1.Role and significance of artificial intelligence preoperative planning in total hip arthroplasty
Meipeng MIN ; Jin WU ; RAFI URBA ; Wenjie ZHANG ; Jia GAO ; Yunhua WANG ; Bin HE ; Lei FAN
Chinese Journal of Tissue Engineering Research 2024;28(9):1372-1377
BACKGROUND:The preoperative planning of traditional X-ray films is often inaccurate,which can lead to some intraoperative and postoperative complications,increase the operation time and intraoperative blood loss,and to some extent affect the surgical outcome of total hip arthroplasty. OBJECTIVE:To investigate the accuracy and effectiveness of artificial intelligence preoperative planning in total hip arthroplasty. METHODS:Sixty patients who underwent primary total hip arthroplasty on the affected side were selected.30 of them used artificial intelligence 3D preoperative planning(trial group)and 30 used conventional X-ray film 2D preoperative planning(control group),and there were no statistically significant differences between the two groups in terms of gender,age,condition and other general data(P>0.05).The actual intraoperative prosthesis placement and preoperative planning prosthesis matching,intraoperative operation time,intraoperative blood loss,bilateral femoral eccentric distance difference,bilateral joint eccentric distance difference and bilateral lower limb length difference,and Harris score at 3 months after operation were compared between the two groups,and the accuracy and application effect of the two preoperative plans were analyzed. RESULTS AND CONCLUSION:(1)Patients in both groups were followed up for 4-6 months postoperatively.One patient in the control group had a posterior dislocation of the prosthesis at 5 days postoperatively,which recovered after performing manual repositioning without re-dislodgement.The rest of the patients did not have postoperative complications or postoperative death.(2)Complete matching rate of the prosthesis on the acetabular side and femoral side was significantly better in the trial group than that in the control group(P<0.05).(3)Operation time and intraoperative blood loss were significantly less in the trial group than those in the control group(P<0.05).(4)The difference in bilateral lower limb length between the two groups was statistically significant(P<0.05),and the difference in bilateral femoral eccentric distance and bilateral joint eccentric distance was not statistically significant(P>0.05).(5)Harris score of patients in the trial group was significantly higher than that in the control group 3 months after operation(P<0.05).(6)These results confirm that compared with traditional film planning,artificial intelligence preoperative planning can predict the prosthesis type more accurately,shorten the operation time,reduce intraoperative blood loss,diminish the occurrence of postoperative bilateral lower limb inequality,and accelerate postoperative recovery.
2.The Role and Possible Mechanisms of Exercise in Combating Osteoporosis by Modulating The Bone Autophagy Pathway
Xin-Yu DAI ; Bin LI ; Dan JIN ; Xue-Jie YI ; Rui-Qi HUANG ; Hai-Ning GAO
Progress in Biochemistry and Biophysics 2024;51(7):1589-1603
Osteoporosis leads to an imbalance in bone remodelling, where bone resorption is greater than bone formation and osteoclast degradation increases, resulting in severe bone loss. Autophagy is a lysosomal degradation pathway that regulates the proliferation, differentiation, and apoptosis of various bone cells (including osteoblasts, osteoclasts, and osteoclasts), and is deeply involved in the bone remodelling process. In recent years, the role of autophagy in the progression of osteoporosis and related bone metabolic diseases has received more and more attention, and it has become a research hotspot in this field. Summarising the existing studies, it is found that senile osteoporosis is the result of a combination of factors. On the one hand, it is the imbalance of bone remodelling and the increase of bone resorption/bone formation ratio with ageing, which causes progressive bone loss. On the other hand, aging leads to a general decrease in the level of autophagy, a decrease in the activity of osteoblasts