1.The IL-33/ST2 Axis Protects Retinal Ganglion Cells by Modulating the Astrocyte Response After Optic Nerve Injury.
Zhigang QIAN ; Mengya JIAO ; Na ZHANG ; Xuhuan TANG ; Shiwang LIU ; Feng ZHANG ; Chenchen WANG ; Fang ZHENG
Neuroscience Bulletin 2025;41(1):61-76
IL-33 and its receptor ST2 play crucial roles in tissue repair and homeostasis. However, their involvement in optic neuropathy due to trauma and glaucoma remains unclear. Here, we report that IL-33 and ST2 were highly expressed in the mouse optic nerve and retina. Deletion of IL-33 or ST2 exacerbated retinal ganglion cell (RGC) loss, retinal thinning, and nerve fiber degeneration following optic nerve (ON) injury. This heightened retinal neurodegeneration correlated with increased neurotoxic astrocytes in Il33-/- mice. In vitro, rIL-33 mitigated the neurotoxic astrocyte phenotype and reduced the expression of pro-inflammatory factors, thereby alleviating the RGC death induced by neurotoxic astrocyte-conditioned medium in retinal explants. Exogenous IL-33 treatment improved RGC survival in Il33-/- and WT mice after ON injury, but not in ST2-/- mice. Our findings highlight the role of the IL-33/ST2 axis in modulating reactive astrocyte function and providing neuroprotection for RGCs following ON injury.
Animals
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Interleukin-33/genetics*
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Interleukin-1 Receptor-Like 1 Protein/genetics*
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Optic Nerve Injuries/pathology*
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Retinal Ganglion Cells/pathology*
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Astrocytes/pathology*
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Mice
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Mice, Knockout
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Mice, Inbred C57BL
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Neuroprotection/physiology*
2.Arsenic trioxide preconditioning attenuates hepatic ischemia- reperfusion injury in mice: Role of ERK/AKT and autophagy.
Chaoqun WANG ; Hongjun YU ; Shounan LU ; Shanjia KE ; Yanan XU ; Zhigang FENG ; Baolin QIAN ; Miaoyu BAI ; Bing YIN ; Xinglong LI ; Yongliang HUA ; Zhongyu LI ; Dong CHEN ; Bangliang CHEN ; Yongzhi ZHOU ; Shangha PAN ; Yao FU ; Hongchi JIANG ; Dawei WANG ; Yong MA
Chinese Medical Journal 2025;138(22):2993-3003
BACKGROUND:
Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI.
METHODS:
In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy.
RESULTS:
A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent.
CONCLUSION
Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
Animals
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Arsenic Trioxide
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Autophagy/physiology*
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Reperfusion Injury/prevention & control*
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Mice
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Male
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Proto-Oncogene Proteins c-akt/physiology*
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Arsenicals/therapeutic use*
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Oxides/therapeutic use*
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Liver/metabolism*
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Extracellular Signal-Regulated MAP Kinases/metabolism*
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Mice, Inbred C57BL
3.Mutation types of CYP3A enzymes and sex differences in sufentanil metabolism
Ying JIANG ; Zhigang QIN ; Liyuan FENG ; Guanlei LIU ; Jieyu LI ; Xianzhe LIU ; Yongshuai LI ; Yan CHEN ; Peng LI ; Jianteng GU
Journal of Army Medical University 2025;47(6):581-590
Objective To explore the sex differences in drug metabolism of sufentanil in Chinese patients based on the mutation classification of cytochrome P450 3A(CYP3A)enzymes.Methods According to the possible effects of combined cytochrome P450 3A4 gene*1G locus(CYP3A4*1G)and cytochrome P450 3A5 gene*3 locus(CYP3A5*3)mutation groups on Chinese population,we added different weights to CYP3A4*1G and CYP3A5*3 polymorphisms and classified patients into 3 groups:GroupⅠ,patients carried either the CYP3A4*1G/*1G allele or both CYP3A4*1/*1G allele and CYP3A5*3/*3 allele;Group Ⅱ,patients with both CYP3A4*1/*1G allele and CYP3A5*1/*3 allele;Group Ⅲ,patients with either the CYP3A4*1/*1 allele or both CYP3A4*1/*1G allele and CYP3A5*1/*1 allele.A single-dose,double-blind,stratified random sampling was performed,and 255 patients undergoing endoscopic surgery in the First Affiliated Hospital of Army Medical University were finally subjected.According to the results of genetic testing,an independent statistician,before operation,randomly selected 30 patients from each stratified group to form a study cohort(male-female ratio of 1∶1)and named each group A,B or C.Clinical investigators and subjects kept double-blind to the