1.Inhibition of Toll-Like Receptor 4 Signaling Pathway Accelerates the Repair of Avascular Necrosis of Femoral Epiphysis through Regulating Macrophage Polarization in Perthes Disease
Ronghui YU ; Cong MA ; Guoyong LI ; Jianyun XU ; Dan FENG ; Xia LAN
Tissue Engineering and Regenerative Medicine 2023;20(3):489-501
BACKGROUND:
Legg-Calvé-Perthes disease (LCPD) is still a refractory disease in children’s orthopedics. With the introduction of the concept of ‘‘osteoimmunology’’, the immune-inflammatory mechanisms between bone and immune system have become a research focus of LCPD. However, few studies have reported on the pathological role of inflammation-related receptors such as toll-like receptors (TLRs) as well as immune cells such as macrophages in LCPD. This study was for investigating the mechanism of TLR4 signaling pathway on the direction of macrophage polarization and the repair of avascular necrosis of femoral epiphysis in LCPD.
METHODS:
With GSE57614 and GSE74089, differentially expressed genes were screened. Through enrichment analysis and protein–protein interaction network, the functions of TLR4 were explored. Furthermore, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), hematoxylin & eosin (H&E) staining, micro-CT, tartrate-resistant acid phosphatase (TRAP) dyeing and western blotting were performed for determining the influences of TAK-242 (a TLR4 inhibitor) on the repair of avascular necrosis of femoral epiphysis in rat models.
RESULTS:
Totally 40 co-expression genes were screened as well as enriched in TLR4 signaling pathway. Immunohistochemistry and ELISA analyses certified that TLR4 facilitated macrophage polarization toward the M1 phenotype and prevented macrophage polarization toward the M2 phenotype. Besides, the results of H&E and TRAP staining, micro-CT, and western blotting showed that TAK-242 can inhibit osteoclastogenesis and promote osteogenesis.
CONCLUSION
Inhibition of TLR4 signaling pathway accelerated the repair of avascular necrosis of femoral epiphysis by regulating macrophage polarization in LCPD.
2.Peripheral blood stem cells collection in pediatric patients with thalassemia major weighing 20 kilogram or less
Jianyun WEN ; Libai CHEN ; Jing DU ; Xiaoxiao XU ; Yuelin HE ; Yongsheng RUAN ; Xiu LI ; Juan LI ; Xuedong WU
Chinese Journal of Blood Transfusion 2023;36(6):500-504
【Objective】 To evaluate the safety and efficacy of the collection of peripheral blood stem cells (PBSCs) in pediatric patients with thalassemia major (TM) weighing 20 kg or less. 【Methods】 PBSCs collection data of 170 pediatric patients with TM weighing 20 kg or less from January 2013 to December 2020 in our center were reviewed. Safety was assessed by the occurrence of adverse events during apheresis procedures, and efficacy was evaluated by the number of CD34+ cells collected. 【Results】 A total of 171 PBSCs procedures were performed on 170 patients with TM weighing 20 kg or less, with a median age of (4.98±1.53) years and a median weight of (17.30±2.18) kg. The probability of collecting at least 1×106 CD34+ cells/kg during a single course of apheresis was 99.41% (169/170), with a median (5.88±4.23) ×106 CD34+ cells collected per kg of weight of the recipient. A minimum pre-apheresis hemoglobin (Hb) of 60 g/L in patients with TM weighing 20 kg or less was safe and feasible. The most common adverse event of G-CSF mobilization in TM patients is bone pain, with the incidence of 7.65% (13/170), which was higher than that of healthy children donors in our center. The most common adverse events during the collection were pain at the puncture site of the femoral vein (6.47%, 11/170) and low pressure of the fluid (2.92%, 5/170). And no serious complications related to PBSCs mobilization, central venous catheter(CVC)placement or the apheresis procedure occurred. 【Conclusion】 PBSCs collection by COM.TEC blood cell separator in children weighing 20 kg or less is safe and efficacious.
