The cellular and molecular components of the tumor immune microenvironment (TIME) and their information exchange processes significantly influence the trends of anti-tumor immunity. In recent years, numerous studies have begun to evaluate TIME in the context of previous cancer treatment strategies. This review will systematically summarize the compositional characteristics of TIME and, based on this foundation, explore the impact of current cancer therapies on the remodeling of TIME, aiming to provide new insights for the development of innovative immune combination therapies that can convert TIME into an anti-tumor profile.
Tumor Microenvironment/immunology* ; Humans ; Neoplasms/therapy* ; Immunotherapy/methods* ; Animals

OBJECTIVE: To construct machine learning prediction model for sepsis-associated encephalopathy (SAE), and analyze the application value of the model on early identification of SAE risk in elderly septic patients. METHODS: Patients aged over 60 years with a primary diagnosis of sepsis admitted to intensive care unit (ICU) from 2008 to 2023 were selected from Medical Information Mart for Intensive Care-IV 2.2 (MIMIC-IV 2.2). Demographic variables, disease severity scores, comorbidities, interventions, laboratory indicators, and hospitalization details were collected. Key factors associated with SAE were identified using univariate Logistic regression analysis. The data were randomly divided into training and validation sets in a 7 : 3 ratio. Multivariable Logistic regression analysis was conducted in the training set and visualized using a nomogram model for prediction of SAE. The discrimination of the model was evaluated in the validation set using the receiver operator characteristic curve (ROC curve), and its calibration was assessed using calibration curve. Furthermore, multiple machine learning algorithms, including multi-layer perceptron (MLP), support vector machine (SVM), naive bayes (NB), gradient boosting machine (GBM), random forest (RF), and extreme gradient boosting (XGB), were constructed in the training set. Their predictive performance was subsequently evaluated on the validation set. Taking the XGB model as an example, the interpretability of the model through the SHapley Additive exPlanations (SHAP) algorithm was enhanced to identify the key predictive factors and their contributions. RESULTS: A total of 2 204 septic patients were finally enrolled, of whom 840 developed SAE (38.1%). A total of 21 variables associated with SAE were screened through univariate Logistic regression analysis. Multivariable Logistic regression analysis showed that endotracheal intubation [odds ratio (OR) = 0.40, 95% confidence interval (95%CI) was 0.19-0.88, P < 0.001], oxygen therapy (OR = 0.76, 95%CI was 0.53-0.95, P = 0.023), tracheotomy (OR = 0.20, 95%CI was 0.07-0.53, P < 0.001), continuous renal replacement therapy (CRRT; OR = 0.32, 95%CI was 0.15-0.70, P < 0.001), cerebrovascular disease (OR = 0.31, 95%CI was 0.16-0.60, P < 0.001), rheumatic disease (OR = 0.44, 95%CI was 0.19-0.99, P < 0.001), male (OR = 0.68, 95%CI was 0.54-0.86, P = 0.001), and maximum anion gap (AG; OR = 0.95, 95%CI was 0.93-0.97, P < 0.001) were associated with an decreased probability of SAE, and age (OR = 1.05, 95%CI was 1.03-1.06, P < 0.001), acute physiology score III (APSIII; OR = 1.02, 95%CI was 1.01-1.02, P < 0.001), Oxford acute severity of illness score (OASIS; OR = 1.04, 95%CI was 1.03-1.06, P < 0.001), and length of hospital stay (OR = 1.01, 95%CI was 1.01-1.02, P < 0.001) were associated with an increased probability of SAE. A nomogram model was constructed based on these variables. In the validation set, ROC curve analysis showed that the model achieved an area under the ROC curve (AUC) of 0.723, and the calibration curve showed good consistency between the predicted probability of the model and the observed probability. Among the machine learning algorithms, including MLP, SVM, NB, GBM, RF, and XGB, the SVM model and RF model demonstrated relatively good predictive performance, with AUC of 0.748 and 0.739, respectively, and the sensitivity was both exceeding 85%. The predictive performance of the XGB model was explained through SHAP analysis, and the results indicated that APSIII score (SHAP value was 0.871), age (SHAP value was 0.521), and OASIS score (SHAP value was 0.443) were important factors affecting the predictive performance of the model. CONCLUSIONS The machine learning-based SAE prediction model exhibits good predictive capability and holds significant application value for the early identification of SAE risk in elderly septic patients.
Humans ; Machine Learning ; Aged ; Sepsis-Associated Encephalopathy ; Sepsis/complications* ; Intensive Care Units ; Logistic Models ; Middle Aged ; Male ; ROC Curve ; Female ; Bayes Theorem ; Nomograms ; Support Vector Machine ; Algorithms

