ObjectiveTo explore the differences in response to bakuchiol-induced hepatotoxicity between Institute of Cancer Research （ICR） mice and Kunming （KM） mice. MethodThe objective manifestations of bakuchiol-induced hepatotoxicity in mice were confirmed by acute and subacute toxicity animal experiments， and enrichment pathways of differential genes between normal ICR mice and KM mice were compared by transcriptomics. The real-time quantitative polymerase chain reaction （real-time qPCR） assay was used to verify the mRNA expression of key genes in the related pathways to confirm the species differences of bakuchiol-induced liver injury. ResultIn the subacute toxicity experiment， compared with the normal mice， the ICR mice showed increased serum content of alkaline phosphatase （ALP）， and 5′-nucleotidase （5′-NT）， without significant difference， and no manifest change was observed in KM mice. Pathological results showed that hepatocyte hypertrophy was the main pathological feature in ICR mice and hepatocyte steatosis in KM mice. In the acute toxicity experiment， KM mice showed erect hair， mental malaise， and near-death 3 days after administration. The levels of serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in KM mice （400 mg·kg^-1） significantly increased（P<0.01）， and the activity of total reactive oxygen species （SOD） in liver significantly decreased（P<0.01）compared with those in normal mice， while the serum content of 5′-NT and cholinesterase （CHE） in ICR mice （400 mg·kg^-1） were significantly elevated （P<0.01）. The liver/brain ratio in ICR mice increased by 20.34% and that in KM mice increased by 29.14% （P<0.01）. The main pathological manifestation of the liver in ICR mice was hepatocyte hypertrophy， while those in KM mice were focal inflammation， hepatocyte hypertrophy， and hepatocyte steatosis. Kyoto Encyclopedia of Genes and Genomes（KEGG）and Reactome pathway enrichment analyses showed that the differential gene expression between ICR mice and KM mice was mainly involved in oxidative phosphorylation， bile secretion， bile acid and bile salts synthesis， and metabolism pathway. CYP7A1 was up-regulated in all groups with drug intervention （P<0.01） and MRP2 was reduced in all groups with drug intervention of KM mice （P<0.01） and elevated in all groups with drug intervention of ICR mice （P<0.01） compared with those in the normal group. The expression of BSEP was lowered in ICR mice with acute liver injury （400 mg·kg^-1） （P<0.05）. SHP1 was highly expressed in KM mice with acute liver injury （400 mg·kg^-1）. The expression of FXR was diminished in ICR mice with subacute liver injury （200 mg·kg^-1） （P<0.01）. SOD1， CAT， and NFR2 significantly decreased in KM mice with acute liver injury （400 mg·kg^-1）， and CAT dwindled in KM mice with subacute liver injury （200 mg·kg^-1） （P<0.01）. GSTA1 and GPX1 significantly increased in KM mice with acute liver injury （400 mg·kg^-1） （P<0.01） and SOD1， CAT， NRF2， and GSTA1 significantly increased in ICR mice with subacute liver injury （200 mg·kg^-1） （P<0.01）. CAT and NRF2 significantly increased in ICR mice with acute liver injury （400 mg·kg^-1） （P<0.01）. ConclusionWith the increase in the dosage of bakuchiol， the liver injury induced by oxidative stress in KM mice was gradually aggravated， and ICR mice showed stronger antioxidant capacity. The comparison of responses to bakuchiol-induced hepatotoxicity between ICR mice and KM mice reveals that ICR mice are more suitable for the investigation of the mechanisms related to bile secretion and bile acid metabolism in the research on bakuchiol-induced hepatotoxicity in mice. KM mice are more prone to liver injury caused by oxidative stress.

The structure and performance of nuclear cytoplasmic autophagosomes was explored. Seventeen cases of hepatocellular carcinoma and liver cells with other diseases from liver tissues were selected. The nuclear cytoplasm were isolated and degraded by the nuclear membrane. Damaged cytoplasm had damaged its own membrane and the surrounding nuclear tissues other than the nuclear membrane, leading to specific nucleolysis and cell death of liver cancer cells and liver cells.

OBJECTIVE： To study the effects of ADRB2 （rs1042713） gene polymorphism on therapeutic efficacy of anticholinergic drug in the treatment for refractory asthma pediatric patients. METHODS： 171 children with refractory asthma were selected from outpatient department of Kunming Children’s Hospital during Nov. 2016 to Jul. 2019. The distribution of ADRB2 （rs1042713） genotype， the clinical efficacy [asthma control test （C-ACT） score， FEV1， FVC， PEF， maximal mid-expiratory flow （MMEF）] of anticholinergic drug were analyzed statistically； the response of different genotypes to the use of anticholinergic drug were also analyzed statistically. RESULTS： 148 of 171 refractory asthmatics pediatric patients were administered anticholinergic drug， among them 50 of the 71 AA genotype and 36 of the 77 GA genotype responded to anticholinergic drug treatment. Statistical analysis showed that 71 children with AA refractory asthma had improved C-ACT score， FEV1， FVC， PEF and MMEF， there was statistical significance， compared with GA genotype （P＜0.05）； the response rate of the AA genotype to anticholinergic drugs was 2.71 times that of the GA genotype [OR＝2.71， 95％CI （1.38， 5.34）， P＝0.005]. CONCLUSIONS： The detection of ADRB2 （rs1042713） gene polymorphism has some guiding significance in the treatment of refractory asthma with anticholinergic drugs， and the response of AA genotype is better.

