1.Cartilage Protection and Anti-Inflammatory Effects of Fraxetin on Monosodium Iodoacetate-Induced Rat Model of Osteoarthritis
Zhiwei LIU ; Ran YANG ; Hao LIAN ; Yu ZHANG ; Lilun JIN
Laboratory Animal and Comparative Medicine 2025;45(3):259-268
ObjectiveTo establish a rat model of osteoarthritis and study the anti-inflammatory effects and mechanisms of fraxetin. MethodsEighteen 8-week-old male SPF-grade SD rats were randomly divided into three groups: Rats in the blank group received a right articular cavity injection of 50 μL of normal saline for 1 week; the model and intervention groups were injected with monosodium iodoacetate (MIA) into the right joint cavity to induce osteoarthritis, while the intervention group subsequently received fraxetin (5 mg·kg-1·d-1) for 1 week. Four weeks after drug intervention, abdominal aortic blood was collected. The animals were then euthanized, and knee joint cartilage were collected. The cartilage samples were stained with hematoxylin-eosin, safranin O-fast green, and toluidine blue for histopathological examination and scoring using the Mankin and OARSI scoring systems. The trabecular bone volume/total volume (Tb.BV/TV), trabecular bone surface density/total volume (Tb.BS/TV), and trabecular number (Tb.N) of each group were compared and analyzed using a micro-CT scanning system. The expression levels of various inflammatory factors [tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6)], and cartilage oligomeric matrix protein (COMP) were measured using enzyme-linked immunosorbent assay (ELISA). The expression levels of mitogen-activated protein kinase p38 (p38 MAPK), phosphorylation-p38 MAPK (p-p38 MAPK), c-Jun N-terminal kinase (JNK), and phosphorylation-JNK (p-JNK) were measured by western blotting. ResultsThe staining of cartilage sections of rat knee joints showed that the articular surface defects in the model group were severe, while the cartilage destruction in the intervention group was relatively reduced. Micro-CT results showed that Tb.BV/TV, Tb.BS/TV and Tb.N in the intervention group were significantly higher than those in the model group (P < 0.05); the Mankin score in the model group was significantly higher than that in the blank group (P < 0.05), the Mankin score in the intervention group was significantly lower than that in the model group (P < 0.05); while the OARSI score in the intervention group was significantly lower than that in the model group (P < 0.05). The results of the enzyme-linked immunosorbent assay showed that the serum levels of TNF-α, IL-1β, IL-6, and COMP in the model group were significantly higher than those in the blank group (all P < 0.05), while those in the intervention group were significantly lower than in the model group (P < 0.05). Western blot results showed that the expression levels of p-p38 MAPK and p-JNK in the knee cartilage tissue were significantly lower in the intervention group than in the model group (both P < 0.05), and significantly higher in the model group than in the blank group (both P < 0.05). ConclusionFraxetin may play a therapeutic role in a monosodium iodoacetate-induced rat model of osteoarthritis through the p38 MAPK pathway.
2.Cartilage Protection and Anti-Inflammatory Effects of Fraxetin on Monosodium Iodoacetate-Induced Rat Model of Osteoarthritis
Zhiwei LIU ; Ran YANG ; Hao LIAN ; Yu ZHANG ; Lilun JIN
Laboratory Animal and Comparative Medicine 2025;45(3):259-268
ObjectiveTo establish a rat model of osteoarthritis and study the anti-inflammatory effects and mechanisms of fraxetin. MethodsEighteen 8-week-old male SPF-grade SD rats were randomly divided into three groups: Rats in the blank group received a right articular cavity injection of 50 μL of normal saline for 1 week; the model and intervention groups were injected with monosodium iodoacetate (MIA) into the right joint cavity to induce osteoarthritis, while the intervention group subsequently received fraxetin (5 mg·kg-1·d-1) for 1 week. Four weeks after drug intervention, abdominal aortic blood was collected. The animals were then euthanized, and knee joint cartilage were collected. The cartilage samples were stained with hematoxylin-eosin, safranin O-fast green, and toluidine blue for histopathological examination and scoring using the Mankin and OARSI scoring systems. The trabecular bone volume/total volume (Tb.BV/TV), trabecular