1.Relationship between coronal angle fluctuation of ankle point and recovery of joint function after ankle fracture
Chinese Journal of Tissue Engineering Research 2025;29(9):1820-1826
BACKGROUND:The morphological indexes of ankle point may change after ankle fracture,and there is a certain correlation between the coronal angle change of ankle point and the functional recovery of ankle joint.Most previous studies have studied the height recovery of ankle point after surgery,so the correlation between the fluctuation of coronal angle of ankle point and the functional recovery of ankle joint after ankle fracture has certain reference significance. OBJECTIVE:To investigate the effect of coronal angle change of ankle point on joint function recovery after ankle fracture. METHODS:A total of 86 patients with ankle fracture who underwent surgical treatment were selected as the study objects,and were divided into excellent group(n=45)and poor group(n=41)according to the results of American Orthopaedic Foot&Ankle Society(AOFAS)hindfoot-ankle score during the last follow-up,and the general data of the two groups were compared.The morphological indexes of ankle points on the affected side and healthy side were compared after surgery based on ankle acupoints and lateral X-rays of the ankle joint,including the width and depth of ankle points,coronal angle and sagittal angle,and the difference of ankle points between the affected side and healthy side,and further comparison and analysis were conducted in each group.A joint model was constructed and Cox regression analysis was used to evaluate the relationship between coronal angle fluctuation and joint function recovery.Least absolute shrinkage and selection operator regression method and multivariate Logistic regression were used to analyze the risk factors affecting the recovery of joint function.The patients were divided into 5-quartile array(Q1-Q5)according to the angle of coronal position at ankle point from low to high.The clinical data characteristics of the five groups were compared,and the correlation between the change of coronal position at ankle point and the risk of poor recovery of joint function was analyzed by multivariate Logistic regression.A restricted cubic spline Logistic regression model was established to analyze the dose-response relationship.The prediction model of regression equation y=1-1/(1+e-z)was established and verified. RESULTS AND CONCLUSION:(1)The width and depth of ankle point on the affected side,coronal angle and sagittal angle were significantly higher than those on the healthy side(all P<0.05),and compared with the excellent group,the difference of ankle point width,depth difference,coronal angle difference and sagittal angle difference were greater in the poor group(P<0.05).(2)The combined model showed that the risk of poor joint function was increased by 3%for every 1? increase in coronal angle,regardless of whether the angle was within the normal range.(3)Least absolute shrinkage and selection operator regression and multivariate Logistics regression analysis showed that after adjusting for potential confounding factors,it was found that age,lack of functional exercise in early stage,no calcaneal traction,failure to remove internal fixation,postoperative complications,and increased ankle coronal angle were independent risk factors for joint function recovery(P<0.05).(4)The coronal angle within 3 months after surgery was independently correlated with the risk of poor joint function recovery(OR=1.57,95%CI:1.38-1.76,P=0.002),and the trend test of the coronal angle from low to high quintile in each postoperative period had statistical significance(Ptrend<0.001).(5)Restricted cubic spline model analysis showed that there was no nonlinear relationship between the coronal angle change of ankle point and the risk of poor joint function recovery in males or females.Through Bootstrap self-sampling,the prediction model has good differentiation and accuracy.(6)The reduction of coronal angle of ankle point after ankle fracture plays a significant role in promoting the recovery of joint function.Therefore,the detection of coronal angle of ankle point after ankle fracture is helpful to understand the recovery of joint function of patients.
2.Research Progress on the Mechanism of Lipocalin-2 in Neurological Diseases
Yongtai ZHOU ; Zhenyu YANG ; Yan LI ; Jiajing WU ; Bo ZHAO
Medical Journal of Peking Union Medical College Hospital 2025;16(2):330-337
Lipocalin-2 (LCN2), a member of the human lipocalin family, has been demonstrated to be closely associated with diabetes, cardiovascular diseases, and renal disorders. Recent studies have indicated that LCN2 plays a significant regulatory role in the pathogenesis and progression of various neurological diseases by mediating pathways such as inflammation, oxidative stress, and ferroptosis. This article reviews the research advancements on the mechanism of LCN2 in neurological disorders, including cerebrovascular diseases, cognitive impairment disorders, Parkinson's disease, depression, and anxiety disorders, aiming to enhance clinical understanding.
