1.The effect of Bushen Huoxue prescription on proliferation and extracellular matrix synthesis of nucleus pulposus cells by regulating circ_0036763/miR-583 axis
Canrong LIANG ; Junjie HE ; Xueyuan ZHU ; Haojian FENG ; Weijun GUO ; Dongling CAI ; Chenghua ZHU ; Xiaofeng CHEN
Journal of Chinese Physician 2024;26(1):63-69
Objective:To explore the possible effects of Bushen Huoxue Formula (the kidney tonifying and blood activating prescription) on the proliferation and extracellular matrix synthesis of nucleus pulposus cells by regulating the circ_0036763/miR-583 axis.Methods:Real time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression levels of circ0036763 and miR-583 in normal and intervertebral disc degeneration (IDD) nucleus pulposus cells; IDD nucleus pulposus cells were divided into pcDNA group, pcDNA circ_0036763 group, pcDNA circ_0036763+ mimic NC group, and pcDNA circ_0036763+ miR-583 mimic group. qRT-PCR was used to detect the expression levels of circ_0036763 and miR-583 in nucleus pulposus cells in each group, methyl thiazolyl tetrazolium (MTT) was used to detect cell proliferation (A value), and Western blot was used to detect the expression of proliferating cell nuclear antigen (PCNA), collagen Ⅰ, and collagen Ⅱ proteins in nucleus pulposus cells, The dual luciferase assay reported experimental validation of the targeting relationship between circ_0036763 and miR-583. 27 mice were divided into sham surgery group, IDD group, and kidney tonifying and blood activating formula group. IDD models were established in all groups except for the sham surgery group. After successful modeling, the sham surgery group and IDD group were given physiological saline by gavage, while the kidney tonifying and blood activating formula group was given 1.5 g/ml of kidney tonifying and blood activating formula by gavage for 3 consecutive weeks. QRT-PCR was used to detect the expression levels of circ0036763 and miR-583 in the nucleus pulposus cells of mice in each group, MTT was used to detect cell proliferation, and Western blot was used to detect the expression of PCNA, collagen Ⅰ, and collagen Ⅱ proteins.Results:The expression level of circ_0036763 in IDD nucleus pulposus cells decreased, while the expression level of miR-583 increased (all P<0.05); Overexpression of circ_0036763 can promote proliferation and extracellular matrix synthesis of nucleus pulposus cells (all P<0.05); Circ_0036763 targets miR-583 and upregulates miR-583 reversible overexpression. Circ_0036763 enhances the proliferation and extracellular matrix synthesis ability of IDD nucleus pulposus cells. Compared with the sham surgery group, the IDD group showed an increase in collagen Ⅰ protein expression and miR-583 expression levels (all P<0.05), while the cell A value, PCNA and collagen Ⅱ protein expression, and circ_0036763 expression levels decreased (all P<0.05); Compared with the IDD group, the Kidney Tonifying and Blood Activating Formula group showed a decrease in collagen Ⅰ protein expression and miR-583 expression levels (all P<0.05), while the cell A value, PCNA and collagen Ⅱ protein expression, and circ_0036763 expression levels increased (all P<0.05). Conclusions:The kidney tonifying and blood activating formula (Bushen Huoxue) may induce proliferation and extracellular matrix synthesis of nucleus pulposus cells by regulating the circ_0036763/miR-583 axis.