results of grouping and genetic testing.After entering the operating room,the subjected 90 patients received a single dose of sufentanil followed by collection of blood samples at 10 time points including 2 min before and from 2 to 120 min after administration.After the surgery,we determined the plasma drug concentration,calculated the pharmacokinetic parameters,and compared the metabolic differences between different genders in each group and unblinded the study.Results The cohort best fitted the two-compartment pharmacokinetic model,and groups A,B and C corresponded to group Ⅰ,Ⅱand Ⅲ,respectively.In different patient groups based on mutatron types of CYP3A enzymes the females had lower plasma drug concentration-time curves at each time point,higher systemic clearance(P≤0.01)and smaller area under the plasma concentration-time curve from zero to infinity(P<0.05)when compared with the males.In addition,in group Ⅰ,the elimination rate of central compartment and movement rate of drug from central compartment to peripheral compartment were obviously greater in the females than the males(P<0.05),while the distribution half-life(P<0.05)and elimination half-life(P<0.01)were notably longer in the males than the females.In both group Ⅱ and group Ⅲ,the males obtained larger total area under the plasma concentration-time curve than the females(P<0.05).Conclusion There are sex differences in the drug metabolism of sufentanil in Chinese patients.Women show faster distribution and higher clearance of sufentanil while men present greater drug exposure.Preoperative CYP3A genotyping and intraoperative personalized medication are of great significance to ensure the safety in clinical practice.
4.Construction of a risk prediction model for moderate to severe orthodontic-induced inflammatory root resorption of maxillary incisors based on cone beam CT radiomics and clinical features
Zhigang ZUO ; Tiantian FU ; Xinlan LI ; Bin YIN ; Feng QIAO ; Jiaye LI ; Ligeng WU
Chinese Journal of Stomatology 2025;60(5):509-517
Objective:To develop a risk prediction model for moderate to severe orthodontic-induced inflammatory root resorption (OIIRR) of maxillary incisors based on cone beam CT (CBCT) radiomics features and clinical characteristics of the orthodontic patients.Methods:Clinical and CBCT data from 101 orthodontic patients treated by the same attending orthodontist in the Department of Orthodontics, Stomatology Hospital of Tianjin Medical University from January 2019 to January 2024 were retrospectively collected. The sample included 42 class Ⅰ patients, 52 class Ⅱ patients and 7 class Ⅲ patients [age: (19.7±6.3) years], and a total of 394 maxillary incisors were analyzed. Potential influencing factors for moderate to severe OIIRR (root volume resorption rate≥10%) were collected from the patients′ CBCT and medical records, including initial age, gender, treatment duration, Angle′s classification, extraction or not, type of orthodontic appliance (fixed or clear aligner), changes in root inclination, root movement distance and direction, pre-treatment cephalometric measurements, pre-treatment root-bone relationship, pre-treatment root length, and pre-treatment radiomics features of the teeth. Univariate analysis was initially performed to screen for factors influencing moderate to severe OIIRR. Subsequently, least absolute shrinkage and selection operator (LASSO) regression, best subset regression, and random forest were used for feature selection to construct the OIIRR risk prediction model. The discrimination, calibration, and net benefit of the three risk prediction models were evaluated, and the optimal model was displayed using a nomogram.Results:LASSO regression identified clinical features including initial age (LASSO coefficient 0.052), treatment duration (LASSO coefficient 0.024), pre-treatment root length (LASSO coefficient -0.023), and vertical root movement distance (LASSO coefficient -0.029). Initial age and treatment duration were positively correlated with the severity of OIIRR, while root length and vertical root movement distance were negatively correlated. A total of 14 radiomics features were identified, including 2 original image features and 12 wavelet features. Best subset regression identified vertical root movement distance as the clinical feature and 7 radiomics features, including 1 original image feature and 6 wavelet features. The random forest model identified 8 wavelet features as important predictors, and all of which were radiomics features. Model performance evaluation showed that the random forest model had the highest discrimination, calibration, and net benefit, making it the optimal model, with radiomics features being the most important predictors.Conclusions:Based on the data from this study, radiomics features were identified as the most important predictors by the optimal model for OIIRR risk prediction. Predicting the occurrence of moderate to severe OIIRR before orthodontic treatment held potential clinical application value.
