1.Correlations of pontine biological indicators on fetal brain median sagittal MRI with gestational week
Lingxiu HOU ; Bingguang LIU ; Ying YUAN ; Yimei LIAO ; Qiaozhen ZHU ; Hongbo GUO ; Ying TAN ; Huiying WEN ; Fang YAN ; Shengli LI
Chinese Journal of Medical Imaging Technology 2024;40(1):88-92
		                        		
		                        			
		                        			Objective To observe the correlations of pontine biological indicators on fetal brain median sagittal MRI with gestational week.Methods Data of head MRI of 226 normal fetuses without obvious abnormalities of central nervous system(normal group)and 17 fetuses with abnormalities(abnormal group)at gestational age of 23 to 38 weeks were retrospectively analyzed.Pontine biological indicators based on median sagittal MRI were obtained,including pons anteroposterior diameter(PAD),total pons area(TPA),pontine basal anteroposterior length(AP),pontine basal cranio-caudal length(CC),basis pontis area(BPA)and pontine angle of midbrain(MAP).According to the gestational week,the fetuses of normal group were divided into 8 subgroups.The distributing ranges of pontine biological indicators at different gestational weeks were analyzed,and the correlations of pontine biological indicators with gestational week in normal group were explored,and the developmental status of fetal pons in abnormal group were assessed.Results In normal group,PAD,TPA,AP,CC and BPA all showed linear positive correlation(r=0.887,0.914,0.787,0.866,0.865,all P<0.001),while MAP was not significantly correlated with gestational week(P>0.05).Among 17 fetuses in abnormal group,abnormal PAD or TPA was found each in 8 fetuses,abnormal AP was observed in 14,abnormal CC was noticed in 3 and abnormal BPA was found in 11 fetuses.Conclusion Fetal pontine biological indicators such as PAD,TPA,AP,CC and BPA on median sagittal MRI were positively correlated with gestational week,hence being able to be used for evaluating fetal pontine development.
		                        		
		                        		
		                        		
		                        	
2.Exploration on the Mechanism of Hydroxyl Safflower Flavin A in the Treatment of Sepsis-induced Liver Injury Based on Metabolomics and Network Pharmacology
Shifan YAN ; Bingbing PAN ; Ting YU ; Changmiao HOU ; Yu JIANG ; Fang CHEN ; Jingjing WANG ; Yanjuan LIU ; Yimin ZHU
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(2):130-137
		                        		
		                        			
		                        			Objective To explore the mechanism of hydroxyl safflower flavin A(HSYA)in the treatment of sepsis-induced liver injury by using metabolomics and network pharmacology.Methods A total of 50 male C57BL/6 mice were randomly divided into sham-operation group(10 mice),sepsis group(20 mice)and HSYA group(20 mice).Cecal ligation and puncture was conducted to establish the sepsis-induced liver injury mouse model.The mice in HSYA group were subcutaneously injected with HSYA after 2 hours of modeling.The content of serum inflammatory factors and liver function were detected,and the pathological changes of liver tissue were observed with HE staining,UPLC-Q-TOF-MS metabolomics was used to analyze liver tissue,screening for differential metabolites using multivariate statistical methods,network pharmacology was used to predict potential targets for HSYA treatment of sepsis-induced liver injury,and conduct GO and KEGG pathway enrichment analysis on potential targets,Metabo Analyst 5.0 database was used to match differential metabolites and potential targets between the model group and HSYA group,a targets metabolite-metabolism pathway network was constructed.AutoDock Vina software was used to perform molecular docking between HSYA and core genes,and finally RT-qPCR was used to verify the expression of core genes.Results HSYA can reduce the contents of IL-6,IL-1β and TNF-α in serum,restore liver function,and alleviate the morphological alternation in liver induced by sepsis.A total of 26 differential metabolites identified by metabolomics were screened out,including flufenamic acid,cryptolepine,opthalmic acid,fenpropathrin etc.,which were mainly involved in 5 metabolic pathways such as biosynthesis of unsaturated fatty acids and alpha-linolenic acid metabolism.Network pharmacology identified 81 potential targets,2 735 items enriched in GO and 124 signaling pathways enriched in KEGG;a total of 5 differential metabolites were matched for joint analysis,corresponding to 14 targets including IL1B,STAT3,PTGS2,TP53,etc.,involved in the regulation of metabolic disorders in sepsis-induced liver injury by HSYA.Molecular docking results showed that HSYA had good binding activity to IL1B,STAT3,PTGS2 and TP53 targets.RT-qPCR results showed that HSYA could inhibit the expressions of IL1B,STAT3 and PTGS2 in liver tissue.Conclusions HSYA may inhibit the release of inflammatory cytokines,maintain metabolic homeostasis,and alleviate sepsis-induced liver injury through modulating the expressions of IL1B,STAT3,and PTGS2.
		                        		