3.Ten surgical pearls adapted from ancient Chinese allusions in managing severe proliferative diabetic retinopathy
Zhe CHEN ; Chan WU ; Yan ZHOU ; Shiqun LIN ; Xingyu XIAO ; Rongping DAI
International Eye Science 2025;25(5):698-705
AIM: To summarize 10 surgical pearls for managing proliferative diabetic retinopathy(PDR)adapted from the ancient Chinese allusions and analyze the application of these pearls in a real-world fashion.METHODS: Retrospective, noncomparative, interventional study. Ten surgical pearls were summarized and adapted from the ancient Chinese philosophy. Totally 346 cases(443 eyes)that underwent pars plana vitrectomy(PPV)at our hospial from January 2016 to February 2024 were selected. Flexible combinations of these pearls were applied according to the specific condition of each patient during surgeries. The efficacy and safety were analyzed, as well as the application frequencies according to the existence of tractional retinal detachment or not.RESULTS: A total of 473 times of surgeries were performed on all the patients. According to ancient Chinese allusions, ten surgical pearls were summarized from these surgeries. All PPVs went smoothly with the application of different combinations. Finally, almost all proliferative membranes were successfully peeled except for 10 patients(11 eyes), who went through strategy No.10(minimal membranectomy)that, only necessary relaxation incisions were made with most of the proliferative membranes left on purpose. The final visual acuities were mostly improved or stable(1.92±0.83 LogMAR preoperatively vs 1.16±0.85 LogMAR postoperatively, P<0.01). Postoperative complications mainly included early inflammatory responses in the anterior chamber and nuclear sclerosis. Recurrent vitreous hemorrhage, retinal detachment, and hyphema or neovascular glaucoma occurred in 1.9%(9/473), 3.2%(15/473), 0.4%(2/473)and 0.4%(2/473)times of PPVs, respectively. After 12/473(2.5%)times of PPVs, retinal detachment at the macular area still existed, and multiple times of subsequent PPVs were conducted. Final retinal attachment at the macular area was realized in 98.9% eyes. Those 5 unattached eyes were with heavily reproliferated membranes and subsequent tractional retinal detachment recurrence under the oil, and three of them were scleral buckled additionally.CONCLUSION:These 10 surgical strategies and technique pearls were mostly effective and safe in the management of severe PDR patients. They were relatively easy to be memorized and applicated once the meaning of each Chinese idiom was understood. One can use different combinations flexibly according to a patient's specific condition.
4.Evaluation of the performance of the artificial intelligence - enabled snail identification system for recognition of Oncomelania hupensis robertsoni and Tricula
Jihua ZHOU ; Shaowen BAI ; Liang SHI ; Jianfeng ZHANG ; Chunhong DU ; Jing SONG ; Zongya ZHANG ; Jiaqi YAN ; Andong WU ; Yi DONG ; Kun YANG
Chinese Journal of Schistosomiasis Control 2025;37(1):55-60
Objective To evaluate the performance of the artificial intelligence (AI)-enabled snail identification system for recognition of Oncomelania hupensis robertsoni and Tricula in schistosomiasis-endemic areas of Yunnan Province. Methods Fifty O. hupensis robertsoni and 50 Tricula samples were collected from Yongbei Township, Yongsheng County, Lijiang City, a schistosomiasis-endemic area in Yunnan Province in May 2024. A total of 100 snail sample images were captured with smartphones, including front-view images of 25 O. hupensis robertsoni and 25 Tricula samples (upward shell opening) and back-view images of 25 O. hupensis robertsoni and 25 Tricula samples (downward shell opening). Snail samples were identified as O. hupensis robertsoni or Tricula by schistosomiasis control experts with a deputy senior professional title and above according to image quality and morphological characteristics. A standard dataset for snail image classification was created, and