5.Effects of normal body weight and overweight status on metabolism of sufentanil in patients with same CYP3A4/5 genotype:A prospective clinical study
Guanlei LIU ; Ying JIANG ; Bo YANG ; Zhigang QIN ; Liyuan FENG ; Zhengwei XUE ; Fang QIU ; Chunmei CHEN ; Wenzhong ZOU ; Peng LI ; Jianteng GU
Journal of Army Medical University 2025;47(22):2774-2782
Objective To explore the pharmacokinetic characteristics of sufentanil in individuals with normal body mass index(BMI),overweight BMI,and different CYP3A4/5 enzyme genotypes.Methods The patients receiving laparoscopic surgery under general anesthesia in the First Affiliated Hospital of Army Medical University from November 2020 to September 2021 were prospectively recruited in this study.Before the operation,the oral swabs were collected from all the patients for genotyping using the human CYP3A4/5 gene kit.Based on the potential impact of combination of their polymorphisms on sufentanil metabolism and the proportion of different genotype combinations of CYP3A4/5 enzymes,the patients were divided into groups I(3A4 homozygous mutation or 3A4 heterozygous mutation+3A5 homozygous mutation),II(3A4 heterozygous mutation+3A5 heterozygous mutation),and III(3A4 wild type or 3A4 heterozygous mutation+3A5 wild type).According to their BMI,they were also assigned into a normal body weight group(18.5~24.0 kg/m2)and an overweight group(24~<28 kg/m2),and the differences in drug metabolism parameters were statistically analyze between the 2 groups.After routine general anesthesia induction(sufentanil 0.5 μg/kg),venous blood samples were collected to detect the changes in its concentration using high performance liquid chromatography-mass spectrometry(HPLC-MS).The pharmacokinetic data of sufentanil were calculated between the normal BMI group and overweight group in all participants and between the 2 body weight groups among those with different genotype combinations.Results Among the 90 participants completing the blood drug concentration test,8 patients had their blood samples contaminated(including 1 case with an anesthesia duration of<2 h),and 3 were excluded due to low weight or overweight.Eventually,79 participants were included in the pharmacokinetic analysis on the normal body weight group and the overweight group.Compared with the normal body weight group,the central compartment volume of distribution in the overweight group was significantly reduced(P<0.05),while no obvious differences were observed between the 2 groups in terms of peripheral compartment volume of distribution,total clearance rate,peripheral compartment clearance rate,distribution half-life,clearance half-life,and area under the blood concentration-time curve.In group Ⅰ(n=26),the overweight patients(n=13)had significantly reduced central compartment volume of distribution,peripheral compartment volume of distribution,and peripheral compartment clearance rate when compared with the normal body weight patients(n=13)(P<0.05),while no differences were observed in other pharmacokinetic parameters.In groups Ⅱ(n=25)and Ⅲ(n=28),the overweight patients and normal body weight patients had no statistical differences in all pharmacokinetic parameters.Conclusion Among the patients with the same genotype combination of CYP3A4/5 mutations,there was no difference in the metabolism of sufentanil between the overweight and normal weight patients.Additionally,in the population of 3A4 homozygous mutation or 3A4 heterozygous mutation+3A5 homozygous mutation,the overweight patients have smaller peripheral distribution range of sufentanil,and weakened metabolic process.