Objective: To analyze the association of eating dining locations and their association with nutritional status among Chinese children aged 6-17 years,so as to provide reference for guiding children s reasonable diet. Methods: Stratified random cluster sampling was used to select children aged 6 to 17 years from 28 cities and rural areas of 14 provinces in East, North, Central, South, Southwest, Northwest, Northeast of China, and a total of 52 535 children were included in the study from 2019 to 2021. Information including dining locations, demographic characteristics, dietary intakes and physical activity were collected through a questionnaire survey. Fasting body height and weight were measured in the morning. Unordered multiclass Logistic regression analysis was conducted to assess the relationship between dining locations and nutritional status in children. Results: Regarding children s dining locations, 66.3% ate breakfast at home,25.8% ate breakfast at school,7.9% ate breakfast outside (small dining tables, restaurants, stalls, etc.); 67.7% ate dinner at home,29.0% ate dinner at school,3.3% ate dinner outside; and 63.6% ate lunch at school,30.8% ate lunch at home,5.7% ate lunch outside. The prevalence rates of overweight/obesity and undernutrition were 28.6% and 9.3%, respectively. The adjusted multiclass Logistic regression analysis (controlling for age, region, parental education, household income, total energy intake, and moderate-to-vigorous physical activity) demonstrated that, compared to eating at home, school based breakfast and dinner consumption was associated with significantly lower overweight/obesity risks for both genders (boys: breakfast OR =0.70, 95% CI =0.65-0.75; dinner OR =0.80, 95% CI = 0.74- 0.86; girls: breakfast OR = 0.89 , 95% CI = 0.82-0.96; dinner OR =0.88, 95% CI =0.81-0.95), whereas eating lunch away from home significantly increased overweight/obesity risks (boys: OR =1.32, 95% CI =1.17-1.48; girls: OR =1.43, 95% CI =1.26- 1.62 ), with all associations being statistically significant ( P <0.05). After adjusting for confounding factors, boys who ate breakfast away from home showed a significantly reduced risk of undernutrition ( OR =0.80,95% CI =0.66-0.97), while those consuming lunch away from home had an increased risk ( OR =1.26, 95% CI =1.01-1.57) ( P <0.05). Conclusions The choice of dining locations for children is becoming more diverse, and a relatively high proportion of children eat meals outside the home and at school. Eating out have a higher risk of malnutrition for children. School feeding may be beneficial to children s physical health.

Objective:To develop radiomics score (RS) based on 18F-FDG PET/CT, and construct the machine learning model combining clinical and other relevant factors for personalized prediction of 2-year event-free survival (2-EFS) in patients with diffuse large B-cell lymphoma (DLBCL), and to perform interpretability analysis of the model. Methods:A total of 91 patients (49 males, 42 females; age (57.8±12.8) years) with pathologically confirmed DLBCL from December 2017 to December 2020 at the First Hospital of Shanxi Medical University were retrospectively analyzed. According to the ratio of 7∶3, patients were randomly divided into training set ( n=63) and test set ( n=28), and divided into non-progression group and progression group according to the follow-up results. The whole-body PET semi-quantitative parameters were calculated from the PET/CT images before treatment, and 328 radiomics features were extracted from the largest target lesions of patients. The least absolute shrinkage and selection operator (LASSO) was used to develop the RS. Clinical and PET characteristic difference analysis was performed through χ2 test and Mann-Whitney U test. Extreme gradient boosting (XGBoost) models were constructed based on clinical, PET radiomics features and RS, and the prediction efficiency of each model was evaluated by ROC AUC. The model interpretability was analyzed by using shapely additive explanation (SHAP). Results:Of all patients, 32 had disease progression and 59 did not. There were no significant differences in baseline characteristics between the training set and the test set ( χ2 values: 0.06-1.84, U values: 665.00-763.00, all P>0.05). The comparison between the progression group and non-progression group in the training set showed statistical differences in the international prognostic index (IPI) score ( χ2=4.87, P=0.027), myelocytomatosis viral oncogene (MYC) protein expression ( χ2=4.29, P=0.038), and metabolic tumor volume (MTV; U=307.00, P=0.038). Seven radiomics features were screened by LASSO. Among XGBoost models with different feature combinations, IPI score, MYC protein expression, MTV combined with RS had the highest predictive efficiency (training set: AUC=0.73; test set: AUC=0.70). Through SHAP analysis, RS was the most predictive feature in the optimal model. Conclusion:The machine learning integrated model of IPI score, MYC protein expression and MTV combined with RS can effectively predict the prognosis of DLBCL patients, and baseline 18F-FDG PET/CT radiomics can be used as a potential means to evaluate the prognosis of DLBCL patients.

