Objective:To investigate the effect of bone mesenchymal stem cells derived exosomes (BMSC-Exo) on improving hippocampal microangiogenesis, energy metabolism, and behaviors in depression mouse models.Methods:(1) Mouse bone marrow mesenchymal stem cells were isolated and cultured to extract BMSC-Exo; BMSC-Exo morphology was observed by transmission electron microscopy, BMSC-Exo particle diameter ranges were determined by Zetaview analyzer, and expressions of CD9 and CD63 in BMSC-Exo were detected by Western blotting. (2) Depression models were established in 2 mice by chronic unforeseeable mild stress (CUMS); 24 h after stereotaxic injection of phosphate buffer solution (PBS) or DiR labeled BMSC-Exo, BMSC-Exo uptake was detected by in vivo imaging system. (3) Thirty-six mice were randomly divided into control group, model group and BMSC-Exo group ( n=12); CUMS was used to establish depression models in the latter 2 groups; brain stereotaxic injection of 1 μL BMSC-Exo was given to mice in the BMSC-Exo group after modeling, and same amount of PBS was given to the control group; behaviors were observed by forced swimming test (FST), tail suspension test (TST) and open field test (OFT); hippocampal microvascular length and number were detected by alkaline phosphatase staining; energy metabolism in the hippocampus was detected by micro positron emission tomography/computed tomography (mPET/CT); glucose transporter 1 (GLUT1) expression in the hippocampus was detected by Western blotting. Results:(1) BMSC-Exo had a typical disk-like vesicle-like structure with particle size of (100.5±1.4) nm; Western blotting confirmed that CD9 and CD63 expressed in BMSC-Exo. (2) In vivo imaging showed no fluorescence in the brain and liver after PBS injection, but obvious local fluorescence after BMSC-Exo injection. (3) Compared with the control group, the model group and BMSC-Exo group had significantly longer rest time in FST and TST and shorter movement distance and time in the central region of OFT ( P<0.05); compared with the model group, BMSC-Exo group had significantly shorter rest time in FST and TST and longer movement distance and time in the central region of OFT ( P<0.05). Compared with the control group, the model group and BMSC-Exo group had significantly decreased standard uptake value (SUV) of regions of interest, microvascular length and number, and GLUT1 expression in the hippocampus ( P<0.05); compared with the model group, the BMSC-Exo group had significantly higher SUV, microvascular length and number, and GLUT1 expression in the hippocampus ( P<0.05). Positive correlations were noted between hippocampal microvascular length and SUV and between microvascular number and SUV in the 3 groups ( r=0.540, P<0.001; r=0.600, P<0.001). Conclusion:BMSC-Exo could promote microangiogenesis energy metabolism in the hippocampus to improve depression-like behaviors in depression mouse models.

Background::Pulmonary embolism (PE) is a severe and acute cardiovascular syndrome with high mortality among patients with autoimmune inflammatory rheumatic diseases (AIIRDs). Accurate prediction and timely intervention play a pivotal role in enhancing survival rates. However, there is a notable scarcity of practical early prediction and risk assessment systems of PE in patients with AIIRD.Methods::In the training cohort, 60 AIIRD with PE cases and 180 age-, gender-, and disease-matched AIIRD non-PE cases were identified from 7254 AIIRD cases in Tongji Hospital from 2014 to 2022. Univariable logistic regression (LR) and least absolute shrinkage and selection operator (LASSO) were used to select the clinical features for further training with machine learning (ML) methods, including random forest (RF), support vector machines (SVM), neural network (NN), logistic regression (LR), gradient boosted decision tree (GBDT), classification and regression trees (CART), and C5.0 models. The performances of these models were subsequently validated using a multicenter validation cohort.Results::In the training cohort, 24 and 13 clinical features were selected by univariable LR and LASSO strategies, respectively. The five ML models (RF, SVM, NN, LR, and GBDT) showed promising performances, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.962-1.000 in the training cohort and 0.969-0.999 in the validation cohort. CART and C5.0 models achieved AUCs of 0.850 and 0.932, respectively, in the training cohort. Using D-dimer as a pre-screening index, the refined C5.0 model achieved an AUC exceeding 0.948 in the training cohort and an AUC above 0.925 in the validation cohort. These results markedly outperformed the use of D-dimer levels alone.Conclusion::ML-based models are proven to be precise for predicting the onset of PE in patients with AIIRD exhibiting clinical suspicion of PE.Trial Registration::Chictr.org.cn: ChiCTR2200059599.

