1.Oxylipidomics Combined with Transcriptomics Reveals Mechanism of Jianpi Huogu Prescription in Treating Steroid-induced Osteonecrosis of Femoral Head in Rats
Lili WANG ; Qun LI ; Zhixing HU ; Qianqian YAN ; Liting XU ; Xiaoxiao WANG ; Chunyan ZHU ; Yanqiong ZHANG ; Weiheng CHEN ; Haijun HE ; Chunfang LIU ; Na LIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):190-199
ObjectiveTo unveil the mechanism of Jianpi Huogu prescription (JPHGP) in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head (SONFH) by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal, model, low-, medium-, and high-dose (2.5, 5, 10 g·kg-1, respectively) JPHGP, and Jiangushengwan (1.53 g·kg-1) groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg-1 on days 1 and 2, and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection, and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head, and the number of adipocytes, the rate of empty bone lacunae, and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB). At the same time, the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed, and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking, immunohistochemistry, and Western blot. ResultsCompared with the normal group, the model group showcased thinning of the femoral head, trabecular fracture, karyopyknosis, subchondral cystic degeneration, increases in the number of adipocytes and the rate of empty bone lacunae (P<0.01), a reduction in the trabecular area (P<0.01), decreases in BMD, Tb.Th, Tb.N, and BV/TV, and increases in Tb.Sp and BS/BV (P<0.01). Compared with the model group, the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae, an increase in the trabecular area (P<0.05, P<0.01), rises in BMD, Tb.Th, Tb.N, and BV/TV, and decreases in Tb.Sp and BS/BV (P<0.05, P<0.01). Compared with the normal group, the model group showcased raised serum levels of TG, TC, LDL, and ApoB and lowered serum levels of HDL and ApoA1 (P<0.01). Compared with the model group, the JPHGP groups had lowered serum levels of TG, TC, LDL, and ApoB (P<0.05, P<0.01) and a risen serum level of ApoA1 (P<0.05, P<0.01). Moreover, the serum level of HDL in the high-dose JPHGP group increased (P<0.01). A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head, and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation, lipids, apoptosis, and osteoclast differentiation. Molecular docking, immunohistochemistry, and Western blot results showed that compared with the normal group, the model group displayed increased content of 5-lipoxygenase (5-LO) and peroxisome proliferator-activated receptor γ (PPARγ) in the femoral head (P<0.01). Compared with the model group, medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ (P<0.05, P<0.01). ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.
2.Oxylipidomics Combined with Transcriptomics Reveals Mechanism of Jianpi Huogu Prescription in Treating Steroid-induced Osteonecrosis of Femoral Head in Rats
Lili WANG ; Qun LI ; Zhixing HU ; Qianqian YAN ; Liting XU ; Xiaoxiao WANG ; Chunyan ZHU ; Yanqiong ZHANG ; Weiheng CHEN ; Haijun HE ; Chunfang LIU ; Na LIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):190-199
ObjectiveTo unveil the mechanism of Jianpi Huogu prescription (JPHGP) in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head (SONFH) by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal, model, low-, medium-, and high-dose (2.5, 5, 10 g·kg-1, respectively) JPHGP, and Jiangushengwan (1.53 g·kg-1) groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg-1 on days 1 and 2, and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection, and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head, and the number of adipocytes, the rate of empty bone lacunae, and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB). At the same time, the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed, and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking, immunohistochemistry, and Western blot. ResultsCompared with the normal group, the model group showcased thinning of the femoral head, trabecular fracture, karyopyknosis, subchondral cystic degeneration, increases in the number of adipocytes and the rate of empty bone lacunae (P<0.01), a reduction in the trabecular area (P<0.01), decreases in BMD, Tb.Th, Tb.N, and BV/TV, and increases in Tb.Sp and BS/BV (P<0.01). Compared with the model group, the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae, an increase in the trabecular area (P<0.05, P<0.01), rises in BMD, Tb.Th, Tb.N, and BV/TV, and decreases in Tb.Sp and BS/BV (P<0.05, P<0.01). Compared with the normal group, the model group showcased raised serum levels of TG, TC, LDL, and ApoB and lowered serum levels of HDL and ApoA1 (P<0.01). Compared with the model group, the JPHGP groups had lowered serum levels of TG, TC, LDL, and ApoB (P<0.05, P<0.01) and a risen serum level of ApoA1 (P<0.05, P<0.01). Moreover, the serum level of HDL in the high-dose JPHGP group increased (P<0.01). A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head, and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation, lipids, apoptosis, and osteoclast differentiation. Molecular docking, immunohistochemistry, and Western blot results showed that compared with the normal group, the model group displayed increased content of 5-lipoxygenase (5-LO) and peroxisome proliferator-activated receptor γ (PPARγ) in the femoral head (P<0.01). Compared with the model group, medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ (P<0.05, P<0.01). ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.
