1.Short-term results of a multicenter study based on a modified N7 induction regimen combined with arsenic trioxide in the treatment of children with high-risk neuroblastoma
Shu YANG ; Kailan CHEN ; Yunyan HE ; Xiaomin PENG ; Hao XIONG ; Wenguang JIA ; Sha WU ; Xunqi JI ; Yuwen CHEN ; Chuan TIAN ; Zhonglü YE ; Zhen YANG ; Jianjun ZHU ; Aiguo LIU ; Xiaohua TIAN ; Fengjuan PAN ; Ke HUANG ; Dunhua ZHOU ; Jianpei FANG ; Yang LI
Chinese Journal of Pediatrics 2024;62(10):949-955
Objective:To analyze the short-term clinical efficacy and safety of arsenic trioxide (ATO) combined with a modified N7 induction regimen in the treatment of children with high-risk neuroblastoma (NB).Methods:This study was a prospective, single-arm, multicenter phase Ⅱ clinical study. Sixty-seven high-risk NB children from eight units of Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Wuhan Children′s Hospital of Tongji Medical College of Huazhong University of Science and Technology, First Affiliated Hospital of Guangxi Medical University, Hainan General Hospital, Affiliated Hospital of Guangdong Medical University, Kunming Children′s Hospital, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, and Guangdong Provincial Agricultural Reclamation Center Hospital were enrolled from January 2019 to August 2023 and were treated with ATO combined with a modified N7 induction regimen. The efficacy and adverse effects at the end of induction chemotherapy were assessed and analyzed, and the differences in the clinical characteristics were further compared between the treatment-responsive and treatment-unresponsive groups by using the Fisher′s exact test.Results:Among 67 high-risk NB children, there were 40 males (60%) and 27 females (40%), with the age of disease onset of 3.5 (2.6, 4.8) years. Primary NB sites were mostly in retroperitoneum (including adrenal gland) (56/67, 84%) and the common metastases sites at initial diagnosis were distant lymph node in 25 cases (37%),bone in 48 cases (72%),bone marrow in 56 cases (84%) and intracalvarium in 3 cases (4%). MYCN gene amplification were detected in 28 cases (42%). At the end of induction, 33 cases (49%) achieved complete remission, 29 cases (43%) achieved partial remission, 1 case (1%) with stable disease, and 4 cases (6%) were assessed as progressive disease (PD). The objective remission rate was 93% (62/67) and the disease control rate was 94% (63/67). The percentage of central system metastases at the initial diagnosis was higher in the treatment-unresponsive group than in the treatment-responsive group (2/5 vs. 2% (1/62), P=0.013), whereas the difference in MYCN gene amplification was not statistically significant between two groups (3/5 vs.40% (25/62), P=0.786). Grade Ⅲ or higher adverse reactions during the induction chemotherapy period were myelosuppression occurred in 60 cases (90%), gastrointestinal symptoms occurred in 33 cases (49%), infections occurred in 20 cases (30%), hepatotoxicity occurred in 4 cases (6%), and cardiovascular toxicity occurred in 1 case (2%). There were no chemotherapy-related deaths. Conclusion:ATO combined with N7-modified induction regimen had a superiority in efficacy and safety, which deserved further promotion in clinical practice.
2.Engineering cannabidiol synergistic carbon monoxide nanocomplexes to enhance cancer therapy via excessive autophagy.
Chang XIAO ; Yue SUN ; Jialong FAN ; William NGUYEN ; Simin CHEN ; Ying LONG ; Wei CHEN ; Aiguo ZHU ; Bin LIU
Acta Pharmaceutica Sinica B 2023;13(11):4591-4606
Although carbon monoxide (CO)-based treatments have demonstrated the high cancer efficacy by promoting mitochondrial damage and core-region penetrating ability, the efficiency was often compromised by protective autophagy (mitophagy). Herein, cannabidiol (CBD) is integrated into biomimetic carbon monoxide nanocomplexes (HMPOC@M) to address this issue by inducing excessive autophagy. The biomimetic membrane not only prevents premature drugs leakage, but also prolongs blood circulation for tumor enrichment. After entering the acidic tumor microenvironment, carbon monoxide (CO) donors are stimulated by hydrogen oxide (H2O2) to disintegrate into CO and Mn2+. The comprehensive effect of CO/Mn2+ and CBD can induce ROS-mediated cell apoptosis. In addition, HMPOC@M-mediated excessive autophagy can promote cancer cell death by increasing autophagic flux via class III PI3K/BECN1 complex activation and blocking autolysosome degradation via LAMP1 downregulation. Furthermore, in vivo experiments showed that HMPOC@M+ laser strongly inhibited tumor growth and attenuated liver and lung metastases by downregulating VEGF and MMP9 proteins. This strategy may highlight the pro-death role of excessive autophagy in TNBC treatment, providing a novel yet versatile avenue to enhance the efficacy of CO treatments. Importantly, this work also indicated the applicability of CBD for triple-negative breast cancer (TNBC) therapy through excessive autophagy.
