1.Effect of Th17-specific Stat3 knockout on anxiety-and depressive-like behaviors in periodontitis mice
Yining ZHOU ; Zhiyun YE ; Huiwen CHEN ; Xinyi XIE ; Wei ZHOU ; Zhongchen SONG
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(7):838-845
Objective·To investigate the effect of Th17 cell-specific Stat3 knockout on anxiety-and depressive-like behaviors.Methods·Mice with specific Stat3 knockout in Th17 cells(Stat3fl/fl;Il17a-CreERT2),named Stat3△Il17a,and wild-type mice(Stat3fl/fl,WT)were generated through the Cre/LoxP system,and Stat3 knockout was induced by intraperitoneal injection of tamoxifen.CD4+T cells were isolated using magnetic-activated cell sorting and induced to differentiate into Th17 cells.Reverse transcription polymerase chain reaction and Western blotting were used to verify Stat3 knockout efficiency.Mice were assigned into 4 groups:WT-C group,Stat3△Il17a-C group,WT-P group,and Stat3△Il17a-P group.The periodontitis model was established in the WT-P group and the Stat3△Il17a-P group by injection of Porphyromonas gingivalis-lipopolysaccharide(P.gingivalis-LPS)into the gingival sulcus.Behavioral tests,including the open field test,elevated zero maze,and forced swimming test,were conducted to evaluate changes in anxiety-and depressive-like behaviors.Micro-computed tomography was used to observe destruction of alveolar bone.Neuronal injury was observed by H-E staining,and the level of brain-derived neurotrophic factor(BDNF)was detected by enzyme-linked immunosorbent assay.Results·mRNA expression and protein levels of Stat3 in Stat3△Il17a mice were inhibited compared to WT mice(P<0.05).Experimental periodontitis model was successfully established in the WT-P group and the Stat3△Il17a-P group.The degree of alveolar bone destruction was reduced in the Stat3△Il17a-P group compared to the WT-P group.In the WT-P group,decreased residence time in the central area and in the open area was observed in the open field test and elevated zero maze respectively,and increased immortal time was recorded in the forced swimming test(P<0.05).Moreover,neuronal injury was detected and significantly decreased expression levels of BDNF in the brain were measured in the WT-P group compared with the WT-C group(P<0.05).The degree of abnormal behaviors and neuronal injury was reduced in the Stat3△Il17a-P group compared to the WT-P group(P<0.05).Moreover,the level of BDNF in the Stat3△Il17a-P was higher than that in the WT-P group(P<0.05).Conclusion·Periodontitis may contribute to anxiety-and depressive-like behaviors and neuronal damage in mice,while Th17-specific conditional knockout of Stat3 could significantly alleviate pathological behaviors and neuronal damage.Stat3-mediated-Th17 cell immune responses may play a crucial role in the correlation between periodontitis and anxiety and depression.
