Purpose: This study aimed to investigate the effect of the N6-methyladenosine (m6A) dependent ferroptosis on cisplatininduced Sertoli cell injury. Materials and Methods: A cisplatin exposure mouse model was established by intraperitoneal injection of cisplatin in our study. TM4 cell lines was used for in vitro study. Ferroptosis was detected according to metabolomic analysis and a series of assays, including malondialdehyde, glutathione, and glutathione disulfide concentration detection, 2′,7′-dichlorodihydrofluorescein diacetate and BODIPY 581/591 C11 probe detection, and transmission electron microscope imaging. Key ferroptosis-related genes were identified via transcriptomic analysis, western blot and immunohistochemistry. The m6A modification was demonstrated via m6A RNA immunoprecipitation and luciferase reporter assays. Immune cell infiltration was detected by mass cytometry, and verified by flow cytometry and immunofluorescence. Results: Ferroptosis, but not other types of programmed cell death, is a significant phenomenon in cisplatin-induced testis damage and Sertoli cell loss. Ferroptosis induced by cisplatin in Sertoli cell/TM4 cell is GPX4 independent but is regulated by SLC7A11 and ALOX12. Both SLC7A11 and ALOX12 are regulated via m6A dependent manner by METTL3. Furthermore, overexpressed ALOX12-12HETE pathway may result in macrophage polarization and inflammatory response in cisplatin exposure testis. Conclusions Cisplatin-induced Sertoli cell injury via ferroptosis and promoted ferroptosis in an m6A dependent manner. m6A modification of both SLC7A11 and ALOX12 mRNA could result in ferroptosis in our in vitro model. Further, overexpressed ALOX12 can cause more production of 12-HETE, which may be responsible for testis inflammation caused by cisplatin.

Purpose: This study aimed to investigate the effect of the N6-methyladenosine (m6A) dependent ferroptosis on cisplatininduced Sertoli cell injury. Materials and Methods: A cisplatin exposure mouse model was established by intraperitoneal injection of cisplatin in our study. TM4 cell lines was used for in vitro study. Ferroptosis was detected according to metabolomic analysis and a series of assays, including malondialdehyde, glutathione, and glutathione disulfide concentration detection, 2′,7′-dichlorodihydrofluorescein diacetate and BODIPY 581/591 C11 probe detection, and transmission electron microscope imaging. Key ferroptosis-related genes were identified via transcriptomic analysis, western blot and immunohistochemistry. The m6A modification was demonstrated via m6A RNA immunoprecipitation and luciferase reporter assays. Immune cell infiltration was detected by mass cytometry, and verified by flow cytometry and immunofluorescence. Results: Ferroptosis, but not other types of programmed cell death, is a significant phenomenon in cisplatin-induced testis damage and Sertoli cell loss. Ferroptosis induced by cisplatin in Sertoli cell/TM4 cell is GPX4 independent but is regulated by SLC7A11 and ALOX12. Both SLC7A11 and ALOX12 are regulated via m6A dependent manner by METTL3. Furthermore, overexpressed ALOX12-12HETE pathway may result in macrophage polarization and inflammatory response in cisplatin exposure testis. Conclusions Cisplatin-induced Sertoli cell injury via ferroptosis and promoted ferroptosis in an m6A dependent manner. m6A modification of both SLC7A11 and ALOX12 mRNA could result in ferroptosis in our in vitro model. Further, overexpressed ALOX12 can cause more production of 12-HETE, which may be responsible for testis inflammation caused by cisplatin.

