An analysis of differences in Carbapenem-resistant Enterobacterales in different regions: a multicenter cross-sectional study.

OBJECTIVE: This study aimed to explore the characteristics of carbapenem-resistant Enterobacterales (CRE) patients in the intensive care unit (ICU) in different regions of Henan Province to provide evidence for the targeted prevention and treatment of CRE. METHODS: This was a cross-sectional study. CRE screening was conducted in the ICUs of 78 hospitals in Henan Province, China, on March 10, 2021. The patients were divided into provincial capital hospitals and nonprovincial capital hospitals for comparative analysis. RESULTS: This study involved 1009 patients in total, of whom 241 were CRE-positive patients, 92 were in the provincial capital hospital and 149 were in the nonprovincial capital hospital. Provincial capital hospitals had a higher rate of CRE positivity, and there was a significant difference in the rate of CRE positivity between the two groups. The body temperature; immunosuppressed state; transfer from the ICU to other hospitals; and use of enemas, arterial catheters, carbapenems, or tigecycline at the provincial capital hospital were greater than those at the nonprovincial capital hospital (P < 0.05). However, there was no significant difference in the distribution of carbapenemase strains or enzymes between the two groups. CONCLUSIONS: The detection rate of CRE was significantly greater in provincial capital hospitals than in nonprovincial capital hospitals. The source of the patients, invasive procedures, and use of advanced antibiotics may account for the differences. Carbapenem-resistant Klebsiella pneumoniae (CR-KPN) was the most prevalent strain. Klebsiella pneumoniae carbapenemase (KPC) was the predominant carbapenemase enzyme. The distributions of carbapenemase strains and enzymes were similar in different regions.

[Expression level of cytokines in patients with sepsis and its effect on prognosis].

OBJECTIVE: To observe the expression level of cytokines in patients with sepsis and its effect on prognosis. METHODS: The clinical data of sepsis patients admitted to the intensive care unit (ICU) of the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2022 were analyzed retrospectively, including gender, age, and acute physiology and chronic health evaluation II (APACHE II), blood routine, procalcitonin (PCT), C-reactive protein (CRP), and cytokines levels [interleukins (IL-2, IL-4, IL-6, IL-10, IL-17), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ)] within 24 hours of admission to ICU. The 28-day prognosis of the patients was followed up. The patients were divided into survival group and death group according to the prognosis. The clinical data between the two groups of sepsis patients with different prognosis were compared. Binary Logistic regression analysis was used to analyze the independent risk factors affecting the prognosis of patients with sepsis, and the receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of each risk factor for the prognosis of patients with sepsis. RESULTS: (1) A total of 227 patients with sepsis were enrolled, including 168 patients in the survival group (survival rate 74.0%) and 59 patients in the death group (mortality 26.0%). There were no significant differences in age (years old: 55.97±2.13 vs. 54.67±1.11) and gender (male: 71.2% vs. 57.1%) between the death group and the survival group (both P > 0.05), indicating that the baseline data of the two groups were comparable. (2) The APACHE II (19.37±0.99 vs. 14.88±0.61, P < 0.001) and PCT (µg/L: 12.39±2.94 vs. 4.14±0.90, P < 0.001) in the death group were significantly higher than those in the survival group, while the platelet count [PLT (×109/L): 144.75±12.50 vs. 215.99±11.26, P = 0.001] and thrombocytocrit [(0.14±0.01)% vs. (0.19±0.01)%, P = 0.001] were significantly lower than those in the survival group. (3) The level of IL-6 in the death group was significantly higher than that in the survival group (ng/L: 577.66±143.16 vs. 99.74±33.84, P < 0.001). There were no statistically significant differences in other cytokines, IL-2, IL-4, IL-10, TNF-α, IFN-γ and IL-17 between the death group and the survival group [IL-2 (ng/L): 2.44±0.38 vs. 2.63±0.27, P = 0.708; IL-4 (ng/L): 3.26±0.67 vs. 3.18±0.34, P = 0.913; IL-10 (ng/L): 33.22±5.13 vs. 39.43±2.85, P = 0.262; TNF-α (ng/L): 59.33±19.21 vs. 48.79±29.87, P = 0.839; IFN-γ (ng/L): 6.69±5.18 vs. 1.81±0.16, P = 0.100; IL-17 (ng/L): 2.05±0.29 vs. 2.58±0.33, P = 0.369]. (4) Binary Logistic regression analysis showed that APACHE II and IL-6 were independent risk factors affecting the prognosis of patients with sepsis [odds ratio (OR) and 95% confidence interval (95%CI) were 1.050 (1.008-1.093) and 1.001 (1.000-1.002), P values were 0.019 and 0.026, respectively]. (5) ROC curve analysis showed that APACHE II and IL-6 had certain predictive value for the prognosis of patients with sepsis, the area under the ROC curve (AUC) was 0.754 (95%CI was 0.681-0.827) and 0.592 (95%CI was 0.511-0.673), P values were < 0.001 and 0.035, respectively. When the optimal cut-off value of APACHE II was 16.50 score, the sensitivity was 72.6% and the specificity was 69.9%. When the optimal cut-off value of IL-6 was 27.87 ng/L, the sensitivity was 67.2% and the specificity was 52.8%. CONCLUSIONS: APACHE II score and IL-6 level have certain predictive value for the prognosis of patients with sepsis, the higher APACHE II score and IL-6 level, the greater the probability of death in patients with sepsis.

[Analysis of lymphocyte subsets in patients with sepsis and its impact on prognosis].