Objective To investigate the repairing effect and mechanism of Chinese patent medicine Weiyangning pill on gastric mucosal injury in rats induced by anhydrous ethanol,and to establish a high-performance liquid chromatography(HPLC)method to determine the five main components of Weiyangning pill.Methods The five components of paeoniflorin,psoralen,atractylenolide Ⅲ,liquiritin and hesperidin in Weiyangning pill were detected by HPLC.SD male rats were randomly divided into normal control group,model control group,Weinaian group,and large and small dose group of Weiyangning pill.All rats were fasted for 24 hours without water fasting.The normal control group and the model control group were given purified water by gavage.While Weinaian group was given Weinaian(3 g·kg-1),the test group were given intragastric perfusion of Weiyangning(3,1.5 g·kg-1)respectively.After 2 hours,all the rats,except the normal control group,were intragastrically administered with anhydrous ethanol(5 mL·kg-1)to establish the model of gastric mucosal injury.An hour later,the experimental materials were collected,and the gross score of gastric mucosal injury was observed and calculated.The gastric mucosal slices were stained by hematoxylin-eosin(HE)to calculate the pathological scores.Immunohistochemistry was employed to detect the expression of gastric mucosa-related proteins.Results The high-performance liquid chromatogram of Weiyangning pill was obtained,and the absorption peaks with the same retention time as the five standard substances(paeoniflorin,psoralen,atractylenolide Ⅲ,liquiritin and hesperidin)were observed.The general score and pathological score of gastric mucosal injury in Weiyangning groups(3,1.5 g·kg-1)were lower than those of the model control group(P<0.05 or P<0.01).Weiyangning pill(3,1.5 g·kg-1)ameliorated the decrease expression of tight junction protein(Claudin-7),adhesion junction proteins(E-cadherin and β-catenin),mucins(MUC1 and MUC5AC),and the gastric transcription factor SOX2 in the gastric mucosa of the rats modeled in anhydrous ethanol(P<0.05 or P<0.01 compared with the model control group).Conclusion The repairing effect of Weiyangning pill on gastric mucosal injury induced by anhydrous ethanol in rats is related to the increase of the expression of tight junction protein,adhesion junction protein,mucin and gastric transcription factor.

Objective To establish an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method for determination of tobramycin in human serum,and examine the utility of the method in a clinical pharmacokinetic study of tobramycin inhalation.Methods Serum samples were pretreated by solid phase extraction with tobramycin-D12 as internal standard.Chromatographic separation was performed on a TitankHilic(2.1 mm × 100 mm,3 μm)column.The mobile phase consisted of0.1％formic acid-acetonitrile and 0.1％formic acid aqueous solution at a flow rate of 0.4 mL/min.Electrospray ionization source and multiple reaction monitoring(MRM)scanning were used for monitoring the quantitative ion pairs with m/z 468.3→m/z 163.3(tobramycin)and m/z 480.6→m/z 166.2(tobramycin-D12).The established method was investigated in terms of selectivity,interaction,concomitant medication,standard curve and lower limit of quantitation,precision and accuracy,recovery,matrix effect,and stability of tobramycinin.Results The linear range of tobramycin was 0.050 0-10.0 mg/L(R2=0.999 5).The intra-and inter-batch precision was satisfactory(coefficient of variation[CV]≤3.6％).The accuracy ranged from-0.4％to 6.0％.The matrix effect factor(MF)in human serum samples(including hemolysis and lipemia)ranged from 92.2％to 94.9％(CV≤2.7％).The recovery of tobramycinin was 79.5％-81.9％in serum samples,while the recovery of internal standard was 78.9％.The analyte was stable in serum samples for 72 h at room temperature and for 274 days at-20℃/-70℃.The pharmacokinetic study of tobramycin inhalation in bronchiectasis patients showed that after continuous administration of tobramycin 300 mg twice a day to 3 patients,the mean Cmax of tobramycin was(0.72±0.61)mg/L on Day 1 and(0.76±0.73)mg/L on Day 28,respectively.The corresponding Tmax was(1.83±0.61)h and(1.50±0.50)h,respectively.Conclusions The UPLC-MS/MS method established in this study is sensitive,accurate and rapid.It is successfully applied to the clinical pharmacokinetic study of tobramycin inhalation.The method may be suitable for therapeutic drug monitoring of tobramycin in clinical practice.

