1.Association between the Non-Fasting Triglyceride-Glucose Index and Hyperglycemia in pregnancy during the Third Trimester in High Altitudes
Qingqing WANG ; Hongying HOU ; Ma NI ; Yating LIANG ; Xiaoyu CHEN ; WA Zhuoga DA ; Qiang LIU ; Zhenyan HAN
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(5):861-871
ObjectiveTo investigate the relationship between the non-fasting triglyceride and glucose (TyG) index and hyperglycemia in pregnancy during the third trimester in high altitudes. MethodsThis study selected clinical and laboratory data of 774 Tibetan singleton pregnant women who delivered at Chaya People's Hospital of Qamdo city in Xizang autonomous region, from January 2023 to April 2025. The non-fasting TyG index was calculated from non-fasting triglyceride (TG) and random plasma glucose (PG). Based on the tertiles of the non-fasting TyG index values, the individuals were split into three groups (corresponding to non-fasting TyG index of 8.89 and 9.21, respectively). The baseline clinical characteristics, lipid levels and the occurrence of developing hyperglycemia in pregnancy were compared among the three groups. Statistical analyses were performed using ANOVA, Kruskal-Wallis H test, Chi-square test, or Fisher exact test and the relationship between the non-fasting TyG index and hyperglycemia in pregnancy were examined using multivariate logistic regression models and curve fitting. ResultsA total of 774 Tibetan singleton pregnant women were included, with a average age of 27.3 ± 6.1 years, a pre-delivery body mass index (Pre-BMI) of (25.2±2.3)kg/m2 , a proportion of 26.7% (207/774) primigravid women, the mean non-fasting TyG index was 9.1 ± 0.4。Thirty pregnant women were diagnosed with hyperglycemia in pregnancy, with a detection rate of 3.9% (30/774). Statistically significant differences in serum total cholesterol (TC), TG, low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels were identified when comparing different non-fasting TyG groups (all P values <0.05). Subsequent trend test analysis indicated that the levels of TC, TG, LDL-C, and PG gradually increased with elevated the non-fasting TyG index ( Ftrend TC=95.61, P<0.001; Ftrend TG=1 051.91, P<0.001; Ftrend LDL-C = 97.20, P < 0.001; Ftrend TG=195.20; P<0.001). After adjustment for maternal age, pre-delivery BMI, altitude, TC, LDL-C, and HDL-C, multivariate Logistic regression models revealed independent positive associations between non-fasting TyG index and hyperglycemia in pregnancy (Model 1: OR=2.72, 95% CI: 1.13-6.53, P=0.026; Model 2: OR=2.56, 95% CI: 1.01-6.50, P=0.048; Model 3: OR=2.72, 95% CI: 1.06-6.97, P=0.037; Model 4: OR=4.02, 95% CI: 1.42-11.40, P=0.009) and the incident of hyperglycemia in pregnancy showed an increasing tendency as increasing with the non-fasting TyG index, however, this association did not statistical significance (P trend >0.05). Curve fitting by restricted cubic splines (RCS) were used to assess linearity between non-fasting TyG and hyperglycemia in pregnancy, and there was a linear dose-response relationship between non-fasting TyG and hyperglycemia in pregnancy (P for non-linear = 0.515). ConclusionNon-fasting TyG index in the third trimester is a risk factor for hyperglycemia in pregnancy among the Tibetan singleton pregnant women at high altitudes and there was a possible linear dose-response relationship between the non-fasting TyG index and hyperglycemia in pregnancy.
2.Effect of moxibustion on small intestinal mucosal immune barrier in rats with diarrhea-predominant irritable bowel syndrome.
Kuiwu LI ; Haoran CHU ; Ling ZOU ; Jingru RUAN ; Lumin LIAO ; Xiaoyu HAN ; Wenli MA ; Ming FANG ; Jingwei ZHU ; Yucheng FANG ; Ziye WANG ; Tingting TONG
Chinese Acupuncture & Moxibustion 2025;45(7):935-944
OBJECTIVE:
To observe the effect of moxibustion on small intestinal mucosal immune barrier in rats with diarrhea-predominant irritable bowel syndrome (IBS-D) and explore its underlying mechanisms.