OBJECTIVE: To explore the characteristics of changes in peripheral blood lymphocyte subsets in patients with sepsis in intensive care unit (ICU) and analyze their predictive value for prognosis. METHODS: The clinical data of sepsis patients admitted to the surgical intensive care unit (SICU) of the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2021 were analyzed retrospectively. The patients met the diagnostic criteria of Sepsis-3 and were ≥ 18 years old. Peripheral venous blood samples were collected from all patients on the next morning after admission to SICU for routine blood test and peripheral blood lymphocyte subsets. According to the 28-day survival, the patients were divided into two groups, and the differences in immune indexes between the two groups were compared. Logistic regression analysis was used to analyze the risk factors of immune indexes that affect prognosis. RESULTS: (1) A total of 279 patients with sepsis were enrolled in the experiment, of which 198 patients survived at 28 days (28-day survival rate 71.0%), and 81 patients died (28-day mortality 29.0%). There were no significant differences in age (years old: 57.81±1.71 vs. 54.99±1.05) and gender (male: 60.5% vs. 63.6%) between the death group and the survival group (both P > 0.05), and the baseline data was comparable.(2) Acute physiology and chronic health evalution II (APACHE II: 22.06±0.08 vs. 14.08±0.52, P < 0.001), neutrophil percentage [NEU%: (88.90±1.09)% vs. (84.12±0.77)%, P = 0.001], procalcitonin [PCT (µg/L): 11.97±2.73 vs. 5.76±1.08, P = 0.011], platelet distribution width (fL: 16.81±0.10 vs. 16.57±0.06, P = 0.029) were higher than those in the survival group, while lymphocyte percentage [LYM%: (6.98±0.78)% vs. (10.59±0.86)%, P = 0.012], lymphocyte count [LYM (×109/L): 0.70±0.06 vs. 0.98±0.49, P = 0.002], and platelet count [PLT (×109/L): 151.38±13.96 vs. 205.80±9.38, P = 0.002], and thrombocytocrit [(0.15±0.01)% vs. (0.19±0.07)%, P = 0.012] were lower than those in the survival group. (3) There was no statistically significant difference in the percentage of lymphocyte subsets between the death group and the survival group, but the absolute value of LYM (pieces/µL: 650.24±84.67 vs. 876.64±38.02, P = 0.005), CD3+ absolute value (pieces/µL: 445.30±57.33 vs. 606.84±29.25, P = 0.006), CD3+CD4+ absolute value (pieces/µL: 239.97±26.96 vs. 353.49±18.59, P = 0.001), CD19+ absolute value (pieces/µL: 111.10±18.66 vs. 150.30±10.15, P = 0.049) in the death group was lower than those in the survival group. Other lymphocyte subsets in the death group, such as CD3+CD8+ absolute value (pieces/µL: 172.40±24.34 vs. 211.22±11.95, P = 0.112), absolute value of natural killer cell [NK (pieces/µL): 101.26±18.15 vs. 114.72±7.64, P = 0.420], absolute value of natural killer T cell [NKT (pieces/µL): 33.22±5.13 vs. 39.43±2.85, P = 0.262], CD4-CD8- absolute value (pieces/µL: 41.07±11.07 vs. 48.84±3.31, P = 0.510), CD4+CD8+ absolute value (pieces/µL: 3.39±1.45 vs. 3.47±0.36, P = 0.943) were not significantly different from those in the survival group. (4)Logistic regression analysis showed that lymphocyte subsets were not selected as immune markers with statistical significance for the prognosis of sepsis. CONCLUSIONS: The changes of immune indexes in sepsis patients are closely related to their prognosis. Early monitoring of the above indexes can accurately evaluate the condition and prognosis of sepsis patients.

Diagnostic performance and clinical impact of blood metagenomic next-generation sequencing in ICU patients suspected monomicrobial and polymicrobial bloodstream infections.

Introduction: Early and effective application of antimicrobial medication has been evidenced to improve outcomes of patients with bloodstream infection (BSI). However, conventional microbiological tests (CMTs) have a number of limitations that hamper a rapid diagnosis. Methods: We retrospectively collected 162 cases suspected BSI from intensive care unit with blood metagenomics next-generation sequencing (mNGS) results, to comparatively evaluate the diagnostic performance and the clinical impact on antibiotics usage of mNGS. Results and discussion: Results showed that compared with blood culture, mNGS detected a greater number of pathogens, especially for Aspergillus spp, and yielded a significantly higher positive rate. With the final clinical diagnosis as the standard, the sensitivity of mNGS (excluding viruses) was 58.06%, significantly higher than that of blood culture (34.68%, P<0.001). Combing blood mNGS and culture results, the sensitivity improved to 72.58%. Forty-six patients had infected by mixed pathogens, among which Klebsiella pneumoniae and Acinetobacter baumannii contributed most. Compared to monomicrobial, cases with polymicrobial BSI exhibited dramatically higher level of SOFA, AST, hospitalized mortality and 90-day mortality (P<0.05). A total of 101 patients underwent antibiotics adjustment, among which 85 were adjusted according to microbiological results, including 45 cases based on the mNGS results (40 cases escalation and 5 cases de-escalation) and 32 cases on blood culture. Collectively, for patients suspected BSI in critical condition, mNGS results can provide valuable diagnostic information and contribute to the optimizing of antibiotic treatment. Combining conventional tests with mNGS may significantly improve the detection rate for pathogens and optimize antibiotic treatment in critically ill patients with BSI.

[Prognostic evaluation of coagulation indicators for patients with acute fatty liver of pregnancy].

OBJECTIVE: To explore the relevant clinical test indicators that affect the prognosis of patients with acute fatty liver of pregnancy (AFLP), and to provide a basis for early diagnosis and correct selection of treatment methods. METHODS: A retrospective analysis was conducted. Clinical data of AFLP patients in the intensive care unit (ICU) of the First Affiliated Hospital of Zhengzhou University from January 2010 to May 2021 were collected. According to the 28-day prognosis, the patients were divided into death group and survival group. The clinical data, laboratory examination indicators, and prognosis of the two groups were compared, and further binary Logistic regression analysis was used to analyze the risk factors affecting the prognosis of patients. At the same time, the values of related indicators at each time point (24, 48, 72 hours) after the start of treatment were recorded. The receiver operator characteristic curve (ROC curve) of prothrombin time (PT) and international normalized ratio (INR) for evaluating the prognosis of patients at each time point was drawn, and the area under the ROC curve (AUC) was calculated to evaluate the predictive value of relevant indicators at each time point for the prognosis of AFLP patients. RESULTS: A total of 64 AFLP patients were selected. The patients developed the AFLP during pregnancy (34.5±6.8) weeks, with 14 deaths (mortality of 21.9%) and 50 survivors (survival rate of 78.1%). There was no statistically significant difference in general clinical data between the two groups of patients, including age, time from onset to visit, time from visit to cessation of pregnancy, acute physiology and chronic health evaluations II (APACHE II), hospitalization time in ICU, and total hospitalization cost. However, the proportion of male fetuses and stillbirths in the death group was higher than that in the survival group. The laboratory examination indicators including the white blood cell count (WBC), alanine transaminase (ALT), serum creatinine (SCr), PT extension, INR elevation, and hyperammonia in the death group were significantly higher than those in the survival group (all P < 0.05). Through Logistic regression analysis of the above indicators showed that PT > 14 s and INR > 1.5 were risk factors affecting the prognosis of AFLP patients [PT > 14 s: odds ratio (OR) = 1.215, 95% confidence interval (95%CI) was 1.076-1.371, INR > 1.5: OR = 0.719, 95%CI was 0.624-0.829, both P < 0.01]. ROC curve analysis showed that both PT and INR at ICU admission and 24, 48, and 72 hours of treatment can evaluate the prognosis of AFLP patients [AUC and 95%CI of PT were 0.772 (0.599-0.945), 0.763 (0.608-0.918), 0.879 (0.795-0.963), and 0.957 (0.904-1.000), respectively; AUC and 95%CI of INR were 0.808 (0.650-0.966), 0.730 (0.564-0.896), 0.854 (0.761-0.947), and 0.952 (0.896-1.000), respectively; all P < 0.05], the AUC of PT and INR after 72 hours of treatment was the highest, with higher sensitivity (93.5%, 91.8%) and specificity (90.9%, 90.9%). CONCLUSIONS: AFLP often occurs in the middle and late stages of pregnancy, and the initial symptoms are mainly gastrointestinal symptoms. Once discovered, pregnancy should be terminated immediately. PT and INR are good indicators for evaluating AFLP patient efficacy and prognosis, and PT and INR are the best prognostic indicators after 72 hours of treatment.

