1.Effects and mechanisms of oliceridine fumarate on postoperative cognitive dysfunction in elderly rats through TLR4/NF-κB pathway
Dong XIE ; Xiaoying GENG ; Yushan ZHU ; Zhengxiang LI ; Hengjie YUAN
China Pharmacy 2026;37(11):1434-1439
OBJECTIVE To investigate the effects and mechanisms of oliceridine fumarate (TRV130) in improving postoperative cognitive dysfunction (POCD) in elderly rats based on the Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway. METHODS Rats were randomly divided into the control group (normal saline), the model group (normal saline), the TRV130 group (2.8 mg/kg), the TLR4/NF-κB pathway inhibitor (TAK-242) group (3 mg/kg), the β -arrestin inhibitor (Barbadin) group (3 mg/kg), and the traditional opioid drug (morphine) group (2.8 mg/kg), with 15 rats in each group. Except for the control group, POCD models were established in all other groups. From the first day after surgery, drugs/normal saline were administered via caudal vein injection once daily for 3 consecutive days. After the last administration, the pathological damage of hippocampal tissue was observed; the cognitive function, serum inflammatory factor levels, hippocampal neurons apoptosis rate, and the expression of ionized calcium-binding adapter molecule 1 (Iba-1), glial fibrillary acidic protein (GFAP), and TLR4/NF-κB pathway-related mRNA and protein in hippocampal tissue were detected. RESULTS In the model group, the neurons in the CA1 region of the hippocampus were disordered and sparse, with decreased number, pyknotic and fragmented nuclei accompanied by inflammatory cell infiltration. Compared with the control group, the escape latency, serum levels of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and IL-1β, hippocampal neurons apoptosis rate, average fluorescence intensities of Iba-1 and GFAP, mRNA expression levels of TLR4 and NF-κB p65, and their protein expression/phosphorylation levels in hippocampal tissue were significantly increased/elevated in the model group ( P <0.05); the time spent in the target quadrant and the number of platform crossings were significantly shortened/decreased ( P <0.05). Compared with the model group, the cognitive function, pathological, inflammatory, and apoptosis-related indicators were significantly improved in the TRV130 group, TAK-242 group, and Barbadin group ( P <0.05); the mRNA expression levels of TLR4 and NF-κB p65 and their protein expression/phosphorylation levels were significantly decreased in the TRV130 group and TAK-242 group ( P <0.05). CONCLUSIONS TRV130 may improve POCD in elderly rats by inhibiting the TLR4/NF-κB pathway and alleviating postoperative central nervous system inflammatory responses.
2.The cumulative effects of lifestyle on different patterns of multimorbidity among children and adolescents aged 9-18 in Tianjin City
Zhonghui LIU ; Xianwei ZHANG ; Saisai ZHAO ; Ke XU ; Zhiying SUN ; Xinli SONG ; Yanhui DONG ; Yi SONG ; Yushan CUI
Chinese Journal of Preventive Medicine 2025;59(2):174-180
Objective:To understand the occurrence of different patterns of multimorbidity among children and adolescents aged 9-18 in Tianjin City and analyze the cumulative effects of lifestyle on these patterns of multimorbidity.Methods:From September to November 2022, a stratified cluster random sampling method was used to select students from primary schools, junior high schools, general high schools, and vocational schools in 16 districts of Tianjin to screen for height, weight, blood pressure, distant vision, and diopter. One year later, a follow-up measurement and questionnaire survey were conducted. The log-binomial model was used to analyze the strength of the association between lifestyle factors and different patterns of multimorbidity.Results:The age of 9 488 students was (12.37±2.49) years old, including 4 999 boys and 4 489 girls. The detection rates of three patterns of multimorbidity of overweight obesity and high blood pressure, overweight obesity and myopia, and overweight obesity with high blood pressure and myopia were 6.63%, 9.32%, and 4.21%, respectively. The detection rates of the three types of multimorbidity in boys were higher than those in girls (all P<0.001). The detection rate of overweight obesity and high blood pressure in suburban areas was higher than that in urban areas ( P=0.002). The detection rate of overweight obesity and myopia in suburban areas was lower than that in urban areas ( P=0.034). The detection rate of overweight obesity and myopia among those aged 9-12 years old was higher than other age groups (all P<0.001). The ARR (95% CI) for the association between favorable physical activity and the occurrence of overweight obesity and high blood pressure was 0.79 (0.68-0.92). The ARR (95% CI) for the association between favorable physical activity and the occurrence of overweight obesity with high blood pressure and myopia was 0.82 (0.67-0.99). Compared with children and adolescents with 0-2 favorable lifestyle factors, those with 4-5 favorable lifestyle factors had a lower risk of overweight obesity and high blood pressure ( ARR=0.84, 95% CI: 0.59-0.92). Conclusion:Boys aged 9-18 in Tianjin City are more prone to multimorbidity of overweight obesity and high blood pressure, overweight obesity and myopia, and overweight obesity with high blood pressure and myopia. Children and adolescents with 4-5 favorable lifestyle factors have a reduced risk of occurrence of overweight obesity and high blood pressure. Lifestyle has cumulative effects on multimorbidity of overweight obesity and high blood pressure.