Purpose: This study aimed to investigate the effect of the N6-methyladenosine (m6A) dependent ferroptosis on cisplatininduced Sertoli cell injury. Materials and Methods: A cisplatin exposure mouse model was established by intraperitoneal injection of cisplatin in our study. TM4 cell lines was used for in vitro study. Ferroptosis was detected according to metabolomic analysis and a series of assays, including malondialdehyde, glutathione, and glutathione disulfide concentration detection, 2′,7′-dichlorodihydrofluorescein diacetate and BODIPY 581/591 C11 probe detection, and transmission electron microscope imaging. Key ferroptosis-related genes were identified via transcriptomic analysis, western blot and immunohistochemistry. The m6A modification was demonstrated via m6A RNA immunoprecipitation and luciferase reporter assays. Immune cell infiltration was detected by mass cytometry, and verified by flow cytometry and immunofluorescence. Results: Ferroptosis, but not other types of programmed cell death, is a significant phenomenon in cisplatin-induced testis damage and Sertoli cell loss. Ferroptosis induced by cisplatin in Sertoli cell/TM4 cell is GPX4 independent but is regulated by SLC7A11 and ALOX12. Both SLC7A11 and ALOX12 are regulated via m6A dependent manner by METTL3. Furthermore, overexpressed ALOX12-12HETE pathway may result in macrophage polarization and inflammatory response in cisplatin exposure testis. Conclusions Cisplatin-induced Sertoli cell injury via ferroptosis and promoted ferroptosis in an m6A dependent manner. m6A modification of both SLC7A11 and ALOX12 mRNA could result in ferroptosis in our in vitro model. Further, overexpressed ALOX12 can cause more production of 12-HETE, which may be responsible for testis inflammation caused by cisplatin.

Purpose: This study aimed to investigate the effect of the N6-methyladenosine (m6A) dependent ferroptosis on cisplatininduced Sertoli cell injury. Materials and Methods: A cisplatin exposure mouse model was established by intraperitoneal injection of cisplatin in our study. TM4 cell lines was used for in vitro study. Ferroptosis was detected according to metabolomic analysis and a series of assays, including malondialdehyde, glutathione, and glutathione disulfide concentration detection, 2′,7′-dichlorodihydrofluorescein diacetate and BODIPY 581/591 C11 probe detection, and transmission electron microscope imaging. Key ferroptosis-related genes were identified via transcriptomic analysis, western blot and immunohistochemistry. The m6A modification was demonstrated via m6A RNA immunoprecipitation and luciferase reporter assays. Immune cell infiltration was detected by mass cytometry, and verified by flow cytometry and immunofluorescence. Results: Ferroptosis, but not other types of programmed cell death, is a significant phenomenon in cisplatin-induced testis damage and Sertoli cell loss. Ferroptosis induced by cisplatin in Sertoli cell/TM4 cell is GPX4 independent but is regulated by SLC7A11 and ALOX12. Both SLC7A11 and ALOX12 are regulated via m6A dependent manner by METTL3. Furthermore, overexpressed ALOX12-12HETE pathway may result in macrophage polarization and inflammatory response in cisplatin exposure testis. Conclusions Cisplatin-induced Sertoli cell injury via ferroptosis and promoted ferroptosis in an m6A dependent manner. m6A modification of both SLC7A11 and ALOX12 mRNA could result in ferroptosis in our in vitro model. Further, overexpressed ALOX12 can cause more production of 12-HETE, which may be responsible for testis inflammation caused by cisplatin.

Purpose: This study aimed to investigate the effect of the N6-methyladenosine (m6A) dependent ferroptosis on cisplatininduced Sertoli cell injury. Materials and Methods: A cisplatin exposure mouse model was established by intraperitoneal injection of cisplatin in our study. TM4 cell lines was used for in vitro study. Ferroptosis was detected according to metabolomic analysis and a series of assays, including malondialdehyde, glutathione, and glutathione disulfide concentration detection, 2′,7′-dichlorodihydrofluorescein diacetate and BODIPY 581/591 C11 probe detection, and transmission electron microscope imaging. Key ferroptosis-related genes were identified via transcriptomic analysis, western blot and immunohistochemistry. The m6A modification was demonstrated via m6A RNA immunoprecipitation and luciferase reporter assays. Immune cell infiltration was detected by mass cytometry, and verified by flow cytometry and immunofluorescence. Results: Ferroptosis, but not other types of programmed cell death, is a significant phenomenon in cisplatin-induced testis damage and Sertoli cell loss. Ferroptosis induced by cisplatin in Sertoli cell/TM4 cell is GPX4 independent but is regulated by SLC7A11 and ALOX12. Both SLC7A11 and ALOX12 are regulated via m6A dependent manner by METTL3. Furthermore, overexpressed ALOX12-12HETE pathway may result in macrophage polarization and inflammatory response in cisplatin exposure testis. Conclusions Cisplatin-induced Sertoli cell injury via ferroptosis and promoted ferroptosis in an m6A dependent manner. m6A modification of both SLC7A11 and ALOX12 mRNA could result in ferroptosis in our in vitro model. Further, overexpressed ALOX12 can cause more production of 12-HETE, which may be responsible for testis inflammation caused by cisplatin.