3.Combination Therapy of Pyrotinib and Metronomic Vinorelbine in HER2+ Advanced Breast Cancer after Trastuzumab Failure (PROVE): A Prospective Phase 2 Study
Chunfang HAO ; Xu WANG ; Yehui SHI ; Zhongsheng TONG ; Shufen LI ; Xiaodong LIU ; Lan ZHANG ; Jie ZHANG ; Wenjing MENG ; Li ZHANG
Cancer Research and Treatment 2025;57(2):434-442
Purpose:
Approximately 50%-74% of patients with metastatic human epidermal growth factor receptor 2 (HER2)–positive breast cancer do not respond to trastuzumab, with 75% of treated patients experiencing disease progression within a year. The combination of pyrotinib and capecitabine has showed efficacy in these patients. This study evaluates the efficacy and safety of pyrotinib combined with metronomic vinorelbine for trastuzumab-pretreated HER2-positive advanced breast cancer patients.
Materials and Methods:
In this phase 2 trial, patients aged 18-75 years with HER2-positive advanced breast cancer who had previously failed trastuzumab treatment were enrolled to receive pyrotinib 400 mg daily in combination with vinorelbine 40mg thrice weekly. The primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety.
Results:
From October 21, 2019, to January 21, 2022, 36 patients were enrolled and received at least one dose of study treatment. At the cutoff date, 20 experienced disease progression or death. With a median follow-up duration of 35 months, the median PFS was 13.5 months (95% confidence interval [CI], 8.3 to 18.5). With all patients evaluated, an ORR of 38.9% (95% CI, 23.1 to 56.5) and a DCR of 83.3% (95% CI, 67.2 to 93.6) were achieved. The median OS was not reached. Grade 3 adverse events (AEs) were observed in 17 patients, with diarrhea being the most common (27.8%), followed by vomiting (8.3%) and stomachache (5.6%). There were no grade 4/5 AEs.
Conclusion
Pyrotinib combined with metronomic vinorelbine showed promising efficacy and an acceptable safety profile in HER2-positive advanced breast cancer patients after trastuzumab failure.
4.Combination Therapy of Pyrotinib and Metronomic Vinorelbine in HER2+ Advanced Breast Cancer after Trastuzumab Failure (PROVE): A Prospective Phase 2 Study
Chunfang HAO ; Xu WANG ; Yehui SHI ; Zhongsheng TONG ; Shufen LI ; Xiaodong LIU ; Lan ZHANG ; Jie ZHANG ; Wenjing MENG ; Li ZHANG
Cancer Research and Treatment 2025;57(2):434-442
Purpose:
Approximately 50%-74% of patients with metastatic human epidermal growth factor receptor 2 (HER2)–positive breast cancer do not respond to trastuzumab, with 75% of treated patients experiencing disease progression within a year. The combination of pyrotinib and capecitabine has showed efficacy in these patients. This study evaluates the efficacy and safety of pyrotinib combined with metronomic vinorelbine for trastuzumab-pretreated HER2-positive advanced breast cancer patients.
Materials and Methods:
In this phase 2 trial, patients aged 18-75 years with HER2-positive advanced breast cancer who had previously failed trastuzumab treatment were enrolled to receive pyrotinib 400 mg daily in combination with vinorelbine 40mg thrice weekly. The primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety.
Results:
From October 21, 2019, to January 21, 2022, 36 patients were enrolled and received at least one dose of study treatment. At the cutoff date, 20 experienced disease progression or death. With a median follow-up duration of 35 months, the median PFS was 13.5 months (95% confidence interval [CI], 8.3 to 18.5). With all patients evaluated, an ORR of 38.9% (95% CI, 23.1 to 56.5) and a DCR of 83.3% (95% CI, 67.2 to 93.6) were achieved. The median OS was not reached. Grade 3 adverse events (AEs) were observed in 17 patients, with diarrhea being the most common (27.8%), followed by vomiting (8.3%) and stomachache (5.6%). There were no grade 4/5 AEs.