		                        		
		                        		
		                        	
3.Diagnostic value of thromboelastography combined with conventional coagulation test for trauma-induced coagulopathy in patients with electric burns in the early stage
Quan LI ; Te BA ; Shengjun CAO ; Fang LI ; Zengqiang YAN ; Zhihui HOU ; Lingfeng WANG
Chinese Journal of Burns 2024;40(8):740-745
		                        		
		                        			
		                        			Objective:To explore the diagnostic value of thromboelastography (TEG) combined with conventional coagulation test (CCT) for trauma-induced coagulopathy (TIC) in patients with electric burns in the early stage.Methods:This study was a retrospective case series research. From February 2018 to February 2024, the clinical data of 128 electric burn patients and 118 thermal burn patients who met the inclusion criteria and admitted to the Department of Burn Surgery of the Third Affiliated Hospital of Inner Mongolia Medical University were collected, including 224 males and 22 females, aged (38±14) years. The patients were divided into electric burn group (128 cases) and thermal burn group (118 cases) according to their injuries. The incidence of TIC, the indicators of CCT, including prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen level, D-dimer level, platelet count, and the detection indicators of TEG, including coagulation reaction time, K value, coagulation angle, maximum thrombus amplitude, comprehensive coagulation index, and lysis rate at 30 minutes after maximum amplitude within 8 hours of admission were compared between the two groups of patients. The Kappa test was used to analyze the consistency between CCT and TEG in diagnosing TIC in patients with electric burns in the early stage after burns. The receiver operating characteristic curves of CCT, TEG, and TEG combined with CCT in diagnosing TIC in 128 patients with electric burns were drawn, and the area under the curve (AUC), the maximum Jordan index, and sensitivity and specificity at this time were calculated.Results:The proportion of patients diagnosed with TIC in electric burn group was 19.5% (25/128) within 8 hours of admission, which was significantly higher than 10.2% (12/118) in thermal burn group ( χ2=4.21, P<0.05). Compared with those in thermal burn group, prothrombin time was significantly shortened ( t=-2.32, P<0.05), D-dimer level, fibrinogen level, and platelet count were significantly increased (with Z values of -2.11 and -4.16, respectively, t=4.69, P<0.05), the coagulation reaction time was significantly shortened ( t=-2.51, P<0.05), and the maximum thrombus amplitude and lysis rate at 30 minutes after the maximum amplitude were significantly increased (with t values of 2.50 and 2.10, respectively, P<0.05) in patients in electric burn group within 8 hours of admission. There were no statistically significant differences in the other CCT indicators and TEG detection indicators between the two groups of patients ( P>0.05). The CCT and TEG showed high consistency in the diagnosis of TIC in patients with electric burns in the early stage after burns (Kappa=0.63, P<0.05). The AUCs of TEG combined with CCT, TEG, and CCT in diagnosis of TIC in 128 patients with electric burns were 0.92, 0.84, and 0.77 (with 95% confidence intervals of 0.86-0.97, 0.71-0.97, and 0.71-0.97, respectively), with the maximum Jordan indexes of 0.86, 0.57, and 0.65. At this time, the specificity was 93.7%, 83.2%, and 88.2%, respectively, and the sensitivity was 92.3%, 87.5%, and 76.5%, respectively. Conclusions:Patients with electric burns are in a state of hypercoagulability of coagulation system and hyperfunction of fibrinolysis system in the early stage after burns, and TEG combined with CCT can increase the diagnostic rate of TIC in patients with electric burns.
		                        		