2.Effect of Th17-specific Stat3 knockout on anxiety-and depressive-like behaviors in periodontitis mice
Yining ZHOU ; Zhiyun YE ; Huiwen CHEN ; Xinyi XIE ; Wei ZHOU ; Zhongchen SONG
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(7):838-845
Objective·To investigate the effect of Th17 cell-specific Stat3 knockout on anxiety-and depressive-like behaviors.Methods·Mice with specific Stat3 knockout in Th17 cells(Stat3fl/fl;Il17a-CreERT2),named Stat3△Il17a,and wild-type mice(Stat3fl/fl,WT)were generated through the Cre/LoxP system,and Stat3 knockout was induced by intraperitoneal injection of tamoxifen.CD4+T cells were isolated using magnetic-activated cell sorting and induced to differentiate into Th17 cells.Reverse transcription polymerase chain reaction and Western blotting were used to verify Stat3 knockout efficiency.Mice were assigned into 4 groups:WT-C group,Stat3△Il17a-C group,WT-P group,and Stat3△Il17a-P group.The periodontitis model was established in the WT-P group and the Stat3△Il17a-P group by injection of Porphyromonas gingivalis-lipopolysaccharide(P.gingivalis-LPS)into the gingival sulcus.Behavioral tests,including the open field test,elevated zero maze,and forced swimming test,were conducted to evaluate changes in anxiety-and depressive-like behaviors.Micro-computed tomography was used to observe destruction of alveolar bone.Neuronal injury was observed by H-E staining,and the level of brain-derived neurotrophic factor(BDNF)was detected by enzyme-linked immunosorbent assay.Results·mRNA expression and protein levels of Stat3 in Stat3△Il17a mice were inhibited compared to WT mice(P<0.05).Experimental periodontitis model was successfully established in the WT-P group and the Stat3△Il17a-P group.The degree of alveolar bone destruction was reduced in the Stat3△Il17a-P group compared to the WT-P group.In the WT-P group,decreased residence time in the central area and in the open area was observed in the open field test and elevated zero maze respectively,and increased immortal time was recorded in the forced swimming test(P<0.05).Moreover,neuronal injury was detected and significantly decreased expression levels of BDNF in the brain were measured in the WT-P group compared with the WT-C group(P<0.05).The degree of abnormal behaviors and neuronal injury was reduced in the Stat3△Il17a-P group compared to the WT-P group(P<0.05).Moreover,the level of BDNF in the Stat3△Il17a-P was higher than that in the WT-P group(P<0.05).Conclusion·Periodontitis may contribute to anxiety-and depressive-like behaviors and neuronal damage in mice,while Th17-specific conditional knockout of Stat3 could significantly alleviate pathological behaviors and neuronal damage.Stat3-mediated-Th17 cell immune responses may play a crucial role in the correlation between periodontitis and anxiety and depression.
3.Establishment of prognostic model for severe primary graft dysfunction in patients with idiopathic pulmonary fibrosis after lung transplantation
Zhiyun SONG ; Taoyin DAI ; Sijia GU ; Xiaoshan LI ; Murong HUANG ; Shixiao TANG ; Chunxiao HU ; Jingyu CHEN
Organ Transplantation 2024;15(4):591-598
Objective To explore the establishment of a prognostic model based on machine learning algorithm to predict primary graft dysfunction(PGD)in patients with idiopathic pulmonary fibrosis(IPF)after lung transplantation.Methods Clinical data of 226 IPF patients who underwent lung transplantation were retrospectively analyzed.All patients were randomly divided into the training and test sets at a ratio of 7∶3.Using regularized logistic regression,random forest,support vector machine and artificial neural network,the prognostic model was established through variable screening,model establishment and model optimization.The performance of this prognostic model was assessed by the area under the receiver operating characteristic curve(AUC),positive predictive value,negative predictive value and accuracy.Results Sixteen key features were selected for model establishment.The AUC of the four prognostic models all exceeded 0.7.DeLong and McNemar tests found no significant difference in the performance among different models(both P>0.05).Conclusions Based on four machine learning algorithms,the prognostic model for grade 3 PGD after lung transplantation is preliminarily established.The overall prediction performance of each model is similar,which may predict the risk of grade 3 PGD in IPF patients after lung transplantation.
4.Progress of ovarian tissue cryopreservation and transplantation in the fertility preservation of female childhood cancer patients
Jinze YANG ; Jianfei GONG ; Mengmeng ZHANG ; Jinghao YAN ; Shen YANG ; Xueling SONG ; Zhiyun ZHU ; Haiyan WANG ; Huanmin WANG ; Jie YAN
Chinese Journal of Reproduction and Contraception 2024;44(10):1036-1041
With the continuous development of cancer treatment technology, the cure rate for tumors in children is increasing. However, the irreversible damage to ovarian development and function by chemotherapy and radiation in surviving children often leads to iatrogenic premature ovarian failure and even infertility. Therefore, it is of great significance to develop fertility preservation techniques for children with tumors. International and domestic guidelines indicate that ovarian tissue cryopreservation and transplantation should be considered first for female children. However, the application of this technique in children is not yet mature. Current research suggests that there are significant structural and functional differences between children's ovaries and adults', and fertility preservation strategies for adults are not fully applicable to children. Therefore, this paper analyzes and reviews the structure and function of children's ovaries, the mechanism of damage to ovarian tissues by chemotherapy and radiation, and the current research and application status of fertility preservation techniques for female children. It also looks forward to the development direction of fertility preservation techniques for female children.
