Objective To analyze the influencing factors of malaria infection of labor service exported to overseas in Langfang City, in order to establish a visualization tool to assist clinicians in predicting the risk of malaria. Methods A total of 4 774 expatriate employees of the Nibei Pipeline Project of the Pipeline Bureau from October 2021 to August 2023 were taken as the subjects, and the gender, age, overseas residence area and Knowledge of malaria controlscores of the study subjects were investigated by questionnaire survey, and the possible risk factors of malaria were screened by logistic regression model. At the same time, the nomogram prediction model was established, and the subjects were divided into the training group and the validation group at a ratio of 2:1, and the area under the curve (ROC) and the decision curve were plotted to evaluate the prediction ability and practicability of the prediction model in this study. Results Among the 4 774 study subjects, 96 cases of malaria occurred, and the detection rate was 2.01%. Junior school （OR=1.723，95% CI:1.361-2.173）， and residence in rural areas（OR=2.091，95%CI:1.760 -3.100）were risk factors (OR>1), while protective measures（OR=0.826，95% CI : 0.781 - 0.901） and high malaria education scores （OR=0.872，95% CI : 0.621 - 0.899）were protective factors.The nomogram prediction model results showed that the area under the curve of the nomogram prediction model in the training group was 0.94 (95% CI : 0.85 - 1.00), while the validation group was 0.93 (95% CI : 0.80 - 1.00). The results of the decision curve showed that when the threshold probability of the population was 0-0.9, the nomogram model was used to predict the risk of malaria occurrence with the highest net income. Conclusion The nomogram prediction model (including gender, education, region, protection and malaria education score) established and validated in this study is of great value for clinicians to screen high-risk patients with malaria.

Objective:To investigate the dynamic changes of cytokine levels in patients with sepsis and to identify potential biomarkers for evaluating the prognosis of the disease.Methods:A total of 195 patients with sepsis hospitalized at the Department of Infectious Diseases and the Department of Critical Care Medicine of the First Affiliated Hospital of Soochow University from August 2022 to October 2024 were recruited, and 70 healthy individuals undergoing physical examinations were recruited as the healthy control group. The levels of 11 cytokines, including interferon γ (IFN-γ), interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-17A, tumor necrosis factor α (TNF-α) and C-reactive protein (CRP) were compared between the sepsis patients and the healthy controls. Spearman correlation analysis was used to assess the correlation between cytokine levels and sequential organ failure assessment (SOFA) scores in sepsis patients. Receiver operating characteristic curves were plotted and the area under the curve (AUC) was calculated to evaluate the diagnostic value of cytokines for sepsis. Delong test was used to compare AUC. Based on the 28-day survival outcomes, the sepsis patients were categorized into non-survival group and survival group. The levels of the 11 cytokines in patients on the 1st, 3rd, 7th, 14th, 21st and 28th days after confirmed sepsis were dynamically monitored, and their change characteristics were analyzed. Mann-Whitney U test was used for statistical comparison. Results:The age of the 195 patients with sepsis was 68.0 (55.0, 76.0) years old, including 124 males (63.6%), 64 died and 131 survived.The levels of IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-17A, TNF-α, CRP in the sepsis group were all higher than those in the healthy control group ( Z=-2.99, -5.42, -4.95, -4.09, -5.05, -11.30, -8.66, -8.23, -5.64, -4.75, -2.12 and -10.75, respectively, all P<0.05). The differences were statistical significance. The levels of IL-2 ( r=0.149, P=0.037), IL-6 ( r=0.223, P=0.002), IL-8 ( r=0.159, P=0.026), and IL-10 ( r=0.188, P=0.009) in patients with sepsis were positively correlated with SOFA scores. The AUC of CRP in diagnosing sepsis was 0.989 with the sensitivity of 97.4% and the specificity of 100.0%. The AUC of IL-6 in diagnosing sepsis was 0.953, with the sensitivity of 93.3% and the specificity of 97.1%, and the AUC of IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12P70, IL-17A, and TNF-α were 0.620, 0.718, 0.699, 0.665, 0.703, 0.850, 0.836, 0.727, 0.691, and 0.574, respectively.The AUC of the 11 cytokines were all lower than that of CRP, and the differences were all statistically significant ( Z=2.34, 10.24, 8.03, 8.08, 10.64, 8.70, 5.91, 5.17, 8.91, 9.25 and 4.10, respectively, all P<0.05).During the dynamic monitoring, the IFN-γ and IL-1β levels in the non-survival group increased gradually. The IFN-γ levels on the 14th and 21st day in the non-survival group were higher than those in the survival group ( Z=0.53 and 0.08, respectively, both P<0.05), and IL-1β levels on the 14th, 21st, and 28th days were also higher than those in the survival group ( Z=0.03, 0.26 and 0.31, respectively, all P<0.05). IL-6 and IL-8 levels reached their peaks on the 14th day, which were significantly higher than those in the survival group ( Z=0.01 and 0.02, respectively, both P<0.05), and then decreased, and the differences were all statistically significant. Conclusions:The levels of IFN-γ and IL-1β in the non-survival sepsis patients show a gradually increasing trend. The dynamic changes of IL-6 have certain significance for the prediction of disease severity and prognosis evaluation in sepsis.

