Based on spleen deficiency-phlegm dampness as the core pathogenesis of obesity， and integrating recent advances in modern medicine regarding the key role of immune inflammation in obesity， this paper proposes a multidimensional pathogenic network of "obesity-spleen deficiency-phlegm dampness-immune imbalance". Various traditional Chinese medicine （TCM） herbs that strengthen the spleen， regulate qi， and resolve phlegm and dampness can treat obesity by improving spleen-stomach transport and transformation， promoting water-damp metabolism， and regulating immune homeostasis. This highlights immune inflammation as an important entry point to elucidate the TCM concepts of "spleen deficiency-phlegm dampness" and the therapeutic principle of "strengthening the spleen and eliminating dampness to treat obesity". By systematically analyzing the intrinsic connection between "spleen deficiency generating dampness， internal accumulation of phlegm dampness" and immune dysregulation in obesity， this paper aims to provide theoretical support for TCM treatment of obesity based on dampness.

The persistent high prevalence and poor survival outcomes of lung cancer underscore the urgent need for innovative therapeutic modalities. Here, we present a novel multifunctional delivery platform for the synergistic treatment of lung malignancies, combining in situ-triggerable photodynamic therapy (PDT) with radiotherapy. The new platform CLL was developed by loading a new reactive oxygen species (ROS)-triggerable photosensitizer, luminol-conjugated chlorin e6 (Ce6), into liposomes. CLL can be activated through the bioluminescence resonance energy transfer effect under oxidative stress, thereby producing singlet oxygen for targeted tumor treatment without external irradiation. In vitro studies showed significant cytotoxic effects of CLL in both 4T1 and A549 tumor cells. Furthermore, a PDT-radiopharmaceutical combination nanotherapy CLL-¹⁷⁷Lu was engineered by incorporating the radionuclide ¹⁷⁷Lu into CLL. CLL-¹⁷⁷Lu demonstrated synergistic antitumor effects in 4T1 and A549 tumor cells, as well as in mouse models of 4T1 breast cancer lung metastasis or A549 tumor xenografts. Mechanistically, CLL-¹⁷⁷Lu can induce singlet oxygen/ROS generation, enhance tumor cell apoptosis, and promote M1 macrophage-mediated immunotherapy. Preliminary assessments showed a favorable profile for CLL-¹⁷⁷Lu, highlighting its potential as a promising nanotherapy for cancer treatment. Additionally, CLL can serve as a versatile platform for delivering a range of therapies to achieve synergistic antitumor effects.

Esophageal cancer is a malignant tumor of the digestive tract,with squamous cell carcinoma and adenocarcinoma accounting for over 99%of cases.Most patients are diagnosed at a locally advanced stage,and the efficacy of surgery alone is unsatisfactory.To improve the survival rate of patients with locally advanced esophageal cancer,researchers have explored a comprehensive treatment model based on neoadjuvant therapy,including neoadjuvant chemotherapy,neoadjuvant chemoradiotherapy,neoadjuvant immunochemotherapy,and neoadjuvant immunotherapy combined with chemoradiotherapy.Due to the differences in treatment sensitivity between squamous cell carcinoma and adenocarcinoma,this article systematically reviewed the response characteristics of different pathological types of esopha-geal cancer to neoadjuvant therapy using the latest clinical research data.

Objective:To analyze the relationship among thyroid autoimmunity (TAI), thyroid function, and gestational diabetes mellitus (GDM) in early pregnant women in Xi'an.Methods:A prospective study included pregnant women who underwent prenatal check-ups at the Northwest Women's and Children's Hospital from November 2020 to October 2021, with a gestational age of 6 to 14 weeks. Thyroid function, thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), and urinary iodine levels were measured, and the prevalence of thyroid disease and GDM was monitored. The subjects were divided into four groups: TPOAb positive only, TgAb positive only, both TPOAb and TgAb positive, and both TPOAb and TgAb negative, to compare the differences in the prevalence of thyroid disease and GDM among the groups. Statistical analysis was performed using Kruskal-Wallis rank-sum test, Bonferroni correction, Chi-square test, and a multivariate logistic regression model was used to analyze the relationship between TAI, thyroid disease, and GDM. Results:A total of 20 243 early pregnant women were included in this study, among which 1 615 (7.98%) were positive for TPOAb only; 865 (4.27%) were positive for TgAb only; 1 672 (8.26%) were positive for both TPOAb and TgAb (both positive group); and 16 091 (79.49%) were negative for both TPOAb and TgAb (both negative group). The thyroid stimulating hormone levels in the TPOAb positive only group, TgAb positive only group, and both positive group were significantly higher than those in the both negative group, respectively (Bonferroni correction, all P<0.05); the free thyroxine level in the TPOAb positive only group was significantly lower than that in the both negative group ( P<0.05). After adjusting for age, pre-pregnancy body mass index, and urinary iodine levels, multivariate logistic regression analysis showed that compared to the both negative group, the risk of developing hypothyroidism during pregnancy was significantly increased in the both positive group ( OR=11.49, 95% CI: 2.84-46.39); the risk of developing subclinical hypothyroidism during pregnancy was significantly increased in the TgAb positive only group ( OR=1.99, 95% CI: 1.05-3.76) and the both positive group ( OR=3.74, 95% CI: 2.49-5.63); the risk of developing GDM was significantly increased in the TgAb positive only group ( OR=1.43, 95% CI: 1.04-1.96) and the both positive group ( OR=1.94, 95% CI: 1.53-2.46). Among early pregnant women with normal thyroid function, after adjusting for age, pre-pregnancy body mass index, and urinary iodine levels, multivariate logistic regression analysis showed that compared to the both negative group, the risk of developing GDM was significantly increased in the TgAb positive only group ( OR=1.46, 95% CI: 1.06-2.02) and the both positive group ( OR=1.80, 95% CI: 1.40-2.32). Conclusion:TgAb positive only is a risk factor for subclinical hypothyroidism and GDM. Screening for thyroid autoantibodies, especially TgAb, during pregnancy helps in the early identification of high-risk pregnant women for thyroid dysfunction and GDM.