Objective:To investigate the clinical value of 18F-NaF PET/CT coronary plague imaging in evaluating the long-term prognosis of patients with coronary artery disease (CAD). Methods:A retrospective cohort study was conducted among 54 patients (37 males and 17 females, aged (57.2±9.8) years) diagnosed with CAD from a multicenter study between September 2015 and October 2022. All patients underwent 18F-NaF PET/CT and coronary angiography (CAG) within 1 week, and the PET/CT imaging was performed at the First Hospital of Shanxi Medical University. Major adverse cardiovascular events (MACE) were followed up. ROC curves were established to obtain the optimal thresholds of SUV max and accumulated SUV max of all lesions of main coronary artery branches (S-SUV max) for predicting MACE. Cox proportional risk model and Kaplan-Meier method (log-rank test) were used to analyze the predictive value of PET parameters for MACE. Differences in metabolic parameters between 2 groups were compared by Mann-Whitney U test. Results:The median follow-up time of the 54 patients was 6.0(1.8, 6.6) years, and 13(24.1%) patients developed MACE, including 7 deaths, 5 myocardial infarction and 1 severe arrhythmia. S-SUV max in MACE group was significantly higher than that in the non-MACE group (2.64(2.08, 4.49) vs 1.83(0.95, 2.90); Z=-2.04, P=0.041). ROC curve showed that the optimal threshold of S-SUV max for MACE prediction was 2.05 (AUC=0.690). Multivariate Cox analysis showed that S-SUV max was a strong predictor of MACE (hazard ratio ( HR)=2.434(95% CI: 1.547-3.828), P<0.001). ROC curve showed that the optimal threshold of SUV max to predict MACE was 0.55 (AUC=0.659), and univariate Cox analysis showed that SUV max was a factor to predict MACE ( HR=10.192 (95% CI: 2.667-38.953), P=0.001). In 25 patients with incomplete revascularization (ICR), Kaplan-Meier analysis showed that the incidence of MACE in patients with positive 18F-NaF uptake (single medium stenosis (40%-70%) with SUV max≥0.55) was significantly higher than that in patients with negative 18F-NaF uptake (5/14 vs 0/11; χ2=6.07, P=0.014). Conclusions:18F-NaF PET/CT can be used as an independent predictor of MACE in patients with CAD and can quantitatively assess the long-term progression of moderate coronary artery stenosis. In the future, it is expected to be a new non-invasive way to guide the revascularization treatment decision of multi-vessel CAD.

In recent years, immunotherapy has become another important treatment for non-small cell lung cancer (NSCLC) after surgery, radiotherapy, chemotherapy and targeted therapy. As an emerging non-invasive tool, PET/CT radiomics provides a new way for precise diagnosis and treatment of NSCLC by quantitatively analyzing the metabolic and structural characteristics of tumors, demonstrating significant promise for applications in NSCLC immunotherapy. This article aims to review the research progress of PET/CT radiomics in NSCLC immunotherapy and to explore its potential value in predicting biomarkers, therapeutic efficacy, adverse effects, and evaluating prognosis.

