1.Synergistic Activation of LEPR and ADRB2 Induced by Leptin Enhances Reactive Oxygen Specie Generation in Triple-Negative Breast Cancer Cells
Chang LIU ; Jing YU ; Yongjun DU ; Yu XIE ; Xiaofei SONG ; Chang LIU ; Yan YAN ; Yue WANG ; Junfang QIN
Cancer Research and Treatment 2025;57(2):457-477
		                        		
		                        			 Purpose:
		                        			Leptin interacts not only with leptin receptor (LEPR) but also engages with other receptors. While the pro-oncogenic effects of the adrenergic receptor β2 (ADRB2) are well-established, the role of leptin in activating ADRB2 in triple-negative breast cancer (TNBC) remains unclear. 
		                        		
		                        			Materials and Methods:
		                        			The pro-carcinogenic effects of LEPR were investigated using murine TNBC cell lines, 4T1 and EMT6, and a tumor-bearing mouse model. Expression levels of LEPR, NADPH oxidase 4 (NOX4), and ADRB2 in TNBC cells and tumor tissues were analyzed via western blot and quantitative real-time polymerase chain reaction. Changes in reactive oxygen species (ROS) levels were assessed using flow cytometry and MitoSox staining, while immunofluorescence double-staining confirmed the co-localization of LEPR and ADRB2. 
		                        		
		                        			Results:
		                        			LEPR activation promoted NOX4-derived ROS and mitochondrial ROS production, facilitating TNBC cell proliferation and migration, effects which were mitigated by the LEPR inhibitor Allo-aca. Co-expression of LEPR and ADRB2 was observed on cell membranes, and bioinformatics data revealed a positive correlation between the two receptors. Leptin activated both LEPR and ADRB2, enhancing intracellular ROS generation and promoting tumor progression, which was effectively countered by a specific ADRB2 inhibitor ICI118551. In vivo, leptin injection accelerated tumor growth and lung metastases without affecting appetite, while treatments with Allo-aca or ICI118551 mitigated these effects. 
		                        		
		                        			Conclusion
		                        			This study demonstrates that leptin stimulates the growth and metastasis of TNBC through the activation of both LEPR and ADRB2, resulting in increased ROS production. These findings highlight LEPR and ADRB2 as potential biomarkers and therapeutic targets in TNBC. 
		                        		
		                        		
		                        		
		                        	
2.Synergistic Activation of LEPR and ADRB2 Induced by Leptin Enhances Reactive Oxygen Specie Generation in Triple-Negative Breast Cancer Cells
Chang LIU ; Jing YU ; Yongjun DU ; Yu XIE ; Xiaofei SONG ; Chang LIU ; Yan YAN ; Yue WANG ; Junfang QIN
Cancer Research and Treatment 2025;57(2):457-477
		                        		
		                        			 Purpose:
		                        			Leptin interacts not only with leptin receptor (LEPR) but also engages with other receptors. While the pro-oncogenic effects of the adrenergic receptor β2 (ADRB2) are well-established, the role of leptin in activating ADRB2 in triple-negative breast cancer (TNBC) remains unclear. 
		                        		
		                        			Materials and Methods:
		                        			The pro-carcinogenic effects of LEPR were investigated using murine TNBC cell lines, 4T1 and EMT6, and a tumor-bearing mouse model. Expression levels of LEPR, NADPH oxidase 4 (NOX4), and ADRB2 in TNBC cells and tumor tissues were analyzed via western blot and quantitative real-time polymerase chain reaction. Changes in reactive oxygen species (ROS) levels were assessed using flow cytometry and MitoSox staining, while immunofluorescence double-staining confirmed the co-localization of LEPR and ADRB2. 
		                        		
		                        			Results:
		                        			LEPR activation promoted NOX4-derived ROS and mitochondrial ROS production, facilitating TNBC cell proliferation and migration, effects which were mitigated by the LEPR inhibitor Allo-aca. Co-expression of LEPR and ADRB2 was observed on cell membranes, and bioinformatics data revealed a positive correlation between the two receptors. Leptin activated both LEPR and ADRB2, enhancing intracellular ROS generation and promoting tumor progression, which was effectively countered by a specific ADRB2 inhibitor ICI118551. In vivo, leptin injection accelerated tumor growth and lung metastases without affecting appetite, while treatments with Allo-aca or ICI118551 mitigated these effects. 
		                        		
		                        			Conclusion
		                        			This study demonstrates that leptin stimulates the growth and metastasis of TNBC through the activation of both LEPR and ADRB2, resulting in increased ROS production. These findings highlight LEPR and ADRB2 as potential biomarkers and therapeutic targets in TNBC. 
		                        		
