 3,61,194). The detail of the data were listed in The analyses conducted in our study were based on public available summary data originated from GWAS group. And, genetic variants related with BP values were performed as IVs for the MR analyses. The summarized GWAS data were extracted from the IEU OpenGWAS project. Blood pressure data were retrieved from the International Consortium of Blood Pressure Genome-Wide Association Studies (ICBP)  and IshiWe conducted separate TSMR approaches to probe the causal associations potentially between systolic BP (SBP) and diastolic BP (DBP) as well as pulse pressure (PP) and the risk of MI, probing the association in two non-overlapping populations. The three vital assumptions underlying the TSMR method are shown in a. The genetic variants must be closely related to the exposure;b. The variants must have an effect on the outcome uniquely via their influence on the exposure;c. The variants ought to be unique of any bias of the affect between the outcome and the exposure .p-value of IVs had to be < 5 × 10−8 in the GWAS data to guarantee a strong relationship between IVs and BP levels. These SNPs were further pruned for linkage disequilibrium  to guarantee independence among the genetic variants. The single-nucleotide polymorphisms (SNPs) must be removed from our analyses when r2 was >0.001. We excluded SNPs associated with acknowledged confounders . Afterwards, palindromic SNPs were eliminated to guarantee that the effects of the SNPs related to the exposure corresponded to the same allele as their effects on MI.IVs must to be related to the exposure. In our forward MR analysis, the In our forward MR analysis, we performed the inverse variance-weighted (IVW) approach to calculate the causal effect . The fixThe weighted median requires that 50% of the weight valued to variables be from valid instruments . In contWe performed leave-one-out sensitivity approach to identify whether a single SNP disproportionately controlled the effect. All of the our work were two-sided. All analyses were calculated in R version 4.0.5.All methods were performed using the “TwoSampleMR” and “MRPRESSO” package.r2 = 0.001, 10,000 kb), 461 SNPs for SBP,460 SNPs for DBP and 16 SNPs for PP were identified as instruments in the GWAS. After assessment for the three key assumptions of TSMR was conducted and the palindromic SNPs were removed, 434 SNPs for SBP,442 SNPs for DBP and 15 SNPs for PP were included in the analysis. Alcohol consumption, diabetes, smoking, and cholesterol and triglyceride levels were used as confounders. The details of our forward MR analysis are shown in P = 1.911e−22 for SBP, OR: 1.0014, 95% CI: 1.0011–1.0016, P = 1.788e-28 for DBP and OR: 1.0092, 95% CI: 0.9958–1.0227, P = 0.179 for PP). Random effect methods were performed to account for the material heterogeneity exposed in IVW  and MR–Egger . Notably, the intercept obtained with the MR–Egger approach was un-noteworthy, hinting that the SNPs correspond to BP did not perform any pleiotropic effects . The overall estimates revealed causal associations between BP and MI . We analyzed the F values to assess the effectiveness of the relationships among IVs and homologous exposures. The F values matching the selected IVs were 28 for SBP, 30 for DBP and 14 for PP, which were efficacious enough to reduce any bias from the results on the causal.Both the raw and outlier-corrected estimates  from the PRESSO approach are consistent to the other results, setting up the association of BP traits with MI on the causal  , 33. AthTraditional observational epidemiology is one of the most strong methods of proving the hypothesis of etiology in epidemiological study and is likely affected by confounding factors that have created many difficulties in revealing causal inference and the cause of disease. For instance, the diagnosis of HT hinges on the precise measurement of BP. As Kaplan stated, “The measurement of blood pressure is likely the clinical procedure of greatest importance that is performed in the sloppiest manner” . The corThe application of MR can dexterously overcome the characteristic of traditional epidemiological study in expounding the etiology, such as confounder and unknown causal sequences, and derivative new tactics and approaches for epidemiological study in etiology . AnotherThere are several limitations in our study. First, we imposed restrictions on the study population to the main individuals of European ancestry to lower bias from population stratification. This restriction imposed lowered the transferability to individuals who have other genetic backgrounds. Second, because the individual data were not available, we could not perform analyses stratified by subtypes and severity