1.Ferroptosis is involved in testicular injury induced by TDCIPP in adolescent male mice
Chuanzhen XIONG ; Ling ZHANG ; Yang ZHANG ; Ruiwen LI ; Yu SUN ; Yunhao LIU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2023;41(8):562-568
Objective:To investigate the role of ferroptosis in testicular injury in adolescent male mice induced by TDCIPP.Methods:In December 2021, 30 healthy 3-week-old male C57BL/6 mice, with a body weight of (13±2) g, were selected and fed adaptive for one week. They were divided into control group, low-dose group, medium-dose group, high-dose group and iron death inhibitor group according to a random number table, with 6 mice in each group. Mice in low, medium and high dose groups were treated with 5, 25 and 125 mg/ (kg·d) TDCIPP for 28 days, respectively, while the control group was treated with the same amount of corn oil for 28 days. The iron death inhibitor group was given 125 mg/ (kg·d) TDCIPP intragastric administration for 28 days, and 30 mg/kg DFO saline solution was intraperitoneally injected three times a week. After the treatment, the mice were killed, the epididymis was separated, and sperm count was performed. HE staining was used to observe the morphological changes of mouse testis, and iron content in testis was detected by tissue iron detection kit. The level of reactive cxygen species, MDA content, and the mitochondrial membrane potential level of mice were detected. Western blot analysis of testicular glutathione peroxidase (GPX4) and internal cyclooxygenase-2 (COX2) protein expression.Results:Compared with the control group, the spermatogenic cells in the testes of mice treated with medium-and high-dose of TDCIPP were disorderly arranged, showing a vacuolar structure. the number of sperm in the epididymis was significantly reduced ( P=0.009, 0.004), while the sperm deformity rate was significantly increased ( P=0.010, 0.000). Moreover, the content of ROS, iron ion and MDA in the testes increased significantly ( P<0.05), and the mitochondrial membrane potential of mouse testicular cells decreased significantly ( P<0.05). The expression of GPX4 proteins decreased ( P<0.05). while the expression of COX2 increased significantly ( P<0.01). Compared with high-dose group group, spermatogenic cells in ferroptosis inhibitor group were closely arranged and normal, and ROS and Fe contents in testicular tissue were significantly decreased ( P<0.01) ; GPX4 protein expression was significantly increased while COX2 protein expression was significantly decreased ( P<0.05) . Conclusion:Ferroptosis is involved in TDCIPP-induced testicular damage in male pubertal mice.
2.Ferroptosis is involved in testicular injury induced by TDCIPP in adolescent male mice
Chuanzhen XIONG ; Ling ZHANG ; Yang ZHANG ; Ruiwen LI ; Yu SUN ; Yunhao LIU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2023;41(8):562-568
Objective:To investigate the role of ferroptosis in testicular injury in adolescent male mice induced by TDCIPP.Methods:In December 2021, 30 healthy 3-week-old male C57BL/6 mice, with a body weight of (13±2) g, were selected and fed adaptive for one week. They were divided into control group, low-dose group, medium-dose group, high-dose group and iron death inhibitor group according to a random number table, with 6 mice in each group. Mice in low, medium and high dose groups were treated with 5, 25 and 125 mg/ (kg·d) TDCIPP for 28 days, respectively, while the control group was treated with the same amount of corn oil for 28 days. The iron death inhibitor group was given 125 mg/ (kg·d) TDCIPP intragastric administration for 28 days, and 30 mg/kg DFO saline solution was intraperitoneally injected three times a week. After the treatment, the mice were killed, the epididymis was separated, and sperm count was performed. HE staining was used to observe the morphological changes of mouse testis, and iron content in testis was detected by tissue iron detection kit. The level of reactive cxygen species, MDA content, and the mitochondrial membrane potential level of mice were detected. Western blot analysis of testicular glutathione peroxidase (GPX4) and internal cyclooxygenase-2 (COX2) protein expression.Results:Compared with the control group, the spermatogenic cells in the testes of mice treated with medium-and high-dose of TDCIPP were disorderly arranged, showing a vacuolar structure. the number of sperm in the epididymis was significantly reduced ( P=0.009, 0.004), while the sperm deformity rate was significantly increased ( P=0.010, 0.000). Moreover, the content of ROS, iron ion and MDA in the testes increased significantly ( P<0.05), and the mitochondrial membrane potential of mouse testicular cells decreased significantly ( P<0.05). The expression of GPX4 proteins decreased ( P<0.05). while the expression of COX2 increased significantly ( P<0.01). Compared with high-dose group group, spermatogenic cells in ferroptosis inhibitor group were closely arranged and normal, and ROS and Fe contents in testicular tissue were significantly decreased ( P<0.01) ; GPX4 protein expression was significantly increased while COX2 protein expression was significantly decreased ( P<0.05) . Conclusion:Ferroptosis is involved in TDCIPP-induced testicular damage in male pubertal mice.