3.Minimally invasive repair of acute closed Achilles tendon rupture with two-way needle suture technique
Changsong CAO ; Zhe LEI ; Jianjun WU ; Song YANG ; Jie CHEN ; Liangliang ZHAO ; Junfang ZHU ; Aiguo WANG
Chinese Journal of Orthopaedic Trauma 2023;25(7):584-588
Objective:To investigate the efficacy of two-way needle suture technique (TNST) in the minimally invasive repair of acute closed Achilles tendon rupture.Methods:From June 2019 to June 2021, 26 patients with acute closed Achilles tendon rupture were treated at Zhengzhou Orthopedic Hospital. They were 20 males and 6 females, with a mean age of 28 (23, 31) years. The rupture end was (4.2±1.3) cm away from the calcaneal insertion, and the interval from injury to operation 4.3 (2.0, 5.0) d. Preoperative MRI examinations revealed in all the patients closed Achilles tendon rupture which was to be repaired by TNST. The operation time, incision length, incidence of complications, ankle dorsiflexion and plantar flexion were recorded. The Arner-Lindholm scoring was used to evaluate the clinical efficacy.Results:The operation time was (20.0±5.0) min and the incision length (2.5±0.4) cm. Postoperatively, all incisions healed by the first stage, with no complications like incision infection, skin edge necrosis, deep vein thrombosis at lower limbs, injury to the sural nerve, or re-rupture of the Achilles tendon. All patients were followed up for (12.0±6.0) months. At the last follow-up, the patients walked normally, their incisions healed well, the continuity of the Achilles tendon was good by palpation, their heel lift was strong, and all their activities were restored to the levels before rupture of the Achilles tendon. The ankle dorsiflexion was 22.6°±3.7° and the plantar flexion 25.3°±3.7°, According to the Arner-Lindholm evaluation, the clinical efficacy was rated as excellent in 25 cases and as good in 1 case, giving an excellent and good rate of 100% (26/26).Conclusion:In the minimally invasive repair of acute closed Achilles tendon rupture, TNST shows the advantages of limited surgical invasion, a low incidence of postoperative complications, and reliable curative effects.
4.Chemotherapeutic nanomaterials in tumor boundary delineation: Prospects for effective tumor treatment.
Ozioma Udochukwu AKAKURU ; Zhoujing ZHANG ; M Zubair IQBAL ; Chengjie ZHU ; Yewei ZHANG ; Aiguo WU
Acta Pharmaceutica Sinica B 2022;12(6):2640-2657
Accurately delineating tumor boundaries is key to predicting survival rates of cancer patients and assessing response of tumor microenvironment to various therapeutic techniques such as chemotherapy and radiotherapy. This review discusses various strategies that have been deployed to accurately delineate tumor boundaries with particular emphasis on the potential of chemotherapeutic nanomaterials in tumor boundary delineation. It also compiles the types of tumors that have been successfully delineated by currently available strategies. Finally, the challenges that still abound in accurate tumor boundary delineation are presented alongside possible perspective strategies to either ameliorate or solve the problems. It is expected that the information communicated herein will form the first compendious baseline information on tumor boundary delineation with chemotherapeutic nanomaterials and provide useful insights into future possible paths to advancing current available tumor boundary delineation approaches to achieve efficacious tumor therapy.
5.Serum macrophage migration inhibitory factor as a potential biomarker to evaluate therapeutic response in patients with allergic asthma: an exploratory study.