and osteoclasts, and an inhibition of osteogenic differentiation. The lack of oestrogen leads to the immune system being in a low activation state, and the antioxidant capacity is weakened and inflammatory response is increased, inducing autophagy-related proteins to participate in the transmission of inflammatory signals, excessive accumulation of reactive oxygen species (ROS) in the skeleton, and negatively regulating bone formation. In addition, with aging and the occurrence of related diseases, glucocorticoid treatments also mediate autophagy in bone tissue cells, contributing to the decline in bone strength. Exercise, as an effective means of combating osteoporosis, improves bone biomechanical properties and increases bone density. It has been found that exercise induces oxidative stress, energy imbalance, protein defolding and increased intracellular calcium ions in the organism, which in turn activates autophagy. In bone, exercise of different intensities activates messengers such as ROS, PI3K, and AMP. These messengers signal downstream cascades, which in turn induce autophagy to restore dynamic homeostasis in vivo. During exercise, increased production of AMP, PI3K, and ROS activate their downstream effectors, AMPK, Akt, and p38MAPK, respectively, and these molecules in turn lead to activation of the autophagy pathway. Activation of AMPK inhibits mTOR activity and phosphorylates ULK1 at different sites, inducing autophagy. AMPK and p38 up-regulate per-PGC-1α activity and activate transcription factors in the nucleus, resulting in increased autophagy and lysosomal genes. Together, they activate FoxOs, whose transcriptional activity controls cellular processes including autophagy and can act on autophagy key proteins, while FoxOs proteins are expressed in osteoblasts. Exercise also regulates the expression of mTORC1, FoxO1, and PGC-1 through the PI3K/Akt signalling pathway, which ultimately plays a role in the differentiation and proliferation of osteoblasts and regulates bone metabolism. In addition, BMPs signaling pathway and long chain non-coding RNAs also play a role in the proliferation and differentiation of osteoblasts and autophagy process under exercise stimulation. Therefore, exercise may become a new molecular regulatory mechanism to improve osteoporosis through the bone autophagy pathway, but the specific mechanism needs to be further investigated. How exercise affects bone autophagy and thus prevents and treats bone-related diseases will become a future research hotspot in the fields of biology, sports medicine and sports science, and it is believed that future studies will further reveal its mechanism and provide new theoretical basis and ideas.
3.Comparison of chemical components of Lonicera fragrantissima and Lonicera japonica based on LC-MS
Ying JIN ; Le-Wen XIONG ; Gao-Bin PU ; Fang ZHANG ; Jia LI ; Long-Fei ZHANG ; Yong-Qing ZHANG
Chinese Traditional Patent Medicine 2024;46(3):850-859
AIM To compare the components difference between Lonicera fragrantissima Lindl.et Paxt.(LFL)and Lonicerae japonicae Flos(LJF),and to evaluate the medicinal value of LFL,so as to provide reference for the development and utilization of LFL and LJF.METHODS With 70%methanol as extraction solvent,the components were analyzed by UPLC-TOF-MS,and the contents of 20 components were determined by HPLC-QQQ-MS.The components difference was determined by multivariate statistical analysis.RESULTS A total of 52 components were identified in the buds of LFL and LJF.There were 4 different components in LJF,and the contents of 20 quantitative components were significantly different.The contents of isochlorogenic acid C,ferulic acid,luteolin and rutin in the buds of LFL were more than 2 times that of LJF,and the contents of marchanic acid and marchanin were 11.96 times and 37.23 times that of LJF respectively.Maganin,isochlorogenic acid A,maganic acid,rutin and dicomachanic acid are the key differentiating components of LFL and LJF.CONCLUSION The buds of LFL and LJF have similar species,but the content difference is obvious.The buds of LFL have important medicinal value,which need further development and utilization.
