1.Mechanism of Buyang Huanwutang in Inhibiting Ferroptosis and Enhancing Neurological Function Recovery After Spinal Cord Injury via GPX4-ACSL4 Axis
Luchun XU ; Guozheng JIANG ; Yukun MA ; Jiawei SONG ; Yushan GAO ; Guanlong WANG ; Jiaojiao FAN ; Yongdong YANG ; Xing YU ; Xiangsheng TANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):20-30
ObjectiveTo explore the mechanism by which Buyang Huanwutang regulates the glutathione peroxidase 4 (GPX4)-acyl-CoA synthetase long-chain family member 4 (ACSL4) axis to inhibit ferroptosis and promote neurological functional recovery after spinal cord injury (SCI). MethodsNinety rats were randomly divided into five groups: sham operation group, model group, low-dose Buyang Huanwutang group (12.5 g·kg-1), high-dose Buyang Huanwutang group (25 g·kg-1), and Buyang Huanwutang + inhibitor group (25 g·kg-1 + 5 g·kg-1 RSL3). The SCI model was established by using the allen method. Tissue was collected on the 7th and 28th days after operation. Motor function was assessed by using the Basso-Beattie-Bresnahan (BBB) scale. Hematoxylin-eosin (HE), Nissl, and Luxol fast blue (LFB) staining were performed to observe spinal cord histopathology. Transmission electron microscopy was used to examine mitochondrial ultrastructure. Immunofluorescence staining was used to detect the number of NeuN-positive cells and the fluorescence intensity of myelin basic protein (MBP), GPX4, and ACSL4. Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) was used to analyze the mRNA expression of GPX4 and ACSL4. Enzyme linked immunosorbent assay (ELISA) was performed to measure the levels of reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD). Colorimetric assays were used to determine the iron content in spinal cord tissue. ResultsCompared to the sham operation group, the model group exhibited significantly reduced BBB scores (P<0.01), severe pathological damage in spinal cord tissue, and marked mitochondrial ultrastructural disruption. In addition, the model group showed a decrease in the number of NeuN-positive cells (P<0.01), reduced fluorescence intensity of MBP and GPX4 (P<0.01), lower levels of GSH and SOD (P<0.01), and downregulated mRNA expression of GPX4 (P<0.01). Moreover, compared to the sham operation group, the model group had elevated levels of ROS, MDA, and tissue iron content (P<0.01), along with increased fluorescence intensity and mRNA expression of ACSL4 (P<0.01). Compared with the model group and Buyang Huanwutang + inhibitor group, the Buyang Huanwutang group showed significantly improved BBB scores (P<0.05, P<0.01) and exhibited less severe spinal cord tissue damage, reduced edema and inflammatory cell infiltration, increased neuronal survival, and more intact myelin structures. Additionally, mitochondrial ultrastructure was significantly improved in the Buyang Huanwutang group. Compared to the model group and Buyang Huanwutang + inhibitor group, the Buyang Huanwutang group significantly increased the number of NeuN-positive cells and the fluorescence intensity of MBP (P<0.05, P<0.01). Furthermore, Buyang Huanwutang significantly increased the fluorescence intensity and mRNA expression of GPX4 (P<0.01) and decreased the fluorescence intensity and mRNA expression of ACSL4 (P<0.01) compared to the model group and Buyang Huanwutang + inhibitor group. Finally, the Buyang Huanwutang group significantly decreased ROS, MDA, and tissue iron content (P<0.01) and significantly increased GSH and SOD levels (P<0.01) compared to the model group and Buyang Huanwutang + inhibitor group. ConclusionBuyang Huanwutang inhibits ferroptosis through the GPX4/ACSL4 axis, reduces secondary neuronal and myelin injury and oxidative stress, and ultimately promotes the recovery of neurological function.