6.Robot system-assisted versus freehand screw revision for ankylosing spondylitis with lower cervical fractures: a multicenter retrospective study
Shuai LI ; Jiaojiao BAI ; Baorong HE ; Yanzheng GAO ; Wei MEI ; Xinyu LIU ; Yue ZHU ; Qingda LI ; Yukuan LEI ; Lei ZHU ; Zhigang ZHAO ; Yunfei HUANG ; Jinpeng DU ; Mingzhe FENG ; Ningbo CHEN ; Yansheng HUANG ; Xuefang ZHANG ; Zhen CHANG
Chinese Journal of Trauma 2025;41(5):440-448
Objective:To compare the efficacy of robot system-assisted versus freehand screw revision for ankylosing spondylitis (AS) with lower cervical fractures.Methods:A multicenter retrospective cohort study was conducted to analyze the clinical data of 57 patients with AS combined with lower cervical fractures admitted to Honghui Hospital Affiliated to Xi'an Jiaotong University School of Medicine, Henan Provincial People's Hospital, Zhengzhou Orthopedic Hospital, and Qilu Hospital of Shandong University, including 46 males and 11 females, aged 38-77 years [(65.4±9.5)years]. Injury segments involved C 3 in 7 patients, C 4 in 13, C 5 in 25, C 6 in 10, and C 7 in 2. All the patients underwent revision surgery, among whom, 22 patients were treated with robot system-assisted cervical pedicle screw placement (robot nailing group, with 190 screws), and 35 with freehand cervical pedicle screw placement (freehand nailing group, with 300 screws). The operative duration, intraoperative bleeding volume, frequency of intraoperative fluoroscopy, incision length, and length of hospital stay of the two groups were compared; the time of single nscrew insertion, the number of single nail revisions, the distance between screws and the anterior cortex, the accuracy of screw placement of grade 0 and grade 0+1 were recorded in the two groups. The visual analogue scale (VAS), Japanese Orthopedic Society (JOA) score, neck dysfunction index (NDI), American Spine Injury Association (ASIA) classification before operation, at 3 days, 3 months after operation and at the last follow-up were compared between the two groups. The complication rate was also noted. Results:All the patients were followed up for 12-16 months [(14.3±2.1)months]. The operative duration, intraoperative bleeding volume, and frequency of intraoperative fluoroscopy were (186.4±12.9)minutes, (486.1±68.6)ml, and (3.4±1.3)times in the robot nailing group, which were shorter or less than (206.7±14.4)minutes, (660.3±45.2)ml, and (13.5±3.6)times in the freehand nailing group ( P<0.01). The incision length was (9.4±2.4)cm in the robot nailing group, longer than (5.6±1.2)cm in the freehand nailing group ( P<0.01), and the length of hospital stay was (3.7±0.4)days, shorter than (4.4±1.4)days in the freehand nailing group ( P<0.01). The length of single nail insertion, the number of single nail revision, and the distance between the screws and the front cortex were (6.5±0.4)minutes, (1.1±0.1)times, and (3.5±1.3)mm in the robot nailing group, which were shorter or less than (11.6±0.2)minutes, (1.5±0.2)times, and (12.4±4.7)mm in the freehand nailing group ( P<0.01). The accuracy of the screw placement in the robot nailing group was 90.0% (171/190) and 95.8% (182/190) with level 0 and 0+1 screws, better than 80.0% (240/300) and 89.0% (267/300) in the freehand nailing group ( P<0.05). There was no significant difference in VAS, JOA score, NDI, or ASIA grading between the two groups before operation ( P>0.05). The VAS, JOA, and NDI scores at 3 days after operation were (3.1±0.6)points, (12.1±1.2)points, and (15.6±2.9)points, respectively in the robot nailing group, which were better than (5.0±1.4)points, (11.3±1.1)points and (22.5±3.7)points, respectively in the freehand nailing group ( P<0.05). No statistically significant difference was observed in the ASIA grade between the two groups at 3 days after operation ( P>0.05). There were no significant differences in VAS, JOA, NDI scores, or ASIA grading between the two groups at 3 months after operation and at the last follow-up ( P>0.05). Compared with those before operation, the VAS, JOA, NDI scores, and ASIA grading were significantly improved at 3 days, 3 months after operation and at the last follow-up in the two groups, which were further improved with the passage of time. Two patients in the robot nailing group had pneumonia, with a complication rate of 9% (2/22), while 2 patients in the freehand nailing group had dural sac rupture and cerebrospinal fluid leakage and 3 had lung infection after operation, with a complication rate of 14% (5/35) ( P<0.05). Conclusion:Compared with freehand nailing, the robot system-assisted nailing revision for AS with lower cervical fracture has more advantages in terms of the operative duration, length of hospital stay, intraoperative bleeding volume, frequency of intraoperative fluoroscopy nailing speed and accuracy, screw holding force, early pain relief, function restoration, and complication rate, despite longer surgical incision.
