Sepsis is a systemic inflammatory response caused by severe infection or trauma, and is one of the common causes of acute lung injury(ALI) and acute respiratory distress syndrome(ARDS). Sepsis-acute lung injury(SALI) is a critical clinical condition with high morbidity and mortality. Its pathogenesis is complex and not yet fully understood, and there is currently a lack of targeted and effective treatment options. Pyroptosis, a novel form of programmed cell death, plays a key role in the pathological process of SALI by activating inflammasomes and releasing inflammatory factors, making it a potential therapeutic target. In recent years, the role of traditional Chinese medicine(TCM) in regulating signaling pathways related to pyroptosis through multi-components and multi-targets has attracted increasing attention. TCM may intervene in pyroptosis by inhibiting the activation of NLRP3 inflammasomes and regulating the expression of Caspase family proteins, thus alleviating inflammatory damage in lung tissues. This paper systematically reviews the molecular regulatory network of pyroptosis in SALI and explores the potential mechanisms and research progress on TCM intervention in cellular pyroptosis. The aim is to provide new ideas and theoretical support for basic research and clinical treatment strategies of TCM in SALI.
Pyroptosis/drug effects* ; Humans ; Sepsis/genetics* ; Acute Lung Injury/physiopathology* ; Animals ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Inflammasomes/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics*

INTRODUCTION

Neonatal sepsis is a significant cause of morbidity and mortality, particularly among preterm infants, and remains a pressing global health concern. Early-onset neonatal sepsis is particularly challenging to diagnose due to its nonspecific clinical presentation, necessitating effective and timely diagnostic tools to reduce adverse outcomes. Traditional methods, such as microbial cultures, are slow and often unavailable in resource-limited settings. This study aimed to develop a robust multivariable risk prediction model tailored to improve early detection of Early Onset Sepsis (EOS) among preterm infants in the Philippines.

We conducted a retrospective analysis at a tertiary hospital in the Philippines using data from 1,354 preterm infants admitted between January 2019 and June 2024. Logistic regression models were employed, and predictors were selected through reverse stepwise elimination. Two scoring methods were developed: one based on beta coefficients divided by standard errors and another standardized to a total score of 100. The models were validated using Receiver Operator Characteristic curve analysis.

Version 1 of the scoring model demonstrated an Area Under the Curve (AUC) of 0.991, with a sensitivity of 90.91% and a specificity of 98.10%. Version 2 achieved an AUC of 0.999, with a sensitivity of 96.4% and a specificity of 92.44%.

The developed models provide a reliable, region specific tool for early detection of neonatal sepsis. Further validation across diverse populations and the integration of emerging diagnostic technologies, such as biomarkers and artificial intelligence, are warranted to enhance their applicability and accuracy.

PURPOSE: Septic shock is associated with high mortality and poor outcomes among sepsis patients with coagulopathy. Although traditional statistical methods or machine learning (ML) algorithms have been proposed to predict septic shock, these potential approaches have never been systematically compared. The present work aimed to develop and compare models to predict septic shock among patients with sepsis. METHODS: It is a retrospective cohort study based on 484 patients with sepsis who were admitted to our intensive care units between May 2018 and November 2022. Patients from the 908th Hospital of Chinese PLA Logistical Support Force and Nanchang Hongdu Hospital of Traditional Chinese Medicine were respectively allocated to training (n=311) and validation (n=173) sets. All clinical and laboratory data of sepsis patients characterized by comprehensive coagulation indexes were collected. We developed 5 models based on ML algorithms and 1 model based on a traditional statistical method to predict septic shock in the training cohort. The performance of all models was assessed using the area under the receiver operating characteristic curve and calibration plots. Decision curve analysis was used to evaluate the net benefit of the models. The validation set was applied to verify the predictive accuracy of the models. This study also used Shapley additive explanations method to assess variable importance and explain the prediction made by a ML algorithm. RESULTS: Among all patients, 37.2% experienced septic shock. The characteristic curves of the 6 models ranged from 0.833 to 0.962 and 0.630 to 0.744 in the training and validation sets, respectively. The model with the best prediction performance was based on the support vector machine (SVM) algorithm, which was constructed by age, tissue plasminogen activator-inhibitor complex, prothrombin time, international normalized ratio, white blood cells, and platelet counts. The SVM model showed good calibration and discrimination and a greater net benefit in decision curve analysis. CONCLUSION The SVM algorithm may be superior to other ML and traditional statistical algorithms for predicting septic shock. Physicians can better understand the reliability of the predictive model by Shapley additive explanations value analysis.
Humans ; Shock, Septic/blood* ; Machine Learning ; Male ; Female ; Retrospective Studies ; Middle Aged ; Aged ; Sepsis/complications* ; ROC Curve ; Cohort Studies ; Adult ; Intensive Care Units ; Algorithms ; Blood Coagulation ; Critical Illness

