Metabonomics and proteomics were employed to investigate the mechanism of Yuzhi Zhixue Granules in treating polycystic ovary syndrome with insulin resistance(PCOS-IR). The disease model was established by feeding a high-fat diet and gavage of letrozole solution and it was then treated with different doses of Yuzhi Zhixue Granules. The therapeutic effect of Yuzhi Zhixue Granules was evaluated based on the body mass, homeostasis model assessment of insulin resistance and insulin sensitivity index, serum levels of adipokines, and histopathological changes of rats. Metabolomics and proteomics were employed to find the action pathways of Yuzhi Zhixue Granules. The results showed that Yuzhi Zhixue Granules reduced the body mass, improved the insulin sensitivity and aromatase activity, improved the levels of leptin, adiponectin and other adipokines, and alleviated insulin resistance, histopathological changes, and metabolic disorders in PCOS-IR rats. Metabolomics results revealed 14 metabolites with altered levels in the ovarian tissue, which were closely related to glutathione metabolism and pyruvate metabolism. Proteomics results showed that the therapeutic effect of Yuzhi Zhixue Granules was mainly related to the adipokine, adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK), phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt), forkhead box protein O(FoxO), and mechanistic target of rapamycin(mTOR) signaling pathways. Western blot results showed that compared with the model group, Yuzhi Zhixue Granules treatment decreased the p-AMPK/AMPK and p-FoxO1/FoxO1 levels, increased the p-mTOR/mTOR level, and up-regulated the expression level of recombinant glucose transporter 4(GLUT4). Yuzhi Zhixue Granules can balance amino acid metabolism and pyruvate metabolism by regulating the AMPK/mTOR/FoxO/GLUT pathway to maintain the homeostasis of the ovarian environment and alleviate insulin resistance, thus treating PCOS-IR.
Animals ; Female ; Insulin Resistance ; Polycystic Ovary Syndrome/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Metabolomics ; Proteomics ; Rats, Sprague-Dawley ; Humans ; Ovary/metabolism* ; Signal Transduction/drug effects*

PURPOSE: Septic shock is associated with high mortality and poor outcomes among sepsis patients with coagulopathy. Although traditional statistical methods or machine learning (ML) algorithms have been proposed to predict septic shock, these potential approaches have never been systematically compared. The present work aimed to develop and compare models to predict septic shock among patients with sepsis. METHODS: It is a retrospective cohort study based on 484 patients with sepsis who were admitted to our intensive care units between May 2018 and November 2022. Patients from the 908th Hospital of Chinese PLA Logistical Support Force and Nanchang Hongdu Hospital of Traditional Chinese Medicine were respectively allocated to training (n=311) and validation (n=173) sets. All clinical and laboratory data of sepsis patients characterized by comprehensive coagulation indexes were collected. We developed 5 models based on ML algorithms and 1 model based on a traditional statistical method to predict septic shock in the training cohort. The performance of all models was assessed using the area under the receiver operating characteristic curve and calibration plots. Decision curve analysis was used to evaluate the net benefit of the models. The validation set was applied to verify the predictive accuracy of the models. This study also used Shapley additive explanations method to assess variable importance and explain the prediction made by a ML algorithm. RESULTS: Among all patients, 37.2% experienced septic shock. The characteristic curves of the 6 models ranged from 0.833 to 0.962 and 0.630 to 0.744 in the training and validation sets, respectively. The model with the best prediction performance was based on the support vector machine (SVM) algorithm, which was constructed by age, tissue plasminogen activator-inhibitor complex, prothrombin time, international normalized ratio, white blood cells, and platelet counts. The SVM model showed good calibration and discrimination and a greater net benefit in decision curve analysis. CONCLUSION The SVM algorithm may be superior to other ML and traditional statistical algorithms for predicting septic shock. Physicians can better understand the reliability of the predictive model by Shapley additive explanations value analysis.
Humans ; Shock, Septic/blood* ; Machine Learning ; Male ; Female ; Retrospective Studies ; Middle Aged ; Aged ; Sepsis/complications* ; ROC Curve ; Cohort Studies ; Adult ; Intensive Care Units ; Algorithms ; Blood Coagulation ; Critical Illness

