1.Baihe Wuyaotang Ameliorates NAFLD by Enhancing mTOR-mediated Liver Autophagy
Rui WANG ; Tiantian BAN ; Lihui XUE ; Xinyi FENG ; Jiyuan GUO ; Jiaqi LI ; Shenghe JIANG ; Xiaolei HAN ; Baofeng HU ; Wenli ZHANG ; Naijun WU ; Shuang LI ; Yajuan QI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(7):66-77
ObjectiveTo investigate the therapeutic effect of Baihe Wuyaotang (BWT) on non-alcoholic fatty liver disease (NAFLD) and elucidate its underlying mechanism. MethodC57BL/6J mice were randomly assigned to six groups: normal control, model, positive drug (pioglitazone hydrochloride 1.95×10-3 g·kg-1), and low-, medium-, and high-dose BWT (1.3,2.5 and 5.1 g·kg-1). Following a 12-week high-fat diet (HFD) inducement, the mice underwent six weeks of therapeutic intervention with twice-daily drug administration. Body weight was monitored weekly throughout the treatment period. At the fifth week, glucose tolerance (GTT) and insulin tolerance (ITT) tests were conducted. Subsequently, the mice were euthanized for the collection of liver tissue and serum, and the subcutaneous adipose tissue (iWAT) and epididymal adipose tissue (eWAT) were weighed. Serum levels of total triglycerides (TG) and liver function indicators,such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), were determined. Histological examinations, including oil red O staining, hematoxylin-eosin (HE) staining, Masson staining, and transmission electron microscopy, were performed to evaluate hepatic lipid deposition, pathological morphology, and ultrastructural changes, respectively. Meanwhile, Western blot and real-time quantitative polymerase chain reaction (Real-time PCR) were employed to analyze alterations, at both gene and protein levels, the insulin signaling pathway molecules, including insulin receptor substrate 1/2/protein kinase B/forkhead box gene O1 (IRS1/2/Akt/FoxO1), glycogen synthesis enzymes phosphoenolpyruvate carboxy kinase (Pepck) and glucose-6-phosphatase (G6Pase), lipid metabolism-related genes stearoyl-coA desaturase-1 (SCD-1) and carnitine palmitoyltransferase-1 (CPT-1), fibrosis-associated molecules α-smooth muscle actin (α-SMA), type Ⅰ collagen (CollagenⅠ), and the fibrosis canonical signaling pathway transforming growth factor-β1/drosophila mothers against decapentaplegic protein2/3(TGF-β1/p-Smad/Smad2/3), inflammatory factors such as interleukin(IL)-6, IL-8, IL-11, and IL-1β, autophagy markers LC3B Ⅱ/Ⅰ and p62/SQSTM1, and the expression of mammalian target of rapamycin (mTOR). ResultCompared with the model group, BWT reduced the body weight and liver weight of NAFLD mice(P<0.05, P<0.01), inhibited liver lipid accumulation, and reduced the weight of white fat: it reduced the weight of eWAT and iWAT(P<0.05, P<0.01) as well as the serum TG content(P<0.05, P<0.01). BWT improved the liver function as reflected by the reduced ALT and AST content(P<0.05, P<0.01). It improved liver insulin resistance by upregulating IRS2, p-Akt/Akt, p-FoxO1/FoxO1 expressions(P<0.05). Besides, it improved glucose and lipid metabolism disorders: it reduced fasting blood glucose and postprandial blood glucose(P<0.05, P<0.01), improved GTT and ITT(P<0.05, P<0.01), reduced the expression of Pepck, G6Pase, and SCD-1(P<0.01), and increased the expression of CPT-1(P<0.01). The expressions of α-SMA, Collagen1, and TGF-β1 proteins were down-regulated(P<0.05, P<0.01), while the expression of p-Smad/Smad2/3 was downregulated(P<0.05), suggesting BWT reduced liver fibrosis. BWT inhibited inflammation-related factors as it reduced the gene expression of IL-6, IL-8, IL-11 and IL-1β(P<0.01) and it enhanced autophagy by upregulating LC3B Ⅱ/Ⅰ expression(P<0.05)while downregulating the expression of p62/SQSTM1 and mTOR(P<0.05). ConclusionBWT ameliorates NAFLD by multifaceted improvements, including improving IR and glucose and lipid metabolism, anti-inflammation, anti-fibrosis, and enhancing autophagy. In particular, BWT may enhance liver autophagy by inhibiting the mTOR-mediated signaling pathway.
