1.Discussion on Mechanisms of "State-Target Differentiation and Treatment" for Diabetic Foot Ulcers from the Perspective of Epithelial-Mesenchymal Transition
Hong CHEN ; Weijing FAN ; Renyan HUANG ; Guobin LIU
Journal of Traditional Chinese Medicine 2025;66(1):23-29
Building on the theory of "state-target differentiation and treatment" proposed by Academician TONG Xiaolin, diabetic foot ulcers (DFUs) are considered to belong to the "collateral injury" stage, characterized by the interplay of five states,i.e. dampness, heat, stasis, deficiency, and impairment. The dynamic biological process of epithelial-mesenchymal transition (EMT) is closely associated with the healing process of DFUs. The treatment of DFUs through staged differentiation under the "state-target differentiation and treatment" theory not only provides a basis for precise clinical treatment, but also offers insights into the regulatory roles of EMT in different states and potential intervention targets. The dampness state typically exits during the inflammatory phase, local inflammation and fluid metabolism disorders inducing EMT. Treatment focuses on draining dampness and alleviating edema, promoting local microcirculation, and improving tissue hypoxia. The heat state often reflects acute local inflammatory responses. Treatment emphasizes clearing heat and resolving toxins, regulating the EMT process to reduce inflammation, control infection, and alleviate redness, swollen, heat, and pain in the affected area. The stasis state mainly occurs during the proliferation phase. Treatment centers on invigorating blood and dissolving stasis, and unblocking the channels and quickening the collaterals. EMT plays a role in remodeling the extracellular matrix, promoting tissue repair and angiogenesis. The deficiency state is common in chronic phase, where treatment prioritizes tonifying qi and nourishing blood while reinforcing healthy qi and dispelling pathogens. EMT regulation focuses on restoring local tissue metabolism and improving the micro-environment to enhance tissue repair capacity. The impairment state represents the progression of disease deterioration. Treatment should focus on supplementing qi, blood, yin, and yang, and also promoting muscle growth and strengthening bones, supplementing by resolving toxins and stasis. EMT plays a role by regulating the activity of extracellular matrix-degrading enzymes to prevent excessive tissue repair and scarring, thereby facilitating the reconstruction of normal tissue structures.
2.Clinical Efficacy of Fuyuan Tongluo Prescription in Prevention and Treatment of Restenosis with Collateral Obstruction Syndrome After Interventional Operation of Lower Limb Arteriosclerosis Obliterans
Fangfang WU ; Xiaoyu LI ; Guobin LIU ; Hongfei WANG ; Weijing FAN ; Renyan HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):134-140
ObjectiveTo observe the effects of the Fuyuan Tongluo prescription (composed of Astragali Radix, Carthami Flos, Spatholobi Caulis, Liquidambaris Fructus, Lycopodii Herba, Centellae Herba, etc.) in the treatment of restenosis with collateral obstruction syndrome after interventional operation of lower limb arteriosclerosis obliterans, and its impact on the primary patency rate. MethodsA total of 88 patients with collateral obstruction syndrome after interventional surgery for lower limb arteriosclerosis obliterans were randomly divided into two groups. The control group (n1=44) received dual antiplatelet therapy with aspirin and clopidogrel. The observation group (n2=44) was treated with Fuyuan Tongluo prescription non-decocted granules in addition to aspirin and clopidogrel. Both groups received treatment for 24 weeks and were followed up for 36 weeks. The changes in primary patency rate, symptom scores, ankle-brachial index (ABI), coagulation function, and inflammatory markers before and after treatment were compared between the two groups. ResultsFor primary patency rate, after 36 weeks of treatment, the observation group had a significantly better primary patency rate than the control group (χ2=4.14,P<0.05). After 24 weeks of treatment, there was no significant difference in primary patency rate between the two groups. Clinical efficacy comparison: Based on symptom quantification scores, and using the Nimodipine method as a reference, the overall efficacy of the observation group was superior to that of the control group after 24 weeks of treatment (χ2=2.24,P<0.05). ABI levels: The observation group had a higher ABI than the control group after 24 and 36 weeks of treatment (P<0.05). Coagulation function indicators: After 24 and 36 weeks of treatment, D-dimer and fibrinogen levels in both groups were lower than before treatment (P<0.05). Inflammatory markers: After 24 and 36 weeks of treatment, CRP levels in the observation group were lower than those in the control group (P<0.05). There were no significant differences in white blood cell (WBC) and erythrocyte sedimentation rate (ESR) levels before and after treatment between the two groups. ConclusionAdding Fuyuan Tongluo prescription non-decocted granules to dual antiplatelet therapy can improve the primary patency rate of the affected vessels in patients with lower limb arteriosclerosis obliterans after interventional surgery. Longer use of Fuyuan Tongluo prescription can significantly improve clinical symptoms, demonstrating clinical application value.