Objective:To investigate the effects of acute sleep deprivation (ASD) on hippocampal glucose metabolism and neuroinflammation in rat models.Methods:Twenty SD rats (10 males and 10 females) were divided into four groups (five in each group) by random sampling method: female ASD group, male ASD group, female control group, and male control group. Among them, the ASD group constructed the ASD model. After 72h sleep deprivation, all rats underwent 18F-FDG and N, N-diethyl-2-(2-(4-(2- 18F-fluoroethoxy)phenyl)-5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl)acetamide ( 18F-DPA-714) microPET/CT brain imaging in 2d to compare the changes of 18F-FDG and 18F-DPA-714 SUV mean in the hippocampus of rats. Brain histopathology, immunohistochemistry and immunofluorescence staining were detected in rats. Independent-sample t test was used to analyze the data. Results:18F-FDG imaging showed the hippocampal SUV mean between ASD group and control group (female: 4.11±0.35 vs 1.89±0.28; male: 3.43±0.47 vs 2.02±0.54) were statistically significant ( t values: 9.65, 3.92, P values: <0.001, 0.002). 18F-DPA-714 imaging showed the hippocampal SUV mean between ASD group and control group (females: 0.28±0.01 vs 0.28±0.02; male: 0.26±0.02 vs 0.31±0.04) were not statistically significant ( t values: -0.18, -2.24, P values: 0.859, 0.056). The 18×10 3 translocator protein (TSPO) immunohistochemistry showed the expression in the hippocampal region of the brain between ASD group and control group (female: 0.19±0.02 vs 0.19±0.01; male: 0.21±0.01 vs 0.20±0.01) were not statistically different ( t values: -0.48, -1.67, P values: 0.651, 0.139). Immunofluorescence staining showed that microglial cytosol in the hippocampal region of the brain decreased after 72h of ASD, and the protrusion points and surrounding branches were significantly reduced. Conclusion:Increased hippocampal glucose metabolism in rats is observed after 72 h of ASD without significant neuroinflammation.

Objective:To evaluate the efficacy and safety of a Chinese herbal mask in the treatment of melanized-type melasma by stereological measurements.Methods:A randomized, controlled, evaluator- and statistician-blind clinical study was conducted. A total of 116 patients with melasma who met the inclusion and exclusion criteria were selected and equally divided into two groups by using a random number table method, with 58 patients in each group. The treatment group received topical treatment with a Chinese herbal mask once a night, while the control group received topical hydroquinone cream in the morning and evening twice daily. The course of treatment lasted 12 weeks, with follow-ups every 4 weeks, and an additional follow-up was performed 12 weeks after discontinuation of treatment. A facial image analyzer and a reflectance confocal microscopy (RCM) were used to collect images before and after treatment. Melasma area and severity index (MASI) scores and RCM scores served as outcome measures, and stereological measurement methods were employed to compare scores before and after treatment; response rates and recurrence rates were calculated, and adverse reactions were observed and recorded. Statistical analyses were performed using the chi-square test and t test. Results:A total of 54 patients in the treatment group and 47 patients in the control group completed the study. After 4- and 8-week treatment, there were no significant differences in MASI scores or RCM scores between the two groups (all P > 0.05) ; after 12-week treatment, the MASI scores and RCM scores were significantly lower in the treatment group (2.91 ± 1.16, 5.48 ± 1.60, respectively) than in the control group (3.99 ± 2.03, 6.66 ± 1.88, t = -3.32, -3.37, respectively, both P < 0.01). After the end of treatment, there was no significant difference in the response rate between the treatment group (44/54, 81.5%) and the control group (34/47, 72.3%; χ2 = 0.12, P > 0.05). Twelve weeks after discontinuation of treatment, 2 patients (3.7%) relapsed in the treatment group, while 15 (31.9%) relapsed in the control group, showing a significant difference in recurrence rates between the two groups ( χ2 = 12.34, P < 0.01). Adverse reactions occurred in 2 patients (3.7%) in the treatment group and 6 (11.5%) in the control group, and there was no significant difference in the incidence of adverse reactions between the two groups ( χ2 = 1.34, P > 0.05) . Conclusions:The Chinese herbal mask was safe and effective in the treatment of melanized-type melasma. The application of the facial image analyzer and RCM technology in combination with stereological measurement methods has certain value in reducing the subjectivity in efficacy evaluation for melasma.