7.Comparative efficacy of navigation system and orthopedic robot-assisted nail placement in the treatment of lower cervical fracture and dislocation
Xinnan CHENG ; Shuai LI ; Jiaojiao BAI ; Qingda LI ; Yukuan LEI ; Lei ZHU ; Zhen CHANG ; Zhigang ZHAO ; Yunfei HUANG ; Mingzhe FENG ; Liang YAN ; Hua HUI ; Lingbo KONG ; Baorong HE
Chinese Journal of Trauma 2025;41(2):148-156
Objective:To compare the clinical efficacy of navigation system and orthopedic robot-assisted nail placement in the treatment of lower cervical fracture and dislocation.Methods:A retrospective cohort study was conducted to analyze the clinical data of 49 patients with fracture and dislocation of the lower cervical spine who were admitted to Honghui Hospital, Xi′an Jiaotong University School of Medicine from May 2021 to October 2022, including 38 males and 11 females, aged 29-61 years [(39.3±7.3)years]. Injury segments involved C 3 in 12 patients, C 4 in 11, C 5 in 8, C 6 in 9 and C 7 in 9. Twenty-one patients were treated with S8 navigation system (navigation group, 84 screws), and 28 with TINAVI orthopedic robot (robot group, 112 screws). The two groups were compared in terms of the total surgical duration, single screw placement time, total screw placement time, distance between the screw and the anterior cortex, incision length, intraoperative radiation dose, intraoperative blood loss and length of hospital stay. The height of intervertebral space, Cobb angle, sliding distance between vertebral bodies and American Spinal Injury Association (ASIA) grade were assessed before surgery and at 3 days after surgery. Visual analogue scale (VAS), Japanese Orthopedic Association (JOA) score and neck dysfunction index (NDI) before surgery, at 3 days, 3 months after surgery and at the last follow-up were compared. The accuracy of screw placement, intraoperative invasion rate of adjacent facet joints and rate of postoperative complications (infection, screw loosening, etc.) were evaluated. Results:All the patients were followed up for 12-16 months [(13.6±1.9)months]. In the navigation group, the total surgical duration, distance from the screw to the anterior cortex and the intraoperative radiation dose were (236.2±30.6)minutes, (2.0±0.2)mm and (374.3±90.3)mGy respectively, which were significantly shorter or less than those in the robot group [(278.4±20.7)minutes, (10.6±2.9)mm and (448.4±77.9)mGy] ( P<0.01). The single screw placement time, total screw placement time, incision length and intraoperative blood loss were (3.5±0.4)minutes, (23.9±0.5)minutes, (9.1±2.4)cm and (422.2±30.4)ml respectively, which were significantly longer or more than those in the robot group [(2.6±0.2)minutes, (17.9±0.7)minutes, (6.6±2.6)cm and (360.3±56.3)ml] ( P<0.01). There was no significant difference in the length of hospital stay between the two groups ( P>0.05). No significant differences were observed in the height of the intervertebral space, Cobb angle, sliding distance between the vertebral bodies and ASIA grade between the two groups ( P>0.05). At 3 days after surgery, the height of intervertebral space, Cobb angle, sliding distance between vertebral bodies and ASIA grade in both groups were significantly improved when compared with those before surgery ( P<0.05 or 0.01). There were no significant differences in VAS, JOA scores or NDI between the two groups before surgery, at 3 days, 3 months after surgery and at the last follow-up ( P>0.05). The VAS, JOA scores and NDI in both groups were gradually improved at 3 days, 3 months and at the last follow-up after surgery when compared with those before surgery ( P<0.05). There was no significant difference in the accuracy of screw placement of levels 0 and 0+1 between the two groups ( P>0.05). No significant difference in the intraoperative invasion rate of adjacent facet joints between the two groups was found ( P>0.05). There were no serious complications such as infection or screw loosening after surgery in both groups. Conclusions:For