Objective:To explore the differentially expressed tRNA-derived RNA fragment(tRF)and tRNA halves(tiRNA)in plasma of collagen-induced arthritis(CIA)rats,analyze the biological functions and related pathways of the tRF and tiRNAs target genes in order to identify new targets for diagnosis and therapy of rheumatoid arthritis(RA).Methods:Rat model of RA was estab-lished by injecting typeⅡ collagen.Arthritis index(AI)score and HE staining were conducted to evaluate the successfully establishment model.Illumina platform was used to obtain the tRF and tiRNA expression profiles.RT-qPCR was performed to validate expressions of tRF and tiRNA.Combining miRanda and TargetScan databases,the target genes of differentially expressed tRF and tiRNA were ob-tained.GO and KEGG enrichment analysis were used to annotate the functions of target genes.Results:A total of 25 tRFs and tiRNAs were significantly differentially expressed in plasma in rats after modeling,of which 23 were up-regulated and 2 were down-regulated.Besides,six specifically expressed tRFs and tiRNAs induced by CIA rats were screened,including Other-36:73-tRNA-Arg-CCT-4,Other-57:70-tRNA-Glu-CTC-1-M3,tRF-1:32-Gly-CCC-1-M2,tRF-1:31-Gly-CCC-1-M2,tRF-1:32-Pro-AGG-1-M4 and tRF-1:32-Glu-TTC-2-M2.GO analysis of target genes mainly involved organelle-associated items.What's more,KEGG analysis enriched multi-ple classical signal pathways associated with RA.Conclusion:Target genes of differentially expressed tRFs and tiRNAs in CIA rats may be involved in regulating important pathophysiological processes of RA and drug therapy targets.

Objective:To explore the differentially expressed tRNA-derived RNA fragment(tRF)and tRNA halves(tiRNA)in plasma of collagen-induced arthritis(CIA)rats,analyze the biological functions and related pathways of the tRF and tiRNAs target genes in order to identify new targets for diagnosis and therapy of rheumatoid arthritis(RA).Methods:Rat model of RA was estab-lished by injecting typeⅡ collagen.Arthritis index(AI)score and HE staining were conducted to evaluate the successfully establishment model.Illumina platform was used to obtain the tRF and tiRNA expression profiles.RT-qPCR was performed to validate expressions of tRF and tiRNA.Combining miRanda and TargetScan databases,the target genes of differentially expressed tRF and tiRNA were ob-tained.GO and KEGG enrichment analysis were used to annotate the functions of target genes.Results:A total of 25 tRFs and tiRNAs were significantly differentially expressed in plasma in rats after modeling,of which 23 were up-regulated and 2 were down-regulated.Besides,six specifically expressed tRFs and tiRNAs induced by CIA rats were screened,including Other-36:73-tRNA-Arg-CCT-4,Other-57:70-tRNA-Glu-CTC-1-M3,tRF-1:32-Gly-CCC-1-M2,tRF-1:31-Gly-CCC-1-M2,tRF-1:32-Pro-AGG-1-M4 and tRF-1:32-Glu-TTC-2-M2.GO analysis of target genes mainly involved organelle-associated items.What's more,KEGG analysis enriched multi-ple classical signal pathways associated with RA.Conclusion:Target genes of differentially expressed tRFs and tiRNAs in CIA rats may be involved in regulating important pathophysiological processes of RA and drug therapy targets.

Objective To achieve intelligent recognition and segmentation of common craniocerebral inju-ries(hereinafter referred to as"segmentation")by training convolutional neural network DeepLabV3+model based on CT images of blunt craniocerebral injury(BCI),and to explore the value of deep learning in automated diagnosis of BCI in forensic medicine.Methods A total of 5 486 CT images of BCI from living persons were collected as the training set,validation set and test set for model training and performance evaluation.Another 255 CT images of BCI and 156 normal craniocerebral CT images from living persons were collected as the blind test set to evaluate the ability of the model to seg-ment the five types of craniocerebral injuries including scalp hematoma,skull fracture,epidural hema-toma,subdural hematoma,and brain contusion.Another 340 BCI and 120 normal craniocerebral CT images from cadavers were collected as the new blind test set to explore the application value of the model trained by living CT images in the segmentation of BCI in cadavers.The five types CT images of all BCI except the blind test set were manually labeled;then,each dataset was inputted into the model to train the model.The performance of the model was evaluated and optimized based on the loss function and accuracy curves of the training set and validation set,and the generalization ability was evaluated based on the Dice value of the test set.According to the accuracy,precision and F1 value of the blind test set,the segmentation performance of the model for five types of BCI was evaluated.Results After training and optimizing the model,the average Dice values of the final optimal model to scalp hematoma,skull fracture,epidural hematoma,subdural hematoma and brain contusion segmen-tation were 0.766 4,0.812 3,0.938 7,0.782 7 and 0.858 1,respectively,all greater than 0.75,meeting the expected requirements.External validation showed that the F1 values were 93.02%,89.80%,87.80%,92.93%and 86.57%in living CT images,respectively;83.92%,44.90%,76.47%,64.29%and 48.89%in cadaveric CT images,respectively.The above suggested that the model was able to accu-rately segment various types of craniocerebral injury on living CT images,while its segmentation ability was relatively poor on cadaveric CT images,but still able to accurately segment scalp hematoma,epidu-ral hematoma and subdural hematoma.Conclusion Deep learning model trained on CT images can be used for BCI segmentation.However,the direct use of living persons'BCI models for the identifica-tion of cadaveric BCI has some limitations.This study provides a new approach for intelligent segmen-tation of virtual anatomical data for BCI.