2.Protective effect of asiatic acid on brain injury after experimental subarachnoid hemorrhage in rats
Xiaoxiao WU ; Yukun HU ; Jiang WU
Tianjin Medical Journal 2024;52(3):285-289
Objective To explore the neuroprotective effect of asiatic acid(AA)on brain damage after experimental subarachnoid hemorrhage(SAH)in rats.Methods A total of 108 adult SD rats were divided into the sham1 group,the SAH+vehicle group and the SAH+AA group,with 36 rats in each group.The 42 rats were divided into the sham2 group,3,6,12,24,48 and 72 h after SAH groups,with 6 rats in each group.Except the sham group,SAH model was established by unilateral external carotid artery puncture method in other groups.After modeling,the SAH+AA group was given AA solution(30 mg/kg)by gavage.Neurobehavioral changes were assessed by foot fault test and modified Garcia score.Western blot assay was used to detect the protein level of glutathione peroxidase 4(GPX4)in brain tissue.ELISA was used to detect the concentrations of glutathione(GSH)and malondialdehyde(MDA).Fluoro Jade B(FJB)staining was used to detect the neuronal death.Results Compared with the sham1 group,the SAH+vehicle group showed a significant increase in the proportion of empty steps and a significant decrease in the modified Garcia score,a significant decrease in GPX4 protein levels,a significant increase in MDA concentration(P<0.05),a decrease in GSH concentration(P<0.01)and a significant increase in the number of dead neurons(P<0.05).Compared with the SAH+vehicle group,a significant decrease in the proportion of empty steps,a significant increase in the modified Garcia score,a significant increase in GPX4 protein level,a significant decrease in MDA concentration,a significant increase in GSH concentration(P<0.05)and a significant decrease in the number of dead neurons in the SAH+AA group(P<0.05).Conclusion AA may reduce brain injury after SAH in rats by inhibiting lipid peroxidation.
3.Buyang Huanwu decoction promotes angiogenesis and improves hemorheological parameters after cervical spinal cord injury
Luchun Xu ; Yongdong Yang ; Guozheng Jiang ; Yushan Gao ; Jiawei Song ; Yukun Ma ; Jiaojiao Fan ; Guanlong Wang ; Xing Yu ; Xiangsheng Tang
Journal of Traditional Chinese Medical Sciences 2024;11(4):456-465
Objective:
To explore the effects of Buyang Huanwu decoction (BYHWD) on vascular neogenesis and hemorheological parameters following cervical spinal cord injury (SCI).
Methods:
An acute cervical SCI model was established using 84 female Sprague–Dawley rats. Functional recovery of the rats was evaluated using the forelimb locomotor scale score, forelimb grip strength test, and Basso-Beattie-Bresnahan score. The animals were subsequently euthanized at days 7 and 28 postoperatively. The gross morphology, neuronal survival, and myelin sheath in the injured area were evaluated using hematoxylin and eosin (HE), Nissl, and luxol fast blue (LFB) staining, respectively. Immunofluorescence staining was used to observe CD31 expression 7 days post-injury. Furthermore, the expression of CD31, neuronal nuclear protein (NeuN), and myelin basic protein (MBP) were evaluated 28 days post-injury. Additionally, vascular endothelial growth factor A (VEGFA) and VEGF receptor-2 (VEGFR-2) expression was evaluated using western blotting. Whole-blood viscosity, plasma viscosity, and red blood cell aggregation were measured using a hemorheometer.
Results:
From postoperative days 3–28, motor function in the BYHWD group began to recover considerably compared to the SCI group. BYHWD effectively restored spinal cord histopathology. In addition, the number of NeuN-positive cells, and fluorescence intensity of CD31at 7 and 28 days and MBP significantly increased in the BYHWD group compared with the SCI group (all P < .05). Moreover, this decoction significantly upregulated the expression of VEGFA and VEGFR-2 (all P < .05). BYHWD improved the hemorheology results (i.e., except erythrocyte aggregation index in the low-dose group), revealing statistically significant differences compared with the SCI group (all P < .05).