We evaluated the role of IL-10- in IL-33-mediated cholesterol reduction in macrophage-derived foam cells (MFCs) and the mechanism by which IL-33 upregulates IL-10. Serum IL-33 and IL-10 levels in coronary artery disease patients were measured. The effects of IL-33 on intra-MFC cholesterol level, IL-10, ABCA1 and CD36 expression, ERK 1/2, Sp1, STAT3 and STAT4 activation, and IL-10 promoter activity were determined. Core sequences were identified using bioinformatic analysis and site-specific mutagenesis. The serum IL-33 levels positively correlated with those of IL-10. IL-33 decreased cellular cholesterol level and upregulated IL-10 and ABCA1 but had no effect on CD36 expression. siRNA-IL-10 partially abolished cellular cholesterol reduction and ABCA1 elevation by IL-33 but did not reverse the decreased CD36 levels. IL-33 increased IL-10 mRNA production but had little effect on its stability. IL-33 induced ERK 1/2 phosphorylation and increased the luciferase expression driven by the IL-10 promoter, with the highest extent within the −2000 to −1752 bp segment of the 5′-flank of the transcription start site; these effects were counteracted by U0126. IL-33 activated Sp1, STAT3 and STAT4, but only the STAT3 binding site was predicted in the above segment. Site-directed mutagenesis of the predicted STAT3-binding sites (CTGCTTCCTGGCAGCAGAA→CTGCCTGGCAGCAGAA) reduced luciferase activity, and a STAT3 inhibitor blocked the regulatory effects of IL-33 on IL-10 expression. Chromatin immunoprecipitation (CHIP) confirmed the STAT3-binding sequences within the −1997 to −1700 and −1091 to −811 bp locus regions. IL-33 increased IL-10 expression in MFCs via activating ERK 1/2 and STAT3, which subsequently promoted IL-10 transcription and thus contributed to the beneficial effects of IL-33 on MFCs.
Binding Sites ; Cholesterol ; Chromatin Immunoprecipitation ; Computational Biology ; Coronary Artery Disease ; Foam Cells* ; Humans ; Interleukin-10* ; Interleukin-33* ; Luciferases ; Macrophages* ; Mutagenesis, Site-Directed ; Phosphorylation ; RNA, Messenger ; Transcription Initiation Site

OBJECTIVETo study the clinicopathologic features and differential diagnosis of alveolar soft part sarcoma (ASPS).

METHODSThe clinical data and pathologic features of 48 cases of ASPS were evaluated. Immunohistochemical study, PAS staining and fluorescence in-situ hybridization (FISH) were carried out in selected examples. Relevant literature was reviewed.

RESULTSAmongst the 48 cases studied, there were 17 males and 31 females, with male-to-female ratio of 1.0∶1.8. The age of patients ranged from 2 to 60 years (median=26 years). The tumor was most commonly located in deep soft tissue, especially that of lower extremities. Histologically, the tumor cells were arranged in alveolar or solid patterns and separated by sinusoidal vessels. They were large and contained abundant eosinophilic granules or crystals in cytoplasm. The nuclei were round to polygonal and vesicular, often with prominent nucleoli. Intravascular tumor extension was common. Some cases showed necrosis, hemorrhage and cystic changes. Immunohistochemical study showed that the tumor cells were positive for TFE3 (100%, 33/33). FISH assay was carried out in 4 cases and all of them had TFE3-ASPL gene fusion.

CONCLUSIONSASPS is a rare malignant neoplasm, often occurs in young patients. TFE3 is a useful immunohistochemical marker for diagnosis. The diagnosis is further confirmed by other markers.

Adolescent ; Adult ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; genetics ; Child ; Child, Preschool ; Diagnosis, Differential ; Female ; Gene Fusion ; Humans ; In Situ Hybridization, Fluorescence ; Male ; Middle Aged ; Oncogene Proteins, Fusion ; genetics ; Sarcoma, Alveolar Soft Part ; diagnosis ; pathology ; Young Adult

ObjectiveTo investigate the pathological characteristics, diagnosis, and differential diagnosis of embryonal rhabdomyosarcoma (ERMS) in the male reproductive system.

METHODSWe obtained the clinicopathological features, immunophenotypes, and electron microscopic findings of 11 male patients with ERMS in the reproductive system from 2000 to 2015, analyzed the data, and reviewed relevant literature.