5.Progress of ovarian tissue cryopreservation and transplantation in the fertility preservation of female childhood cancer patients
Jinze YANG ; Jianfei GONG ; Mengmeng ZHANG ; Jinghao YAN ; Shen YANG ; Xueling SONG ; Zhiyun ZHU ; Haiyan WANG ; Huanmin WANG ; Jie YAN
Chinese Journal of Reproduction and Contraception 2024;44(10):1036-1041
With the continuous development of cancer treatment technology, the cure rate for tumors in children is increasing. However, the irreversible damage to ovarian development and function by chemotherapy and radiation in surviving children often leads to iatrogenic premature ovarian failure and even infertility. Therefore, it is of great significance to develop fertility preservation techniques for children with tumors. International and domestic guidelines indicate that ovarian tissue cryopreservation and transplantation should be considered first for female children. However, the application of this technique in children is not yet mature. Current research suggests that there are significant structural and functional differences between children's ovaries and adults', and fertility preservation strategies for adults are not fully applicable to children. Therefore, this paper analyzes and reviews the structure and function of children's ovaries, the mechanism of damage to ovarian tissues by chemotherapy and radiation, and the current research and application status of fertility preservation techniques for female children. It also looks forward to the development direction of fertility preservation techniques for female children.
6.Stress Relaxation Behavior of Collagen Type II- Silk Fibroin Composite Cartilage Scaffold under Different Degradation Cycles
Zhiyun SONG ; Lilan GAO ; Ying WEI ; Yansong TAN ; Ruixin LI ; Chunqiu ZHANG
Journal of Medical Biomechanics 2023;38(2):E331-E337
Objective To study stress relaxation behaviors of cartilage scaffolds under different degradation cycles by using finite element analysis combined with theoretical models. Methods Based on the established degradation theoretical model, the elastic modulus of the scaffold was calculated under different degradation cycles. The finite element model of cartilage scaffolds was established and stress relaxation simulation was performed to analyze the variation of scaffold relaxation stress with time. The stress relaxation constitutive model was established to predict mechanical properties of the scaffold. Results The elastic modulus of cartilage scaffolds at 14 th, 28th, 42nd, 56th day after degradation was 32. 35, 31. 12, 29. 91, 28. 74 kPa, respectively. The upper layer for cartilage scaffolds was the largest. The overall relaxation stress of the scaffold decreased rapidly with time and then tended to be stable. At 8th week after degradation, the stress which the scaffold couldwithstand was still within the physiological load range of the cartilage. The predicted results of the stress relaxation constitutive model were in good agreement with the finite element simulation results. Conclusions The elastic modulus of the scaffold gradually decreases with the increase of degradation time. The longer the degradation period is, the less stress the scaffold can withstand. At the same degradation period, the larger the applied compressive strain, the larger the stress on the scaffold. Both the finite element simulation and stress relaxation constitutive model can effectively predict stress variations of cartilage scaffolds under degradation
7.Transcatheter tricuspid valve replacement via vena jugularis interna: A case report
Jingyi CAO ; Fan QIAO ; Zhigang SONG ; Qing XUE ; Chengliang CAI ; Fan YANG ; Guangwei ZHOU ; Bailing LI ; Jun WANG ; Lin HAN ; Zhiyun XU ; Fanglin LU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2022;29(11):1540-1544
We reported a 54-year-old female patient with severe tricuspid regurgitation, who received mechanic valve in the mitral position 15 years ago. The patient’s Society of Thoracic Surgeons score was 8.27%, and was intolerant to open heart surgery, so she was recommended for transcatheter tricuspid valve replacement via right vena jugularis interna. The procedures were guided by echocardiography and X ray fluoroscopy on November 13, 2021, the prosthesis was implanted successfully, and the patient was recoved without any adverse events. After 1 month follow-up, her general condition was apparently improved.