		                        		
		                        		
		                        	
4.The Role of Mechanical Sensitive Ion Channel Piezo in Digestive System Diseases
Si-Qi WANG ; Xiang-Yun YAN ; Yan-Qiu LI ; Fang-Li LUO ; Jun-Peng YAO ; Pei-Tao MA ; Yu-Jun HOU ; Hai-Yan QIN ; Yun-Zhou SHI ; Ying LI
Progress in Biochemistry and Biophysics 2024;51(8):1883-1894
		                        		
		                        			
		                        			The Piezo protein is a non-selective mechanosensitive cation channel that exhibits sensitivity to mechanical stimuli such as pressure and shear stress. It converts mechanical signals into bioelectric activity within cells, thus triggering specific biological responses. In the digestive system, Piezo protein plays a crucial role in maintaining normal physiological activities, including digestion, absorption, metabolic regulation, and immune modulation. However, dysregulation in Piezo protein expression may lead to the occurrence of several pathological conditions, including visceral hypersensitivity, impairment of intestinal mucosal barrier function, and immune inflammation.Therefore, conducting a comprehensive review of the physiological functions and pathological roles of Piezo protein in the digestive system is of paramount importance. In this review, we systematically summarize the structural and dynamic characteristics of Piezo protein, its expression patterns, and physiological functions in the digestive system. We particularly focus on elucidating the mechanisms of action of Piezo protein in digestive system tumor diseases, inflammatory diseases, fibrotic diseases, and functional disorders. Through the integration of the latest research findings, we have observed that Piezo protein plays a crucial role in the pathogenesis of various digestive system diseases. There exist intricate interactions between Piezo protein and multiple phenotypes of digestive system tumors such as proliferation, apoptosis, and metastasis. In inflammatory diseases, Piezo protein promotes intestinal immune responses and pancreatic trypsinogen activation, contributing to the development of ulcerative colitis, Crohn’s disease, and pancreatitis. Additionally, Piezo1, through pathways involving co-action with the TRPV4 ion channel, facilitates neutrophil recruitment and suppresses HIF-1α ubiquitination, thereby mediating organ fibrosis in organs like the liver and pancreas. Moreover, Piezo protein regulation by gut microbiota or factors like age and gender can result in increased or decreased visceral sensitivity, and alterations in intestinal mucosal barrier structure and permeability, which are closely associated with functional disorders like irritable bowel sydrome (IBS) and functional consitipaction (FC). A thorough exploration of Piezo protein as a potential therapeutic target in digestive system diseases can provide a scientific basis and theoretical support for future clinical diagnosis and treatment strategies. 
		                        		
		                        		
		                        		
		                        	
5.Comparison of Anterior-posterior and Posterior-anterior Internal Fixation With Screws for Posterior Malleolar Fractures in Trimalleolar Fractures
Tianyi LIU ; Guojin HOU ; Fang ZHOU ; Hongquan JI ; Zhishan ZHANG ; Yan GUO ; Yang LV ; Yun TIAN
Chinese Journal of Minimally Invasive Surgery 2024;24(6):415-421
		                        		
