1.The Combination of Gefitinib and Acetaminophen Exacerbates Hepatotoxicity via ROS-Mediated Apoptosis
Jiangxin XU ; Xiangliang HUANG ; Yourong ZHOU ; Zhifei XU ; Xinjun CAI ; Bo YANG ; Qiaojun HE ; Peihua LUO ; Hao YAN ; Jie JIN
Biomolecules & Therapeutics 2024;32(5):647-657
Gefitinib is the well-tolerated first-line treatment of non-small cell lung cancer. As it needs analgesics during oncology treatment, particularly in the context of the coronavirus disease, where patients are more susceptible to contract high fever and sore throat.This has increased the likelihood of taking both gefitinib and antipyretic analgesic acetaminophen (APAP). Given that gefitinib and APAP overdose can predispose patients to liver injury or even acute liver failure, there is a risk of severe hepatotoxicity when these two drugs are used concomitantly. However, little is known regarding their safety at therapeutic doses. This study simulated the administration of gefitinib and APAP at clinically relevant doses in an animal model and confirmed that gefitinib in combination with APAP exhibited additional hepatotoxicity. We found that gefitinib plus APAP significantly exacerbated cell death, whereas each drug by itself had little or minor effect on hepatocyte survival. Mechanistically, combination of gefitinib and APAP induces hepatocyte death via the apoptotic pathway obviously. Reactive oxygen species (ROS) generation and DNA damage accumulation are involved in hepatocyte apoptosis. Gefitinib plus APAP also promotes the expression of Kelch-like ECH-associated protein 1 (Keap1) and downregulated the antioxidant factor, Nuclear factor erythroid 2-related factor 2 (Nrf2), by inhibiting p62 expression.Taken together, this study revealed the potential ROS-mediated apoptosis-dependent hepatotoxicity effect of the combination of gefitinib and APAP, in which the p62/Keap1/Nrf2 signaling pathway participates and plays an important regulatory role.
2.Effect of radiofrequency radiation from 5G mobile phone on blood-brain barrier in mice
Guiqiang ZHOU ; Yizhe XUE ; Zhaowen ZHANG ; Tongzhou QIN ; Ling GUO ; Panpan LAI ; Peng GAO ; Xing WANG ; Zhifei HUANG ; Yuhang ZANG ; Yuntao JING ; Guirong DING
Chinese Journal of Radiological Medicine and Protection 2023;43(3):176-181
Objective:To investigate the effect of radiofrequency radiation (RF) from 5G mobile phone communication frequency bands (3.5 GHz and 4.9 GHz) on the permeability of the blood-brain barrier (BBB) in mice.Methods:A total of 24 healthy adult male C57BL/6 mice (6-8 weeks old) were randomly divided into Sham, 3.5 GHz RF and 4.9 GHz RF groups, and 8 mice in each group. Mice in the RF groups were systemically exposed to 5G cell phone radiation for consecutive 35 d(1 h/d) with 50 W/m 2 power density. The BBB permeability of mice was detected by Evans Blue (EB) fluorescence experiment. The expression levels of the BBB tight junction-related proteins (ZO-1, occludin and claudin-11) and the gap junction-related protein Connexin 43 were determined by Western blot. Results:The number of spots, fluorescence intensity and comprehensive score of EB were significantly increased in 3.5 GHz RF group and 4.9 GHz RF group compared with the Sham group ( t=12.98, 17.82, P<0.001). Compared with the Sham group, the content of S100B in mouse serum was significantly increased in 3.5 GHz RF group and 4.9 GHz RF group ( t=19.34, 14.68, P<0.001). The BBB permeability was increased in the RF group. The expression level of occludin protein was significantly reduced in the 3.5 GHz RF group ( t=-3.13, P<0.05), and this decrease was much profound in the 4.9 GHz RF group ( t=-6.55, P<0.01). But the protein levels of ZO-1, Claudin-11 and Connexin 43 in the cerebral cortex of the RF groups had no significantly difference in comparison with the Sham group( P>0.05). Conclusions:The continuous exposure of mobile phone RF at 3.5 GHz or 4.9 GHz for 35 d (1 h/d) induces an increase of BBB permeability in the mouse cerebral cortex, perhaps by reducing the expression of occludin protein.