2.Early experience with mechanical hemodynamic support for catheter ablation of malignant ventricular tachycardia
Mengmeng LI ; Yang YANG ; Deyong LONG ; Chenxi JIANG ; Ribo TANG ; Caihua SANG ; Wei WANG ; Xin ZHAO ; Xueyuan GUO ; Songnan LI ; Changyi LI ; Man NING ; Changqi JIA ; Li FENG ; Dan WEN ; Hui ZHU ; Yuexin JIANG ; Fang LIU ; Tong LIU ; Jianzeng DONG ; Changsheng MA
Chinese Journal of Cardiology 2024;52(7):768-776
Objective:To explore the role of mechanical hemodynamic support (MHS) in mapping and catheter ablation of patients with hemodynamically unstable ventricular tachycardia (VT), report single-center experience in a cohort of consecutive patients receiving VT ablation during MHS therapy, and provide evidence-based medical evidence for clinical practice.Methods:This was a retrospective cohort study. Patients with hemodynamically unstable VT who underwent catheter ablation with MHS at Beijing Anzhen Hospital, Capital Medical University between August 2021 and December 2023 were included. Patients were divided into rescue group and preventive group according to the purpose of treatment. Their demographic data, periprocedural details, and clinical outcomes were collected and analyzed.Results:A total of 15 patients with hemodynamically unstable VT were included (8 patients in the rescue group and 7 patients in the preventive group). The acute procedure was successful in all patients. One patient in the rescue group had surgical left ventricular assist device (LVAD) implantation, remaining 14 patients received extracorporeal membrane oxygenation (ECMO) for circulation support. ECMO decannulation was performed in 12 patients due to clinical and hemodynamic stability, of which 6 patients were decannulation immediately after surgery and the remaining patients were decannulation at 2.0 (2.5) d after surgery. Two patients in the rescue group died during the index admission due to refractory heart failure and cerebral hemorrhage. During a median follow-up of 30 d (1 d to 12 months), one patient with LVAD had one episode of ventricular fibrillation at 6 months after discharge, and no further episodes of ventricular fibrillation and/or VT occurred after treatment with antiarrhythmic drugs. No malignant ventricular arrhythmia occurred in the remaining 12 patients who were followed up.Conclusions:MHS contributes to the successful completion of mapping and catheter ablation in patients with hemodynamically unstable VT, providing desirable hemodynamic status for emergency and elective conditions.
3.Clinical effects of flaps or myocutaneous flaps transplantation after titanium mesh-retaining debridement in repairing the wounds with exposed titanium mesh after cranioplasty
Lin HE ; Rui WANG ; Chan ZHU ; Xueyuan YU ; Youcheng HE ; Lin ZHOU ; Zhuo ZHANG ; Maoguo SHU
Chinese Journal of Burns 2024;40(3):273-280
Objective:To explore the clinical effects of flaps or myocutaneous flaps transplantation after debridement to repair the wounds with exposed titanium mesh after cranioplasty on the premise of retaining the titanium mesh.Methods:This study was a retrospective observational study. From February 2017 to October 2022, 22 patients with titanium mesh exposure after cranioplasty who met the inclusion criteria were admitted to the Department of Plastic, Aesthetic & Maxillofacial Surgery of the First Affiliated Hospital of Xi'an Jiaotong University, including 15 males and 7 females, aged from 19 to 68 years. After admission, treatments such as bacterial culture of wound exudate sample, anti-infection, and dressing change were carried out. Thorough surgical debridement was performed when the wound improved, and the wound area was 3.0 cm×2.0 cm to 11.0 cm×8.0 cm after debridement. The wound was repaired with local flaps, expanded flaps, or free latissimus dorsi myocutaneous flaps according to the size, location, severity of infection, and surrounding tissue condition of the wounds, and the areas of flaps or myocutaneous flaps were 5.5 cm×4.0 cm to 18.0 cm×15.0 cm. The donor areas of flaps were sutured directly or repaired by split-thickness skin grafts from head. The wound repair method was recorded. The survivals of flaps or myocutaneous flaps after surgery and wound healing in 2 weeks after surgery were recorded. During postoperative follow-up, recurrence of infection or titanium mesh exposure in the implanted area of titanium mesh was observed; the head shapes of patients, scar formation of the operative incision, and baldness were observed. At the last follow-up, the satisfaction of patients with the treatment effect (dividing into three levels: satisfied, basically satisfied, and dissatisfied) was evaluated. The total treatment costs of patients during their hospitalization were calculated.Results:The