2.Advances on reprogramming of fatty acid metabolism in pulmonary fibrosis
Lu BAI ; Jiaxin WANG ; Xue WANG ; Wei ZENG ; Meiyue SONG ; Tiantian ZHANG ; Jing WANG
Basic & Clinical Medicine 2024;44(4):548-552
Pulmonary fibrosis is a progressive interstitial fibrotic lung disease with high mortality.Its pathogenesis is complex and involves the reprogramming of fatty acid metabolism.This reprogramming includes changes in de novo fatty acid synthesis,uptake,oxidation,and derivatives.It crucially influences alveolar epithelial cell survival,macrophage polarization,and fibroblast activation,thereby playing a significant role in either exacerbating or miti-gating the disease.Understanding and intervening in the reprogramming of fatty acid metabolism offers potential strategies for prevention,diagnosing and treatment of pulmonary fibrosis.
3.Clinical and CT findings of 25 patients with bronchiolar adenoma
Minghui ZHANG ; Minghua SUI ; Tiantian QIU ; Xue SUN ; Xiao TAN ; Dailun HOU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(08):1127-1132
Objective To study the clinical and CT findings of bronchiolar adenoma. Methods Patients diagnosed with bronchiolar adenoma confirmed by surgical pathology at Linyi People's Hospital and Yantai Yuhuangding Hospital from 2016 to 2021 were collected. Their clinical and CT imaging features were retrospectively analyzed. Results Finally, 25 patients were collected, including 6 males and 19 females, aged 32-73 (58.6±10.1) years. The immunohistochemical Ki-67 (MIB1) of all lesions was <5%. The lesions were located in the upper and middle lobe of both lungs in 9 patients, lower lobes in 16 patients, extrapulmonary zone in 22 patients, intrapulmonary middle zone in 3 patients, round in 11 patients, irregular in 14 patients, well-defined in 22 patients, pure ground-glass/mixed ground-glass nodules in 6 patients, solid nodules in 19 patients. There were 11 patients with central small cavity, 18 patients with single bronchioles sign, 19 patients without adhesion with adjacent pleura, and 24 patients without mediastinal lymph node enlargement. Conclusion Bronchiolar adenomas usually occur in the middle-aged and elderly, mostly in the lower lobe of both lungs and the distribution of the peripheral lung field, most of the patients do not have any clinical symptoms, and the postoperative prognosis is good. CT may show large nodules or masses, pure ground-glass/mixed ground-glass nodules, irregular solid nodules and central small cavities. Irregular stellate nodules, central small cavity shadow, and single bronchiolar vascular bundle connected with the lesions are relatively specific imaging findings of bronchiolar adenoma.
4.Association between Triglyceride-Glucose Index and Major Adverse Cardiovascular Events Risk in Coronary Heart Disease Patients with Blood Stasis Syndrome after Percutaneous Coronary Intervention
Shiyi TAO ; Lintong YU ; Jun LI ; Li HUANG ; Zicong XIE ; Deshuang YANG ; Tiantian XUE ; Yuqing TAN
Journal of Traditional Chinese Medicine 2024;65(17):1784-1793
ObjectiveTo explore the association between triglyceride-glucose (TyG) index and major adverse cardiovascular events (MACEs) risk in coronary heart disease (CHD) patients with blood stasis syndrome after percutaneous coronary intervention (PCI). MethodsA total of 857 CHD patients with blood stasis syndrome after PCI were enrolled and divided into four groups according to the baseline TyG index quartiles, Q1 (TyG < 8.51), Q2 (8.51 ≤ TyG < 8.88), Q3 (8.88 ≤ TyG < 9.22), and Q4 (TyG ≥ 9.22). The clinical outcome was defined as a compound endpoint of cardiovascular events including cardiac death, non-fatal myocardial infarction, unplanned revascularization, in-stent restenosis and stroke. The machine learning Boruta algorithm was used for feature selection related to MACEs risk. Kaplan-Meier survival analysis and Cox proportional hazards regression model were used to compare the differences in MACEs risk among the four groups. Restricted cubic spline (RCS) and subgroup analysis were performed to determine the relationship between the TyG index and MACEs risk. The area under the receiver operating characteristic (ROC) curve (AUC), calibration curve and Hosmer-Lemeshow test, and decision curve analysis (DCA) were plotted to evaluate the predictive value of the TyG index for MACEs risk. ResultsThe median follow-up time of the included patients was 2.45 years. During the follow-up period, 313 cases (36.52%) of new MACEs occurred. The incidence of MACEs in Q1, Q2, Q3, Q4 group was 28.17% (60/213), 29.05% (61/210), 39.45% (86/218) and 