Objective:To investigate the region-specific characteristics of the gut microbiota and evaluate the association of speci?c gut microbes with type 2 diabetes mellitus (T2DM) from the Dongxiang Group in Gansu province, Northwest China.Methods:Fifty-three participants who was born in Dongxiang Autonomous County (Gansu Province) from April 2020 to January 2021 were enrolled, including 25 patients with T2DM recruited from the outpatient departments of internal medicine at The People′s Hospital of Dongxiang County(T2DM group) and 28 healthy controls recruited from the health screening center (HC group). Gut microbiome composition was analyzed using a 16S ribosomal RNA gene-based sequencing protocol.Results:A total of 936 operational taxonomic units (OTU) were obtained in the two groups. Of note, the HC and T2DM groups had 633 OTU in common. The alpha and beta diversity were different between the two groups ( P<0.05). Shannon index was significantly higher than that in the HC group, and Simpson index was significantly lower than that in the HC group, displacement multivariate analysis of variance was used to compare β diversity between the two groups, and the difference was statistically significant ( P<0.05). At the Phylum level, firmicutes and actinomycetes in T2DM group were significantly higher than those in the HC group (37.97% vs. 22.89%, 5.09% vs. 2.08%), and the differences were statistically significant ( P<0.05). The abundance of Bacteroidetes was significantly decreased (68.00% in T2DM group and 49.75% in HC group), and the difference was statistically significant ( P<0.05). At the genus level, there were 20 genera statistically significant differences between the two groups. The abundance of Bifidobacterium, Escherichia, Shigella, and Tyzzerella_4 levels were significantly increased in the T2DM group, but Prevotella_9, Erysipelotrichaceae_UCG-003, and Roseburia levels were significantly decreased in the T2DM group compared to those in the HC group. Conclusions:There is a significant difference in the gut microbiota between patients with T2DM and healthy individuals of the Dongxiang group in Northwest China. So as to preliminary exploration the intestinal flora characteristics of T2DM in the Dongxiang group.The findings of this study provide a theoretical basis for the prevention and control of T2DM in Dongxiang group in the future.

Objective: To understand the dilemma of different participants in school psychological crisis intervention, so as to provide guidance for the implementation of comprehensive psychological crisis intervention from multiple perspectives. Methods: From March 2022 to January 2023, a total of 10 psychological consultants, 10 counselors, 10 peer students, 10 parents and 10 clients were selected from a certain university using convenient sampling method was interviewed with semi structured interviews, and the transcribed data were analyzed according to grounded theory. Results: The predicaments of psychological crisis intervention mainly involved three core themes: early warning, ethical dilemma and negative emotion. Early warning approaches mainly included three core themes: school, social media and other institutions, and 50 participants reported mainly on peer students in schools(18 cases) and online media in social media(18 cases). Ethical dilemmas mainly focued on the conflict between confidentiality breaches and privacy protection. The negative emotions mainly include three core themes of anxiety, fear and powerlessness, which were characterized by dispersion. The optimization expectation of psychological crisis intervention mainly consisted of two core themes: professional expectation and collaborative expectation, both of which were the common expectation of the people involved. Conclusion School psychological crisis intervention should pay attention to the establishment of crisis early warning system and dialectic between confidentiality breaches and privacy protection. Schools should prevent the dispersion of negative emotions of participants, deepen professional construction and the coordination between home and school, and implement psychological crisis intervention from a comprehensive perspective.

OB JECTIVE To study the protective effects of saponins from Gleditsia sinensis on ischemic stroke with phlegm and blood stasis （ISPBS）model rats ，and to explore its mechanism. METHODS Totally 119 rats were randomly divided into normal group （normal saline ），sham operation group （normal saline ），model group （normal saline ），nimodipine group （positive control group ，5 mg/kg），G. sinensis saponin low-dose ，medium-dose and high-dose groups （3.21，6.42 and 12.84 mg/kg），with 17 rats in each group. Except for normal group ，other groups were all given high-fat diet+suture-occluded method to induce ISPBS model. The neurological function score ，water content of brain tissue ，pathological morphology of brain tissue ，the changes of hemorheology indexes （whole blood viscosity ， erythrocyte aggregation index ， Casson-viscosity）， four items of blood lipid [triacylglycerol （TG），total cholesterol （TC），low-density lipoprotein cholesterol （LDL-C），high-density lipoprotein cholesterol（HDL-C）] and inflammatory factors in serum and oxidative stress indexes [malondialdehyde （MDA），nitric oxide （NO），superoxide dismutase （SOD）] in brain tissue were determined or observed in rats. The protein expressions of B lymphocytoma 2（Bcl-2），Bcl-2 associated X protein （Bax）and caspase- 3 in cerebral tissue were also detected. RESULTS Compared with normal group ，the score of nerve function ，5 kinds of serum indexes （TC，TG，LDL-C，TNF-α，IL-1β）， hemorheology indexes ，the contents of MDA and NO and protein expressions of Bax and caspase- 3 in cerebral tissue were all increased significantly in model group （P＜0.01）. The levels of HDL-C and IL- 10 in serum ，SOD activity and protein expression of Bcl- 2 in cerebral tissue were decreased significantly （P＜0.01），and obvious lesions such as nuclear pyknosis and cell membrane fragmentation occurred in brain tissue. Compared with model group ，above indexes of administration groups were improved to different extents ，among which there was statistical significance in above indexes of G. sinensis saponin high-dose group （P＜ 0.01）. CONCLUSIONS Saponin from G. sinensis has a good protective effect on ISPBS model rats. Its mechanism may beassociated with reducing oxidative damage ， reducing the production of pro-inflammatory mediators and resisting neuronal apoptosis.