4.Arterial prophylactic occlusion technique in the application of surgery for locally advanced pancreatic cancer with arterial involvement after conversion therapy
Kailian ZHENG ; Xinyu LIU ; Xiaohan SHI ; Huan WANG ; Xiaoyi YIN ; Xinqian WU ; Lingyun GU ; Penghao LI ; Yikai LI ; Wei JING ; Shiwei GUO ; Bin SONG ; Suizhi GAO ; Gang JIN
Chinese Journal of Surgery 2024;62(10):938-946
Objective:To investigate and compare the clinical outcomes of the arterial pre-occlusion technique(APOT) and the traditional technique in the surgery of locally advanced pancreatic cancer with arterial involvement after conversion therapy.Methods:This is a retrospective cohort study. The clinical data of 145 patients with locally advanced pancreatic cancer with arterial involvement admitted to the Department of Hepato-Biliary-Pancreatic Surgery of the First Hospital Affiliated to Naval Medical University,from January 2020 to December 2022 were retrospectively analyzed. All patients completed neoadjuvant therapy for tumors, and the feasibility of radical surgical treatment was determined by a multidisciplinary collaborative team evaluation before surgery. According to whether the intraoperative artery was pre-occluded, 145 patients were divided into two groups, including 28 cases in the APOT group(16 males, 12 females, aged (59.0±9.4) years), and 117 cases in the routine surgery group(76 males, 41 females, aged (55.1±8.2) years). To ensure comparability of baseline data between the APOT group and the routine surgery group, a 1∶2 match was performed using the propensity score matching method, and the caliper value was 0.006 45. The t-test,the Mann-Whitney U test, χ2 test or Fisher′s exact test were used to compare the data between the two groups,respectively. Results:After matching the propensity score,there were 28 cases in the APOT group and 56 cases in the routine surgery group. There were no significant differences in gender,age,preoperative comorbidities,preoperative body mass index,surgical approaches,chemotherapy regimen,stereotactic body radiation therapy ratio,tumor markers,and type of invaded artery between the two groups (all P>0.05).The arterial occlusion time M(IQR) in the APOT group was 7.0(3.8)minutes(range:3 to 15 minutes),and no ischemic manifestations were observed in the distal target organs that blocked blood vessels after surgery. The operation time was (170.3±57.7)minutes in the APOT group and (235.0±80.2)minutes in the routine surgery group,and the difference was statistically significant ( t=-3.800, P<0.01). The APOT group also experienced less intraoperative blood loss(650(588)ml vs. 800(600)ml; U=1 026.500, P=0.021). No significant differences were found between the groups in combined vein resection and reconstruction,celiac trunk resection,early postoperative complications, readmission rates at 30 days,and postoperative length of stay(all P>0.05). Extra-arterial dissection was performed in all patients,with arterial resection and reconstruction in 3 cases: 2 cases in the APOT group(1 case involving the superior mesenteric artery and 1 case involving the common hepatic artery) and 1 case in the routine group(involving the common hepatic artery). Postoperative abdominal bleeding occurred in 4 cases,with 3 cases in the routine group,1 case in the routine group. The R0 resection rate was 85.7%(24/28) in the APOT group and 80.4%(45/56) in the routine group,without significant differences between the groups( P=0.763). The median overall survival time was 27.6 months for the APOT group and 22.5 months for the routine group,while the median disease-free survival was 11.7 months and 16.8 months,respectively,with no significant differences between the two groups( P=0.532, P=0.927). Conclusion:The arterial pre-occlusion technique can be used for extra-arterial dissection in patients with locally advanced pancreatic cancer involving the arteries,reducing surgery time and intraoperative blood loss.
5.Analysis of FU Wen-Bin's Experience in the Treatment of Radiation Encephalopathy
Jin-Feng GAO ; Shan-Ze WANG ; Ying DENG ; Xi-Chang HUANG ; Si-Bo WEI ; Wen-Bin FU
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(6):1493-1498
Based on the principle of'treating disease and seeking the root cause',Professor FU Wen-Bin proposed'treating radiation encephalopathy(REP)from yang',pointing out that the main pathogenesis of REP is yang qi deficiency,brain spirit dystrophy,phlegm and blood stasis blocking orifices.Using'supplementing yang and unblocking yang simultaneously','treating spirit from heart and gallbladder',combined with the method of regulating spirit and unblocking orifices at acupoints of governor vessol and conception vessel,and using the integrated acupuncture mode of'firstly applying needling,secondly using moxibustion,thirdly focusing on consolidation'to play the role of supporting yang and treating spirit can effectively relieve symptoms and delay the development of the disease.