3.N-acetyl-D-glucosamine inhibits oxidative stress and promotes M2 macrophage polarization to alleviate acute pancreatitis in rats
Zuzhi XU ; Liang ZHANG ; Xin HUANG ; Lei YU ; Pengfei CHEN ; Xuewen XIE ; Zhifei CHEN ; Kaihan FANG ; Shuke FEI
Acta Laboratorium Animalis Scientia Sinica 2023;31(11):1389-1398
Objective To investigate the effects of N-acetyl-D-glucosamine(GlcNAc)on acute pancreatitis in rats.Methods Twenty male SD rats were randomly divided into a control group,AP group,low GlcNAc + AP group and high GlcNAc + AP group,with five rats in each group.Acute pancreatitis was induced in AP group,low GlcNAc + AP group and high GlcNAc + AP group by two intraperitoneal injections of 2.5 g/kg L-arginine with a 1 hour interval.Among them,low GlcNAc + AP group and high GlcNAc + AP group were administered 50 and 200 mg/kg GlcNAc,respectively,by intraperitoneal injection at 24 hours before the first intraperitoneal injection of L-arginine.Group control and AP were intraperitoneally injected with the same volume of normal saline.After 24 h,the rats were sacrificed,and serum and pancreatic tissues were collected.Pancreatic tissue morphology was observed by HE staining,and serum levels of amylase(AMY),lipase(LPS),interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),superoxide dismutase(SOD)and malondialdehyde(MDA)were measured by enzyme-linked immunosorbent assay.Protein expression of nuclear factor E2-related factor 2(NRF2),heme oxygenase-1(HO-1),and peroxisome proliferator-activated receptor-γ(PPAR-γ)in pancreatic tissue was detected by Western Blot.Cluster of differentiation(CD)86,CD206 and macrophage markers(F4/80)were detected by immunofluorescence.Expression of CD86 and CD206 in pancreatic tissue was detected by immunohistochemistry.Results(1)Compared with control group,AMY,LPS,IL-1β,IL-6,TNF-α,and MDA levels and pancreatic CD86 expression in AP group were significantly increased(P<0.05),while SOD activity,protein expression levels of NRF2,HO-1,and PPAR-γ,and pancreatic CD206 expression were significantly decreased(P<0.05).(2)Compared with AP group,serum IL-1β,IL-6,TNF-α,MDA,and LPS and the pancreatic CD86 expression in low GlcNAc + AP group were significantly decreased(P<0.05).The PPAR-γ protein level in the pancreas was significantly increased(P<0.05).(3)Compared with AP group,serum AMY,LPS,IL-1β,IL-6,TNF-α,and MDA and pancreatic CD86 expression in high GlcNAc + AP group were significantly decreased(P<0.05),while serum SOD,and NRF2,HO-1,PPAR-γ,and pancreatic CD206 expression were significantly increased(P<0.05).(4)Compared with low GlcNAc + AP group,serum LPS,IL-1β and IL-6 in high GlcNAc + AP group were significantly decreased(P<0.05).Pancreatic expression of HO-1,PPAR-γ,and pancreatic CD206 were significantly increased(P<0.05).Conclusion GlcNAc treatment attenuates acute pancreatitis injury in AP rats,possibly by activating the NRF2/HO-1 signaling pathway to inhibit oxidative stress and promoting M2 macrophage polarization to attenuate pancreatic injury in AP rats.
4.Application of artificial intelligence in vascular reconstruction based on cerebral CT perfusion data
Xiaoying HUANG ; Yunfeng BAO ; Xiamin LI ; Fangkai GUO ; Zhifei LI ; Chunhui SHAN ; Yingmin CHEN
Chinese Journal of Radiology 2021;55(8):817-822
Objective:To explore the application value of artificial intelligence (AI) in image post-processing of reconstructed CTA based on CT cerebral perfusion (CTP).Methods:Clinical and radiological data of 100 patients suspected of cerebrovascular diseases in Hebei General Hospital from January to July 2020 were retrospectively selected. All patients were divided into A and B group on average according to the different examination schemes. Cerebral CTP examination was performed in group A (the temporal maximum intensity projective data set generated by the first 5 time phases in the maximum period of the difference between arteriovenous CT values selected as subgroup A1, and the corresponding original thin-layer images selected as subgroup A2), single phase CTA examination was performed in group B, manual and AI image post-processing were performed respectively. Subjective scoring of the image data was performed, and the objective bid evaluation indexes such as CT value, noise (SD), signal-to-noise ratio (SNR), contrast to noise ratio (CNR) were measured, the qualified rate of artificial and AI vascular segmentation was counted, and post-processing time were recorded. The objective evaluation indexes were compared between three groups using one-way ANOVA, and the Kruskal-Wallis H test was used to compare the difference of subjective scores.Results:Statistically significant differences were observed in subjective score and objective evaluation index of original images among group A1, group A2 and group B (all P<0.05). Among them, arterial enhancement, arteriolar detail display score, cerebral artery CT value, SNR and CNR in group A1 were higher than those in group A2 and group B (all P<0.05). In a total of 100 patients with 1 100 blood vessels, the qualified rates of AI vascular segmentation in group A1 [98.4% (541/550)] and group B [98.7% (543/550)] were higher than those of manual [82.9% (456/550), 87.1% (479/550), χ2=77.392, 56.521, P<0.001], but the qualified rate of AI vascular segmentation of group A2 [78.4% (431/550)] was lower than that of manual [85.6% (471/550), χ2=9.855, P=0.002]. The completion time of AI post-processing were reduced by 56.30%, 49.63%, 50.81%, respectively than those with manual. Conclusion:Compared with manual image post-processing, AI has certain advantages in image quality and work efficiency of reconstructed CTA post-processing based on CTP de-noising dataset, and it is worth popularizing and applying in the image post-processing of cerebrovascular disease, combined with artificial quality control.