3.The cumulative effects of lifestyle on different patterns of multimorbidity among children and adolescents aged 9-18 in Tianjin City
Zhonghui LIU ; Xianwei ZHANG ; Saisai ZHAO ; Ke XU ; Zhiying SUN ; Xinli SONG ; Yanhui DONG ; Yi SONG ; Yushan CUI
Chinese Journal of Preventive Medicine 2025;59(2):174-180
Objective:To understand the occurrence of different patterns of multimorbidity among children and adolescents aged 9-18 in Tianjin City and analyze the cumulative effects of lifestyle on these patterns of multimorbidity.Methods:From September to November 2022, a stratified cluster random sampling method was used to select students from primary schools, junior high schools, general high schools, and vocational schools in 16 districts of Tianjin to screen for height, weight, blood pressure, distant vision, and diopter. One year later, a follow-up measurement and questionnaire survey were conducted. The log-binomial model was used to analyze the strength of the association between lifestyle factors and different patterns of multimorbidity.Results:The age of 9 488 students was (12.37±2.49) years old, including 4 999 boys and 4 489 girls. The detection rates of three patterns of multimorbidity of overweight obesity and high blood pressure, overweight obesity and myopia, and overweight obesity with high blood pressure and myopia were 6.63%, 9.32%, and 4.21%, respectively. The detection rates of the three types of multimorbidity in boys were higher than those in girls (all P<0.001). The detection rate of overweight obesity and high blood pressure in suburban areas was higher than that in urban areas ( P=0.002). The detection rate of overweight obesity and myopia in suburban areas was lower than that in urban areas ( P=0.034). The detection rate of overweight obesity and myopia among those aged 9-12 years old was higher than other age groups (all P<0.001). The ARR (95% CI) for the association between favorable physical activity and the occurrence of overweight obesity and high blood pressure was 0.79 (0.68-0.92). The ARR (95% CI) for the association between favorable physical activity and the occurrence of overweight obesity with high blood pressure and myopia was 0.82 (0.67-0.99). Compared with children and adolescents with 0-2 favorable lifestyle factors, those with 4-5 favorable lifestyle factors had a lower risk of overweight obesity and high blood pressure ( ARR=0.84, 95% CI: 0.59-0.92). Conclusion:Boys aged 9-18 in Tianjin City are more prone to multimorbidity of overweight obesity and high blood pressure, overweight obesity and myopia, and overweight obesity with high blood pressure and myopia. Children and adolescents with 4-5 favorable lifestyle factors have a reduced risk of occurrence of overweight obesity and high blood pressure. Lifestyle has cumulative effects on multimorbidity of overweight obesity and high blood pressure.
4.Acute effects of exposure to PM 2.5 components on the lung function of primary school students
CHEN Lu, ZHANG Jingwei, YUAN Wen, DONG Yanhui, CUI Yushan
Chinese Journal of School Health 2024;45(7):1031-1035
Objective:
To analyze the acute effects of exposure to fine particulate matter (PM2.5) components on primary school students lung function, so as to provide a scientific basis for protecting childrens respiratory health.