49.07% (106/216), respectively. Kaplan-Meier survival analysis suggested statistically significant differences in MACEs risk among the four groups (P<0.001). Cox proportional hazards regression model analysis found that the risk of MACEs in patients with high TyG index increased by 60.1% (P<0.01). Using Q1 as the reference, the MACEs risk in Q2, Q3 and Q4 groups gradually increased, and the trend was statistically significant (P<0.05). RCS model suggested that the TyG index was nonlinearly associated with the MACEs risk (P<0.001). The TyG index had a good predictive performance for MACEs risk according to ROC analysis (AUC=0.758, 0.724-0.792) and Hosmer-Lemeshow test (χ2 = 4.319, P = 0.827). Additionally, DCA analysis also suggested a good clinical efficacy of the TyG index for predicting MACEs. Subgroup analysis showed that different baseline TyG index was positively correlated with the MACEs risk in the stratification of age, male, BMI, history of diabetes and hypertension, and low-density lipoprotein cholesterol (LDL-C)≥1.8 mmol
5.Epidemiological characteristics and risk factors of brucellosis in Yan'an City from 2019 to 2023
Xiaoyan ZHANG ; Yun CAO ; Yao ZHANG ; Le XUE ; Xiaoqin YAN ; Tiantian XIN
Chinese Journal of Endemiology 2024;43(11):912-915
Objective:To analyze the epidemiological characteristics and risk factors of brucellosis in Yan'an City, and to provide a theoretical basis for scientifically formulating prevention and control measures for brucellosis.Methods:A descriptive analysis method was used to analyze the general information, epidemiological characteristics of confirmed brucellosis cases at General Hospital of Yan'an Second Medical Group from 2019 to 2023. Univariate and multivariate logistic regression models were used to analyze the risk factors for brucellosis infection in the population.Results:From 2019 to 2023, a total of 301 cases of brucellosis were confirmed, and the number of cases in each year was 1, 7, 85, 85 and 123 cases, respectively. There were 231 males and 70 females, with a gender ratio of 3.3 ∶ 1.0. The patients were mainly aged between 15 and 64 years old (88.70%, 267/301), with a higher incidence in summer and autumn (36.55%, 110/301; 30.23%, 91/301). The occupation was dominated by farmers (62.98%, 182/289). The area with the highest number of cases was Ansai District (20.67%, 62/300), followed by Baota District (19.33%, 58/300) and Zhidan County (17.67%, 53/300). The results of multivariate logistic analysis showed that contact with livestock and unprotected contact were risk factors for brucellosis infection ( OR = 2.81, 6.75, 95% CI: 1.14 - 5.98, 1.23 - 15.72, P < 0.05). Conclusions:From 2019 to 2023, the number of brucellosis cases in Yan'an has been increasing year by year, with a higher incidence among young and middle-aged people. Summer and autumn are the high incidence seasons for the disease, and Ansai District, Baota District, and Zhidan County are key areas for brucellosis prevention and control in Yan'an City. Failure to take protective measures when in contact with livestock can increase the probability of brucellosis infection.
6.Effectiveness of O-AMAS teaching model in clinical teaching of blood purification training nurses
Yajuan JIA ; Yan WANG ; Tiantian XU ; Xiaoling XUE ; Xiaohong YUE
Chinese Journal of Modern Nursing 2024;30(25):3491-3495
Objective:To explore the effectiveness of the O-AMAS teaching model in clinical teaching for blood purification training nurses.Methods:Convenience sampling was used to select 187 training nurses from the Blood Purification Center of the First Affiliated Hospital of Zhengzhou University from January 2021 to December 2022 as research subjects. Eighty training nurses enrolled from January to December 2021 were selected as the control group, and 107 training nurses enrolled from January to December 2022 were selected as the experimental group. After three months of intervention, the training nurses' theoretical scores, operational skills assessment scores, and satisfaction were compared between the two groups.Results:The theoretical and operational skills assessment scores of the experimental group were higher than those of the control group ( P<0.05). The satisfaction of the experimental group with the teaching model, teaching effectiveness, completion of theoretical training, guidance on operational skills, and overall teaching was higher than that of the control group ( P<0.05) . Conclusions:The O-AMAS teaching model for clinical teaching can help improve the training effectiveness and satisfaction of blood purification training nurses.