		                        		
		                        		
		                        	
3.Synergistic Activation of LEPR and ADRB2 Induced by Leptin Enhances Reactive Oxygen Specie Generation in Triple-Negative Breast Cancer Cells
Chang LIU ; Jing YU ; Yongjun DU ; Yu XIE ; Xiaofei SONG ; Chang LIU ; Yan YAN ; Yue WANG ; Junfang QIN
Cancer Research and Treatment 2025;57(2):457-477
		                        		
		                        			 Purpose:
		                        			Leptin interacts not only with leptin receptor (LEPR) but also engages with other receptors. While the pro-oncogenic effects of the adrenergic receptor β2 (ADRB2) are well-established, the role of leptin in activating ADRB2 in triple-negative breast cancer (TNBC) remains unclear. 
		                        		
		                        			Materials and Methods:
		                        			The pro-carcinogenic effects of LEPR were investigated using murine TNBC cell lines, 4T1 and EMT6, and a tumor-bearing mouse model. Expression levels of LEPR, NADPH oxidase 4 (NOX4), and ADRB2 in TNBC cells and tumor tissues were analyzed via western blot and quantitative real-time polymerase chain reaction. Changes in reactive oxygen species (ROS) levels were assessed using flow cytometry and MitoSox staining, while immunofluorescence double-staining confirmed the co-localization of LEPR and ADRB2. 
		                        		
		                        			Results:
		                        			LEPR activation promoted NOX4-derived ROS and mitochondrial ROS production, facilitating TNBC cell proliferation and migration, effects which were mitigated by the LEPR inhibitor Allo-aca. Co-expression of LEPR and ADRB2 was observed on cell membranes, and bioinformatics data revealed a positive correlation between the two receptors. Leptin activated both LEPR and ADRB2, enhancing intracellular ROS generation and promoting tumor progression, which was effectively countered by a specific ADRB2 inhibitor ICI118551. In vivo, leptin injection accelerated tumor growth and lung metastases without affecting appetite, while treatments with Allo-aca or ICI118551 mitigated these effects. 
		                        		
		                        			Conclusion
		                        			This study demonstrates that leptin stimulates the growth and metastasis of TNBC through the activation of both LEPR and ADRB2, resulting in increased ROS production. These findings highlight LEPR and ADRB2 as potential biomarkers and therapeutic targets in TNBC. 
		                        		
		                        		
		                        		
		                        	
4.Analysis of the trend of radiological diagnostic examination frequency and the related influencing factors
Yongxian ZHANG ; Yantao NIU ; Tianliang KANG ; Yunfu LIU ; Liping XU ; Lin XU ; Senlin GUO ; Dandan LIU ; Binbin YU ; Junfang XIAN
Chinese Journal of Radiological Medicine and Protection 2024;44(1):29-35
		                        		
		                        			
		                        			Objective:To investigate the trend of radiological diagnostic examination frequency and the related influencing factors in a general hospital in recent four years.Methods:The hospital information system and the radiology information system were used to collect the information on the numbers of the outpatients, the emergency patients, and the inpatients and the radiology examination information from 2019 to 2022. The examination frequency and proportion of various imaging equipment were counted by using the perspective table of data, and the examination items and the proportion of the radiological diagnostic examinations were calculated. The positive rates of the radiological examinations were measured from 2019 to 2022. The gender and age distribution of the patients were analyzed. Spearman correlation analysis was used to analyze the relationships between the numbers of the patients undergoing radiological examinations and the numbers of the outpatients, emergency patients and the inpatients.Results:The annual frequency of radiological diagnostic examinations from 2019 to 2022 were 307 306, 245 418, 317 250 and 325 625, respectively, with a total of 1 195 599. Among them, the proportions of CT, X-rays, bedside X-rays, bone density, gastrointestinal imaging and mammography were 59.74%, 38.04%, 1.39%, 0.42%, 0.21% and 0.19%, respectively. In each year, the proportion of CT in all radiological diagnostic examinations was 49.58%, 63.40%, 60.40% and 65.20%, respectively. The frequency of emergency CT and emergency chest CT was correlated with the number of emergency patients( r =0.63, 0.61, P<0.05), and the frequency of non-emergency CT was correlated with the number of outpatients and inpatients ( r =0.61, 0.66, P<0.05). The positive rates of the CT examinations were higher than 80% except the lowest of 79.95% in 2021. Conclusions:Radiological examinations especially CT examinations have increased significantly, and played an important role in the diagnosis of diseases. However, attention should be paid to the Justification of the CT examinations. Timely statistical analysis of radiological examination information can provide data supports and references for scientific management of radiological examinations.
		                        		
