1.Mechanism of Wumen Zhiqiao gancao decoction inhibiting pathological angiogenesis in degenerative intervertebral discs by regulating HIF-1α/VEGF/Ang signal axis
Zeling HUANG ; Zaishi ZHU ; Yuwei LI ; Bo XU ; Junming CHEN ; Baofei ZHANG ; Binjie LU ; Xuefeng CAI ; Hua CHEN
China Pharmacy 2025;36(7):807-814
OBJECTIVE To explore the effect and mechanism of Zhiqiao gancao decoction (ZQGCD) on pathological angiogenesis of degenerative intervertebral disc. METHODS The rats were randomly divided into sham operation group (normal saline), model group (normal saline), hypoxia inducible factor-1α (HIF-1α) inhibitor (YC-1) group [2 mg/(kg·d), tail vein injection], and ZQGCD low-dose, medium-dose and high-dose groups [3.06, 6.12, 12.24 g/(kg·d)], with 8 rats in each group. Except for sham operation group, lumbar disc degeneration model of rat was constructed in all other groups. After modeling, they were given relevant medicine once a day, for consecutive 3 weeks. After the last medication, pathological changes and angiogenesis of the intervertebral disc tissue in rats were observed; the levels of inflammatory factors [interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α)] and the expressions of angiogenesis-related proteins [HIF-1α, vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR2), angiotensin 1(Ang 1), Ang 2] in the com intervertebral disc tissue in rats were all determined. In cell experiment, the primary nucleus pulposus cells were isolated and cultured from rats, and cellular degeneration was induced using 50 ng/mL TNF-α. The cells were divided into blank control group (10% blank control serum), TNF-α group (10% blank control serum), YC-1 group (10% blank control serum+0.2 mmol/L YC-1), and 5%, 10%, 15% drug-containing serum group (5%, 10%, 15% drug-containing serum). After 24 hours of intervention, the nucleus pulposus cells were co-cultured with HUVEC. The expressions of Collagen Ⅱ, matrix metalloproteinase-3 (MMP-3) in nucleus pulposus cells were detected. HUVEC proliferation, migration and tube forming ability were detected, and the expression levels of the HIF-1α/VEGF/Ang signal axis and angiogenesis- related proteins (add MMP-2, MMP-9) in HUVEC were detected. RESULTS Animal experiments had shown that compared with model group, the positive expression of CD31 in the intervertebral disc tissues of rats in each drug group was down-regulated (P< 0.05), the levels of inflammatory factors and angiogenesis-related proteins were decreased significantly (P<0.05), and the pathological changes in the intervertebral disc were alleviated. Cell experiments had shown that compared with TNF-α group, the expression of Collagen Ⅱ in nucleus pulposus cells of all drug groups was significantly up-regulated (P<0.05), and the expression of MMP-3 was significantly down-regulated (P<0.05); the proliferation, migration and tubulogenesis of HUVEC were significantly weakened (P<0.05). The mRNA and protein expressions of HIF-1α, VEGF, Ang 2 as well as the expression of angiogenesis-related proteins (except for the expression of Ang 2 mRNA and HIF-1α, VEGFR2, Ang 2 protein in 5% drug- containing serum group) were significantly down-regulated (P<0.05). CONCLUSIONS ZQGCD may inhibit the HIF-1α/VEGF/ Ang signal axis to weaken the angiogenic ability of vascular endothelial cells, improve pathological angiogenesis in the intervertebral disc, and delay the degeneration of the intervertebral disc.