Effect of an Herbal-Based Injection on 28-Day Mortality in Patients With Sepsis: The EXIT-SEP Randomized Clinical Trial.

Importance: Previous research has suggested that Xuebijing injection (XBJ), an herbal-based intravenous preparation, may reduce mortality among patients with sepsis. Objective: To determine the effect of XBJ vs placebo on 28-day mortality among patients with sepsis. Design, Setting, and Participants: The Efficacy of Xuebijing Injection in Patients With Sepsis (EXIT-SEP) trial was a multicenter, randomized double-blind, placebo-controlled trial conducted in intensive care units at 45 sites and included 1817 randomized patients with sepsis (sepsis 3.0) present for less than 48 hours. Patients aged 18 to 75 years with a Sequential Organ Failure Assessment score of 2 to 13 were enrolled. The study was conducted from October 2017 to June 2019. The final date of follow-up was July 26, 2019. Data analysis was performed from January 2020 to August 2022. Interventions: The patients were randomized to receive either intravenous infusion of XBJ (100 mL, n = 911) or volume-matched saline placebo (n = 906) every 12 hours for 5 days. Main Outcomes and Measures: The primary outcome was 28-day mortality. Results: Among the 1817 patients who were randomized (mean [SD] age, 56.5 [13.5] years; 1199 [66.0%] men), 1760 (96.9%) completed the trial. In these patients, the 28-day mortality rate was significantly different between the placebo group and the XBJ group (230 of 882 patients [26.1%] vs 165 of 878 patients [18.8%], respectively; P < .001). The absolute risk difference was 7.3 (95% CI, 3.4-11.2) percentage points. The incidence of adverse events was 222 of 878 patients (25.3%) in the placebo group and 200 of 872 patients (22.9%) in the XBJ group. Conclusions and Relevance: In this randomized clinical trial among patients with sepsis, the administration of XBJ reduced 28-day mortality compared with placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT03238742.

[Predictive value of the maximum aggregation rate of platelet for septic shock and septic shock with disseminated intravascular coagulation].

OBJECTIVE: To investigate the predictive value of the maximum aggregation rate (MAR) of platelet for septic shock and septic shock with disseminated intravascular coagulation (DIC). METHODS: A retrospective case-control study enrolled patients with sepsis admitted to department of critical care medicine of the First Affiliated Hospital of Zhengzhou University from January 2021 to November 2022. The basic data, dynamic platelet aggregation rate, blood routine, inflammation indicators, sequential organ failure assessment (SOFA) and other clinical indicators within 24 hours after admission were collected. Septic patients were divided into the shock group and the non-shock group according to the presence of septic shock; then refer to the International Society on Thrombosis and Hemostasis (ISTH) standard, patients with septic shock were divided into the shock DIC group and the shock non-DIC group according to the presence of dominant DIC. Compared the differences in platelet aggregation function between these groups, and the receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of the MAR for septic shock and septic shock with DIC. Spearman correlation analysis was used to analyze the correlation of MAR with inflammation indicators and the severity of illness in patients with sepsis. RESULTS: A total of 153 sepsis patients were included and 61 with septic shock (including 17 with dominant DIC and 44 without dominant DIC). Compared with the non-shock group, the level of procalcitonin (PCT), C-reactive protein (CRP), and SOFA score were significantly higher in the shock group [PCT (mg/L): 6.90 (2.50, 23.50) vs. 0.87 (0.26, 5.75), CRP (mg/L): 156.48 (67.11, 230.84) vs. 90.39 (46.43, 182.76), SOFA score: 11.00 (8.00, 14.00) vs. 5.00 (3.00, 8.00), all P < 0.05]. The platelet count (PLT) and the MAR induced by adenosine diphosphate (ADP), adrenaline (A), collagen (COL), and arachidonic acid (AA; ADP-MAR, A-MAR, COL-MAR, AA-MAR) in the shock group were significantly decreased [PLT (×109/L): 101.00 (49.00, 163.50) vs. 175.50 (108.25, 254.50), ADP-MAR: 28.50% (22.00%, 38.05%) vs. 45.90% (33.98%, 60.28%), A-MAR: 38.90% (30.00%, 55.40%) vs. 65.15% (54.38%, 72.53%), COL-MAR: 27.90% (20.85%, 36.55%) vs. 42.95% (33.73%, 54.08%), AA-MAR: 24.70% (16.40%, 34.20%) vs. 46.55% (28.33%, 59.20%), all P < 0.05]. Subgroup analysis revealed that, compared with the shock non-DIC group, the SOFA scores were significantly higher in patients in the shock DIC group (13.29±5.23 vs. 10.39±3.58, P < 0.05), the PLT and COL-MAR in the shock DIC group were significantly reduced [PLT (×109/L): 36.00 (22.00, 67.50) vs. 115.50 (84.25, 203.75), COL-MAR: 21.50% (17.85%, 32.60%) vs. 30.95% (22.98%, 38.53%), all P < 0.05]. ROC curve analysis showed that A-MAR had a higher predictive value for septic shock, and the area under the ROC curve (AUC) was 0.814 [95% confidence interval (95%CI) was 0.742-0.886, P = 0.000]. When the optimal cut-off value was 51.35%, the sensitivity was 68.9%, the specificity was 82.6%, the positive predictive value was 0.724 and the negative predictive value was 0.800. COL-MAR had some predictive value for septic shock with DIC, and the AUC was 0.668 (95%CI was 0.513-0.823, P = 0.044). When the optimal cut-off value was 21.90%, the sensitivity was 52.9%, the specificity was 79.5%, the positive predictive value was 0.500, and the negative predictive value was 0.813. Spearman correlation analysis showed that the MAR induced by each inducer was negatively correlated with inflammatory indicators and SOFA scores in sepsis patients, with A-MAR showing the strongest correlation with SOFA score (r = -0.327, P = 0.000). CONCLUSIONS: MAR, an indicator of platelet aggregation function, shows predictive value for septic shock and septic shock with DIC, and it could be used to for evaluating the severity of patients with sepsis. In addition, tt also can be used as a monitoring index to predict the changes of sepsis patients and to guide the treatment.

