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Early diagnosis of septic shock in children is critical for prognosis. This study committed to investigate the signature genes and their connection with immune cells in pediatric septic shock. We screened a dataset of children with septic shock from the GEO database and analyzed differentially expressed genes (DEGs). Functional enrichment analysis was performed for these DEGs. Weighted gene co-expression network analysis (WCGNA) was used to screen the key modules. Least absolute shrinkage and selection operator (LASSO) and random forest analysis were finally applied to identify the signature genes. Then gene set enrichment analysis (GSEA) was exerted to explore the signaling pathways related to the hub genes. And the immune cells infiltration was subsequently classified using CIBERSORT. A total of 534 DEGs were screened from GSE26440. The data then was clustered into 17 modules WGCNA, which MEgrey module was significantly related to pediatric septic shock (cor=-0.62, <0.0001). LASSO and random forest algorithms were applied to select the signature genes, containing UPP1, S100A9, KIF1B, S100A12, SLC26A8. The receiver operating characteristic curve (ROC) of these signature genes was 0.965, 0.977, 0.984, 0.991 and 0.989, respectively, which were verified in the external dataset from GSE13904. GSEA analysis showed these signature genes involve in positively correlated fructose and mannose metabolism and starch and sucrose metabolism signaling pathway. CIBERSORT suggested these signature genes may participate in immune cells infiltration. UPP1, S100A9, KIF1B, S100A12, SLC26A8 emerge remarkable diagnostic performance in pediatric septic shock and involved in immune cells infiltration.

Background The triglyceride-glucose (TyG) index is a reliable alternative biomarker of insulin resistance (IR). However, whether the TyG index has prognostic value in critically ill patients with coronary heart disease (CHD) remains unclear. Methods Participants from the Medical Information Mart for Intensive Care III (MIMIC-III) were grouped into quartiles according to the TyG index. The primary outcome was in-hospital all-cause mortality. Cox proportional hazards models were constructed to examine the association between TyG index and all-cause mortality in critically ill patients with CHD. A restricted cubic splines model was used to examine the associations between the TyG index and outcomes. Results A total of 1,618 patients (65.14% men) were included. The hospital mortality and intensive care unit (ICU) mortality rate were 9.64% and 7.60%, respectively. Multivariable Cox proportional hazards analyses indicated that the TyG index was independently associated with an elevated risk of hospital mortality (HR, 1.71 [95% CI 1.25–2.33] P = 0.001) and ICU mortality (HR, 1.50 [95% CI 1.07–2.10] P = 0.019). The restricted cubic splines regression model revealed that the risk of hospital mortality and ICU mortality increased linearly with increasing TyG index (P for non-linearity = 0.467 and P for non-linearity = 0.764). Conclusions The TyG index was a strong independent predictor of greater mortality in critically ill patients with CHD. Larger prospective studies are required to confirm these findings.

Background Triglyceride-glucose (TyG) index as a reliable surrogate of insulin resistance (IR) has been shown to be related to adverse clinical outcomes in patients with acute coronary syndrome, heart failure, ischemic stroke and so on. However, the relationship between TyG index and all-cause mortality in intensive care unit (ICU) patients remains unknown. The purpose of this study was to investigate the correlation between TyG index and all-cause mortality to evaluate the impact of IR on the prognosis of this population. Methods This was a retrospective observational study that included 3026 patients who had an initial triglyceride and glucose data on the first day of ICU admission, and all data were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. These patients were grouped into quartiles (Q1–Q4) according to TyG index. The Kaplan–Meier analysis was used to compare all-cause mortality among the above four groups. Cox proportional hazards analyses were performed to examine the association between TyG index and all-cause mortality. Results During 10.46 years of follow-up, 1148 (37.9%) patients died, of which 350 (11.6%) occurred during the hospital stay and 258 (8.5%) occurred during the ICU stay. Kaplan–Meier analysis showed that the risk of all-cause mortality was significantly higher in patients with higher TyG index (log-rank P  = 0.021). Multivariable Cox proportional hazards analyses showed that the TyG index was an independent risk predictor of ICU death (HR: 1.72, 95% CI 1.18–2.52, P  = 0.005) and hospital death (HR: 2.19, 95% CI 1.59–3.03, P  < 0.001), and each 1-unit increased in the TyG index, a 1.19-fold increase in the risk of death during the hospital stay. Conclusions TyG index is strongly related to the all-cause mortality increasing in critically ill patients. This finding indicates that the TyG index might be useful in identifying people at high risk of ICU death and hospital death.