Methods:
From 2019 to 2021, the study selected a total of 2 120 primary school students from grades 3 to 5 in Tianjin using a stratified random sampling method to undergo lung function tests. At the same time, the shortterm exposure levels were simulated by combining PM2.5 components and student addresses, and the acute impact of PM2.5 exposure on primary school students lung function was analyzed by generalized linear models (GLM) and weighted quantile sum (WQS) regression models.
Results:
The average daily concentration of PM2.5 in the air of Tianjin from 2019 to 2021 was 81.14 μg/m3, which was higher than the national standard. The results of lung function testing showed that there was no statistically significant difference in lung function measurement indicators such as forced vital capacity (FVC), forced expiratory volume at 1 second (FEV1), peak expiratory flow (PEF), 75% forced expiratory volume in 75 (FEF75), and 25% forced expiratory volume in 25 (FEF25) among primary school students in different regions of Tianjin (F=1.23, 0.87, 2.34, 1.56, 0.98, P>0.05). But the GLM analysis results showed that all components of PM2.5 in the air had adverse effects on the lung function indicators of primary school students. When the concentrations of fluorene (FLU) and pyrene (PYR) increased by 10 ng/m3, the FVC of primary school students decreased by 166.44 and 61.94 L respectively. The WQS regression model analysis results showed that the mixed exposure of PM2.5 components particularly significant damaging effects on lung function indicators in primary school students, especially the FLU and PYR components in polycyclic aromatic hydrocarbons, as well as the heavy metal lead.
Conclusions
Both single and mixed exposure to various PM2.5 components in the air have adverse effects on the lung function of primary school students. Among them, the influences of FLU and PYR in polycyclic aromatic hydrocarbons, as well as heavy metal Pb, are particularly significant.Potential pollution sources should be controlled to protect the respiratory health of primary school students by comprehensive prevention and control measures.
5.Peripheral blood cell count and characteristics of dyshaematopoiesis in patients with myelodysplastic syndrome
Yuan GAO ; Yushan LUO ; Kai TONG ; Tianjiao WANG ; Jing MA ; Runqing LI ; Jingxiao DONG
International Journal of Laboratory Medicine 2024;45(18):2201-2206
Objective To investigate peripheral blood cell count and characteristics of dyshaematopoiesis of peripheral blood and bone marrow cells in patients with myelodysplastic syndrome(MDS).Methods A total of 40 patients with MDS newly diagnosed in the hospital from January 2015 to December 2022 were selected as the experimental group,while 17 patients with megaloblastic anemia(MA group),11 patients with aplastic a-nemia(AA group),and 24 patients with autoimmune disease(AID group)were selected as the non-MDS group.Blood routine of patients in each group was detected by whole blood cell analyzer Sysmex XN20,and the white blood cell count(WBC),red blood cell count(RBC),hemoglobin(Hb),platelet count(PLT),mean red blood cell volume(MCV)and coefficient of variation of red blood cell distribution width(RDW-CV)of patients in 4 groups were compared and analyzed.Bone marrow and peripheral blood cell morphology in 4 groups were observed and recorded by artificial microscopy.The positive rate of common dyshaematopoiesis of peripheral in 4 groups was compared and analyzed.Results Compared with MA group,RBC and Hb in MDS group were significantly increased(P<0.05),while MCV was significantly decreased(P<0.05).Compared with AA group,WBC,MCV,RDW-CV and PLT in MDS group were significantly increased(P<0.05).Com-pared with AID group,WBC,RBC,Hb and PLT in MDS group were significantly decreased(P<0.05),while MCV and RDW-CV were significantly increased(P<0.05).The positive rate of peripheral blood primitive cells in MDS group was significantly higher than that in non-MDS group(P<0.05).Large red blood cells and polylobulated granulocyte were the main dysplasia types in the peripheral blood of MA group,and the positive rate of dyshematopoietic was significantly higher than that in MDS group(P<0.05).Compared with the non-MDS group,the positive rates of five types of dyshaematopoiesis in the MDS group were significantly higher than those in the control group(P<0.05),including increased blasts,decreased or absent cytoplasmic gran-ules,pseudo Pelger neutrophils,binucleated granulocytes and micromegakaryocytes.The positive rates of polylobulation and giant change in granulocytes,giant change,large red cells,basophilic stippling erythrocyte and H-J corpuscle in erythrocytes in MA group were significantly higher than those in MDS group(P<0.05).Dyshematopoiesis was absent or rare in the bone marrow smears of AA group and AID group.Conclu-sion Specific dyshaematopoiesis combined with peripheral blood cell count is helpful for the diagnosis and differential diagnosis of MDS,and reduces the possibility of misdiagnosis and missed diagnosis.