3.Clinical Efficacy of Fuyuan Tongluo Prescription in Prevention and Treatment of Restenosis with Collateral Obstruction Syndrome After Interventional Operation of Lower Limb Arteriosclerosis Obliterans
Fangfang WU ; Xiaoyu LI ; Guobin LIU ; Hongfei WANG ; Weijing FAN ; Renyan HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):134-140
ObjectiveTo observe the effects of the Fuyuan Tongluo prescription (composed of Astragali Radix, Carthami Flos, Spatholobi Caulis, Liquidambaris Fructus, Lycopodii Herba, Centellae Herba, etc.) in the treatment of restenosis with collateral obstruction syndrome after interventional operation of lower limb arteriosclerosis obliterans, and its impact on the primary patency rate. MethodsA total of 88 patients with collateral obstruction syndrome after interventional surgery for lower limb arteriosclerosis obliterans were randomly divided into two groups. The control group (n1=44) received dual antiplatelet therapy with aspirin and clopidogrel. The observation group (n2=44) was treated with Fuyuan Tongluo prescription non-decocted granules in addition to aspirin and clopidogrel. Both groups received treatment for 24 weeks and were followed up for 36 weeks. The changes in primary patency rate, symptom scores, ankle-brachial index (ABI), coagulation function, and inflammatory markers before and after treatment were compared between the two groups. ResultsFor primary patency rate, after 36 weeks of treatment, the observation group had a significantly better primary patency rate than the control group (χ2=4.14,P<0.05). After 24 weeks of treatment, there was no significant difference in primary patency rate between the two groups. Clinical efficacy comparison: Based on symptom quantification scores, and using the Nimodipine method as a reference, the overall efficacy of the observation group was superior to that of the control group after 24 weeks of treatment (χ2=2.24,P<0.05). ABI levels: The observation group had a higher ABI than the control group after 24 and 36 weeks of treatment (P<0.05). Coagulation function indicators: After 24 and 36 weeks of treatment, D-dimer and fibrinogen levels in both groups were lower than before treatment (P<0.05). Inflammatory markers: After 24 and 36 weeks of treatment, CRP levels in the observation group were lower than those in the control group (P<0.05). There were no significant differences in white blood cell (WBC) and erythrocyte sedimentation rate (ESR) levels before and after treatment between the two groups. ConclusionAdding Fuyuan Tongluo prescription non-decocted granules to dual antiplatelet therapy can improve the primary patency rate of the affected vessels in patients with lower limb arteriosclerosis obliterans after interventional surgery. Longer use of Fuyuan Tongluo prescription can significantly improve clinical symptoms, demonstrating clinical application value.