wounds in 11 cases were repaired with local flaps, the wounds in 5 cases were repaired with expanded flaps, and the wounds in 6 cases were repaired with free latissimus dorsi myocutaneous flaps. All flaps or myocutaneous flaps survived completely after surgery, and all wounds healed well in 2 weeks after surgery. Follow up for 6 to 48 months after operation, only one patient with local flap grafting experienced a recurrence of infection in the titanium mesh implanted area at more than one month after surgery, and the titanium mesh was removed because of ineffective treatment. Except for one patient who had a local depression in the head after removing the titanium mesh, the rest of the patients had a full head shape. Except for myocutaneous flap grafting areas in 6 cases and skin grafting area in 1 case with local flaps grafting had no hair growth, the other patients had no baldness. All the scars in surgical incision were concealed. At the last follow-up, 19 cases were satisfied with the treatment effects, 2 cases were basically satisfied, and 1 case was dissatisfied. The total treatment cost for patients in this group during hospitalization was 11 764-36 452 (22 304±6 955) yuan.Conclusions:For patients with titanium mesh exposure after cranioplasty, on the premise of adequate preoperative preparation and thorough debridement, the wound can be repaired with appropriate flaps or myocutaneous flaps according to the wound condition. The surgery can preserve all or part of the titanium mesh. The postoperative wound healing is good and the recurrence of infection or titanium mesh exposure in the titanium mesh implanted area is reduced, leading to good head shape, reduced surgical frequency, and decreased treatment costs.
4.Effects of thinned anterolateral thigh perforator flaps combined with finger splitting and webplasty in sequential treatment of degloving destructive wound of total hand
Shanqing YIN ; Feng ZHU ; Yaopeng HUANG ; Jiadong PAN ; Dongchao XIAO ; Linhai LIU ; Xueyuan LI ; Xin WANG
Chinese Journal of Burns 2024;40(11):1052-1058
Objective:To investigate the effects of thinned anterolateral thigh perforator flaps combined with finger splitting and webplasty in sequential treatment of degloving destructive wound of total hand.Methods:This study was a retrospective observational study. From January 2012 to January 2023, a total of 15 cases who met the inclusion criteria with degloving destructive wound of total hand were admitted to Ningbo No.6 Hospital, including 10 males and 5 females, aged 17-75 years. The wounds were all combined with exposed bones or tendon. Emergency debridement and vacuum sealing drainage were performed in all cases before flap transplantation in stage Ⅰ. After thorough debridement, the wound area was 11.0 cm×3.0 cm-23.0 cm×13.5 cm. One or both anterolateral thigh perforator flaps with size of 12.5 cm×5.0 cm-25.0 cm×15.5 cm were designed, cut, and thinned to repair the skin and soft tissue defects of the hand. The donor site was sutured directly or repaired with medium-thickness skin graft from the opposite thigh. As needed, the flap was reconstructed by finger splitting and webplasty once or more times every 3 months after stage Ⅰoperation. The survival and complications of flap and wound healing at the donor site were observed after stage Ⅰoperation. The appearance of flap, two-point discrimination distance, and hand function were observed during the follow-up. At the final follow-up, the function of the affected hand was evaluated by the trial standards for evaluation of partial function of upper extremity by the Hand Surgery Society of Chinese Medical Association.Results:After the operation of stage Ⅰ, all the flaps of 15 cases of patients survived completely, including 1 case that had arterial crisis of flap but survived completely after exploration and re-anastomosis of blood vessels; all the wounds at the donor site healed. During the follow-up period of 6 to 18 months after stage Ⅰ, the flap was slightly swollen, with a little pigmentation, and the two-point discrimination distance in the finger flap was 8-11 mm. The fingers could complete the basic life actions such as flexion, extension, pinch, and grip. At the final follow-up, 3 cases were excellent, 9 cases were good, and 3 cases were acceptable in function evaluation of the affected hand.Conclusions:For degloving destructive wound of total hand, free transplantation of one or both thinned anterolateral thigh perforator flaps is used for repair in stage Ⅰ, and finger splitting and webplasty are used to reconstruct the flaps in the later stage, which can basically restore the pinch and grip function of the affected hand that is required for daily life, and is worthy of clinical promotion.