lower cervical fracture and dislocation, although there are more advantages in total surgical duration, screw holding force and radiation control regarding the navigation system, and more outstanding performance in screw placement efficiency, incision length and intraoperative blood loss regarding the orthopedic robot, both of them can effectively rebuild the cervical structure, improve neurological function, relieve postoperative pain, improve screw placement accuracy and reduce facet joint injury and serious complications. Selection of the best auxiliary screw placement system should comprehensively consider patients′ conditions and the experience of the surgical team.
8.Construction of a risk prediction model for moderate to severe orthodontic-induced inflammatory root resorption of maxillary incisors based on cone beam CT radiomics and clinical features
Zhigang ZUO ; Tiantian FU ; Xinlan LI ; Bin YIN ; Feng QIAO ; Jiaye LI ; Ligeng WU
Chinese Journal of Stomatology 2025;60(5):509-517
Objective:To develop a risk prediction model for moderate to severe orthodontic-induced inflammatory root resorption (OIIRR) of maxillary incisors based on cone beam CT (CBCT) radiomics features and clinical characteristics of the orthodontic patients.Methods:Clinical and CBCT data from 101 orthodontic patients treated by the same attending orthodontist in the Department of Orthodontics, Stomatology Hospital of Tianjin Medical University from January 2019 to January 2024 were retrospectively collected. The sample included 42 class Ⅰ patients, 52 class Ⅱ patients and 7 class Ⅲ patients [age: (19.7±6.3) years], and a total of 394 maxillary incisors were analyzed. Potential influencing factors for moderate to severe OIIRR (root volume resorption rate≥10%) were collected from the patients′ CBCT and medical records, including initial age, gender, treatment duration, Angle′s classification, extraction or not, type of orthodontic appliance (fixed or clear aligner), changes in root inclination, root movement distance and direction, pre-treatment cephalometric measurements, pre-treatment root-bone relationship, pre-treatment root length, and pre-treatment radiomics features of the teeth. Univariate analysis was initially performed to screen for factors influencing moderate to severe OIIRR. Subsequently, least absolute shrinkage and selection operator (LASSO) regression, best subset regression, and random forest were used for feature selection to construct the OIIRR risk prediction model. The discrimination, calibration, and net benefit of the three risk prediction models were evaluated, and the optimal model was displayed using a nomogram.Results:LASSO regression identified clinical features including initial age (LASSO coefficient 0.052), treatment duration (LASSO coefficient 0.024), pre-treatment root length (LASSO coefficient -0.023), and vertical root movement distance (LASSO coefficient -0.029). Initial age and treatment duration were positively correlated with the severity of OIIRR, while root length and vertical root movement distance were negatively correlated. A total of 14 radiomics features were identified, including 2 original image features and 12 wavelet features. Best subset regression identified vertical root movement distance as the clinical feature and 7 radiomics features, including 1 original image feature and 6 wavelet features. The random forest model identified 8 wavelet features as important predictors, and all of which were radiomics features. Model performance evaluation showed that the random forest model had the highest discrimination, calibration, and net benefit, making it the optimal model, with radiomics features being the most important predictors.Conclusions:Based on the data from this study, radiomics features were identified as the most important predictors by the optimal model for OIIRR risk prediction. Predicting the occurrence of moderate to severe OIIRR before orthodontic treatment held potential clinical application value.