Prediction of potential severe coronavirus disease 2019 patients based on CT radiomics: A retrospective study.

PURPOSE: Coronavirus disease 2019 (COVID-19) is a recently declared worldwide pandemic. Triaging of patients into severe and non-severe could further help in targeted management. "Potential severe patients" is a category of patients who did not have severe symptoms at their initial diagnosis, but eventually progressed to be severe patients and are easily overlooked in the early stage. This work aimed to develop and evaluate a CT-based radiomics signature for the prediction of these potential severe COVID-19 patients. METHODS: One hundred fifty COVID-19 patients were enrolled and randomly divided into cross-validation and independent test sets. First, their clinical characteristics were screened using the univariate and multivariate logistic regression step by step. Then, radiomics features were extracted from the lesions on their chest CT images. Subsequently, the inter- and intra-class correlation coefficients (ICC) analysis, minimum-redundancy maximum-relevance (mRMR) selection, and the least absolute shrinkage and selection operator (LASSO) algorithm were used step by step for feature selection and construction of a radiomics signature. Finally, the screened clinical risk factors and constructed radiomics signature were combined for the combined model and Radiomics+Clinics nomogram construction. The predictive performance of the Radiomics and Combined models were evaluated and compared using receiver operating characteristic curve (ROC) analysis, Hosmer-Lemeshow test and Delong test. RESULTS: Clinical characteristics analysis resulted in the screening of five clinical risk factors. The combination of ICC, mRMR, and LASSO methods resulted in the selection of ten radiomics features, which made up of the radiomics signature. The differences in the radiomics signature between the potential severe and non-severe groups in cross-validation set and test sets were both p < 0.001. All Radiomics and Combined models showed a very good predictive performance with the accuracy and AUC of nearly or above 0.9. Additionally, we found no significant difference in the predictive performance between these two models. CONCLUSIONS: A CT-based radiomics signature for the prediction of potential severe COVID-19 patients was constructed and evaluated. Constructed Radiomics and Combined model showed good feasibility and accuracy. The Radiomics+Clinical nomogram, acted as a useful tool, may assist clinicians to better identify potential severe cases to target their management in the COVID-19 pandemic prevention and control.

circHECTD1 attenuates apoptosis of alveolar epithelial cells in acute lung injury.

Circular RNAs (circRNAs) play important roles in many lung diseases. This study aimed to investigate the role of circHECTD1 in acute lung injury (ALI). The mouse and cell models of ALI were induced by lipopolysaccharide (LPS). The apoptosis of alveolar epithelial cells (AECs) was detected by flow cytometry. The relationships between circHECTD1, miRNAs, and target genes were assessed by RNA pull-down, luciferase reporter gene, and RNA-FISH assays. circHECTD1 was downregulated in LPS-induced human and mouse AECs (HBE and MLE-12). The knockdown of circHECTD1 increased the apoptotic rates and the expressions of miR-136 and miR-320a, while its overexpression caused opposite effects in LPS-induced HBE and MLE-12 cells. Mechanistically, circHECTD1 bound to miR-320a and miR-136. miR-320a targeted PIK3CA and mediated the effect of circHECTD1 on PIK3CA expression. miR-136 targeted Sirt1 and mediated the effect of circHECTD1 on Sirt1 expression. Silencing PIK3CA and/or Sirt1 reversed the effect of circHECTD1 overexpression on the apoptosis of LPS-induced HBE and MLE-12 cells. In vivo, overexpression of circHECTD1 alleviated the LPS-induced ALI of mice. Our findings suggested that circHECTD1 inhibits the apoptosis of AECs through miR-320a/PIK3CA and miR-136/Sirt1 pathways in LPS-induced ALI.

Actively implementing an evidence-based feeding guideline for critically ill patients (NEED): a multicenter, cluster-randomized, controlled trial.

BACKGROUND: Previous cluster-randomized controlled trials evaluating the impact of implementing evidence-based guidelines for nutrition therapy in critical illness do not consistently demonstrate patient benefits. A large-scale, sufficiently powered study is therefore warranted to ascertain the effects of guideline implementation on patient-centered outcomes. METHODS: We conducted a multicenter, cluster-randomized, parallel-controlled trial in intensive care units (ICUs) across China. We developed an evidence-based feeding guideline. ICUs randomly allocated to the guideline group formed a local "intervention team", which actively implemented the guideline using standardized educational materials, a graphical feeding protocol, and live online education outreach meetings conducted by members of the study management committee. ICUs assigned to the control group remained unaware of the guideline content. All ICUs enrolled patients who were expected to stay in the ICU longer than seven days. The primary outcome was all-cause mortality within 28 days of enrollment. RESULTS: Forty-eight ICUs were randomized to the guideline group and 49 to the control group. From March 2018 to July 2019, the guideline ICUs enrolled 1399 patients, and the control ICUs enrolled 1373 patients. Implementation of the guideline resulted in significantly earlier EN initiation (1.20 vs. 1.55 mean days to initiation of EN; difference - 0.40 [95% CI - 0.71 to - 0.09]; P = 0.01) and delayed PN initiation (1.29 vs. 0.80 mean days to start of PN; difference 1.06 [95% CI 0.44 to 1.67]; P = 0.001). There was no significant difference in 28-day mortality (14.2% vs. 15.2%; difference - 1.6% [95% CI - 4.3% to 1.2%]; P = 0.42) between groups. CONCLUSIONS: In this large-scale, multicenter trial, active implementation of an evidence-based feeding guideline reduced the time to commencement of EN and overall PN use but did not translate to a reduction in mortality from critical illness. TRIAL REGISTRATION: ISRCTN, ISRCTN12233792 . Registered November 20th, 2017.