6.Effects of Shenfu yixin granule on mitochondrial autophagy of cardiomyocytes in rats with heart failure after acute yocardial infarction
Yaxuan CAO ; Rongfei ZHENG ; He WANG ; Yingjie CAO ; Wenjie DONG ; Lin CUI ; Bin LI ; Yushan CHEN ; Mingjun ZHU
China Pharmacy 2022;33(10):1183-1188
OBJECTIVE To study the effects of Shenfu yixin granule on mitochondrial autophagy of cardiomyocytes in rats with heart failure after acute myocardial infarction. METHODS The model of heart failure after acute myocardial infarction was established by ligaturing the anterior descending branch of the left coronary artery in rats. The model rats were divided into model group,Shenfu yixin granule low-dose and high-dose groups (1.76,8.8 g/kg),Fosinopril sodium tablets group (positive control ,4 mg/kg),sham operation group was set up (only threading without ligation at the same position ),with 8 rats in each group. After 4 weeks of drug intervention ,the hemodynamic indexes of rats in each group were measured by physiological recorder. The pathological changes of myocardial tissue were observed in each group. The level of oxidative stress in cardiomyocytes , mitochondrial membrane potential ,protein expression of PTEN-induced putative kinase 1(PINK1),E3 ubiquitin ligase Parkin and ubiquitin binding protein P 62 in myocardial tissue of rats in each group were detected. RESULTS Compared with sham operation group ,the pathological injuries such as myocardial fiber morphology disorder and inflammatory cell infiltration were serious. The left ventricular end systolic pressure (LVESP),maximum rate of rise of left ventricular internal pressure (+dp/dtmax), maximun rate of decrease of left ventricular internal pressure (-dp/dtmax),total antioxidant capacity ,mitochondrial membrane potential,PINK1,Parkin and P 62 protein expression were significantly decreased in model group (P<0.01). The left ventricular end diastolic pressure (LVEDP),the level of reactive oxygen species and the activity of reduced nicotinamide adenine dinucleotide phosphate in left ventricular ischemic cardiomyocytes were significantly increased (P<0.01). Compared with model group ,the pathological injuries of myocardial tissue in intervention groups were alleviated ,and above indexes were improved in varying degrees(P<0.01 or P<0.05). CONCLUSIONS Shenfu y ixin granule can reduce the level of oxidative stress and alleviate heart failure after acute myocardial infarction ,which may be related to the activation of Parkin-dependent pathway to strengthen mitochondrial autophagy and reduce mitochondrial dysfunction.
7.Reform and practice of precise teaching for experiment in medical laboratory technology
Shaozhuang LIU ; Chunyan GAO ; Weijun DONG ; Xinying ZHANG ; Tingting LI ; Xijuan ZHAO ; Songhe LIANG ; Yushan QI ; Minghui XU
Chinese Journal of Medical Education Research 2021;20(6):652-654
In order to train professionals in medical laboratory technology who are directly engaged in medical examination and medical laboratory work and who have strong practical ability and can adapt to the development of precision medicine, the reform of precise teaching for experiment is implemented. Through the precise stratification of experimental projects and knowledge points, the design of precise teaching activity and the construction of precise evaluation system for experiments, guided by precision medicine during the experimental process, the standardization and precision training of basic skills for students are strengthened in clinical laboratory test. The students can more well adapt to the needs of society for technical and innovative talent in the new period. The precise teaching for experiment will become one of the main characteristics of medical laboratory technology education in our school.