3.Bladder-sparing treatment following noninvasive down-staging after transurethral resection of bladder tumor plus systemic chemotherapy for muscle-invasive bladder cancer
Youyan GUAN ; Xingang BI ; Jun TIAN ; Zhendong XIAO ; Zejun XIAO ; Dong WANG ; Kaopeng GUAN ; Hongzhe SHI ; Linjun HU ; Chuanzhen CAO ; Jie WU ; Changling LI ; Jianhui MA ; Yueping LIU ; Aiping ZHOU ; Jianzhong SHOU
Chinese Journal of Urology 2022;43(6):411-415
Objective:To investigate the long-term survival and safety in patients with muscle-invasive bladder cancer (MIBC) who experienced a noninvasive down-staging (≤pT 1)after transurethral resection of bladder tumor (TURBT) plus systemic chemotherapy and received bladder-sparing treatment. Methods:The records of patients with MIBC who underwent maximal TURBT plus systemic chemotherapy-guided bladder-sparing treatment were reviewed retrospectively from Dec 2013 to Dec 2020. Eventually, 22 patients who achieved noninvasive down-staging underwent conservative management. The total patient cohort contained 10 males and 12 females. A majority of patients had single lesion and stage T2 disease. The median age of the patients was 66 years and the median tumor size was 3.0 cm. All patients underwent maximal TURBT to resect all visible diseases and followed by 3-4 cycles platinum-based systemic chemotherapy. After achieving noninvasive down-staging, 14 patients received concurrent chemoradiotherapy, and the other 8 patients underwent surveillance. Overactive bladder symptom score (OABSS) was used to assess the bladder function after treatment.Results:Twelve patients achieved pT 0 and 10 patients were down-staged to cT a-T 1. At a median follow-up of 36.7 months, 90.9%(20/22) patients retained their bladder function successfully. Among the 14 patients who received concurrent chemoradiotherapy, 4 had grade 3 or 4 adverse events. Among the 8 patients who underwent surveillance, 3 had grade 3 or 4 adverse events after systemic chemotherapy.Nine patients experienced tumor recurrence in the bladder, and 2 patients died of bladder cancer. Seven (31.8%) patients experienced Ⅲ/Ⅳ grade complications. The 5-year recurrence-free survival (RFS) and overall survival (OS) in patients achieved pT0 were 66.7% and 100.0%, respectively. The 5-year RFS and OS in patients achieved cTa-T1 were 40% and 72%, respectively. The OABSS score of 20 patients who retained their bladder successfully was (1.00±1.03). Conclusions:MIBC patients who achieved noninvasive down-staging might be candidates for the bladder-sparing treatment with maximum TURBT followed by systemic chemotherapy.The patients who achieved pT 0 might have better prognosis with functional bladder.
4.Neoadjuvant Chemotherapy–Guided Bladder-Sparing Treatment for Muscle-Invasive Bladder Cancer: Results of a Pilot Phase II Study
Hongzhe SHI ; Wen ZHANG ; Xingang BI ; Dong WANG ; Zejun XIAO ; Youyan GUAN ; Kaopeng GUAN ; Jun TIAN ; Hongsong BAI ; Linjun HU ; Chuanzhen CAO ; Weixing JIANG ; Zhilong HU ; Jin ZHANG ; Yan CHEN ; Shan ZHENG ; Xiaoli FENG ; Changling LI ; Yexiong LI ; Jianhui MA ; Yueping LIU ; Aiping ZHOU ; Jianzhong SHOU
Cancer Research and Treatment 2021;53(4):1156-1165
Purpose:
Reduced quality of life after cystectomy has made bladder preservation a popular research topic for muscle-invasive bladder cancer (MIBC). Previous research has indicated significant tumor downstaging after neoadjuvant chemotherapy (NAC). However, maximal transurethral resection of bladder tumor (TURBT) was performed before NAC to define the pathology, impacting the real evaluation of NAC. This research aimed to assess real NAC efficacy without interference from TURBT and apply combined modality therapies guided by NAC efficacy.
Materials and Methods:
Patients with cT2-4aN0M0 MIBC were confirmed by cystoscopic biopsy and imaging. NAC efficacy was assessed by imaging, urine cytology, and cystoscopy with multidisciplinary team discussion. Definite responders (≤ T1) underwent TURBT plus concurrent chemoradiotherapy. Incomplete responders underwent radical cystectomy or partial cystectomy if feasible. The primary endpoint was the bladder preservation rate.