8.Application of extracorporeal membrane oxygenationduring pulmonary transplantation for patients with idiopathic pulmonary fibrosis complicated with pulmonary hypertension
Huizhi YU ; Chunlan HU ; Jing WANG ; Sijia GU ; Zhiyun SONG ; Taoyin DAI ; Xiaoshan LI ; Jingyu CHEN ; Chunxiao HU
Chinese Journal of Organ Transplantation 2022;43(5):281-286
Objective:To compare the effect of extracorporeal membrane oxygenation(ECMO)on pulmonary transplantation(LTx)in patients with idiopathic pulmonary fibrosis(IPF)complicated with pulmonary hypertension(PH).Methods:From January 2017 to December 2020, clinical data were retrospectively reviewed for 112 IPF patients complicated with PH undergoing LTx assisted by venous ECMO(VV-ECMO group, n=68)or venous arterial ECMO(VA-ECMO group, n=44). Gender, age, mechanical ventilation time, oxygenation index, cold ischemic time, preoperative gender, age, smoking history, PO 2, PCO 2, PH degree, NYHA cardiac function grade, right cardiac function, ejection fraction(EF)and complications(hypertension & diabetes)of two groups were compared. Intraoperative approach, operative duration, ECMO transfer time, blood loss, blood transfusion, urine volume, postoperative blood transfusion, mechanical ventilation time, ICU stay time, re-thoracotomy, pulmonary infection, primary graft dysfunction(PGD)and renal insufficiency were recorded. And the effects of two different diversion modes on early postoperative complications and short-term outcomes of LTx were further analyzed by multiple factors. Cox proportional risk model was employed for comparing VV-ECMO and VA-ECMO flow patterns with factors related to recipient survival after transplantation. Results:The preoperative PO 2 of 58.3(51.3, 72.0)mmHg was significantly lower in VV-ECMO bypass group than that of 73.2(63.3, 96.8)mmHg in VA-ECMO group and the difference was statistically significant( P<0.006). Compared with VV-ECMO group, 24(54.5%), 15(34.1%)and 22(50.0%)had NYHA class Ⅲ, severe PH and preoperative right heart enlargement in VA-ECMO group respectively and the differences were statistically significant compared with 17(25.0%), 6(8.8%)and 16(23.5%)in VV-ECMO group( P<0.05 for all). No significant inter-group differences existed in postoperative PGD, postoperative mechanical ventilation time(≥3 d), pulmonary infection, postoperative thoracotomy ratio, postoperative renal insufficiency, ICU stay, hospital stay and other aspects( P>0.05). And 6-month postoperative survival rates of VV-ECMO and VA-ECMO groups were 80.9% and 61.4%, respectively and no significant inter-group difference existed in short-term survival rate(6 months)after adjustment by multivariate Cox regression model( P>0.05). Multivariate statistics indicated that the risk of delayed postoperative withdrawal was 14.452-fold higher in VV-ECMO group than in VA-ECMO group and the inter-group difference was statistically significant(95% CI: 2.448-85.323, P=0.03). Conclusions:No differences exist in postoperative complications or short-term survival rate between IPF recipients with mild PH on VV-ECMO mode and IPF recipients with severe PH on VA-ECMO mode. VV-ECMO flow reversal can delay the transplant back-off time.