bone surface density/total volume (Tb.BS/TV), and trabecular number (Tb.N) of each group were compared and analyzed using a micro-CT scanning system. The expression levels of various inflammatory factors [tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6)], and cartilage oligomeric matrix protein (COMP) were measured using enzyme-linked immunosorbent assay (ELISA). The expression levels of mitogen-activated protein kinase p38 (p38 MAPK), phosphorylation-p38 MAPK (p-p38 MAPK), c-Jun N-terminal kinase (JNK), and phosphorylation-JNK (p-JNK) were measured by western blotting. ResultsThe staining of cartilage sections of rat knee joints showed that the articular surface defects in the model group were severe, while the cartilage destruction in the intervention group was relatively reduced. Micro-CT results showed that Tb.BV/TV, Tb.BS/TV and Tb.N in the intervention group were significantly higher than those in the model group (P < 0.05); the Mankin score in the model group was significantly higher than that in the blank group (P < 0.05), the Mankin score in the intervention group was significantly lower than that in the model group (P < 0.05); while the OARSI score in the intervention group was significantly lower than that in the model group (P < 0.05). The results of the enzyme-linked immunosorbent assay showed that the serum levels of TNF-α, IL-1β, IL-6, and COMP in the model group were significantly higher than those in the blank group (all P < 0.05), while those in the intervention group were significantly lower than in the model group (P < 0.05). Western blot results showed that the expression levels of p-p38 MAPK and p-JNK in the knee cartilage tissue were significantly lower in the intervention group than in the model group (both P < 0.05), and significantly higher in the model group than in the blank group (both P < 0.05). ConclusionFraxetin may play a therapeutic role in a monosodium iodoacetate-induced rat model of osteoarthritis through the p38 MAPK pathway.
3.The effect of local application of tranexamic acid on reducing drainage volume after thyroidectomy
Zhiwei LUO ; Hongli JI ; Jinshan LIAN ; Yamei CHEN ; Jiang GAO ; Jiaqi CHANG ; Longlong WANG
Chinese Journal of Postgraduates of Medicine 2024;47(5):456-460
Objective:To explore the effect and safety of local spraying tranexamic acid after thyroidectomy.Methods:Randomized double-blind placebo-controlled study method was used. Sixty-four patients underwent scheduled thyroidectomy from December 2022 to August 2023 in Baotou Cancer Hospital were selected. The patients were divided into tranexamic acid group and control group by random digits table method with 32 cases each. Before closing the wound during surgery, 16 ml of tranexamic acid injection with concentration of 25 mg/ml was used to wash the wound and 1 ml of tranexamic acid injection (tranexamic acid 100 mg) used to locally spray in tranexamic acid group; 16 ml of the sterile water for injection was used to wash the wound and 1 ml of sterile water for injection was used locally spray in control group, and then the drainage tube was clipped for 20 min. The neck drainage volume on the first to fourth day after surgery and complication were recorded; the C-reactive protein level before and after surgery was detected.Results:Two patients in each group withdrew from the study midway. The drainage volume on the first, second and third day and total drainage volume in tranexamic acid group were significantly lower than those in control group: (29.10 ± 8.04) ml vs. (38.50 ± 8.67) ml, (18.00 ± 7.33) ml vs. (27.20 ± 10.66) ml, (10.70 ± 5.75) ml vs. (14.60 ± 6.83) ml and (69.20 ± 24.48) ml vs. (96.70 ± 31.90) ml, and there was statistical difference ( P<0.01); there was no statistical difference in the drainage volume on the fourth day after surgery between two groups ( P>0.05). There was no statistical difference in C-reactive protein before and after surgery between two groups ( P>0.05). There was 1 case of fever (body temperature 37.5 ℃) in the control group, and there were no complications such as intermuscular thrombosis, venous thrombosis, incision infection and delayed wound healing in both groups. Conclusions:Local application of tranexamic acid after thyroidectomy can reduce postoperative drainage volume and does not increase the risk of thrombosis, infection and delayed healing.