Conclusion
BYHWD effectively promoted angiogenesis, improved hemorheological parameters, and protected neurons and myelin sheaths, ultimately promoting the recovery of neurological function after cervical SCI in rats. These findings suggest that BYHWD promotes vascular neogenesis through the VEGFA/VEGFR-2 pathway.
4.Research progress on graphene and its derivatives modulating the bone regeneration microenvironment
Yuanchen LAN ; Hengyi LIN ; Yukun JIANG ; Zhiai HU ; Shujuan ZOU
Journal of Prevention and Treatment for Stomatological Diseases 2024;32(7):539-547
Graphene family nanomaterials(GFNs)are highly popular in the field of bone tissue engineering because of their excellent mechanical properties,biocompatibility,and ability to promote the osteogenic differentiation of stem cells.GFNs play a multifaceted role in promoting the bone regeneration microenvironment.First,GFNs activate the ad-hesion kinase/extracellularly regulated protein kinase(FAK/ERK)signaling pathway through their own micromorphology and promote the expression of osteogenesis-related genes.Second,GFNs adapt to the mechanical strength of bone tis-sue,which helps to maintain osseointegration;by adjusting the stiffness of the extracellular matrix,they transmit the me-chanical signals of the matrix to the intracellular space with the help of focal adhesions(FAs),thus creating a favorable physiochemical microenvironment.Moreover,they regulate the immune microenvironment at the site of bone defects,thus directing the polarization of macrophages to the M2 type and influencing the secretion of relevant cytokines.GFNs also act as slow-release carriers of bioactive molecules with both angiogenic and antibacterial abilities,thus accelerating the repair process of bone defects.Multiple types of GFNs regulate the bone regeneration microenvironment,including scaffold materials,hydrogels,biofilms,and implantable coatings.Although GFNs have attracted much attention in the field of bone tissue engineering,their application in bone tissue regeneration is still in the basic experimental stage.To promote the clinical application of GFNs,there is a need to provide more sufficient evidence of their biocompatibility,elucidate the mechanism by which they induce the osteogenic differentiation of stem cells,and develop more effective form of applications.
5.Application of real-time ultrasound-guided transurethral ureteroscopic metal stent placement to treat ureteral obstruction caused by malignant tumor
Shuangjian JIANG ; Baohua BAI ; Yukun WU ; Jincheng PAN ; Chengqiang MO ; Rongpei WU
Chinese Journal of Urology 2024;45(6):467-468
This study retrospectively analyzed the clinical data of four patients with malignant tumor-induced ureteral strictures admitted to our hospital. All patients successfully underwent ureteroscopic metal stent placement surgery under real-time ultrasound guidance, with a surgical duration of (64±33) minutes. Postoperatively, there was a creatinine decrease of (74±127) mmol/L. Only two cases experienced Clavien-Dindo grade I complications postoperatively. The stents were well positioned in all patients, with a postoperative hospital stay of (2.5±0.6) days. This surgical approach for malignant tumor-induced ureteral obstruction can compensate for the limitations of endoscopic visualization.