3.The epidemic situation and influencing factors of plague in the foci of Meriones unguiculatus in Inner Mongolia Plateau
Xiaolei ZHOU ; Xinru WAN ; Jianyun LI ; Dong YAN ; Kuidong SHAO ; Zhongbing ZHANG ; Zhibin ZHANG ; Guoyi DU ; Cheng JU ; Cheng XU
Chinese Journal of Endemiology 2022;41(9):695-702
Objective:To analyze the epidemic situation of plague among animals in the foci of Meriones unguiculatus in Inner Mongolia Plateau, and to find out key influencing factors affecting the epidemic of the plague, and to provide theoretical basis for the prediction, early warning and risk assessment of the plague. Methods:The monitoring data including gerbils density, gerbils body flea index, plague epidemic intensity, etc., as well as environmental data including temperature, precipitation and El Ni?o activity (Southern Oscillation Index, SOI) from 19 banners (counties, cities and districts) in Ulanqab Plateau area, the foci of Meriones unguiculatus in Inner Mongolia Plateau were selected. The methods of correlation analysis, structural equation model and rank correlation were used to analyze the epidemic and key influencing factors of plague among animals in the foci. Results:The plague epidemic cycle in the foci of Meriones unguiculatus in Inner Mongolia Plateau was 5 to 10 years. The correlation analysis results showed that all the factors had influence on each other. Structural equation model screened out that the main influencing factors of plague epidemic were SOI, gerbils density and temperature. SOI had a negative effect on plague epidemic intensity (-0.022) and temperature (-0.029), while gerbils density had a positive effect on plague epidemic intensity (0.014), and temperature had a negative effect on plague epidemic intensity (-0.065). In rank correlation, when the gerbils density was at a high value, the probability of high plague epidemic intensity in that year was 4/9; when SOI was at a low value, the probability was 5/9; when the temperature was at a low value, the probability was 5/9. When the plague epidemic intensity was at a high value in that year, the probability of the plague epidemic intensity being high in the following year was 5/8; when the gerbils density was at a high value in that year, the probability was 4/9; when SOI was at a low value in that year, the probability was 4/9. Conclusion:Climate and biological factors can affect prevalence of plague, and countermeasures should be taken in advance to prevent plague outbreaks when El Ni?o phenomenon, low temperature, high density of gerbils, and high previous-year prevalence of plague appear.
4.Effects of Lycium barbarum polysaccharides on blood indexes andliver tissue morphology in rats with intrahepatic cholestasis
XIA Yong ; CAI Delei ; FU Jianyun ; XU Caiju ; SONG Yanhua ; MENG Zhen ; XIE Jiaying
Journal of Preventive Medicine 2021;33(10):1003-1008
Objective:
To study the effects of Lycium barbarum polysaccharides ( LBP ) on blood indexes and liver tissue morphology in rats with intrahepatic cholestasis.
Methods:
Sprague-Dawley rats were randomly divided into the control group, the model group, and LBP low, medium and high dose group. The rats in the model group and LBP dose groups were given 60 mg/kg alpha-naphthylisothiocyanate ( ANIT ) by gavage every three days of the experiment, and the rats in the control group were given salad oil instead of ANIT. From the third day, the rats in each dose group were given 40, 150 and 600 mg/kg LBP, and the rats in the model group were given distilled water. After four weeks, the blood and urine indexes were measured, and the morphological changes of liver tissue were observed.
Results:
From the third day of the experiment, the activity of rats in the model group and LBP dose groups decreased, and the color of urine changed to dark yellow. There was no abnormality in the group. In the model group, the levels of serum total bilirubin, direct bilirubin, total bile acid ( TBA ), alkaline phosphatase ( ALP ), γ-glutamyltransferase(γ-GGT), cholesterol, alanine aminotransferase ( ALT ), aspartate aminotransferase ( AST ), white blood cell ( WBC ), percentage of granulocyte, urinary bilirubin, urinary bile acid, liver mass and liver to body ratio were higher than those in the control group, while red blood cell and percentage of lymphocyte were lower than those in the control group ( all P<0.05 ). Pathological changes of liver tissue were observed. The levels of serum TBA, ALP, γ-GGT, ALT, AST, WBC and liver to body ratio in LBP high dose group were lower than those in the model group ( all P<0.05 ). The infiltration of inflammatory cells, proliferation and expansion of bile duct, degeneration and necrosis of liver cells were alleviated.