served as a gold standard for recognition of snail samples. A total of 100 snail sample images were recognized with the AI-enabled intelligent snail identification system based on a WeChat mini program in smartphones. Schistosomiasis control professionals were randomly sampled from stations of schistosomisis prevention and control and centers for disease control and prevention in 18 schistosomiasis-endemic counties (districts, cities) of Yunnan Province, for artificial identification of 100 snail sample images. All professionals are assigned to two groups according the median years of snail survey experiences, and the effect of years of snail survey experiences on O. hupensis robertsoni sample image recognition was evaluated. A receiver operating characteristic (ROC) curve was plotted, and the sensitivity, specificity, accuracy, Youden’s index and the area under the curve (AUC) of the AI-enabled intelligent snail identification system and artificial identification were calculated for recognition of snail sample images. The snail sample image recognition results of AI-enabled intelligent snail identification system and artificial identification were compared with the gold standard, and the internal consistency of artificial identification results was evaluated with the Cronbach’s coefficient alpha. Results A total of 54 schistosomiasis control professionals were sampled for artificial identification of snail sample image recognition, with a response rate of 100% (54/54), and the accuracy, sensitivity, specificity, Youden’s index, and AUC of artificial identification were 90%, 86%, 94%, 0.80 and 0.90 for recognition of snail sample images, respectively. The overall Cronbach’s coefficient alpha of artificial identification was 0.768 for recognition of snail sample images, and the Cronbach’s coefficient alpha was 0.916 for recognition of O. hupensis robertsoni snail sample images and 0.925 for recognition of Tricula snail sample images. The overall accuracy of artificial identification was 90% for recognition of snail sample images, and there was no significant difference in the accuracy of artificial identification for recognition of O. hupensis robertsoni (86%) and Tricula snail sample images (94%) (χ2 = 1.778, P > 0.05). There was no significant difference in the accuracy of artificial identification for recognition of snail sample images with upward (88%) and downward shell openings (92%) (χ2 = 0.444, P > 0.05), and there was a significant difference in the accuracy of artificial identification for recognition of snail sample images between schistosomiasis control professionals with snail survey experiences of 6 years and less (75%) and more than 6 years (90%) (χ2 = 7.792, P < 0.05). The accuracy, sensitivity, specificity and AUC of the AI-enabled intelligent snail identification system were 88%, 100%, 76% and 0.88 for recognition of O. hupensis robertsoni snail sample images, and there was no significant difference in the accuracy of recognition of O. hupensis robertsoni snail sample images between the AI-enabled intelligent snail identification system and artificial identification (χ2 = 0.204, P > 0.05). In addition, there was no significant difference in the accuracy of artificial identification for recognition of snail sample images with upward (90%) and downward shell openings (86%) (χ2 = 0.379, P > 0.05), and there was a significant difference in the accuracy of artificial identification for recognition of snail sample images between schistosomiasis control professionals with snail survey experiences of 6 years and less and more than 6 years (χ2 = 5.604, Padjusted < 0.025). Conclusions The accuracy of recognition of snail sample images is comparable between the AI-enabled intelligent snail identification system and artificial identification by schistosomiasis control professionals, and the AI-enabled intelligent snail identification system is feasible for recognition of O. hupensis robertsoni and Tricula in Yunnan Province.