		                        		
		                        		
		                        	
5.Effect of short-chain fatty acids on microglial synapse engulfment in aged rats with postoperative cognitive dysfunction
Xiang LIU ; Menglin LIU ; Xiaona TAN ; Yaozong YU ; Junfang NIU ; Qiujun WANG
Chinese Journal of Anesthesiology 2024;44(8):958-962
		                        		
		                        			
		                        			Objective:To evaluate the effect of short-chain fatty acids on microglial synapse engulfment in aged rats with postoperative cognitive dysfunction (POCD).Methods:Forty-eight healthy male Sprague-Dawley rats, aged 18 months, weighing 520-650 g, were divided into 4 groups ( n=12 each) using a random number table method: control group (group C), short-chain fatty acids group (group S), POCD group (group P), and POCD+ short-chain fatty acids group (group PS). Rats received short-chain fatty acids (sodium propionate 25.9 mmol/L, sodium butyrate 40 mmol/L and sodium acetate 67.5 mmol/L) in the free drinking water for 28 days in S and PS groups. On day 29, anesthesia was induced with 4%-5% sevoflurane and maintained with 3% sevoflurane, and the tibial fracture internal fixation was performed to prepare a rat model of POCD in P group and PS group. Morris water maze test was performed at day 7 after surgery. The escape latency, times of crossing the original platform, mean swimming speed and time spent in the original platform quadrant were recorded. The rats were sacrificed at the end of Morris water maze test, and the brains were collected to analyze the number and density of dendritic spines in the hippocampal CA1 region (by Golgi staining) and to determine the expression of postsynaptic density 95 (PSD95) and complement 1q (C1q) in the hippocampal CA1 region (by immunofluorescence). Results:Compared with group C, the times of crossing the original platform were significantly decreased, the time spent in the original platform quadrant was shortened, the escape latency was prolonged, the number and density of dendritic spines and the number of intersection points between dendrites and concentric circles were decreased, the expression of PSD95 was down-regulated, and the expression of C1q was up-regulated in P and PS groups ( P<0.05). Compared with group P, the times of crossing the original platform were significantly increased, the time spent in the original platform quadrant was prolonged, the escape latency was shortened, the number and density of dendritic spines and the number of intersection points between dendrites and concentric circles were increased, the expression of PSD-95 was up-regulated, and the expression of C1q was down-regulated in group PS ( P<0.05). Conclusions:The mechanism by which short-chain fatty acids attenuates POCD is related to decreased microglial engulfment of synapses in aged rats.
		                        		
		                        		
		                        		
		                        	
6.Mid-term Efficacy of Autologous Hamstring Tendon Implantation in the Treatment of Severe Anterior Vaginal Wall Prolapse
Ying YAO ; Yiting WANG ; Junfang YANG ; Yiqi GUAN ; Yu MEI ; Jingsong HAN ; Kun ZHANG
Chinese Journal of Minimally Invasive Surgery 2024;24(4):271-277
		                        		
