Objective To analyze differential metabolites (DMs) in the urine of workers with occupational nickel exposure using non-targeted metabolomics, and to screen differential metabolic pathways. Methods A total of 30 nickel exposed workers were selected as the exposure group, and 30 administrative staff from the same factory were selected as the control group using the judgment sampling method. Urine samples of the individuals from the two groups were collected. The ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry and non-targeted metabolomics were used to detect and identify metabolites. The differential metabolic profiles were compared between workers of the two groups, and key differential metabolic pathways and potential biomarkers were screened. The association of DMs and urinary nickel level were evaluated by Spearman correlation coefficients. The sensitivity and specificity of biomarkers were assessed by receiver operating characteristic (ROC) curve analysis. Results A total of 418 metabolites were identified in the urine of worker in the exposure and control groups. The result of principal component analysis and orthogonal partial least squares analysis showed that there were 128 DMs in the urine of workers in the exposure group compared with the control group. These DMs were mainly enriched in glutathione metabolism, carnitine synthesis, and amino acid and nucleotide metabolism pathways, including glycine and serine metabolism. The result of correlation analysis and ROC curve analysis revealed that 4-methylcatechol, 4-vinylphenol sulfate, 2-hydroxyphenylacetone sulfate, 2-dodecylbenzenesulfonic acid, and decylbenzenesulfonic acid could be the potential biomarkers for nickel exposure (all area under the ROC curve >0.800). Conclusion There were significant differences in the urinary metabolic profiles of workers with occupational nickel exposure. The five DMs including 4-methylcatechol, 4-vinylphenol sulfate, 2-hydroxyphenylacetone sulfate, 2-dodecylbenzenesulfonic acid, and decylbenzenesulfonic acid. These DMs could be potential biomarkers of occupational nickel exposure.

Biotoxins, which include bacterial, fungal, marine, plant, and animal toxins, are widespread in living and occupational environments, posing potential threats to human health. Rapid detection of biotoxins in blood is crucial for preventing health hazards and enabling timely disease diagnosis and treatment. Biosensors and immunoassay technologies have critical advantages in the rapid detection of biotoxins in blood. Common biosensors, such as surface plasmon resonance biosensors and fluorescent biosensors, enhance sensitivity and reduce detection limits through signal amplification. Common immunoassay methods, such as colloidal gold immunochromatography, fluorescence immunochromatography, and chemiluminescence immunoassay, improve detection efficacy and sensitivity through specific antibody-antigen binding and nanotechnology. However, current rapid detection technologies of bitoxins in blood face challenges such as matrix interference and insufficient specificity, and they fall short in high-throughput detection of multiple toxins simultaneously. Future developments should focus on improving sample pretreatment, innovating signal amplification methods, enhancing specificity on recognition of elements, and designing portable detection devices and high-throughput platforms for simultaneous toxin analysis. These advancements aim to improve the sensitivity and reliability of detection methods, providing more accurate and convenient solutions for biotoxin detection in blood.

Objective To explore the correlation between the expression level of interferon gamma(IFN-γ)and the severity of patients with septic shock and its prognostic value.Methods The clinical data and serum of 96 septic shock patients admitted to the Department of Critical Care Medicine,the First Affiliated Hospital of Guangxi Medical University from March 2022 to August 2023 were collected,and divided into survival group and death group according to the 28-day outcome;collected at the same time Sera from 30 healthy people undergoing physi-cal examination during the same period served as the control group.The enzyme-linked immunosorbent(ELISA)method was used to detect the expression levels of IFN-γ in the three groups,and the expression levels of IFN-γ and various clinical data between the groups were analyzed.Results The serum IFN-γ expression level of patients with septic shock was lower than that of healthy people undergoing physical examination,212.80(151.11,255.79)ng/L compared with 343.37(314.5,427.95)ng/L,P<0.01.Among the 96 cases of septic shock,There were 54 cases in the survival group and 42 cases in the death group.The clinical data of the two groups were com-pared.The gender,smoking history,SBP,DBP,SI,Lac,IL-6,IFN-γ,PCT,SOFA score,and APACHEⅡscore of the two groups of patients were compared.The difference is statistically significant(P<0.01).Logistic regression analysis showed that decreased expression of Lac,IFN-γ,and APACHEⅡ score were independent risk factors for death in patients with septic shock.[Odds ratio(OR)and 95%confidence interval(95%CI)were 6.491(1.404～30.004)respectively.0.954(0.954～0.999),3.476(1.210～9.984),P<0.05].The Spearman correlation analysis of INF-γ,Lac and APACHEⅡ showed a negative correlation,and the correlation coefficients were-0.38 and-0.35 respectively.Drawing the ROC curves of Lac,IFN-γ,and APACHEII,the AUCs of the three were 0.847,0.869,and 0.833 respectively.The AUC of the three joint predictions was 0.978.The joint prediction value of the three was better than that of a single indicator,P<0.001.Conclusion The decrease in IFN-γ expression level and the severity of septic shock patients have good prognostic value.