Conclusion
Pyrotinib combined with metronomic vinorelbine showed promising efficacy and an acceptable safety profile in HER2-positive advanced breast cancer patients after trastuzumab failure.
5.Combination Therapy of Pyrotinib and Metronomic Vinorelbine in HER2+ Advanced Breast Cancer after Trastuzumab Failure (PROVE): A Prospective Phase 2 Study
Chunfang HAO ; Xu WANG ; Yehui SHI ; Zhongsheng TONG ; Shufen LI ; Xiaodong LIU ; Lan ZHANG ; Jie ZHANG ; Wenjing MENG ; Li ZHANG
Cancer Research and Treatment 2025;57(2):434-442
Purpose:
Approximately 50%-74% of patients with metastatic human epidermal growth factor receptor 2 (HER2)–positive breast cancer do not respond to trastuzumab, with 75% of treated patients experiencing disease progression within a year. The combination of pyrotinib and capecitabine has showed efficacy in these patients. This study evaluates the efficacy and safety of pyrotinib combined with metronomic vinorelbine for trastuzumab-pretreated HER2-positive advanced breast cancer patients.
Materials and Methods:
In this phase 2 trial, patients aged 18-75 years with HER2-positive advanced breast cancer who had previously failed trastuzumab treatment were enrolled to receive pyrotinib 400 mg daily in combination with vinorelbine 40mg thrice weekly. The primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety.
Results:
From October 21, 2019, to January 21, 2022, 36 patients were enrolled and received at least one dose of study treatment. At the cutoff date, 20 experienced disease progression or death. With a median follow-up duration of 35 months, the median PFS was 13.5 months (95% confidence interval [CI], 8.3 to 18.5). With all patients evaluated, an ORR of 38.9% (95% CI, 23.1 to 56.5) and a DCR of 83.3% (95% CI, 67.2 to 93.6) were achieved. The median OS was not reached. Grade 3 adverse events (AEs) were observed in 17 patients, with diarrhea being the most common (27.8%), followed by vomiting (8.3%) and stomachache (5.6%). There were no grade 4/5 AEs.
Conclusion
Pyrotinib combined with metronomic vinorelbine showed promising efficacy and an acceptable safety profile in HER2-positive advanced breast cancer patients after trastuzumab failure.
6.Network meta-analysis of the modeling effects of different factors on rabbit models of steroid-induced osteonecrosis of femoral head
Zhixing HU ; Qun LI ; Chao YANG ; Xiaoxiao WANG ; Luochangting FANG ; Wuqiong HOU ; Na LIN ; Weiheng CHEN ; Chunfang LIU ; Ya LIN
Chinese Journal of Tissue Engineering Research 2024;28(6):976-984
OBJECTIVE:The rabbit model of steroid-induced osteonecrosis of femoral head is the most commonly used animal model of femoral head necrosis.The pathological changes of the femoral head are close to clinical practice,however,the conditions,methods and evaluation standards of animal models reported in and outside China are not uniform,which leads to the low scientific value of animal models and is difficult to popularize.This study aimed to clarify the influence of different mold-making conditions on the establishment of steroid-induced osteonecrosis of femoral head rabbit model and analyze the appropriate conditions for the successful model establishment. METHODS:We searched the CNKI,WanFang,VIP,CBM,WoS,PubMed and EMbsae databases for the literature on the modeling of steroid-induced osteonecrosis of femoral head rabbits up to April 1,2022,completed the screening of the literature according to the inclusion and exclusion criteria and literature quality evaluation,and extracted the outcome index data in the literature.RevMan Stata and ADDIS statistical software were used to conduct a meta-analysis of the included data. RESULTS:(1)A total of 82 articles with 1 366 rabbits were included in the study.The steroid-induced osteonecrosis of femoral head modeling methods were divided into three types:steroid-alone method,steroid combined lipopolysaccharide method and steroid combined serum method.Among these,33 articles used steroid-alone method;20 articles used steroid combined lipopolysaccharide method;29 articles used steroid combined serum method.(2)Meta-analysis results showed that the three modeling methods significantly increased the rate of empty bone lacunae in the femoral head of steroid-induced osteonecrosis of femoral head rabbits(P<0.001),and significantly decreased the ratio of the trabecular bone area in the femoral head of steroid-induced osteonecrosis of femoral head rabbits(P<0.001).The order of empty bone lacunae rate of each modeling method was:steroid combined with lipopolysaccharide method>steroid-alone method>steroid combined with serum method>normal group,and the order of trabecular bone area rate of each modeling method was:normal group>steroid combined with serum method>steroid-alone method>steroid combined with lipopolysaccharide method.