8.Stratified outcomes of "Kidney Disease: Improving Global Outcomes" serum creatinine criteria in critical ill patients: a secondary analysis of a multicenter prospective study
Guiying DONG ; Junping QIN ; Youzhong AN ; Yan KANG ; Xiangyou YU ; Mingyan ZHAO ; Xiaochun MA ; Yuhang AI ; Yuan XU ; Yushan WANG ; Chuanyun QIAN ; Dawei WU ; Renhua SUN ; Shusheng LI ; Zhenjie HU ; Xiangyuan CAO ; Fachun ZHOU ; Li JIANG ; Jiandong LIN ; Erzhen CHEN ; Tiehe QIN ; Zhenyang HE ; Lihua ZHOU ; Bin DU
Chinese Critical Care Medicine 2020;32(3):313-318
Objective:To investigate the different outcomes of two types of acute kidney injury (AKI) according to standard of Kidney Disease: Improving Global Outcomes-AKI (KDIGO-AKI), and to analyze the risk factors that affect the prognosis of intensive care unit (ICU) patients in China.Methods:A secondary analysis was performed on the database of a previous study conducted by China Critical Care Clinical Trial Group (CCCCTG), which was a multicenter prospective study involving 3 063 patients in 22 tertiary ICUs in 19 provinces and autonomous regions of China. The demographic data, scores reflecting severity of illness, laboratory findings, intervention during ICU stay were extracted. All patients were divided into pure AKI (PAKI) and acute on chronic kidney disease (AoCKD). PAKI was defined as meeting the serum creatinine (SCr) standard of KDIGO-AKI (KDIGO-AKI SCr) and the estimated glomerular filtration rate (eGFR) at baseline was ≥ 60 mL·min -1·1.73 m -2, and AoCKD was defined as meeting the KDIGO-AKI SCr standard and baseline eGFR was 15-59 mL·min -1·1.73 m -2. All-cause mortality in ICU within 28 days was the primary outcome, while the length of ICU stay and renal replacement therapy (RRT) were the secondary outcome. The differences in baseline data and outcomes between the two groups were compared. The cumulative survival rate of ICU within 28 days was analyzed by Kaplan-Meier survival curve, and the risk factors of ICU death within 28 days were screened by Cox multivariate analysis. Results:Of the 3 063 patients, 1 042 were enrolled, 345 with AKI, 697 without AKI. The AKI incidence was 33.11%, while ICU mortality within 28 days of AKI patients was 13.91% (48/345). Compared with PAKI patients ( n = 322), AoCKD patients ( n = 23) were older [years old: 74 (59, 77) vs. 58 (41, 72)] and more critical when entering ICU [acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score: 23 (19, 27) vs. 15 (11, 22)], had worse basic renal function [eGFR (mL·min -1·1.73 m -2): 49 (38, 54) vs. 115 (94, 136)], more basic complications [Charlson comorbidity index (CCI): 3 (2, 4) vs. 0 (0, 1)] and higher SCr during ICU stay [peak SCr for diagnosis of AKI (μmol/L): 412 (280, 515) vs. 176 (124, 340), all P < 0.01]. The mortality and RRT incidence within 28 days in ICU of AoCKD patients were significantly higher than those of PAKI patients [39.13% (9/23) vs. 12.11% (39/322), 26.09% (6/23) vs. 4.04% (13/322), both P < 0.01], while no significant difference was found in the length of ICU stay. Kaplan-Meier survival curve analysis showed that the 28-day cumulative survival rate in ICU in AoCKD patients was significantly lower than PAKI patients (Log-Rank: χ2 = 5.939, P = 0.015). Multivariate Cox regression analysis showed that admission to ICU due to respiratory failure [hazard ratio ( HR) = 4.458, 95% confidence interval (95% CI) was 1.141-17.413, P = 0.032], vasoactive agents treatment in ICU ( HR = 5.181, 95% CI was 2.033-13.199, P = 0.001), and AoCKD ( HR = 5.377, 95% CI was 1.303-22.186, P = 0.020) were independent risk factors for ICU death within 28 days. Conclusion:Further detailed classification (PAKI, AoCKD) based on KDIGO-AKI SCr standard combined with eGFR is related to ICU mortality in critical patients within 28 days.