5.Biomechanical effects of postural and cognitive loads on trunk of workers performing assembly tasks at hand functional height
Huishuan WU ; Yu JIN ; Yan LIU ; Siyi ZENG ; Cunwen QIAN ; Kezhi JIN
Journal of Environmental and Occupational Medicine 2025;42(4):392-399
Background The neck, shoulders, and lower back are the primary affected areas of work-related musculoskeletal disorders. In manual tasks, combinations of hand functional height (defined as working height below the waist), awkward postures, and cognitive load are common risk factors. However, there is limited literature documenting how these factors specifically alter biomechanical load on the neck, shoulders, and lower back when working at hand functional height. Objective To explore quantitative differences in biomechanical load on the neck, shoulders, and lower back of workers performing manual tasks at hand functional height under different postures and cognitive load combinations. Methods A 3x2 within-subject design was implemented, with three postures (squat, kneeling, and stoop) and two levels of cognitive load (with cognitive load induced by a 2back task and without cognitive load). Ten male university students were recruited to perform a predetermined assembly task (a sequence of loosening and tightening screws) at hand functional height. Surface electromyography (sEMG) and 3D motion capture system were employed to assess the participants’ trunk biomechanical load in executing the tasks. Additionally, subjective perception, including fatigue, muscle pain, and cognitive load, were evaluated using scales. Results Significant variations in biomechanical load were observed across the three postures (P<0.05). The stoop posture exhibited the lowest muscle activation in most target muscles, except for the sternocleidomastoid, and showed the fastest decline in instantaneous median frequency (IMF) of the erector spinae, with a rate of (-0.050±0.008) Hz per unit time (0.128 s), and the greatest trunk flexion angle (35.14°±4.40°). Performing the task by squatting resulted in the highest muscle activation, especially in the upper trapezius, where maximum voluntary contraction percentage reached 20.07%±1.26%. In addition, the squatting posture also resulted in larger joint angles in the sagittal plane for the neck (−7.03°±2.70°), shoulders (60.20°±7.89°), and lower back (34.42°±4.20°). The kneeling posture showed intermediate muscle activation, the slowest IMF decline for the erector spinae in the lower back (−0.005±0.008) Hz per unit time (0.128s), and the joint angles were closest to neutral. The task performance results were also superior in the kneeling posture. Regarding cognitive load, no significant differences were found for most biomechanical indicators, except for subjective cognitive load scores, neck flexion, and shoulder external rotation angles. Conclusion In assembly tasks performed at hand functional height, kneeling results in moderate biomechanical load on the neck, shoulders, and lower back while also improves task performance compared to squatting and forward bending. Additionally, no significant effects of cognitive load under the 2back condition on biomechanical load are observed.
6.Modulation of colonic DNA methyltransferase by mild moxibustion and electroacupuncture in ulcerative colitis TET2 knockout mice
Gege FENG ; Yue ZHANG ; Huangan WU ; Lu ZHU ; Hongxiao XU ; Zhe MA ; Yan HUANG
Digital Chinese Medicine 2025;8(1):100-110
Objective:
To investigate the mechanism of in alleviating colonic mucosal inflammation in ten-eleven translocation (TET) protein 2 gene knockout (TET2-/-) mice with ulcerative colitis (UC) by regulating DNA methyltransferase (DNMT) and DNA hydroxymethylase.
Methods:
Male specific pathogen-free (SPF) grade C57BL/6J wild-type (WT) mice (n = 8) and TET2-/- mice (n = 20) were used to establish UC models by freely drinking 3% dextran sulfate sodium solution for 7 d. After UC model validation through histopathological examination in two mice from each type, the remaining mice were divided into four groups (n = 6 in each group): WT model (WT + UC), TET2-/- model (TET2-/- + UC), TET2-/- mild moxibustion (TET2-/- + MM), and TET2-/- electroacupuncture (TET2-/- + EA) groups. TET2-/- + MM group received mild moxibustion on Tianshu (ST25) and Qihai (CV6) for 10 min daily for 7 d. The TET2-/- + EA group also applied electroacupuncture (1 mA, 2/100 Hz) at the same acupoints for 10 min daily for 7 d. The disease activity index (DAI) scores of each group of mice were accessed daily. The colon lengths of mice in groups were measured following intervention. The pathological changes in the colon tissues were observed with hematoxylin and eosin (HE) staining. The concentrations of interleukin (IL)-6, C-C motif chemokine 17 (CCL17), and C-X-C motif chemokine ligand 10 (CXCL10) in serum were detected by enzyme-linked immunosorbent assay (ELISA). The expression of DNMT proteins (DNMT1, DNMT3A, and DNMT3B) in the colon tissues was detected by immunohistochemistry. The expression of 5-methylcytosine (5-mC), 5-hydroxymethylcytosine (5-hmC), histone deacetylase 2 (HDAC2), and DNA hydroxymethylase family proteins (TET 1 and TET3) was detected using immunofluorescence, which also determined the co-localization of TET1 and IL-6 protein.