Huiyuan ZHU ; Shaochun YAN ; Jingshuo WU ; Zhong ZHANG ; Xiaolin LI ; Zheng LIU ; Xing MA ; Lina ZHOU ; Lin ZHANG ; Mingming FENG ; Yiwei GENG ; Aixin ZHANG ; Sabina JANCIAUSKIENE ; Aiguo XU
Journal of Zhejiang University. Science. B 2021;22(6):512-520
6.Effects of siRNA interference with Nrf2 on the regulation of glutathione S-transferase and IL-1β in A549 cells exposed to hyperoxia
Yizi CAI ; Aiguo LI ; Yingying ZHU ; Xiaoyue ZHANG ; Xiaohui GONG ; Cheng CAI
Chinese Journal of Neonatology 2021;36(5):58-62
Objective:To study the gene expression of nuclear factor erythroid-2-related factor 2 (Nrf2), glutathione-S-transferase (GST) and interleukin-1 β (IL-1β) in A549 cells exposed to hyperoxia and cell apoptosis after siRNA interference with Nrf2.Method:Normal A549 cell lines were assigned into normoxia+siRNA group, normoxia+control group, hyperoxia+siRNA group and hyperoxia+control group according to whether siRNA interference was used and the exposure environment (normoxia/hyperoxia). The hyperoxia environment contained 95%O 2 and 5%CO 2. The levels of mRNA expression of Nrf2, GST and IL-1β were detected using quantitative real-time polymerase chain reaction (qRT-PCR). Flow cytometry was used to examine cell apoptosis of the hyperoxia+control group and hyperoxia+siRNA group at different time points. Analysis of variance (ANOVA) was used to test the relative gene expression and apoptosis of A549 cells. Result:(1) Compared with the normoxia+control group, the expression of Nrf2 and GST in the hyperoxia+control group was significantly increased ( P<0.05), and the expression of IL-1β was significantly decreased ( P<0.05); the expression of Nrf2 and GST in the normoxia+siRNA group decreased significantly ( P<0.05), while the expression of IL-1β increased significantly ( P<0.05). (2) Compared with the normoxia+siRNA group, Nrf2 expression in the hyperoxia+siRNA group showed no significant changes ( P=0.230), GST expression increased slightly ( P=0.057), and IL-1β expression decreased slightly ( P=0.112). (3) Compared with the hyperoxia+control group, the expression of Nrf2 and GST in the hyperoxia+siRNA group decreased significantly ( P<0.05), and the expression of IL-1β increased significantly ( P=0.042). (4) Compared with the hyperoxia+control group, the apoptosis of A549 cells in the hyperoxia+siRNA group increased significantly at 24 h, 48 h and 72 h ( P<0.05). Conclusion:After interfering with Nrf2, siRNA may regulate the expression of GST and IL-1β, preventing oxidative stress, reducing inflammatory response and inhibiting apoptosis.
7.Protective effect and mechanisms of umbilical cord tissue transplantation on radiation-induced learning and memory impairment in rats
Zejun ZHU ; Yang ZHAO ; Aiguo ZHANG ; Naiyao CHEN ; Hui ZHAO ; Disi BAI ; Xiujun ZHANG
Chinese Journal of Behavioral Medicine and Brain Science 2020;29(1):8-13
Objective:To investigate the protective effect and mechanisms of umbilical cord tissue transplantation on radiation-induced learning and memory impairment in rats.Methods:Sixty SD rats were randomly divided into three groups with 20 in each group: control group, model group (whole brain X-ray irradiation, dose 20 Gy) and treatment group (whole brain X-ray irradiation, dose 20 Gy + umbilical cord tissue transplantation). The changes of body mass were observed, and the learning and memory of rats were observed by water maze test on the 14th and 28th day after irradiation, the neuron state of hippocampus was observed by HE staining, and the expressions of NF-κB pathway related proteins and IL-6 in hippocampus were detected by Western blot.Descriptive analysis and hypothesis testing were processed by SPSS 17.0.Results:(1) On the 28th day, the escaping latency in the water maze experiment of the treatment group was significantly higher than that of the control group and lower than that of the model group (control group: (11.77±3.02) s, model group: (23.75±3.27)s, treatment group: (18.49±2.32)s; t=3.940, -2.943, both P<0.05); the number of crossing platform in the treatment group was significantly lower than that in the control group and higher than that in the model group (control group: (7.20±0.84), model group (3.60±1.14 ), treatment group (5.00±1.00); t=-3.773, 2.064, both P<0.05). (2)HE staining showed that the neurons in the control group were arranged orderly and the cytoplasm was transparent.The neurons in the model group were arranged disorderly and the contraction of the cell body was triangular or irregular.The number of neurons in the treatment group was less than that in the model group. (3) On the 14th day, the relative expression of TLR4 in the treatment group was significantly higher than that in the control group and lower than that in the model group (control group: (0.69±0.03), model group: (1.06±0.11), treatment group: (0.90±0.04); t=7.275, -2.368, both P<0.05). The relative expression of NF-κB p65 in the treatment group was significantly higher than that in the control group and lower than that in the model group (control group: (1.67±0.12), model group: (2.08 ±0.06), treatment group: (1.93±0.08); t=3.236, -2.684, both P<0.05). The relative expression of IL-6 in the treatment group was significantly higher than that in the control group and lower than that in the model group (control group: (0.77±0.08), model group: (1.12±0.07), treatment group: (0.95±0.06); t=3.274, -3.495, both P<0.05). The relative expression of Bcl-2 / Bax in the treatment group was significantly lower than that in the control group and higher than that in the model group (control group: (1.40±0.52), model group: (0.48±0.06), treatment group: (0.72±0.0 3); t=-2.263, 6.350, both P<0.05). The expression trend of IL-6 and Bcl-2 / Bax protein on the 28th day was the same as that on the 14th day. Conclusion:Cord tissue transplantation can improve the learning and memory impairment caused by radiotherapy, which may be related with the inhibition of inflammation caused by radiotherapy.