2.Application of mild hypothermia arch-clamping technique for DeBakey Ⅰ aortic dissection
Chengnan LI ; Bo JIA ; Yipeng GE ; Yongliang ZHONG ; Hai YU ; Yi YANG ; Zhiyu QIAO ; Haiou HU ; Yongmin LIU ; Junming ZHU
Chinese Journal of Thoracic and Cardiovascular Surgery 2025;41(3):136-142
Objective:To evaluate the safety and efficacy of mild hypothermia arch-clamping technique in the surgical treatment of DeBakey Type Ⅰ aortic dissection.Methods:From December 2019 to November 2023, a total of 97 patients with DeBakey type Ⅰ aortic dissection who underwent arch-clamping technique in Beijing Anzhen Hospital were prospectively enrolled. The patients were divided into mild hypothermia group and moderate hypothermia group according to the lowest rectal temperature during the circulatory arrest period. The perioperative data of the two groups were compared, and complex adverse outcomes consisting of 30-day death, stroke, paraplegia and CRRT were used as the primary endpoint. Multivariate logistic regression was used to determine the predictors of clinical adverse outcomes. Survival analysis was evaluated by the Kaplan- Meier method. Results:The overall incidence of complex adverse outcomes was 20.6%, 13.6% in the mild hypothermia group and 22.7% in the moderate hypothermia group( P=0.535), and the incidence of stroke was 4.6% and 6.7%( P=1.000), respectively. The cardiopulmonary bypass time and aortic-clamping time in the mild hypothermia group were significantly shortened (147.5 min vs. 163.0 min, P=0.032; 89 min vs. 99 min, P=0.042). There was no significant difference in long-term survival and reintervention between the two groups(91.9% vs. 89.3%, P=0.87; 9.1% vs. 5.3%, P=0.13). Conclusion:Mild hypothermia arch-clamping technique is a safe and effective method for the treatment of DeBakey type Ⅰ aortic dissection, with satisfactory short-term and long-term efficacy.
3.Research progress of machine learning-based magnetic resonance imaging technology in diagnosis of autism spectrum disorder
Junming ZHANG ; Wang LI ; Yuefu ZHAN
International Journal of Biomedical Engineering 2025;48(2):182-189
In recent years, machine learning and its subset, deep learning, have made significant progress in medical image analysis. Magnetic resonance imaging (MRI) technology has become a critical tool for the diagnosis of autism spectrum disorder (ASD) by providing high-resolution data of brain structure and function. In this review, the characteristics of ASD in MRI were summarized, ASD-related MRI datasets and preprocessing methods were discussed, MRI feature selection and extraction techniques of ASD were examined, machine learning-based diagnostic approaches and their interpretablility were evaluated, and future research directions were proposed.
4.The Effect of Zhiqiao Gancao Decoction (枳壳甘草汤) on Intervertebral Disc Nucleus Pulposus Cell Apoptosis and the Hippo-YAP/TAZ Signaling Pathway in Tail Intervertebral Disc Degeneration Model Rats
Zaishi ZHU ; Zeling HUANG ; Junming CHEN ; Bo XU ; Binjie LU ; Hua CHEN ; Xingxing DUAN ; Yuwei LI ; Xiaofeng SHEN
Journal of Traditional Chinese Medicine 2025;66(5):509-517
ObjectiveTo investigate the possible mechanism by which Zhiqiao Gancao Decoction (枳壳甘草汤, ZGD) delays intervertebral disc degeneration (IDD) based on the Hippo-yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) signaling pathway. MethodsA total of 50 SD rats were randomly divided into sham surgery group, model group, low-dose ZGD group, high-dose ZGD group, and high-dose ZGD + inhibitor group, with 10 rats in each group. In the sham surgery group, the rats were pierced in the skin and muscle at the Co6/7/8 segments of the tail with a 21G needle (depth approximately 2 mm) without damaging the intervertebral disc. In the other groups, rats were injected with a 21G needle at the Co6/7/8 segments of the tail to establish an IDD model by piercing the tail intervertebral disc 5 mm. One week after modeling, rats in the low-dose and high-dose ZGD groups were given 6.24 and 12.24 g/(kg·d) of the decoction via gastric gavage, respectively. The high-dose ZGD + inhibitor group was given 12.24 g/(kg·d) of the decoction and an intraperitoneal injection of YAP/TAZ inhibitor Verteporfin 10 mg/kg. The sham surgery and model groups were given 5 ml/(kg·d) of normal saline via gavage. The gavage was given once a day, and the intraperitoneal injection was given every other day. After 4 weeks of continuous intervention, the pathological changes of the tail intervertebral discs were observed using HE staining, Oil Red O-Green staining, and Toluidine Blue staining. Immunohistochemistry