5.Research progress on the mechanism of cartilage damage induced by matrix metalloproteinase in Kashin-Beck disease
Xinke ZHU ; Kun ZUO ; Zhengming SUN ; Xueyuan WU
Chinese Journal of Endemiology 2024;43(8):678-682
Kashin-Beck disease (KBD) is a chronic endemic bone and joint disease, with severe cases of short stature, joint deformities, and significantly reduced quality of life. Its etiology is currently unclear. Matrix metalloproteinases (MMPs) are endopeptidases that can degrade the extracellular matrix of articular cartilage cells, and are closely related to the occurrence and development of bone and joint diseases. At present, some scholars have found that MMPs can cause cartilage damage in KBD patients and promote the progression of KBD, but its specific mechanism of action is still unclear. This article reviews the research progress on the etiology of KBD, MMPs and its related genes, and their relationship with KBD cartilage injury both domestically and internationally. In order to provide theoretical support for in-depth research on the pathogenesis of KBD and to improve and update its treatment methods.
6.Image fusion-based recurrence patterns and dosimetry after concurrent chemoradiotherapy for thoracic esophageal squamous cell carcinoma
Ke YAN ; Xueyuan ZHANG ; Shuguang LI ; Wenzhao DENG ; Xingyu DU ; Xiaobin WANG ; Jingwei SU ; Wenbin SHEN ; Shuchai ZHU
Chinese Journal of Radiological Medicine and Protection 2023;43(7):505-512
Objective:To analyze the local recurrence patterns after concurrent chemoradiotherapy (CCRT) for thoracic esophageal squamous cell carcinoma (ESCC) through image fusion, and to explore the risk factors of local recurrence and its relationships with dosimetric indices.Methods:A retrospective analysis was conducted for 209 thoracic ESCC patients who received radical CCRT in Fourth Hospital of Hebei Medical University during 2016-2019. For the patients diagnosed as the local recurrence of esophageal lesions, their CT images were fused with the original planning CT images using image registration software to identify the recurrence sites. Through 1∶1 propensity score matching (PSM) of the clinal data of patients with local recurrence (the recurrence group, nbefore = 81, nafter = 62) and those without local recurrence (the recurrence-free group, nbefore = 128, nafter=62), the dose and volume parameters of the treatment plans for the two groups were compared. Univariate and multivariate analyses were conducted using the Kaplan-Meier method and the Cox regression model to analyze the factors affecting the overall survival (OS), progression-free survival (PFS), and recurrence-free survival (RFS). Results:All patients had 1-, 3-, and 5-year OS rates of 80.9%, 42.6%, and 33.0%, respectively, 1-, 3-, and 5-year PFS rates of 67.9%, 34.0%, and 27.9%, respectively, and 1-, 3-, and 5-year RFS rates of 71.3%, 39.2%, and 30.5%, respectively. T stage, N stage, and radiation dose were independent prognostic factors for the OS, PFS, and RFS ( HR = 1.42-1.87, P < 0.05) of the patients, respectively. Among 68 patients with local recurrence, 62 cases (91.2%) suffered recurrence within the gross tumor volume (GTV). The dose and volume parameters of patients with local recurrence, such as GTV- D95%, clinical target volume (CTV)- D95%, GTV- D50%, CTV- D50%, and planning target volume (PTV)- D50%, GTV- V60, CTV- V60, and PTV- V60, were significantly lower than those of patients free from the local recurrence ( t=1.90-2.15, P < 0.05). Conclusions:Local recurrence of patients with thoracic ESCC after radical CCRT occurs mainly within the GTV. Increasing radiation doses may contribute to their survival benefits. The D50% for each target volume in the radiotherapy plan may be related to local recurrence, and it is necessary to conduct further research.