9.Effects of Optimized Formulas of Radix Astragali and Radix Angelicae Sinensis Extracts on Survival Status of Idiopathic Pulmonary Fibrosis Mice and on Expression of Cytogenesis-related Factors in Lung Tissues
Qingxia GENG ; Hongzhao ZHAO ; Chenzhong ZONG ; Lina LI ; Shuyan WANG ; Yushan GAO ; Ruijuan DONG
Journal of Guangzhou University of Traditional Chinese Medicine 2017;34(3):408-412
Objective To observe the effect of the optimized formulas of extracts of Radix Astragali and Radix Angelicae Sinensis on the survival status of the idiopathic pulmonary fibrosis (IPF) mice,and on the expression levels of transforming growth factor-β (TGF-β) and vascular endothelial growth factor(VEGF),so as to optimize the therapeutic regimen and to explore the therapeutic mechanism.Methods One hundred and five SPF ICR male mice were randomly divided into normal group,model group and 5 Chinese medicine treatment groups (group 1,2,3,4,5 of the optimized formula of Radix Astragali and Radix Angelicae Sinensis extracts).The mice in the model group and the 5 treatment groups were intratracheally injected with bleomycin (5 mg/kg) to induce the pulmonary fibrosis model.On day 21,the lung tissues were taken out for the test.Hydroxyproline content was detected by alkaline hydrolysis method,and morphological changes of lung tissues were observed by hematoxylineosin (HE) staining and Mallory's staining methods.The expression levels of TGF-β and VEGF were detected by polymerase chain reaction (PCR).Results The HE staining and Mallory's staining results showed that the pulmonary fibrosis in the 5 treatment groups was relieved as compared with that in the model group,especially in the group 1,and the alveolar structure recovered better.The 21-day overall death rate in the treatment groups were lower than those in the model group,and group 1 and group 5 had the lowest rates,the difference being statistically significant (P< 0.05).Compared with the model group,the content of hydroxyproline in the lung tissues of the treatment groups were decreased to some degrees,and there was significant difference (P < 0.05 or P < 0.01).The expression levels of TGF-β and VEGF in model group were higher than those in normal group,but were deceased in the treatment groups to some degrees,except TGF-β expression in group 5,and the difference was significant(P < 0.05 or P < 0.01).Conclusion When the contents of Radix Astragali water-extract and Radix Angelicae Sinensis alcohol-extract were predominated,the extract formula exerts certain effects on decreasing hydroxyproline content in the lung tissues,inhibiting the expression levels of TGF-β and VEGF,and relieving the degree of pulmonary fibrosis in IPF mice.
10.Effects of Shizidaiping formula on MIN6 cell apoptosis and expressions of MEK1/2 and ERK1/2
Ruiting CHENG ; Yushan DONG ; Jian LI ; Xiaojin LA ; Chunyu TIAN ; Xiujuan GAO ; Xuemei ZHOU ; Qianru FU ; Bo WU ; Siqi DONG
Chinese Journal of Tissue Engineering Research 2017;21(4):603-608
BACKGROUND:Apoptosis of islet cel s is closely related to the long-term hyperglycemia-and hyperlipemia-induced injuries. OBJECTIVE:To observe the effect of Shizidaiping formula on the apoptosis and insulin secretion in MIN6 cel s under the high glucose and lipid environment, and to explore the protective effect of Shizidaiping formula and the related apoptosis mechanism. METHODS:MIN6 cel s were divided into normal, model, melbine, low-, medium-and high-dose Shizidaiping formula groups. The cel activity was examined by cel counting kit-8, the insulin secretion was measured by ELISA, the rate of apoptosis was measured by Annexin V-FITC&PI and the expression levels of MEK1/2, ERK1/2 and p-ERK1/2 were examined by western blot assay. RESULTS AND CONCLUSION:Shizidaiping formula significantly improved MIN6 cel activity under high glucose and lipid condition (P<0.05), decreased early cel apoptosis, increased the level of insulin stimulated by low glucose in cel supernatant (P<0.05), and improved the expression levels of MEK1/2, ERK1/2 and p-ERK1/2 (P<0.05). These results suggest that Shizidaiping formula can protect islet cel s from hyperglycemia and hyperlipemia damage by improving the activity of MIN6 cel s, reducing the insulin secretion and inhibiting the apoptosis of pancreaticβcel s in MIN6 cel s.


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