In hypoxic-ischemic brain damage (HIBD), the programmed cell death known as ferroptosis is significantly activated. Microglial cells demonstrate a high level of sensitivity to iron accumulation. Understanding how to regulate the dual role of microglia and transforming the microglial ferroptosis to a moderate and controllable process has considerable implications for the targeted treatment in HIBD. This paper serves as an overview of microglia-mediated ferroptosis in HIBD as a disease model. We discuss various aspects centered around microglia, including pathophysiological mechanisms, polarization and functions of microglia, molecular mechanisms of ferroptosis, signaling pathways, and therapeutic strategies. The review aims to provide a reference for studies of ferroptosis in microglia.
Microglia/physiology* ; Ferroptosis/physiology* ; Humans ; Animals ; Hypoxia-Ischemia, Brain/pathology* ; Signal Transduction

OBJECTIVES: To evaluate the therapeutic effect of gastrodin against hypoxic-ischemic brain damage (HIBD) in neonatal mice and explore the role of GPX4/SLC7A11/FTH1 signaling in mediating its effect. METHODS: Twenty-four 9- to 11-day-old C57BL/6J mice were randomized equally into 4 groups for sham operation, HIBD modeling by right common carotid artery ligation and subsequent exposure to hypoxia for 1 h, or gastrodin treatment at 100 or 200 mg/kg before and at 1 and 2 days after modeling. The mice then underwent neurological assessment (Zea-Longa scores), and the cerebral cortical penumbra tissue were collected for HE and Nissl staining, detection of ferroptosis biomarkers and protein expressions of GPX4, SLC7A11, and FTH1 with Western blotting and immunofluorescence co-localization, and observation of mitochondrial ultrastructure with electron microscopy. In cultured HT22 neuronal cells with oxygen-glucose deprivation (OGD) for 2 h, the effects of pretreatments with 0.5 mmol/L gastrodin, 10 μmol/L RSL3 (a GPX4 inhibitor), alone or in combination, were analyzed on expressions of ferroptosis-related proteins, cellular Fe²⁺, ROS, lipid peroxidation, MDA, and GSH levels, mitochondrial membrane potential (JC-1), and cell viability. RESULTS: Gastrodin treatment at the two doses both significantly ameliorated HIBD and neurological deficits of the mice, reduced mitochondrial damage and Fe²⁺, MDA and ROS levels, increased GSH level, and upregulated GPX4, SLC7A11, and FTH1 protein expressions. In HT22 cells, gastrodin pretreatment obviously attenuated OGD-induced ferroptosis and improved cell viability and mitochondrial function. Co-treatment with RSL3 potently abrogated the inhibitory effects of gastrodin on Fe²⁺, ROS, BODIPY-C11, and MDA levels and attenuated its protective effects on GSH level, cell viability, and mitochondrial membrane potential. CONCLUSIONS Gastrodin provides neuroprotective effects in neonatal mice with HIBD by suppressing neuronal ferroptosis via upregulating the GPX4/SLC7A11/FTH1 signaling pathway.
Animals ; Ferroptosis/drug effects* ; Hypoxia-Ischemia, Brain/drug therapy* ; Mice ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Glucosides/pharmacology* ; Animals, Newborn ; Benzyl Alcohols/pharmacology* ; Amino Acid Transport System y+/metabolism*