6.Surveillance of bacterial resistance in tertiary hospitals across China:results of CHINET Antimicrobial Resistance Surveillance Program in 2022
Yan GUO ; Fupin HU ; Demei ZHU ; Fu WANG ; Xiaofei JIANG ; Yingchun XU ; Xiaojiang ZHANG ; Fengbo ZHANG ; Ping JI ; Yi XIE ; Yuling XIAO ; Chuanqing WANG ; Pan FU ; Yuanhong XU ; Ying HUANG ; Ziyong SUN ; Zhongju CHEN ; Jingyong SUN ; Qing CHEN ; Yunzhuo CHU ; Sufei TIAN ; Zhidong HU ; Jin LI ; Yunsong YU ; Jie LIN ; Bin SHAN ; Yunmin XU ; Sufang GUO ; Yanyan WANG ; Lianhua WEI ; Keke LI ; Hong ZHANG ; Fen PAN ; Yunjian HU ; Xiaoman AI ; Chao ZHUO ; Danhong SU ; Dawen GUO ; Jinying ZHAO ; Hua YU ; Xiangning HUANG ; Wen'en LIU ; Yanming LI ; Yan JIN ; Chunhong SHAO ; Xuesong XU ; Wei LI ; Shanmei WANG ; Yafei CHU ; Lixia ZHANG ; Juan MA ; Shuping ZHOU ; Yan ZHOU ; Lei ZHU ; Jinhua MENG ; Fang DONG ; Zhiyong LÜ ; Fangfang HU ; Han SHEN ; Wanqing ZHOU ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU ; Jihong LI ; Qian SUN ; Jinju DUAN ; Jianbang KANG ; Xiaobo MA ; Yanqing ZHENG ; Ruyi GUO ; Yan ZHU ; Yunsheng CHEN ; Qing MENG ; Shifu WANG ; Xuefei HU ; Wenhui HUANG ; Juan LI ; Quangui SHI ; Juan YANG ; Abulimiti REZIWAGULI ; Lili HUANG ; Xuejun SHAO ; Xiaoyan REN ; Dong LI ; Qun ZHANG ; Xue CHEN ; Rihai LI ; Jieli XU ; Kaijie GAO ; Lu XU ; Lin LIN ; Zhuo ZHANG ; Jianlong LIU ; Min FU ; Yinghui GUO ; Wenchao ZHANG ; Zengguo WANG ; Kai JIA ; Yun XIA ; Shan SUN ; Huimin YANG ; Yan MIAO ; Mingming ZHOU ; Shihai ZHANG ; Hongjuan LIU ; Nan CHEN ; Chan LI ; Jilu SHEN ; Wanqi MEN ; Peng WANG ; Xiaowei ZHANG ; Yanyan LIU ; Yong AN
Chinese Journal of Infection and Chemotherapy 2024;24(3):277-286
Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5%were gram-positive and 70.5%were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3%,76.7%and 77.9%,respectively.Overall,94.0%of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8%of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2%in the isolates from children and 95.7%in the isolates from adults.The resistance rate to carbapenems was lower than 13.1%in most Enterobacterales species except for Klebsiella,21.7%-23.1%of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1%to 13.3%.The prevalence of meropenem-resistant strains decreased from 23.5%in 2019 to 18.0%in 2022 in Pseudomonas aeruginosa,and decreased from 79.0%in 2019 to 72.5%in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.
7.Arterial prophylactic occlusion technique in the application of surgery for locally advanced pancreatic cancer with arterial involvement after conversion therapy
Kailian ZHENG ; Xinyu LIU ; Xiaohan SHI ; Huan WANG ; Xiaoyi YIN ; Xinqian WU ; Lingyun GU ; Penghao LI ; Yikai LI ; Wei JING ; Shiwei GUO ; Bin SONG ; Suizhi GAO ; Gang JIN
Chinese Journal of Surgery 2024;62(10):938-946
Objective:To investigate and compare the clinical outcomes of the arterial pre-occlusion technique(APOT) and the traditional technique in the surgery of locally advanced pancreatic cancer with arterial involvement after conversion therapy.Methods:This is a retrospective cohort study. The clinical data of 145 patients with locally advanced pancreatic cancer with arterial involvement admitted to the Department of Hepato-Biliary-Pancreatic Surgery of the First Hospital Affiliated to Naval Medical University,from January 2020 to December 2022 were retrospectively analyzed. All patients completed neoadjuvant therapy for tumors, and the feasibility of radical surgical treatment was determined by a multidisciplinary collaborative team evaluation before surgery. According to whether the intraoperative artery was pre-occluded, 145 patients were divided into two groups, including 28 cases in the APOT group(16 males, 12 females, aged (59.0±9.4) years), and 117 cases in the routine surgery group(76 males, 41 females, aged (55.1±8.2) years). To ensure comparability of baseline data between the APOT group and the routine surgery group, a 1∶2 match was performed using the propensity score matching method, and the caliper value was 0.006 45. The t-test,the Mann-Whitney U test, χ2 test or Fisher′s exact test were used to compare the data between the two groups,respectively. Results:After matching the propensity score,there were 28 cases