was used to detect the expression of aggrecan and MMP3 in the nucleus pulposus. TUNEL fluorescence staining was performed to detect apoptosis in the nucleus pulposus, and the apoptosis rate was calculated. Western blot was used to detect the Hippo-YAP/TAZ signaling pathway, including YAP, phosphorylated YAP (p-YAP), phosphorylated MST1/2 (p-MST1/2), phosphorylated TAZ (p-TAZ) and apoptosis-related proteins, such as Cleaved Caspase 3, P53, Bcl-2 and Bax. ResultsCompared with sham surgery group, the rats in the model group showed significant degenerative changes in the intervertebral disc. The levels of aggrecan, Bcl-2, and YAP proteins in the nucleus pulposus decreased, while the levels of p-MST1/2, p-YAP, p-TAZ, P53, Bax, Cleaved Caspase 3, MMP3 proteins, and the apoptosis rate increased (P < 0.01). Compared with the model group, the drug intervention groups showed partial recovery in intervertebral disc degeneration. The levels of aggrecan, Bcl-2, and YAP proteins increased, while the levels of p-MST1/2, p-YAP, p-TAZ, P53, Bax, Cleaved Caspase 3, MMP3 proteins, and the apoptosis rate decreased (P<0.05 or P<0.01). The high-dose ZGD group showed more significant recovery in intervertebral disc degeneration compared to the low-dose ZGD group, with a decrease in the levels of p-MST1/2, p-YAP, p-TAZ, P53, Bax, Cleaved Caspase 3, MMP3 proteins, and apoptosis rate, and an increase in the levels of aggrecan, Bcl-2, and YAP proteins (P<0.05 or P<0.01). Compared with the high-dose ZGD group, the high-dose ZGD + inhibitor group showed a reduced recovery in intervertebral disc degeneration, with an increase in the levels of p-MST1/2, p-YAP, p-TAZ, P53, Bax, Cleaved Caspase 3, MMP3 proteins, and apoptosis rate, and a decrease in the levels of aggrecan, Bcl-2, and YAP proteins (P<0.05 or P<0.01). ConclusionZGD may delay intervertebral disc degeneration by inhibiting the phosphorylation of YAP in the nucleus pulposus, maintaining the function of the Hippo-YAP/TAZ signaling pathway, and reducing apoptosis of nucleus pulposus cells.
5.Clinical effect of aortic root replacement in adolescent patients with aortic root aneurysm
Chenhan ZHANG ; Xiaoyang ZHANG ; Suwei CHEN ; Zhiyu QIAO ; Haiou HU ; Yipeng GE ; Chengnan LI ; Junming ZHU
Journal of Chinese Physician 2025;27(8):1125-1129
Objective:To evaluate the clinical effect of different types of aortic root replacement in adolescent patients with aortic root aneurysm by analyzing the perioperative and follow-up conditions of surgical treatment for adolescent aortic root aneurysm.Methods:The clinical data of patients aged ≤18 years who were admitted to the Beijing Anzhen Hospital from November 2012 to February 2025, diagnosed with aortic root aneurysm by ultrasound or aortic computed tomography angiography (CTA) and requiring surgical intervention, were collected retrospectively. They were divided into the valve-sparing aortic root replacement group (David operation group) and the aortic root replacement group (Bentall operation group) according to the surgical method. The perioperative results and long-term follow-up results of the two groups were analyzed. Kaplan-Meier survival curves were drawn to compare the reoperation intervention rate between the two groups.Results:A total of 25 patients were included in this study, including 17 in the Bentall group and 8 in the David group. There were no statistically significant differences in gender, age, blood routine, liver and kidney function, coagulation function, and electrolyte internal environment between the two groups (all P>0.05). There were no statistically significant differences in operation time and intensive care unit stay between the two groups (all P>0.05). Compared with the Bentall operation group, the intraoperative blood loss in the David operation group was more ( P<0.05). During the follow-up, no reoperation occurred in the Bentall operation group, while 3 patients in the David operation group had long-term re-intervention. The long-term reoperation intervention rate in the David operation group was higher than that in the Bentall group ( P=0.042), but there was no statistically significant difference in the aortic valve-related surgical intervention rate between the two groups ( P=0.15). Conclusions:For adolescent patients with aortic root aneurysm, although David operation may face long-term reoperation intervention, this intervention may not be due to the difference in surgical methods. Both Bentall operation and David operation are safe and reliable, with good perioperative results and stable medium and long-term prognosis.
