TFE3/TFEB translocation renal cell carcinoma(TFE3/TFEB tRCC)occupies a prominent position in the molecular pathological classification of renal cancers due to its distinctive genetic abnormalities and its clinical pre-dilection for younger patients.Over nearly two decades of research,the spectrum of TFE3/TFEB fusion partner genes has expanded,highlighting the increasing morphological heterogeneity of TFE3/TFEB tRCC.This article reviews the clinicopathological and molecular features of TFE3/TFEB tRCC,emphasizing the associations between the major fusion subtypes and their morphological manifestations as well as immunophenotypes.Additionally,the practical value of an-cillary diagnostic techniques,such as molecular testing,is summarized,aiming to provide a reference for the routine and differential diagnosis of TFE3/TFEB tRCC.

Objective:To investigate the clinicopathological features including immunophenotype, molecular characteristics, differential diagnosis and prognosis of SMARCB1-deficient renal medullary carcinoma (RMC) without sickle cell trait.Methods:The clinicopathological data of 12 cases of SMARCB1-deficient RMC without sickle cell trait were collected from 7 domestic institutions during the period of 2015 to 2024. Their clinical characteristics, morphological features and immunohistochemical properties were observed and analyzed. High-throughput DNA-targeted next-generation sequencing was performed, and follow-up data were gathered along with relevant literature review.Results:Among the 12 patients, 5 were female and 7 were male. The patients age ranged from 27 to 84 years with a median age of 58.5 (46.0, 71.0) years. None of them had sickle cell disease or other hemoglobinopathies. Eight cases occurred in the left kidney and 4 cases were located in the right kidney. The average maximum diameter of the tumor was 6.1 (4.0,7.5) cm, with a range of 2.0 to 14.9 cm (the median maximum diameter 5.5 cm). Histologically, the tumors showed poorly differentiated adenocarcinoma, arranged in solid and tubular patterns. Papillary structure was noted in 5 cases, cribriform structure in 3 cases, rhabdoid differentiation in 3 cases, and sarcomatoid differentiation in 2 cases. Inflammatory desmoplastic stromal reaction was observed in 8 cases, among which stromal myxoid degeneration was seen in 6 cases. Tumor necrosis was apparent in 6 cases. The tumor cells had abundant eosinophilic or clear cytoplasm and prominent nucleoli. The nuclear grading was grade 3 or 4 according to the International Society of Urological Pathology (ISUP). Immunohistochemical staining showed that the tumor cells of all 12 cases expressed PAX8 and loss of SMARCB1/INI1 protein expression, and 5 of 10 cases expressed OCT3/4. Seven samples had valid archived paraffin tissues for high-throughput DNA-targeted next-generation sequencing. The results showed that all 7 cases had pathogenic mutations in the SMARCB1 gene. The mutation sites included exon5 c.595A>T (p.K199*), exon2 c.200_207del (p.S67*), exon2 p.G69VfsTer16, exon7 c.986G>T (p.S329I), exon7 c.886A>T (p.K296*), exon6 c.635T>A (p.L212*), exon5 c.577del (p.M193Wfs16), and exon6 c.784del (p.V262Sfs5). Follow-up data were obtained for 6 of 12 patients. Among them, 1 patient had lung and bone metastases, 1 patient had liver and bone metastases and 1 patient had multiple bone metastases at the time of diagnosis; 1 patient had bone metastases 5 months after surgery. One patient died of postoperative complications 10 days after surgery, 4 patients died of tumors (the survival time ranged from 4 to 8 months), and 1 patient had no recurrence or metastasis during the 8-month follow-up after surgery.Conclusions:SMARCB1-deficient RMC without sickle cell trait is a highly aggressive and poorly differentiated renal cell carcinoma. It has similar histomorphology, immunophenotype, molecular characteristics and prognosis to RMC, which further supports that it is a sporadic subtype of RMC related to sickle cell trait.