in the APOT group and 56 cases in the routine surgery group. There were no significant differences in gender,age,preoperative comorbidities,preoperative body mass index,surgical approaches,chemotherapy regimen,stereotactic body radiation therapy ratio,tumor markers,and type of invaded artery between the two groups (all P>0.05).The arterial occlusion time M(IQR) in the APOT group was 7.0(3.8)minutes(range:3 to 15 minutes),and no ischemic manifestations were observed in the distal target organs that blocked blood vessels after surgery. The operation time was (170.3±57.7)minutes in the APOT group and (235.0±80.2)minutes in the routine surgery group,and the difference was statistically significant ( t=-3.800, P<0.01). The APOT group also experienced less intraoperative blood loss(650(588)ml vs. 800(600)ml; U=1 026.500, P=0.021). No significant differences were found between the groups in combined vein resection and reconstruction,celiac trunk resection,early postoperative complications, readmission rates at 30 days,and postoperative length of stay(all P>0.05). Extra-arterial dissection was performed in all patients,with arterial resection and reconstruction in 3 cases: 2 cases in the APOT group(1 case involving the superior mesenteric artery and 1 case involving the common hepatic artery) and 1 case in the routine group(involving the common hepatic artery). Postoperative abdominal bleeding occurred in 4 cases,with 3 cases in the routine group,1 case in the routine group. The R0 resection rate was 85.7%(24/28) in the APOT group and 80.4%(45/56) in the routine group,without significant differences between the groups( P=0.763). The median overall survival time was 27.6 months for the APOT group and 22.5 months for the routine group,while the median disease-free survival was 11.7 months and 16.8 months,respectively,with no significant differences between the two groups( P=0.532, P=0.927). Conclusion:The arterial pre-occlusion technique can be used for extra-arterial dissection in patients with locally advanced pancreatic cancer involving the arteries,reducing surgery time and intraoperative blood loss.
8.Genomic characteristics of the Vibrio cholerae O1 group isolated from humans in Fujian Province,2008 to 2022
Zi-Li KE ; Xiao-Xuan ZHANG ; Hai-Bin XU ; Ya-Dong GAO ; Chao-Chen LUO ; Meng-Ying HUANG ; Yu-Feng QIU ; Jin-Song YANG
Chinese Journal of Zoonoses 2024;40(8):708-715
This study was aimed at understanding the genomic characteristics of the Vibrio cholerae O1 group isolated from humans in Fujian Province,to provide essential data for the molecular epidemiological study of cholera.From 2008 to 2022,16 strains of the V.cholerae O1 group from patients and carriers were collected,and antibiotic sensitivity was determined accord-ing to the minimum inhibitory concentration(MIC).The whole genome sequences obtained through second generation sequen-cing were analyzed in open source software,including snippy,Roary,and Prokka,as well as online analysis websites,inclu-ding NCBI and BacWGSTdb,for core-genome multilocus sequence typing(cgMLST),core-genome single nucleotide polymor-phism analysis(cgSNP),virulence gene analysis,drug resistance gene prediction,and pan-genomic diversity analysis.The whole genome sequences of V.cholerae were divided into five sequence types(STs),among which the newly discovered ST182 and ST1480 were the evolutionary branches of the current dominant clonal group ST75 in China,and were highly related to two strains isolated from Taiwan in 2010 and 2013,respectively.Both toxigenic strains and non-toxigenic strains carried a variety of virulence factors and showed gene variation to varying degrees.Thirteen drug resistance genes in seven categories were predicted,among which the distribution of colistin and tetracycline resistance genes was consistent with the drug resistance phenotype.Pan-ge-nomic analysis indicated that V.cholerae had an open pan-genome,and Roary cluster analysis showed higher resolution than cgMLST.In summary,V.cholerae O1 group isolates from humans in Fujian Province have polymorphisms in genome structure and function,and the newly discovered ST1480 clone group has epidemic potential.Therefore,the monitoring of such strains must be strengthened.