6.Preliminary screening of neutrophil proteomics in diagnosis of pulmonary tuberculosis
Xue LI ; Yuije GAO ; Jiu LIU ; Zikun HUANG ; Junming LI
Chinese Journal of Immunology 2025;41(11):2682-2688,2694
Objective:To analyze the different expression of neutrophil's protein from the patients with active pulmonary tuber-culosis(TB)and healthy controls(HC)from the perspective of proteomics,and to explore the diagnosis of the secreted proteins related to neutrophil activation in serum.Methods:Neutrophil protein in peripheral blood of 15 patients with TB and 15 HC was identified by label free quantitative proteomics,which were further validated in by ELISA and nephelometry.Results:A total of 358 differentially expressed proteins were identified in our study,54 differentially expressed proteins related to neutrophil activation or degranulation were focused,and seven proteins AHSG,AACT,C3,AAT,AAG,HP and A1BG were validated in 40 TB patients and 40 HC,and the results confirmed that the following proteins were highly expressed in the serum of the TB group:AACT,C3,AAT,AAG,HP and A1BG,while AHSG was lowly expressed,and only the validation results of AHSG were consistent with the trend of proteomics results.In addition,we further investigated the expression level of AHSG in the diagnosis of 24 patients with active pulmonary TB,24 patients with lung cancer,24 HC,and 16 patients with latent tuberculosis infection(LTBI),and found the expression of AHSG was down-regu-lated in TB group compared with the other groups.The sensitivity and specificity of AHSG in differentiating TB patients from HC patients,lung cancer patients,LTBI patients and non-TB patients in the test set were 83.33%,79.17%;78.00%,91.67%;75.00%,87.50%;75.00%,85.94%.Conclusion:Proteomic profiles of neutrophils from TB and HC are obtained from a proteomic perspective,and further validation shows that AHSG has a good differential diagnostic ability for HC,lung cancer and LTBI.
7.Role,mechanism and application of IL-2 in occurrence and development of systemic lupus erythematosus
Chinese Journal of Immunology 2025;41(10):2535-2539
IL-2 is a multifunctional cytokine whose main functions include activating and maintaining T cell survival.Re-search has shown that the level and function of IL-2 in peripheral blood of patients with systemic lupus erythematosus(SLE)have sig-nificantly decreased,and are associated with the activity of SLE disease.In recent years,the decrease in IL-2 level has been found to play a crucial role in the occurrence and development of SLE,and is one of the important mechanisms for T cell homeostasis imba-lance and immune regulation disorders in SLE patients.The low-dose IL-2 treatment regimen for SLE based on this discovery has en-tered clinical application.However,there is still considerable controversy regarding the mechanism of decreased IL-2 level and sup-pressed functions in SLE patients.Clarifying this mechanism is of great significance for further clarifying the occurrence and develop-ment mechanism of SLE and developing new treatment regimens.
8.Role,mechanism and application of IL-2 in occurrence and development of systemic lupus erythematosus
Chinese Journal of Immunology 2025;41(10):2535-2539
IL-2 is a multifunctional cytokine whose main functions include activating and maintaining T cell survival.Re-search has shown that the level and function of IL-2 in peripheral blood of patients with systemic lupus erythematosus(SLE)have sig-nificantly decreased,and are associated with the activity of SLE disease.In recent years,the decrease in IL-2 level has been found to play a crucial role in the occurrence and development of SLE,and is one of the important mechanisms for T cell homeostasis imba-lance and immune regulation disorders in SLE patients.The low-dose IL-2 treatment regimen for SLE based on this discovery has en-tered clinical application.However,there is still considerable controversy regarding the mechanism of decreased IL-2 level and sup-pressed functions in SLE patients.Clarifying this mechanism is of great significance for further clarifying the occurrence and develop-ment mechanism of SLE and developing new treatment regimens.