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 mechanism of Astragali Complanati Semen in the prevention and treatment of hyperlipidemia;To provide theoretical basis for its clinical application.Methods The active components of Astragali Complanati Semen were retrieved and screened through TCMSP,TCMID and TDT databases to obtain the action targets of the active components.Hyperlipidemia targets were obtained through GeneCards,DisGeNET,and TTD databases,and the drug active component targets were intersected with hyperlipidemia targets.Cytoscape 3.9.1 software and STRING database were used to construct active component-target network and protein-protein interaction network,screening for major active components and core targets.GO and KEGG pathway enrichment analysis was performed using the DAVID database,and the CB-Dock platform was used for molecular docking.HepG2 cells were induced to construct a high-fat cell model using oleic acid and palmitic acid,and intervened with Astragali Complanati Semen freeze-dried powder solution.The mRNA expression of the core target was detected by RT-qPCR.Results A total of 10 active components of Astragali Complanati Semen and 67 potential action targets of hyperlipidemia were identified,involving signaling pathways such as AGE-RAGE,lipid metabolism,HIF-1,etc.Experimental results showed that intervention with Astragali Complanati Semen could reduce lipid accumulation in the high-lipid cell model,with an optimal intervention concentration of 500 μg/mL;RT-qPCR revealed significant down-regulation of TNFα,IL6,AKT1,PPARG,and other genes after intervention with Astragali Complanati Semen.Conclusion Astragali Complanati Semen exerts lipid-regulating effects through multiple targets and pathways,providing a basis for its application in the prevention and treatment of hyperlipidemia.

Objective To translate the good death inventory-short form(GDI-SF)into Chinese and test its reliability and validity among bereaved family members of cancer patients.Methods A Chinese version of GDI-SF was created through translation,reconciliation,back translation,expert panel review and pilot testing.Then the inventory was administered to 699 bereaved family members of cancer patients recruited by convenience sampling.Reliability and validity were assessed.Results Toally 305 family members finished the study.The item-level content validity index(I-CVI)and average content validity index(S-CVI/Ave)were both 1.00.Exploratory factor analysis yielded 5 common factors:professional medical care(6 items),preparation for farewell(4 items),dignity and life value(4 items),natural death and moral support(2 items),and physical and mental comfort(2 items).These factors explained 52.176%of total variance.Overall Cronbach α coefficient of the Chinese version GDI-S was 0.779,and split-half reliability was 0.731.The Pearson correlation coefficient range between the score of each item of the Chinese version of GDI-SF and the score of its corresponding dimension was 0.591 to 0.769(P<0.01).Conclusion The Chinese version GDI-SF exhibits acceptable reliability and validity assessment of the quality of good dying in cancer patients from the perspective of bereaved family members.