Objective To evaluate the value of high-frequency color ultrasound for different types of thyroid nodules during healthy examinations. Methods A total of 150 subjects with ultrasound diagnosis of thyroid nodule abnormality were enrolled. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of ultrasound diagnosis for differentiating benign and malignant thyroid nodules were evaluated with histopathological examinations of surgical thyroid specimens as a gold standard. Results A single thyroid nodule was found in all patients, and histopathological examinations identified 102 benign thyroid nodules and 48 malignant nodules. Microcalcification showed the highest accuracy for prediction of benign and malignant thyroid nodules (98.1%; χ² = 45.67, P = 0.001), followed by taller than wider shape of thyroid nodule (92.1%; χ² = 34.06, P = 0.001), central vascularity (82.0%; χ² = 13.29, P = 0.001), halo (76.0%; χ² = 6.15, P = 0.008) and hypoechogenicity (70.3%; χ² = 10.63, P = 0.001). In addition, ultrasound diagnosis showed a 100.0% sensitivity, a 94.1% specificity, a 88.9% positive predictive value, a 100.0% negative predictive value and a 96.0% accuracy for differentiation between benign and malignant thyroid nodules (χ² = 41.830, P < 0.001). Conclusion High-frequency color ultrasound has a high diagnostic accuracy for differentiating benign and malignant thyroid nodules, and microcalcification and taller than wider shape of thyroid nodule exhibit high values for predicting the malignancy of thyroid nodules.

Background: Thyroid diseases are highly prevalent worldwide, but their diagnosis remains a challenge. We established reference intervals (RIs) for thyroid-associated hormones and evaluated the prevalence of thyroid diseases in China. Methods: After excluding outliers based on the results of ultrasound screening, thyroid antibody tests, and the Tukey method, the medical records of 20,303 euthyroid adults, who visited the Department of Health Care at Peking Union Medical College Hospital from January 2014 to December 2018, were analyzed. Thyroid-associated hormones were measured by the Siemens Advia Centaur XP analyzer. The RIs for thyroid-associated hormones were calculated according to the CLSI C28-A3 guidelines, and were compared with the RIs provided by Siemens. The prevalence of thyroid diseases over the five years was evaluated and compared using the chi-square test. Results: The RIs for thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), total thyroxine (TT4), and total triiodothyronine (TT3) were 0.71–4.92 mIU/L, 12.2–20.1 pmol/L, 3.9–6.0 pmol/L, 65.6–135.1 nmol/L, and 1.2–2.2 nmol/L, respectively. The RIs of all hormones except TT4 differed significantly between males and females. The RIs of TSH increased with increasing age. The prevalence of overt hypothyroidism, overt hyperthyroidism, subclinical hypothyroidism, and subclinical hyperthyroidism was 0.5% and 0.8%, 0.2% and 0.6%, 3.8% and 6.1%, and 3.3% and 4.7% in males and females, respectively, which differed from those provided by Siemens. Conclusions Sex-specific RIs were established for thyroid-associated hormones, and the prevalence of thyroid diseases was determined in the Chinese population.

Objective:To investigate the risk factors of non-obstructive gastric retention before endoscopic retrograde cholangiopancreatography (ERCP) in patients with biliopancreatic disease.Methods:The matched case-control study included 109 patients with non-obstructive gastric retention before ERCP as the case group, and 218 patients without gastric retention as the control group. The patients′ medical records including comorbidities, preoperative medication and laboratory indicators were compared between the two groups. Multivariate conditional logistic regression models were subsequently used to determine the risk factors for non-obstructive gastric retention before ERCP.Results:Logistic regression revealed that the jaundice ( OR=12.359, P<0.001), opiates use ( OR=3.009, P=0.001), somatostatin use ( OR=2.445, P=0.033), fasting hyperglycemia ( OR=1.513, P=0.045), hypokalemia ( OR=4.634, P=0.001) and hyponatremia ( OR=1.805, P=0.023) were independent risk factors for non-obstructive gastric retention before ERCP in patients with biliopancreatic disease. Conclusion:Except for gastrointestinal obstruction, jaundice, opiates use, somatostatin use, fasting hyperglycemia, hypokalemia and hyponatremia are all risk factors for gastric retention in patients with biliopancreatic disease. Comprehensive evaluation and early intervention for patients showing these risk factors are needed.