Objective:This study aimed to investigate the correlation between the levels of serum amyloid A protein (SAA) and apolipoprotein A-Ⅰ (ApoA-Ⅰ) with the severity and prognosis of septic patients, in order to find new clinical prognostic markers for sepsis patients.Methods:This study prospectively included patients admitted to the intensive care unit of Northern Jiangsu People's Hospital from September 2021 to February 2022. Patients were diagnosed with sepsis according to the Sepsis-3 criteria and aged between 18 and 80 years old. Peripheral venous blood samples were collected at 0 h, 24 h, and 72 h after inclusion in the study, measured the levels of ApoA-Ⅰ and SAA, and the 72 h ΔSAA and 72 h ΔApoA-Ⅰwere calculated.. Patient demographics, laboratory parameters, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) scores, sequential organ failure assessment scores, etc., were recorded. Patients were divided into survival and death groups based on outcomes, and were divided into shock and non-shock groups based on the presence of shock. Logistic regression was used to combine ApoA-I and SAA to establish a new combined index. Receiver Operating Characteristic curve analysis was performed to evaluate the predictive value of SAA, ApoA-Ⅰ, 72 h ΔApoA-Ⅰ, 72 h ΔSAA and the combined SAA and ApoA-Ⅰ for the prognosis of sepsis patients.Results:A total of 108 patients were included in the analysis, with 48 cases in the non-septic shock group and 60 cases in the septic shock group; 77 cases in the survival group and 31 cases in the death group. There were statistically significant differences in SAA and ApoA-Ⅰ levels at each time point between the shock and non-shock groups (all P<0.05), as well as between the death and survival groups (all P<0.05). SAA levels at each time point were positively correlated with APACHEⅡ scores (all P<0.001), while ApoA-Ⅰ levels at each time point were negatively correlated with APACHEⅡ scores (all P<0.01). SAA levels could predict the risk of death in sepsis patients, with the highest area under curve (AUC) value at 24 h SAA (AUC=0.713, P=0.001), sensitivity was 65.3%, and specificity was 72.7% for predicting 28-day mortality in sepsis. ApoA-Ⅰ levels at each time point could also predict the risk of death in sepsis patients, with the highest AUC value at 72 h ApoA-Ⅰ (AUC=0.743, P<0.001), sensitivity was 69.4%, and specificity was 77.1% for predicting 28-day survival in sepsis. The combined detection of 24 h SAA and 72 h ApoA-Ⅰ increased the AUC value (AUC=0.758, P<0.05), but the Z test showed that the prediction of death risk in patients with sepsis was not significantly higher than that of a single index ( P>0.05). Conclusions:Serum levels of SAA and ApoA-Ⅰ could reflect the severity of sepsis in patients and serve as independent indicators for predicting the prognosis of sepsis patients. The overall diagnostic efficacy of the combined SAA and ApoA-Ⅰ was not significantly different from that of a single index.