9.Construction and application of oral squamous cell carcinoma organoid bank
Shang XIE ; Luming WANG ; Xinyuan ZHANG ; Qiushi FENG ; Yangyang XIA ; Ziwei DAI ; Xiaofeng SHAN ; Zhigang CAI
Journal of Peking University(Health Sciences) 2025;57(5):847-851
Oral squamous cell carcinoma(OSCC)accounts for over 90%of oral malignancies,with more than 370 000 new cases and approximately 188 000 deaths annually worldwide.In China,there are roughly 65 000 new cases and 35 000 deaths each year,showing a significant upward trend compared with 2015 statistics.Despite continuous advancements in treatment modalities,the 5-year survival rate remains stagnant at 50%-60%,where tumor heterogeneity and therapy resistance persist as fundamental barriers to precision oncology.To address these critical challenges,this study established a standardized bioban-king protocol for OSCC patient-derived organoids(PDOs)(Patent:Method for constructing an oral squa-mous cell carcinoma organoid bank,ZL202311378598.3).Through groundbreaking optimization of cul-ture media,enzymatic digestion kinetics,and stepwise cryopreservation,we achieved a biobanking suc-cess rate exceeding 95%and pioneered synchronous cultivation of matched primary tumors,lymph node metastases,and adjacent normal mucosa from individual patients,preserving spatial heterogeneity and stromal interactions.Leveraging this platform,we developed high-throughput drug screening:Quantified heterogeneity-driven differential chemoresponse using adenosine triphosphate(ATP)-based viability as-says;We discovered resistance mechanisms:Identified sialylated cancer IgG(SIA-cIgG)-mediated cis-platin resistance(primary/secondary)through PTPN13 suppression,with anti-SIA-cIgG combination therapy demonstrating synergistic efficacy.Besides,we elucidated metastatic drivers:CRISPR-Cas9-edited organoids revealed WDR54 promoted metastasis via H3K4me3/H4K16ac epigenetic reprogramming,activating epithelial-mesenchymal plasticity(EMP)and inducing partial epithelial-mesenchymal transi-tion(pEMT).This"holographic patient-mirroring"platform provided unprecedented resolution for OSCC precision therapy and had been formally incorporated into the Chinese Stomatological Association Techni-cal Guidelines(Technical guideline for establishing patient-derived oral squamous cell carcinoma or-ganoid banks,CHSA 2024-08).Future integration of immune-competent organoids,3D-bioprinted vas-culature,and multi-omics-AI systems will accelerate personalized oncology.These innovations will accelerate clinical translation of personalized therapeutic regimens,ultimately bridging the gap between bench research and bedside application.