Objective:To investigate the clinicopathological features, immunophenotype, molecular characteristics, and differential diagnosis of MED15-TFE3 gene fusion renal cell carcinoma (MED15-TFE3 RCC).Methods:A total of 12 MED15-TFE3 RCCs, diagnosed from 2016 to 2023, were collected from the Department of Pathology of Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China for clinicopathologic, immunohistochemical, fluorescence in situ hybridization (FISH) and RNA sequencing (RNA-seq) analyses and follow-up. In addition, its diagnosis and differential diagnosis were also explored.Results:There were five males and seven females. The patients′ ages ranged from 16 to 60 years, with an average age of 40.4 years. The follow-up time ranged from 15 to 92 months, and no recurrence or metastasis was observed. Histologically, 6 cases exhibited extensive cystic structures with almost no solid sheet components, while the remaining 6 cases displayed a cysto-solid growth pattern. The cytoplasm of the tumor cells appeared flocculent, with a clear or faintly eosinophilic appearance, and nucleoli were inconspicuous. Psammoma bodies were observed in 12 cases. There was deposition of basement membrane-like material in 5 cases. All cases showed strong expression of TFE3, GPNMB, Cathepsin K, Melan A, and PAX8, while no expression of CAⅨ or CK7. FISH analyses showed that all 12 cases were positive for the MED15-TFE3 fusion, while the MED15-TFE3 fusion gene and specific fusion sites were detected in 2 cases using RNA-seq.Conclusions:MED15-TFE3 RCC is a type of TFE3-rearranged renal cell carcinoma that exhibits both identifiable diagnostic characteristics and highly deceptive morphology. Its distinct extensive cystic structure can be easily confused with multilocular cystic renal neoplasm of low malignant potential, necessitating careful differentiation in routine practice.

TFE3/TFEB translocation renal cell carcinoma(TFE3/TFEB tRCC)occupies a prominent position in the molecular pathological classification of renal cancers due to its distinctive genetic abnormalities and its clinical pre-dilection for younger patients.Over nearly two decades of research,the spectrum of TFE3/TFEB fusion partner genes has expanded,highlighting the increasing morphological heterogeneity of TFE3/TFEB tRCC.This article reviews the clinicopathological and molecular features of TFE3/TFEB tRCC,emphasizing the associations between the major fusion subtypes and their morphological manifestations as well as immunophenotypes.Additionally,the practical value of an-cillary diagnostic techniques,such as molecular testing,is summarized,aiming to provide a reference for the routine and differential diagnosis of TFE3/TFEB tRCC.

Objective:To investigate the clinicopathological features including immunophenotype, molecular characteristics, differential diagnosis and prognosis of SMARCB1-deficient renal medullary carcinoma (RMC) without sickle cell trait.Methods:The clinicopathological data of 12 cases of SMARCB1-deficient RMC without sickle cell trait were collected from 7 domestic institutions during the period of 2015 to 2024. Their clinical characteristics, morphological features and immunohistochemical properties were observed and analyzed. High-throughput DNA-targeted next-generation sequencing was performed, and follow-up data were gathered along with relevant literature review.Results:Among the 12 patients, 5 were female and 7 were male. The patients age ranged from 27 to 84 years with a median age of 58.5 (46.0, 71.0) years. None of them had sickle cell disease or other hemoglobinopathies. Eight cases occurred in the left kidney and 4 cases were located in the right kidney. The average maximum diameter of the tumor was 6.1 (4.0,7.5) cm, with a range of 2.0 to 14.9 cm (the median maximum diameter 5.5 cm). Histologically, the tumors showed poorly differentiated adenocarcinoma, arranged in solid and tubular patterns. Papillary structure was noted in 5 cases, cribriform structure in 3 cases, rhabdoid differentiation in 3 cases, and sarcomatoid differentiation in 2 cases. Inflammatory desmoplastic stromal reaction was observed in 8 cases, among which stromal myxoid degeneration was seen in 6 cases. Tumor necrosis was apparent in 6 cases. The tumor cells had abundant eosinophilic or clear cytoplasm and prominent nucleoli. The nuclear grading was grade 3 or 4 according to the International Society of Urological Pathology (ISUP). Immunohistochemical staining showed that the tumor cells of all 12 cases expressed PAX8 and loss of SMARCB1/INI1 protein expression, and 5 of 10 cases expressed OCT3/4. Seven samples had valid archived paraffin tissues for high-throughput DNA-targeted next-generation sequencing. The results showed that all 7 cases had pathogenic mutations in the SMARCB1 gene. The mutation sites included exon5 c.595A>T (p.K199*), exon2 c.200_207del (p.S67*), exon2 p.G69VfsTer16, exon7 c.986G>T (p.S329I), exon7 c.886A>T (p.K296*), exon6 c.635T>A (p.L212*), exon5 c.577del (p.M193Wfs16), and exon6 c.784del (p.V262Sfs5). Follow-up data were obtained for 6 of 12 patients. Among them, 1 patient had lung and bone metastases, 1 patient had liver and bone metastases and 1 patient had multiple bone metastases at the time of diagnosis; 1 patient had bone metastases 5 months after surgery. One patient died of postoperative complications 10 days after surgery, 4 patients died of tumors (the survival time ranged from 4 to 8 months), and 1 patient had no recurrence or metastasis during the 8-month follow-up after surgery.Conclusions:SMARCB1-deficient RMC without sickle cell trait is a highly aggressive and poorly differentiated renal cell carcinoma. It has similar histomorphology, immunophenotype, molecular characteristics and prognosis to RMC, which further supports that it is a sporadic subtype of RMC related to sickle cell trait.