of MI. Additionally, the application of a genetic instrument including number of genetic variants for each component part of BP elevates the risk of including pleiotropic SNPs. However, we addressed horizontal pleiotropy through MR sensitivity analysis. Nevertheless, we could not address unobserved pleiotropy. When some instrumental SNPs show horizontal pleiotropy, our estimates of IVW effect are apt to be biased.Performing a genetic method, we verified that BP levels are causally associated with MI risk.The original contributions presented in the study are included in the article/Ethical review and approval was not required for this study in accordance with the local legislation and institutional requirements.Z-QY and T-TF conceived the study, participated in the design, performed the statistical analyses, and drafted the manuscript. B-LX conceived the study, participated in the design, and helped to draft the manuscript. QW revised the paper. All authors gave final approval and agree to be accountable for all aspects of work ensuring integrity and accuracy.This present study was supported by the Second Affiliated Hospital of Anhui Medical University – Hefei Institute of Intelligent Machinery, Chinese Academy of Sciences–Joint Research Fund for Prevention and Control of Chronic Diseases (MBLHJJ202007).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


To determine whether the visceral adiposity index (VAI) was linked to the risk of kidney stones (KS) in the representative U.S. adults.We investigated 59842 participants who joined the 2007–2018 National Health and Nutrition Examination Survey. The association between the visceral adiposity index (VAI) and KS was identified by logistic regression analysis. Meanwhile, the subgroup analysis as well as the calculation of dose−response curves were also utilized to identify sensitive groups.Data from 29384 participants were available, including 2781 self-reported ever experiencing KS diseases. Overall, the VAI was 0.74  in the KS group, while 0.55  in the control group. After adjusting for confounders, the prevalence of KS increased by 13% for each unit of VAI increment . Moreover, a linear relationship was found between the VAI and the prevalence of KS. By subgroup analysis, we found that a positive correlation between VAI and the risk of KS both in male  and female , White  and other race, all aged subgroups, nonhypertensive  and nondiabetic subgroups .Elevated VAI was strongly associated with KS in representative U.S. adults, which may be a promising indicator for the risk of kidney stones. Kidney stones (KS) are widespread diseases of the urinary system, that clinically manifest as hematuria, renal colic, urinary tract infection, urinary tract obstruction, and, in severe cases may manifest as renal failure and are even life-threatening –3. EpideCurrently, accumulated evidence suggests that metabolic syndrome (MS) is implicated in an elevated risk of KS –11, in wInterestingly, researchers have recognized that adipose tissue has complex functions and that not all adipose tissue is harmful to the body, such as brown fat , so thatThe visceral adiposity index (VAI) is an indicator of abdominal fat distribution and adipose tissue function proposed by Amato et al. . Its calThe baseline clinical data included in this analysis were derived from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018, in which only participants aged over 20 years participated in the KS questionnaire; we preserved information on people who answered affirmatively as to whether they had kidney stones. A total of 59842 participated in the questionnaire. After excluding 30098 nontargeted participants, 29384 participants were available in this work Figure 1The VAI was developed as an exposure variable utilizing the below gender-specific equations. For males VAI=[WC(cm)/(39.68 + 1.88×BMI(kg/m2))]×(TG(mmol/L)/1.03)×(1.31/HDL(mmol/L)); for females VAI=[WC(cm)/(36.58 + 1.89×BMI(kg/m2))]×(TG(mmol/L)/0.81)×(1.52/HDL(mmol/L)) . Serum thttp://www.cdc.gov/nchs/nhanes/. All NHANES protocols were implemented following the Human Research Subject Protection Policy of the U.S and reviewed and standardized by the NCHS Research Ethics Review Committee. Informed consent forms were signed by all participants. There was no additional authorization or ethical review required for the release of NHANES data for this study.In multivariate adjusted models, we summarized covariates that may confound the relationship between VAI and KS. The following factors were included in the study’s covariates: gender, race, age, education level, cholesterol concentration, marital status, alcohol intake, poverty-to-income ratio (PIR), smoking status, physical activity, diabetes, hypertension, and