9.PGE2 regulates expression of OAT1 in synoviocytes via EP4/PKA signaling pathway and effect of CP-25
Kang-Jun XIAO ; Jin-Zhang GAO ; Yong WANG ; Bin WANG ; Wei WEI ; Chun WANG
Chinese Pharmacological Bulletin 2024;40(9):1658-1664
Aim To investigate the regulatory mecha-nism of prostaglandin E2(PGE2)on the membrane expression of organic anion transporter 1(OAT1)in synoviocytes and the effect of paeoniflorin-6'-O-ben-zene sulfonate(CP-25).Methods Immunofluores-cence was used to detect the effects of CP-25 on the expression of OAT1 and prostaglandin E receptor 4(EP4)in PGE2 stimulated synoviocytes.EP4 agonists(TCS2510)and antagonists(GW627368X)were used to explore the role of EP4 in regulation of OAT1.CP-25 and protein kinase A(PKA)inhibitor H-89 were used to investigate the effects of CP-25 and PKA on OAT1 expression in synoviocytes.Results Membrane expression of EP4 and OAT1 was down-regulated with-in 0~10 min,and thereby up-regulated between 20~60 min in the presence of PGE2 simulation(P<0.05).CP-25 significantly up-regulated the expres-sions of OAT1 and EP4 in PGE2 stimulated synovio-cytes(P<0.05).TCS2510 significantly up-regulated the expression of OAT1 in cell membrane of synovio-cytes(P<0.01).CP-25 up-regulated the expression of OAT1 in PGE2-treated cells,while the effect of CP-25 on expression of OAT1 was significantly inhibited after the together use of GW627368X and H-89.(P<0.01).Conclusions PGE2-mediated EP4/PKA sig-naling pathway regulates the expression of OAT1 on membranes of synoviocytes.CP-25 can significantly in-crease the membrane expression of OAT1 in synovio-cytes by activating the EP4/PKA signaling pathway.
10.The regulatory role and mechanism of CP-25 on OAT1 in rats with collagen-induced arthritis
Fei DUAN ; Jin-Zhang GAO ; Yong WANG ; Bin WANG ; Wei WEI ; Chun WANG
Chinese Pharmacological Bulletin 2024;40(12):2295-2302
Aim The present study was conducted to investigate the expression of organic anion transporter 1(OAT1)in synovial tissue of collagen-induced arthritis(CIA)rats and the effect of paeoniflorin-6'-O-benzene sulfonate(CP-25),and meanwhile reveal its potential regulatory mechanism.Methods The rat CIA model was established and treated with CP-25(50 mg·kg-1·d-1),paroxetine(15 mg·kg-1·d-),prosta-glandin E receptor 4(EP4)antagonist(3 mg·kg-1·d-1),or a combination of CP-25(50 mg·kg-1·d-1)plus EP4 antagonist(3 mg·kg-1·d-1),while methotrexate(0.5 mg·kg-1·3d-1)was used as the positive control drug.Clinical manifestation of CIA rats,including arthritis index,numbers of swollen joints,paw volume of non-injected hind and clinical scores was measured.Moreover,X-ray imaging of paw,pathological examination of the ankle joint and quantitative assessment were conducted.The concen-tration of serum prostaglandin E2(PGE2)was quanti-fied using the ELISA.Western blot analysis was em-ployed to assess the levels of phospho-G protein-cou-pled receptor kinase 2(p-GRK2),protein kinase A(PKA),EP4 and OAT1 membrane proteins of rat syn-ovial tissues following CP-25 treatment.Results The administration of CP-25 resulted in a reduction in foot swelling,global score,arthritis index,paw volume of non-injected,and numbers of swollen joints in CIA rats.Pathological examination and X-ray analysis re-vealed that CP-25 significantly ameliorated the patho-logical changes and bone erosion degree of CIA rats.CP-25 significantly lowered PGE2 concentration in the serum of CIA rats.In the CIA model group,membrane expression of OAT1 and EP4 in synovial tissues of rats was significantly downregulated.Treatment with CP-25 or paroxetine resulted in a significant upregulation of OAT1 and EP4 expression and the effect of CP-25 on OAT1 was blocked when EP4 antagonist was used to-gether.Furthermore,the expression of p-GRK2 in syn-ovial tissue from CIA rats was significantly upregulat-ed,and however,CP-25 or paroxetine interventions led to a significant reduction in p-GRK2 expression.The expression trend of PKA was similar to that of OAT1.Conclusion OAT1 membrane expression is reduced in the synovial tissue of CIA rats,and CP-25 treatment increases OAT1 membrane expression.The PGE2-EP4-PKA pathway may be involved in the regu-lation of OAT1 by CP-25.

Result Analysis
Print
Save
E-mail