1.Pancreatic cancer neuroecology: Current status, mechanisms, and prospect from multi-dimensional perspectives
Shangyou ZHENG ; Honghui JIANG ; Chonghui HU ; Tingting LI ; Tianhao HUANG ; Rihua HE ; Yong JIANG ; Rufu CHEN
Journal of Clinical Hepatology 2025;41(4):611-618
		                        		
		                        			
		                        			Pancreatic cancer is characterized by nerve invasion and a high mortality rate, and its pathological process depends on the complex interaction network between tumor and the nervous system. Based on the concept of “pancreatic cancer neuroecology”, this article analyzes the mechanism of action of peripheral motor nerve, sensory nerve, and central nerve in tumorigenesis, pain regulation, and cachexia formation and emphasizes the synergistic regulatory role of immune cells, Schwann cells, and extracellular matrix in the microenvironment of perineural invasion. At the same time, this article further elaborates on the metabolic interaction and chemotaxis between neuraxis and tumor, the effect on promoting chemotherapy resistance, and the dynamic relationship between neuroplasticity and tumor adaptability. In clinical practice, this article summarizes the key value of perineural invasion in prognostic evaluation, preoperative evaluation, and the selection of surgical strategy. In addition, this article reviews the basic research advances in the biomarkers and potential targets associated with perineural invasion in pancreatic cancer and points out the limitations of current model and transformation research. In the future, systematically analyzing the nerve-tumor-immune network and targeting its key nodes may provide multi-dimensional strategies and new breakthroughs for the precise intervention of pancreatic cancer, the reversal of drug resistance, and the relief of symptoms. 
		                        		
		                        		
		                        		
		                        	
2.Exogenous leptin improves cerebral ischemia-reperfusion-induced glutamate excitotoxic injury in mice by up-regulating GLT-1 and GLAST expression in astrocytes
Jie CHEN ; Chenxu LIU ; Chun WANG ; Li LI ; Weiting TAO ; Jingru XUN ; Honghui TANG ; Li HUANG
Journal of Southern Medical University 2024;44(6):1079-1087
		                        		
		                        			
		                        			Objective To investigate the protective effect of exogenous leptin against focal cerebral ischemia-reperfusion(I/R)injury in mice and explore the underlying mechanism.Methods A total of 100 C57BL/6 mice were randomly divided into 5 groups,including a sham-operated group,cerebral I/R model group,and 3 leptin treatment groups with intraperitoneal injections of 0.5,1.0 or 2.0 leptin immediately after occlusion of the internal carotid artery.At 24 h after reperfusion,neurological function scores of the mice were assessed,and TTC staining was used to determine the area of cerebral infarction.The pathological changes in the cortical brain tissue of the mice were observed using HE staining,and degenerative damage of the cortical neurons were assessed with Fluoro-Jade C staining.The expression of glial fibrillary acidic protein in cortical brain tissues was detected using immunohistochemistry and Western blotting.In another 45 C57BL/6 mice with sham operation,I/R modeling,or leptin(1 mg/kg)treatment,glutamic acid in the cortical brain tissue was detected using glutamate assay,and cortical glutamate-aspartate transporter(GLAST)and glutamate transporter-1(GLT-1)protein expressions were detected using immunohistochemistry.Results Compared with the I/R model mice,the leptin-treated mice had significantly lower neurological deficit scores,smaller cerebral infarct area,milder pathologies in the cortical brain tissue,and lessened cortical neuronal damage with normal morphology and less excessive proliferation of the astrocytes.Leptin treatment significantly up-regulated the expressions of GLT-1 and GLAST and lowered the content of glutamic acid in the brain tissue of the I/R mice.Conclusion Exogenous leptin has obvious neuroprotective effect against cerebral I/R injury in mice,mediated probably by controlling excessive astrocyte proliferation and up-regulating cortical GLT-1 and GLAST expressions to reduce glutamate-mediated excitotoxic injury of the astrocytes.
		                        		