Results:
Fifty-nine patients were enrolled, and the median age was 63 years. Patients with cT3-4 accounted for 75%. The median number of NAC cycles was three. Definite responders were 52.5%. The complete response (CR) was 10.2%, and 59.3% of patients received bladder-sparing treatments. With a median follow-up of 44.6 months, the 3-year overall survival (OS) was 72.8%. Three-year OS and relapse-free survival were 88.4% and 60.0% in the bladder-sparing group but only 74.3% and 37.5% in the cystectomy group. The evaluations of preserved bladder function were satisfactory.
Conclusion
After stratifying MIBC patients by NAC efficacy, definite responders achieved a satisfactory bladder-sparing rate, prognosis, and bladder function. The CR rate reflected the real NAC efficacy for MIBC. This therapy is worth verifying through multicenter research.
5.Impact of motivational interviewing combined with feedback teaching on the active cycle of breathing technique training among lung cancer patients
Jiudi ZHONG ; Chuanzhen LI ; Ziya XIN ; Yuxia HUANG ; Li LIU
Chinese Journal of Practical Nursing 2021;37(22):1688-1694
Objective:To explore the effect of motivational interview combined with feedback teaching on active cycle of breathing technique(ACBT) training in lung cancer patients.Methods:A total of 632 patients with lung cancer undergoing radical resection from September 2017 to March 2019 in Sun Yat-sen University Cancer Center were selected and divided into the experimental group and the control group with 316 cases in each group by operation time. The experimental group received motivational interview combined with feedback teaching education, while the control group received routine education. The patients were followed up for 2 months. The compliance and accuracy of ACBT training, self-care ability, sputum discharge and incidence of pulmonary complications were compared between the two groups.Results:The sputum volume in the control group was (6.25±2.44), (9.28±2.63), (10.33±3.15) g in the control group and (8.74±4.17),(13.87±3.19),(14.18±4.16) g in the experimental group at 1, 2, 3 days after operation, and the differences between the two groups were statistically significant ( t values were -1.149, -2.316, -4.124, P<0.01 or 0.05). There were 56 cases(17.72%) of pulmonary complications in the control group and 33 cases (10.44%) in the experimental group. The difference in the incidence of pulmonary complications between the two groups was statistically significant ( χ2 value was 4.743, P<0.01).Two months after operation, the compliance and accuracy of ACBT training in the experimental group were better than those in the control group ( χ2 values were - 4.57, - 2.15, P<0.01).The improvement in the four dimensions after intervention in the experimental group were better than those in the control group, and the differences were statistically significant ( t values were 8.314-19.719, P<0.01). Conclusions:The motivational interview combined with feedback teaching is an effective method of health education, which is conducive to improving lung cancer patients' compliance and accuracy of postoperative ACBT training, improving patients' self-care ability, promoting the discharge of patients' sputum and reducing the incidence of pulmonary complications to promote the recovery of lung function.
6.Intravitreal injection of conbercept after operation in the treatment of proliferatived diabetic retinophathy complicated with vitreous hemorrhage
Jinping ZHANG ; Xinjun REN ; Chuanzhen ZHENG ; Dejia WEN ; Xiaorong LI ; Xiaomin ZHANG
Chinese Journal of Ocular Fundus Diseases 2020;36(2):105-109
Objective:To observe the efficacy and safety of intravitreal injection of conbercept in the treatment of proliferatived diabetic retinophathy (PDR) complicated with vitreous hemorrhage by minimally invasive vitreoretinal surgery.Methods:Prospective clinical study. A total of 50 patients with PDR complicated with vitreous hemorrhage clinically diagnosed in Tianjin Medical University Eye Hospital who needed vitrectomy were recruited in this study. According to the principle of informed consent, the patients were divided into two groups: postoperative injection group and the control group. Twenty-five eyes of 25 patients in each group were examined before operation. No significant proliferative changes in the posterior pole and traction retinal detachment were observed. There was significant difference of age between two groups ( t=-24.697, P=0.030), but no significant difference of sex ( χ2=0.330, P=0.564), duration of diabetes ( t=-1.144, P=0.258), logMAR BCVA ( t=-0.148, P=0.883), lens state ( χ2=0.397, P=0.529), panretinal laser photocoagulation ( χ2=1.333, P=0.248). The postoperative injection group was treated with intravitreous injection of 0.05 ml conbercept (10 mg/ml) immediately after 27G minimally invasive vitrectomy. The other treatment and follow-up were the same as those in the postoperative injection group except for