Objective:To investigate the clinicopathological features, immunophenotype, molecular characteristics, and differential diagnosis of MED15-TFE3 gene fusion renal cell carcinoma (MED15-TFE3 RCC).Methods:A total of 12 MED15-TFE3 RCCs, diagnosed from 2016 to 2023, were collected from the Department of Pathology of Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China for clinicopathologic, immunohistochemical, fluorescence in situ hybridization (FISH) and RNA sequencing (RNA-seq) analyses and follow-up. In addition, its diagnosis and differential diagnosis were also explored.Results:There were five males and seven females. The patients′ ages ranged from 16 to 60 years, with an average age of 40.4 years. The follow-up time ranged from 15 to 92 months, and no recurrence or metastasis was observed. Histologically, 6 cases exhibited extensive cystic structures with almost no solid sheet components, while the remaining 6 cases displayed a cysto-solid growth pattern. The cytoplasm of the tumor cells appeared flocculent, with a clear or faintly eosinophilic appearance, and nucleoli were inconspicuous. Psammoma bodies were observed in 12 cases. There was deposition of basement membrane-like material in 5 cases. All cases showed strong expression of TFE3, GPNMB, Cathepsin K, Melan A, and PAX8, while no expression of CAⅨ or CK7. FISH analyses showed that all 12 cases were positive for the MED15-TFE3 fusion, while the MED15-TFE3 fusion gene and specific fusion sites were detected in 2 cases using RNA-seq.Conclusions:MED15-TFE3 RCC is a type of TFE3-rearranged renal cell carcinoma that exhibits both identifiable diagnostic characteristics and highly deceptive morphology. Its distinct extensive cystic structure can be easily confused with multilocular cystic renal neoplasm of low malignant potential, necessitating careful differentiation in routine practice.

Sepsis is an organ dysfunction syndrome secondary to a host's dysfunctional response to infection.Its pathogenesis is complex,and inflammatory factors play an important role in its course.Sepsis has a high mortality and is difficult to treat.Clinicians are constantly exploring new treatment methods to reduce the fatality rate.Blood purification therapy is a developing auxiliary treatment method for sepsis.Blood purification therapies for sepsis include plasma exchange,continuous renal replacement therapy,and hemoperfusion.Though operating through different mechanisms-removing cytokines,endotoxins,or pathogens-these therapies share the goal of improving patient outcomes.This article aims to summarize the application progress of various blood purification methods in the treatment of sepsis,in order to clarify the effectiveness of blood purification therapy in infectious diseases.However,the specific implementation timing and frequency still need further exploration,laying a foundation for subsequent research.

Sepsis is an organ dysfunction syndrome secondary to a host's dysfunctional response to infection.Its pathogenesis is complex,and inflammatory factors play an important role in its course.Sepsis has a high mortality and is difficult to treat.Clinicians are constantly exploring new treatment methods to reduce the fatality rate.Blood purification therapy is a developing auxiliary treatment method for sepsis.Blood purification therapies for sepsis include plasma exchange,continuous renal replacement therapy,and hemoperfusion.Though operating through different mechanisms-removing cytokines,endotoxins,or pathogens-these therapies share the goal of improving patient outcomes.This article aims to summarize the application progress of various blood purification methods in the treatment of sepsis,in order to clarify the effectiveness of blood purification therapy in infectious diseases.However,the specific implementation timing and frequency still need further exploration,laying a foundation for subsequent research.