		                        		
		                        		
		                        	
3.Concomitant extragenital malformations of female reproductive tract anomalies: analysis of 444 cases in Peking Union Medical College Hospital
Si SU ; Xinmiao BAO ; Shu WANG ; Na CHEN ; Zhufeng LIU ; Dawei SUN ; Jinhua LENG ; Qingbo FAN ; Honghui SHI ; Zhijing SUN ; Juan CHEN ; Haiyuan LIU ; Xin YU ; Junji ZHANG ; Yi DAI ; Jinghe LANG ; Lan ZHU
Chinese Journal of Obstetrics and Gynecology 2024;59(5):346-352
		                        		
		                        			
		                        			Objective:To analyze the incidence and clinical phenotype of the concomitant extragenital malformations in the patients with female reproductive tract anomalies.Methods:A retrospective study was conducted using clinical data of hospitalized patients diagnosed with uterine, cervical, or vaginal malformations from January 2003 to December 2022 in Peking Union Medical College Hospital. The malformations were classified according to American Society for Reproductive Medicine müllerian anomalies classification 2021, and in each type, the incidence and specific manifestations of concomitant extragnital malformations were analyzed.Results:A total of 444 patients were included. The overall incidence of concomitant extragenital malformations was 43.5% (193/444), including urinary system, skeletal system, and other system malformations. Renal malformations on the obstructed side were present in all patients with oblique vaginal septum syndrome (100.0%, 78/78). The total incidence of concomitant extragnital malformations was as high as 8/11 in uterus didelphys, 43.5% (10/23) in unicornuate uterus, 33.6% (79/235) in Mayer-Rokitansky-Küster-Hauser syndrome, 18.8% (6/32) in septate uterus and 18.5% (12/65) in cervical agenesis. Urinary system malformations (30.6%, 136/444) and skeletal system malformations (13.5%, 60/444) were the most common concomitant malformations in all types, in which, unilateral renal agenesis and scoliosis were the most common.Conclusions:Urinary and skeletal system malformations are important features of female reproductive tract anomalies. Urologic ultrasonography and spinal roentgenogram are recommended for all patients with female reproductive tract anomalies.
		                        		
		                        		
		                        		
		                        	
4.Construction of risk prognosis model for malignant pleural mesothelioma based on ferroptosis gene and study on tumor immune microenvironment
Zilin CHEN ; Sihai YANG ; Honghui MA ; Yongyi WANG ; Xiaoying YE ; Haoyu HUANG ; Wenqian WANG
Chinese Journal of Immunology 2024;40(5):961-969
		                        		
		                        			
		                        			Objective:To screen ferroptosis genes related to prognosis of malignant pleural mesothelioma(MPM),explore the relationship between ferroptosis and tumor immune microenvironment and provide a new perspective for targeting and immunotherapy of MPM patients.Methods:The differentially expressed genes(DEGs)in MPM tumor group and normal group were analyzed in GEO database;intersection of DEGs and ferroptosis genes to obtain differentially expressed ferroptosis-related genes(DE-FRGs).GO,KEGG function enrichment and protein protein interaction(PPI)were used to identify the signal pathways mainly involved by DE-FRGs.The prognosis related ferroptosis genes were identified by univariate COX analysis.LASSO regression analysis was used to screen the best DE-FRGs for establishing the risk prediction model,and a risk prognosis model based on the best DE-FRGs was estab-lished by multivariate cox analysis to verify the prediction effect of the model.Finally,CIBERSORT and other algorithms were used to analyze tumor immune cell infiltration and evaluate immune microenvironment.Results:Twenty-four prognosis related DE-FRGs were screened,which were mainly concentrated in ferroptosis,transcriptional regulation and response to inorganic substances.A MPM risk prediction model based on five ferroptosis-related genes(ALDH3A2,CAV1,HRAS,CDCA3 and RRM2)was established and vali-dated.In the model,the proportion of CD8+T cells and macrophages in high-risk group were higher,while the proportion of B lympho-cytes was lower.In addition,PD-1,CTLA-4 and their ligands at immune checkpoint had higher expression status in high-risk group.Conclusion:The MPM risk prediction model based on five ferroptosis-related genes is established,and the immune status in the model is clarified.It provides a certain research basis for targeting and immunotherapy of MPM.The predictive ability of this model in MPM needs to be further verified in clinical practice to better predict disease stratification and treatment management.
		                        		