Objective:To discuss the clinical and pathological features of the patients with renal oncocytoma.Methods:Making a retrospective analysis of the clinical data of 35 patients with renal oncocytoma who were admitted to the department of urology in the First affiliated Hospital of China Medical University from January 2013 to August 2020, discussing their clinical features, pathological characteristics, treatment and prognosis. The age range of the 35 patients was 35-79 years, with an average age of (59.0±11.3) years, there were 15 males and 20 females. The tumors of the 35 patients were unilateral, concluded 22 cases on the left side and 13 cases on the right side.Among the 35 patients, the tumors of 7 cases located in the upper pole, 14 in the middle pole, and 14 in the lower pole. At the time of admission, 5 patients complained with flank pain, 3 patients had gross hematuria, and the other patients were found during physical examination or examination due to other diseases. In the imaging examination, there were 33 cases of ultrasound data, including 18 cases of hypoechoic, 10 cases of hyperechoic, 3 cases of isoechoic and 2 cases of mixed echo. The data of CT were collected in 30 cases. The tumors showed isointense or slightly hypointense on plain scan, after enhancement, it showed low enhancement with clear boundary to the renal parenchyma and 12 patients had typical central stellate scar sign. All patients accepted surgical treatment, including 23 cases of retroperitoneal laparoscopic surgery and 12 cases of open surgery, but only 12 cases had partial nephrectomy.Results:The tumors were incised after the operation, the range of the tumors’diameter was 1.3-14.0 cm, with an average of (4.0±2.3) cm. The color of the cross-section was tawny in 14 cases, mahogany in 19 cases and 2 cases of other colors. The typical features of tumor cell under microscope were arranged in nests, alveolar or tubular shapes, the cells were round or polygonal.The cell size was uniform, the cytoplasm was rich in eosinophilic granules, the nuclei was deeply stained and the nucleoli was small. There are 9 indicators reach to 20 cases in immunohistochemical stain, and the positive rates of each indicator are respectively EMA 100.0%(23/23), E-cadherin 100.0%(20/20), CK 96.2%(25/26), CD117 95.5%(21/22), p504S(AMACR)35.0%(7/20), CD10 33.3%(9/27), CK7 31.0%(9/29), Vimentin 17.2%(5/29), Ki-67(0/28). Thirty-five patients were followed up after surgery, 4 patients were lost to follow-up, and the follow-up time of the other 31 patients ranged from 7 to 90 months, with an average of (46.9±25.0) months. All patients had a good prognosis without recurrence or metastasis. Among them, 3 patients had mild renal insufficiency in a short time after operation, and they have all recovered. Three patients with gross hematuria before the operation disappeared after the operation. In 5 patients with low back pain, only two patients felt significant improvement, and the other three still felt intermittent episodes of dull lumbar pain.Conclusions:Renal oncocytoma is a relatively rare benign tumor of the kidney. Because of the lack of effective diagnostic methods, it is difficult to differentiate from renal malignant tumors preoperatively. Pathological results are the golden standard for the diagnosis and differential diagnosis of renal oncocytoma. The main treatment of renal oncocytoma is surgery, and after surgery, the patient's prognosis is good, but renal oncocytoma has the possibility of recurrence and metastasis, regular follow-up and surveillance are still required.