LncRNA OIP5-AS1 reduces renal epithelial cell apoptosis in cisplatin-induced AKI by regulating the miR-144-5p/PKM2 axis.

BACKGROUND: The abnormal expression of long non-coding RNA (lncRNA) Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) has been observed in many human cancers and the underlying mechanisms have been well studied. However, the function of OIP5-AS1 in acute kidney injury (AKI) remains unclear. METHODS: To explore the role of OIP5-AS1 in the progression of AKI, the cisplatin-induced AKI mouse and cell model were established. To confirm the potential protective effect of OIP5-AS1 during cisplatin-induced AKI, rescue experiments were performed. Targetscan was used to predict the potential targets of miR-144-5p. To further determine whether the effect of miR-144-5p during cisplatin-induced AKI was mediated by PMK2, the recuse experiments using PMK2 overexpressing vector was applied. RESULTS: OIP5-AS1 was significantly downregulated both in cisplatin-induced AKI mice and human renal tubular cell line HK-2 cells. Moreover, overexpression of OIP5-AS1 efficiently promoted cell growth and reduced cisplatin-induced apoptosis of HK-2 cells. Furthermore, OIP5-AS1 was identified as a sponge of miR-144-5p, and upregulation of miR-144-5p could significantly reverse overexpression of OIP5-AS1-induced protective effect on the damage of cisplatin to HK-2 cells. In addition, pyruvate kinase M2 (PKM2) was found to be a direct target of miR-144-5p, and overexpression of PKM2 efficiently reversed the effect of miR-144-5p mimics on the damage in cisplatin-stimulated HK-2 cells. CONCLUSIONS: OIP5-AS1 reduced the apoptosis of cisplatin-stimulated renal epithelial cells by targeting the miR-144-5p/PKM2 axis, which extended the regulatory network of lncRNAs in cisplatin-induced AKI and also provided a novel therapeutic target for AKI treatment.

Beneficial Effect of Immune-Enhanced Enteral Nutrition on Immune Function in Patients With Severe Neurological Diseases: A Single-Center Randomized Controlled Trial.

Background: Undernutrition is the main reason for the use of artificial nutrition in patients with severe neurological diseases. However, the clinical and immunological outcomes of enteral nutrition supplemented with immunomodulatory nutrients in these patients remain unclear. Methods: In this single-center, randomized controlled study, 57 patients with severe neurological diseases were randomly divided into the following two groups according to the type of enteral nutrition they would receive: immune-enhancing (IE) (n = 27) and non-IE (NIE) (n = 30). The IE and NIE groups received enteral nutrition supplemented with immunomodulatory nutrients and standard enteral nutrition, respectively. We compared the nutritional status and the state of cellular immunity between the patients of the two groups. Clinical and immunological variables were evaluated following nutritional treatment. Results: Feeding intolerance was lower in the IE than that in the NIE group (P = 0.04). However, there were no significant differences between the results of the two groups in terms of length of stay in the intensive care unit or hospital, extubation time, or body mass index (P > 0.05). The CD4+ T-lymphocyte count and CD4+/CD8+ ratio in the peripheral blood increased significantly in the IE group. The expression of CD28 activated cell surface markers was higher in the IE than in the NIE group. In addition, increased plasma interferon-γ levels were recorded in the IE group, whereas the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8, and IL-10 decreased. Conclusions: Immune-enhanced enteral nutrition could improve the immune status and feeding tolerance in patients with severe neurological diseases. Trial Registration:www.chictr.org.cn/index.aspx, identifier: ChiCTR-IPR-17013909.

Radiomics analysis of chest CT to predict the overall survival for the severe patients of COVID-19 pneumonia.

Personalized assessment and treatment of severe patients with COVID-19 pneumonia have greatly affected the prognosis and survival of these patients. This study aimed to develop the radiomics models as the potential biomarkers to estimate the overall survival (OS) for the COVID-19 severe patients. A total of 74 COVID-19 severe patients were enrolled in this study, and 30 of them died during the follow-up period. First, the clinical risk factors of the patients were analyzed. Then, two radiomics signatures were constructed based on two segmented volumes of interest of whole lung area and lesion area. Two combination models were built depend on whether the clinic risk factors were used and/or whether two radiomics signatures were combined. Kaplan-Meier analysis were performed for validating two radiomics signatures and C-index was used to evaluated the predictive performance of all radiomics signatures and combination models. Finally, a radiomics nomogram combining radiomics signatures with clinical risk factors was developed for predicting personalized OS, and then assessed with respect to the calibration curve. Three clinical risk factors were found, included age, malignancy and highest temperature that influence OS. Both two radiomics signatures could effectively stratify the risk of OS in COVID-19 severe patients. The predictive performance of the combination model with two radiomics signatures was better than that only one radiomics signature was used, and became better when three clinical risk factors were interpolated. Calibration curves showed good agreement in both 15 d survival and 30 d survival between the estimation with the constructed nomogram and actual observation. Both two constructed radiomics signatures can act as the potential biomarkers for risk stratification of OS in COVID-19 severe patients. The radiomics+clinical nomogram generated might serve as a potential tool to guide personalized treatment and care for these patients.

[Risk factors for death and their predictive value on diabetic kidney disease patients in intensive care unit based on MIMIC-III database].