The quality of covalent organic frameworks (COFs) crucially influences their mechanistic research and subsequent practical implementations. However, it has been widely observed that the structure damage induced by the activation procedure could compromise the quality of COFs. Here we develop a self-sacrificing guest method for synthesizing high-quality two-dimensional COFs (SG-COFs) by incorporating salt guests into the pores of the COF structure. These introduced salts play an indispensable role in supporting COF pores and mitigating quality loss during the activation process. Interestingly, due to the unique characteristic of salts decomposing into gases upon heating, this method can ultimately enable the synthesis of highly pure, high-quality COFs without the presence of residual guest molecules. The resulting sixteen COFs display superior crystallinity and porosity compared to those synthesized using conventional routes. Moreover, these high-quality SG-COFs have demonstrated to be highly efficient adsorbents for removal of per- and polyfluoroalkyl substances. The quality of covalent organic frameworks is often compromised by structural damages induced during their activation procedure which influences their subsequent applications. Here, the authors describe a self-sacrificing guest strategy to synthesize high-quality two-dimensional COFs by incorporating salt guests within the pores of the COF structure.

Objective To investigate the effects of Treatment and Education of Autistic and Related Communication Handicapped Children (TEACCH) on social functioning in individuals with autism spectrum disorders (ASD). Methods Relevant studies on TEACCH intervention in ASD individuals were systematically searched in PubMed, The Cochrane Library, Embase, CNKI, and Wanfang from inception to March 2024. The main outcome measures were social, cognitive performance, fine motor, communication, daily living, imitation, and cognitive verbal skills. Data were meta-analyzed using R studio (4.1.2). Results Eleven studies involving 701 ASD individuals were included in this study. The TEACCH group had significantly higher socialization score [MD = 0.6, 95% CI(0.2, 1.0)], Cognitive Performance Scale score [MD = 1.34, 95% CI(0.09, 2.58)], and fine motor score [MD = 0.7, 95% CI(0.4, 1.0)] but significantly lower Autism Behavior Checklist score [MD = -1.57, 95% CI(-2.11, -1.02)], Childhood Autism Rating Scale score [MD= -0.7, 95%CI(-1.0, -0.3)], and Autism Treatment Evaluation Checklist score [MD= -0.7, 95% CI(-1.0, -0.3)] compared to the control group. There were no significant differences in other outcome measures. Conclusion TEACCH is a promising intervention for improving the social skills, cognitive performance, and fine motor functions of ASD individuals. However, further studies are warranted to confirm the effectiveness of TEACCH on ASD core symptoms.

Background Thyroid cancer is a common thyroid malignancy. The majority of thyroid lesion needs intraoperative frozen pathology diagnosis, which provides important information for precision operation. As digital whole slide images (WSIs) develop, deep learning methods for histopathological classification of the thyroid gland (paraffin sections) have achieved outstanding results. Our current study is to clarify whether deep learning assists pathology diagnosis for intraoperative frozen thyroid lesions or not. Methods We propose an artificial intelligence-assisted diagnostic system for frozen thyroid lesions that applies prior knowledge in tandem with a dichotomous judgment of whether the lesion is cancerous or not and a quadratic judgment of the type of cancerous lesion to categorize the frozen thyroid lesions into five categories: papillary thyroid carcinoma, medullary thyroid carcinoma, anaplastic thyroid carcinoma, follicular thyroid tumor, and non-cancerous lesion. We obtained 4409 frozen digital pathology sections (WSI) of thyroid from the First Affiliated Hospital of Sun Yat-sen University (SYSUFH) to train and test the model, and the performance was validated by a six-fold cross validation, 101 papillary microcarcinoma sections of thyroid were used to validate the system’s sensitivity, and 1388 WSIs of thyroid were used for the evaluation of the external dataset. The deep learning models were compared in terms of several metrics such as accuracy, F1 score, recall, precision and AUC (Area Under Curve). Results We developed the first deep learning-based frozen thyroid diagnostic classifier for histopathological WSI classification of papillary carcinoma, medullary carcinoma, follicular tumor, anaplastic carcinoma, and non-carcinoma lesion. On test slides, the system had an accuracy of 0.9459, a precision of 0.9475, and an AUC of 0.9955. In the papillary carcinoma test slides, the system was able to accurately predict even lesions as small as 2 mm in diameter. Tested with the acceleration component, the cut processing can be performed in 346.12 s and the visual inference prediction results can be obtained in 98.61 s, thus meeting the time requirements for intraoperative diagnosis. Our study employs a deep learning approach for high-precision classification of intraoperative frozen thyroid lesion distribution in the clinical setting, which has potential clinical implications for assisting pathologists and precision surgery of thyroid lesions.