		                        			
		                        			Objective To compare the efficacy of anterior-posterior and posterior-anterior screw fixation for posterior malleolar fractures surgery.Methods A retrospective analysis of 376 cases of posterior malleolar fractures treated with lag screws from January 2011 to October 2022 with more than 12 months of follow-up period was conducted.The patients were divided into two subgroups based on the thickness of the fracture fragment,with 167 cases in the small fracture subgroup having a fracture fragment thickness<17 mm(screw thread length)and 209 cases in the large fracture subgroup having a fracture fragment thickness ≥ 17 mm.Each subgroup was further divided into anterior-posterior and posterior-anterior groups based on the direction of screw fixation in the posterior malleolar fracture surgery.In the small fracture subgroups,there were 74 cases in the anterior-posterior group and 93 cases in the posterior-anterior group.In the large fracture subgroup,there were 88 cases in the anterior-posterior group and 121 cases in the posterior-anterior group.The American Orthopaedic Foot and Ankle Society(AOFAS)ankle-hindfoot score was measured at the last follow-up.The displacement of the fracture fragment in the direction of the fracture line(Dn)and perpendicular to the fracture line(Dt)were measured on the first day after surgery and at the last follow-up,and the displacement of the fracture fragment was calculated,which was the difference between Dn+Dt at the last follow-up and Dn+Dt on the first day after surgery.Results On the first day after surgery,X-ray showed no significant difference in Dn and Dt between the anterior-posterior and posterior-anterior groups in both of the small and large fracture subgroups(P>0.05).The entire group was followed up for 12-85 months,with an average of 19.3 months.In the small fracture subgroup,the displacement of the fracture fragment in the posterior-anterior group[(0.11±0.19)mm]was superior to that in the anterior-posterior group[(0.19±0.21)mm;P=0.011],and the AOFAS score was also superior to that in the anterior-posterior group[(80.2±8.4)points vs.(76.2±8.6)points,P=0.003].In the large fracture subgroup,there was no significant difference in fracture displacement between the posterior-anterior group[(0.11±0.18)mm]and the anterior-posterior group[(0.12±0.19)mm;P=0.630],and there was also no significant difference in AOFAS scores[(84.1±7.8)points vs.(82.8±7.6)points,P=0.246].Conclusions There is no significant difference in the reduction effect between anterior-posterior and posterior-anterior lag screw internal fixation for posterior malleolar fractures in trimalleolar fractures.For patients with fracture thickness<17 mm,posterior-anterior fixation is superior to anterior-posterior fixation;for patients with fracture thickness ≥17 mm,there is no significant difference in the efficacy between anterior-posterior and posterior-anterior fixation.
		                        		
		                        		
		                        		
		                        	
6.Diagnostic value of serum serine protease Corin in patients with chronic renal failure complicated with heart failure
Pengfei ZHOU ; Shiyu LIU ; Wen FANG ; Ruihua CHEN ; Zihan ZHOU ; Xiaomei HOU ; Yutong YAN ; Yahui HU
Chinese Journal of Laboratory Medicine 2024;47(6):610-618
		                        		