4.Effects of Zizhu Ointment Combined with Tendon Clearance on Serum Levels of NLRP3, IL-1β, and IL-18, in Treatment of Non-ischemic Diabetic Foot Ulcers
Yaoqing SUN ; Weijing FAN ; Renyan HUANG ; Huimin LU ; Hong CHEN ; Guobin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(21):212-218
ObjectiveTo observe the effect of tendon clearing combined with Zizhu ointment on the serum levels of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasomes, interleukin (IL)-1β, and IL-18 in the treatment of non-ischemic diabetic foot ulcers. MethodA total of 106 patients with non-defective diabetic foot ulcers who attended the outpatient clinic and wards of the Vascular Surgery Department of Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine from March 2023 to March 2024 were selected. The patients with non-ischemic diabetic foot ulcers who met the inclusion criteria were assigned with the random number table method into an observation group and a control group, with 53 patients in each group. Patients in both groups received basic treatment. The local ulcers in the observation group received tendon clearing combined with Zizhu ointment, while those in the control group received conventional debridement combined with topical solution of bovine basic fibroblast growth factor. The serum NLRP3, IL-1β, and IL-18 levels, ulcer area, traditional Chinese medicine (TCM) symptom scores, visual analogue scale (VAS) score, and DMIST score were measured and recorded in the two groups before and after treatment. The ulcer healing rate and incidence of adverse reactions were compared between the two groups. ResultThe observation group had higher ulcer healing rate than the control group (P<0.01). After treatment, both groups showed lowered serum NLRP3, IL-1β, and IL-18 levels, reduced ulcer area, and declined TCM symptom score, VAS score, and DMIST score (P<0.01). Moreover, these indicators were lower in the observation group than in the control group (P<0.05, P<0.01). Neither group showed significant changes in the liver and kidney function indicators after treatment. Significant adverse reactions occurred in neither group during the treatment course. ConclusionTendon clearance combined with Zizhu ointment was effective and safe in treating non-ischemic diabetic foot ulcers. It may exert the therapeutic effect by reducing the inflammation of the local ulcers.
5.Baseline hematoma mean CT value and shape regularity index predict hematoma enlargement in patients with spontaneous intracerebral hemorrhage
Xinhui FAN ; Xiaofan WANG ; Nini ZHANG ; Yongfeng HUANG ; Bingdong FENG ; Weijing ZHANG
International Journal of Cerebrovascular Diseases 2023;31(11):830-835
Objective:To investigate the predictive values of baseline hematoma mean CT value and shape regularity (SR) for hematoma enlargement (HE) in patients with spontaneous intracerebral hemorrhage (ICH).Methods:Patients with ICH admitted to Yulin First Hospital from June 2018 to December 2021 were retrospectively included. The first head CT scan was performed within 24 h of onset, and the second head CT scan was performed within 72 h of the first scan. HE was defined as an increase in hematoma volume of at least 6 ml or 33% from the first CT. 3D Slicer software was used to reconstruct 3D images and SR was calculated. Multivariate logistic regression analysis was used to determine the independent factor for HE. Receiver operator characteristic (ROC) curve was used to evaluate the predictive value of baseline hematoma mean CT value for HE. Results:A total of 249 patients with ICH were enrolled, including 134 males (53.8%), and aged 62.2±12.1 years. The median baseline Glasgow Coma Scale score was 12, and the median time from onset to first CT scan was 3.1 h. The median baseline hematoma volume was 10.9 ml, and 58 patients (23.3%) showed HE. The baseline hematoma mean CT value in the HE group (58.5±3.2 HU vs. 60.3±3.3 HU; P<0.01) and baseline SR (0.615±0.146 vs. 0.688±0.100; P<0.001) were significantly lower in the non-HE group. Multivariate logistic regression analysis showed that the time from onset to first CT scan (odds ratio [ OR] 0.867, 95% confidence interval [ CI] 0.786-0.957; P=0.004), the baseline hematoma volume ( OR 1.050, 95% CI 1.028-1.073; P<0.001), and the baseline hematoma mean CT value ( OR 0.809, 95% CI 0.725-0.902; P<0.001) were the independent predictors of HE, while the baseline SR had no significant independent correlation with HE. ROC curve analysis showed that the area under the curve of baseline hematoma mean CT value for predicting HE was 0.652 (95% CI 0.573-0.731; P<0.001), with an optimal cutoff value of 57.97 HU. The sensitivity and specificity for predicting HE were 50% and 75.9%, respectively. Conclusion:The baseline hematoma mean CT value is an independent factor for HE in patients with ICH and has certain predictive value for HE.