conbercept injection. All patients underwent routine slit-lamp examination, indirect ophthalmoscope and B-ultrasound examination before operation. The main outcome measure included the time of operation, the incidence rate of iatrogenic retinal holes and silicone oil filling. The recurrence of vitreous hemorrhage, BCVA, intraocular pressure, central retinal thickness (CRT), postoperative complications and progression were recorded 1 week, 1 month, 3 months and 6 months after operation. Results:At 1 week and 1, 3, 6 months after operation, there was significant difference of logMAR BCVA between the two groups ( t=-4.980, -4.840, -4.892, -5.439; P<0.001). At 3 and 6 months after operation, the recurrence of vitreous hemorrhage in the postoperative injection group was lower than that in the control group, but there was no statistical difference between two groups ( χ2=3.030, 4.153; P=0.192, 0.103). At 1 week and 1, 3, 6 months after operation, the CRT in the postoperative injection group was lower than that in the control group, the difference was significant ( t=-2.622, -2.638, -3.613, -3.037; P=0.012, 0.010, 0.001, 0.004, 0.005). There was no complications such as choroid detachment, proliferative vitreoretinopathy, retinal detachment, iris redness and neovascular glaucoma in all the eyes after operation. Conclusions:Intravitreal injection of conbercept in the treatment of PDR after operation is safe and effective. It can reduce the recurrence of vitreous hemorrhage after vitrectomy, improve the BCVA.
7.Research progress of cytokines in vitreous of diabetic retinopathy
Dejia WEN ; Xinjun REN ; Chuanzhen ZHENG ; Ye HE ; Qiong WANG ; Yaru HONG ; Xiaorong LI
Chinese Journal of Ocular Fundus Diseases 2020;36(2):151-155
Blood-retina barrier destruction, nerve injury, formation of neovascularization and fibroblast proliferation membrane are important pathological changes of DR, which are related to the combined effects of various vitreous cytokines. VEGF is mainly involved in increasing retinal vascular permeability and inducing neovascularization. Pigment epithelium derived factor is vital reducing vascular permeability and neuroprotection; IL plays a key role in mediating inflammatory response. TNF-α is related to inflammation, which is significantly up-regulated by hypoxia. TGF-β is an important cytokine regulating cell proliferation and differentiation. Connective tissue growth factor can promote the growth, migration and adhesion of endothelial cell. In addition, many other molecular mechanisms have not been fully elucidated, and further study on the molecular mechanism of DR is urgent. With the further study of molecular mechanism, the early intervention and targeted treatment of DR will be more effective.
8.Patching retinal breaks with Healaflow in 27G vitrectomy in the treatment of rhegmatogenous retinal detachment
Xinjun REN ; Chuanzhen ZHENG ; Dejia WEN ; Yifeng KE ; Xiaorong LI
Chinese Journal of Ocular Fundus Diseases 2020;36(3):200-204
Objective:To observe the safety and effectiveness of patching retinal breaks with Healaflow in 27G vitrectomy combined with air tamponade in the treatment of rhegmatogenous retinal detachment (RRD).Methods:Clinical-based prospective continuous study. From March 2017 to May 2018, 51 eyes of 50 RRD patients diagnosed in Tianjin Medical University Eye Hospital were included in the study. All eyes were treated with 27G vitrectomy, and laser photocoagulation was performed around retinal hiatus and denaturation zone after complete retinal reattachment. A blunt 27G needle was used to completely cover the surface of the retinal tear with the Healaflow. The injection amount was determined according to the size of the retinal tear, and the standard was that the tear was completely contained. There was no postoperative position limitation. The average follow-up was 15.8±6.3 months. The primary and final anatomic attachment rate, BCVA after operation, the intraoperative and postoperative complications, the recurrence of retinal detachment and so on were recorded.Results:51 eyes of 50 patients were enrolled, including 29 males (58.0%) and 21 females (42.0%). The average age was 58.5±1 years. A single break was present in 28 eyes (54.9%) and 2 to 5 breaks in 23 eyes (45.1%). The macula was involved in 32 eyes (62.7%) and attached in 19 eyes (37.3%) intraoperatively. Initial reattachment was achieved in 50 eyes (98.0%) and final reattachment in 51 eyes (100.0%). The logMAR BCVA before and 3 months after operation were 0.95±0.80 and 0.22±0.17, respectively. The difference of logMAR BCVA between before and after operation was significant ( t=7.336, P<0.001). The intraocular pressure was elevated transiently in 31 eyes (60.8%). No other complications occurred during follow-up. Conclusion:The treatment of primary RRD with 27G vitrectomy combined with Healaflow patch and air tamponade is a safe, effective and convenient method with high success rate and rapid recovery of visual function.