Objective:To establish a risk predictive model nomogram of acute kidney injury (AKI) in critically ill patients by combining urinary tissue inhibitor of metalloproteinase 2 (TIMP2) and insulin-like growth factor-binding protein 7 (IGFBP7), and to verify the predictive value of the model.Methods:A prospective observational study was conducted. The patients with acute respiratory failure or circulatory disorder admitted to the intensive care unit (ICU) of Northern Jiangsu People's Hospital from November 2017 to April 2020 were enrolled. The patients were enrolled within 24 hours of ICU admission, and their general conditions and relevant laboratory test indicators were collected. At the same time, urine was collected to determine the levels of biomarkers TIMP2 and IGFBP7, and TIMP2·IGFBP7 was calculated. Patients were divided into non-AKI and AKI groups according to whether grade 2 or 3 AKI occurred within 12 hours after enrollment. The general clinical data and urinary TIMP2·IGFBP7 levels of patients between the two groups were compared. The indicators with P < 0.1 in univariate analysis were included in the multivariate Logistic regression analysis to obtain the independent risk factors for grade 2 or 3 AKI within 12 hours in critical patients. An AKI risk predictive model nomogram was established, and the application value of the model was evaluated. Results:A total of 206 patients were finally enrolled, of whom 54 (26.2%) developed grade 2 or 3 AKI within 12 hours of enrollment, and 152 (73.8%) did not. Compared with the non-AKI group, the patients in the AKI group had higher body mass index (BMI), pre-enrollment serum creatinine (SCr), urinary TIMP2·IGFBP7 and proportion of using vasoactive drugs, and additional exposure to AKI (use of nephrotoxic drugs before enrollment) was more common. Multivariate Logistic regression analysis showed that BMI [odds ratio ( OR) = 1.23, 95% confidence interval (95% CI) was 1.10-1.37, P = 0.000], pre-enrollment SCr ( OR = 1.01, 95% CI was 1.00-1.02, P = 0.042), use of nephrotoxic drugs ( OR = 2.84, 95% CI was 1.34-6.03, P = 0.007) and urinary TIMP2·IGFBP7 ( OR = 2.19, 95% CI was 1.56-3.08, P = 0.000) was an independent risk factor for the occurrence of grade 2 or 3 AKI in critical patients. An AKI risk predictive model nomogram was constructed based on the independent risk factors of AKI. Bootstrap validation results showed that the model had good discrimination and calibration in internal validation. Receiver operator characteristic curve (ROC curve) analysis showed that the area under the ROC curve (AUC) of urinary TIMP2·IGFBP7 alone in predicting grade 2 or 3 AKI within 12 hours in critical patients was 0.74 (95% CI was 0.66-0.83), the optimal cut-off value was 1.40 (μg/L) 2/1?000 (sensitivity was 66.7%, specificity was 85.0%), and the predictive performance of the model incorporating urinary TIMP2·IGFBP7 was significantly better than that of the model without urinary TIMP2·IGFBP7 [AUC (95% CI): 0.85 (0.79-0.91) vs. 0.77 (0.70-0.84), P = 0.005], net reclassification index (NRI) was 0.29 (95% CI was 0.08-0.50, P = 0.008), integrated discrimination improvement (IDI) was 0.13 (95% CI was 0.07-0.19, P < 0.001). Conclusion:The AKI risk predictive model based on urinary TIMP2·IGFBP7 has high clinical value and is expected to be used to early predict the occurrence of AKI in critically ill patients.

Sepsis-associated liver injury (SALI) is a common complication of sepsis, which is characterized by systemic immune disorders induced by sepsis leading to liver damage. Currently, there are no effective treatments for SALI, which is related to its complex pathophysiological mechanisms. In recent years, the disorder of intestinal environment after sepsis has been considered as an important factor for SALI, but the specific molecular mechanism of the above process is still unclear. This article will review the pathological role and molecular mechanisms between intestinal environmental disturbance and SALI, aiming to analyze the potential research direction of SALI and identify potential therapeutic targets for its treatment.

Sepsis is a life-threatening organ dysfunction caused by the host's dysfunctional response to infection. Sepsis-induced cardiomyopathy (SICM), as a serious complication of sepsis, is an acute reversible cardiac dysfunction syndrome unrelated to myocardial ischemia, which affects the outcome and prognosis of sepsis. As a complex microbial system, gut microbiota has been confirmed to be involved in the development of coronary heart disease, hypertension, heart failure and other cardiovascular diseases, and is also related to the occurrence and development of sepsis. However, there are few studies on the relationship between gut microbiota and SICM. This paper reviews the current research progress on gut microbiota and SICM, aiming at provide a new idea for clinical treatment of SICM.

