1.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.
2.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.
3.Efficacy of stented elephant trunk procedure for right-sided aortic arch with Kommerell's diverticulum
Yongliang ZHONG ; Bing TANG ; Suwei CHEN ; Yipeng GE ; Hai' ; ou HU ; Zhiyu QIAO ; Chengnan LI ; Yongmin LIU ; Junming ZHU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(07):1020-1026
Objective To summarize our experience and the early and midterm outcomes of stented elephant trunk procedure for right-sided aortic arch (RAA) with Kommerell's diverticulum (KD). Methods From April 2013 to July 2020, patients with RAA and KD who underwent stented elephant trunk procedure at our center were collected. Surgery was performed under moderate hypothermic circulatory arrest combined with selective antegrade cerebral perfusion via median sternotomy. Results A total of 8 patients were included, including 7 males and 1 female with a mean age of 51.88±9.61 years. All patients had an aneurysmal KD and aberrant left subclavian artery. Preoperative comorbidities included acute Stanford type B aortic dissection in 1 patient, aortic arch pseudoaneurysm in 1 patient, acute type B intramural hematoma in 2 patients, and coronary artery disease in 1 patient. Concomitant procedures included reconstruction of the left subclavian artery in all patients and coronary artery bypass grafting in 1 patient. The mean time of operation, cardiopulmonary bypass, aortic cross-clamping, and selective cerebral perfusion was 6.25±1.16 h, 157.75±40.07 min, 77.75±33.10 min, and 28.50±5.55 min, respectively. No intraoperative death occurred. There was 1 in-hospital death. Follow-up was completed in all patients with a mean period of 3.58±2.08 years. No late death occurred. A persistent anastomotic leak of the proximal arch was detected in 1 patient, but reintervention was not performed because neither aortic dilatation nor symptoms of tracheal and esophageal compression were observed during the follow-up. The remaining 6 patients showed positive aortic remodeling with complete thrombosis of the aneurysmal KD, and neither aortic event nor tracheal and esophageal compression occurred. Conclusion Stented elephant trunk procedure is a safe and feasible technique for selected patients with RAA and KD, which can achieve favorable early and midterm outcomes.
4.Influential factors and interventions of aortic remodeling in residual aortic dissection after surgical repairs
Chenhan ZHANG ; Yongliang ZHONG ; Suwei CHEN ; Junming ZHU
Chinese Journal of Thoracic and Cardiovascular Surgery 2024;40(3):172-178
The aortic dissection is a critical emergency in cardiovascular surgery and can be classified as Stanford type A and type B aortic dissection depending on whether the ascending aorta is involved. Currently, the mainstream treatment option for type A aortic dissection is open surgery, while type B dissection can be treated by interventional therapy, open surgery, or optimal medical therapy depending on the situation. However, regardless of the treatment option, it is difficult to resolve all the problems at once. As a result, residual aortic dissection is commonly found in patients with aortic dissection. This article will review the hot issues of aortic remodeling in terms of the definition, prognosis, and risk factors.
5.Surgical treatment of Stanford type A aortic dissection after coronary artery stenting
Shichao GUO ; Zhiyu QIAO ; Chengnan LI ; Lizhong SUN ; Junming ZHU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(01):111-115
Objective To retrospectively analyze the surgical treatment of Stanford type A aortic dissection after coronary artery stenting, and to explore the surgical techniques and surgical indications. Methods Clinical data of 1 246 consecutive patients who underwent operations on Stanford type A aortic dissection from April 2016 to July 2019 in Beijing Anzhen Hospital were retrospectively analyzed. Patients with Stanford type A aortic dissection after coronary artery stenting were enrolled. Results Finally 19 patients were collected, including 16 males and 3 females with an average age of 54±7 years ranging from 35 to 66 years. There were 11 patients in acute phase, 15 patients with AC (DeBakey Ⅰ) type and 4 patients with AS (DeBakey Ⅱ) type. In AC type, there were 10 patients receiving Sun's surgery and 5 patients partial arch replacement. Meanwhile, coronary artery bypass grafting was performed in 7 patients and mitral valve replacement in 1 patient. Stents were removed from the right coronary artery in 4 patients. In this group, 1 patient died of multiple organ failure in hospital after operation combined with malperfusion of viscera. Eighteen patients recovered after treatment and were discharged from hospital. The patients were followed up for 30 (18-56) months. One patient underwent aortic pseudoaneurysm resection, one thoracic endovascular aortic repair, one emergency percutaneous coronary intervention due to left main artery stent occlusion, and one underwent femoral artery bypass due to iliac artery occlusion. Conclusion Iatrogenic aortic dissection has a high probability of coronary artery bypass grafting at the same time in patients with Stanford type A aortic dissection after coronary artery stenting. Complicated type A aortic dissection after percutaneous coronary intervention should be treated with surgery aggressively.