9.Latest progress and research status of atopic dermatitis complicated with retinal detachment
Chuanzhen ZHENG ; Xinjun REN ; Xiaorong LI
Chinese Journal of Ocular Fundus Diseases 2020;36(9):735-738
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by severe itching and recurrent eczema-like lesions. With the increase in the global incidence of AD, the incidence of ocular complications in patients also increases. Retinal detachment (RD) seriously affects the vision of patients, and is more common in young and middle-aged people, often involving both eyes with poor prognosis. What’s more, there are many similarities between RD associated with AD and traumatic RD, such as peripheral retinal breaks, giant retinal tears and retinal dialysis. Regarding the mechanism of AD complicated with RD, the trauma theory is widely accepted. Scholars have also reported on the theory of anterior eye developmental abnormalities, inflammation-traction theory, and ectodermal origin theory. On AD complicated with RD, regardless of scleral buckling surgery or vitrectomy surgery, the rate of first retinal reattachment is low with severe proliferative vitreoretinopathy or chronic uveolar inflammation after surgery, which cause traction on the ciliary body and the retina separation appearance again or new cracks appearance. Combination of behavioral therapy, drug therapy and psychotherapy can effectively reduce the occurrence of RD; prevention of eye rubbing, reduction of traumatic exercise, rational use of glucocorticoids or immunosuppressants under the guidance of dermatologists are effective ways for AD patients to prevent RD occurrence. Regular eye examinations can help patients find RD as soon as possible so that they can be treated in time.
10.The clinical characteristic analysis of preoperative misdiagnosis of renal vein tumor thrombus in renal cell carcinoma
Weixing JIANG ; Jianzhong SHOU ; Chuanzhen CAO ; Xiangpeng KANG ; Xingang BI ; Jin ZHANG ; Zhendong XIAO ; Changling LI ; Jianhui MA
Chinese Journal of Urology 2019;40(2):86-90
Objective To improve the accuracy of preoperative diagnosis of renal vein tumor thrombus in renal cell carcinoma (RCC),the clinical characteristics of RCC with misdiagnosis of renal vein tumor thrombus (RVTT) were analyzed.Methods Clinical data of 128 patients with RCC accompanied with RVTT from January 2000 to September 2015 were studied retrospectively.According to whether RVTT failed to be detected preoperatively,all patients were divided into 39 cases of misdiagnosis group and 89 cases of no misdiagnosis group.Forty cases of RCC with pathologically confirmed no RVTT were selected as no tumor thrombus group from January 2015 to June 2015.Misdiagnosis group included 29 males and 10 females,with age of (61.4 ± 11.1) years old,body mass index of (26.74 ±3.12) kg/m2,KPS <80 in 2 cases,paraneoplastic syndrome and Mayo grade 0 in 1 case.No misdiagnosis group consisted of 74 males and 15 females,with age of (60.2 ± 9.7) years old,body mass index of (25.12 ± 1.93) kg/m2,KPS < 80 in 5 cases,paraneoplastic syndrome and Mayo grade 0 in 7 cases.No tumor thrombus group comprised of 31 males and 9 females,with age of (59.5 ± 10.7) years old,body mass index of (24.48 ± 2.56) kg/m2,KPS < 80 in 3 cases,and paraneoplastic syndrome in 3 cases.There was no significant difference in general clinical data between misdiagnosis group and no misdiagnosis group,and misdiagnosis group and no tumor thrombus group (P > 0.05).The tumor location,tumor diameter and imaging data were compared between misdiagnosis group and no misdiagnosis group,and misdiagnosis group and no tumor thrombus group.Results There was no significant difference in term of tumor locating in the middle pole [56.4% (22/39) vs.38.2% (34/89)],tumor with collateral vessels [33.3% (13/39) vs.31.5% (28/89)] and renal vein contrast agents filling defect [42.9% (9/21) vs.61.8% (21/34)] between misdiagnosis group and no misdiagnosis group (P > 0.05).The proportion of renal tumor locating in the middle pole,tumor with collateral vessels and renal vein contrast agents filling defect in misdiagnosis group was significantly higher than that of no tumor thrombus group [30.0% (12/40),P =0.018;10.0% (4/40),P =0.012;16.7% (4/24),P =0.002].Conclusions RVTT is vulnerable of misdianosis in RCC.It should be alert to the possibility of complicating tumor thrombus in the presence of renal tumor locating in the middle pole,renal tumor with collateral vessels and renal vein contrast agents filling defect.The clinical understanding of these features should be improved.

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