6.Clinical Observation on Treatment of Diabetic Foot Ulcer of Wagner Grade 1-2 by Compound Huangbai Liquid Fomentation
Lei XU ; Weijing FAN ; Xuhong WANG ; Guobin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(6):104-110
ObjectiveTo observe the clinical efficacy of compound Huangbai liquid fomentation on diabetic foot ulcer of Wagner grade 1-2. MethodPatients were classified into the observation group and control group, with 41 cases in either group. The observation group received routine therapy and compound Huangbai liquid fomentation, while the control group was treated by routine therapy and medical silver nanoparticles-containing dressing. Ulcer area, ulcer depth, traditional Chinese medicine (TCM) syndrome score, ankle-brachial index, transcutaneous oxygen pressure, vascular endothelial growth factor, epidermal growth factor, advanced glycation end product, high-sensitivity C-reactive protein, interleukin-6, erythrocyte sedimentation rate, and adverse events were observed before and after treatment in two groups. ResultAfter treatment, the ulcer area, ulcer depth, TCM syndrome score, vascular endothelial growth factor, epidermal growth factor, advanced glycation end product, high-sensitivity C-reactive protein, interleukin-6(IL-6), and erythrocyte sedimentation rate were lower than those before treatment in two groups (P<0.05), and ankle-brachial index, transcutaneous oxygen pressure, vascular endothelial growth factor, and epidermal growth factor were higher than those before treatment in two groups (P<0.05). After treatment, the ulcer area, ulcer depth, TCM syndrome score, advanced glycation end product, high-sensitivity C-reactive protein, IL-6, and erythrocyte sedimentation rate were lower in the observation group than in the control group (P<0.05), and ankle-brachial index, transcutaneous oxygen pressure, vascular endothelial growth factor, and epidermal growth factor were higher in the observation group than in the control group (P<0.05). The clinical efficacy of observation group was better than that of the control group (P<0.05). There was no significant difference in the incidence of adverse events and endpoint events between two groups. ConclusionCompound Huangbai liquid fomentation is effective for diabetic foot ulcer of Wagner grade 1-2, as it is beneficial to the healing of the ulcer. This study provides clinical evidence for the further promotion of Chinese medicine fomentation.
7.Clinical Observation on Wagner 2-3 Diabetic Foot Ulcer Treated by TCM External Treatment Scheme for Euriching Pus for Tissue Growth
Weijing FAN ; Hongfei WANG ; Baozhong YANG ; Lei XU ; Guobin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(14):107-114
ObjectiveTo observe the clinical efficacy and safety of traditional Chinese medicine (TCM) external therapeutic protocol of enriching pus for tissue growth (EPTG) in the treatment of Wagner 2-3 diabetic foot ulcer. MethodThe randomized controlled trial (RCT) design was adopted. Patients receiving basic treatment were divided into the EPTG group and the control group (debridement and change of nano-silver medical antibacterial dressing). Ulcer healing rate, ulcer area, ulcer depth, TCM symptom score, visual analogue scale(VAS), transcutaneous partial pressure of oxygen, wound blood flow, inflammatory factors [C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)], growth factors [vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1), and fibroblast growth factor-β (FGF-β)], adverse events, and outcome events of the two groups before and after treatment were observed. ResultCompared with the conditions before treatment, the ulcer healing rate, ulcer area, ulcer depth, TCM symptom score, VAS score, transcutaneous partial pressure of oxygen, wound blood flow, CRP, IL-6, TNF-α, VEGF, TGF-β1, and FGF-β were significantly improved (P<0.01). In terms of the improvement in the ulcer healing rate, ulcer area, ulcer depth, VAS score, transcutaneous partial pressure of oxygen, wound blood flow, CRP, IL-6, TNF-α, VEGF, TGF-β1, and FGF-β, the EPTG group was superior to the control group (P<0.01). There were no statistically significant differences in adverse events and outcome events between the two groups. ConclusionThe TCM external therapeutic protocol of EPTG is safe and effective in the treatment of Wagner 2-3 diabetic foot ulcer. It can greatly reduce the area and depth of diabetic foot ulcer, improve the ulcer healing rate and TCM symptom score, relieve the pain of patients, and improve the microcirculatory blood supply in the local ulcer. Its mechanism of action may be related to the reduction of the local inflammatory response of the wound and the improvement of the proliferation of fibroblasts and vascular endothelial cells.