7.Research progress on the role of oxidative stress in cardiovascular disease in zebrafish
Tiantian FEI ; Tengyun LIANG ; Panxia CAO ; Xue MENG ; Hong WU
Chinese Journal of Comparative Medicine 2024;34(9):172-178
Cardiovascular disease presents a serious threat to human life,and oxidative stress has been identified as an important factor affecting the occurrence and development of cardiovascular disease.The construction of reliable animal models of oxidative stress is important for the in-depth study of the pathogenesis of cardiovascular diseases and the development of therapeutic drugs.Zebrafish have often been for research into cardiovascular diseases,due to their advantages of easy reproduction,a short developmental cycle,transparent embryos for easy observation,and a highly homologous cardiovascular genetic background with humans.In this paper,we review the application of the zebrafish oxidative stress model in cardiovascular disease and related research progress,to provide a reference for its further application in cardiovascular disease-related research.
8.Beam trajectory correction and dose distribution in the presence of fringe fields in magnetic resonance imaging-guided proton therapy
Guodong LI ; Ming WANG ; Jingshuo XUE ; Lang DONG ; Tiantian SUN ; Wei DAI ; Lei ZHANG
Chinese Journal of Medical Physics 2024;41(6):661-666
Objective To explore the correction of beam trajectories in the presence of fringe fields in magnetic resonance imaging-guided proton therapy and dose changes in the body before and after correction.Methods The open-source treatment planning software matRad was used to design plans for brain tumor,liver tumor,and prostate cancer cases,and simulation studies were conducted in the Monte Carlo simulation toolkit TOPAS to calculate proton dose distribution.A proton beam trajectory correction model suitable for three-dimensional magnetic fields was established,and a beam trajectory correction algorithm was developed.The deflection of the proton Bragg peak in the presence of fringe fields was analyzed.Furthermore,3 treatment plans were simulated and dose correction was carried out when the fringe field existed.Gamma analysis method is used to evaluate the correction effect;and the dose changes in the target area and organs-at-risk after correction were quantitatively analyzed.Results The perturbation of the magnetic field would cause lateral deflection of the proton beam trajectory,and the presence of fringe fields would significantly increase this effect,which increased with the increasing of beam energy.When the fringe field existed,the treatment plans for brain tumor,liver tumor,and prostate cancer were corrected.Under the 3%/3 mm criterion,the gamma passing rates for target area were 94.844%,92.054%,and 97.863%,respectively,and after correction,the total dose in the body was increased by 2.8%,2.5%,and 1.5%,respectively.The increased dose was mainly contributed by incident protons.Conclusion In magnetic resonance imaging-guided proton therapy,the effects of fringe fields should be considered.The increase in incident proton beam energy after correction will lead to an increase in the total dose in the body.Since the beam trajectory still has curvature,the dose changes differently in different organs-at-risk.