		                        			
		                        			Objective To explore the safety and mid-term efficacy of autologous hamstring tendon implantation in the treatment of severe anterior vaginal wall prolapse.Methods We performed a prospective single arm clinical study.From May 2021,pelvic organ prolapse(POP)patients with severe anterior vaginal wall prolapse as the main cause who had symptoms and required surgical treatment were included.The patient was fully informed and voluntarily selected autologous hamstring tendon implantation and high sacral ligament suspension.Postoperative follow-ups were carried out on the Pelvic Organ Prolapse Quantification(POP-Q),Pelvic Floor Distress Inventory-Short Form 20(PFDI-20),postoperative satisfaction score,and Patient Global Impression of Improvement(PGI-I).Function of the lower limb on the tendon removal side,as well as postoperative complications and re-operations were recorded.Results The operation time of tendon removal was(19.7±8.3)min,the operation time of pelvic floor was(122.1±37.8)min,the median intraoperative bleeding volume was 70 ml(range,50-400 ml),and there was no intraoperative co-morbidity or postoperative fever.A total of 12 cases were followed up for(26.4±2.5)months.The measured values of Aa,Ba,and C were 3(-1-3),5(2-10),and 4(-1-10)before operation and-3(-3-3),-3(-3-3),and-6(-6-3)at 24 months after operation,respectively,with significant difference(P<0.05).The PFDI-20 scores of the 12 patients before surgery and at 24 months after surgery were 88.0 points(range,16.7-204.2 points)and 8.3 points(range,0-32.3 points),respectively,with significant difference(Z=-2.803,P=0.005).The PGI-I questionnaire showed 11 patients with significant improvement in postoperative symptoms and 1 patient with improvement.The satisfaction scores at 6 and 24 months after surgery were(4.8±0.4)points and(4.6±0.7)points,respectively.One patient experienced vaginal prolapse at 12 months after surgery,with a Ⅲ degree prolapse of the anterior wall and vaginal vault,the recurrence rate being 8.3%(1/12).Two patients had pulmonary embolism at 9 d and 2 weeks after surgery,with Clavien-Dindo Ⅱ and Ⅲ grades,and recovered after outpatient and hospitalization treatment.One patient was found fascia exposure at the vagina,and had improvement with medication treatment.All the patients had good wound healing at the tendon removal site,with normal muscle strength and lower limb activity.No re-operation was required due to recurrence or complications of tendon surgery.Conclusions Autologous hamstring tendon implantation is safe in the treatment of severe anterior vaginal wall prolapse with satisfactory mid-term efficacy.Before surgery,it is necessary to educate patients on lower limb exercise to prevent complications of venous thrombosis.
		                        		
		                        		
		                        		
		                        	
7.Clinical implementation of iterative cone-beam computed tomography guided online adaptive radiotherapy for the pelvic malignancies
Guangyu WANG ; Junfang YAN ; Zhiqun WANG ; Yu ZHANG ; Yuliang SUN ; Zheng ZENG ; Xiansong SUN ; Wenbo LI ; Bo YANG ; Fuquan ZHANG
Chinese Journal of Radiation Oncology 2023;32(6):526-532
		                        		
		                        			
		                        			Objective:To evaluate the clinical application of online adaptive radiotherapy based on iterative cone-beam computed tomography (iCBCT) for the pelvic malignancies.Methods:This was a prospective clinical trial of iCBCT guided online adaptive radiotherapy for pelvic malignancies in Department of Radiation Oncology, Peking Union Medical College Hospital. Clinical data of 13 patients with pelvic malignancies who received online adaptive radiotherapy from August to November, 2022 were preliminarily analyzed (2 cases of cervical cancer, 4 postoperative cervical cancer, 3 postoperative endometrial cancer, 3 bladder cancer and 1 prostate cancer). The feasibility of online adaptive radiotherapy, adaptive radiotherapy time, the frequency and magnitude of edits for organs at risk and target volume, target volume coverage and organs at risk doses were analyzed. Statistical analysis was performed by SPSS software. Data conforming to normal distribution were described by Mean±SD, and data with non-normal distribution were expressed by M ( Q1, Q3). Data with homogeneous variances were analyzed by t-test, and data with non-normal distribution or heterogeneous variances were analyzed by nonparametric test. Results:The average adaptive time was 15 min and 38 s (from acceptance of acquired CBCT scan to completion of the final plan selection). 85.4% (830/972 fractions) of influencer structures (system-defined organs adjacent to and with high impact on the generation of clinical target volume and planning target volume, primarily bladder, rectum and small intestine in pelvic neoplasms) automatically generated by artificial intelligence required no edits or minor editors, and 89.8% (491/547 fractions) of clinical target volume automatically generated by artificial intelligence required no edits or minor editors. The adapted plan was adopted in 98.5% (319/324 fractions) of radiotherapy fractions. Compared with the scheduled plan, the adapted plan showed better target volume coverage and reduced the dose of organs at risk.Conclusions:iCBCT guided online adaptive radiotherapy for the pelvic malignancies can be achieved within clinically acceptable timeslots. In addtion, better dose coverage of target volume shows the advantages of online adaptive radiotherapy.
		                        		
		                        		
		                        		
		                        	
8.Influence of CT scanning mode on the variability of radiation dose measurements of superficial organs
Yongxian ZHANG ; Yantao NIU ; Senlin GUO ; Dandan LIU ; Binbin YU ; Tianliang KANG ; Junfang XIAN
Chinese Journal of Radiological Medicine and Protection 2021;41(12):956-960
		                        		