Objective:To explore the relationship between rumination and depression and suicide attempts, and the mediating effect of rumination between depression and suicide attempts in adolescents with depressive disorder.Methods:Clinical interviews and questionnaires were conducted on 331 adolescents aged 11-18 with depressive disorders.Depressive symptoms were assessed with patient health questionnaire-9 (PHQ-9). Rumination was assessed with ruminative responses scale-10 (RRS-10), and Chinese version of the sociality module of MINI5.0 was used to assess suicide.SPSS 23.0 software was applied to descriptive statistics, Chi-square test, t-test, Spearman correlation analysis and hierarchical regression analysis, and the SPSS macro program PROCESS V 3.4 was used for Bootstrap mediating effect. Results:The incidence of suicide attempts in adolescents with depressive disorder was 53.78%, which was significantly higher in girls (59.48%) than that in boys (40.40%), and the difference was significant ( χ2=10.16, P<0.01). In contrast to the non-suicide attempt group, suicide attempt group had higher scores on PHQ-9((11.08±9.26) vs (14.43±7.49), t=-3.634, P<0.01), brooding ((10.76±3.89) vs (12.44±3.87), t=-3.926, P<0.01), reflection ((10.05±3.54) vs (11.20±3.33), t=-3.044, P<0.01) and rumination total score ((20.81±6.78) vs (23.64±6.42), t=-3.898, P<0.01). Regression analysis revealed that girl ( β=0.175, t=3.228, P=0.001), depressive symptoms ( β=0.168, t=3.082, P=0.002), rumination ( β=0.138, t=2.364, P=0.019) were risk factors for suicide attempts.Rumination played a complete mediating effect between depressive symptoms and suicide attempts (effect value=0.013, 95% CI=0.003-0.027). Depression symptoms significantly and positively predicted rumination ( P<0.01), and rumination significantly and positively predicted suicide attempts ( P<0.05). Conclusion:The incidence of suicide attempts was high in adolescents with depressive disorders.Depressive symptoms affect suicide attempts mainly through rumination.Clinicians should assess the rumination of adolescents with depressive disorders.In addition, clinicians should implement concurrent psychotherapy to adjust the cognitive response and reduce rumination, in order to improve the mental health and reduce suicide attempts.

Objective:To investigate the diagnostic role of NR4A3/NOR-1 immunohistochemistry in acinic cell carcinoma (AciCC) of the salivary gland.Methods:A total of 142 tumors were collected from 2004 to 2020 at Nanjing Jinling Hospital, including 24 cases of AciCCs, 12 salivary gland secretory carcinomas,14 salivary duct carcinomas,16 adenoid cystic carcinomas,3 basal cell carcinomas,13 mucoepidermoid carcinomas,7 myoepithelial carcinomas,15 pleomorphic adenomas,15 warthin tumor, 8 myoepithelioma,8 basal cell adenomas, and 7 oncocytomas; 28 normal salivary gland tissues and 2 pancreatic AciCC were also included.Results:NR4A3/NOR-1,a nuclear marker,was positive in 91.7% (22/24) of AciCC of the salivary gland,while DOG1,a membranous and cytoplasmic marker, demonstrated a sensitivity of 95.8% (23/24);there was no significant difference in the overall positive rates( P=0.551), but the stain pattern was different. NR4A3/NOR-1 was negative in normal salivary gland tissues and any other types of tumors in the salivary gland; however,DOG1 showed apical staining in the acinar cells in the salivary gland,as well as salivary gland secretory carcinomas,adenoid cystic carcinomas,basal cell carcinomas,mucoepidermoid carcinomas,myoepithelial carcinomas and basal cell adenomas( P<0.001). NR4A3/NOR-1 showed a high sensitivity(91.7%) and specificity(100%) to identify AciCC of the salivary gland,and in combination with DOG1, the sensitivity increased to 100%. Furthermore, NR4A3/NOR-1 were only positive for AciCC arising from salivary glands but not pancreas(0/2)( P=0.018). Conclusion:NR4A3/NOR-1 is a special and sensitive biomarker for AciCC of salivary glands; combined NR4A3/NOR-1 and DOG1 can be an ideal diagnostic immunohistochemical panel for AciCC.