5.Clinical comparative study of 3D and 2D single-portal inflatable mediastinoscopic and laparoscopic esophagectomy for esophageal cancer
Rongqiang WEI ; Zihao CHEN ; Kenan HUANG ; Xinyu DING ; Zhifei XU ; Hua TANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2021;28(02):233-238
Objective To investigate the safety and efficacy of 3D single-portal inflatable mediastinoscopic and laparoscopic esophagectomy for esophageal cancer. Methods Clinical data of 28 patients, including 25 males and 3 females, aged 51-76 years, with esophageal squamous cell carcinoma undergoing single-portal inflatable mediastinoscopic and laparoscopic esophagectomy from June 2018 to June 2019 were retrospectively analyzed. Patients were divided into two groups according to different surgical methods including a 3D mediastinoscopic group (3D group, 10 patients) and a 2D mediastinoscopic group (2D group, 18 patients). The perioperative outcome of the two groups were compared. Results Compared with the 2D group, the 3D group had shorter operation time (P=0.017), more lymph nodes resected (P=0.005) and less estimated blood loss (P=0.015). There was no significant difference between the two groups in the main surgeon's vertigo and visual ghosting (P>0.05). The other aspects including the indwelling time, postoperative hospital stay, pulmonary infection, arrhythmia, anastomotic fistula, recurrent laryngeal nerve injury were not statistically significant between the two groups (P>0.05). Conclusion The 3D inflatable mediastinoscopic and laparoscopic esophagectomy for esophageal cancer, which optimizes the surgical procedures of 2D, is safe and feasible, and is worthy of clinical promotion in the future.
6.Short-term follow-up results of inflatable mediastinoscopy combined with laparoscopy versus video-assisted thoracoscopic surgery combined with laparoscopy for esophageal cancer
Yunhao FANG ; Zihao CHEN ; Rongqiang WEI ; Kenan HUANG ; Xinyu DING ; Chengdong LIU ; Zhifei XU ; Bin WU ; Hua TANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2021;28(02):239-242
Objective To investigate the short-term follow-up results of inflatable mediastinoscopy combined with laparoscopy in the treatment of esophageal cancer. Methods Clinical data of 102 patients with esophageal cancer who underwent minimally invasive esophagectomy were enrolled in our hospital from January 2017 to January 2019. Patients were divided into two groups according to different surgical methods, including a single-port inflatable mediastinoscopy combined with laparoscopy group (group A, n=59, 53 males and 6 females, aged 63.3±7.6 years, ranging from 45 to 75 years) and a video-assisted thoracoscopy combined with laparoscopy group (group B, n=43, 35 males and 8 females, aged 66.7±6.7 years, ranging from 50-82 years). The short-term follow-up results of the two groups were compared. Results Compared with the group A, the rate of postoperative pulmonary complication of the group B was significantly lower (18.64% vs. 4.65%, P<0.05). There was no significant difference between the two groups in other postoperative complications (P>0.05). The 6-month, 1-year, and 2-year survival rates were 96.61%, 89.83%, and 73.33%, respectively in the group A, and were 95.35%, 93.02%, and 79.17%, respectively in the group B. There was no significant difference in short-term survival rate after operation (P>0.05). Conclusion In the treatment of esophageal cancer, the incidence of pulmonary complications of inflatable mediastinoscopy combined with laparoscopy is lower than that of traditional video-assisted thoracoscopy combined with laparoscopy, and there is no significant difference in other postoperative complications or short-term survival rate between the two methods. Inflatable mediastinoscopy combined with laparoscopy for radical esophageal cancer is a relatively safe surgical method with good short-term curative effects, and long-term curative effects need to be further tested.