Results:
Compared with WT + UC group, TET2-/- + UC group exhibited significantly higher DAI scores and shorter colon lengths (P < 0.01). Both mild moxibustion and electroacupuncture significantly decreased DAI scores and ameliorated colon shortening in TET2-/- mice (P < 0.001). Histopathological scores of TET2-/- + UC mice were significantly higher than those of WT + UC group (P < 0.001) and were significantly reduced after both mild moxibustion and electroacupuncture interventions (P < 0.001). Serum levels of IL-6, CCL17, and CXCL10 were significantly elevated in TET2-/- + UC group compared with WT + UC group (P < 0.001). Mild moxibustion significantly reduced IL-6, CCL17, and CXCL10 levels (P < 0.001, P < 0.001, and P < 0.01, respectively), while electroacupuncture also significantly reduced IL-6, CCL17, and CXCL10 levels (P < 0.05, P < 0.01, and P < 0.01, respectively). TET2-/- + UC mice showed increased expression levels of DNMT1, DNMT3A , DNMT3B, and 5-mC (P < 0.05, P < 0.01 and P < 0.001, respectively), with decreased expression levels of TET1, TET3, 5-hmC, and HDAC2 (P < 0.001). Mild moxibustion significantly reduced DNMT1, DNMT3B, and 5-mC levels (P < 0.05, P < 0.01, and P < 0.001, respectively), while increasing expression levels of TET1, TET3, 5-hmC, and HDAC2 (P < 0.001, P < 0.001, P < 0.05, and P < 0.001, respectively). Electroacupuncture significantly decreased 5-mC and DNMT3B levels (P < 0.001 and P < 0.01, respectively) and increased 5-hmC and HDAC2 levels (P < 0.05 and P < 0.001, respectively), but did not significantly affect TET1 and TET3 expression (P > 0.05). Compared with TET2-/- + MM group, TET2-/- + EA group showed significantly higher 5-mC expression (P < 0.001). TET2-/- + UC group exhibited markedly increased IL-6 expression and higher co-localization of TET1 and IL-6 in mucosal epithelium, whereas minimal IL-6 expression was observed in the other groups.
Conclusion
Mild moxibustion and electroacupuncture significantly ameliorate colonic inflammation exacerbated by TET2 deficiency in UC mice via epigenetic modulation. Distinct mechanisms exist between the two interventions: mild moxibustion regulates both DNMT and hydroxymethylase, whereas electroacupuncture primarily affects DNMT.
7.Expression of KCNN4 in pancreatic cancer tissues, its correlation with prognosis, and impact on pancreatic cancer cell proliferation
YANG Xuan ; CHEN Xinyuan ; RUAN Xiaoyu ; WU Qingru ; GU Yan
Chinese Journal of Cancer Biotherapy 2025;32(4):371-377
[摘 要] 目的:探究钾钙激活通道亚家族N成员4(KCNN4)在胰腺癌组织中的表达及其对胰腺癌进展的影响,解析KCNN4在胰腺癌临床诊断及预后判断中的作用。方法:利用GEPIA2数据分析平台,结合TCGA和GTEx数据库的数据分析KCNN4在胰腺癌组织中的表达水平及其与患者预后的关系。收集24例海军军医大学长海医院手术切除的胰腺癌患者的癌及癌旁组织标本,通过qPCR、WB法和免疫组化染色技术验证KCNN4在胰腺癌组织中的表达水平。利用shRNA敲低人胰腺癌细胞中BXPC3和PANC-1中KCNN4的表达,通过CCK-8和克隆形成实验检测细胞增殖与生长情况。利用小鼠胰腺癌KPC细胞构建胰腺癌原位成瘤模型,观察敲低KCNN4对胰腺原位成瘤的影响,统计小鼠生存期(OS)。结果:整合TCGA和GTEx数据库数据分析结果发现,KCNN4在胰腺癌组织中高表达(P < 0.05),且与患者OS和DFS缩短相关(均P < 0.05)。胰腺癌组织中KCNN4 mRNA和蛋白表达量均显著高于癌旁组织(均P < 0.01)。KCNN4敲低后,胰腺癌细胞生长速率显著减慢、克隆形成数量显著减少(均P < 0.01)。小鼠胰腺原位荷瘤实验结果表明,KCNN4敲低可抑制肿瘤细胞在胰腺原位的生长并延长小鼠OS。结论:KCNN4在胰腺癌组织中高表达,其能促进胰腺癌细胞增殖和胰腺癌进展,与患者预后密切相关,有望作为胰腺癌临床诊断及预后评估的靶点。
8.A Case Report of Pachydermoperiostosis by Multidisciplinary Diagnosis and Treatment
Jie ZHANG ; Yan ZHANG ; Li HUO ; Ke LYU ; Tao WANG ; Ze'nan XIA ; Xiao LONG ; Kexin XU ; Nan WU ; Bo YANG ; Weibo XIA ; Rongrong HU ; Limeng CHEN ; Ji LI ; Xia HONG ; Yan ZHANG ; Yagang ZUO
JOURNAL OF RARE DISEASES 2025;4(1):75-82
A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in
9.Mechanism of Paeonol in Alleviating Alcohol-induced Liver Injury in Mice Through Regulating SCFAs-GPR43/MAPK Signaling Pathway Mediated by Intestinal Flora