6.Surgical treatment strategy for acute type A aortic dissection involving severe stenosis or occlusion of the carotid arteries
Jianji WANG ; Runqiao LI ; Jiazhen MEI ; Yongliang ZHONG ; Yu XIA ; Chengnan LI ; Zhiyu QIAO ; Haiou HU ; Yipeng GE ; Junming ZHU
Chinese Journal of Thoracic and Cardiovascular Surgery 2024;40(11):660-663
Objective:To explore surgical strategies for acute type A aortic dissection involving severe stenosis or occlusion of the carotid arteries.Methods:From January 2019 to March 2023, a total of 29 patients with acute type A aortic dissection involving severe stenosis or occlusion of the carotid arteries were included in the study. All patients underwent emergency surgery, with simultaneous intraoperative neck incision and replacement of the unilateral or bilateral carotid arteries. Among them, there were 19 males with a mean age of(49.57±2.14)years old. Preoperative brain CT indicated abnormalities in 15 cases, transient neurological dysfunction occurred in 5 cases, and syncope in 1 case.Results:Procedures included ascending aorta replacement in 10 cases, Bentall procedure in 18 cases, and Wheat procedure in 1 case. Arch operations involved partial arch replacement in 3 cases and Sun’s procedure in 26 cases. Simple left carotid artery replacement was performed in 6 cases, simple right carotid artery replacement in 19 cases, and bilateral carotid artery replacement in 4 cases. Cerebral protection measures during circulatory arrest included unilateral cerebral perfusion in 24 cases and bilateral cerebral perfusion in 5 cases. The mean operation time was(7. 6±0. 3) h, with a mean cardiopulmonary bypass time of(196. 3±8. 7) min, aortic cross-clamp time of(113.2±6.4) min, ischemic time 12(5-16.5) min, and lowest temperature of(26.3±0.4)°C. One patient experienced in-hospital mortality. Postoperatively, new neurological dysfunction occurred in 2 cases, including 1 case with coma and permanent neurological deficit.Conclusion:In patients with acute type A aortic dissection involving severe stenosis or occlusion of the carotid arteries, simultaneous carotid artery replacement via neck incision during aortic surgery is a safe and reliable surgical approach.