7.Application of mixed reality technique in medicine
Ning XIN ; Xinyu DING ; Kenan HUANG ; Rongqiang WEI ; Zihao CHEN ; Chengdong LIU ; Heng LI ; Zhifei XU ; Hua TANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2021;28(05):597-602
Mixed reality is a new digital hologram technology after virtual reality and augmented reality, which combines the real world with the virtual world to form a new visualization environment. At present, mixed reality has been applied in various fields, but its application in medical field is still in the exploratory stage. With the rapid development of the digital age, the prospect of the combination of mixed reality and medicine is boundless. It is believed that mixed reality will bring subversive changes in medical training, disease diagnosis, doctor-patient communication, clinical diagnosis, treatment and so on in the near future. In this paper, the application of mixed reality in medicine was summarized.
8.Clinical study of 3D versus 2D thoracoscopic surgeries in uniportal lobectomy
Kenan HUANG ; Xinyu DING ; Zihao CHEN ; Rongqiang WEI ; Yu CHEN ; Zhifei XU ; Hua TANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2020;27(07):770-774
Objective To investigate the safety and efficacy of 3D thoracoscopic surgery in uniportal lobectomy. Methods Clinical data of 248 patients with lung cancer who underwent uniportal thoracoscopic lobectomy in our hospital from September 2018 to May 2019 were retrospectively analyzed. Patients were divided into two groups according to different surgical methods, a 3D thoracoscopic group (76 patients, including 52 males and 24 females with an average age of 58.59±7.62 years) and a 2D thoracoscopic group (172 patients, including 102 males and 70 females with an average age of 57.75±8.59 years). Statistical analysis of clinical and pathological data, lymph node dissection, surgical complications, postoperative hospital stay, etc was performed. Results Compared with the 2D thoracoscopic group, the 3D thoracoscopic group had shorter operation time, more lymph nodes dissected and pleural effusion on the first day after operation (P<0.05). There was no significant difference in the postoperative chest tube duration, postoperative hospital stay, incidence of pulmonary infection, arrhythmia, bronchopleural fistula, or recurrent laryngeal nerve injury between the two groups. Conclusion Compared with the traditional 2D thoracoscopic minimally invasive surgery, uniportal lobectomy with 3D thoracoscopic surgery is safer and more efficient during operation, and lymph node dissection is more thorough, which is worth promoting.
9.Mixed reality technique in preoperative discussion and intraoperative pulmonary nodules surgery
Zihao CHEN ; Kenan HUANG ; Xinyu DING ; Rongqiang WEI ; Chengdong LIU ; Zhifei XU ; Hua TANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2020;27(07):797-801
Objective To introduce the application of mixed reality technique to the preoperative and intraoperative pulmonary nodules surgery. Methods One 49-year female patient with multiple nodules in both lobes of the lung who finally underwent uniportal thoracoscopic resection of superior segment of left lower lobe and wedge resection of left upper lobe was taken as an example. The Mimics medical image post-processing software was used to reconstruct the patient's lung image based on the DICOM data of the patient's chest CT image before the surgery. The three-dimensional reconstructed image data was imported into the HoloLens glasses, and the preoperative discussions were conducted with the assistance of mixed reality technology to formulate the surgical methods, and the preoperative conversation with the patients was also conducted. At the same time, mixed reality technology was used to guide the surgery in real time. Results Mixed reality technology can clearly pre-show the important anatomical structures of blood vessels, trachea, lesions and their positional relationship. With the help of mixed reality technology, the operation went smoothly. The total operation time was 49 min, the precise dorsal resection time was 27 min, and the intraoperative blood loss was about 39 mL. The patient recovered well and was discharged from hospital smoothly after surgery. Conclusion Mixed reality technology has certain application value before and during the surgery for pulmonary nodules. The continuous maturity of this technology and its further application in clinics will not only bring a new direction to the development of thoracic surgery, but also provide a wide prospect.
10. Feasibility study of the multi-slice dual-source CT double turbo flash mode for one-step coronary and carotid-cerebrovascular CT angiography in patients with heart rate variability
Yunfeng BAO ; Xiaoying HUANG ; Zhifei LI ; Fangkai GUO ; Mingjuan ZHAO ; Kaihong WANG ; Shenjie CAO ; Yingmin CHEN
Chinese Journal of Radiology 2020;54(2):95-100
Objective:
To investigate the feasibility of one-step coronary and carotid-cerebrovascular computed tomography angiography (CTA) using high-pitch Double Turbo Flash mode and to analyze the image quality and radiation dose in patients with heart rate variability using multi-slice detector dual-source CT.
Methods:
A total of 79 patients with heart rate variability higher than 3 beat/min (bpm) were retrospectively analyzed. They were grouped by the scanning methods. Group A (

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