4.Evaluation and Analysis of Health Informatization Construction Policies Based on PMC Index Model
Zhiwei LU ; Jianli WANG ; Lian HE ; Ningning WANG ; Caiwen LI ; Peiying XU ; Jun GAO ; Yinmei XIE
Journal of Medical Informatics 2024;45(9):37-43
Purpose/Significance To quantitatively analyze and evaluate 26 health informatization construction policies issued at the national level,so as to provide basis for improving related policies.Method/Process Based on the policy modeling consistency(PMC)index model,a health informatization construction policy evaluation index system is constructed,which includes 9 first-level indicators and 36 second-level indicators.Appling it to the evaluation of various policy texts,and the health informatization construction policies are analyzed in a holistic and concrete way.Result/Conclusion The overall score of the health informatization construction policies is ex-cellent.2 policies are at the perfect level,80.6%of policies are at the excellent level,and there are no bad level policy texts.However,the driving force of the policy and the balance of policy recipients need to be further improved.
5.Risk factors of substandard drug blood concentration of meropenem in patients with hospital -acquired pneumonia
Lu SHI ; Fang CHEN ; Guangxian LU ; Lufen DUAN ; Jian LU ; Zhiwei ZHUANG ; Jinhui XU ; Hongtao XU ; Chao WU ; Qin ZHOU ; Lian TANG
China Pharmacy 2022;33(19):2388-2392
OBJECTIVE To analyze the risk factors of substandard drug blood concentration of meropenem in patients with hospital acquired pneumonia (HAP). METHODS Totally 130 HAP patients who were admitted to the intensive care unit of Suzhou Hospital Affiliated to Nanjing Medical University from January 2020 to June 2021 and received steady -state blood concentration test of meropenem were selected as the study subjects . The patient ’s age ,sex,body mass and other medical history were recorded . The steady-state blood trough concentration of meropenem was determined and its target was determined . Univariate and multivariate Logistic regression analysis were used to screen the risk factors for the substandard steady -state blood trough concentration of meropenem. The receiver operating characteristic (ROC)curve was drawn to screen the warning value of the risk factors and evaluate the predictive value of the risk factors . RESULTS The steady -state blood trough concentrations of 85 cases were ≥2 mg/L, and those of 45 cases were <2 mg/L. Multivariate Logistic regression analysis showed that age ,negative balance and brain injury were independent risk factors for the substandard steady-state blood trough concentration of meropenem (P< 0.05).ROC curve showed that when the patient was 58 years old,the area under the ROC curve was the largest (0.744), the sensitivity was 0.882,the specificity was 0.556,and the Youden index was 0.438;when the negative balance was 520.5 mL/24 h,the area under the ROC curve reached the maximum (0.827),the sensitivity was 0.722,the specificity was 0.905,and th e Youden index was 0.628. The creatinine clearance rate in the brain injury group was significantly higher than that in the non -brain injury group ,and the steady -state blood trough concentration of meropenem in the brain injury group was significantly lower than that in the non -brain injury group (P<0.001). CONCLUSIONS When the HAP patient ’s age is less than 58 years old ,the brain injury and the negative balance is more than 520.5 mL/24 h,the risk of substandard steady -state blood trough concentration of meropenem will increase .
6.Effect of hydrogen on activation of A1 astrocytes in hippocampus of mice with sepsis-associated encephalopathy
Bo QI ; Huaying LIN ; Zhiwei WANG ; Naqi LIAN ; Yaoqi WANG ; Keliang XIE
Chinese Journal of Anesthesiology 2021;41(10):1247-1251
Objective:To evaluate the effect of hydrogen on activation of A1 astrocytes in the hippocampus of mice with sepsis-associated encephalopathy (SAE).Methods:A total of 164 clean-grade healthy male C57BL/6J mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups ( n=41 each) using a random number table method: sham operation group (group Sham), sham operation plus hydrogen group (group Sham+ H 2), group SAE and SAE plus hydrogen group (group SAE+ H 2). The SAE model was established by cecal ligation and perforation.Group Sham+ H 2 and group SAE+ H 2 inhaled 2% hydrogen starting from 1 and 6 h after operation, respectively.Twenty mice in each group were selected to observe the 7-day survival rate after operation.The remaining mice were sacrificed at 12 h after operation, and