dietary intake factors. The 24-hour dietary recall was conducted on each participant in 2007 and 2018, and we will analyse the average consumption of both recalls. Detailed measurement protocols using the research variables are available at ® 4.0.2 was utilized for all analyses .The NHANES sample weights, clustering and stratification were used in all statistical analyses to illustrate the elaborate sampling methodology used to select a representative sample of U.S. noninstitutionalized adults. Continuous variables are presented as weighted survey means and 95% CIs, while categorical variables are presented as weighted surveys and 95% CIs. As VAI have skewed distributions, LN transformations convert them into normal distributions. In our study, we performed VIF covariate screening and removed covariates if the VIF value was greater than 5. Based on the guidelines , a multiThe baseline demographic characteristics among the enrolled participants are summarized in The VIF for all indices of covariate screening was less than 5, and all variables were analyzed in the final adjusted model. The results showed that a positive correlation was identified between the VAI and the prevalence of KS. This positive correlation remained stable in the model 3 , indicating that the prevalence of KS increased by 13% with each unit increase in the LN-transformed VAI. Meanwhile, we converted the VAI to a categorical variable (triple quantile) from a continuous variable for sensitivity analysis and found that a significant 0.25-fold increase in KS presence was observed in Tertile 3  compared to the lowest VAI lowest tertile (Tertile 1), as shown in To assess the robustness of the VAI-KS relationship, subgroup analyses were conducted Table 3.Generalized additive model regression as well as smoothed curve fitting were applied to assess the relationship between the VAI and KS. Our results showed that VAI was linearly related to KS presence Figure 2Although obesity is involved in the high prevalence of KS , 19, 27,VAI as a specific index of visceral adiposity disorders has been widely associated with cardiovascular diseases, hypertension, human purine metabolism, insulin resistance and thyroid function –32. ReceKS is a common urological disease with a high global prevalence but an unknown mechanism. On the one hand, the specific mechanism of its occurrence is still unclear, and there is no effective etiologic prevention method; on the other hand, the treatment method of KS is constantly adjusted according to the progress of the patient’s stones, and early detection of KS can reduce the possibility of invasive operations for patients, reduce the pain suffered by patients and reduce the cost of treatment . TherefoSubgroup analysis showed that the relationship between the VAI and KS incidence was robust and generalized, and this positive correlation still existed in different gender, ethnicities, and age groups. This result needs to be supported by a larger sample size study. After further subgroup studies, the lowest VAI group (Tertile 1) showed a significant 25% increase in the prevalence of KS compared with the highest VAI group (Tertile 3), reflecting the considerable sensitivity of the VAI. A promising point in this study was that in different age subgroups, patients with a high VAI in the younger age group had a stronger correlation with KS presence than patients with a high VAI in the older age group, which gives us a new strategy for KS prevention, namely the management and control of the VAI in younger patients. We hypothesized that an elevated VAI is an important factor in the development of pro-KS and contributes to cardiovascular disease, metabolic syndrome and other disorders. However, the low age of the patient itself is a protective factor for cardiovascular disease, metabolic syndrome but has no significant protective effect on the development of KS, so the prediction of KS by the high VAI may have a higher specificity within younger individuals. No relevant reports in this regard have been published, and follow-up large-scale prospective studies are needed to confirm this causal relationship.Our study has the following advantages. First, NHANES study participants are representative U.S. adults, which closely followed a well-designed study protocol with extensive guarantee and conformance. Second, we controlled for confounding variables and performed subgroup analyses to make our findings reliably and stably applicable to a wider range of individuals. Third, we further demonstrated that the VAI was linearly related to the prevalence of KS. However, the limitations of our study cannot be ignored. First, our cross-sectional investigation was based on the NHANES