		                        			
		                        			Objective:To investigate the diagnostic value of serum serine protease (Corin) in chronic renal failure (CRF) complicated with heart failure.Methods:A retrospective analysis was conducted on 120 patients, (64.05±13.89) years old, 77 male (64.17%), with chronic renal failure combined with heart failure admitted to Zhengzhou People′s Hospital from January 1, 2023, to December 31, 2023. The control group consisted of 87 patients, (60.59±8.78) years old, 54 male (62.07%), with simple chronic renal failure. Clinical information, laboratory test indicators and echocardiographic parameters were collected. Serum Corin concentration was measured using enzyme-linked immunosorbent assay (ELISA). The experimental group was divided into grade Ⅱ(31 cases), grade Ⅲ(47 cases) and grade Ⅳ(42 cases) according to the New York College of Cardiology heart function classification system. Serum Corin levels were compared between the experimental group and the control group and among different cardiac function grades. Spearman correlation analysis was performed to evaluate the relationship between serum Corin and brain natriuretic peptide (BNP), D-dimer. ROC analysis was conducted to assess the predictive value of serum Corin in CRF complicated with heart failure and cardiac function classification; Binary Logistic regression was used to construct a multi-index joint prediction model, the joint prediction probability was obtained, and ROC curve was drawn to compare the diagnostic value of serum Corin and BNP in CRF combined with heart failure and the diagnostic value of serum Corin combined with D-dimer and BNP in CRF combined with heart failure.Results:The serum Corin level[2 568.97±477.70 pg/ml vs. 1 727.81±480.60 pg/ml, t=12.47, P<0.001], BNP [700.00(256.00, 2 089.75) pg/ml compared with 88.00 (43.00, 230.00) pg/ml, Z=-9.00, P<0.001], D-dimer [1 150.00(643.00, 1 874.75)μg/L compared with 556.00 (301.00, 865.00)μg/L, Z=-6.57, P<0.001] in chronic renal failure complicated with heart failure group was higher than that in simple CRF group, and the difference was statistically significant. Among patients with CRF complicated with heart failure, serum Corin[2 231.74±311.39 pg/ml vs. 2 562.09±365.30 pg/ml vs. 2 825.57±536.83 pg/ml, F=74.33, P<0.001], BNP [234.00(168.00, 612.00) pg/ml compared with 514.00(260.00, 1 455.00) pg/ml compared with 2 200.00(640.50, 4 682.75) pg/ml, H=29.42, P<0.001], D-dimer [753.00(514.00, 1 280.00) μg/L compared with 1 187.00(590.00, 1 840.00) μg/L compared with 1 603.00(810.00, 3 313.25) μg/L, H=14.98, P<0.001] increased with the increase of cardiac function grade, and the difference was statistically significant. According to Spearman correlation analysis, serum Corin was positively correlated with BNP ( r=0.409) and D-dimer ( r=0.299), P<0.001. According to the ROC analysis, the AUC of serum Corin in the diagnosis of CRF complicated with heart failure and cardiac function grade Ⅱ, Ⅲ, Ⅳ were 0.890(95% CI 0.846-0.935), 0.807 (95% CI 0.728-0.885), 0.911 (95% CI 0.864-0.959), 0.927 (95% CI 0.882-0.972) respectively; the AUC of BNP in the diagnosis of CRF complicated with heart failure was 0.867 (95% CI 0.817-0.916), the AUC of serum Corin combined with D-dimer, BNP combined with D-dimer, serum Corin combined with D-dimer and BNP in the diagnosis of CRF complicated with heart failure were respectively 0.930 (95% CI 0.897-0.962), 0.892 (95% CI 0.847-0.936), 0.952 (95% CI 0.927-0.977). Conclusions:Serum Corin expression is elevated in patients with CRF complicated with heart failure, and the degree of elevation is related to cardiac function grade. Serum Corin has a good diagnostic value for CRF complicated with heart failure and its severity. Serum Corin is expected to become a new biomarker for diagnosis of CRF complicated with heart failure.
		                        		
		                        		
		                        		
		                        	
7.Selection and application of implementation strategies in implementation research.
Yan Yan HOU ; Bei Bei ZHU ; Fang Biao TAO
Chinese Journal of Preventive Medicine 2023;57(3):438-442
		                        		
		                        			
		                        			Implementation research is a discipline that attempts to promote the application of evidence-based interventions in different settings and populations by using various methods and measures. Implementation strategies are the central part of implementation research, and as the field of implementation science evolves, more and more implementation strategies have been developed to facilitate the application of evidence-based interventions in the real world. To help researchers better understand and apply implementation strategies, this study will introduce implementation strategies in three aspects: classification, selection and application, and report.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Implementation Science
		                        			
		                        		
		                        	
8.Pulmonary granular cell tumors: a clinicopathological analysis of five cases.
Hui Fang LIU ; Yan HUANG ; Chun Yan WU ; Yuan LI ; Yi Chen WANG ; Li Ping ZHANG ; Li Kun HOU ; Hui Kun XIE
Chinese Journal of Pathology 2023;52(2):136-141
		                        		