7.Effects of HMGB1 on clinical prognosis of esophagus squamous cell carcinoma patients after chemoradiotherapy and the radiosensitivity of xenograft in nude mice
Xueyuan ZHANG ; Xingxiao YANG ; Naiyi ZOU ; Shuguang LI ; Wenbin SHEN ; Shuchai ZHU
Chinese Journal of Radiation Oncology 2023;32(1):48-54
Objective:To evaluate the effects of high mobility group protein box 1 (HMGB1) on clinical prognosis of esophagus squamous cell carcinoma (ESCC) patients treated with chemoradiotherapy and the radiosensitivity of xenograft in nude mice.Methods:A total of 90 endoscopic biopsy specimens were obtained from ESCC patients treated with chemoradiotherapy. The expression level of HMGB1 was determined by immunohistochemical staining. High expression level was defined when staining was observed on ≥50% of the tumor cells. All patients were divided into the high expression group ( n=48) and low expression group ( n=42), and their survival information was retrospectively analyzed. Cell transfection was performed with the plasmid carrying human HMGB1-shRNA to knockdown HMGB1 expression in ECA109 cells and xenograft mouse models were established. The tumor volume and mass were calculated after irradiation with a dose of 15 Gy. The cell apoptosis in xenograft tissues were detected. Survival analysis was performed using Kaplan-Meier method. Univariate prognostic analysis was conducted by log-rank test. Intergroup comparison was performed by analysis of variance (ANOVA). Results:The expression level of HMGB1 was significantly associated with gross tumor volume, longest diameter of tumor, T staging and distant metastasis ( χ2=9.663, 5.625, 4.068, 7.146, all P<0.05). In the low expression group, the overall survival (OS) ( χ2=4.826, P=0.028), progression-free survival (PFS) ( χ2=4.390, P=0.036) were longer compared with that in the high expression group. Further analysis of HMGB1-high expression patients showed that the radiation dose and the combination of chemoradiotherapy did not significantly affect the OS or PFS of ESCC patients. We observed that knockdown of HMGB1 slowed the growth rate of xenograft, decreased the tumor volume and increased the apoptosis rate after irradiation. Conclusions:ESCC patients with high expression level of HMGB1 obtain poor prognosis after chemoradiotherapy, which can be enhanced by increasing the sensitivity to radiotherapy and chemotherapy. HMGB1 knockdown can effectively increase the radiosensitivity of xenograft in ESCC nude mice.
8.Postoperative hypoalbuminemia in patients with acute ischemic stroke with successful recanalization by endovascular therapy: risk factors and their impact on outcomes
Hao LU ; Qiang GUO ; Yongnan HAO ; Dongxu YANG ; Ya’nan CHEN ; Zhi ZHU ; Xueyuan LI
International Journal of Cerebrovascular Diseases 2023;31(10):721-727
Objective:To investigate the risk factors of hypoalbuminemia (HA) in patients with acute ischemic stroke (AIS) caused by large vessel occlusion (LVO) after endovascular mechanical thromboectomy (EMT) and impact on outcomes.Methods:Patients first diagnosed with anterior circulation LVO-AIS and underwent emergency EMT at the Department of Acute Stroke, the Affiliated Hospital of Jining Medical University from June 1, 2020 to April 31, 2023 were retrospectively included. According to the first follow-up serum albumin examination after procedure (6-8 d), the patients were divided into HA group (<35 g/L) and non-HA group (≥35 g/L). According to the modified Rankin Scale score at 90 d after EMT, the patients were divided into a good outcome group (0-2) and a poor outcome group (3-6). Univariate and multivariate logistic analysis was used to determine independent risk factors for HA after EMT and their impact on outcomes. Results:A total of 144 patients were enrolled, including 107 males (74.30%) with a median age of 64 years (interquartile range, 56-71 years). There were 50 patients (34.72%) in the HA group and 94 (65.28%) in the non-HA group; 60 (41.67%) in the good outcome group, and 84 (58.33%) in the poor outcome group. Multivariate logistic regression analysis showed that age (odds ratio [ OR] 1.061, 95% confidence interval [ CI] 1.014-1.111; P=0.011) and pulmonary infection ( OR 5.136, 95% CI 1.917-13.760; P=0.001) were independent risk factors for HA; HA ( OR 4.345, 95% CI 1.367-13.814; P=0.013), pneumonia ( OR 5.113, 95% CI 1.217-12.528; P=0.026), and onset to reperfusion time ( OR 5.473, 95% CI 1.090-16.05; P=0.038) were independent risk factors for poor outcomes. Conclusions:Age and pulmonary infection are independent risk factors for HA in LVO-ASI patients after EMT, and HA is the independent risk factor for poor outcomes of the patients.