Optimizing the management of medical service appointment is an important measure to enhance the patient′s medical experience and promote the high-quality development of hospitals. In 2022, a tertiary comprehensive hospital in Jiangsu Province focused on the demand for digital appointments, and carried out coordinated management of intelligent appointment for medical examination both inside and outside the hospital, online and offline. By constructing an intelligent examination appointment system, enriching appointment categories, exchanging appointment information, improving supporting services, and establishing appointment supervision mechanisms, this practice provided intelligent, personalized, and precise examination appointment services for patients in multi-campus hospitals and member units of medical group. The average waiting time of patients for CT, MRI, and ultrasound examinations in this hospital decreased from 7.43 h, 8.75 h, and 4.63 h in 2021 to 4.63 h, 4.72 h, and 2.18 h in 2023, respectively, as well as the average satisfaction rate of patients with examination appointments increased from 90.7% to 96.5%. The intelligent examination appointment management had achieved good results, which could provide references for other hospitals to optimize appointment of medical services.

OBJECTIVE: To investigate the correlation of hemoglobin (Hb) level with prognosis of elderly patients diagnosed as sepsis. METHODS: A retrospective cohort study was conducted. Information on the cases of elderly patients with sepsis in the Medical Information Mart for Intensive Care-IV (MIMIC-IV), including basic information, blood pressure, routine blood test results [the Hb level of a patient was defined as his/her maximum Hb level from 6 hours before admission to intensive care unit (ICU) and 24 hours after admission to ICU], blood biochemical indexes, coagulation function, vital signs, severity score and outcome indicators were extracted. The curves of Hb level vs. 28-day mortality risk were developed by using the restricted cubic spline model based on the Cox regression analysis. The patients were divided into four groups (Hb < 100 g/L, 100 g/L ≤ Hb < 130 g/L, 130 g/L ≤ Hb < 150 g/L, Hb ≥ 150 g/L groups) based on these curves. The outcome indicators of patients in each group were analyzed, and the 28-day Kaplan-Meier survival curve was drawn. Logistic regression model and Cox regression model were used to analyze the relationship between Hb level and 28-day mortality risk in different groups. RESULTS: A total of 7 473 elderly patients with sepsis were included. There was a "U" curve relationship between Hb levels within 24 hours after ICU admission and the risk of 28-day mortality in patients with sepsis. The patients with 100 g/L ≤ Hb < 130 g/L had a lower risk of 28-day mortality. When Hb level was less than 100 g/L, the risk of death decreased gradually with the increase of Hb level. When Hb level was ≥ 130 g/L, the risk of death gradually increased with the increase of Hb level. Multivariate Logistic regression analysis revealed that the mortality risks of patients with Hb < 100 g/L [odds ratio (OR) = 1.44, 95% confidence interval (95%CI) was 1.23-1.70, P < 0.001] and Hb ≥ 150 g/L (OR = 1.77, 95%CI was 1.26-2.49, P = 0.001) increased significantly in the model involving all confounding factors; the mortality risks of patients with 130 g/L ≤ Hb < 150 g/L increased, while the difference was not statistically significant (OR = 1.21, 95%CI was 0.99-1.48, P = 0.057). The multivariate Cox regression analysis suggested that the mortality risks of patients with Hb < 100 g/L [hazard ratio (HR) = 1.27, 95%CI was 1.12-1.44, P < 0.001] and Hb ≥ 150 g/L (HR = 1.49, 95%CI was 1.16-1.93, P = 0.002) increased significantly in the model involving all confounding factors; the mortality risks of patients with 130 g/L ≤ Hb < 150 g/L increased, while the difference was not statistically significant (HR = 1.17, 95%CI was 0.99-1.37, P = 0.053). Kaplan-Meier survival curve showed that the 28-day survival rate of elderly septic patients in 100 g/L ≤ Hb < 130 g/L group was significantly higher than that in Hb < 100 g/L, 130 g/L ≤ Hb < 150 g/L and Hb ≥ 150 g/L groups (85.26% vs. 77.33%, 79.81%, 74.33%; Log-Rank test: χ² = 71.850, P < 0.001). CONCLUSIONS Elderly patients with sepsis exhibited low mortality risk if their 100 g/L ≤ Hb < 130 g/L within 24 hours after admission to ICU, and both higher and lower Hb levels led to increased mortality risks.
Humans ; Male ; Female ; Aged ; Retrospective Studies ; Sepsis/diagnosis* ; Critical Care ; Intensive Care Units ; Prognosis ; Hemoglobins ; ROC Curve