		                        			
		                        			Objective: To investigate the clinicopathological features of pulmonary granular cell tumors (pGCTs) and to improve the diagnostic accuracy of the tumor. Methods: A total of 5 pGCTs were diagnosed from February 2016 to January 2022 at Shanghai Pulmonary Hospital, Tongji University School of Medicine and Fudan University Shanghai Cancer Center, China. Immunohistochemical staining, and analysis of the clinicopathological characteristics were performed. Results: The average age of the pGCTs patients was 46 years (ranging from 24 to 54 years), with 3 females and 2 males. One case occurred in the bronchus with multiple nodules in the lung, 2 cases occurred in the bronchial opening, and 2 cases were solitary nodules in the lung. The maximum diameter of the tumors ranged from 12 to 15 mm (mean size 14 mm). Microscopically, the tumor showed infiltrative growth and consisted of round, oval or polygonal cells. Abundant eosinophilic cytoplasm was noted, and the nucleoli were prominent. None of the 5 cases showed any mitosis or necrosis. Immunohistochemical and histochemical study showed positive staining for S-100 (5/5), SOX10 (5/5), Vimentin (5/5), TFE3 (4/5), PAS (3/5), and amylase-digested-PAS (3/5), while 4 cases were negative for CD68. TFE3 FISH analyses on 2 cases showed that no signal abnormality was detected in these 2 cases. The average proliferation index of Ki-67 was 2.2% (range 0-5%). There was no recurrence in 4 cases of pGCTs with a follow-up time ranging from 2 months to 60 months. Conclusions: pGCTs are very rare tumors, most likely originating from Schwann cells. Immunohistochemical staining is the conventional diagnostic tool for pGCTs diagnosis. Recognition of this entity is essential for pathologists to avoid misdiagnosis and unnecessary treatments.
		                        		
		                        		
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
		                        			;
		                        		
		                        			Biomarkers, Tumor
		                        			;
		                        		
		                        			Bronchi
		                        			;
		                        		
		                        			China
		                        			;
		                        		
		                        			Granular Cell Tumor/surgery*
		                        			;
		                        		
		                        			Lung
		                        			;
		                        		
		                        			S100 Proteins
		                        			;
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Middle Aged
		                        			
		                        		
		                        	
9.Quality evaluation of Cnidii Fructus in commodity grade based on theory of "quality evaluation through morphological identification".
Hui-Fang HU ; Shao-Yang XI ; Hou-Kang CAO ; Yan-Xiu GUO ; Yuan-Meng WANG ; Ling-Hui GE ; Xiao-Hui MA ; Zhi-Lai ZHAN ; Ling JIN
China Journal of Chinese Materia Medica 2023;48(4):900-907
		                        		
		                        			
		                        			From the perspective of market classification of Cnidii Fructus, this paper revealed the scientific connotation of evaluating the quality grade of Cnidii Fructus by its appearance traits. Thirty batches of Cnidii Fructus in different grades were selected as the research objects. The canonical correlation analysis and principal component analysis(PCA) were used to explore the measurement values of 15 appearance traits and intrinsic content indexes. The results of correlation analysis showed that except the aspect ratio, the 5 appearance trait indexes(length, width, 1 000-grain weight, broken grain weight proportion, and chroma) and 9 internal content indexes(the content of moisture, total ash, acid insoluble ash, osthole, imperatorin, 5-methoxy psoralen, isopimpinellin, xanthotoxin, and xanthotol) showed significant correlation to varying degrees. In addition, there was a significant positive correlation between the first typical variable U_1 composed of appearance traits and the first typical variable V_1 composed of internal content indexes(CR_1=0.963, P<0.01). The results of PCA showed that the classification results of appearance traits for 30 batches of Cnidii Fructus were consistent with the actual information of the samples. Under the same analysis conditions, 30 batches of Cnidii Fructus were reclassified by 9 groups of internal content indexes, and the analysis results were consistent. From the classification standard of the appearance traits of the system study, the statistical results of 6 appearance traits of Cnidii Fructus showed a correlation with grades. There was a good correlation between the appearance and the internal content of Cnidii Fructus, and the appearance quality effectively predicted the level of the internal content. There is a certain scientific basis for the quality classification of Cnidii Fructus by main appearance traits. Appearance classification can replace quality grading to realize the "quality evaluation through morphological identification" of Cnidii Fructus.
		                        		