Objective To use superparamagnetic iron oxide nanoparticles(SPIONs)to label chimeric antigen receptor(CAR)T cells targeting carcinoembryonic antigen(CEA),and perform magnetic resonance imaging(MRI)to real time trace CEA CAR-T cells in vivo.Methods Appropriate amount of ferumoxytol,heparin sodium and protamine sulfate were mixed at high(ferumoxytol 100 μg/mL,heparin sodium 4 IU/mL,protamine sulfate 120 μg/mL),medium(ferumoxytol 50 μg/mL,heparin sodium 2 IU/mL,protamine sulfate 60 μg/mL),and low(ferumoxytol 25 μg/mL,heparin sodium 1 IU/mL,protamine sulfate 30 μg/mL)concentrations to form a SPIONs complex ferumoxytol/heparin/protamine(FHP),and then co-incubated with CEA CAR-T cells for cell labeling.The biocompatibility of FHP was detected by CCK-8 assay,EdU assay and flow cytometry.The uptake of FHP was detected by Prussian blue staining,and SPIONs content in the cells was quantitatively detected by inductively coupled plasma-mass spectrometry(ICP-MS).Flow cytometry was used to detect the lytic effect of FHP-labeled CEA CAR-T cells on tumor cells,and MRI was employed to scan FHP-labeled CEA CAR-T cells.Results FHP at high,medium,and low concentrations had no significant effect on the activity of CEA CAR-T cells,with cell activity above 100％determined by CCK-8 assay.DNA proliferation was above 94.3％in EdU assays.Prussian blue staining showed that CEA CAR-T cells could take FHP up,with the uptake increased with the increment of FHP concentration.ICP-MS showed that the intracellular Fe content was 440.23±189.36 ng/mL.Tumor cell killing experiment showed that FHP-labeled CEA CAR-T cells had excellent killing capability against tumor cells.MRI scans indicated that T2WI signals of FHP-labeled CEA CAR-T cells were significantly reduced with increasing FHP concentration(P＜0.01).Conclusion SPIONs complex FHP shows good biocompatibility and can effectively label CEA CAR-T cells.SPIONs complex FHP can be used as a magnetic marker for CEA CAR-T cells and a feasible MRI tracer for clinical application.

Objective To observe the curative effect of comprehensive traditional Chinese medicine(TCM)therapy for the treatment of refractory sudden hearing loss(i.e.,suffering sudden hearing loss more than 2 weeks),and to analyze the factors that may affect the prognosis.Methods A retrospective analysis was carried out in 405 hospitalized patients with refractory sudden hearing loss who were treated in the Department of Otorhinolaryngology,the First Affiliated Hospital of Guangzhou University of Chinese Medicine from 2005 to 2022.The patients were all treated by comprehensive TCM therapy including oral administration of Chinese medicine,acupuncture,acupoint seed-pressing application after individualized syndrome differentiation.The overall clinical efficacy was evaluated,and the difference of efficacy in the patients with various courses of disease,degrees of deafness,types of hearing curve,concomitant symptoms and TCM syndrome types,having or not having previous treatment history was analyzed.Results For the 405 patients with refractory sudden hearing loss,the cure rate was 5.7％and the total effective rate was 28.1％.Among the 405 patients,the best efficacy was achieved in the patients with mild hearing loss,low-frequency decline type of hearing curve,and having no previous treatment history,and the differences were statistically significant(P＜0.05 or P＜0.01).There was no significant difference in the efficacy of patients with different courses of disease,with or without concomitant symptoms,or with various syndrome types(P＞0.05).Conclusion The comprehensive TCM therapy has a certain effect on refractory sudden hearing loss.Patients with poor efficacy after conventional western medicine can still benefit from the comprehensive TCM therapy.