METHODS:
Of 38 newborn rats from 4 healthy SPF pregnant rats, 12 neonatal rats were randomly selected in a normal group. IBS-D model was prepared by the combined measures for the rest rats, including neonatal maternal separation, acetic acid enema and chronic restraint stress. Twenty-four successfully-modeled rats were randomized into a model group and a moxibustion group, 12 rats in each one. In the moxibustion group, suspending moxibustion was delivered at bilateral "Tianshu" (ST25) and "Shangjuxu" (ST37), 20 min each time, once daily and for 7 consecutive days. Separately, before acetic acid enema (aged 35 days), after modeling (aged 45 days) and after intervention (aged 53 days), the body mass, loose stool rate (LSR) and and the minimum volume threshold when abdominal withdrawal reflex (AWR) scored 3 were observed in the rats of each group. After intervention (aged 53 days), using HE and PAS staining, the morphology of duodenum was observed, the length of villus and the depth of crypt were measured, the ratio of the length of villus to the depth of crypt was calculated; and the numbers of mucosal intraepithelial lymphocytes (IELs) and goblet cells were counted. With ELISA adopted, the contents of γ-interferon (IFN-γ), interleukin-4 (IL-4) and secretory immunoglobulin A (sIgA) in duodenal mucosa of rats were detected. The proportion of T cell subsets in duodenal mucosa was detected using flow cytometry. The microvilli and tight junctions of duodenal mucosal epithelial cells were observed by transmission electron microscopy, and the integrity of duodenal mucosa observed by scanning electron microscopy.
RESULTS:
Compared with the normal group, for the rats in the model group, the body mass, the minimum volume threshold when AWR scored 3, the length of duodenal villus and the the ratio of the length of villus to the depth of crypt, as well as the proportion of CD8+ T subset were all reduced (P<0.01, P<0.05), the counts of goblet cells in duodenal mucosa decreased (P<0.01); LRS, the proportion of CD4+ T subset and CD4+/CD8+, as well as the contents of IFN-γ, IL-4 and sIgA in duodenal mucosa and IFN-γ/IL-4 were all elevated (P<0.01); and the numbers of IELs rose (P<0.01). The morphology of duodenal mucosa was irregular, the villi got shorter, sparse and scattered, with uneven density. The morphology of epithelial cells was destroyed and the tight junctions damaged, with larger spaces. When compared with the model group, in the moxibustion group, the body mass, the minimum volume threshold when AWR scored 3, the length of duodenal villus and the ratio of the length of villus to the depth of crypt, as well as the counts of goblet cells in duodenal mucosa increased (P<0.01); LRS, the proportion of CD4+ T subset, and CD4+/CD8+, as well as the contents of IFN-γ, IL-4 and sIgA in duodenal mucosa and IFN-γ/IL-4 were reduced (P<0.01); and the numbers of IELs was dropped (P<0.01). The morphology of duodenal mucosa was more regular, the villi were grew, got longer and arranged regularly, with even density. The morphology of epithelial cells was slightly destroyed, and the tight junctions partially damaged.
CONCLUSION
Moxibustion at "Tianshu" (ST25) and "Shangjuxu" (ST37) can reduce visceral hypersensitivity in IBS-D rats and relieve abdominal pain, diarrhea and other symptoms. Its effect mechanism may be related to the repair of small intestinal mucosal immune barrier and the improvement in the immune function in IBS-D.
Animals
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Irritable Bowel Syndrome/immunology*
;
Rats
;
Moxibustion
;
Intestinal Mucosa/immunology*
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Female
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Diarrhea/therapy*
;
Intestine, Small/immunology*
;
Male
;
Humans
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Rats, Sprague-Dawley
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Disease Models, Animal
3.Efficacy and safety of avatrombopag in the treatment of thrombocytopenia after umbilical cord blood transplantation.
Aijie HUANG ; Guangyu SUN ; Baolin TANG ; Yongsheng HAN ; Xiang WAN ; Wen YAO ; Kaidi SONG ; Yaxin CHENG ; Weiwei WU ; Meijuan TU ; Yue WU ; Tianzhong PAN ; Xiaoyu ZHU
Chinese Medical Journal 2025;138(9):1072-1083
BACKGROUND:
Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT), and there is no standard therapy. Avatrombopag (AVA) is a second-generation thrombopoietin (TPO) receptor agonist (TPO-RA) that has shown efficacy in immune thrombocytopenia (ITP). However, few reports have focused on its efficacy in patients diagnosed with thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT).