OBJECTIVE: To develop a method for identifying high-risk patients among septic populations requiring mechanical ventilation, and to conduct phenotypic analysis based on this method. METHODS: Data from four sources were utilized: the Medical Information Mart for Intensive Care (MIMIC-IV 2.0, MIMIC-III 1.4), the Philips eICU-Collaborative Research Database 2.0 (eICU-CRD 2.0), and the Anhui Medical University Second Affiliated Hospital dataset. The adult patients in intensive care unit (ICU) who met Sepsis-3 and received invasive mechanical ventilation (IMV) on the first day of first admission were enrolled. The MIMIC-IV dataset with the highest data integrity was divided into a training set and a test set at a 6:1 ratio, while the remaining datasets were served as validation sets. The demographic information, comorbidities, laboratory indicators, commonly used ICU scores, and treatment measures of patients were extracted. Clinical data collected within first day of ICU admission were used to calculate the sequential organ failure assessment (SOFA) score. K-means clustering was applied to cluster SOFA score components, and the sum of squared errors (SSE) and Davies-Bouldin index (DBI) were used to determine the optimal number of disease subtypes. For clustering results, normalized methods were employed to compare baseline characteristics by visualization, and Kaplan-Meier curves were used to analyze clinical outcomes across phenotypes. RESULTS: This study enrolled patients from MIMIC-IV dataset (n = 11 166), MIMIC-III dataset (n = 4 821), eICU-CRD dataset (n = 6 624), and a local dataset (n = 110), with the four datasets showing similar median ages and male proportions exceeding 50%; using 85% of the MIMIC-IV dataset as the training set, 15% as the test set, and the rest dataset as the validation set. K-means clustering based on the six-item SOFA score was performed to determine the optimal number of clusters as 3, and patients were finally classified into three phenotypes. In the training set, compared with the patients with phenotype II and phenotype III, those with phenotype I had the more severe circulatory and respiratory dysfunction, a higher proportion of vasoactive drug usage, more obvious metabolic acidosis and hypoxia, and a higher incidence of congestive heart failure. The patients with phenotype II was dominated by respiratory dysfunction with higher visceral injury. The patients with phenotype III had relatively stable organ function. The above characteristics were consistent in both the test and validation sets. Analysis of infection-related indicators showed that the patients with phenotype I had the highest SOFA score within 7 days after ICU admission, initial decreases and later increases in platelet count (PLT), and higher counts of neutrophils, lymphocytes, and monocytes as compared with those with phenotype II and phenotype III, their blood cultures had a higher positivity rates for Gram-positive bacteria, Gram-negative bacteria and fungi as compared with those with phenotype II and phenotype III. The Kaplan-Meier curve indicated that in the training, test, and validation sets, the 28-day cumulative mortality of patients with phenotype I was significantly higher than that of patients with phenotypes II and phenotype III. CONCLUSIONS Three distinct phenotypes in septic patients receiving IMV based on unsupervised machine learning is derived, among which phenotype I, characterized by cardiorespiratory failure, can be used for the early identification of high-risk patients in this population. Moreover, this population is more prone to bloodstream infections, posing a high risk and having a poor prognosis.
Humans ; Machine Learning ; Sepsis/therapy* ; Respiration, Artificial ; Intensive Care Units ; Organ Dysfunction Scores ; Male ; Female ; Middle Aged ; Adult