Objective:To investigate the effect of mild hypothermia on macrophage polarization in lipopolysaccharide (LPS)-induced acute lung injury (ALI) mice and to clarify its role in lung injury.Methods:According to a random number table method, 18 male C57BL/6 mice were divided into sham operation group (Sham group), ALI normothermic model group (NT group) and ALI mild hypothermia treatment group (HT group), with 6 mice in each group. The ALI model in mice was established by the method of tracheal instillation of LPS, and temperature control was administered at 1 hour after surgery. The anus temperature in NT group was kept at 36-38?℃, while the anus temperature in HT group was kept at 32-34?℃. The target anus temperature in both groups were maintained for 6 hours and then slowly rewarmed to 36-38 ℃. The Sham group was infused with an equal amount of physiological saline through the trachea without temperature control. After 24 hours of modeling, serum was collected and mice were sacrificed to obtain lung tissue. Pathological changes in lung tissue were observed under light microscopy and semi-quantitative lung injury score was performed. Enzyme linked immunosorbent assay (ELISA) was used to detect the serum levels of interleukins (IL-1β, IL-10). Real-time quantitative polymerase chain reaction (RT-qPCR) was used to test the indicators of macrophage polarization, such as the mRNA expressions of CD86, IL-6, CD206 and arginase 1 (Arg1) in the lung tissue. The protein expression of M1 macrophage marker inducible nitric oxide synthase (iNOS) and M2 macrophage marker Arg1 were detected by Western blotting.Results:Compared with the Sham group, the NT group appeared significant pulmonary hemorrhage and edema, thickened lung septum, inflammatory cell infiltration, and lung injury score was significantly increased; serum IL-1β level was significantly elevated; IL-10 level was increased without statistical significance; the expressions of CD86 mRNA, IL-6 mRNA and iNOS protein were significantly elevated, and CD206 mRNA was significantly decreased; the mRNA and protein expressions of Arg1 decreased, but there were no significant differences. Compared with the NT group, the pathological injury of lung tissue in HT group was significantly reduced, and the lung injury score was significantly decreased (4.78±0.96 vs. 8.56±1.98, P < 0.01); serum IL-1β level was decreased (ng/L: 13.52±1.95 vs. 27.18±3.87, P < 0.01), and IL-10 level was significantly increased (ng/L: 42.59±15.79 vs. 14.62±4.47, P < 0.01); IL-6 mRNA expression was decreased in lung tissue (2 -ΔΔCt: 3.37±0.92 vs. 10.04±0.91, P < 0.05), the expression of M1 macrophage markers CD86 mRNA and iNOS protein were significantly decreased [CD86 mRNA (2 -ΔΔCt): 0.52±0.16 vs. 1.95±0.33, iNOS protein (iNOS/β-actin): 0.57±0.19 vs. 1.11±0.27, both P < 0.05], the expression of M2 macrophage markers CD206 mRNA, Arg1 mRNA and Arg1 protein were significantly increased [CD206 mRNA (2 -ΔΔCt): 3.99±0.17 vs. 0.34±0.17, Arg1 mRNA (2 -ΔΔCt): 2.33±0.73 vs. 0.94±0.23, Arg1 protein (Arg1/β-actin): 0.96±0.09 vs. 0.31±0.11, all P < 0.05]. Conclusion:Mild hypothermia can alleviate the inflammatory response and protect lung tissue in ALI mice, which may be related to the inhibition of M1 macrophage polarization and promotion of M2 macrophage polarization.