Objective:To compare and analyze the similarities and differences in clinical manifestations, laboratory findings, pathological characteristics, and prognosis between urticarial vasculitis (UV) and chronic spontaneous urticaria with pigmentation (CSUwp) .Methods:A retrospective analysis was conducted on the clinical data and follow-up results from 35 UV patients and 54 CSUwp patients who attended the Department of Dermatology, Southwest Hospital, Army Medical University from 2014 to 2024. The clinical characteristics (duration of rash, pigmentation, petechiae and ecchymosis, itching, burning sensation, fever, fatigue, skin lesion characteristics, etc.) , laboratory test results, pathological features, and prognosis were compared between the two groups. Statistical analysis was carried out by t test, chi-square test, Mann-Whitney U test, and Kaplan-Meier survival analysis. Results:There were no significant differences in gender, age, or age of onset between the UV group and CSUwp group (all P < 0.05) . The proportions of patients with petechiae/purpura (68.57% [24/35] vs. 11.11% [6/54]) , and those with burning sensation (22.86% [8/35] vs. 3.70% [2/54]) were significantly higher in the UV group than in the CSUwp group (both P < 0.05) . Compared with the CSUwp patients, the UV patients presented with a greater number of lesions, larger lesion areas, and more frequent involvement of the lower limbs (all P < 0.05) , also showed significantly higher incidence rates of peripheral blood complement reduction, perivascular neutrophil infiltration, nuclear dust, fibrinoid necrosis of the vessel wall, and erythrocyte extravasation (all P < 0.05) , as well as more extensive dermal perivascular inflammation ( Z = -4.506, P < 0.001) . Among patients who achieved remission, the natural disease course was significantly longer in the CSUwp patients than in the UV patients (6.00 [2.5, 24] months vs. 2.00 [0.5, 24] months; Z = -2.618, P = 0.009]. However, the survival analysis showed no significant difference in the natural disease course or clinical outcomes between the two groups ( χ2 = 2.771, P = 0.096) . There were also no significant differences in rash duration or in the incidence rates of itching, angioedema, or joint pain between the two groups (all P > 0.05) . Conclusions:UV patients exhibited certain differences from CSUwp patients in clinical characteristics, laboratory test results, histopathological features, and prognosis. However, whether their natural disease courses differ requires further follow-up studies to confirm.

OBJECTIVE To observe intervention effect of salvianolic acid B based on JAK2/STAT3 pathways on the rats with Escherichia coli infection-induced pyelonephritis.METHODS Totally 60 SPF grade male SD rats were in-cluded in the study and were randomly divided into the control group with 21 rats,the model group(Escherichia coli infection-induced pyelonephritis)with 18 rats and the salvianolic acid B group(Escherichia coli infection-in-duced pyelonephritis+salvianolic acid B)with 18 rats.The control group and the model group were treated with same volume of normal saline for gavage,the salvianolic acid B group was given 12.5 mg/kg salvianolic acid B wa-ter solution for gavage.The levels of related biochemical indexes[secretory immunoglobulin A(SlgA),urine cre-atinine and serum creatinine]were detected for the groups.The organ indexes and relative expression levels of JAK2/STAT3 signaling pathways were observed and compared among the groups.RESULTS There were significant differences in the levels of blood indexes among the three groups of rats(P＜0.05).The SlgA level of the model group was(13.51±1.18)μg/ml,lower than(25.64±4.51)μg/ml of the control group(P＜0.05);the SlgA level of the salvian-olic acid B group was(25.34±2.95)μg/ml,higher than that of the model group(P＜0.05).There were no significant differences in the bladder indexes among the three groups;the ratio of left kidney to right kidney and the renal indexes were higher in the model group than in the control group(P＜0.05);the ratio of left kidney to right kidney and the renal indexes were lower in the salvianolic acid B group than in the model group(P＜0.05).There were significant differences in the relative expression levels of JAK2/STAT 3 signaling pathways among the three groups(P＜0.05);the levels of JAK2 and STAT 3 of the model group were higher than those of the control group(P＜0.05);the levels of JAK2 and STAT 3 of the salvianolic acid B group were lower than those of the model group(P＜0.05).CONCLUSION The salvian-olic acid B based on JAK2/STAT3 pathways may improve the indexes of the rats with E.coli infection-induced pyelonephritis and effectively improve the overall symptoms.