brain tissues were removed for examination of the pathological changes in hippocampal CA1 region (with a light microscope) and for determination of the apoptosis in neurons (by TUNEL), co-expression of hippocampal glial fibrillary acidic protein (GFAP) and complement C3 (by immunofluorescence staining), expression of A1 astrocyte marker C3 (by Western blot), and contents of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and high-mobility group box 1 protein (HMGB1) (by enzyme-linked immunosorbent assay). The abnormal cell ratio and apoptosis rate were calculated.Six mice in each group were selected at 7 days after operation to perform Y-Maze paradigm. Results:Compared with group Sham, the 7-day survival rate after operation was significantly decreased, the abnormal cell ratio and apoptosis rate of hippocampal neurons were increased, the contents of TNF-α, IL-6 and HMGB1 were increased, the expression of C3 was up-regulated, the number of cells coexpressing GFAP and C3 was increased, the exploration time spent in the novel arm in Y-Maze paradigm was shortened, and the preference index was decreased in group SAE ( P<0.05). Compared with group SAE, the 7-day survival rate after operation was significantly increased, the abnormal cell ratio and apoptosis rate of hippocampal neurons were decreased, the contents of TNF-α, IL-6 and HMGB1 were decreased, the expression of C3 was down-regulated, the number of cells coexpressing GFAP and C3 was decreased, the exploration time spent in the novel arm in Y-Maze paradigm was prolonged, and the preference index was increased in group SAE+ H 2 ( P<0.05). There was no significant difference in each parameter mentioned above between Sham group and Sham+ H 2 group ( P>0.05). Conclusion:The mechanism by which hydrogen improves SAE may be related to inhibiting activation of A1 type astrocytes in mice.
7.Effects of Augmented Renal Clearance on Blood Trough Concentration of Patients Receiving High-dose Regimen of Teicoplanin
Lian TANG ; Lu SHI ; Hongzhi XUE ; Zhiwei ZHUANG ; Yunlong YUAN ; Chunxia QIAN ; Jinwei ZHU ; Xiaowen XU ; Yasong ZHU ; Jisong LIU ; Yi SHEN ; Jian LU
China Pharmacy 2020;31(21):2650-2655
OBJECTIVE:To study the effects of augmented renal clearance (ARC)on blood trough concentration of patients receiving high-dose regimen of teicoplanin. METHODS :Patients who received high-dose regimen of teicoplanin in the ICU were prospectively collected from the Affiliated Suzhou Hospital of Nanjing Medical University/Suzhou Municipal Hospital during Jul. 2018-Jun. 2020. They were divided into ARC group and normal renal function group according to corrected creatinine clearance. The dosage regimen of teicoplanin in the two groups were loading dose of 600 mg,q12 h×3 doses,maintenance dose of 6-10 mg/kg,qd,and the dosage was adjusted in combination with creatinine clearance rate and blood trough concentration. The trough concentration of blood samples which were collected 30 min before the 4th and 8th-10th dosage of teicoplanin were determined by HPLC. Trough concentration ,clinical efficacy ,Gram-positive bacterial clearance rate and the occurrence of ADR were compared between 2 groups. RESULTS :A total of 56 patients were included and divided into ARC group (18 cases)and normal renal function group (38 cases). ARC group had younger age (P<0.001)and lower serum albumin level (P=0.025)than normal renal function group. The trough concentrations before administration of the 4th and 8th-10th dosage in ARC group were lower than normal renal function group (P=0.034;P=0.035). The trough concentrations in the ARC group and normal renal function group before 8th-10th dosage were all higher than 30 min before the 4th dosage (P=0.003;P<0.001). The clinical efficacy rate and the clearance rate of Gram-positive bacteria in ARC group were 77.8% and 76.2%,which were lower than those of the normal renal function group ,but there was no statistical difference (P=0.195;P=0.223). There was no liver function damage ,hemocytopenia and allergic reaction in both groups ,but in the normal renal function group ,the causal relationship between acute renal damage and teicoplanin was assessed as “very likely ”in one patient. CONCLUSIONS :ARC patients are younger ,most of them have hypoproteinemia,and the blood trough concentrations of teicoplanin in high-dose regimen are significantly lower than those of normal renal function patients. For critical ill ARC patients ,it is advisable to increase the loading dose of teicoplanin to make the trough concentration reach the target concentration range quickly.