10.Robot system-assisted versus freehand screw revision for ankylosing spondylitis with lower cervical fractures: a multicenter retrospective study
Shuai LI ; Jiaojiao BAI ; Baorong HE ; Yanzheng GAO ; Wei MEI ; Xinyu LIU ; Yue ZHU ; Qingda LI ; Yukuan LEI ; Lei ZHU ; Zhigang ZHAO ; Yunfei HUANG ; Jinpeng DU ; Mingzhe FENG ; Ningbo CHEN ; Yansheng HUANG ; Xuefang ZHANG ; Zhen CHANG
Chinese Journal of Trauma 2025;41(5):440-448
Objective:To compare the efficacy of robot system-assisted versus freehand screw revision for ankylosing spondylitis (AS) with lower cervical fractures.Methods:A multicenter retrospective cohort study was conducted to analyze the clinical data of 57 patients with AS combined with lower cervical fractures admitted to Honghui Hospital Affiliated to Xi'an Jiaotong University School of Medicine, Henan Provincial People's Hospital, Zhengzhou Orthopedic Hospital, and Qilu Hospital of Shandong University, including 46 males and 11 females, aged 38-77 years [(65.4±9.5)years]. Injury segments involved C 3 in 7 patients, C 4 in 13, C 5 in 25, C 6 in 10, and C 7 in 2. All the patients underwent revision surgery, among whom, 22 patients were treated with robot system-assisted cervical pedicle screw placement (robot nailing group, with 190 screws), and 35 with freehand cervical pedicle screw placement (freehand nailing group, with 300 screws). The operative duration, intraoperative bleeding volume, frequency of intraoperative fluoroscopy, incision length, and length of hospital stay of the two groups were compared; the time of single nscrew insertion, the number of single nail revisions, the distance between screws and the anterior cortex, the accuracy of screw placement of grade 0 and grade 0+1 were recorded in the two groups. The visual analogue scale (VAS), Japanese Orthopedic Society (JOA) score, neck dysfunction index (NDI), American Spine Injury Association (ASIA) classification before operation, at 3 days, 3 months after operation and at the last follow-up were compared between the two groups. The complication rate was also noted. Results:All the patients were followed up for 12-16 months [(14.3±2.1)months]. The operative duration, intraoperative bleeding volume, and frequency of intraoperative fluoroscopy were (186.4±12.9)minutes, (486.1±68.6)ml, and (3.4±1.3)times in the robot nailing group, which were shorter or less than (206.7±14.4)minutes, (660.3±45.2)ml, and (13.5±3.6)times in the freehand nailing group ( P<0.01). The incision length was (9.4±2.4)cm in the robot nailing group, longer than (5.6±1.2)cm in the freehand nailing group ( P<0.01), and the length of hospital stay was (3.7±0.4)days, shorter than (4.4±1.4)days in the freehand nailing group ( P<0.01). The length of single nail insertion, the number of single nail revision, and the distance between the screws and the front cortex were (6.5±0.4)minutes, (1.1±0.1)times, and (3.5±1.3)mm in the robot nailing group, which were shorter or less than (11.6±0.2)minutes, (1.5±0.2)times, and (12.4±4.7)mm in the freehand nailing group ( P<0.01). The accuracy of the screw placement in the robot nailing group was 90.0% (171/190) and 95.8% (182/190) with level 0 and 0+1 screws, better than 80.0% (240/300) and 89.0% (267/300) in the freehand nailing group ( P<0.05). There was no significant difference in VAS, JOA score, NDI, or ASIA grading between the two groups before operation ( P>0.05). The VAS, JOA, and NDI scores at 3 days after operation were (3.1±0.6)points, (12.1±1.2)points, and (15.6±2.9)points, respectively in the robot nailing group, which were better than (5.0±1.4)points, (11.3±1.1)points and (22.5±3.7)points, respectively in the freehand nailing group ( P<0.05). No statistically significant difference was observed in the ASIA grade between the two groups at 3 days after operation ( P>0.05). There were no significant differences in VAS, JOA, NDI scores, or ASIA grading between the two groups at 3 months after operation and at the last follow-up ( P>0.05). Compared with those before operation, the VAS, JOA, NDI scores, and ASIA grading were significantly improved at 3 days, 3 months after operation and at the last follow-up in the two groups, which were further improved with the passage of time. Two patients in the robot nailing group had pneumonia, with a complication rate of 9% (2/22), while 2 patients in the freehand nailing group had dural sac rupture and cerebrospinal fluid leakage and 3 had lung infection after operation, with a complication rate of 14% (5/35) ( P<0.05). Conclusion:Compared with freehand nailing, the robot system-assisted nailing revision for AS with lower cervical fracture has more advantages in terms of the operative duration, length of hospital stay, intraoperative bleeding volume, frequency of intraoperative fluoroscopy nailing speed and accuracy, screw holding force, early pain relief, function restoration, and complication rate, despite longer surgical incision.

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