		                        		
		                        		
		                        	
5.Investigation on current health literacy among military personnel on plateau and analysis of influencing factors
Peng JIN ; Honghui RONG ; Ling ZHANG ; Chuanfen ZHENG ; Ji'an CHEN
Journal of Army Medical University 2024;46(11):1306-1315
		                        		
		                        			
		                        			Objective To investigate the status quo of health literacy among military personnel stationing on plateau and analyze its influencing factors.Methods National Health Literacy Monitoring Questionnaire(2015),self-made questionnaire for demographic data based on literature,Connor-Davidson Resilience Scale,Simplified Coping Style Questionnaire,and Positive and Negative Affect Scale were employed to survey 2 516 officers and soldiers stationing on plateau with aid of a WeChat APP Questionnaire Star.Their current status of health literacy and its influencing factors were analyzed.Results The survey results showed that the overall health literacy level was 20.03%among the 2 516 participants.The literacy levels of basic knowledge and concepts,healthy lifestyles and behaviors,and health skills were 31.08%,26.23%,and 26.63%,respectively,and the health literacy levels of scientific health concepts,infectious disease prevention and treatment,chronic disease prevention and treatment,safety and first aid,basic medical care,and health information were 40.58%,19.36%,9.62%,82.75%,29.61%,and 45.03%,respectively.Multivariate unconditional logistic regression analysis indicated that the influencing factors of health literacy level were years of working(OR=1.857,95%CI:1.391~2.479;OR=4.657,95%CI:3.297~6.578),ethnicity(OR=0.394,95%CI:0.251~0.620),marriage(OR=0.609,95%CI:0.430~0.861),only-child family(OR=0.759,95%CI:0.585~0.985),home location(OR=0.545,95%CI:0.359~0.827),smoking(OR=1.579,95%CI:1.254~1.988),education level(OR=3.638,95%CI:1.500~8.822),weekly online game time(OR=0.517,95%CI:0.365~0.731;OR=0.351,95%CI:0.172~0.716),number of physical checkups per year(OR=3.251,95%CI:1.359~7.778;OR=4.545,95%CI:1.841~11.221),father's occupation(OR=5.185,95%CI:1.800~14.933;OR=3.229,95%CI:1.261~8.270),mother's occupation(OR=0.221,95%CI:0.086~0.568;OR=0.218,95%CI:0.081~0.587;OR=0.046,95%CI:0.018~0.118),positive coping(OR=1.052,95%CI:1.033~1.072),and negative coping(OR=0.950,95%CI:0.929~0.972).Conclusion The overall health literacy level is quite low among the plateau military personnel in this ministry,and the relevant departments should actively explore effective interventions to comprehensively improve their health literacy based on the influencing factors.
		                        		
		                        		
		                        		
		                        	
6.Exogenous leptin improves cerebral ischemia-reperfusion-induced glutamate excitotoxic injury in mice by up-regulating GLT-1 and GLAST expression in astrocytes
Jie CHEN ; Chenxu LIU ; Chun WANG ; Li LI ; Weiting TAO ; Jingru XUN ; Honghui TANG ; Li HUANG
Journal of Southern Medical University 2024;44(6):1079-1087
		                        		
