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.

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.

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.

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

This study explores the potential antiepileptic mechanism of ursolic acid(UA)and its improvement of GABAergic interneuron damage induced by epilepsy based on transcriptome analysis.Hippocampal tissues from rats in the control group(NC group),epilepsy group(SE group),and epilepsy UA treatment group(UA group)were subjected to full-length transcriptome sequencing.The obtained sequencing data were analyzed,using gene ontology(GO),the Kyoto Encyclopedia of Genes and Genomes(KEGG),and protein-protein interaction(PPI)to perform the analysis of differential genes(DEGs).The expression levels of key differential genes were verified using RT-qPCR in hippocampal tissue.Finally,an epilepsy in vitro model was constructed on primary neurons,RT-qPCR was used to verify the expression levels of key differential genes,and the expression level of GABAA receptor γ2 subunit(GABRG2)on neurons was further examined using immunofluorescence and Western blot.The heatmap of pairwise sample expression correlation and the clustering analysis of differentially expressed genes showed that the SE group was farthest from the NC group,and that after UA treatment,the overall trend shifted towards the normal group.Compared with the SE group,a total of 220 differential genes were screened in the UA group,including 143 upregulated genes and 77 downregulated genes.GO enrichment analysis showed that it involved three processes in the primary classification:biological processes,cellular components,and molecular functions.KEGG pathway enrichment analysis showed that DEGs were involved in 36 biological pathways,including cAMP signaling pathway and calcium signaling pathway.PPI analysis showed that DEGs were closely related to GABA and inflammation.RT-qPCR results showed that UA treatment increased the expression levels of GABA receptor-related gene(Gng4),GABA synthesis-related gene(Camk2a,Vgf,and Npy)and inflammation-related gene(Timp1 and Spp1)in hippocampal tissue,and decreased the expression levels of GABA synthesis-related gene(Nptx2)and cAMP-related pathway gene(Gnas).It further confirmed that UA treatment increased the expression levels of Gng4 and Camk2a on neurons and decreased the expression level of Gnas.Immunofluorescence and Western blot results showed that,compared with the SE group,the expression level of GABRG2 on primary neurons increased after UA treatment.This study enriched the transcriptome data of UA's antiepileptic effect and laid a theoretical foundation for further research on UA's antiepileptic and neuroprotective effects.

Objective To study the effects of the intelligent hearing-assistive system incorporated in Nuro-tron cochlear implants(CI),including the autonomic acoustic scene recognition(ASR),intelligent strategy config-uration as well as the objective and subjective hearing improvements on recipients.Methods ① To evaluate the per-formance of the ASR matule,in a sound-proof room,the preset five kinds of test audios,including speech,noise,speech in noise,pure music(without human voice)and non-pure Music(with human voice)were played.Each type of scenes included 6 to 9 5 min test files.The prediction accuracy and scene switching times were calculated.② In order to evaluate the noise-reduction performance of the ABeam technology in the speech enhancement module,13 Nurotron? CI recipients were recruited and their speech recognition rate when ABeam was"ON"and"OFF"with noise coming from 90°,180°or 270°were tested,individually.Also,their subjective hearing feedback was evaluated through visual analogue scale(VAS)evaluation.Results The ASR module achieved high prediction performance,with prediction accuracy 99％±4％,96％±9％,94％±12％,94％±15％,92％±13％for speech,noise,noisy speech,pure music and non-pure music,respectively.The scene transation times for each individual scene were 1.1 ±0.3,1.4±0.7,1.3±0.5,1.4±0.8 and 1.3±0.5,indicating that the prediction was also stable.When noise came from the sides and behind of recipients and speech signal from the front,the adaptive dual microphone noise re-duction algorithm ABeam significantly increased the speech recognition score(SRS)in 5 dB signal-to-noise(SNR)environment(P＜0.001),with an average increase of 15.92％.Especially when the noise came from 180 degree backward,the SRS increased 28.68％when ABeam was"0N",which was significantly higher than when ABeam was"OFF"(P＜0.01).Conclusion The intelligent hearing-assistive system can help CI recipients automatically configure appropriate SPSs under different environments,improving the speech intelligibility and hearing comfort.