database, which prevented us from assessing a causal relationship between VAI and KS. Second, the prevalence of KS was obtained from patient self-reports, and recall bias was inevitable. Despite these limitations, our study clearly revealed a positive correlation between the VAI and KS presence.We demonstrated that the elevated VAI was strongly associated with KS in representative U.S. adults in a cross-sectional study. VAI may be a promising indicator for the risk of KS, which is beneficial for prevention guidance of KS.The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.https://www.cdc.gov/nchs/nhanes/irba98.htm). The patients/participants provided their written informed consent to participate in this study.The studies involving human participants were reviewed and approved by the NCHS Research Ethics Review Committee approved the NHANES survey protocol  and the Natural Science Foundation of Anhui Province .We thank all other researchers in our laboratory for their valuable help in our work.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


We assessed the outcomes and characteristics of culture-negative septic shock (CNSS) and culture-positive septic shock (CPSS) in pediatric intensive care unit (PICU).We performed a retrospective study on the data of children admitted to the PICU due to septic shock between January 2018 and December 2021. The primary outcome was in-hospital mortality. The secondary outcomes were the length of stay (LOS) of hospital, the need for mechanical ventilation (MV) and continue renal replacement therapy (CRRT).P = 0.866), PRISM-III score , PIM-3 score , pSOFA score  or the need for MV  and CRRT  between the CNSS group and the CPSS group. The Procalcitonin  and C-reactive protein  levels were significantly lower in the CNSS group than in the CPSS group, while WBC count  and serum sodium  was significantly higher in CNSS. The LOS of hospital was significantly longer  in the CPSS group than in the CNSS group, while the LOS of PICU  stay was not significantly different.Overall, 238 patients were enrolled. 114 patients (47.9%) had positive cultures , 18 of whom were cultured positive at two sites, 1 at three sites, and 3 had two different types of bacteria at same site. The in-hospital mortality was 47.1%. There were no significant differences in the in-hospital mortality (47.6% vs. 46.5%, Compared with children with CNSS, children with CPSS had higher PCT and CRP levels, but lower WBC count. Children with CPSS had longer LOS of hospital. However, positive or negative culture results were not associated with in-hospital mortality, the LOS of PICU, the need for MV or CRRT in children with septic shock. Sepsis is a leading cause of health loss worldwide and consumes significant medical resources . ChildreWhen treating sepsis, the current guidelines recommend obtaining cultures before initiating antimicrobial therapy . PhysiciAlthough the culture of biological specimens is an indispensable part of the initial therapy of sepsis, the impact of culture results on mortality, therapy requirements and other clinical outcomes in pediatrics is still not well studied. Exploratory studies were made in the adult field. Kim et al.  showed tWe hypothesized that children with positive cultures would have worse clinical outcomes than children with negative cultures, as positive cultures may represent higher pathogen load and hint at more severe illness scores for patients with septic shock. To verify this, we compared the clinical parameters, therapy requirements and outcomes of culture-negative septic shock (CNSS) and culture-positive septic shock (CPSS) children.We performed a retrospective cohort study to analyze the clinical data and outcomes of children with septic shock admitted to the PICU of Children's Hospital of Chongqing Medical University from January 1, 2018, to December 31, 2021. The PICU is a comprehensive central intensive care unit with 80 open beds divided into a medical subunit and a surgical subunit. The Institutional Review Board of Children's Hospital of Chongqing Medical University approved this study. The data of patients were anonymized and deidentified prior to analysis. The requirement for informed consent was waived due to the retrospective nature of this study.Infection was clinically diagnosed by the children's attending physicians according to the clinical manifestation, laboratory examination and imaging. Septic shock was diagnosed as severe infection leading to cardiovascular dysfunction , referring to the 2017 clinical practice and 2020 guidelines for children , 11. ThePatients were identified according to the discharge diagnosis from the hospital electronic medical databases and admission to the PICU due to septic shock. We excluded the patients diagnosed with septic shock in other departments of the hospital but not transferred to the PICU and the patients with combined viral infections. We also excluded the patients from surgery department undergoing abdominal surgery transferred to PICU for postoperative anesthetic ventilation support only and returned to surgery department in the next day.