PURPOSE: To compare the efficacy of continuous renal replacement therapy (CRRT) using either oXiris or conventional hemopurification filters in the treatment of intra-abdominal sepsis. METHODS: We conducted a retrospective analysis of septic patients with severe intra-abdominal infections admitted to our hospital from October 2019 to August 2023. Patients who meet the criteria for intra-abdominal sepsis based on medical history, symptoms, physical examination, and laboratory/imaging findings were included. EXCLUSION CRITERIA: pregnancy, terminal malignancy, prior CRRT before intensive care unit admission, pre-existing liver or renal failure. Heart rate (HR), mean arterial pressure, oxygenation index, lactic acid level (Lac), platelet count (PLT), neutrophil percentage, serum levels of procalcitonin, C-reactive protein, interleukin (IL)-6, norepinephrine dosage, acute physiology and chronic health evaluation II (APACHE II), and sequential organ failure assessment (SOFA) scores before and after 24 h and 72 h of treatment, as well as ventilator use time, hemopurification treatment time, intensive care unit and hospital lengths of stay, and 14-day and 28-day mortality were compared between patients receiving CRRT using either oXiris or conventional hemofiltration. Statistical analysis was performed using SPSS Statistics 26.0 software, including the construction of predictive models via logistic regression equations and repeated measures ANOVA. RESULTS: Baseline values including time to antibiotic administration, time to source control, and time to initiation of CRRT were similar between the 2 groups (all p>0.05). Patients receiving conventional CRRT exhibited significant changes in HR but of none of the other indexes at the 24 h and 72 h time points (p=0.041, p=0.026, respectively). The oXiris group showed significant improvements in HR, Lac, IL-6, and APACHE II score 24 h after treatment (p<0.05); after 72 h, all indexes were improved except PLT (all p<0.05). Intergroup comparison disclosed significant differences in HR, Lac, norepinephrine dose, APACHE II, SOFA, neutrophil percentage, and IL-6 after 24 h of treatment (p<0.05). Mean arterial pressure, serum levels of procalcitonin, C-reactive protein, SOFA score, and norepinephrine dosage were similar between the 2 groups at 24 h (p>0.05). Except for HR, oxygenation index, and PLT, post-treatment change rates of △ (%) were significantly greater in the oXiris group (p < 0.05). Duration of ventilator use, CRRT time, and intensive care unit and hospital lengths of stay were similar between the 2 groups (p>0.05). The 14-day mortality rates of the 2 groups were similar (p=0.091). After excluding patients whose CRRT was interrupted, 28-day mortality was significantly lower in the oXiris than in the conventional group (25.0% vs. 54.2%; p=0.050). The 28-day mortality rate increased by 9.6% for each additional hour required for source control and by 21.3% for each 1-point increase in APACHE II score. CONCLUSIONS In severe abdominal infections, the oXiris filter may have advantages over conventional CRRT, which may provide an alternative to clinical treatment. Meanwhile, early active infection source control may reduce the case mortality rate of patients with severe abdominal infections.
Humans ; Retrospective Studies ; Female ; Male ; Middle Aged ; Sepsis/mortality* ; Aged ; Adult ; Continuous Renal Replacement Therapy/methods* ; Intraabdominal Infections/mortality* ; APACHE ; Organ Dysfunction Scores ; Intensive Care Units ; Treatment Outcome

OBJECTIVES: To investigate the expression of soluble factor-related apoptosis ligand (sFasL) in peripheral blood and microRNA-147b (miR-147b) in monocytes in children with sepsis and their value in assessing prognosis. METHODS: A prospective study was conducted on 124 children with sepsis (sepsis group), 60 children with common infections (infection group), and 60 healthy children undergoing physical examinations (healthy control group). The independent risk factors for poor prognosis in children with sepsis were analyzed, and the value of serum sFasL and monocyte miR-147b in predicting poor prognosis in children with sepsis was assessed. RESULTS: The serum level of sFasL and the relative expression of miR-147b in monocytes were highest in the sepsis group, followed by the infection group and the healthy control group (P<0.05). The multivariate logistic regression analysis showed that the serum level of sFasL and the relative expression of miR-147b in monocytes were closely associated with the poor prognosis of children with sepsis (P<0.05). The receiver operating characteristic curve analysis showed that the combination of serum sFasL level and relative expression of miR-147b in monocytes had a larger area under the curve compared to each indicator alone in predicting the prognosis of children with sepsis (P<0.05). CONCLUSIONS There are significant increases in the level of sFasL in peripheral blood and the relative expression of miR-147b in monocytes in children with sepsis. The combined use of these two indicators has relatively high clinical value in assessing the prognosis of children with sepsis.
Humans ; Sepsis/diagnosis* ; MicroRNAs/blood* ; Male ; Female ; Monocytes/metabolism* ; Prognosis ; Child, Preschool ; Prospective Studies ; Child ; Infant ; TNF-Related Apoptosis-Inducing Ligand/blood* ; Logistic Models