6.Cutibacterium acnes phylotypes and its association with epidermal barrier function in patients with acne vulagris
Shiyu JIANG ; Yuanmin HE ; Yukun HUANG ; Xia XIONG ; Yongqiong DENG
Chinese Journal of Medical Aesthetics and Cosmetology 2024;30(6):551-555
Objective:To analyze the correlation between Cutibacterium acnes (C. acne) ribotypes (RTs) on the skin surface and epidermal barrier function in patients with acne vulgaris.Methods:Sixty patients with acne vulgaris were enrolled in this prospective study from the Department of Dermatology, the Affiliated Hospital of Southwest Medical University from November 2018 to May 2019, including 23 males and 37 females, aged (21.6±2.6) years. According to the General Acne Grading System (GAGS) score, the patients were divided into three groups: 28 mild cases, 14 moderate cases, and 18 severe or above cases. Twenty healthy controls aged 18 to 30 years were recruited in the same period from the community, including 5 males and 15 females, aged (24.2±2.3) years. The VISIA skin testing device was used to detect the percentage of red areas and porphyrins on the facial skin of all subjects. The hydration of the stratum corneum (SCH), transepidermal water loss (TEWL), PH value and the skin surface sebum level on the facial skin were detected by CK system. The RTs of C. acne were further analyzed based on the 16s rDNA sequences. The correlation between the abundance of each RT and epidermal barrier function was analyzed using Pearson correlation analysis.Results:Compared with the healthy controls, the percentage of porphyrins [(41.69±23.10) % vs (61.33±24.27) %, t=2.98, P<0.01] and the percentage of red area [(26.71±17.13) % vs (67.97±15.22) %, t=10.78, P<0.01] decreased in the acne vulgaris patients. Meanwhile, the patients of different severity levels had decreased SCH ( P<0.01), but increased TEWL, pH value, and the skin surface sebum level ( P<0.05) compared to healthy controls. Six different RTs (RT1, RT2, RT7, RT12, RT13 and RT14) were found in both healthy controls and acne vulgaris patients with varying degrees of severity, while there was no statistically significant difference of C. acne abundance between the mild patients and the controls ( P>0.05). As the severity of disease increased, the abundance of the above RTs showed a changing trend, with the gradually decreasing abundance of RT1 and the gradually increasing abundance of RT2, RT7, RT12, RT13, and RT14 (all P<0.05). The abundance of RT1 was negatively correlated with pH value ( r=-0.33, P=0.04) and GAGS score ( r=-0.39, P=0.01). The abundance of RT2 ( r=0.39, P=0.02) and RT7 ( r=0.39, P=0.01) were positively correlated with GAGS score. The abundance of RT13 was negatively correlated with SCH ( r=-0.34, P=0.02) and positively correlated with TEWL ( r=0.30, P=0.05). Conclusions:As the severity of disease increases, the abundance of various RTs of C. acne on the skin surface of acne vulgaris patients shows a trend of gradually increasing or decreasing, and the abundance of differential RTs of C. acne is closely related to the function of the epidermal barrier.
7.Ultrasonography Combined with Antibody Status for Predicting ATA Recurrence Risk Stratification of Papillary Thyroid Carcinoma in the Context of Hashimoto's Background
Naiqiao GE ; Yuexiang WANG ; Yu LAN ; Bo JIANG ; Molin LI ; Guanghui XING ; Yukun LUO
Chinese Journal of Medical Imaging 2024;32(9):891-896
Purpose To predict the 2015 American thyroid association(ATA)recurrence risk stratification based on ultrasonographic features and Hashimoto's thyroiditis(HT)-specific antibody status of papillary thyroid carcinoma(PTC)in the context of HT.Materials and Methods A retrospective analysis was conducted on the ultrasonographic and clinical data of 479 patients with coexisting PTC and HT,who underwent their first thyroid surgery at the First Medical Center of Chinese PLA General Hospital from January 2017 to December 2019.All patients were divided in chronological order into a training group(n=327)and a validation group(n=152).Multivariate Logistic regression analysis was utilized to identify independent factors associated with high recurrence risk stratification according to the ATA guidelines.Predictive models were constructed and screened,and the efficacy of these models was evaluated using the area under the curve,calibration curves and Brier scores.Results Multivariate Logistic regression analysis identified the following as independent predictive factors for high recurrence risk stratification:multifocal malignancy of nodules(OR=3.812,95%CI 1.275-11.397,P=0.017),nodule contact with the capsule(OR=8.012,95%CI 1.647-38.972,P=0.010),microcalcifications(OR=4.220,95%CI 1.302-13.678,P=0.016),an aspect ratio>1(OR=4.017,95%CI 1.286-12.548,P=0.017),abundant nodule vascularity(OR=6.120,95%CI 2.225-16.832,P<0.001),maximum nodule diameter ≥1 cm(OR=4.784,95%CI 1.360-16.833,P=0.015),a glandular echo characteristic of typical HT(OR=0.114,95%CI 0.039-0.330,P<0.001),and anti-thyroid peroxidase antibody monopositivity(OR=0.088,95%CI 0.006-1.299,P=0.077).The predictive model demonstrated strong performance,as evidenced by the area under the curve of 0.942(95%CI 0.911-0.972)in the training set and 0.933(95%CI 0.878-0.990)in the validation set.Both groups exhibited well-fitting calibration curves.The Brier scores were 0.054 and 0.058 for the training and validation sets,respectively,indicating excellent predictive efficacy of the model.Conclusion The preoperative prediction model,based on ultrasonographic features combined with antibody status,demonstrates good efficacy in assessing ATA recurrence risk stratification for coexisting PTC and HT patients,which can assist clinicians in formulating treatment plans.