7.Surgical repair of type Ⅱ right-sided aortic arch with Kommerell diverticulum
Bing TANG ; Yongliang ZHONG ; Yipeng GE ; Haiou HU ; Zhiyu QIAO ; Chengnan LI ; Yongmin LIU ; Junming ZHU
Chinese Journal of Thoracic and Cardiovascular Surgery 2023;39(8):454-460
Objective:To summarize our experience and outcomes of surgical repair of type Ⅱ right-sided aortic arch(RAA) with Kommerell's diverticulum(KD).Methods:From May 2010 to August 2020, a total of 13 patients with type Ⅱ RAA and KD underwent surgery at our center. Mean age was(50.46±10.31) years, 10 were male, and 3 were female. All patients had an aneurysmal KD and aberrant left subclavian artery(ALSA). Preoperative comorbidities included type B aortic dissection in 1 case, aortic arch pseudoaneurysm in 2 cases, and type B intramural hematoma in 2 cases, respectively. Eight(61.5%) patients underwent stented elephant trunk procedures under moderate hypothermic circulatory arrest combined with selective antegrade cerebral perfusion via median sternotomy, and all of them had ALSA reconstruction. Five(38.5%) patients underwent distal arch and descending thoracic aortic replacement through a right posterolateral thoracotomy, the ALSA was reconstructed or ligated in 1 each, and ALSA embolization was performed before surgery in the other 3 cases.Results:No operation deaths occurred. Recurrent laryngeal nerve injury occurred in 2 cases. There was 1(7.69%) in-hospital death. Follow-up was complete in 100 % at mean(5.28±3.84) years. No late death occurred. A persistent anastomotic leak of the proximal arch was detected in a patient who underwent stented elephant trunk procedure, but no aortic dilatation or tracheal and esophageal compression was observed during follow-up. Meanwhile, aortic events, limb ischemia, or symptoms of tracheal and esophageal compression were not observed in the remaining 11 patients.Conclusion:Surgical repair of type Ⅱ RAA with KD can achieve favorable early and midterm outcomes. Surgical strategies should be chosen based on the anatomy of the aorta and whether it is combined with compression symptoms.
8.New aortic arch-clamping technique in Sun’s procedure to repair acute Type A aortic dissection: an early clinical analysis of 67 cases in a single center
Cheng LUO ; Bo JIA ; Yongliang ZHONG ; Yipeng GE ; Chengnan LI ; Zhiyu QIAO ; Haiou HU ; Junming ZHU
Chinese Journal of Thoracic and Cardiovascular Surgery 2023;39(9):564-567
Objective:To evaluate the efficacy of new arch-clamping technique in Sun’s procedure to repair acute type A aortic dissection.Methods:67 consecutive patients with acute type A aortic dissection who underwent total arch replacement and frozen elephant trunk implantation(TAR+ FET) from Dec 2019 to Dec 2022 with using new arch-clamping technique during operation. Relative intraoperative and postoperative variables and complications were compared.Results:Cardiopulmonary bypass time was(166.66±32.81)min, the aortic occlusion time was(100.49±19.96)min, the circulatory arrest time was(3.97±1.63)min, the lowest nasopharyngeal temperature was(25.716±1.304)℃, and the lowest bladder temperature was(26.209±1.552)℃. The whole group died in hospital in 2 cases(2.98%), cerebral infarction in 3 cases(4.48%), transient neurological dysfunction in 4 cases(5.97%), paraplegia patients in 1 case(1.49%), renal failure requiring continuous dialysis in 4 cases(5.97%).Conclusion:New arch-clamping technique decrease postoperative complication, and is a safe and feasible innovative approach to effectively improve surgical outcome of Sun’s procedure for repair of acute type A aortic dissection.
9.Characteristics of TCM syndrome elements and syndromes of hypertension with insomnia in the real world
Chunqiu ZHU ; Xiaoya LI ; Hui LI ; Junming FAN ; Hui QING ; Yongshu DONG ; Weifeng CUI
International Journal of Traditional Chinese Medicine 2023;45(12):1482-1489
Objective:To analyze the distribution of TCM syndrome elements and syndromes in patients with hypertension with insomnia (HWI) in the real world.Methods:A cross-sectional study and retrospectively enrolled. The positive symptoms and TCM syndrome type entries of 359 patients with HWI who were collected from Henan Integrated Medicine Hospital,Henan Provincial People's Hospital,the First Affiliated Hospital of Henan University of Chinese Medicine from December 2020 to August 2022 were retrospectively studied. Based on factor analysis dimension reduction and systematic cluster analysis, the TCM syndrome elements and potential syndrome types of patients were summarized. The Latern 5.0 software was used to establish a latent