METHODS:
We conducted a retrospective study at the First Affiliated Hospital of the University of Science and Technology of China to evaluate the efficacy of AVA as a first-line TPO-RA in 65 patients after UCBT; these patients were compared with 118 historical controls. Response rates, platelet counts, megakaryocyte counts in bone marrow, bleeding events, adverse events and survival rates were evaluated in this study. Platelet reconstitution differences were compared between different medication groups. Multivariable analysis was used to explore the independent beneficial factors for platelet implantation.
RESULTS:
Fifty-two patients were given AVA within 30 days post-UCBT, and the treatment was continued for more than 7 days to promote platelet engraftment (AVA group); the other 13 patients were given AVA for secondary failure of platelet recovery (SFPR group). The median time to platelet engraftment was shorter in the AVA group than in the historical control group (32.5 days vs . 38.0 days, Z = 2.095, P = 0.036). Among the 52 patients in the AVA group, 46 achieved an overall response (OR) (88.5%), and the cumulative incidence of OR was 91.9%. Patients treated with AVA only had a greater 60-day cumulative incidence of platelet engraftment than patients treated with recombinant human thrombopoietin (rhTPO) only or rhTPO combined with AVA (95.2% vs . 84.5% vs . 80.6%, P <0.001). Patients suffering from SFPR had a slightly better cumulative incidence of OR (100%, P = 0.104). Patients who initiated AVA treatment within 14 days post-UCBT had a better 60-day cumulative incidence of platelet engraftment than did those who received AVA after 14 days post-UCBT (96.6% vs . 73.9%, P = 0.003).
CONCLUSION
Compared with those in the historical control group, our results indicate that AVA could effectively promote platelet engraftment and recovery after UCBT, especially when used in the early period (≤14 days post-UCBT).
Humans
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Female
;
Male
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Thrombocytopenia/etiology*
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Adult
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Retrospective Studies
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Cord Blood Stem Cell Transplantation/adverse effects*
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Middle Aged
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Adolescent
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Young Adult
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Thiazoles/adverse effects*
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Platelet Count
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Receptors, Thrombopoietin/agonists*
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Child
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Thiophenes
4.Incidence, mortality, and burden of Parkinson's disease in China: A time-trend analysis and comparison with the global burden based on Global Burden of Disease Study 2021.
Fan GAO ; Xiaoyu CHENG ; Junyi LIU ; Yinlian HAN ; Chengjie MAO ; Chongke ZHONG ; Chunfeng LIU
Chinese Medical Journal 2025;138(23):3176-3183
BACKGROUND:
Parkinson's disease (PD) is a leading cause of death and disability worldwide, and is associated with a significant Global Burden of Disease (GBD). We analyzed the trends in PD incidence, mortality, and disability-adjusted life year (DALY) burden in China, and compared them with global data.
METHODS:
Estimates and 95% uncertainty intervals (UIs) for incidence, mortality, DALYs, years lived with disability (YLDs), and years of life lost (YLLs) for PD were extracted from the GBD, Injuries, and Risk Factors Study 2021. We describe the epidemiology of PD at global and Chinese levels, analyze trends in incidence and mortality from 1990 to 2021 by joinpoint regression models, and decompose PD burden according to population size, age structure, and epidemiological changes.
RESULTS:
GBD 2021 estimated 508,378 (95% UI: 430,499-592,748) incident cases of PD, 92,035 (95% UI: 75,908-108,133) deaths, and 2,159,514 (95% UI: 1,826,196-2,521,344) DALYs in China, with the higher age-standardized rate (ASR) in incidence, mortality and DALYs than the global levels. The DALY burden of PD in China increased slightly from 1990 to 2021, consistent with the global upward trend. Joinpoint regression analysis indicated that the ASR of incidence in China increased faster than the global average, while the ASR of mortality decreased, with the fastest decline in 2004-2014. Decomposition analysis revealed that men and the middle sociodemographic index (SDI) quintile (32.82%) were responsible for the most significant DALYs, whose changes were primarily driven by population growth and aging.