		                        			
		                        			Objective To investigate the protective effect of exogenous leptin against focal cerebral ischemia-reperfusion(I/R)injury in mice and explore the underlying mechanism.Methods A total of 100 C57BL/6 mice were randomly divided into 5 groups,including a sham-operated group,cerebral I/R model group,and 3 leptin treatment groups with intraperitoneal injections of 0.5,1.0 or 2.0 leptin immediately after occlusion of the internal carotid artery.At 24 h after reperfusion,neurological function scores of the mice were assessed,and TTC staining was used to determine the area of cerebral infarction.The pathological changes in the cortical brain tissue of the mice were observed using HE staining,and degenerative damage of the cortical neurons were assessed with Fluoro-Jade C staining.The expression of glial fibrillary acidic protein in cortical brain tissues was detected using immunohistochemistry and Western blotting.In another 45 C57BL/6 mice with sham operation,I/R modeling,or leptin(1 mg/kg)treatment,glutamic acid in the cortical brain tissue was detected using glutamate assay,and cortical glutamate-aspartate transporter(GLAST)and glutamate transporter-1(GLT-1)protein expressions were detected using immunohistochemistry.Results Compared with the I/R model mice,the leptin-treated mice had significantly lower neurological deficit scores,smaller cerebral infarct area,milder pathologies in the cortical brain tissue,and lessened cortical neuronal damage with normal morphology and less excessive proliferation of the astrocytes.Leptin treatment significantly up-regulated the expressions of GLT-1 and GLAST and lowered the content of glutamic acid in the brain tissue of the I/R mice.Conclusion Exogenous leptin has obvious neuroprotective effect against cerebral I/R injury in mice,mediated probably by controlling excessive astrocyte proliferation and up-regulating cortical GLT-1 and GLAST expressions to reduce glutamate-mediated excitotoxic injury of the astrocytes.
		                        		
		                        		
		                        		
		                        	
8.Musculoskeletal multibody dynamics investigation for the different medial-lateral installation position of the femoral component in unicompartmental knee arthroplasty.
Jiaxuan REN ; Zhenxian CHEN ; Jing ZHANG ; Yongchang GAO ; Feng QIAO ; Zhongmin JIN
Journal of Biomedical Engineering 2023;40(3):508-514
		                        		
		                        			
		                        			The surgical installation accuracy of the components in unicompartmental knee arthroplasty (UKA) is an important factor affecting the joint function and the implant life. Taking the ratio of the medial-lateral position of the femoral component relative to the tibial insert (a/A) as a parameter, and considering nine installation conditions of the femoral component, this study established the musculoskeletal multibody dynamics models of UKA to simulate the patients' walking gait, and investigated the influences of the medial-lateral installation positions of the femoral component in UKA on the contact force, joint motion and ligament force of the knee joint. The results showed that, with the increase of a/A ratio, the medial contact force of the UKA implant was decreased and the lateral contact force of the cartilage was increased; the varus rotation, external rotation and posterior translation of the knee joint were increased; and the anterior cruciate ligament force, posterior cruciate ligament force and medial collateral ligament force were decreased. The medial-lateral installation positions of the femoral component in UKA had little effect on knee flexion-extension movement and lateral collateral ligament force. When the a/A ratio was less than or equalled to 0.375, the femoral component collided with the tibia. In order to prevent the overload on the medial implant and lateral cartilage, the excessive ligament force, and the collision between the femoral component and the tibia, it is suggested that the a/A ratio should be controlled within the range of 0.427-0.688 when the femoral component is installed in UKA. This study provides a reference for the accurate installation of the femoral component in UKA.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Arthroplasty, Replacement, Knee
		                        			;
		                        		
		                        			Knee Joint/surgery*
		                        			;
		                        		
		                        			Knee Prosthesis
		                        			;
		                        		
		                        			Gait
		                        			;
		                        		
		                        			Rotation
		                        			
		                        		
		                        	
9.Effect of prosthetic joint line installation height errors on insert wear in unicompartmental knee arthroplasty.
Shoulin XIONG ; Yafei QU ; Jiaxuan REN ; Jing ZHANG ; Hui LI ; Zhenxian CHEN
Journal of Biomedical Engineering 2023;40(6):1192-1199
		                        		