Objective To investigate the clinical efficacy of standardized comprehensive pure traditional Chinese medicine(TCM)treatment for short-course sudden deafness and to explore the influencing factors of clinical efficacy.Methods The clinical data of 516 short-course sudden deafness inpatients(TCM group)who were given standardized comprehensive pure TCM treatment were retrospectively analyzed,and their efficacy were compared with the efficacy of 1 024 cases in the Chinese multicenter clinical study of sudden deafness(western medicine group).The analysis was carried out for the influence of the gender,left or right ear,age group,degree of deafness,type of hearing curve,concomitant symptoms(tinnitus,vertigo,and dullness of the ear),and the TCM syndrome types on the efficacy.Results(1)The comparison of baseline data showed that in comparison with the western medicine group,TCM group had relatively low proportion of low-frequency descending type while relatively high proportion of total deafness type,and had relatively high treatment difficulty.The course of treatment in TCM group was shortened by nearly 2/3 in comparison with the western medicine group(12.60 days vs 30 days).(2)Among the 516 patients of the TCM group,175 cases were cured,121 cases were markedly effective,90 cases were effective and 130 cases were ineffective,and the total effective rate was 74.80%.Compared with the 1 024 cases in the western medicine group,there was no significant difference in the overall efficacy or the efficacy evaluated with the hearing curve classification(P＞0.05).(3)Analysis of influencing factors of curative effect showed that the type of hearing curve was closely related to the curative effect of sudden deafness(P＜0.001).The curative effect of low frequency descent type was the best,and the curative effect of total deafness type was the worst.The cure of deafness was correlated with the degree of deafness,the milder the degree of deafness,the greater the likelihood of recovery(P＜0.001).The curative effect of the patients without vertigo was superior to that of the patients with vertigo(P＜0.001).The curative effect of adolescent patients was superior to that of middle-aged and elderly patients(P＜0.05).There was no correlation between TCM syndrome types and curative effect(P＞0.05).Conclusion Standardized comprehensive pure TCM treatment exerts certain curative effect on short-course sudden deafness,and may have some advantages compared with conventional western medicine treatment.The type of hearing curve,degree of deafness,accompanied by vertigo or not,and age group are the influencing factors of the efficacy.

Objective To verify the safety and efficacy of a new portable extracorporeal membrane oxygenation(ECMO)system(Xijing Advanced Life Support System JC-Ⅲ)in large animals.Methods A total of 10 healthy small fat-tail sheep underwent veno-arterial extracorporeal membrane oxygenation(VA-ECMO)support by carotid arterial-jugular catheterization to evaluate the performance of the JC-Ⅲ ECMO system.Systemic anticoagulation was achieved by continuous infusion of heparin.Active coagulation time(ACT)was recorded every 2 hours during the experiment,and the ACT was maintained between 200-250 s.Centrifugal pump speed is set at 3 000-3 500 r/min.The changes of hemoglobin,blood cell counts,hematocrit,liver and kidney function were monitored before and 24 h after ECMO initiation,respectively.After the experiment,the pump and oxygenator were dissected to probe the thrombosis.Results The success rate of VA-ECMO operation was 100％,and there was no hemolysis,pump thrombosis and oxygenator thrombosis after 24 h of ECMO.Before and after the operation,there were no significant changes in indicators such as hemoglobin content,white blood cell counts,platelet counts,alanine aminotransferase concentration,aspartate aminotransferase concentration,urea,creatinine,high-sensitivity troponin Ⅰ,and N-terminal pro-brain natriuretic peptide(all P＞0.05).Conclusions This in vivo study confirms that Xijing Advanced Life support System JC-Ⅲ is safe and effective.

In recent years,the growing public awareness of personal health has sparked a surge in inter-est in the beneficial effects of polyphenols on the human organism.Extensive research by domestic and international scholars has established that polyphenols,due to their unique chemical properties,exhibit remarkable anti-inflammatory and antioxidant properties,leading to improvements in various diseases,in-cluding cancer,diabetes,and colitis.Notably,China stands as one of the world's largest producers and consumers of flax,a crop rich in lignans,a subclass of polyphenols.These flax lignans possess significant effects on the body,demonstrating immense potential for therapeutic applications.This paper delves into the origins,metabolic processes,and health benefits of flax lignans in China.It offers a comprehensive review of the mechanisms underlying flax lignans role in disease intervention,focusing on their interac-tions with relevant signalling pathways.Our findings suggest that flaxseed lignans can promote organismic health by either directly modulating gene expression or indirectly regulating signalling pathways.Further-more,flaxseed lignans can exhibit diverse effects depending on specific physiological conditions.