8.Applicability of CT examination decision rules in head injured children
Zhen REN ; Guilong FENG ; Kai FAN ; Weijing WEN ; Rui ZHANG ; Yuanwei FU ; Jiali ZHANG ; Weizong LIU
Chinese Journal of Emergency Medicine 2019;28(8):956-961
Objective To explore the applicability of the three commonly used CT examination decision rules in Chinese head injured children. Methods This prospective observational study included 1538 children and adolescents (aged < 18 years), who were treated at the Emergency Department of First Hospital of Shanxi Medical University after head injuries. The three clinical decision rules include the Children's Head Injury Algorithm for the Prediction of Important Clinical Events (CHALICE; UK); the prediction rule for the identification of children at very low risk of clinically important traumatic brain injury, that was developed by the Pediatric Emergency Care Applied Research Network (PECARN; USA), and the Canadian Assessment of Tomography for Childhood Head Injury (CATCH) rule. Diagnostic accuracy had been evaluated by using the rule-specific predictor variables to predict each rule-specific outcome measure in populations who met inclusion and exclusion criteria for each rule. Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and ROC curve were referred to the diagnostic accuracy. Indicators were characterized by 95% CI. Results Of the 1538 patients, CTs were obtained for 339 patients (22.04%). Forty-nine patients (3.19%) had positive CT results, 8 patients (0.52%) underwent neurosurgery, 2 patients (0.13%) died, and 1 patient (0.07%) may be missed. In this study, CHALICE was applied for 1394 children (90.70%; 95% CI: 89.24%-92.15%), PECARN for 801 children (52.11%; 95% CI: 49.62%-54.61%), and CATCH for 325 patients (21.15%; 95%CI: 19.10%-23.19%). The validation sensitivities of CHALICE, PECARN, and CATCH rules were 92.6%(74.2%-98.7%), 100% (56.1%-100%), and 85.7% (42.0%-99.2%), respectively; the specificities were 78.1%(75.7%-80.2%), 48.0% (44.5%-51.5%) and 70.8% (65.4%-75.6%); positive predictive value were 7.7% (5.1%-11.3%), 0.9% (0.4%-1.9%) and 6.1% (2.5%-13.2%); and negative predictive value were 99.8% (99.2%-100%), 99.1% (98.1%-99.6%), and 99.6% (97.2%-100%), respectively. Conclusions The clinical decision rules of CHALICE, PECARN and CATCH have high sensitivities. The specificity of PECARN rule is lower than those of CHALICE and CATCH rules. The above three clinical decision rules can be used for the decision of CT examination in Chinese children with head injury in practice.
9.Effect of transcutaneous electrical acupoint stimulation on intestinal mucosal injury in patients undergoing laparoscopic radical resection of colorectal cancer
Xueming FAN ; Fangxiang ZHANG ; Ling HUANG ; Bingning CHEN ; Weijing ZHANG ; Jingchao ZHANG
Chinese Journal of Anesthesiology 2019;39(1):52-55
Objective To evaluate the effect of transcutaneous electrical acupoint stimulation (TEAS) on intestinal mucosal injury in patients undergoing laparoscopic radical resection of colorectal cancer.Methods Fifty-six American Society of Anesthesiologists physical status Ⅱ or Ⅲ patients,aged 35-64 yr,with body mass index of 18-25 kg/m2,scheduled for elective laparoscopic radical resection of colorectal cancer,were selected and divided into 2 groups (n =28 each) using a random number table method:general anesthesia group (group G) and TEAS combined with general anesthesia group (group TG).In group TG,patients received continuous TEAS at bilateral Neiguan,Hegu,Zusanli,Shangjuxu and Xiajuxu acupoints from 30 min before anesthesia induction until the end of surgery,with a frequency 2/100HZ,disperse dense waves,intensity the maximum current that could be tolerated (3-8 mA).After induction of anesthesia,the patients were endotracheally intubated and mechanically ventilated,and combined intravenous-inhalational anesthesia was used to maintain anesthesia in both groups.Peripheral venous blood samples were collected when entering the operating room (T1),at the end of operation (T2),and at 24 and 72 h after operation (T3,4) for determination of intestinal fatty acid binding protein (I-FABP) and diamine oxidase (DAO) in palsma using enzyme-linked immunosorbent assay.Quality of Recovery-9 (QoR9) was used to assess the postoperative quality of recovery at 24 h before surgery (T0),T3 and T4.Results The concentrations of plasma I-FABP and DAO were significantly higher at T2 and T3 than at T1 in G and TG groups (P<0.05).Compared with the baseline at T0,QoR-9 scores were significantly decreased at T3 and T4 in G and TG groups (P<0.05).Compared with group G,the concentrations of plasma I-FABP at T2-T4 and DAO at T2 and T3 were significantly decreased,and QoR-9 scores were increased at T3 and T4 in group TG (P<0.05).Conclusion TEAS can attenuate intestinal mucosal injury in patients undergoing laparoscopic radical resection of colorectal cancer.