+) and serum potassium (K+). The blood samples was collected at admission, such as PCT, CRP and other blood parameters.The culture results were collected. The following demographic and clinical data were examined: age, sex, comorbidity, white blood cell (WBC), hemoglobin (Hb), platelet (PLT), Procalcitonin (PCT), C-reactive protein (CRP), lactate, glucose, bilirubin, albumin, creatinine, urea, alanine aminotransferase (ALT), international normalized ratio (INR), serum sodium -3 , pediatrThe primary outcome was in-hospital mortality at any time. The secondary outcomes were the length of PICU stay, the length of hospital stay, and the need for MV and CRRT. To account for death as a competing outcome, PICU-free days and hospital-free days with a maximum of 14 and 28 days were used, respectively.P values < 0.05 were considered to be statistically significant.Statistical analysis was performed with SPSS Statistics for Windows, Version 26 . Data were stratified by culture results . Continuous variables are expressed as the medians (interquartile range), and categorical variables are shown as the counts (frequency or percentage). Continuous variables were compared using the Mann-Whitney U test, and categorical variables were analyzed using the chi-squared or Fisher's exact test. Kaplan-Meier survival curves were subjected to the log-rank test based on culture results. P = 0.700). In terms of laboratory tests, there was no significant difference in bilirubin (6.65 vs. 9.20 μmol/L), albumin (26.9 vs. 24.9 g/L), lactate (2.0 vs. 2.0 mmol/L), creatinine (46.0 vs. 48.0 μmol/L), glucose (6.0 vs. 6.2 mmol/L), urea (5.91 vs. 6.60 mmol/L), INR (1.37 vs. 1.44), or K+ (3.6 vs. 3.5 mmol/L) between the CNSS group and the CPSS group. There were also no significant differences in the PIM-3, PRISM-III and pSOFA scores. Moreover, the requirements of CRRT and MV were similar between the two groups. Although the days of CRRT and MV in CPSS group were greater than those in CNSS group, the difference was not statistically significant.In total, 238 children with septic shock were enrolled during the study period, which included 124 (52.1%) in the CNSS group and 114 (47.9%) in the CPSS group. The clinical characteristics of the children according to the culture results are listed in P = 0.001) and CRP  levels were significantly lower in the CNSS group than in the CPSS group, while the reverse was true for the WBC , PLT , Hb  counts and serum sodium   .P = 0.033) in the two groups, patients with hematologic malignancy (n = 45) were excluded, and characteristic data were reanalyzed (P = 0.003) and CRP  in the CPSS group were still significantly higher, while WBC  and serum sodium  was still significantly lower in the CPSS group after exclusion  and Hb  were not significantly different between the two groups  in in-hospital mortality between the CNSS group and the CPSS group. The length of stay (LOS) of hospital stay was significantly longer  in the CPSS group than in the CNSS group, while the length of PICU stay was not significantly different . The CPSS group had fewer hospital-free days (P = 0.025).As shown in P = 0.875) in in-hospital mortality between the two groups  in the CNSS group than in the CPSS group , while the reverse was true for skin and soft tissue infections  and digestive system (34.5%) were dominant in children with septic shock . The proStaphylococcus species (21.9%). However, gram-negative bacteria accounted for 51.8% of all bacteria, and Klebsiella species were the most common gram-negative bacteria. 56 children were infected with gram-negative bacteria only, and 38 children were infected with gram-positive bacteria only. There was no significant difference in PCT  between children infected with gram-negative bacteria only and those infected with gram-positive bacteria only. However, children infected with gram-positive bacteria only had significantly elevated CRP , compared with children infected with gram-negative bacteria only.The pathogens of the positive cultures are shown in P = 0.312).The 60-day survival rate in the CNSS group was slightly lower than that in the CPSS group . However+ in the two groups were significantly different.In the diagnosis and treatment of septic shock in children, it is routine to identify pathogenic microorganisms by culture. However, the positive rate of culture is