OBJECTIVE: To analyze the influencing factors of prognosis of patients with diabetic kidney disease (DKD) in intensive care unit (ICU), and analyze their predictive value. METHODS: Based on the inpatient information of more than 50 000 patients from June 2001 to October 2012 in the latest version of American Intensive Care Medical Information Database (MIMIC-III v1.4), the data of DKD patients were screened out, including gender, age, body weight, comorbidities [hypertension, coronary heart disease, chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD)], sequential organ failure assessment (SOFA) score, the length of ICU stay, the incidence of mechanical ventilation, vasoactive drugs and renal replacement therapy during the ICU hospitalization, complications of other diseases [ventilator-associated pneumonia (VAP), urinary tract infection (UTI), diabetic ketoacidosis (DKA), acute myocardial infarction (AKI)] and prognosis of ICU. At the same time, the blood routine and biochemical data of the first 24 hours in ICU and the extremum values during the ICU hospitalization were collected. Multivariate Logistic regression analysis was used to screen the prognostic factors of DKD patients in ICU, and receiver operating characteristic (ROC) curve was plotted to analyze the predictive value of death risk factors. RESULTS: 416 DKD patients were screened out, 20 patients were excluded due to data missing, and finally 396 patients were enrolled, including 220 survival patients and 176 dead patients. Compared with the survival group, the patients in the death group were older (years old: 57.13±13.04 vs. 52.61±14.15), with lower rates of hypertension and CKD (11.4% vs. 23.6%, 26.7% vs. 41.4%), higher SOFA scores and baseline values of blood urea nitrogen (BUN), serum creatinine (SCr) and blood K+ [SOFA score: 5.86±2.79 vs. 4.49±2.56, BUN (mmol/L): 18.4±10.0 vs. 14.8±9.0, SCr (µmol/L): 387.2±382.8 vs. 284.6±244.9, K+ (mmol/L): 4.64±0.99 vs. 4.33±0.86], and longer ICU stay [days: 2.65 (1.48, 5.21) vs. 2.00 (1.00, 4.00)], and the differences were statistically significant (all P < 0.01). Further analysis of laboratory tests extremum values during ICU hospitalization showed that the maximum (max) and minimum (min) values of white blood cell (WBC), BUN and SCr, and K+max in the death group were significantly higher than those in the survival group [WBCmax (×109/L): 17.3±10.3 vs. 14.5±7.3, WBCmin (×109/L): 7.9±4.1 vs. 6.7±2.7, BUNmax (mmol/L): 23.8±10.4 vs. 18.8±10.2, BUNmin (mmol/L): 11.0±6.6 vs. 9.3±6.6, SCrmax (µmol/L): 459.7±392.5 vs. 350.1±294.4, SCrmin (µmol/L): 246.6±180.3 vs. 206.9±195.4, K+max (mmol/L): 5.35±0.93 vs. 5.09±0.99], and the minimum values of hemoglobin (Hbmin) and glucose (Glumin) were significantly lower than those in the survival group [Hbmin (g/L): 87.4±14.5 vs. 90.6±16.5, Glumin (mmol/L): 4.0±1.7 vs. 4.6±2.0], and the differences were statistically significant (all P < 0.05). The incidences of mechanical ventilation and vasoactive drugs during ICU hospitalization in the death group were significantly higher than those in the survival group (37.5% vs. 24.1%, 32.4% vs. 20.0%, both P < 0.01), and the incidences of UTI and AMI in the death group were significantly higher than those in the survival group (29.5% vs. 19.1%, 8.5% vs. 3.6%, both P < 0.05). Multivariate Logistic regression analysis showed that age [odds ratio (OR) = 1.019, 95% confidence interval (95%CI) was 1.003-1.036, P = 0.023], SOFA score (OR = 1.142, 95%CI was 1.105-1.246, P = 0.003), WBCmin (OR = 1.134, 95%CI was 1.054-1.221, P = 0.001) and BUNmax (OR = 1.010, 95%CI was 1.002-1.018, P = 0.018) were risk factors of death of DKD patients in ICU. ROC curve analysis showed that the area under ROC curve (AUC) of combination of risks factors of death was 0.706, the sensitivity was 61.6%, and the specificity was 73.2%. CONCLUSIONS: In order to prevent DKD patients from getting worse in ICU, we should pay close attention to the blood biochemical indexes, especially the renal function indexes, and give timely treatment. At the same time, we should actively prevent the occurrence of complications such as infection and cardiovascular disease.

STAT3-Induced Upregulation of lncRNA CASC9 Promotes the Progression of Bladder Cancer by Interacting with EZH2 and Affecting the Expression of PTEN.

OBJECTIVE: Long non-coding RNA (lncRNA) cancer susceptibility candidate 9 (CASC9) has been reported to play a vital role in tumorigenesis. This study explored the biological role of CASC9 and its regulation mechanism in bladder cancer (BC). METHODS: Gene expression was evaluated using quantitative reverse transcription polymerase chain reaction and Western blot. The functional role of CASC9 in BC was studied using Cell Counting Kit-8, colony formation assay, scratch wound healing assay, transwell invasion assay, and xenograft tumor assay. In addition, the mechanism of CASC9 function in BC was determined using RNA immunoprecipitation assay and chromatin immunoprecipitation assay. RESULTS: CASC9 was upregulated in BC tissues and cell lines, and correlated with the staging and metastasis in BC. Knockdown of CASC9 inhibited the proliferation, migration, and invasion of BC cells. Similarly, silencing of CASC9 inhibited tumor growth in vivo. Signal transducer and activator of transcription 3 (STAT3) was upregulated in BC tissues and cell lines, and positively correlated with CASC9 in BC tissues. Moreover, CASC9 was shown to be regulated by STAT3 in BC cells. Furthermore, CASC9 regulated phosphatase and tensin homolog (PTEN) expression by interacting with enhancer of zeste homolog 2 (EZH2). More significantly, CASC9 silencing-mediated inhibition of BC progression was partly reversed by EZH2 overexpression or PTEN inhibition. CONCLUSION: Upregulation of CASC9 induced by STAT3 promoted the progression of BC by interacting with EZH2 and affecting the expression of PTEN, representing a novel regulatory mechanism for BC progression.

[Effect of Xuebijing on inflammatory response and prognosis in patients with septic shock].