Objective:To investigate the mutations of TP53 and KRAS genes in the patients with six common types of digestive system tumors,including colorectal cancer(COAD),cholangiocarcinoma(CHOL),gallbladder cancer(GBC),liver hepatocellular carcinoma(LIHC),stomach adenocarcinoma(STAD),and pancreatic adenocarcinoma(PAAD),and to analyze the relationships between TP53 and KRAS gene mutations and clinical pathological characteristics,tumor mutation burden(TMB),and microsatellite instability(MSI)of the patients.Methods:The pathological paraffin or biopsy samples of 112 patients from January 2022 to December 2023 diagnosed with six types of tumors based on imaging and pathology were collected.Hybrid capture-based gene sequencing technology was used to detect TP53 and KRAS gene mutations in the patients with different types of tumors;mutation landscapes of common digestive system tumor samples were constructed.The patients were divided into high and low TMB groups according to the TMB levels.The mutation statuses of TP53 and KRAS genes in the patients with different types of digestive system tumors were compared,and the TP53 and KRAS gene mutations in the patients with different clinicopathological characteristics were examined.Results:A total of 276 mutations were detected in the 112 samples,with the highest mutation rate in TP53 gene(67％),followed by KARS gene(34％).TP53 gene mutation was most prominent in COAD,followed by LIHC,while KRAS gene mutation was most significant in PAAD.TP53 gene mutation mainly occurred in exons 5-8,while the KRAS gene mutation primarily occurred in exon 2.There was no statistically significant difference in TP53 gene mutation rate among the six types of digestive system tumors(P＞0.05),while the KRAS gene mutation rate showed statistically significant difference(P＜0.05).The mutation rates of TP53 and KRAS gene co-mutation also showed statistically significant difference among the six types of tumors(P＜0.05).There were statistically significant differences in TP53 and KRAS gene mutation rates between the patients with high TMB and low TMB(P＜0.05),while there were no statistically significant differences in TP53 and KRAS mutation rates between the patients with different sex,age,tumor size,differentiation degree,TNM stage,lymph node and/or distant metastasis and MSI(P＞0.05).Conclusion:The mutation rates of TP53 and KRAS genes are higher in common digestive system tumors,which are related to tumor types and TMB.

Objective:To investigate the dynamic changes of cytokine levels in patients with sepsis and to identify potential biomarkers for evaluating the prognosis of the disease.Methods:A total of 195 patients with sepsis hospitalized at the Department of Infectious Diseases and the Department of Critical Care Medicine of the First Affiliated Hospital of Soochow University from August 2022 to October 2024 were recruited, and 70 healthy individuals undergoing physical examinations were recruited as the healthy control group. The levels of 11 cytokines, including interferon γ (IFN-γ), interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-17A, tumor necrosis factor α (TNF-α) and C-reactive protein (CRP) were compared between the sepsis patients and the healthy controls. Spearman correlation analysis was used to assess the correlation between cytokine levels and sequential organ failure assessment (SOFA) scores in sepsis patients. Receiver operating characteristic curves were plotted and the area under the curve (AUC) was calculated to evaluate the diagnostic value of cytokines for sepsis. Delong test was used to compare AUC. Based on the 28-day survival outcomes, the sepsis patients were categorized into non-survival group and survival group. The levels of the 11 cytokines in patients on the 1st, 3rd, 7th, 14th, 21st and 28th days after confirmed sepsis were dynamically monitored, and their change characteristics were analyzed. Mann-Whitney U test was used for statistical comparison. Results:The age of the 195 patients with sepsis was 68.0 (55.0, 76.0) years old, including 124 males (63.6%), 64 died and 131 survived.The levels of IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-17A, TNF-α, CRP in the sepsis group were all higher than those in the healthy control group ( Z=-2.99, -5.42, -4.95, -4.09, -5.05, -11.30, -8.66, -8.23, -5.64, -4.75, -2.12 and -10.75, respectively, all P<0.05). The differences were statistical significance. The levels of IL-2 ( r=0.149, P=0.037), IL-6 ( r=0.223, P=0.002), IL-8 ( r=0.159, P=0.026), and IL-10 ( r=0.188, P=0.009) in patients with sepsis were positively correlated with SOFA scores. The AUC of CRP in diagnosing sepsis was 0.989 with the sensitivity of 97.4% and the specificity of 100.0%. The AUC of IL-6 in diagnosing sepsis was 0.953, with the sensitivity of 93.3% and the specificity of 97.1%, and the AUC of IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12P70, IL-17A, and TNF-α were 0.620, 0.718, 0.699, 0.665, 0.703, 0.850, 0.836, 0.727, 0.691, and 0.574, respectively.The AUC of the 11 cytokines were all lower than that of CRP, and the differences were all statistically significant ( Z=2.34, 10.24, 8.03, 8.08, 10.64, 8.70, 5.91, 5.17, 8.91, 9.25 and 4.10, respectively, all P<0.05).During the dynamic monitoring, the IFN-γ and IL-1β levels in the non-survival group increased gradually. The IFN-γ levels on the 14th and 21st day in the non-survival group were higher than those in the survival group ( Z=0.53 and 0.08, respectively, both P<0.05), and IL-1β levels on the 14th, 21st, and 28th days were also higher than those in the survival group ( Z=0.03, 0.26 and 0.31, respectively, all P<0.05). IL-6 and IL-8 levels reached their peaks on the 14th day, which were significantly higher than those in the survival group ( Z=0.01 and 0.02, respectively, both P<0.05), and then decreased, and the differences were all statistically significant. Conclusions:The levels of IFN-γ and IL-1β in the non-survival sepsis patients show a gradually increasing trend. The dynamic changes of IL-6 have certain significance for the prediction of disease severity and prognosis evaluation in sepsis.