(3)The results of subgroup analysis suggested that the rate of empty bone lacunae in the rabbit model induced by steroid alone might be related to the rabbit variety and the type of steroid used for modeling(difference between groups P<0.05),in which the combined effect amount of New Zealand white rabbits was higher than that of Chinese white rabbits(P<0.05)and Japanese white rabbits,and the combined effect amount of dexamethasone was higher than that of other steroids.The rate of empty bone lacunae induced by steroid combined with lipopolysaccharide was related to the administration mode of lipopolysaccharide and the type of steroid(P<0.05),among which the combined effect of methylprednisolone sodium succinate was significantly higher than that of other steroids(P<0.05),and the combined effect of prednisolone was significantly lower than that of other steroids(P<0.05).The combined effect of lipopolysaccharide 100 μg/kg×twice was significantly lower than 10 μg/kg×twice and 50 μg/kg×twice(P<0.05).The rate of empty bone lacunae in the model induced by steroid combined with serum was related to serum dose and steroid type(P<0.05),among which the combined effect amount of dexamethasone sodium phosphate was significantly higher than other steroid types(P<0.05),and the combined effect amount of dexamethasone was significantly lower than other steroid types(P<0.05);the combined effect amount of serum"10 mL/kg+6 mL/kg"combined dose was lower than other serum doses(P<0.05). CONCLUSION:(1)With the rate of empty bone lacunae and the ratio of trabecular bone area as the judgment standard for the successful establishment of the model,the three modeling methods can successfully construct the rabbit steroid-induced osteonecrosis of femoral head model,of which the steroid combined with lipopolysaccharide method is the best.(2)New Zealand white rabbits and dexamethasone are recommended when selecting the steroid-alone method.Methylprednisolone sodium succinate and low-dose lipopolysaccharide are recommended when selecting the steroid combined with lipopolysaccharide method.Dexamethasone sodium phosphate is recommended when selecting the steroid combined with serum modeling method.
7.Therapeutic impact of agomelatine in elderly patients with acute cerebral infarction and comorbid anxiety-depression disorders
Guoyang HE ; Qingfang LIU ; Zhihua WANG ; Chunfang LI ; Qigen WAN ; Wei OUYANG
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(6):678-682
Objective To investigate the effect of agomelatine on the clinical efficacy in elderly patients with acute cerebral infarction(ACI)and comorbid anxiety-depression disorders by regu-lating serum neurotransmitters and nerve cytokines.Methods A total of 160 elderly ACI patients with anxiety and depression symptoms admitted in Pingxiang Second People's Hospital from June 2020 to December 2023 were enrolled in this study.All of them received thrombolysis or interven-tional therapy,and then were randomly divided into control and observation groups,with 80 patients in each group.The control group received conventional psychological intervention,while the observation group was given additional oral administration of agomelatine.Cognitive function,neurological function,neurotransmitters and neuronal cytokines,anxiety and depression scores,sleep quality,quality of life,daily activity ability and adverse reactions were compared between the two groups.Results After intervention,Mini Mental State Examination(MMSE)scores,levels of neuropeptide Y(NPY),5-hydroxytryptamine(5-HT),norepinephrine(NE),dopamine and brain-derived neurotrophic factor(BDNF),36-item Brief Health Questionnaire(SF-36)score,and Bar-thel index scale score were significantly higher in both 2 groups when compared with above indicators before the intervention(P<0.01).And the MMSE score,NPY,5-HT,NE,dopamine and BDNF levels,SF-36 score and Barthel index scale score were obviously higher in the observa-tion group than the control group(P<0.01).Both groups obtained notably lower NIHSS score,S100 calcium binding protein B(S100B)and myelin basic protein(MBP)levels,Hamilton Anxiety Rating Scale(HAMA)score,and Hamilton Depression Rating Scale 17(H AMD-17)score and Pittsburgh Sleep Quality Index(PSQI)score after intervention(P<0.01).And the NIHSS score,S100B and MBP levels,HAMA score,HAMD-17 score,and PSQI score were statistically lower in the observation group than the control group(P<0.01).During the treatment process,no signifi-cant difference was observed in the incidence of total adverse reactions between the two groups(3.75%vs 6.25%,x2=0.526,P=0.468).Conclusion When agomelatine tablets are indicated for ACI patients with concomitant anxiety-depression disorders,they can effectively rehabilitate cog-nitive function,enhance neurological function,improve sleep quality and quality of life,optimize activities of daily living,eliminate negative emotions,and correct the expression of neurotransmit-ters and neurotrophic factors.