ObjectiveTo observe the effect of water extract of Mori Folium （MLE） on oxidative stress in adipose tissue of type 2 diabetes mellitus （T2DM） mice and explore its mechanism. MethodTwenty-four male db/db mice were randomly divided into model group， metformin group， low-dose MLE （MLE-L） group， and high-dose MLE （MLE-H） group according to their body weight and blood glucose， with six mice in each group， and other six C57BLKS/JGpt wild littermate mice were selected as normal group. The mice in the metformin group were given 200 mg·kg^-1 metformin suspension， and the mice in the MLE-L and MLE-H groups were respectively given 2 g·kg^-1 and 4 g·kg^-1 MLE， while the mice in the normal group and model group were given the same dose of deionized water by daily gavage for eight weeks. Body weight， subcutaneous fat index， fasting blood glucose （FBG）， and oral glucose tolerance level （OGTT） of the mice were detected， and serum superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px）， and malondialdehyde （MDA） were measured. The expression levels of silent information regulator 1 （SIRT1） and NADPH oxidase type 4 （NOX4） protein in subcutaneous adipose tissue of the mice were detected by Western blot. ResultThe FBG level， OGTT， and subcutaneous fat index of T2DM mice were significantly decreased （P<0.05， P<0.01） after administration of MLE compared with the blank group. The contents of serum SOD and GSH were significantly increased， while the level of oxidative stress damage marker MDA was significantly decreased （P<0.05， P<0.01）. The expression of SIRT1 protein in adipose tissue was significantly increased， while the expression of NOX4 protein was significantly decreased （P<0.05， P<0.01）. ConclusionMLE can ameliorate T2DM by alleviating oxidative stress in adipose tissue of T2DM mice and reducing blood glucose.

ObjectiveTo investigate the protective effects of Mori Folium extract （MLE） on the kidney of db/db diabetic mice and its mechanism. MethodTwenty-four male C57BLKS/JGpt-Leprdb/Leprdb （db/db） mice were randomly divided into model group， metformin group， low-dose group of MLE （MLE-L）， and high-dose group of MLE （MLE-H） according to their fasting blood glucose （FBG）， with six mice in each group， and other six C57BLKS/JGpt wild littermate （m/m） mice were selected as normal group. The mice in the drug administration groups were given corresponding drugs by gavage， and the mice in the normal group and model group were given the same dose of deionized water by gavage once a day for continuous eight weeks. Body weight， bilateral kidney weight， and FBG were measured， and an oral glucose tolerance test （OGTT） was performed. The pathological changes in the kidney tissue of mice were observed by hematoxylin-eosin （HE） and periodic acid-silver （PAS） staining， and serum creatinine （SCr） and blood urea nitrogen （BUN） levels were detected. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of tumor necrosis factor-alpha （TNF-α） and interleukin-6 （IL-6） in serum and urinary microalbumin （U-mAlb） of mice. The expression levels of toll-like receptor 4 （TLR4）， myeloid differentiation factor 88 （MyD88）， and nuclear factor-kappa B p65 （NF-κB p65） protein in kidney tissue of mice were tested by Western blot. ResultCompared with the normal group， the body weight， absolute renal weight， FBG， and the area under the curve （AUC） of OGTT of mice in the model group were significantly increased （P<0.01）， and the levels of SCr， BUN， and U-mAlb， as well as TNF-α and IL-6 in serum were significantly increased （P<0.01）. The glomerular basement membrane in the kidney tissue of mice was thicker， with obvious inflammatory cell infiltration. The protein expression levels of TLR4， MyD88， and NF-κB p65 in the kidney tissue of mice were increased significantly （P<0.01）. Compared with the model group， there was no statistical difference in the body weight of mice in each drug administration group. The absolute renal weight of mice in the MLE-H and metformin groups was significantly reduced （P<0.05， P<0.01）. The FBG levels of mice in the metformin， MLE-L， and MLE-H groups started to decrease after treatment for four to eight weeks （P<0.05， P<0.01）. The AUC of mice in the MLE-H and metformin groups was significantly decreased （P<0.01）. The levels of SCr， BUN， and U-mAlb of mice in the MLE-H and metformin groups were significantly decreased （P<0.01）， and those of SCr and U-mAlb of mice in the MLE-L group were significantly decreased （P<0.01）. The levels of TNF-α and IL-6 in the serum of mice in the MLE-H and metformin groups were significantly decreased （P<0.01）. The renal tissue pathology of mice in each drug administration group was improved to varying degrees， and the protein expression levels of TLR4， MyD88， and NF-κB p65 in the MLE-H group were decreased significantly （P<0.05， P<0.01）. ConclusionMLE can improve the renal structure and function of db/db diabetic mice， and its mechanism may be related to the inhibition of the TLR4/MyD88/NF-κB signaling pathway.