Objective:To retrospectively seek any correlation between hemoglobin (Hb) levels and post-stroke cognitive impairment (PSCI), and to explore the value of Hb levels in PSCI diagnosis and prediction.Methods:The Mini-mental State Examination (MMSE) was used to sort elderly persons who had suffered a first stroke into a PSCI group showing cognitive impairment and a PSNCI group which was not cognitively impaired. Healthy counterparts undergoing physical examinations were selected into a healthy group. Everyone′s white blood cell count (WBC), neutrophil count (NC), lymphocyte count (LC), monocyte count (MONO), platelet count (PLT) and Hb, total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) were recorded. Monocyte to high density lipoprotein cholesterol ratios (MHRs), neutrophil to lymphocyte ratios (NLRs), and platelet to lymphocyte ratios (PLRs) were calculated. The differences among the three groups were compared seeking to identify risk factors predicting PSCI.Results:There were no significant differences in age, gender, WBC, MONO, PLT, TG or MHR among the three groups, on average. But there were significant differences in NC, LC, Hb, TC, HDL-C, LDL-C, NLR and PLR. Spearman correlation analysis showed that NC, NLR and PLR were negatively correlated with the average MMSE score, while LC, Hb, TC, HDL-C and LDL-C were positively correlated with it. Logistic regression analysis showed that a low level of Hb was an independent risk factor for PSCI for the elderly stroke survivors. The area under the receiver operating characteristics curve (AUC) for Hb was 0.794 for predicting PSCI in elderly stroke patients, with a maximum Youden index of 0.496. The critical value of Hb was estimated as 138.5g/L.Conclusions:Hb levels can significantly predict the cognitive functioning of elderly stroke survivors. An Hb level below 138.5g/L is an independent risk factor for PSCI, while higher Hb levels may indicate cognitive benefits.

Objective To investigate the mechanism of Astragali Complanati Semen in the prevention and treatment of hyperlipidemia;To provide theoretical basis for its clinical application.Methods The active components of Astragali Complanati Semen were retrieved and screened through TCMSP,TCMID and TDT databases to obtain the action targets of the active components.Hyperlipidemia targets were obtained through GeneCards,DisGeNET,and TTD databases,and the drug active component targets were intersected with hyperlipidemia targets.Cytoscape 3.9.1 software and STRING database were used to construct active component-target network and protein-protein interaction network,screening for major active components and core targets.GO and KEGG pathway enrichment analysis was performed using the DAVID database,and the CB-Dock platform was used for molecular docking.HepG2 cells were induced to construct a high-fat cell model using oleic acid and palmitic acid,and intervened with Astragali Complanati Semen freeze-dried powder solution.The mRNA expression of the core target was detected by RT-qPCR.Results A total of 10 active components of Astragali Complanati Semen and 67 potential action targets of hyperlipidemia were identified,involving signaling pathways such as AGE-RAGE,lipid metabolism,HIF-1,etc.Experimental results showed that intervention with Astragali Complanati Semen could reduce lipid accumulation in the high-lipid cell model,with an optimal intervention concentration of 500 μg/mL;RT-qPCR revealed significant down-regulation of TNFα,IL6,AKT1,PPARG,and other genes after intervention with Astragali Complanati Semen.Conclusion Astragali Complanati Semen exerts lipid-regulating effects through multiple targets and pathways,providing a basis for its application in the prevention and treatment of hyperlipidemia.

OBJECTIVE To establish HPLC fingerprint for Jianpi hewei formula(JPHWF),conduct chemical pattern recognition analysis,and determine the contents of seven components in the formula,aiming to provide a scientific basis for quality control and further research of JPHWF.METHODS Taking 15 batches of standard decoctions of JPHWF as samples,the HPLC fingerprint was established using the Similarity Evaluation System of TCM Chromatographic Fingerprint(2012 edition).Subsequently,similarity evaluation,as well as identification and attribution analysis of chromatographic peaks,were conducted.Using the common peak areas from the 15 batches of samples as variables,chemical pattern recognition analyses were performed on the samples through hierarchical cluster analysis,principal component analysis,and orthogonal partial least squares-discriminant analysis.The contents of adenine,5-hydroxymethylfurfural,tetrahydropalmatine,naringin,dehydrocorydaline,neohesperidin and glycyrrhizic acid in 15 batches of samples were determined by HPLC.RESULTS There were 19 common peaks in the characteristic chromatograms for 15 batches of samples with the similarities of more than 0.95.Results of chemical pattern recognition analysis showed that 15 batches of samples could be clustered into 3 categories,and 3 differential compounds were found[peak 7(5-hydroxymethylfurfural),peak 17(neohesperidin),and peak 15(naringin)].The 7 components were linearly good in the respective concentration ranges(R2≥0.999 4);RSDs of precision,stability and repeatability tests were less than 2%(n=6);the average recovery rate of 98.95%-103.81%,RSD of 0.61%-2.75%(n=6);the contents of them were 0.031-0.106,0.267-0.824,0.089-0.144,1.344-2.091,0.089-0.178,1.328-2.028,0.040-0.150 mg/g,respectively.CONCLUSIONS Established HPLC fingerprinting method coupled with multi-index content determination is validated to be accurate and reliable,and its combination with chemical pattern recognition analysis can be applied to the quality control of JPHWF.