OBJECTIVE: To study the effect of Xuebijing on inflammatory response and prognosis in patients with septic shock. METHODS: A prospective randomized controlled study was conducted. Eighty septic shock patients admitted to department of critical care medicine of the First Affiliated Hospital of Zhengzhou University from January to December in 2019 were enrolled. The enrolled patients were divided into Xuebijing group and control group by randomized number table method, with 40 cases in each group. Both groups were strictly followed the guidelines for the diagnosis and treatment of septic shock to take comprehensive treatment measures against sepsis. On this basis, Xuebijing group received intravenous 100 mL Xuebijing injection twice a day for 7 days. Baseline data of enrolled patients were recorded. The levels of interleukin-6 (IL-6), procalcitonin (PCT), C-reactive protein (CRP) and heparin binding protein (HBP) were measured before treatment and 3, 7 and 10 days after treatment. Mechanical ventilation time, the length of intensive care unit (ICU) stay, total hospitalization time and 28-day mortality were recorded. The differences of every indicator between the two groups were compared. Independent risk factors affecting patient prognosis were analyzed by binary Logistic regression. RESULTS: (1) There was no significant difference in baseline data such as gender, age, infection site, acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure score (SOFA) between the two groups. (2) The levels of serum inflammatory factors in both groups showed a decreasing trend after treatment. Compared with the control group, IL-6 and HBP in the Xuebijing group significantly decreased on day 7 [IL-6 (ng/L): 66.20 (16.34, 163.71) vs. 79.81 (23.95, 178.64), HBP (ng/L): 95.59 (45.23, 157.37) vs. 132.98 (73.90, 162.05), both P < 0.05]; on day 10, PCT, CRP, IL-6 and HBP significantly decreased [PCT (µg/L): 1.14 (0.20, 3.39) vs. 1.31 (0.68, 4.21), CRP (mg/L): 66.32 (19.46, 115.81) vs. 89.16 (20.52, 143.76), IL-6 (ng/L): 31.90 (13.23, 138.74) vs. 166.30 (42.75, 288.10), HBP (ng/L): 62.45 (29.17, 96.51) vs. 112.33 (58.70, 143.96), all P < 0.05]. (3) Compared with the control group, mechanical ventilation time and the length of ICU stay were significantly shortened and the total hospitalization expenses were significantly reduced in Xuebijing group [mechanical ventilation time (hours): 57.0 (0, 163.5) vs. 168.0 (24.0, 282.0), the length of ICU stay (days): 8.80±4.15 vs. 17.13±7.05, the total hospitalization expenses (ten thousand yuan): 14.55±7.31 vs. 20.01±9.86, all P < 0.05]. There was no significant difference in 28-day mortality and the total hospitalization time [28-day mortality: 37.5% vs. 35.0%, the total hospitalization time (days): 13.05±8.44 vs. 18.30±9.59, both P > 0.05]. (4) Patients were divided into death and survival groups according to the prognosis, and univariate analysis showed that white blood cell (WBC), neutrophil percentage (NEU%), CRP, lactic acid (Lac), APACHE II score, IL-6, HBP were the factors influencing the prognosis of patients. The above indicators were further analyzed by Logistic regression, which showed that CRP, IL-6, and APACHE II score were independent risk factors for prognosis [odds ratio (OR) was 1.007, 1.828, 1.229, all P < 0.05]. CONCLUSIONS: Combined with Xuebijing to treat septic shock can reduce the body's inflammatory response to a certain extent, thereby reducing the time of mechanical ventilation, shortening the stay of ICU and reducing the total cost of hospitalization. But it cannot reduce the 28-day mortality of patients with septic shock.

[The role of recombinant human thrombopoietin in critically ill patients with sepsis-associated thrombocytopenia: a clinical study].

OBJECTIVE: To investigate the effect of recombinant human thrombogenin (rhTPO) on sepsis-associated thrombocytopenia. METHODS: A prospective randomized controlled study was conducted. One hundred patients with sepsis-associated thrombocytopenia admitted to the department of critical care medicine of the First Affiliated Hospital of Zhengzhou University from August 2019 to October 2020 were enrolled. The enrolled patients were divided into rhTPO-using group (TPO group) and routine group (control group) by random number table method, with 50 cases in each group. Both groups were treated according to the guideline of Sepsis-3. In addition, TPO group received rhTPO 15 000 U, once daily for 7 days. Geneal information and acute physiology and chronic health evaluation II (APACHE II) were recorded. The levels of platelet count (PLT), blood coagulation function [prothrombin time (PT) and prothrombin activity (PTA)], myocardial enzyme indexes [troponin (Tn) and creatine kinase (CK)], liver and kidney function [aspartate aminotransferase (AST), total bilirubin (TBil) and creatinine (Cr)] and inflammatory biomarkers [procalcitonin (PCT) and C-reactive protein (CRP)] were recorded before treatment and 1, 3, 5 and 7 days after treatment. The infusion volume of blood components, duration of mechanical ventilation, length of stay in ICU, total length of hospitalization, total cost of hospitalization and 28-day outcome were recorded. According to whether the PLT was lower than 50×109/L, the patients in TPO group were divided into the TPO A group (PLT ≥ 50×109/L, 16 cases) and TPO B group (PLT < 50×109/L, 34 cases), and the absolute value of PLT increase, duration of mechanical ventilation, length of stay in ICU, total length of hospitalization, total cost of hospitalization and 28-day outcome of the two groups were compared. RESULTS: (1) In TPO and control groups, there were no statistically significant differences in gender, age, proportion of patients with primary infection site, APACHEII score, PLT, coagulation function, myocardial enzymes, liver and kidney function and inflammation indexes before treatment (all P > 0.05). (2) The PLT levels of the TPO group were significantly higher than those of the control group on the 5th and 7th day after treatment (×109/L: day 5, 63.94±44.01 vs. 49.85±29.26, day 7, 125.85±112.31 vs. 76.81±50.87, both P < 0.05), and there were no statistically significant differences in PT, PTA, Tn, CK, AST, TBil, Cr, PCT or CRP before and on the 1, 3, 5, 7 days after treatment between TPO and control groups (all P > 0.05). (3) The amount of platelet transfusion in the TPO group was lower than that in the control group [treatment amount: 0 (0, 0) vs 0 (0, 2.00), P = 0.001]. (4) There were no statistically significant differences in mechanical ventilation time, length of stay in ICU, total length of hospitalization, total cost of hospitalization or 28-day outcome between TPO and control groups (all P > 0.05). The mechanical ventilation time, ICU stay time and total hospitalization time of TPO A group were longer than those in TPO B group, but the differences were not statistically significant [mechanical ventilation time (hours): 131.00 (0, 311.00) vs. 50.00 (0, 192.00), ICU stay time (days): 14.44±8.57 vs. 11.73±9.24, total hospitalization time (days): 15.00 (6.00, 23.50) vs. 18.00 (8.00, 31.00), all P > 0.05]. The absolute value of PLT increase in TPO A group was higher than that of TPO B group, but the difference was not statistically significant [×109/L: 65.00 (16.50, 131.50) vs. 36.00 (18.00, 130.00), P > 0.05]. CONCLUSIONS: RhTPO can significantly increase the PLT of patients with sepsis-related thrombocytopenia, thereby reduce the amount of platelet transfusion, but it cannot shorten the length of ICU stay time and total hospitalization time, and it cannot reduce 28-day mortality.