		                        		
		                        		
		                        			Fruit
		                        			;
		                        		
		                        			Phenotype
		                        			;
		                        		
		                        			Principal Component Analysis
		                        			;
		                        		
		                        			Social Group
		                        			
		                        		
		                        	
10.Baimai Ointment relieves chronic pain induced by chronic compression of dorsal root ganglion in rats by regulating neuroactive ligand-receptor interaction and HIF-1 signaling pathway.
Fang-Ting ZHOU ; Ying ZONG ; Wu-Qiong HOU ; Sen-Sen LI ; Fei YANG ; Li-Ting XU ; Xia MAO ; Yu-Dong LIU ; Xiao-Hui SU ; Hong-Ye WAN ; Jing-Feng OUYANG ; Qiu-Yan GUO ; Wei-Jie LI ; Zhen WANG ; Chao WANG ; Na LIN
China Journal of Chinese Materia Medica 2023;48(23):6457-6474
		                        		
		                        			
		                        			The Baimai Ointment with the effect of relaxing sinew and activating collaterals demonstrates a definite effect on Baimai disease with pain, spasm, stiffness and other symptoms, while the pharmacodynamic characteristics and mechanism of this agent remain unclear. In this study, a rat model of chronic compression of L4 dorsal root ganglion(CCD) was established by lumbar disc herniation, and the efficacy and mechanism of Baimai Ointment in the treatment of CCD were preliminarily explored by behavioral tests, side effect evaluation, network analysis, antagonist and molecular biology verification. The pharmacodynamic experiment indicated that Baimai Ointment significantly improved the pain thresholds(mechanical pain, thermal pain, and cold pain) and gait behavior of CCD model rats without causing tolerance or obvious toxic and side effects. Baimai Ointment inhibited the second-phase nociceptive response of mice in the formalin test, increased the hot plate threshold of normal mice, and down-regulated the expression of inflammatory cytokines in the spinal cord. Network analysis showed that Baimai Ointment had synergistic effect in the treatment of CCD and was related to descending inhibition/facilitation system and neuroinflammation. Furthermore, behavioral tests, Western blot, and immunofluorescence assay revealed that the pain-relieving effect of Baimai Ointment on CCD may be related to the regulation of the interaction between neuroactive ligand and receptors(neuroligands) such as CHRNA7, ADRA2A, and ADRB2, and the down-regulation of the expression of NOS2/pERK/PI3K, the core regulatory element of HIF-1 signaling pathway in spinal microglia. The findings preliminarily reveal the mechanism of relaxing sinew and activating collaterals of Baimai Ointment in the treatment of Baimai disease, providing a reference for the rational drug use and further research of this agent.
		                        		
		                        		
		                        		
		                        			Rats
		                        			;
		                        		
		                        			Mice
		                        			;
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Chronic Pain/metabolism*
		                        			;
		                        		
		                        			Rats, Sprague-Dawley
		                        			;
		                        		
		                        			Ganglia, Spinal/metabolism*
		                        			;
		                        		
		                        			Ligands
		                        			;
		                        		
		                        			Signal Transduction
		                        			;
		                        		
		                        			Hyperalgesia/metabolism*
		                        			;
		                        		
		                        			Drugs, Chinese Herbal
		                        			
		                        		
		                        	
            
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