8.Evidence-based practice for a prevention and management programme of peristomal moisture-associated skin damage in patients
Qiong GUO ; Chunfang LIU ; Jing ZHANG ; Qi TANG ; Mengyuan ZHANG ; Xiuchuan LI
Chinese Journal of Nursing 2024;59(12):1413-1421
Objective To construct an evidence-based prevention and management programme for peristomal moisture-associated skin damage in patients with enterostomy,and to evaluate its clinical effectiveness in improving the knowledge level of nurses and patients about peristomal moisture-associated skin damage in patients with enterostomy and reducing the incidence and severity of peristomal moisture-associated skin damage.Methods Through literature screening,evaluation,and summary,the best evidence for the prevention and management programme of peristomal moisture-associated skin damage in patients with enterostomy was summarized.From October 2021 to March 2022,based on the Ottawa research application model,review indicators were developed based on the best evidence for clinical review,identifying obstacles and promoting factors in evidence application,and developing action strategies to improve the evidence-based practice content for the prevention and management of peristomal moisture-associated skin damage in patients with enterostomy.From April to June 2022,evidence-based practice was conducted in the oncology surgery ward of a tertiary hospital in Anhui Province.The implementation rate of various review indicators by nurses,the knowledge level of peristomal moisture-associated skin damage of nurses and patients,and the incidence and severity of peristomal moisture-associated skin damage were compared before and after evidence-based practice.Results 46 cases were included before the evidence-based practice and 49 cases were included after the evidence-based practice.After evidence-based practice,the implementation rate of each review index was improved;the overall implementation rate increased from(0-66.67%)to(83.33%-100%);the score of the patient's knowledge questionnaire on peristomal moisture-associated skin damage was increased from(69.67±8.31)to(80.18±8.07).The score of the nurse's knowledge questionnaire on peristomal moisture-associated skin damage was increased from(79.83±5.97)to(88.28±5.43).At 4 weeks and 12 weeks of discharge,the incidence of peristomal moisture-associated skin damage was decreased,with a statistically significant difference(P<0.05);the severity of peristomal moisture-associated skin damage was also significantly reduced,with a statistically significant difference(P<0.05).Conclusion Conducting evidence-based practice for the prevention and management of peristomal moisture-associated skin damage can effectively improve the implementation rate of nurse review indicators,improve the knowledge level of nurses and patients with peristomal moisture-associated skin damage,and reduce the incidence and severity of peristomal moisture-associated skin damage in patients with enterostomy.
9.Meta-analysis of Effect of Tripterygium wilfordii Polyglycoside Tablets Combined with Methotrexate and/or Leflunomide on Autoantibodies in Rheumatoid Arthritis
Chao YANG ; Zhixing HU ; Ruirui MING ; Tengteng XU ; Luochangting FANG ; Xiaoxiao WANG ; Taixian LI ; Lin CHEN ; Chunfang LIU
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(5):39-48
ObjectiveTo evaluate the effect of Tripterygium wilfordii polyglycoside tablets (TWPT) combined with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) including methotrexate (MTX) and/or leflunomide (LEF) on autoantibodies in rheumatoid arthritis (RA) patients. MethodPubMed, EMBASE, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP, Wanfang Data, and China Biomedical Literature Service System (SinoMed) were searched for randomized controlled trials (RCTs) of TWPT combined with MTX and/or LEF in the treatment of RA patients from database inception to December 1, 2021. Primary outcome indicators included rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA), and secondary outcome indicators included immunoglobulin (IgA, IgG, and IgM) and adverse drug events (ADE). ResultThirty-one RCTs, involving 2 643 adult patients, were included, including 20 RCTs of TWPT combined with MTX, 10 of TWPT combined with LEF, and one of TWPT combined with MTX and TWPT. The follow-up time ranged from two weeks to 13 months. Compared with csDMARDs alone, TWPT combined with other drugs significantly improved serum RF of RA patients [SMD=-2.45, 95% CI [-2.97, -1.93], P<0.000 01], anti-CCP [SMD=-1.41, 95% CI (-2.35, -0.48), P=0.003], IgM [SMD=-1.90, 95% CI (-3.03, -0.76), P=0.001], and IgA [SMD=-1.18, 95% CI (-2.23, -0.12), P=0.03]. There were no significant effects on IgG [SMD=-1.02, 95% CI (-2.04, 0.01), P=0.05] and ADE [RR=0.87, 95% CI (0.66, 1.15), P=0.32]. ConclusionThe results of this study show that compared with csDMARDs alone, TWPT combined with csDMARDs can effectively improve the levels of autoantibodies in RA patients without increasing the incidence of ADE. However, due to the limited quality and quantity of the included RCTs, the relevant conclusions are only used as a reference for the clinical diagnosis and treatment of RA, and more high-quality studies are still needed to further confirm their efficacy.