9.Analysis on the Ethical Principles of Traditional Chinese Medicine Health Preservation Thought from the Perspective of Healthy China: Taking Master Lyu’s Spring and Autumn Annals as an Example
Meng YANG ; Xueyuan ZHU ; Yajun LI
Chinese Medical Ethics 2023;36(6):646-650
"Healthy China 2030" states that health is a necessary requirement for all-round human development and a basic condition for economic and social development. Achieving national health and longevity is an important symbol of national prosperity and rejuvenation, and also the common aspiration of the people of all ethnic groups in China. Traditional Chinese medicine (TCM) health preservation has been fully integrated into the construction of "Healthy China", and the development of TCM health preservation culture and thought has a profound historical origin. Starting from the development of TCM health preservation culture thought and ethical principles, this paper analyzed the TCM health preservation thought contained in Master Lyu’s Spring and Autumn Annals, and further discussed and summarized the ethical principles contained in them, with a view to comprehensively and systematically promoting the development of TCM health preservation culture and providing a theoretical basis for people to use health preservation ethical principles to achieve physical fitness, disease prevention and longevity.
10.Temozolomide Drives Ferroptosis via a DMT1-Dependent Pathway in Glioblastoma Cells
Qingxin SONG ; Shanxin PENG ; Zhiqing SUN ; Xueyuan HENG ; Xiaosong ZHU
Yonsei Medical Journal 2021;62(9):843-849
Purpose:
Temozolomide is used in first-line treatment for glioblastoma. However, chemoresistance to temozolomide is common in glioma patients. In addition, mechanisms for the anti-tumor effects of temozolomide are largely unknown. Ferroptosis is a form of programmed cell death triggered by disturbed redox homeostasis, overloaded iron, and increased lipid peroxidation. The present study was performed to elucidate the involvement of ferroptosis in the anti-tumor mechanisms of temozolomide.
Materials and Methods:
We utilized the CCK8 assay to evaluate cytotoxicity. Levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), iron, and glutathione (GSH) were measured. Flow cytometry and fluorescence microscope were used to detect the production of reactive oxygen species (ROS). Western blotting, RT-PCR and siRNA transfection were used to investigate molecular mechanisms.
Results:
Temozolomide increased the levels of LDH, MDA, and iron and reduced GSH levels in TG905 cells. Furthermore, we found that ROS levels and DMT1 expression were elevated in TG905 cells treated with temozolomide and were accompanied by a decrease in the expression of glutathione peroxidase 4, indicating an iron-dependent cell death, ferroptosis. Our results also showed that temozolomide-induced ferroptosis is associated with regulation of the Nrf2/HO-1 pathway. Conversely, DMT1 knockdown by siRNA evidently blocked temozolomide-induced ferroptosis in TG905 cells.
Conclusion
Taken together, our findings indicate that temozolomide may suppress cell growth partly by inducing ferroptosis by targeting DMT1 expression in glioblastoma cells.

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