Ferroptosis is a non-apoptotic form of cell death newly discovered in 2012.It is characterized by a lethal accumulation of iron-dependent reactive oxygen species and lipid hydroperoxides,resulting in mitochondrial morphological changes and phospholipid peroxidation damage of cell membrane.As a strong oxidizing agent in biological systems,iron overloaded,can directly cause acute kidney injury(AKI)through oxidative damage.Iron homeostasis disturbance and ferroptosis are directly involved in AKI caused by ischemia-reperfusion,drugs and rhabdomyolysis,etc.This article reviews the relevant evidence and the important mechanism of iron homeostasis and ferroptosis in AKI,and provides new ideas and new targets for further research and treatment of AKI.

Objective:Sepsis patients usually have a fever, but it is still controversial about whether sepsis patients with fever need cooling treatment. This study aimed to evaluate the effect of external physical cooling on the prognosis of sepsis patients.Methods:This study was a single-center, open-label, randomized clinical trial. Adult sepsis patients with body temperature above 38.3 °C admitted to the Critical Care Medicine of Northern Jiangsu People's Hospital from June 2020 to December 2020 were selected, and randomly assigned in a 1∶1 ratio to the cooling group and control group. Patients in the cooling group used external physical cooling methods to reduce their core body temperature to the normal range (36.5-37.5°C) within 4 h of enrollment and maintained for 48 h. Standard care was implemented in the control group at all times, and all antipyretic treatments were prohibited. The 28-day mortality, 72 h-Δ sequential organ failure assessment (SOFA) score (SOFA score at enrollment–SOFA score after 72 h), length of hospital stay and length of ICU stay were compared between the two groups.Results:A total of 53 patients (32 males and 21 females) were enrolled in the study, including 26 patients in the cooling group and 27 patients in the control group. There were no statistical differences in age, sex, source of infection, SOFA score and body temperature between the two groups (all P>0.05). There was no significant difference in the 28-day mortality between the cooling group and the control group ( RR=1.38, 95% CI: 0.62-3.07, P=0.430). The 72 h-ΔSOFA score of the cooling group was significantly higher than that of the control group, the mean difference between the two groups was 1.90 (95% CI: 0.09-3.71, P=0.040), and there was no significant difference in length of hospital stay, length of ICU stay and 28-day mortality between the two groups. Conclusions:External physical cooling management can not significantly reduce the 28-day mortality of sepsis patients. However, external physical cooling can reduce the 72-h SOFA score in sepsis patients, and improve the organ function of patients.

Sepsis is an important cause of acute kidney injury (AKI). About 60% of sepsis patients will develop AKI. At present, the standard of clinical diagnosis of AKI is still based on the changes in serum creatinine and urine volume. Because of its lag in time, it may lead to delay in treatment and increase the mortality. To find a new biomarker similar to "troponin" for the diagnosis of AKI, and to achieve the early diagnosis and prevention of AKI, is of great significance to reduce the mortality of AKI. In recent years, it has been found that tissue inhibitors of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) can be used for early diagnosis of sepsis associated-acute kidney injury (SA-AKI). They also have important values in risk stratification, prognosis judgment, intervention and other aspects of SA-AKI. In this paper, the research progress of the application of TIMP-2 and IGFBP7 in SA-AKI is reviewed.