limited, and the impact of positive or negative culture results on the treatment and prognosis of children with septic shock remains unclear. Our study showed that: (1) approximately 52.1% of septic shock children had negative culture results; (2) the in-hospital mortality of CNSS patients and CPSS patients was very similar, while the length of hospital stay of CPSS patients was longer than that of CNSS patients; and (3) PCT, CRP and NaThis study showed fairly common negative culture results in children with septic shock, which was consistent with the previous findings of several retrospective studies of adult patients with septic shock or severe sepsis , 16, 17.In the past decade, many studies have explored the impact of culture results on the prognosis of adult patients with sepsis. Kim et al.  indicateIn the field of children's sepsis, there have been few studies on the impact of culture results on death. One study found that children with severe sepsis/septic shock with positive bacterial blood cultures had higher mortality than those with negative bacterial blood cultures . This stPatients with severe sepsis/septic shock usually accompanied by respiratory failure, acute kidney injury and other organ dysfunction and need to be hospitalized for a long time. The LOS of hospital and MV duration were both longer in the culture-positive septic group than in the culture-negative septic group, while the CRRT duration and the requirements of MV and CRRT were similar between the two groups . Gupta eFew articles in the current research focus on the relationship between serum sodium and culture results. Our study found that the serum sodium in the CPSS group was significantly lower than that in the CNSS group, which may mean that patients in the CPSS group need more aggressive measures to maintain electrolyte balance.PCT may reflect the severity of infection, guide antimicrobial treatment and reduce unnecessary antibiotic use in clinic –20. SomeCRP is also a nonspecific inflammatory marker. Phua et al.  showed tIn this study, no significant difference in clinical outcomes between the two groups, while hospital stays were indeed longer in the CPSS group. Our study hinted that significantly elevated PCT and CRP may be related to positive culture results and prolonged hospital stay in children with septic shock. The high mortality of sepsis/septic shock may be attributed to the heterogeneity, that is, the complexity and diversity of sepsis/septic shock from etiology, pathogenesis to clinical outcome. With the deepening understanding of sepsis heterogeneity, it is necessary to classify sepsis from its clinical phenotype. It may be of great significance to analyze the subtype characteristics, treatment needs and inflammatory response of pediatric septic shock from the aspects of bacterial culture results or infection sites. However, there are few researches on these aspects. Exploring the subgroup characteristics of children with septic shock may be able to standardize the definition of pediatric sepsis, find more targeted and effective treatment measures, and better predict the prognosis.There are several limitations in this study. First, the findings were retrospectively derived from a single center and at risk of bias. Second, the size of the samples included in the study was relatively small. Third, the high rate of antibiotic use before PICU admission may have affected the culture results. Fourth, children with hematological malignancies accounted for 18.9% of all patients, which may have had a certain impact on blood test indicators. After excluding such children, we still found that there was no change in statistical trends. Sixth, in this study, a considerable number of children who admitted to the PICU had multiple organ dysfunctions. Therefore, the patients included in our study may be more serious than other studies. Finally, although the PICU medical staff were experienced in culture sample collection, it was difficult to guarantee whether each culture-negative or -positive specimen was strictly qualified because of the inherent defect of retrospective research. However, this may be the first clinical study concerning the relationship between the culture results and the clinical outcome in children with septic shock in the PICU.Approximately 47.9% of children with septic shock were culture-positive. Children with CPSS had higher PCT and CRP levels, but lower WBC count and serum sodium. And the length of hospital stay of children with CPSS was longer than that of children with CNSS. However, in-hospital mortality, the length of PICU stay, the requirements of MV and CRRT were not associated with positive or negative culture results in children with septic shock in the PICU.