Conclusions
LBP can improve the blood indexes and pathological changes of liver tissue in rats with intrahepatic cholestasis at the dosage of 600 mg/kg. Inhibition of inflammatory response and reduction of oxidative stress injury may be the mechanism for alleviating cholestatic liver injury.
5.Study on pigmentation in the livers and kidneys of rats caused by a compound Chinese medicine preparationXIA
Xia Yong ; XU Caiju ; LU Wei ; SONG Yanhua ; DONG Xiaolan ; FU Jianyun ; ZHENG Xiaoyan
Journal of Preventive Medicine 2020;32(10):1004-1009
Objective:
To explore the cause and type of pigmentation in the livers and kidneys of rats caused by a compound Chinese medicine preparation.
Methods:
The experiment consist of low, medium, and high dose groups and a control group, the Sprague-Dawley rats in these groups were orally given 1.0, 2.0 and 4.0 g/kgbw of a compound Chinese medicine preparation of gardenia and distilled water for 30 days, respectively. The body weight, diet, hematology and histopathology of the rats in each group were observed for changes in pigment metabolism.
Results:
In the first and second weeks of the experiment, the rats in the low, medium, high dose groups and the control group showed no abnormal symptoms or signs. From the third weekend, the urine of the rats in the high dose group turned thick yellow and green, and the stool color became light. During the experiment, no rats died. There were statistically significant differences in body weights and weight gains among these groups ( P<0.05 ) . There were statistically significant differences in total food utilization, direct bilirubin, r-glutamyl transferase, alkaline phosphatase, and liver/body ratios among these groups ( P<0.05 ). Gross examination revealed that the livers and kidneys of rats in the high dose group were dull and green. Microscopic examination revealed changes in dark pigment particles in the livers and kidneys of rats in the high dose group. Histochemical staining confirmed that pigments in the livers and kidneys were bile pigments.
Conclusions
At a dosage of 4.0 g/kgbw, a compound Chinese medicine preparation of gardenia can lead to bile pigment deposition in the livers and kidneys of rats due to cholestasis.
6.Safety evaluation of a compound Chinese medicine preparation of gardenia
Yong XIA ; Jianyun FU ; Delei CAI ; Shixin ZHANG ; Caiju XU ; Qing CHEN ; Jun YAN
Journal of Preventive Medicine 2019;31(8):786-790
Objective:
To evaluate the toxicological safety of a compound Chinese medicine preparation of gardenia.
Methods:
Eighty healthy SD rats with half males and half females were randomly divided into four groups. The low-,moderate- and high-dose group were given 1.00 g/kgbw,2.00 g/kgbw and 4.00 g/kgbw of the preparation,while the control group was given distilled water,by gavage for 30 days. The changes of diet,weight,hematological parameters and major organs of rats were observed,and the histopathological examination of the main organs was performed.
Results:
The rats in the high-dose group reduced activities and their urine turned dark yellow or green,while the other rats showed no abnormality. No rats died during the experimental period. Compared with the control group,the weight,the total weight gain,the food utilization rate,the fasted weight of the rats in the high-dose group and the hemoglobin content of the female rats in the high-dose group were significantly decreased(P<0.05);the ratio of liver to body weight,the ratio of kidney to body weight,the serum creatinine levels of the rats in the high-dose group and the serum urea nitrogen levels of the male rats in the high-dose group were significantly higher(P<0.05). The livers and kidneys of the rats in high-dose group turned different degrees of dark green;the hepatic pigmentation,hepatocyte vacuolar degeneration,bile duct hyperplasia accompanied with inflammatory cell infiltration,renal pigmentation,renal tubular epithelial cellular swelling,and renal interstitial inflammatory cell infiltration were observed.
Conclusion
This preparation at a dose of 4.0 g/kgbw has hepatotoxicity and nephrotoxicity to rats. A dose of 2.0 g/kgbw has no harmful effect but less than 100 times of the possible human intake,the safety is not guaranteed.
7.Effects of low dose persistent organic pollutants on rats
Delei CAI ; Yanhua SONG ; Caiju XU ; Wei LU ; Yong XIA ; Jianyun FU ; Haitao SHEN
Journal of Preventive Medicine 2019;31(6):558-563
Objective :
To evaluate the health effects of persistent organic pollutants(POPs)on body weight,food intake,internal organs,blood biochemistry,metabolic enzymes and antioxidant ingredients of rats.