Objective:To investigate the correlation factors of complete clinical response in idiopathic inflammatory myopathies(IIMs)patients receiving conventional treatment.Methods:Patients diagnosed with IIMs hospitalized in Peking University People's Hospital from January 2000 to June 2023 were in-cluded.The correlation factors of complete clinical response to conventional treatment were identified by analyzing the clinical characteristics,laboratory features,peripheral blood lymphocytes,immunological indicators,and therapeutic drugs.Results:Among the 635 patients included,518 patients finished the follow-up,with an average time of 36.8 months.The total complete clinical response rate of IIMs was 50.0％(259/518).The complete clinical response rate of dermatomyositis(DM),anti-synthetase syn-drome(ASS)and immune-mediated necrotizing myopathy(IMNM)were 53.5％,48.9％and 39.0％,respectively.Fever(P=0.002)and rapid progressive interstitial lung disease(RP-ILD)(P=0.014)were observed much more frequently in non-complete clinical response group than in complete clinical re-sponse group.The aspartate transaminase(AST),lactate dehydrogenase(LDH),D-dimer,erythrocyte sedimentation rate(ESR),C-reaction protein(CRP)and serum ferritin were significantly higher in non-complete clinical response group as compared with complete clinical response group.As for the treat-ment,the percentage of glucocorticoid received and intravenous immunoglobin(IVIG)were significantly higher in non-complete clinical response group than in complete clinical response group.Risk factor analysis showed that IMNM subtype(P=0.007),interstitial lung disease(ILD)(P=0.001),eleva-ted AST(P=0.012),elevated serum ferritin(P=0.016)and decreased count of CD4+T cells in peripheral blood(P=0.004)might be the risk factors for IIMs non-complete clinical response.Conclu-sion:The total complete clinical response rate of IIMs is low,especially for IMNM subtype.More effec-tive intervention should be administered to patients with ILD,elevated AST,elevated serum ferritin or decreased count of CD4+T cells at disease onset.

OBJECTIVE: To explore lung ultrasound radiomics features which related to extravascular lung water index (EVLWI), and to predict EVLWI in critically ill patients based on lung ultrasound radiomics combined with machine learning and validate its effectiveness. METHODS: A retrospective case-control study was conducted. The lung ultrasound videos and pulse indicated continuous cardiac output (PiCCO) monitoring results of critically ill patients admitted to the department of critical care medicine of the First Affiliated Hospital of Guangxi Medical University from November 2021 to October 2022 were collected, and randomly divided into training set and validation set at 8:2. The corresponding images from lung ultrasound videos were obtained to extract radiomics features. The EVLWI measured by PiCCO was regarded as the "gold standard", and the radiomics features of training set was filtered through statistical analysis and LASSO algorithm. Eight machine learning models were trained using filtered radiomics features including random forest (RF), extreme gradient boost (XGBoost), decision tree (DT), Naive Bayes (NB), multi-layer perceptron (MLP), K-nearest neighbor (KNN), support vector machine (SVM), and Logistic regression (LR). Receiver operator characteristic curve (ROC curve) was plotted to evaluate the predictive performance of models on EVLWI in the validation set. RESULTS: A total of 151 samples from 30 patients were enrolled (including 906 lung ultrasound videos and 151 PiCCO monitoring results), 120 in the training set, and 31 in the validation set. There were no statistically significant differences in main baseline data including gender, age, body mass index (BMI), mean arterial pressure (MAP), central venous pressure (CVP), heart rate (HR), cardiac index (CI), cardiac function index (CFI), stroke volume index (SVI), global end diastolic volume index (GEDVI), systemic vascular resistance index (SVRI), pulmonary vascular permeability index (PVPI) and EVLWI. The overall EVLWI range in 151 PiCCO monitoring results was 3.7-25.6 mL/kg. Layered analysis showed that both datasets had EVLWI in the 7-15 mL/kg interval, and there was no statistically significant difference in EVLWI distribution. Two radiomics features were selected by using LASSO algorithm, namely grayscale non-uniformity (weight was -0.006 464) and complexity (weight was -0.167 583), and they were used for modeling. ROC curve analysis showed that the MLP model had better predictive performance. The area under the ROC curve (AUC) of the prediction validation set EVLWI was higher than that of RF, XGBoost, DT, KNN, LR, SVM, NB models (0.682 vs. 0.658, 0.657, 0.614, 0.608, 0.596, 0.557, 0.472). CONCLUSIONS The gray level non-uniformity and complexity of lung ultrasound were the most correlated radiomics features with EVLWI monitored by PiCCO. The MLP model based on gray level non-uniformity and complexity of lung ultrasound can be used for semi-quantitative prediction of EVLWI in critically ill patients.
Humans ; Extravascular Lung Water/diagnostic imaging* ; Retrospective Studies ; Critical Illness ; Case-Control Studies ; Bayes Theorem ; China ; Lung/diagnostic imaging*