8.Contrast-Enhanced Ultrasound in the Differential Diagnosis of Gallbladder Polypoid Lesions:A Multicenter Study
Ligang JIA ; Xiang FEI ; Xiang JING ; Mingxing LI ; Fang NIE ; Dong JIANG ; Shaoshan TANG ; Wei ZHANG ; Hong DING ; Tao SONG ; Qi ZHOU ; Bei ZHANG ; Zhixia SUN ; Xiaojuan MA ; Nianan HE ; Fang LI ; Yingqiao ZHU ; Wen CHENG ; Yukun LUO
Chinese Journal of Medical Imaging 2024;32(11):1147-1154
Purpose To explore the value of contrast-enhanced ultrasound(CEUS)in the differential diagnosis of gallbladder polypoid lesions(GPLs)(diameter≥10 mm).Materials and Methods A prospective enrollment of 229 patients with GPLs who underwent cholecystectomy in 17 hospitals from December 1 2021 to June 30 2024 was conducted to analyze the relationship between general data,conventional ultrasound,CEUS characteristics and the nature of GPLs.Multivariate Logistic regression was employed to identify independent risk factors for neoplastic polyps,the differential diagnostic value of different indicators was compared.Results Among 229 patients with GPLs,there were 108 cases of cholesterol polyps,102 cases of adenoma and 19 cases of gallbladder cancer.Age(Z=-4.476,P<0.001),polyp number(χ2=15.561,P<0.001),diameter(Z=-8.149,P<0.001),echogenicity(χ2=9.241,P=0.010),vascularity(χ2=23.107,P<0.001),enhancement intensity(χ2=47.610,P<0.001),enhancement pattern(χ2=6.468,P=0.011),vascular type(χ2=84.470,P<0.001),integrity of gallbladder wall(χ2=7.662,P=0.006)and stalk width(Z=-9.831,P<0.001)between cholesterol polyps and neoplastic polyps were statistically significant.Age,location,diameter,echogenicity,enhancement pattern,vascular type and stalk width between adenoma and gallbladder cancer were statistically significant(Z=-4.333,-3.902,-5.042,all P<0.05).Multivariate Logistic regression analysis showed that hyper-enhancement,branched vascular type and stalk width were independent risk factors for neoplastic polyps(OR=4.563,5.770,3.075,all P<0.001).The combination of independent risk factors was better than single factor and diameter in the differential diagnosis of cholesterol polyps and neoplastic polyps(all P<0.01).Conclusion CEUS can effectively identify the nature of GPLs and provide a valuable imaging reference for the selection of treatment methods.
9.Prediction of Screw Loosening After Dynamic Pedicle Screw Fixation With Lumbar Polyetheretherketone Rods Using Magnetic Resonance Imaging-Based Vertebral Bone Quality Score
Guozheng JIANG ; Luchun XU ; Yukun MA ; Jianbin GUAN ; Yongdong YANG ; Wenqing ZHONG ; Wenhao LI ; Shibo ZHOU ; JiaWei SONG ; Ningning FENG ; Ziye QIU ; Zeyu LI ; YiShu ZHOU ; Letian MENG ; Yi QU ; Xing YU
Neurospine 2024;21(2):712-720
Objective:
To investigate the correlation between magnetic resonance imaging-based vertebral bone quality (VBQ) score and screw loosening after dynamic pedicle screw fixation with polyetheretherketone (PEEK) rods, and evaluate its predictive value.