Methods :
Sixteen healthy Sprague-Dawley(SD)rats were randomly divided into the experimental group exposed to 10 mL/kg mixture of POPs(10 ng/mL PCBs,5 ng/mL PBDEs,1 ng/mL PCDD/F)everyday for 28 days by gavage,and the control group exposed to the same volume of soybean oil in the same way. Body weight and food intake of the rats were recorded regularly;blood routine and biochemical indices were detected;liver,kidney,spleen and testicles(ovary)of the rats were weighed to calculate organ coefficients;metabolic enzymes and antioxidant ingredients were detected from livers of the rats.
Results :
No obviously abnormal symptoms and no deaths were found in both groups. Compared to the control group,the weekly food intake in the experimental group increased more for there was an interaction between grouping and time(P< 0.05). The ratio of liver to body weight of male rats in the experimental group was higher than that in the control group [(3.87± 0.19)% vs.(3.53± 0.06)%,P< 0.05]. The haemoglobin and red blood cell of female rats in the experimental group were lower than those in the control group[(145.25± 6.18)g/L vs.(154.50± 4.20)g/L;(6.90± 0.14)× 1012/L vs.(7.39± 0.24)× 1012/L;both P< 0.05]. The glutathione-S-transferase(GST)of female rats in the experimental group was higher than that in the control group [(13.37± 1.05)U/mgprot vs.(9.43± 1.08)U/mgprot,P< 0.05]. The cytochrome P4501A1of rats in the experimental group was higher than that in the control group [female:(88.23± 5.81)ng/mgprot vs.(73.85± 5.86)ng/mgprot;male:(96.80± 13.32)ng/mgprot vs.( 72.20± 2.01)ng/mgprot;both P< 0.05].
Conclusion
After exposed to low dose of POPs,the cytochrome P4501A1 increased in all rats,the liver to body weight ratio increased in male rats,GST activity increased while red blood cell and haemoglobin decreased in female rats,which indicated possible body damages in rats.
8. Analysis of teaching quality and influencing factors of undergraduate teachers in a Medical University in western China
Shunyue YANG ; Shan YAN ; Jianyun YU ; Chuanzhi XU ; Guofeng SONG ; Faqian LU ; Fuli LI ; Weitang SHAO ; Dingyun YOU
Chinese Journal of Medical Education Research 2019;18(12):1244-1248
Objective:
In order to understand the current situation and influencing factors of teaching quality in a Medical University in Yunnan, thus improving the teaching quality of the teachers.
Methods:
The self-made evaluation forms for teachers' teaching quality which include 9 first-level indicators were adopted. In December 2016, a survey was conducted on some students from grade 2013 to 2016 about the teachers who gave them lectures from September to December 2016, involving 7 different majors, 23 teachers and 18 courses. SPSS 21.0 was used for data analysis. Enumeration data were described by frequencies and percentages. Univariate and multivariate
9.Evaluation value of dynamic monitoring of neutrophil/lymphocyte ratio in peripheral blood in severity of illness and prognosis of bacterial sepsis
Jianyun XU ; Fuxiang XU ; Yichuan ZHU ; Jian SHEN
Clinical Medicine of China 2017;33(2):130-133
Objective To explore the evaluation value of dynamic monitoring of neutrophil/lymphocyte ratio(NLR)in severity of illness and prognosis of bacterial sepsis.Methods Clinical data and laboratory index of 72 cases of patients with bacterial sepsis in ICU of Yangpu Hospital Affiliated to Tongji University were retrospectively analyzed.According to the severity of illness,patients were divided into sepsis group(n=20),severe sepsis group(n=30)and septic shock group(n=22).According to the mortality within 28 d,patients were divided into survival group(n=47),death group(n=25).The 0 h NLR,48 h NLR and change rate of NLR between two groups were compared,and the influence factors of prognosis were analyzed.Results