ObjectiveThe American Heart Association (AHA) proposed the concept of ideal cardiovascular health (CVH) to reduce the risk of cardiovascular mortality. We attempted to broaden the impact of CVH and further contribute to AHA 2030 goals by identifying the relationship between CVH and non-cardiovascular diseases such as sarcopenia.DesignCross-sectional surveySettingNational Health and Nutrition Examination Survey conducted in the USA from 2011 to 2018.ParticipantsThis study included participants with reliable first 24-hour dietary recall and ≥20 years of age and excluded those who could not diagnose sarcopenia or insufficient data to calculate the CVH scores.Primary and secondary outcome measuresThe prevalence of sarcopenia as measured by dual-energy X-ray absorptiometry.ResultsThis cohort study involving 9326 adults≥20 years comprised 4733 females (50.0%). The number of intermediate or ideal and poor CVH participants was 5654 and 3672 with mean CVH score of 9.70±0.03 and 5.66±0.04, respectively. After adjusting for related confounding factors, intermediate or ideal CVH was associated with an odds reduction of sarcopenia than poor CVH (adjusted OR (aOR): 0.36, 95% CI 0.26 to 0.50, p<0.001) and the odds of sarcopenia was significantly lower for each incremental increase of 1 in CVH metrics (aOR: 0.75, 95% CI 0.71 to 0.79, p<0.001). Moreover, if the number of ideal CVH metrics was>5, the odds of sarcopenia decreased by up to 84% (aOR: 0.16, 95% CI 0.08 to 0.30).ConclusionsOur findings suggest a relationship between the CVH and the prevalence of sarcopenia in adults. The results of our study can contribute to achieving the 2030 public health goal of achieving CVH for all, which may be supported by efforts to reduce the prevalence of sarcopenia.

The drilling fluid cooling system is a key technology for reducing wellbore temperatures, improving the working environment of downhole equipment, and ensuring safe and efficient drilling in high-temperature wells. Based on the existing drilling fluid cooling system, this article designs and develops a closed drilling fluid cooling system according to the working environment and cooling requirements of the GH-02 dry hot rock trial production well in the Gonghe Basin, Qinghai Province. The system mainly includes a cascade cooling module, a convective heat exchange module, and a monitoring and control module. Based on the formation conditions and drilling design of the GH-02 well, a transient temperature prediction model for wellbore circulation is established to provide a basis for the design of the cooling system. Under the conditions of a drilling fluid displacement of 30 L/s and a bottomhole circulation temperature not exceeding 105 °C, the maximum allowable inlet temperature of the drilling fluid is 55.6 °C, and the outlet temperature of the drilling fluid is 69.2 °C. The heat exchange of the drilling fluid circulation is not less than 1785 kW. Considering the heat transfer efficiency and reserve coefficient, the heat transfer area of the spiral plate heat exchanger calculated using the average temperature difference method is not less than 75 m2. By applying this drilling fluid cooling system in the 3055 m~4013 m section of well GH-02, the inlet temperature is controlled at 45 °C~55 °C, and the measured bottomhole circulation temperature remains below 105 °C. After adopting the drilling fluid cooling system, the performance of the drilling fluid is stable during the drilling process, downhole tools such as the drill bits, screws, and MWD work normally, and the failure rate of the mud pump and logging instruments is significantly reduced. The drilling fluid cooling system effectively maintains the safe and efficient operation of the drilling system, which has been promoted and applied in shale oil wells in Dagang Oilfield.

Background Optical genome mapping (OGM) has developed into a highly promising method for detecting structural variants (SVs) in human genomes. Complex chromosomal rearrangements (CCRs) and cryptic translocations are rare events that are considered difficult to detect by routine cytogenetic methods. In this study, OGM was applied to delineate the precise chromosomal rearrangements in three cases with uncertain or unconfirmed CCRs detected by conventional karyotyping and one case with a cryptic translocation suggested by fetal chromosomal microarray analysis (CMA). Results In the three cases with CCRs, OGM not only confirmed or revised the original karyotyping results but also refined the precise chromosomal structures. In the case with a suspected translocation not detected by karyotyping, OGM efficiently identified the cryptic translocation and defined the genomic breakpoints with relatively high accuracy. Conclusions Our study confirmed OGM as a robust alternative approach to karyotyping for the detection of chromosomal structural rearrangements, including CCRs and cryptic translocations.

Background Numerous studies have confirmed the involvement of extracellular vesicles (EVs) in various physiological processes, including cellular death and tissue damage. Recently, we reported that EVs derived from ischemia-reperfusion heart exacerbate cardiac injury. However, the role of EVs from healthy heart tissue (heart-derived EVs, or cEVs) on myocardial ischemia-reperfusion (MI/R) injury remains unclear. Results Here, we demonstrated that intramyocardial administration of cEVs significantly enhanced cardiac function and reduced cardiac damage in murine MI/R injury models. cEVs treatment effectively inhibited ferroptosis and maintained mitochondrial homeostasis in cardiomyocytes subjected to ischemia-reperfusion injury. Further results revealed that cEVs can transfer ATP5a1 into cardiomyocytes, thereby suppressing mitochondrial ROS production, alleviating mitochondrial damage, and inhibiting cardiomyocyte ferroptosis. Knockdown of ATP5a1 abolished the protective effects of cEVs. Furthermore, we found that the majority of cEVs are derived from cardiomyocytes, and ATP5a1 in cEVs primarily originates from cardiomyocytes of the healthy murine heart. Moreover, we demonstrated that adipose-derived stem cells (ADSC)-derived EVs with ATP5a1 overexpression showed much better efficacy on the therapy of MI/R injury compared to control ADSC-derived EVs. Conclusions These findings emphasized the protective role of cEVs in cardiac injury and highlighted the therapeutic potential of targeting ATP5a1 as an important approach for managing myocardial damage induced by MI/R injury. Graphical Abstract