Clinical scientific research is based on clinical reality, through organized scientific behavior, to answer the difficult questions encountered in clinical work, so as to improve the level of clinical diagnosis and treatment. After 35 years of medical work, I have gotten some insights in the practice of clinical scientific research. First, in order to do a good job in clinical scientific research, we have to be good at finding problems in clinical practice and pay attention to the collection of clinical data. Second, we should be diligent in learning and good at thinking. Young doctors should deal with the problems encountered in clinical work, combine with learning and think repeatedly, determine new problems, and then look for literature to study, in order to find out clinical research topics. Third, we should have a clear theme and continue to dig in depth. When having a clear research direction, it is suggested to carry out in-depth research from clinical practice to clinical basis, gradually form a scientific research system, and improve young doctors’own professional ability and professional quality. Clinical research should be the starting point and lasting driving force for success of young doctors.

Objective To investigate the diagnosis and therapy by improving the further understanding of adrenal hemorrhage.Methods The clinical data of 12 cases of adrenal hemorrhage confirmed by pathology admitted to the First Hospital of China Medical University from October 2006 to October 2017 were retrospectively analyzed.Observe the patient's clinical manifestations,imaging features,treatment methods and prognosis.Results All 12 cases were unilateral adrenal hemorrhage,8 cases manifested lumbago in troubled side,2 cases manifested abdominal pain,and 2 cases were found during physical examination incidentally with no obvious symptoms.Ultrasound-B was performed in 10 cases,revealed low echo of masses in 5 cases,mixed echo of masses in 2 cases,cystic echo of masses in 2 cases,and no abnormality in 1 case.All 12 cases were scanned by CT,9 cases showed cystic masses with mixed density,and 3 cases showed solid masses.The value of plain CT ranged from 31 HU to 77 HU,no obvious enhancement was found in enhanced scan.One case was scanned by MRI,showed round mass in left adrenal gland,with uneven signal.The main signal was iso-signal in T1-weighted and T2-weighted.Six cases underwent adrenal and mass resection through the 11th rib,3 cases underwent retroperitoneoscopic adrenalectomy,2 cases underwent abdominal exploration and accepted adrenalectomy and hematoma removal,and 1 case was discharged after conservative treatment because of surgery contraindication.11 cases of the pathology of postoperation were adrenal hemorrhage.Conclusions Preoperative diagnosis of adrenal hemorrhage is relatively difficult,ultrasound-B,CT,and MRI examination can help diagnose.Surgical treatment should be performed for patients who can tolerate surgery and with larger hematoma (＞5 cm).

Objective To assess the efficacy and side effects of intravesical instillation of BCG after transurethral resection of the bladder tumor (TURBT) in non-muscle invasive bladder cancer (NMIBC) patients.Methods The clinical data of patients treated with BCG 120 mg per course induced perfusion or more after TURBT from December 2013 to October 2016 in 18 hospitals of northeast China region,were analyzed retrospectively.The first part,data of 106 patients with moderate,high-risk NMIBC were collected.A total of 83 patients were male,while the other 23 patients were female.The average age was 66.7 years old.The clinical staging were T1 in 86(81.1％) cases,Ta in 20(18.9％) cases and carcinoma in situ in 6 (5.7％) patients.Intravesical instillation of BCG was executed after transurethral resection of the bladder tumor.The incidence rate of recurrence and progression during more than 6 months' follow-up time were observed.Multivariate analyses were done by using logistic analysis and Cox proportional hazards regression model with Kaplan-Meier method.The second part,treatment compliance of 276 patients with bladder cancer,including moderate/high-risk NMIBC in 263 cases,moderate/high-risk NMIBC followed with renal pelvis/ureteral carcinoma in 8 cases were and moderate/high-risk NMIBC with renal pelvis/ureteral carcinoma in 5 cases who treated with BCG after the surgeries,were observed.Patients consisted of 211 males and 65 females with average age of 68.3 years.Results With a median follow-up of 12 months,9 (8.5％) patients experienced tumor recurrence and 2 (1.9％) patients were found progression in the first part.The one-year cancer free recurrence rate of the patients was 91.5％.Statistically significant prognostic factors for recurrence identified by multivariable analyses were prior recurrence of the tumors (OR =3.214,95％CI0.804-12.845,P =0.099).In the second port,an incidence rate of adverse effects was 64.1％ (177/276).The Ⅲ/Ⅳ degree complications were occurred in 11 patients and satisfactory outcomes achieved with active treatment.A total of 36 patients withdrawal with the major causes were recurrence and progression of bladder tumor in 12 cases (4.4 ％),9 cases (3.3 ％) with economic reasons and 11 cases (4.0％) with serious complications.Conclusions NMIBC patients treated with intravesical BCG therapy have approving cancer free recurrence rates and acceptable adverse effects.Prior recurrence may be prognostic factor of recurrence after intravesical BCG therapy.