With the increase of severity of illness,the time of mechanical ventilation was shortened((8.8±1.9)d,(4.6±0.6)d,(3.9±0.4)d),and PLT((146.4±45.8)×109/L,(110.6±41.3)×109/L,(102.5±38.6)×109/L),NLR rate(0.61±0.26,0.26±0.11,0.22±0.09)were decreased significantly,APEACHE Ⅱ score,CRP,PCT,0 h NLR,48 h NLR were increased obviously((18.5±2.3)points,(20.4±3.6)points,(23.1±3.9)points;(72.6±10.4)mg/L,(78.2±11.6)mg/L,(85.2±12.5)mg/L;(1.5±0.4)μg/L,(2.3±0.6)μg/L,(2.7±0.9)μg/L;11.3±2.6,14.2±3.4,15.7±3.5;3.4±0.9,9.7±2.4,11.2±2.6),the differences were statistically significant(P<0.05).Compared with death group,the time of mechanical ventilation in survival group was prolonged((4.1±0.3)d vs.(8.7±1.4)d),APEACHE Ⅱ score,CRP,PCT,0 h NLR,48 h NLR were decreased obviously((21.4±3.5)points vs.(18.3±2.6)points,(78.2±11.6)mg/L vs.(71.5±10.8)mg/L,(2.5±0.7)μg/L vs.(1.4±0.6)μg/L,(15.0±3.3)vs.(11.6±2.4),(10.5±2.8)vs.(3.2±0.8)),and PLT,NLR rate were increased significantly((106.5±41.5)×109/L vs.(148.4±50.8)×109/L,0.24±0.10 vs.0.65±0.24),the differences were statistically significant(t=16.18,4.26,2.44,6.99,5.01,16.73,3.54,8.15,P<0.05).Multivariate logistic regression analysis showed that APEACHE Ⅱ score,0 h NLR were the independent risk factors of death in patients with bacterial sepsis(OR=3.99,3.01,95%CI:1.65-2.38,1.99-4.54,P<0.05),and NLR rate was independent protection factor(OR=0.95,95%CI:0.91-0.97,P<0.05).Conclusion Dynamic monitoring of peripheral blood NLR can help to judge the prognosis and severity of illness of patients with bacterial sepsis,and NLR before treatment and change rate of NLR are an independent predictors of death.
10.Drug-coated balloon with paclitaxel for in-stent restenosis of femoral popliteal artery: initial experience in 18 patients
Xupin XIE ; Xin FANG ; Changpin HUANG ; Yongchang LIU ; Dong XU ; Jianyun LONG ; Naigong LIN
Journal of Interventional Radiology 2017;26(6):544-547
Objective To evaluate the short-term effect of drug-coated balloon (DCB) with paclitaxel in treating in-stent restenosis (ISR) of femoral popliteal artery.Methods A total of 18 patients with femoral popliteal artery ISR,who were admitted to authors' hospital during the period from June 2016 to December 2016 to receive paclitaxel DCB treatment,were enrolled in this study.The patients included 15 males and 3 females,with a mean age of (72.7±9.8) years old.According to Fontaine classification,grade Ⅱ B was seen in 9 patients,grade Ⅲ in 8 patients,and grade Ⅳ in one patient.Preoperative CT angiography showed that ISR could be confirmed in 3 patients and complete occlusion of the stent in 15 patients.After the diseased artery was re-opened,pre-dilatation with common balloon was conducted,which was followed by dilatation with paclitaxel DCB;remedial stent implantation was carried out when the restrictive dissection was observed or if the residual stenosis was beyond 50%.Angiography was performed immediately after the procedure to check the vascular patency.On the third day afterthe treatment,the ankle-brachial index (ABI) of diseased lower extremity was determined to assess the improvement of ischemia.Three month after the treatment,the patients were followed up to detemine the incidence of restenosis,the clinically-driven target lesion revascularization (TLR) rate,and the occurrence of serious clinical events within 3 months.Results Successful re-opening of the diseased artery was achieved in all 18 patients,the technical success rate was 100%.At 3 months after the treatment,the restenosis rate and TLR rate were 10% (1/10) and 6.67% (1/15) respectively.No procedure-related complications occurred in all patients.Conclusion For the treatment of femoral popliteal artery ISR,the use of paclitaxel DCB is safe and effective.


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