Shengnan JIANG ; Qifeng WU ; Zining WANG ; Hao PU ; Guiming YAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):129-139
ObjectiveTo investigate the ameliorative effect of paeonol on acute alcohol-induced hepatic inflammation in mice via the regulation of the short-chain fatty acids (SCFAs)-specific receptor GPR43/mitogen-activated protein kinase (MAPK) signaling pathway. MethodsC57BL/6 mice were randomly divided into five groups: blank control group, model group, low-dose paeonol group (120 mg·kg-1), high-dose paeonol group (480 mg·kg-1), and silybin group (36.8 mg·kg-1). A mouse model of alcohol-induced liver disease (ALD) was established by ad libitum administration of a Lieber-DeCarli alcohol liquid diet. Serum lipid levels, liver function, inflammatory cytokines, and oxidative stress markers were measured. Liver hematoxylin-eosin (HE) staining and Oil Red O staining were performed to validate successful modeling. Western blot analysis was used to assess the expression levels of zonula occludens-1 (ZO-1), Claudin-1, and proteins related to the GPR43/MAPK signaling pathway in the colonic tissue. Immunohistochemistry was employed to detect the protein expression of GPR43, ZO-1, and Claudin-1 in the colon. Then 16S rDNA sequencing was performed to analyze differences in intestinal flora between the model group and the high-dose paeonol group. Additionally, fecal microbiota transplantation (FMT) experiments were conducted to validate the regulatory effect of paeonol on ALD via modulation of intestinal flora. ResultsCompared with the blank control group, the model group showed significantly elevated serum lipid levels, oxidative stress, and inflammatory cytokine expression (P<0.01). Liver histology revealed increased inflammatory infiltration and lipid droplet accumulation. Colonic mucosal injury and impaired intestinal barrier function were observed. Levels of MAPK pathway-related proteins in the colonic tissue were upregulated (P<0.01), while GPR43, ZO-1, and Claudin-1 protein expression levels were significantly decreased (P<0.01). The composition and abundance of the intestinal flora were markedly altered, with a reduced Bacteroidetes-to-Firmicutes ratio and decreased relative abundances of Eubacterium, Parabacteroides, Erysipelothrix, and Adlercreutzia, alongside increased abundances of Clostridium butyricum, Enterococcus, and Helicobacter pylori in the model group. Compared with the model group, paeonol significantly reduced serum lipid levels, oxidative stress responses, and the expression of inflammatory cytokines in ALD mice (P<0.05, P<0.01). It also attenuated hepatic lipid accumulation, restored intestinal barrier function, and repaired the structural integrity of liver and colonic tissues. The protein expression levels of ZO-1, Claudin-1, and GPR43 in the colonic tissue were significantly increased (P<0.05, P<0.01), while those of MAPK pathway-related proteins were significantly decreased (P<0.05, P<0.01). The intestinal flora dysbiosis was effectively alleviated, rendering its composition closer to that of normal mice. The efficacy of paeonol in modulating ALD was further confirmed by FMT experiments, supporting its mechanistic involvement in the SCFAs-GPR43/MAPK signaling pathway. ConclusionPaeonol exerts a protective effect against ALD in mice, which may be mediated through regulation of the SCFAs-GPR43/MAPK signaling pathway, thereby achieving anti-inflammatory effects and improving intestinal barrier function.