10.Anti-swelling and Analgesic Mechanism of Jianpi Tongluo Prescription from MAPKs Signaling Pathway
Ruirui MING ; Changting FANG-LUO ; Xiaoxiao WANG ; Zhixing HU ; Chao YANG ; Tengteng XU ; Hongjie WANG ; Chunfang LIU ; Na LIN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(12):85-93
ObjectiveTo observe the anti-swelling and analgesic effects of Jianpi Tongluo prescription (JPTL) and to explore its mechanism initially. MethodA total of 120 ICR mice were divided into normal group, model group, JPTL low-, medium- and high-dose groups (5, 10, 20 g·kg-1) and positive drug (celecoxib, 0.03 g·kg-1) group, with 10 in each group (po,once a day). Complete freund's adjuvant (CFA) was used to induce the model of chronic inflammatory pain, and xylene-induced ear swelling test, hot plate test and acetic acid writhing test were performed to observe the anti-swelling and analgesic effects of different doses of JPTL in these four acute and chronic models. Further, enzyme-linked immunosorbent assay (ELISA) was used to detect the expressions of prostaglandin E2 (PGE2), interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in serum and inflammatory paw of mice with chronic inflammatory pain, and the expressions of aquaporin 1 (AQP1), aquaporin 3 (AQP3), cyclooxygenase 1 (COX1), cyclooxygenase 2 (COX2) and mitogen-activated protein kinases (MAPKs) in inflammatory paw were detected by Western blot, to explore the preliminary mechanism of JPTL. ResultCompared with the conditions in the normal group, there was a significant increase in the ear swelling of xylene-induced model mice, a shortened paw withdrawal latency in the hot plate test (P<0.01). Compared with the model group, JPTL remarkably increased the inhibition rate of xylene-induced ear swelling (P<0.05, P<0.01), prolonged the latency period of writhing caused by acetic acid and reduced the number of writhing (P<0.05, P<0.01). Compared with normal group, the degree of feet swelling in chronic inflammatory pain mice was significantly increased, the threshold of mechanical pain was decreased and the threshold of cold pain was increased (P<0.05, P<0.01), the protein contents of AQP1 and AQP3 in inflammatory feet were increased, and the contents of IL-1β, IL-6, TNF-α, PGE2 and COX2 in inflammatory feet were increased in serum and/or inflammatory feet. The protein expression levels of p-p38 MAPK, p-JNK and p-ERK in inflammatory feet were increased (P<0.01). Compared with the model group, JPTL relieved paw swelling of mice with chronic inflammatory pain, elevated mechanical withdrawal threshold while decreased cold withdrawal threshold, with analgesia lasting for 4 h and the optimal time point for analgesia being 2 h after administration (P<0.05, P<0.01). Moreover, JPTL down-regulated AQP1, AQP3, COX2, p-p38 MAPK, p-JNK and p-ERK in inflammatory paw of mice with chronic inflammatory pain and reduced IL-1β, IL-6, TNF-α, and PGE2 in serum and/or inflammatory paw, but it had no significant effect on COX1 (P<0.05, P<0.01). ConclusionJPTL has anti-swelling and analgesic effects, and its mechanism is related to inhibiting the production of cytokines and inflammatory mediators via the down-regulation of MAPKs signaling pathway, which provides an experimental basis for the clinical application of JPTL.

Result Analysis
Print
Save
E-mail