9.Inhibitory effect of methylene blue mediated photodynamic therapy combined with berberine on Porphyromonas gingivalis in vitro
Tiantian LI ; Shiwen YAN ; He JIANG ; Mengwen WANG ; Wenting PAN ; Peng XUE
International Journal of Biomedical Engineering 2023;46(1):23-29
Objective:To investigate the in vitro inhibitory effect of methylene blue mediated photodynamic therapy (PDT) combined with berberine on Porphyromonas gingivalis (P.g). Methods:P.g was cultured until the middle to late log phase, and methylene blue was added to P.g suspension at different mass concentrations for 5 min, and a laser (wavelength 660 nm, power 140 mW/cm 2) was irradiated for 2 min to find the optimal concentration of methylene blue combined with the laser for in vitro inhibition of P.g. The effect of methylene blue mediated PDT on the in vitro inhibition of P.g and the effect of berberine on the growth curve of P.g were observed. The inhibitory effect of methylene blue mediated PDT and berberine on P.g was investigated by successive combined applications. The effect of methylene blue mediated PDT on P.g morphology was observed by scanning electron microscopy. The absorption peaks of each component were measured by ultraviolet spectrophotometer. Results:The best inhibition was achieved at a methylene blue mass concentration of 24.414 1 μg/ml under 660 nm laser excitation. The differences were statistically significant in both the methylene blue and PDT groups compared with the control group (all P<0.001). 0.05 mg/ml berberine had an inhibitory effect on the planktonic bacteria of P.g. After P.g was treated with methylene blue mediated PDT, the bacterial cell walls were crumpled into clusters. Compared with the control group, the number of colonies was reduced in the 0.05 mg/ml berberine group, and the difference was statistically significant ( P<0.01). The difference between the 0.05 mg/ml berberine + light group and the control group was not statistically significant ( P>0.05). When PDT was combined with berberine, there was a synergistic inhibitory effect on P.g. PDT followed by berberine shows a better inhibitory effect on bacteria, and the differences were statistically significant (all P<0.01). After the berberine treatment, the bacterial surface became smooth, and the length of the bacterial body increased compared with the control group. Conclusions:Methylene blue mediated PDT has an inhibitory effect on P.g. When combined with berberine, it has a synergistic inhibitory effect on P.g., and the inhibition effect is better when PDT is applied first and then berberine is applied in combination.
10.Prognostic value of systemic immune-inflammation index in patients with hepatitis B virus-related acute-on-chronic liver failure
Hong XUE ; Tiantian LIU ; Jianming ZHENG ; Wenhong ZHANG
Chinese Journal of Infectious Diseases 2023;41(1):89-94
Objective:To investigate the prognostic value of systemic immune-inflammation index (SII) in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF).Methods:The clinical data, including age, gender, complications, laboratory examination results post-admission, SII, model for end-stage liver disease (MELD) score, MELD-Na score, Child-Turcotte Pugh (CTP) score of HBV-ACLF patients treated in Huashan Hospital, Fudan University from January 2016 to August 2021 were retrospectively analyzed. The patients were divided into survival group and death group according to the outcome at 90 days of follow-up.Paired sample t test, Mann-Whitney U test and chi-square test were used for statistical analysis.Pearson correlation was used to analyze the correlation between SII and the prognosis prediction model of HBV-ACLF. The area under the curve (AUC) was used to analyze the clinical efficacies of SII, MELD score, MELD-Na score and CTP score in predicting the prognosis of HBV-ACLF patients, and the optimal cut-off value of SII for predicting the prognosis of HBV-ACLF was calculated. Kaplan-Meier method was used for survival analysis. Results:A total of 140 patients with HBV-ACLF were included. There were 88 patients in the survival group, including 65 males and 23 females, with the age of (47.69±11.96) years. There were 52 cases in the death group, including 40 males and 12 females, with the age of (52.73±12.22) years. The age, aspartate aminotransferase, total bilirubin, serum creatinine, international normalized ratio, neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, SII, MELD score, MELD-Na score, CTP score and the incidence of infection in the death group were all significantly higher than those in the survival group, and albumin, lymphocyte count, platelet count, prognostic nutritional index in the death group were all significantly lower than those in the survival group, and the differences were all statistically significant ( t=-2.39, Z=-2.84, t=-4.81, Z=-2.15, Z=-4.91, Z=-3.47, Z=-3.36, Z=-3.83, Z=-4.69, Z=-4.56, Z=-6.31, χ2=24.96, t=3.06, t=3.03, Z=-7.57 and t=4.12, respectively, all P<0.05). Pearson correlation analysis showed that SII was positively correlated with CTP score ( r=0.272 7, P=0.001), MELD score ( r=0.365 8, P<0.001) and MELD-Na score ( r=0.381 1, P<0.001). The AUC of SII was the largest of 0.80, and 0.76 for MELD score, 0.74 for MELD-Na score and 0.73 for CTP score. The optimal cut-off value of SII was 447.49. Kaplan-Meier analysis showed that the 90 days survival rate of patients with SII≥447.49(38.60%(22/57)) was lower than that of SII<447.49 group (79.52%(66/83)), and the difference between the two groups was significant ( χ2=23.80, P<0.001). Conclusions:SII can be used to assess the severity and prognosis of HBV-ACLF patients. SII ≥447.49 indicates poor prognosis.

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