10.Mechanism of Paeonol in Alleviating Alcohol-induced Liver Injury in Mice Through Regulating SCFAs-GPR43/MAPK Signaling Pathway Mediated by Intestinal Flora
Shengnan JIANG ; Qifeng WU ; Zining WANG ; Hao PU ; Guiming YAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):129-139
ObjectiveTo investigate the ameliorative effect of paeonol on acute alcohol-induced hepatic inflammation in mice via the regulation of the short-chain fatty acids (SCFAs)-specific receptor GPR43/mitogen-activated protein kinase (MAPK) signaling pathway. MethodsC57BL/6 mice were randomly divided into five groups: blank control group, model group, low-dose paeonol group (120 mg·kg-1), high-dose paeonol group (480 mg·kg-1), and silybin group (36.8 mg·kg-1). A mouse model of alcohol-induced liver disease (ALD) was established by ad libitum administration of a Lieber-DeCarli alcohol liquid diet. Serum lipid levels, liver function, inflammatory cytokines, and oxidative stress markers were measured. Liver hematoxylin-eosin (HE) staining and Oil Red O staining were performed to validate successful modeling. Western blot analysis was used to assess the expression levels of zonula occludens-1 (ZO-1), Claudin-1, and proteins related to the GPR43/MAPK signaling pathway in the colonic tissue. Immunohistochemistry was employed to detect the protein expression of GPR43, ZO-1, and Claudin-1 in the colon. Then 16S rDNA sequencing was performed to analyze differences in intestinal flora between the model group and the high-dose paeonol group. Additionally, fecal microbiota transplantation (FMT) experiments were conducted to validate the regulatory effect of paeonol on ALD via modulation of intestinal flora. ResultsCompared with the blank control group, the model group showed significantly elevated serum lipid levels, oxidative stress, and inflammatory cytokine expression (P<0.01). Liver histology revealed increased inflammatory infiltration and lipid droplet accumulation. Colonic mucosal injury and impaired intestinal barrier function were observed. Levels of MAPK pathway-related proteins in the colonic tissue were upregulated (P<0.01), while GPR43, ZO-1, and Claudin-1 protein expression levels were significantly decreased (P<0.01). The composition and abundance of the intestinal flora were markedly altered, with a reduced Bacteroidetes-to-Firmicutes ratio and decreased relative abundances of Eubacterium, Parabacteroides, Erysipelothrix, and Adlercreutzia, alongside increased abundances of Clostridium butyricum, Enterococcus, and Helicobacter pylori in the model group. Compared with the model group, paeonol significantly reduced serum lipid levels, oxidative stress responses, and the expression of inflammatory cytokines in ALD mice (P<0.05, P<0.01). It also attenuated hepatic lipid accumulation, restored intestinal barrier function, and repaired the structural integrity of liver and colonic tissues. The protein expression levels of ZO-1, Claudin-1, and GPR43 in the colonic tissue were significantly increased (P<0.05, P<0.01), while those of MAPK pathway-related proteins were significantly decreased (P<0.05, P<0.01). The intestinal flora dysbiosis was effectively alleviated, rendering its composition closer to that of normal mice. The efficacy of paeonol in modulating ALD was further confirmed by FMT experiments, supporting its mechanistic involvement in the SCFAs-GPR43/MAPK signaling pathway. ConclusionPaeonol exerts a protective effect against ALD in mice, which may be mediated through regulation of the SCFAs-GPR43/MAPK signaling pathway, thereby achieving anti-inflammatory effects and improving intestinal barrier function.

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