10.Effects of apolipoprotein E deficiency on neuromyelitis model in vitro
Weijing LIAO ; Yifeng LI ; Yulan TANG ; Lijun FAN ; Fan HUANG
Chinese Journal of Neurology 2018;51(2):111-117
Objective To investigate the effects of apolipoprotein E (ApoE) deficiency on neuromyelitis optica (NMO) model of spinal cord sections induced by NMO-IgG and complement in vitro.Methods NMO-IgG was extracted from the patients with NMO,and complementary serum from healthy people.The spinal cord sections of seven days old C57BL / 6J mice with wild type (WT) or ApoE knockout (ApoE-/-) were cultured for seven days.The spinal cords of the two genotypes were randomly divided into experimental groups (NMO-ApoE-/-group,NMO-WT group) and control groups (C-AopE-/-group,C-WT group),respectively.The experimental groups were treated with NMO-IgG and complementary serum,and the control groups only with complementary serum.Then all the sections were continued incubating for 24 h before harvested.Immunofluorescence staining and modified thick tissue film immunofluorescence were used to detect the expression of aquaporin 4 (AQP4),glial fibrillary acidic protein (GFAP),ionic calcium fibronectin (IBA1),myelin basic protein (MBP) and human neurofilament protein L (NFL) respectively.The lesion score was calculated according to the areas percentage of AQP4 and GFAP deficiency in spinal cord sections.Results Compared with the respective control groups,the expressions of AQP4,GFAP,MBP and NFL were deficient in the experimental groups (The percentages of missing area in the NMO-ApoE-/-group were 83.88% ± 5.01%,82.44% ± 6.11%,45.02% ± 5.11% and 54.65% ± 7.66% respectively,while the percentages of missing area in the C-ApoE-/-group were 10.44% ± 4.07%,5.73% ±0.82%,9.12% ±1.41% and 5.72% ±0.81%,t=34.143,37.269,20.300,19.051,allP <0.05;The percentages of missing area in the NMO-WT group were 77.74% ± 6.75%,75.62% ± 5.76%,37.60% ± 4.88% and 46.29% ± 4.98%,while the percentages of missing area in the C-WT group were 9.31% ± 2.97%,5.80% ± 0.82%,9.10% ± 1.63%,5.80% ± 0.81% respectively,t =27.828,35.934,16.613,24.057,all P < 0.05).While IBA1 was up-regulated and the damage scores were higher in both the NMO-ApoE-/-group and the NMO-WT group.The percentages of missing area in the NMO-ApoE-/-group and the NMO-WT group showed statistically significant difference (t =2.194,2.436,3.149,2.746,all P < 0.05).The expression level of IBA1 in the NMO-WT group was higher than that in the C-WT group (19.88 ± 1.11 vs 11.18 ±0.65,t =25.270,P <0.05),while the expression level of IBA1 in the NMO-ApoE-/-group was higher than that in the NMO-WT group (25.81 ± 1.61 vs 19.88 ± 1.11,t =9.101,P <0.05).The degree of deficiency or up-regulation of above-mentioned proteins was more obvious in the NMO-ApoE-/-group than that in the NMO-WT group.Conclusions NMO-IgG extracted from NMO patients can induce NMO-like damage in isolated tissue at the presence of complement.ApoE deficiency promotes the further activation of microglia,thereby aggravates the injury of astrocyte in the model of NMO.

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