structure model and comprehensive clustering based on the mountain climbing method (LTM-EAST) algorithm, and analyze and judge the common syndrome types, providing a basis for proposing the clinical common syndrome types of this disease.Results:Factor analysis extracted 14 common factors, and the cumulative contribution rate was 63.254%. Among the 36 symptom variables with frequency ≥ 70, more than half of the patients with hypertension and insomnia were upset, irritable, less sleepy, dreamy, dizzy, palpitations, stuffy chest, dry mouth, easy to wake up, and tired. The tongue color was mainly light red tongue and red tongue. The tongue is mainly thin and greasy. The first three pulse conditions are string pulse, number pulse and slippery pulse. The disease location and syndrome elements of hypertension with insomnia were mainly liver (52.09%), heart (33.43%), spleen (26.46%) and kidney (23.68%); The disease syndrome elements are mainly phlegm dampness (34.54%), yin deficiency (29.25%), heat (fire) (25.35%), and qi stagnation (25.07%). Ten syndrome types are obtained by frequency statistics, nine syndrome types are obtained by factor clustering, and seven syndrome types are inferred by implicit structure clustering. Among the syndrome types inferred by the above three methods, there are seven syndrome types that recur at least twice, which can be identified as the common syndrome type of hypertension with insomnia.Conclusions:The common clinical symptoms of HWI are upset and irritable, less sleep, more dreams, dizziness, palpitations, stuffy chest, dry mouth, easy to wake up, mental fatigue and body tiredness. The disease location and syndrome elements are mainly in liver, heart, spleen and kidney. The disease mainly involves phlegm dampness, yin deficiency, heat and qi stagnation. The common clinical syndrome types are liver depression transforming fire type, yin deficiency and yang hyperactivity type, phlegm dampness intrinsic type, yin deficiency and internal heat type, heart and gallbladder qi deficiency type, heart and spleen deficiency type, and heart kidney disjunction type.
10.Midterm clinical results of Sun's procedure with median resternotomy
Ningning LIU ; Yipeng GE ; Jun ZHENG ; Xiaolong WANG ; Tao BAI ; Chengnan LI ; Zhiyu QIAO ; Haiou HU ; Yongmin LIU ; Junming ZHU ; Lizhong SUN
Chinese Journal of Thoracic and Cardiovascular Surgery 2023;39(2):71-76
Objective:To summarize the clinical data of Sun's procedure(total aortic arch replacement with frozen elephant trunk technique) in the treatment of complex aortic arch disease after previous cardiac surgery.Methods:From January 1, 2018 to December 31, 2020, a total of 55 patients underwent resternotomy Sun's procedure in the Aortic Surgery Center of Beijing Anzhen Hospital, including 41 males and 14 females, with a mean age of(45.4±12.7) years old, were retrospectively analyzed. The indications of primary cardiac surgery included type A aortic dissection, aortic root or ascending aortic aneurysm, heart valve surgery, and coronary heart disease. Indications for reoperation included residual aortic dissection larger than 55 mm in diameter, aortic aneurysm dilation, new type A aortic dissection, anastomotic leakage with symptoms, and pseudoaneurysm. All the operations were performed under general anesthesia and median resternotomy, total aortic arch replacement with the stented elephant trunk implantation and were performed by anterograde unilateral or bilateral cerebral perfusion.Results:There was no intraoperative death, and the postoperative mortality was 9.1%(5/55). The causes of death were 2 cases of low cardiac output, 1 case of respiratory failure, 1 case of cerebral complications, and 1 case of gastrointestinal bleeding. Except death, there were 2 cases of postoperative cerebral complications(2/50, 4%), 5 cases of spinal cord injury(transient paraplegia)(5/50, 10%), the median duration of ventilator use was 17 hours(14-42 h). Other postoperative complications included respiratory insufficiency requiring ventilatory support longer than 48 hours(8/50, 16%), renal insufficiency requiring temporary dialysis(2/50, 4%). The follow-up time was(25.9±11.2) months(10-47 months), during which 1 case died due to cerebral complication, 4 cases underwent total thoracoabdominal aorta replacement, and 1 case underwent anastomotic leakage repair.Conclusion:It is safe and effec to perform Sun's procedure(total aortic arch replacement with frozen elephant trunk technique) in the treatment of complex arch disease after previous cardiac surgery.

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