Objective:To study the signaling pathway of the up-regulation of claudin-5 expression by Xuebijing injection.Methods:Animal and cell models of acute respiratory distress syndrome (ARDS) were induced by lipopolysaccharide (LPS). ① In vivo study, 20 male Sprague-Dawley (SD) rats were randomly divided into 4 groups: control group, LPS group (LPS injection 10 mg/kg for 12 hours), Xuebijing control group (Xuebijing injection 1 mg/kg, twice a day, for 3 days), and Xuebijing intervention group (LPS injection after pretreatment of Xuebijing injection), according to random number method with 5 rats in each group. The lung tissues were taken to detect lung dry/wet weight ratio (W/D) and the morphological changes in each group. Claudin-5, phosphorylated forkhead box transcription factor O1 (p-FOXO1), total FOXO1 (t-FOXO1), phosphorylated Akt (p-Akt) and total Akt (t-Akt) in lung tissues were detected by immunohistochemical staining (IHC) and Western blotting. ② In vitro study, human pulmonary microvascular endothelial cells (HPMECs) were divided into 6 groups (5 holes in each group): control group, Xubijing control group (incubated with 2 g/L Xubijing for 24 hours), phosphoinositide 3-kinases (PI3K) signaling pathway LY294002 control group (incubated with 10 μmol/L LY294002 for 1 hour), LPS group (incubated with 1 mg/L LPS for 12 hours), Xubijing intervention group (incubated with 2 g/L Xuebijing for 24 hours, then with 1 mg/L LPS for 12 hours) and LY294002 intervention group (incubated with 10 μmol/L LY294002 for 1 hour, then with 2 g/L and Xubijing for 24 hours, and then with 1 mg/L LPS for 12 hours). The expression levels of claudin-5, p-FOXO1, t-FOXO1, p-Akt and t-Akt of HPMECs in each group were assessed by Western blotting. Results:In vivo study: ① Compared with the control group, the lung W/D ratio increased significantly in LPS group (6.79±0.42 vs. 4.19±0.13), and decreased significantly after the intervention of Xuebijing (4.92±0.38 vs. 6.79±0.42, P < 0.01). ② Morphological changes of lung tissue: compared with the control group, the injury of lung tissue in LPS group was more serious, which was significantly improved after Xuebijing intervention. ③ Expression levels of claudin-5, p-Akt/t-Akt and p-FOXO1/t-FOXO1: the expression levels of claudin-5, p-Akt/t-Akt and p-FOXO1/t-FOXO1 in LPS group were significantly decreased as compared with the control group (claudin-5/GAPDH: 0.33±0.03 vs. 1.03±0.07, p-Akt/t-Akt: 0.18±0.02 vs. 1.01±0.13, p-FOXO1/t-FOXO1: 0.16±0.06 vs. 1.00±0.19, all P < 0.01). After the intervention of Xuebijing, the expression levels were significantly increased as compared with the LPS group (claudin-5/GAPDH: 0.53±0.05 vs. 0.33±0.03, p-Akt/t-Akt: 0.56±0.12 vs. 0.18±0.02, p-FOXO1/t-FOXO1: 0.68±0.10 vs. 0.16±0.06, all P < 0.01). In vitro study: compared with the control group, the expression level of claudin-5 in the LPS group was significantly decreased (claudin-5/β-actin: 0.45±0.03 vs. 1.01±0.15, P < 0.01), and the expression level of claudin-5 in Xuebijing intervention group was also significantly decreased (claudin-5/β-actin: 0.80±0.08 vs. 1.01±0.15, P < 0.01). After the intervention of LY294002, the expression of claudin-5 was significantly decreased as compared with the Xubijing intervention group (claudin-5/β-actin: 0.41±0.02 vs. 0.80±0.08, P < 0.01). Conclusion:Xuebijing injection improve pulmonary vascular barrier function in rats with ARDS by up-regulating claudin-5 expression through PI3K/Akt/FOXO1 signaling pathway.