CONCLUSIONS
The burden of PD showed an overall increasing trend from 1990 to 2021, which was primarily driven by population growth and aging. This study highlights the significant challenges in controlling and managing PD, including the increase in cases and gender differences, which may provide guidance for comprehensive strategies to address the changing profiles of PD in China.
Humans
;
Parkinson Disease/mortality*
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China/epidemiology*
;
Global Burden of Disease
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Male
;
Incidence
;
Female
;
Disability-Adjusted Life Years
;
Middle Aged
;
Aged
;
Adult
;
Quality-Adjusted Life Years
;
Aged, 80 and over
;
Cost of Illness
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Adolescent
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Pattern Analysis, Machine
5.Autophagy in skeletal muscle dysfunction of chronic obstructive pulmonary disease: implications, mechanisms, and perspectives.
Xiaoyu HAN ; Peijun LI ; Meiling JIANG ; Yuanyuan CAO ; Yingqi WANG ; Linhong JIANG ; Xiaodan LIU ; Weibing WU
Journal of Zhejiang University. Science. B 2025;26(3):227-239
Skeletal muscle dysfunction is a common extrapulmonary comorbidity of chronic obstructive pulmonary disease (COPD) and is associated with decreased quality-of-life and survival in patients. The autophagy lysosome pathway is one of the proteolytic systems that significantly affect skeletal muscle structure and function. Intriguingly, both promoting and inhibiting autophagy have been observed to improve COPD skeletal muscle dysfunction, yet the mechanism is unclear. This paper first reviewed the effects of macroautophagy and mitophagy on the structure and function of skeletal muscle in COPD, and then explored the mechanism of autophagy mediating the dysfunction of skeletal muscle in COPD. The results showed that macroautophagy- and mitophagy-related proteins were significantly increased in COPD skeletal muscle. Promoting macroautophagy in COPD improves myogenesis and replication capacity of muscle satellite cells, while inhibiting macroautophagy in COPD myotubes increases their diameters. Mitophagy helps to maintain mitochondrial homeostasis by removing impaired mitochondria in COPD. Autophagy is a promising target for improving COPD skeletal muscle dysfunction, and further research should be conducted to elucidate the specific mechanisms by which autophagy mediates COPD skeletal muscle dysfunction, with the aim of enhancing our understanding in this field.
Pulmonary Disease, Chronic Obstructive/physiopathology*
;
Autophagy/physiology*
;
Humans
;
Muscle, Skeletal/pathology*
;
Mitophagy
;
Animals
;
Mitochondria/metabolism*
;
Lysosomes
6.Expert consensus on clinical randomized controlled trial design and evaluation methods for bone grafting or substitute materials in alveolar bone defects.
Xiaoyu LIAO ; Yang XUE ; Xueni ZHENG ; Enbo WANG ; Jian PAN ; Duohong ZOU ; Jihong ZHAO ; Bing HAN ; Changkui LIU ; Hong HUA ; Xinhua LIANG ; Shuhuan SHANG ; Wenmei WANG ; Shuibing LIU ; Hu WANG ; Pei WANG ; Bin FENG ; Jia JU ; Linlin ZHANG ; Kaijin HU
West China Journal of Stomatology 2025;43(5):613-619
Bone grafting is a primary method for treating bone defects. Among various graft materials, xenogeneic bone substitutes are widely used in clinical practice due to their abundant sources, convenient processing and storage, and avoidance of secondary surgeries. With the advancement of domestic production and the limitations of imported products, an increasing number of bone filling or grafting substitute materials isentering clinical trials. Relevant experts have drafted this consensus to enhance the management of medical device clinical trials, protect the rights of participants, and ensure the scientific and effective execution of trials. It summarizes clinical experience in aspects, such as design principles, participant inclusion/exclusion criteria, observation periods, efficacy evaluation metrics, safety assessment indicators, and quality control, to provide guidance for professionals in the field.
Humans
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Bone Substitutes/therapeutic use*
;
Randomized Controlled Trials as Topic/methods*
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Consensus
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Bone Transplantation
;
Research Design
7.Cloning and expression analysis of the laccase gene RcLAC15 from Rosa chinensis.