8.Associations between lifestyle and social network and cognitive impairment among the elderly in three communities in China
Jinlei LI ; Pingyue JIN ; Zijuan WANG ; Zhikai ZHU ; Zhiwei LIAN ; Yuanli LIU
Chinese Journal of Health Management 2019;13(3):220-223
Objective To investigate the associations between lifestyle factors and social network and cognitive impairment among the elderly in three communities in China.Methods From November 2017 to May 2018,1 200 elderly individuals were selected from three Chinese communities (Beijing,Hefei,and Lanzhou) using a random cluster sampling method.Data were collected on lifestyle,social network,and cognition.A conditional logistic regression analysis was conducted to identify the associations between lifestyle and social network and cognitive impairment.Results A total 1 115 participants (92.9%) were administered both social network and cognition questionnaires.After adjustment by age,sex,education,marital status,health,and living status,only low participation in physical activity was found to be associated with cognitive impairment (OR=0.65,95% CI=0.45-0.93,P=0.019).A larger social network (OR=0.50,95% CI=0.29-0.85,P=0.010),especially more friends (0R=0.44,95% CI=0.29-0.65,P<0.001),may decrease the risk of cognitive impairment.The interactions between lifestyle factors and social network were not associated with cognitive impairment.Conclusion Our findings suggest that larger social networks and physical activity are associated with cognitive function among the elderly.Identification and intervention of risk factors are crucial in the delay and prevention of cognitive impairment and the improvement of quality of life among the elderly.
9.Multiple sgRNAs facilitate base editing-mediated i-stop to induce complete and precise gene disruption.
Kun JIA ; Zongyang LU ; Fei ZHOU ; Zhiqi XIONG ; Rui ZHANG ; Zhiwei LIU ; Yu'e MA ; Lei HE ; Cong LI ; Zhen ZHU ; Dejing PAN ; Zhengxing LIAN
Protein & Cell 2019;10(11):832-839
10.Clinical significance of serum prealbumin-bilirubin score (PALBI) in predicting posthepatectomy liver failure in patients with HBV-related hepatocellular carcinoma
Rongyun MAI ; Jiazhou YE ; Jie ZENG ; Xianmao SHI ; Zhongrong LONG ; Jinwu LIU ; Zhiwei CHEN ; Shan HUANG ; Fang LIAN ; Lequn LI ; Feixiang WU ; Guobin WU
Chinese Journal of Hepatobiliary Surgery 2018;24(11):737-741
Objective To study the value of serum prealbumin-bilirubin score (PALBI) in predicting posthepatectomy liver failure (PHLF) for patients with HBV related hepatocellular carcinoma (HCC).Methods A retrospective study was conducted on 919 HBV-related HCC patients who underwent hepatectomy from September 2013 to December 2016 at the Affiliated Tumor Hospital of Guangxi Medical University.These patients were divided into a training cohort (n =689) and a validation cohort (n =230) using the 3 ∶ 1 matching principle.The training cohort was divided into the control group (n=546) and the PHLF group (n=143) according to whether PHLF occurred.The multivariate logistic regression model was used to analyze the factors related to PHLF in the training cohort,and then the PALBI score was established.The ability of the PALBI score to predict PHLF was evaluated by the area under the receiver operating characteristic curve (AUC) and compared with the Child-Pugh,model for end-stage liver disease (MELD),and albumin-bilirubin (ALBI) scores.Results Univariate and multivariate logistic regression analyses showed the factors including HBV-DNA≥ 103 IU/ml,total bilirubin,prealbumin,platelet count,AST,prothrombin time,intraoperative blood loss ≥400 ml and major liver resection were closely related to PHLF.The ability of the PALBI score (AUC =0.733) to predict PHLF preoperatively was superior to the ChildPugh score (AUC =0.562),the MELD score (AUC =0.652) and the ALBI score (AUC =0.683) in the entire training cohort.Similar results were obtained in the entire validation cohort (AUC:0.752 vs.0.599 vs.0.641 vs.0.678).To eliminate the effect of a small residual liver volume on PHLF,the ability of each of these scores in the training and validation cohorts to predict PHLF was calculated respectively in these 2 cohorts of patients who underwent only minor liver resection,and similar results were obtained.Conclusion The PALBI score was significantly superior to the Child-Pugh,MELD and ALBI scores in predicting PHLF in patients with HBV-related HCC who underwent liver resection.The PALBI score is a simple,non-invasive and reliable novel model in predicting PHLF.

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