OBJECTIVES: To evaluate the effect of colostrum oral immune therapy (COIT) on clinical outcomes in very low birth weight (VLBW) infants. METHODS: A computer-based search was conducted in databases including China National Knowledge Infrastructure, Wanfang Data, Weipu Database, Chinese Biomedical Literature Service System, PubMed, Embase, Web of Science, the Cochrane Library, and CINAHL for randomized controlled trials regarding the application of COIT in VLBW infants published from the establishment of the database to February 2024. Meta analysis was performed using RevMan 5.3 software. RESULTS: A total of 14 randomized controlled trials were included, involving 1 386 VLBW infants, with 690 in the COIT group and 696 in the control group. The results showed that COIT significantly reduced the incidence of clinical late-onset sepsis (LOS) (RR=0.75, 95%CI: 0.64-0.88, P<0.001), the incidence of blood culture-proven LOS (RR=0.72, 95%CI: 0.57-0.92, P=0.008), mortality rate (RR=0.70, 95%CI: 0.52-0.95, P=0.020), the incidence of necrotizing enterocolitis (RR=0.65, 95%CI: 0.46-0.92, P=0.020), and the incidence of feeding intolerance (RR=0.49, 95%CI: 0.29-0.80, P=0.004). It also shortened the time to achieve full enteral nutrition (MD=-2.13, 95%CI: -4.03 to -0.23, P=0.030). CONCLUSIONS COIT can reduce the incidence rates of LOS, necrotizing enterocolitis, and feeding intolerance, as well as the mortality rate, while also shortening the time to achieve full enteral nutrition in VLBW infants.
Humans ; Infant, Very Low Birth Weight ; Colostrum/immunology* ; Infant, Newborn ; Sepsis/prevention & control* ; Randomized Controlled Trials as Topic ; Administration, Oral

OBJECTIVES: To study the clinical characteristics and risk factors of pyogenic liver abscess complicated by sepsis in children. METHODS: A retrospective analysis was conducted on the clinical data of 120 children with pyogenic liver abscess admitted from May 2004 to January 2024. According to the presence of sepsis, the children were divided into a sepsis group (82 cases) and a non-sepsis group (38 cases). The clinical characteristics of the two groups were compared, and risk factors associated with the occurrence of sepsis were identified. RESULTS: Among the 120 children with pyogenic liver abscess, 68.3% (82/120) had sepsis. Multivariate logistic regression analysis showed that fever, elevated white blood cell count, and decreased albumin level were closely associated with the occurrence of sepsis (P<0.05). Receiver operating characteristic curve analysis indicated that white blood cell count and albumin levels had significant predictive value for sepsis (P<0.05), and the combination of white blood cell count and albumin level showed higher predictive value for sepsis than the albumin level alone (P<0.05). CONCLUSIONS The clinical manifestations of children with pyogenic liver abscess complicated by sepsis are non-specific. Fever, elevated white blood cell count, and decreased albumin level are risk factors for sepsis in children with pyogenic liver abscess. Clinically, for children with unexplained fever and imaging suggestive of liver abscess, pyogenic liver abscess should be considered. If laboratory tests show elevated white blood cell count and decreased albumin level simultaneously, there should be a high level of suspicion for the development of sepsis.
Humans ; Liver Abscess, Pyogenic/blood* ; Male ; Female ; Risk Factors ; Retrospective Studies ; Sepsis/etiology* ; Child, Preschool ; Infant ; Child ; Leukocyte Count ; Logistic Models ; Adolescent ; Serum Albumin/analysis*

Neonatal sepsis is one of the major life-threatening diseases in neonates, with significant regional variations in mortality. The Subspecialty Group of Neonatology, Society of Pediatrics, Chinese Medical Association, together with the Editorial Board of the Chinese Journal of Contemporary Pediatrics, organized neonatology experts to integrate the latest advances in clinical research on neonatal sepsis. Taking into account the current situation of primary healthcare institutions in China, they addressed nine common clinical questions regarding the diagnosis, treatment, and referral of neonatal sepsis for primary healthcare providers, and resulting in 19 expert consensus recommendations. This consensus aims to help primary healthcare providers promptly identify neonatal sepsis, ensure timely intervention or referral, and improve clinical outcomes.
Humans ; Infant, Newborn ; Neonatal Sepsis/therapy* ; Primary Health Care ; Consensus