Qi LI ; Yifang PENG ; Qijing DONG ; Qian YANG ; Xiaoyu LIU ; Yu HAN
Chinese Journal of Biotechnology 2025;41(2):845-856
Laccases (LACs), belonging to the multicopper oxidase family, are closely associated with various biological functions including lignin synthesis and responses to biotic and abiotic stresses in plants. However, few studies have reported the laccase genes in China rose (Rosa chinensis). Prickles cause difficulties to the management and harvest of R. chinensis and have become a trait concerned in the breeding. To investigate the expression patterns of laccase genes in roses, we cloned a laccase gene from an ancient variety R. chinensis 'Old Blush' and named it RcLAC15. The expression level of RcLAC15 in prickles was significantly higher than those in roots, stems, and leaves. Fifty-eight laccase genes were identified in the genome of R. chinensis, and bioinformatics analysis revealed that RcLAC15 was a homolog of AtLAC15, predicting that RcLAC15 was a stable hydrophilic protein without transmembrane structures. The recombinant expression vector pBI121-proRcLAC15:: GUS was introduced into Arabidopsis, and GUS staining results showed that the RcLAC15 promoter specifically drove GUS gene expression at the edges of Arabidopsis leaves. In summary, RcLAC15 is a gene specifically expressed in the prickles of R. chinensis. This discovery provides a reference for exploring the biological functions of laccase genes in the prickles of R. chinensis.
Laccase/metabolism*
;
Rosa/enzymology*
;
Cloning, Molecular
;
Gene Expression Regulation, Plant
;
Plant Proteins/metabolism*
;
Arabidopsis/metabolism*
;
Plants, Genetically Modified/metabolism*
8.Evolution of global disease burden,risk factors and trend projection of chronic obstructive pulmonary disease among individuals under 50 years old from 1990 to 2021
Yide WANG ; Hongxia DUAN ; Yingqi WANG ; Yidie BAO ; Linhong JIANG ; Xiaoyu HAN ; Peijun LI ; Weibing WU ; Xiaodan LIU
Journal of Army Medical University 2025;47(12):1388-1400
Objective To systematically assess the spatiotemporal distribution,risk factors,and future trends of chronic obstructive pulmonary disease(COPD)among individuals under 50 years of age globally from 1990 to 2021 based on Global Burden of Disease(GBD)data in order to provide support for the formulation of prevention and control strategies of the disease.Methods The GBD data from 1990 to 2021 were analyzed for the incidence,mortality,disability-adjusted life years(DALYs),and estimated annual percentage change(EAPC)of COPD in<50-year-old individuals across 204 countries and regions.The data were stratified by age,sex,region,country,and sociodemographic index(SDI).The COPD trends until 2035 were predicted.Results In 2021,the global incidence of early-onset COPD was estimated at 2.5 million cases(95%uncertainty interval:2.09~2.96 million),representing a 50.55%increase compared to 1990.Significant regional heterogeneity was observed,with low SDI regions experiencing a 134.08%increase,whereas high SDI regions exhibited a rise-then-fall trend.Risk factor analysis identified environmental and occupational exposures(air pollution,ambient ozone pollution,household air pollution from solid fuels,etc.)and smoking as the primary etiological factors.Notably,household solid fuel exposure accounted for 50.90%of COPD-related deaths in low SDI regions,compared to only 0.03%in high SDI regions.Projections indicated that by 2035,the global burden of early-onset COPD will increase to 2.59 million cases.Conclusion The global disease burden of COPD among people under 50 years increased significantly from 1990 to 2021,with pronounced disparities across regions and socioeconomic levels.COPD deaths in low-SDI regions are strongly associated with solid fuel exposure and particulate matter pollution,and these regions are expected to remain the main drivers of global COPD incidence growth through 2035.