		                        			
		                        			The clinical performance and failure issues are significantly influenced by prosthetic malposition in unicompartmental knee arthroplasty (UKA). Uncertainty exists about the impact of the prosthetic joint line height in UKA on tibial insert wear. In this study, we combined the UKA musculoskeletal multibody dynamics model, finite element model and wear model to investigate the effects of seven joint line height cases of fixed UKA implant on postoperative insert contact mechanics, cumulative sliding distance, linear wear depth and volumetric wear. As the elevation of the joint line height in UKA, the medial contact force and the joint anterior-posterior translation during swing phase were increased, and further the maximum von Mises stress, contact stress, linear wear depth, cumulative sliding distance, and the volumetric wear also were increased. Furthermore, the wear area of the insert gradually shifted from the middle region to the rear. Compared to 0 mm joint line height, the maximum linear wear depth and volumetric wear were decreased by 7.9% and 6.8% at -2 mm joint line height, and by 23.7% and 20.6% at -6 mm joint line height, the maximum linear wear depth and volumetric wear increased by 10.7% and 5.9% at +2 mm joint line height, and by 24.1% and 35.7% at +6 mm joint line height, respectively. UKA prosthetic joint line installation errors can significantly affect the wear life of the polyethylene inserted articular surfaces. Therefore, it is conservatively recommended that clinicians limit intraoperative UKA joint line height errors to -2-+2 mm.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Arthroplasty, Replacement, Knee
		                        			;
		                        		
		                        			Knee Joint
		                        			;
		                        		
		                        			Knee Prosthesis
		                        			;
		                        		
		                        			Mechanical Phenomena
		                        			;
		                        		
		                        			Polyethylene
		                        			;
		                        		
		                        			Osteoarthritis, Knee/surgery*
		                        			;
		                        		
		                        			Tibia/surgery*
		                        			;
		                        		
		                        			Biomechanical Phenomena
		                        			
		                        		
		                        	
10.Clinical analysis and curative effect of reactivation of retinopathy of prematurity after intravitreous injection of ranibizumab
Fengxia LAN ; Guoming ZHANG ; Honghui HE ; Ruyin TIAN ; Yi CHEN ; Xianlu ZENG ; Miaohong CHEN
Chinese Journal of Ocular Fundus Diseases 2023;39(6):471-475
		                        		
		                        			
		                        			Objective:To observe the clinical characteristics and therapeutic effect of reactivation of retinopathy of prematurity (ROP) patients after intravitreal injection of ranibizumab (IVR).Methods:A retrospective case series study. Eleven children with ROP (21 eyes) who were reactivated after IVR in Shenzhen Eye Hospital from January 2019 to October 2021 were included in the study. Among them, there were 6 males (11 eyes) and 5 females (10 eyes), with the gestational age of (27.6±2.2) weeks and birth weight of (1 034.6±306.5) g. At the first IVR treatment, 14 eyes (63.7%, 14/22) had acute ROP (AROP), 8 eyes (36.3%, 8/22) had threshold lesions. Post-reactivation treatments include IVR, retinal laser photocoagulation (LP), or minimally invasive vitrectomy (MIVS). The follow-up time after treatment was 12 to 18 months. Birth gestational age, birth weight, treatment method, corrected gestational age at treatment, lesion stage before and after treatment, lesion reactivation and regression time were recorded. The clinical characteristics and efficacy were observed and analyzed.Results:The time from initial IVR treatment to reactivation was (8.2±3.5) weeks. The corrected gestational age of the child was (43.62±4.08) weeks. In 21 eyes, AROP, threshold lesion, prethreshold lesion, and stage 4 lesion were in 2, 4, 12, and 3 eyes, respectively. The patients were treated with IVR, LP, IVR+LP, IVR+MIVS in 2, 13, 4 and 2 eyes, respectively. After the first reactivation treatment, the time of regression and stability was (8.4±4.9) weeks after treatment. There were 5 eyes with secondary reactivation of the lesion, and the lesion stages were stage 3, stage 4a and stage 5 in 2, 1 and 2 eyes, respectively. The mean reactivation time was (19.3±6.0) weeks after the last treatment. The patients in stage 3, stage 4a and stage 5 were treated with LP, LP+MIVS and IVR, respecitively, and the lesions subsided steadily during follow-up. At the last follow-up, 19 out of 21 eyes showed complete regression of the lesions, stable photocoagulation, regression of crista-like lesions, no additional lesions, and retinal leveling. All retinal detachment was "funnel-shaped" in 2 eyes.Conclusions:The lesion reactivation of AROP after IVR treatment is more common. The early reactivation rate is higher after treatment. There is a possibility of reactivation twice after re-treatment.
		                        		
		                        		
		                        		
		                        	
            
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