A 39-year-old male patient was admitted to hospital with abdominal distension, unconsciousness, and anuria. Head computed tomography (CT) showed subarachnoid hemorrhage and diffuse cerebral edema. The high-density area of contrast accumulation region in the high-density CT plaque was 38 HU, and the preliminary diagnosis was SAH, incomplete intestinal obstruction, and sepsis caused by acute cerebrovascular disease. After admission, the patient displayed upturned eyes, limb convulsions, serum procalcitonin level exceeding 100 ng/mL, low blood pressure and septic shock. Imipenem was given for intensive anti-infection therapy. After treatment, procalcitonin levels showed a slow decline, renal function, and intra-abdominal pressure returned to normal, urine volume gradually increased, but platelets still showed a downward trend. Lumbar puncture showed colorless and clear cerebrospinal fluid, and the biochemical and routine results of cerebrospinal fluid were normal. SAH and intracranial infection were excluded, and it was considered that the head CT showed pseudo-subarachnoid hemorrhage. On the 3rd day of admission, laparoscopic exploratory laparotomy+appendectomy+abdominal drainage under general anesthesia were performed. During surgery, purulent gangrene in the appendix was found, with pus adhering to the surface of the intestines and a large amount of pus present in the abdominal cavity. Rhabdomyolysis syndrome developed after surgery. After continuous renal replacement therapy, the indicators gradually returned to normal. The patient was conscious, and the head CT results were normal. The patient was discharged from the hospital on the 19th day after surgery, and no special discomfort and abdominal pain and distension occurred during the 3-month follow-up.
Humans ; Male ; Adult ; Tomography, X-Ray Computed ; Sepsis/diagnostic imaging* ; Multiple Organ Failure/etiology* ; Subarachnoid Hemorrhage/complications*

OBJECTIVE: To identify the underlying mechanism by which quercetin (Que) alleviates sepsis-related acute respiratory distress syndrome (ARDS). METHODS: In vivo, C57BL/6 mice were assigned to sham, cecal ligation and puncture (CLP), and CLP+Que (50 mg/kg) groups (n=15 per group) by using a random number table. The sepsisrelated ARDS mouse model was established using the CLP method. In vitro, the murine alveolar macrophages (MH-S) cells were classified into control, lipopolysaccharide (LPS), LPS+Que (10 μmol/L), and LPS+Que+acetylcysteine (NAC, 5 mmol/L) groups. The effect of Que on oxidative stress, inflammation, and apoptosis in mice lungs and MH-S cells was determined, and the mechanism with reactive oxygen species (ROS)/p38 mitogen-activated protein kinase (MAPK) pathway was also explored both in vivo and in vitro. RESULTS: Que alleviated lung injury in mice, as reflected by a reversal of pulmonary histopathologic changes as well as a reduction in lung wet/dry weight ratio and neutrophil infiltration (P<0.05 or P<0.01). Additionally, Que improved the survival rate and relieved gas exchange impairment in mice (P<0.01). Que treatment also remarkedly reduced malondialdehyde formation, superoxide dismutase and catalase depletion, and cell apoptosis both in vivo and in vitro (P<0.05 or P<0.01). Moreover, Que treatment diminished the release of inflammatory factors interleukin (IL)-1β, tumor necrosis factor-α, and IL-6 both in vivo and in vitro (P<0.05 or P<0.01). Mechanistic investigation clarifified that Que administration led to a decline in the phosphorylation of p38 MAPK in addition to the suppression of ROS expression (P<0.01). Furthermore, in LPS-induced MH-S cells, ROS inhibitor NAC further inhibited ROS/p38 MAPK pathway, as well as oxidative stress, inflammation, and cell apoptosis on the basis of Que treatment (P<0.05 or P<0.01). CONCLUSION Que was found to exert anti-oxidative, anti-inflammatory, and anti-apoptotic effects by suppressing the ROS/p38 MAPK pathway, thereby conferring protection for mice against sepsis-related ARDS.
Animals ; Sepsis/drug therapy* ; Quercetin/therapeutic use* ; Respiratory Distress Syndrome/enzymology* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; Mice, Inbred C57BL ; Reactive Oxygen Species/metabolism* ; Apoptosis/drug effects* ; Male ; Oxidative Stress/drug effects* ; MAP Kinase Signaling System/drug effects* ; Lung/drug effects* ; Mice ; Lipopolysaccharides ; Macrophages, Alveolar/pathology* ; Inflammation/pathology* ; Protective Agents/therapeutic use*