Humans ; Prognosis ; Treatment Outcome ; Pulmonary Disease, Chronic Obstructive

Objective:To investigate the effect of gastrodin(GAS)on the sex-determining region Y-box2(SOX2)/β-catenin pathway in microglia induced by lipopolysaccharide(LPS).Methods:BV2 microglia was cultured in vitro and divided into the following groups:Control group(Control),LPS group(LPS),LPS+0.17 mmol/L gastrodin treatment group(LPS+GAS-L),LPS+0.34 mmol/L gastrodin treatment group(LPS+GAS-H),SOX2 inhibitor pronethalolgroup(PR),LPS+PR group(LPS+PR),and LPS+PR+GAS group(LPS+PR+GAS).Effect of PR on BV2 microglia viability was detected by CCK-8.The expression of SOX2,β-catenin,mannose receptor(CD206)and tumor necrosis factor-α(TNF-α)was assessed using Western Blot and immunofluorescence double staining.Results:PR did not induce significant BV2 cell death in the 0～40 μmol/L range.After LPS treatment,the expression levels of SOX2,β-catenin,and TNF-α significantly increased in the LPS group,while CD206 decreased(P＜0.05).Following GAS treatment,the expression levels of SOX2,β-catenin,and TNF-α significantly decreased,while CD206 increased(P＜0.05).Compared to the LPS group,the expression levels of β-catenin and TNF-α significantly de-creased in the PR group(P＜0.05),but no significant difference was observed between the LPS+GAS and LPS+PR+GAS group.Conclusion:GAS significantly inhibits LPS-induced microglia activation potentially through the inhibi-tion of the SOX2/β-catenin signaling pathway,and exerts anti-inflammatory effects.

Objective:To establish a scoring system for preoperative prediction of the malignant potential of gastric stromal tumors based on gastroscopic and endoscopic ultrasound features, along with validation.Methods:A total of 286 patients who were treated in Jiangsu Province Hospital of Chinese Medicine from January 1, 2017 to December 31, 2023 and diagnosed as having gastric stromal tumors by postoperative pathology were enrolled in the modeling group. According to National Institutes of Health classification system, 227 very-low/low-risk patients were classified into the low malignant potential (LMP) group, and the 59 intermediate/high-risk patients into the high malignant potential (HMP) group. LASSO regression analysis was performed to identify predictive factors for HMP gastric stromal tumors, and a nomogram prediction model was developed. Internal validation using the Bootstrap method was performed on the modeling group, and external validation was performed on data from 85 patients who were treated and diagnosed as having gastric stromal tumors by postoperative pathology in Taizhou People's Hospital from January 1, 2021 to December 31, 2023. The receiver operator characteristic (ROC) curves, calibration curves, and decision curve analyses were employed in both the modeling and external validation groups.Results:Tumor size (coef=0.755), tumor shape (coef=0.015), tumor location (coef=0.008), growth pattern (coef=-0.026), cystic change (coef=0.685), and surface unceration change (coef=-0.545) were the independent predictive factors for HMP gastric stromal tumors. The nomogram-based prediction model constructed using these factors achieved an area under the ROC curve of 0.959 (95% CI: 0.898-0.903) in the modeling group and 0.959 (95% CI: 0.857-1.000) in the external validation group. The model demonstrated good accuracy (0.917) and a Kappa value of 0.737 in internal validation. Calibration curve and decision curve analyses indicated strong calibration and high net benefit in both the modeling and the external validation groups. Conclusion:Tumor size, tumor shape, tumor location, growth pattern, cystic change, and surface ulceration change are independent predictive factors for HMP gastric stromal tumors. The nomogram model developed based on these factors offers effective and convenient visualization for clinicians to predict the malignant potential of gastric stromal tumors preoperatively.

Objective To detect the apoptosis effects of dioscin in HepG2 cells and its possible anti-hepatocellular carcinoma mechanisms.Methods HepG2 human hepatocellular carcinoma cells were exposed to 0.25,0.5,1,2,4,6,or 8 μmol/L dioscin,and cell proliferation was measured via MTT assay.The half-maximal inhibitory concentration(IC50)was calculated with the software.A scratch test was used to analyze cell migration ability.Western blot was employed to evaluate the expression of apoptosis and Wnt/β-catenin-pathway-related proteins.Results Compared with the control group,the dioscin-treated HepG2 cells'proliferation was significantly more inhibited,and the inhibition increased in a time-and dose-dependent manner(P＜0.01).HepG2 cells showed morphological characteristics of apoptosis after they were treated with 1 μmol/L or 2 μmol/L dioscin.The scratch test indicated that the migration distance of HepG2 cells was remarkably reduced when treated with dioscin.In the Western blot experiment,the expression levels of Caspase-3 and cleaved Caspase-3 were visibility up-regulated,while those of Bcl-2 and β-catenin were significantly down-regulated when the cells were treated with dioscin for 24 h(P＜0.05,P＜0.01).When LiCl reagent was added to the HepG cells to activate the Wnt/β-catenin signaling pathway,the expression levels of Wnt1 and β-catenin were remarkably increased compared with those of the control group(P＜0.01).Compared with the LiCl group,the LiCl+DIO group's expression of Wnt1,β-catenin,and GSK-3β was significantly decreased(P＜0.01).Conclusions DIO can promote the apoptosis of HepG2 cells by inhibiting β-catenin protein expression and thereby down-regulating the Wnt/β-catenin signaling pathway.This inhibits apoptosis-related gene Bcl-2 expression,which leads to the induction of cell apoptosis.Therefore,DIO can have an anti-hepatocellular carcinoma effect.