8.High ligation versus low ligation of the inferior mesenteric artery and lymph node dissection in laparoscopic rectal cancer surgery
Wenqing FENG ; Yaping ZONG ; Jing SUN ; Wenchang LI ; Congcong ZHU ; Yiming MIAO ; Minhua ZHENG ; Aiguo LU
Chinese Journal of General Surgery 2018;33(7):563-566
Objective To evaluate the surgical complications and root vascular lymph node dissection by high versus low ligation the inferior mesenteric artery (IMA) retaining left colonic artery (LCA) in laparoscopic radical resection of rectal cancer.Methods Clinical data of 357 cases of rectal cancer in our center from Jan 2015 to Dec 2016,were retrospectively analyzed,including 247 cases in high ligation group,110 cases of low ligation group.Results There was no statistically significant difference in operative time and intraoperative blood loss between the two groups [(105 ± 10)min vs.(113 ±9)min,t =0.138,P =0.092;(96 ± 21) ml vs.(99 ± 23) ml,t =0.171,P =0.118].Nor that in the incidence of anastomotic leakage between the two groups (7.3% vs.4.5%,x2 =0.949,P =0.330).The incidence of low anterior resection syndrome in the two groups was statistically significant (21% vs.12%,x2 =4.358,P =0.037).There was no significant difference in the total number of lymph nodes dissected between the two groups ([(14.5±4.3) vs.(13.6±3.5),t=1.851,P=0.065].Conclusion Low ligation of IMA with preservation of LCA in laparoscopic radical operation for rectal cancer provides better blood supply for proximal colon,while achieving same radical clearance of lymph nodes as with high ligation of IMA.
9.Application and research progress of respiratory muscle training in COPD lung rehabilitation
Wei ZHOU ; 421001 湖南省衡阳,南华大学 ; Liming ZHU ; Dan ZENG ; Aiguo DAI
Journal of Chinese Physician 2017;19(11):1627-1630
Chronic obstructive pulmonary disease (COPD) is a common disease with high prevalence,high mortality and high disability.A large number of studies have confirmed that lung rehabilitation is an effective treatment for patients with COPD in addition to oxygen therapy and drug therapy.Respiratory muscle training is one of the basic methods of COPD lung rehabilitation,so do a good job in COPD patients with respiratory muscle training to improve the quality of life of patients,delay the disease process is of great significance.This paper focuses on the application progress of respiratory muscle training in COPD lung rehabilitation.
10.Application of ultrasound-guided temporary balloon occlusion in performing cesarean section for patients with pernicious placenta previa: initial results in 13 cases
Kunqian CHEN ; Fangwang LI ; Enquan ZHU ; Kui XIE ; Wenliang LI ; Mingli ZHANG ; Chao GENG ; Aiguo WANG ; Jianfeng LIU ; Hao GUO
Journal of Interventional Radiology 2017;26(10):915-917
Objective To discuss the clinical application of ultrasound-guided temporary balloon occlusion in performing cesarean section for patients with pernicious placenta previa.Methods At Qujing Municipal First People's Hospital,the Interventional Department and Ultrasonography Department assisted the Obstetrics Department to accomplished cesarean section for 13 patients with pernicious placenta previa.The diagnosis of central placenta previa was confirmed by both color ultrasound and MRI in all the 13 patients.Before cesarean section,the balloons were placed in bilateral common iliac arteries or in abdominal aorta,and the balloons were inflated at the same time when the fetus was delivered so as to temporarily obstruct the target vessels.Based on the hemostatic condition,the balloon was timely withdrawn.Results Among the 13 patients,temporary abdominal aorta occlusion was employed in one and temporary bilateral common iliac artery occlusion in 12.Ultrasound-guided occlusion was successfully accomplished in 12 patients,and the average blocking time was <15 min.The amount of intraoperative blood loss was 800-1500 ml.Conclusion Ultrasound-guided temporary balloon occlusion before cesarean section is safe with reliable effect in treating pernicious placenta previa,it can remarkably reduce the amount of intraoperative blood loos,and it has no X-ray radiation damage,therefore,this technique is worthy of clinical application.

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