Objective To explore the clinical value of NOD-like receptor pyrin domain-containing protein 3(NLRP3)inflammasome levels combined with eosinophil cationic protein(ECP)/myeloperoxidase(MPO)ratio in predicting the recurrence of chronic rhinosinusitis after endoscopic sinus surgery.Methods 205 patients with chronic sinusitis who received treatment from the hospital from February 2018 to December 2022 after endoscopic sinus surgery were selected for prospective analysis.The patients were divided into non-recurrence group and recurrence group according to whether they relapsed one year after surgery.The factors influencing the recurrence of patients with chronic sinusitis after endoscopic sinus surgery were screened,and the predictive efficacy was evaluated by receiver operating characteristic curve(ROC).Results The NLRP3 inflammasome level,ECP/MPO ratio,sinus CT score,Lund-Kennedy score and immunoglobulin E in the relapsing group were higher than non-relapsing group(P<0.05).NLRP3 inflammasome level,ECP/MPO ratio,sinus CT score,Lund-Kennedy score and immu-noglobulin E were the influencing factors of postoperative recurrence in patients with chronic sinusitis(P<0.05).The area under the curve(AUC)values of NLRP3 inflammasome level,ECP/MPO ratio and combined prediction of postoperative recurrence in patients with chronic sinusitis were 0.823,0.815 and 0.899,respectively(P<0.05),and the AUC value of combined NLRP3 was higher(P<0.05).Conclusion NLRP3 inflammasome level combined with ECP/MPO ratio has a high value in predicting the risk of recurrence after nasal endoscopy.

Objective:To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults.Methods:A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test.Results:A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI: 2.23-3.88) points ( P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI: 4.03-5.37) points ( P<0.001). Ba Duan Jin showed significant improvement ( P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions:This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.

Objective:To enhance the understanding of the diagnosis and individualized treatment of myelodysplastic syndrome/myeloproliferative neoplasms with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T).Methods:A retrospective case series study was conducted. The clinical data, diagnosis and treatment process and prognosis of 4 patients with MDS/MPN-RS-T admitted to Affiliated Hospital of Hebei University from September 2015 to May 2021 were retrospectively analyzed, and the related literature was reviewed.Results:All the 4 patients were male, aged 63 to 75 years. Patients 1 and 2 were classified as revised international prognostic scoring system (IPSS-R) high-risk group, combined with ASXL1 mutation and high risk cytogenetic abnormality. The therapeutic effect of various treatment regimens was poor, and they were converted to acute myeloid leukemia (AML) and then died due to disease progression. Patient 3 was classified as IPSS-R medium-risk group. His main manifestation was myelodysplastic syndrome (MDS) combined with ring sideroblasts in the early stage and was transformed into MDS/MPN-RS-T during the treatment, and JAK2 mutation occurred in the subsequent treatment. After lenalidomide treatment, the patient was removed from blood transfusion and the condition was stable at present. Patient 4 was classified as IPSS-R medium-risk group, and lenalidomide showed significant therapeutic effects and he was in stable condition.Conclusions:Lenalidomide can significantly improve transfusion dependence in patients with MDS/MPN-RS-T, and ASXL1 mutation and high-risk cytogenetic abnormality may be associated with AML transformation.