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 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.

AIM: To evaluate the macular microcirculation changes in patients with diabetic retinopathy(DR)by optical coherence tomography angiography(OCTA), and correlate the risk factors that may affect the macular microcirculation, so as to provide a clinical basis for early screening, diagnosis and therapeutic intervention for DR.METHODS: Retrospective study. A total of 75 patients(75 eyes)with type 2 diabetes mellitus(DM)who came to the ophthalmology outpatient clinic and ward of Xi'an Central Hospital from May to October 2022 were collected, and the DM patients were further divided into non-DR(NDR)group, non-proliferative DR(NPDR)group and proliferative DR(PDR)group, with 28 eyes, 25 eyes and 22 eyes in each group respectively. OCTA was applied to perform a 3mm×3mm blood flow imaging scan of the macular retina to automatically obtain the vascular density(VD)of the superficial retinal macular foveal, the parafoveal(1～3mm), as well as the macular 3mm×3mm and the area of macular foveal avascular zone(FAZ). Furthermore, the alteration of these parameters in patients with different degrees of DR was analyzed.RESULTS: Compared with the NDR group, the VD of the 3mm×3mm superficial retinal capillary(SCP)in the macular region was decreased in both PDR and NPDR group(all P<0.017), and the VD of the parafoveal was decreased in each quadrant(P<0.017), with the most significant decrease in the PDR group. The FAZ area of patients in the PDR and NPDR groups was significantly larger than that in the NDR group(P<0.017). Age, homocysteine, best corrected visual acuity(LogMAR), axial length and glycosylated hemoglobin(HbA1c)of patients with DR were negatively correlated with VD in the macular foveal(P<0.05), while homocysteine, best corrected visual acuity(LogMAR), axial length, and the duration of diabetes were negatively correlated with VD in the macular 3mm×3mm(P<0.05). Triglycerides, best corrected visual acuity(LogMAR), and HbA1c were negatively correlated with VD in the parafoveal(P<0.05), while total cholesterol and central macular thickness had no significant correlation with VD(P>0.05).CONCLUSION: The microcirculation changes in the macular area of DR patients can be monitored by OCTA, and the systemic condition of DR patients is closely related to their macular microcirculation.

Objective To investigate the Gram-positive coccus resistance in nationwide's tertiary hospitals and understand the trend of antimicrobial resistance.Methods All the clinical isolates were collected from 19 hospitals and the minimal inhibitory concentrations(MICs)were tested using agar/broth dilution method recommended.Results A total of 1 974 pathogenic Gram-positive coccus from 19 tertiary hospitals in 19 cities nationwide over the period from July 2021 to June 2022 were studied.Based on the MIC results,the prevalence of methicillin resistant Stapylococcus aureus(MRSA)and methicillin resistant Stapylococcus epidermidis(MRSE)were 36.4％and 79.9％respectively.No vancomycin insensitivity Staphylococcus was detected.Staphylococcus aureus were 100％susceptibility to linezolid and teicoplanin.Antibiotic resistance rate of Enterococcus faecalis and Enterococcus faecium to ampicillin were 3.1％and 92.9％.The detectation rate of vancomycin resistant Enterococcus(VRE)was 1.6％.Nonsusceptibility rate of Enterococcus faecalis to linezolid was 32.2％,two consecutive monitoring rises and nonsusceptibility rate of Enterococcus faecium(12.5％)was also significantly increased.The prevalence of penicillin non-susceptible Streptococcus pneumoniae(PNSSP)was 0.8％based on non-meningitis and parenteral administration criterion,decrease of nearly 30 percentage points from the previous surveillance.While for cases of oral penicillin,the rate was 71.8％,showing similar to last time.The results indicated that the number of strains with higher MIC value of penicillin(MIC ≥4 mg·L-1)decreased significantly.There were no significant differences of resistance rates of Stapylococcus aureus,Stapylococcus epidermidis,Enterococcus faecalis,Enterococcus faecium and Streptococcus pneumoniae among various groups such as different department,age,or specimen source.Conclusion VRE detection ratio stablized at a relatively low level.The number of Streptococcus pneumoniae with higher MIC value of penicillin decreased significantly compared with the previous monitoring.The increase of linezolidin-insensitive Enterococcus was noteworthy.

Objective To investigate the Gram-negative bacteria resistance in nationwide's tertiary hospitals and understand the trend of antimicrobial resistance.Method All the clinical isolates were collected from 19 hospitals and the minimal inhibitory concentrations(MICs)were tested using agar/broth dilution method recommended.Results A total of 4 066 pathogenic isolates from 19 tertiary hospitals in 19 cities nationwide over the period from July 2021 to June 2022 were studied.Based on the MIC results,Escherichia coli and Klebsiella pneumoniae showed extended spectrum β-lactamase(ESBLs)phenotype rates of 55.0％and 21.0％,respectively,ESBLs phenotype rate of Klebsiella pneumoniae keep going down.The ratios of carbapenems resistance Klebsiella pneumoniae increased by 5 percentage points compared with the previous monitoring.Carbapenems,moxalactam,sitafloxacin,β-lactam combination agents,fosfomycin trometamol,and amikacin displayed desirable antibacterial activity against Enterbacterales,susceptibal rates were above 75％.In addition,tigacycline,omacycline,colistin and fluoxefin maintained good antibacterial activity against their respective effective bacteria/species,and the bacterial sensitivity rates by more than 80％.Resistance rates of Pseudomonas aeruginosa and Acinetobacter baumannnii to imipenem were 26.3％and 72.1％and multidrug-resistant(MDR)detection rates were 41.1％and 77.3％,extensively drug-resistant(XDR)were 12.0％and 71.8％,respectively.Comparison of drug resistance rates from different wards,ages and specimen sources indicated that the proportion of resistance in Klebsiella pneumoniae and Acinetobacter baumannii isolated from intensive care unit(ICU)were significantly higher than non-ICU.Carbapenem resistance rates of Klebsiella pneumoniae isolated from ICU were more than 35％.Resistance rates of Haemophilus influenzae isolated in children to β-lactam,macrolide,clindamycin and ESBLs detection rate in Klebsiella pneumoniae isolated from children were more than those from adults and the old people,so bacterial resistance in children is an important problem in China.Conclusion ESBLs detection rate of Escherichia coli increased slightly after years of continuous decline.The proportion of carbapenem resistant Pseudomonas aeruginosa was stable,but the resistance rate of Klebsiella pneumoniae and Acinetobacter baumannii to carbapenems was still increased,which should be paid more attention.