9.Clinical analysis of redo aortic root replacement after cardiac surgery
Jie LU ; Qing XUE ; Yangfeng TANG ; Zhigang SONG ; Hao TANG ; Fanglin LU ; Lin HAN ; Zhiyun XU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2021;28(01):99-103
Objective To analyze the etiologies, operation techniques and outcomes of redo aortic root replacement after cardiac surgery. Methods Between December 2013 and December 2019, 30 patients who had at least one previous cardiac operation received aortic root replacement in our hospital, including 20 males and 10 females with an average age of 50.4±12.7 years. The mean time interval between this operation and the previous one was 8.0±8.5 years. The principal indication for surgery was aortic sinus dilatation and ascending aortic aneurysm in 14 patients (47%), acute aortic dissection in 5 patients (17%), pseudoaneurysm in 3 patients (10%), prosthetic valve endocarditis in 4 patients (13%), prosthetic leakage in 4 patients (13%). Bentall procedure was used in all 30 patients, with concomitant mitral valve plasticity or replacement in 5 patients, tricuspid valve plasticity in 6 patients, coronary artery bypass grafting in 3 patients, and total aortic arch replacement and elephant trunk procedure in 2 patients. Results The mean cardiopulmonary bypass time was 96-296 (161.3±43.0) min, and the mean aortic occlusion time was 48-117 (85.7±20.4) min. There were 5 in-hospital deaths with an overall in-hospital mortality of 17%. The causes of deaths were low cardiac output syndrome in 2 patients and septic shock in 3 patients. The follow-up time was 3-75 (33.5±21.1) months. Three patients died during the follow-up, 1 patient died of septic shock and 2 died of cerebral hemorrhage. Conclusion Redo aortic root replacement is difficult to deal with, and the risk is high. Preoperative evaluation is required, appropriate surgical approach, adequate myocardial protection, and a complete surgical plan are essential to ensure the success of the operation.
10.Clinical amalysis of left subclavian artery revascularization by stented trunk fenestration for acute Stanford type A aortic dissection
Yangfeng TANG ; Lin HAN ; Fanglin LU ; Zhigang SONG ; Xilong LANG ; Liangjian ZOU ; Zhiyun XU
Chinese Journal of Surgery 2016;54(7):504-507
Objective To summarize the results and methods of left subclavian artery revascularization by stented trunk fenestration for acute Stanford type A aortic dissection.Methods Clinical data of 67 patients (54 male and 13 female,mean age of (50 ± 10) years) underwent surgical treatment of left subclavian artery fenestration for acute Stanford A aortic dissection in Department of Cardiothoracic Surgery,Changhai Hospital,Second Military Medical College between September 2008 and December 2014 were analyzed retrospectively.The origin of the left subclavian artery was in the true lumen and no dissection existed near the artery's starting.There were 18 cases of Marfan's syndrome.Preoperative echocardiography showed moderate to severe aortic regurgitation in 10 cases,and mitral regurgitation in 3 cases.Electrocardiogram showed myocardial ischemia in 5 cases.Three patients had acute impaired renal function.All the patients received total arch replacement combined with stented elephant trunk implantation.Left subclavian artery revascularization was performed by stented trunk fenestration as follows:firstly,stented elephant trunk was implanted to completely cover the left subclavian artery,then part of stented trunk's polyester lining was removed which is located at the origin of left subclavian artery.Aortic root procedures included aortic valve replacement in 2 cases,Bentall procedure in 21 cases and aortic valve sparing in 44 cases.Three patients received mitral valve repair and 6 patients received coronary artery bypass grafting.Results The cardiopulmonary bypass time,cross-clamp time,and circulatory arrest time were (179 ± 32) minutes,(112 ± 25) minutes,and (26 ± 10) minutes,respectively.The in-hospital mortality was 7.5% (5/67):2 patients died of multiple organ failure,1 patient died of acute renal failure and another 2 patients died of severe infection shock.Two patients required reexploration for root bleeding.Transient neurology dysfunction developed in 6 patients.Six patients received tracheotomy and prolonged ventilation due to pulmonary infection.All patients discharged from the hospital were followed up for 1 to 5 years.During long-term follow-up,the survival rate was 100% and 89.8% at 1 and 5 years,respectively.CT angiography was performed once per year after discharged.The left subclavian artery perfusion was good.No dissection or anastomosis leakage was identified in any case.Stroke and left limb ischemia did not develope.Conclusion For acute Stanford type A aortic dissection whose origin of the left subclavian artery is in the true lumen and no dissection existed near the artery's starting,the left subclavian artery revascularization by stented trunk fenestration technique during total arch replacement combined with stented elephant trunk implantation is reliable and effective.

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