Association of Ang-2, vWF, and EVLWI with risk of mortality in sepsis patients with concomitant ARDS: A retrospective study.

BACKGROUND/PURPOSE: This study aimed to determine the potential effects of angiopoietin-2 (Ang-2), von Willebrand factor (vWF), and extravascular lung water index (EVLWI) on the risk of mortality in sepsis patients with concomitant acute respiratory distress syndrome (ARDS). METHODS: This retrospective study recruited 41 sepsis patients with concomitant ARDS from January 2015 to June 2018. Data of Ang-2 and vWF levels, EVLWI, and sequential organ failure assessment scores were collected at 0, 24, and 48 h after admission to the hospital. RESULTS: The length of intensive care unit stay (P = 0.041) and Acute Physiology and Chronic Health Evaluation-2 (APACHE II) score (P = 0.003) were associated with the risk of mortality. Furthermore, increased Ang-2 levels and EVLWI at 24 h and 48 h were associated with an increased risk of mortality. Moreover, the APACHE II score at hospital admission significantly predicted the risk of mortality (area under the curve [AUC], 0.834; 95% confidence interval [CI], 0.665-0.983). Finally, the models containing a combination of Ang-2 level and EVLWI at 24 h (AUC, 0.908; 95% CI, 0.774-0.996) and Ang-2 level and EVLWI at 48 h (AUC, 0.981; 95% CI, 0.817-1.000) had high diagnostic values for predicting risk of mortality. CONCLUSION: The study findings indicate that Ang-2 levels and EVLWI at 24 h and 48 h after admission are significantly associated with the risk of mortality.

[Effects of different fluid replenishment methods on internal environment, body thermal regulation response and severe heatstroke of 5-km armed cross-country training soldiers].

OBJECTIVE: To explore the effects of different fluid replenishment methods on the internal environment, body thermal regulatory response and severe heatstroke of 5-km armed cross-country training soldiers. METHODS: A Special Force officers and soldiers who participated in 5-km armed cross-country training (2-3 times a week, 25-30 minutes each time for 3 weeks) during summer training from June to July in 2018 were enrolled, and they were divided into three groups according to the random number table, with 300 trainees in each group. 200 mL of drinking fluids were given to each group 15 minutes before and after each 5-km armed cross-country training: A group with boiled water, B group with purified water, and C group with beverage prepared by pharmaceutical laboratory of the 990th Hospital of PLA Joint Logistics Support Force (100 mL containing 6 g carbohydrates, 42 mg sodium, and 11 mg potassium). The venous blood was collected before and after the last training or during the onset of severe heatstroke to do the following tests: serum cardiac troponin I (cTnI, chemiluminescence), MB isoenzyme of creatine kinase (CK-MB, immunosuppressive), serum creatinine (SCr, enzymatic method), urea nitrogen (BUN, enzymatic method), alanine aminotransferase (ALT, tryptase), aspartate transaminase (AST, tryptase), and Na+, K+, Cl- (electrode method). The heart rate (HR) and core temperature (Tc, anal temperature) were monitored at the same time. The amount of sweat in training and the occurrence of severe heatstroke were also recorded. RESULTS: There was no significant difference in heart, liver, kidney function, electrolyte and body heat regulation reaction among three groups of 5-km armed cross-country trainees before training. Compared with before training, the levels of serum cTnI, CK-MB, SCr, BUN, ALT, AST, HR and Tc were significantly increased after training or during the onset of severe heatstroke in three groups, while the contents of Na+, K+, Cl- were significantly decreased, but the increase or decrease of group C was relatively smaller compared with group A and group B [cTnI (µg/L): 0.9 (0.6, 1.4) vs. 1.1 (0.7, 2.8), 1.0 (0.6, 3.3); CK-MB (U/L): 7.0 (5.0, 11.0) vs. 9.0 (6.0, 14.5), 8.0 (6.0, 15.0); SCr (µmol/L): 92.09±18.64 vs. 102.78±18.77, 103.64±20.07; BUN (mmol/L): 7 (6, 9) vs. 9 (8, 11), 10 (8, 13); ALT (U/L): 27 (22, 34) vs. 36 (30, 43), 34 (27, 43); AST (U/L): 37 (31, 48) vs. 41 (34, 50), 39 (34, 51); HR (bpm): 87.01±17.07 vs. 95.88±21.06, 96.59±22.04; Tc (centigrade): 37.73±0.81 vs. 38.03±1.05, 38.10±1.04; Na+ (mmol/L): 150.14±3.86 vs. 144.18±8.89, 144.04±9.39; K+ (mmol/L): 4.32±0.57 vs. 4.15±0.62, 4.13±0.51; Cl- (mmol/L): 100.43±3.71 vs. 98.42±4.24, 98.41±4.58; all P < 0.01]. The incidence of severe heatstroke in group C was significantly lower than that in group A and group B [1.67% (5/300) vs. 5.00% (15/300), 5.33% (16/300), χ2 = 6.424, P = 0.040]. There was no significant difference in sweating volume in groups A, B, C (g: 370.47±48.71, 370.85±50.66, 370.17±50.21, F = 0.014, P = 0.986). There was no significant difference in the above indexes between group A and group B (all P > 0.05). Bi-classification Logistic regression analysis showed that the increase of HR, Tc and excessive loss of Na+, K+, Cl- were risk factors for severe heatstroke [odds ratio (OR) was 0.848, 0.138, 1.565, 17.996 and 2.328 respectively, all P < 0.01]. CONCLUSIONS: Timely supplementation of carbohydrate, sodium and potassium ions can effectively change the internal environment and body heat regulation reaction of 5-km armed cross-country trainees, so as to reduce the occurrence of severe heatstroke. The increases of HR, Tc and excessive loss of Na+, K+, Cl- are risk factors for severe heatstroke.