Methods:
A retrospective analysis was conducted on the patients who underwent dynamic pedicle screw fixation with PEEK rods from March 2017 to June 2022. Data on age, sex, body mass index, hypertension, diabetes, hyperlipidemia history, long-term smoking, alcohol consumption, VBQ score, L1–4 average Hounsfield unit (HU) value, surgical fixation length, and the lowest instrumented vertebra were collected. Logistic regression analysis was employed to assess the relationship between VBQ score and pedicle screw loosening (PSL).
Results:
A total of 24 patients experienced PSL after surgery (20.5%). PSL group and non-PSL group showed statistical differences in age, number of fixed segments, fixation to the sacrum, L1–4 average HU value, and VBQ score (p < 0.05). The VBQ score in the PSL group was higher than that in the non-PSL group (3.56 ± 0.45 vs. 2.77 ± 0.31, p < 0.001). In logistic regression analysis, VBQ score (odds ratio, 3.425; 95% confidence interval, 1.552–8.279) were identified as independent risk factors for screw loosening. The area under the receiver operating characteristic curve for VBQ score predicting PSL was 0.819 (p < 0.05), with the optimal threshold of 3.15 (sensitivity, 83.1%; specificity, 80.5%).
Conclusion
The VBQ score can independently predict postoperative screw loosening in patients undergoing lumbar dynamic pedicle screw fixation with PEEK rods, and its predictive value is comparable to HU value.
10.Prediction of Screw Loosening After Dynamic Pedicle Screw Fixation With Lumbar Polyetheretherketone Rods Using Magnetic Resonance Imaging-Based Vertebral Bone Quality Score
Guozheng JIANG ; Luchun XU ; Yukun MA ; Jianbin GUAN ; Yongdong YANG ; Wenqing ZHONG ; Wenhao LI ; Shibo ZHOU ; JiaWei SONG ; Ningning FENG ; Ziye QIU ; Zeyu LI ; YiShu ZHOU ; Letian MENG ; Yi QU ; Xing YU
Neurospine 2024;21(2):712-720
Objective:
To investigate the correlation between magnetic resonance imaging-based vertebral bone quality (VBQ) score and screw loosening after dynamic pedicle screw fixation with polyetheretherketone (PEEK) rods, and evaluate its predictive value.
Methods:
A retrospective analysis was conducted on the patients who underwent dynamic pedicle screw fixation with PEEK rods from March 2017 to June 2022. Data on age, sex, body mass index, hypertension, diabetes, hyperlipidemia history, long-term smoking, alcohol consumption, VBQ score, L1–4 average Hounsfield unit (HU) value, surgical fixation length, and the lowest instrumented vertebra were collected. Logistic regression analysis was employed to assess the relationship between VBQ score and pedicle screw loosening (PSL).
Results:
A total of 24 patients experienced PSL after surgery (20.5%). PSL group and non-PSL group showed statistical differences in age, number of fixed segments, fixation to the sacrum, L1–4 average HU value, and VBQ score (p < 0.05). The VBQ score in the PSL group was higher than that in the non-PSL group (3.56 ± 0.45 vs. 2.77 ± 0.31, p < 0.001). In logistic regression analysis, VBQ score (odds ratio, 3.425; 95% confidence interval, 1.552–8.279) were identified as independent risk factors for screw loosening. The area under the receiver operating characteristic curve for VBQ score predicting PSL was 0.819 (p < 0.05), with the optimal threshold of 3.15 (sensitivity, 83.1%; specificity, 80.5%).
Conclusion
The VBQ score can independently predict postoperative screw loosening in patients undergoing lumbar dynamic pedicle screw fixation with PEEK rods, and its predictive value is comparable to HU value.


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