		                        			
		                        			Objective:To investigate the uncertainty of the dose measurements of superficial organs and the image noise in CT scanning.Methods:GE Revolution CT was used to perform 20 repeated scans on the isolated skull specimen in sequential and helical mode. The chest phantom was scanned for 45 times with the pitch 1.0 and the collimation 80 mm for two scanners (GE Revolution CT, Philips Brilliance iCT) and 40 mm for the Siemens Somatom Definition Flash CT. The volume CT dose index (CTDI vol) was maintained during the above scannings. A dosimeter was used to measure the dose at the position of the right eye lens of the specimen and the center of right breast of the chest phantom. The position of dosimeter sensor remained unchanged. The standard deviation of CT values (image noise) in the air region of cross-sectional images at the center of the sensor reconstructed with lung/soft tissue algorithms were measured. The mean values ( Av), standard deviations ( SD), coefficients of variation ( CV) and relative ranges ( RR) of the dosimetric values and the standard deviations of CT values of 3, 5, 10, 20, 30 and 45 scans were calculated. Pearson and Spearman correlation analysis were used to evaluate the correlation between the dosimetric values and the standard deviations of CT values. Results:The measured dosimetric values of the skull specimen were almost unchanged in the sequential scannings. The relative range of dose in helical mode was 10.67%. The relative ranges of the measured values of the three CT scanners for 45 scans reached 43.83%, 25.31%, and 14.32%. The standard deviations of CT values of the lung/soft tissue images varied greatly and the differences were not completely related to the dosimetric values.Conclusions:The dosimetric values of superficial organs were stable in the sequential scanning mode. The dose measurements of superficial organs and the image noise changed greatly in helical scanning mode.
		                        		
		                        		
		                        		
		                        	
9.Research progress on postoperative application of vaginal brachytherapy in patients with early endometrial carcinoma
Xue QIN ; Junfang YAN ; Bo YANG ; Xiaorong HOU ; Lang YU ; Jie QIU
Chinese Journal of Radiation Oncology 2021;30(10):1089-1093
		                        		
		                        			
		                        			Radiation therapy plays an important role in the adjuvant treatment of patients with early endometrial carcinoma. Vaginal stump is a common site of disease failure for early endometrial carcinoma patients with intermediate-high risk factors for recurrence. Compared with external beam radiotherapy, vaginal brachytherapy (VBT) can achieve comparable local control rate with fewer toxicities. In this article, research progresses upon the application of VBT in patients with early endometrial carcinoma after hysterectomy were investigated from multiple perspectives of the selection of patients, the selection of vaginal applicator, factors influencing dose distribution, image-guided adaptive brachytherapy, the design and implementation of radiotherapy regime. In addition, the application of intensity-modulated VBT and the usage of novel quality assurance equipment were also discussed.
		                        		
		                        		
		                        		
		                        	
10.The CT findings of ossification in sinonasal inverted papilloma and its comparison with the originating site determined during surgery
Wenling YU ; Zhaohui LIU ; Shuling LI ; Yingshi PIAO ; Chengshuo WANG ; Junfang XIAN
Chinese Journal of Radiology 2021;55(6):633-637
		                        		
		                        			
		                        			Objective:To evaluate the CT characteristics of ossifying foci in sinonasal inverted papilloma (IP) and to compare with the tumor root shown intraoperatively.Methods:The clinical and CT imaging data of 127 patients with IP, which were proved by histopathology, were reviewed retrospectively from Beijing Tongren Hospital, Capital Medical University, during the period from January 2012 to December 2018. The number, location, shape, density of ossifying foci in sinonasal IP and the relationship with the wall of sinus were observed. The sites of ossification on CT scans were compared with the root of the tumors described in the corresponding patient′s operative records.Results:In 127 IP patients, 51 (40.2%) patients showed the ossification in the tumor on CT. Single ossifying foci were found in 35 cases and multiple in 16 cases. The ossification affected single site of the sinonasal tract ( n=16) or distributed diffusely ( n=35). In the 50 cases, the ossifying foci extended along the long axis of the affected sinus appearing as branched ( n=19), striped ( n=16), linear ( n=7), lumpy ( n=2) or mixed type ( n=6), and 1 case was located at the edge of the maxillary sinus. Totally 66.7% (34/51) of the ossifying focis contained peripherally hyperdense bone tissue and centrally hypodense adipose tissue, which corresponded to bone cortices and fatty marrow of the trabecular bone. And 96.1% (49/51) of the ossifying focis were attached to the adjacent bone of the sinus, and the sites of attachment were concordant with the actual origin of tumor confirmed in operation . Conclusions:Ossification can be seen in some sinonasal IPs. Tracing along ossifying focus to the site of attachment with sinus might facilitate preoperative prediction of the originating site of tumor.
		                        		
		                        		
		                        		
		                        	
            
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