Objective To compare the different pathological type of renal tumor,clinical epidemiology,imaging and pathological features,summarize its value in the diagnosis of renal tumor.Methods The clinical data of 2198 patients who underwent surgical treatment in our hospital due to renal tumors from January 2010 to January 2019 were retrospectively analyzed.There were 1 404 males and 794 females with an average age of (56.5 ± 11.7) years old.The clinical epidemiology,image features and pathological features were compared.Results Among them,the pathological results concluded 1 891 cases of renal clear cell carcinoma (86.0％),112 cases of papillary renal cell carcinoma (5.1％),76 cases of chromophobe cell carcinoma (3.5％),23 cases of multilocular cystic renal tumors with low malignant potential (1.0％),13 cases of Xp11.2 translocation carcinoma (0.6％),4 cases of collecting duct carcinoma (0.2％),58 cases of anadipotic angiomyolipoma (2.6％),18 cases of acidophiloma (0.8％),and 3 cases of metanephric adenoma (0.1％).The overall differences in age and gender among patients with renal tumors of different pathological types were statistically significant (F =13.8,P ＜ 0.05;x2 =20.5,P ＜ 0.05),Xpl 1.2-translocated carcinoma had the lowest mean age of onset,which was (44.9 ± 17.1 years old).The percentage of women with anadipotic angiomyolipoma was higher (41,70.7％),and the percentage of men with clear cell carcinoma and papillary renal cell carcinoma was higher (1 253,66.3％) and(77,68.8％).There was no statistically significant difference in side sex and clinical manifestations among patients with different pathological types of renal tumors (x2 =16.27,P ＞ 0.05).No significant difference in the distribution of left and right side,the clinical manifestations were mainly sporadic (x2 =19.63,P ＞ 0.05).The results of renal tumors ultrasound ith different pathological types showed statistically significant difference (x2 =67.l,P ＜ 0.05).Hyperechoic (20,34.5％) and mixed echogenicity (16,27.6％) were the main manifestations of lipoma.Multilocular cystic renal tumors with low malignant potential were mostly cystic and solid mixed echogenicity (14,60.9％).CT values of renal tumors of different pathological types at all stages showed statistically significant differences (P ＜ 0.05).The CT values of clear cell carcinoma at the arterial phase of CT enhanced scan were significantly higher than those of other types of tumors (F =11.6,P ＜ 0.05),but decreased significantly in the parenchymal phase,showing the enhancement characteristics of "fast in and fast out".The CT values of papillary cell carcinoma in the third phase of enhanced scan were all lower than those of clear cell carcinoma and chromophobe cell carcinoma (P ＜ 0.05),showing a "progressive enhancement".The enhancement effect of chromophobe cell carcinoma is somewhere in between.The CT value on plain scan of anadipotic angiomyolipoma was higher than that of clear cell carcinoma,and the enhancement was followed by continuous enhancement,showing the characteristics of "fast in and slow out".The majority of clear cell carcinoma and papillary cell carcinoma were tan section (1 235,72.55％;51,52.13％).The grey-white section was the most common type of adipogenic angiomyolipoma (21,40.4％).Conclusions The epidemiological characteristics,imaging and pathological features of renal tumors of different pathological types have certain characteristics,especially the enhanced CT features of renal clear cell carcinoma,papillary renal cell carcinoma,chromophobe cell carcinoma and anadipotic angiomyolipoma,which are of certain value for the differential diagnosis of renal tumors of different pathological types.