9.Preliminary screening of neutrophil proteomics in diagnosis of pulmonary tuberculosis
Xue LI ; Yuije GAO ; Jiu LIU ; Zikun HUANG ; Junming LI
Chinese Journal of Immunology 2025;41(11):2682-2688,2694
Objective:To analyze the different expression of neutrophil's protein from the patients with active pulmonary tuber-culosis(TB)and healthy controls(HC)from the perspective of proteomics,and to explore the diagnosis of the secreted proteins related to neutrophil activation in serum.Methods:Neutrophil protein in peripheral blood of 15 patients with TB and 15 HC was identified by label free quantitative proteomics,which were further validated in by ELISA and nephelometry.Results:A total of 358 differentially expressed proteins were identified in our study,54 differentially expressed proteins related to neutrophil activation or degranulation were focused,and seven proteins AHSG,AACT,C3,AAT,AAG,HP and A1BG were validated in 40 TB patients and 40 HC,and the results confirmed that the following proteins were highly expressed in the serum of the TB group:AACT,C3,AAT,AAG,HP and A1BG,while AHSG was lowly expressed,and only the validation results of AHSG were consistent with the trend of proteomics results.In addition,we further investigated the expression level of AHSG in the diagnosis of 24 patients with active pulmonary TB,24 patients with lung cancer,24 HC,and 16 patients with latent tuberculosis infection(LTBI),and found the expression of AHSG was down-regu-lated in TB group compared with the other groups.The sensitivity and specificity of AHSG in differentiating TB patients from HC patients,lung cancer patients,LTBI patients and non-TB patients in the test set were 83.33%,79.17%;78.00%,91.67%;75.00%,87.50%;75.00%,85.94%.Conclusion:Proteomic profiles of neutrophils from TB and HC are obtained from a proteomic perspective,and further validation shows that AHSG has a good differential diagnostic ability for HC,lung cancer and LTBI.
10.Clinical effect of aortic root replacement in adolescent patients with aortic root aneurysm
Chenhan ZHANG ; Xiaoyang ZHANG ; Suwei CHEN ; Zhiyu QIAO ; Haiou HU ; Yipeng GE ; Chengnan LI ; Junming ZHU
Journal of Chinese Physician 2025;27(8):1125-1129
Objective:To evaluate the clinical effect of different types of aortic root replacement in adolescent patients with aortic root aneurysm by analyzing the perioperative and follow-up conditions of surgical treatment for adolescent aortic root aneurysm.Methods:The clinical data of patients aged ≤18 years who were admitted to the Beijing Anzhen Hospital from November 2012 to February 2025, diagnosed with aortic root aneurysm by ultrasound or aortic computed tomography angiography (CTA) and requiring surgical intervention, were collected retrospectively. They were divided into the valve-sparing aortic root replacement group (David operation group) and the aortic root replacement group (Bentall operation group) according to the surgical method. The perioperative results and long-term follow-up results of the two groups were analyzed. Kaplan-Meier survival curves were drawn to compare the reoperation intervention rate between the two groups.Results:A total of 25 patients were included in this study, including 17 in the Bentall group and 8 in the David group. There were no statistically significant differences in gender, age, blood routine, liver and kidney function, coagulation function, and electrolyte internal environment between the two groups (all P>0.05). There were no statistically significant differences in operation time and intensive care unit stay between the two groups (all P>0.05). Compared with the Bentall operation group, the intraoperative blood loss in the David operation group was more ( P<0.05). During the follow-up, no reoperation occurred in the Bentall operation group, while 3 patients in the David operation group had long-term re-intervention. The long-term reoperation intervention rate in the David operation group was higher than that in the Bentall group ( P=0.042), but there was no statistically significant difference in the aortic valve-related surgical intervention rate between the two groups ( P=0.15). Conclusions:For adolescent patients with aortic root aneurysm, although David operation may face long-term reoperation intervention, this intervention may not be due to the difference in surgical methods. Both Bentall operation and David operation are safe and reliable, with good perioperative results and stable medium and long-term prognosis.

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