9.Epidemiological Characteristics of Influenza-like Illness Outbreaks in Yunnan Province from 2017 to 2023
Yaoyao CHEN ; Xingchen WEI ; Xiaoyu HAN ; Lifen ZHANG
Journal of Kunming Medical University 2025;46(8):27-32
Objective To analyze the epidemiological characteristics of influenza-like illness outbreaks in Yunnan Province from 2017 to 2023,and to provide the evidence for the prevention and control of influenza in Yunnan Province.Methods The data of influenza-like illness outbreaks and outbreak specimens were collected in Yunnan Province from 2017 to 2023.Descriptive epidemiological methods were used to describe and analyze the epidemic time,population,region and pathogen distribution.Results A total of 340 influenza-like illness outbreaks were reported in Yunnan Province from 2017 to 2023,with 12586 reported cases and a cumulative incidence of 2.34%.The outbreaks were mainly concentrated in November to January and March of the following year,with a high incidence in winter and spring.Schools were the most important place of outbreak,with primary and secondary school students being the main affected group.The cumulative number of reported cases in Dali Prefecture,Dehong Prefecture,Yuxi City and Kunming City ranked among the top in the province,accounting for 79.71%of the total number of outbreaks in the province.The pathogen types alternated and were mainly prevalent in H1N1(119 cases),H3N2(81 cases),and Victoria(83 cases).Conclusion The outbreak of influenza-like illness in Yunnan Province shows the obvious seasonality,and primary and secondary schools are the main outbreak sites.The outbreak surveillance in schools should be strengthened continuously to control the occurrence and development of the epidemic.
10.Evaluation of the effect of puerarin on rheumatoid arthritis in rats based on AKT-FOXO1-IL-9 pathway
Xiaoyu Liu ; Han Yu ; Jie Yu ; Jingru Gao ; Qingqing Ma ; Jihai Shi ; Xiangli Dong ; Jinqi Hao ; Ruolan Yin ; Yanqin Yu
Acta Universitatis Medicinalis Anhui 2025;60(10):1839-1846
Objective:
To explore the therapeutic mechanism of puerarin in treating rheumatoid arthritis (RA) rats based on the serine/tyrosine protein kinase B (AKT)-phosphorylated forkhead box protein O1 (FOXO1)-interleukin-9 (AKT-FOXO1-IL-9) signaling pathway.
Methods :
36 rats were randomly divided into a blank group , a model group , a positive control group , and low , medium , and high dose groups of puerarin. Except for the blank group , the other groups were induced with type Ⅱ collagen to establish a RA rat model. After successful modeling , different doses of puerarin and methotrexate were given to treat the rats. The body mass and toe thickness of the rats were measured , and biochemical indicators of rat blood rheology were detected. X-ray was used to observe changes in rat joint morphology. Safranin green staining were used to observe the pathology of rat joint tissue. ELISA was used to detect the levels of IL-9 and rheumatoid factors in rat serum , and Western blot was used to detect changes in levels of AKT and FOXO1 . 36 rats were randomly divided into a blank group , a model group , a positive control group , and low , medium , and high dose groups of puerarin. Except for the blank group , the other groups were induced with type Ⅱ collagen to establish a RA rat model. After successful modeling , different doses of puerarin and methotrexate were given to treat the rats. The body mass and toe thickness of the rats were measured , and biochemical indicators of rat blood rheology were detected. X-ray was used to observe changes in rat joint morphology. Safranin green staining were used to observe the pathology of rat joint tissue. ELISA was used to detect the levels of IL-9 and rheumatoid factors in rat serum , and Western blot was used to detect changes in levels of AKT and FOXO1 .
Results:
Compared with the blank group , the model group had the lowest toe thickness , and X-ray images showed more obvious segmental stenosis and more severe marginal bone invasion ; scaly like changes appeared at the edges of joints stained with safranin green , accompanied by the exudation of inflammatory cells and increased proliferation and secretion of chondrocytes ; the expression levels of inflammatory factors IL-9 and rheumatoid factors were the highest , and the expression levels of AKT and FOXO1 proteins were the highest (P < 0. 05) . Compared with the model group , the toe thickness of rats treated with different doses of puerarin decreased ; X-ray images showed that the puerarin treatment group of rats showed improvement in plantar joint stenosis and marginal bone invasion ; the results of safranin green staining showed that after treatment with different doses of puerarin , the infiltration of inflammatory cells decreased , and the expression levels of inflammatory factor IL-9 , rheumatoid factors , AKT , and FOXO1 proteins decreased significantly ( P < 0. 05 ) , with the high-dose puerarin group showing the most significant difference. Compared with the high-dose puerarin group , the positive control group showed a significant decrease in the above results and statistical differences (P < 0. 05) .
Conclusion
Puerarin has a good therapeutic effect on rats with RA by inhibiting the AKT-FOXO1-IL-9 pathway. The high-dose puerarin group (60 mg/kg) has the best therapeutic effect and the results show a dose-response relationship.


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