【Objective】 To discuss the repair effect of lyophilized platelet lysate (PL) products on articular cartilage injury model of rats. 【Methods】 A total of 25 SD rats were injected with typeⅡcollagenase at the right knuckle articular cavity respectively on day 1, 3 and 5 of experiment, and the modeling conditions were observed 14 days after the last injection of collagenase. The SD rats with successful modeling were randomly divided into three groups, and were injected with lyophilized PL [Group A, 1 mL/(mouse·time)], PL [Group B, 1 mL/(mouse·time)], and normal saline[Group C, 1 mL/(mouse·time)]. The above three substances were injected with corresponding drugs on day 0, 7, 14 and 21 of experiment based on the grouping conditions, and the changes of knee joint diameters of the rats from the three groups were observed and compared. On day 14 and 28, one rat in each group was randomly killed and two knuckle articular cavities of each were taken for tissue sampling, using hematoxylin-eosin staining (HE) and immunohistochemistry. 【Results】 After 14 days of modeling by injection of type Ⅱ collagenase, the proportion of successful modeling in rats was 84% (21/25), with the knee joint diameter (mm) before and after modeling at 12.84±1.14 vs 14.11±1.17(P<0.01). On day 14, 21 and 28, groups A and B were superior to group C in the knee joint diameter and activity improvement (P<0.05), with 13.33±1.16 vs 13.37±1.08 vs 14.21±1.08, 13.10±1.09 vs 13.01±1.04 vs 14.09±1.09 and 12.38±1.08 vs 12.51±1.03 vs 14.01±1.07, respectively. Histological observation showed that group A and B were superior to group C in the production and arrangement of chondrocytes and the positive expression of type Ⅱ collagen, and there was no significant difference between group A and group B. 【Conclusion】 The lyophilized PL has similar therapeutic effect to PL in the treatment and repair of articular cartilage injury, and is worthy of clinical application.

【Objective】 To explore the clinical effects of autologous platelet-rich plasma (PRP) in the treatment of postoperative bone nonunion for long bone shaft fractures during operation and after operation. 【Methods】 A total of 34 patients with postoperative bone nonunion for long bone shaft fracture, who were admitted and cured in the Orthopedics Department of our hospital from January 2019 to June 2020, were selected. They were randomly divided into the experimental group(n=17) and control group(n=17). Individuals in the control were treated with autologous iliac bone alone., while the experimental group were treated with autologous iliac bone graft plus autologous PRP during and after operation. After surgery, the autogenous PRP was accurately injected with ultrasound guidance every 7 days (5 mL/person, 4 occasions in total). The clinical healing time of the fracture, the grading of callus formation and the functional rehabilitation level of limbs on the affected side at different time were observed in both groups. 【Results】 All 34 patients were followed up. In the experimental group and the control group, the clinical healing time (month) of the fracture was (5.03±1.24) vs (6.91±1.41), P<0.05. The healing rate of the fracture for 6 months and 9 months was 94%(16/17)vs 59%(10/17)and 94%(16/17)vs 82%(14/17), respectively (P<0.05). The grading of callus formation within 3, 6 and 9 months was (2.11±0.69) vs (1.53±0.80), (3.06±0.90) vs (2.59±0.87) and (3.82±0.73) vs (3.35±0.86), respectively (P<0.05). The acceptance rate of functional rehabilitation of limbs on the affected side was 82.35%(14/17)vs 76.47%(13/17), P<0.05. 【Conclusion】 The application of autologous PRP in the treatment of postoperative bone nonunion for long bone shaft fractures during operation and after operation can achieve good clinical treatment.