RESULTSERMS developed in these patients at a median age of 17 (9－58) years, 3 cases in the testis, 4 in the scrotum, 1 in the epididymis, and 3 in the prostate. ERMS presented no clinical specificity, which made it difficult to be differentiated from inflammatory and other benign lesions. Microscopically, the tumor cells were arranged in a diffuse or fascicular distribution and mainly composed of short spindle-like, round, or irregularly shaped cells with nuclear hyperchromatism, the cytoplasm strongly eosinophilic, with differentiation of the striated muscle. Some of the cells were naively differentiated or tennis racket-shaped and some exhibited vacuolar degeneration in the cytoplasm. The nuclei were round or short spindle-shaped with visible nucleoli and mitoses. Immunohistochemically, the tumor cells were positive for Myogenin (5/6), Desmin (11/11), MyoD1 (8/9), and Myosin (1/2). Electron microscopy revealed early myofibrils in the cytoplasm of the tumor cells.

CONCLUSIONSERMS is a rare and highly malignant tumor characterized by local invasion and early metastasis and apt to develop in the reproductive system of young males. The diagnosis of the malignancy is mainly based on its histopathological and immunohistochemical manifestations, combined with electron microscopy when necessary. Early surgical resection in combination with radio- and chemotherapy is recommended for its treatment, which could reduce the recurrence of the tumor and improve the survival of the patients.

OBJECTIVETo study the clinicopathological characteristics of papillary cystadenoma of the epididymis.

METHODSUsing routine pathology and immunohistochemistry, we observed the surgically obtained samples from 2 cases of papillary cystadenoma of the epididymis, analyzed their pathological features and clinical presentations, and reviewed the related literature.

RESULTSThe 2 patients were both adult males. The tumors typically manifested as painless swelling in the epididymis, with occasionally dull pain and tenesmus in 1 of the cases. Pathologically, the lesions exhibited three morphological features, i. e., dilated ducts and small cysts surrounded by fibrous connective tissue, adenoid papillary hyperplasia into the cysts embraced by fibrovascular stroma, and acidophil substance present in the cysts. Immunohistochemistry showed that the tumors were strongly positive for CK8/18, CK7, and EMA, but negative for CK20, CEA, MC, Calretenin, P53, P63, SMA, VHL, and CD10, with the positive rate of Ki-67 <1%. Follow-up visits revealed good prognosis in both cases.

CONCLUSIONPapillary cystadenoma of the epididymis is a rare benign tumor in the male urogenital system, which may be accompanied by the VHL syndrome. Surgery is the first choice for its treatment.

Adult ; Cystadenoma, Papillary ; chemistry ; pathology ; Epididymis ; Genital Neoplasms, Male ; chemistry ; pathology ; Humans ; Immunohistochemistry ; Male ; von Hippel-Lindau Disease

Purpose To investigate the clinicopathological and immunohistochemical features of primary renal lymphomas ( PRL) , and to discuss the diagnosis, differential diagnosis, treatment and prognosis of the tumors. Methods Clinical data of 19 patients with PRL from January 2005 to October 2014 were retrospectively analyzed. Result The 19 patients in this study, there were 11 males and 8 females and the age ranged from 37 to 85 years old (averaged 55). Patients were mainly presented with unilateral renal masses, with lumbodynia as the main symptom. 13 patients underwent nephrectomy, 6 patients underwent renal biopsy and 17 patients received CHOP or R-CHOP chemotherapy. All of them were diagnosed as non-Hodgkin’ s lymphoma, with 14 cases of diffuse large B cell lym-phoma (DLBCL) (73. 684%, 14/19), 4 cases of B cell small cell lymphoma (21. 053%, 4/19), and 1 cases of T cell lymphoma (5. 263%, 1/19). Follow-up information was available in 15 patients. 12 were still alive and survived for 1~78 months, while the other 3 were dead with 1 case who died of cerebral infarction, and survived for 3~38 months ( averaged 23 months) . Conclusion PRL is an extranodal lymphoma which is rare in kidney and is often misdiagnosed as renal carcinomas due to its nonspecific clinical manifestations. The diagnosis of PRL can be confirmed by histopathological examination, immunohistochemistry and molecular analy-sis. The majority of the lymphomas are B cell lymphomas and most of them are DLBCL. The recommended treatment is surgery com-bined with chemotherapy and the prognosis is associated with the age, clinicopathological characteristics, tumor types and treatment.

Objective Cervical lymph node enlargement may be attributed to inflammation or tumors .This study was to analyze the pitfalls in fine-needle aspiration cytology ( FNAC) of cervical lymph nodes and the measures for avoiding misdiagnosis of cervical lymph node lesions . Methods We retrospectively analyzed the data about 435 cases of FNAC in comparison with the results of corre-sponding tissue biopsies in cervical lymph nodes . Results Among the 435 cases, 7 showed disagreement between the results of cytolog-ic and histologic diagnoses, which included 5 males and 2 females, at the age of 41 to 71 (58.4 ±8.9) years.Six of the cases presented with local lymph node enlargement and 1 with generalized lymphadenopathy, all with enlarged lymph nodes palpable 1-4 cm in diameter . Based on the results of FNAC, 1 case of malignant lymphoma was misdiagnosed as lowly differentiated adenocarcinoma, 1 case of lympho-ma misdiagnosed as poorly differentiated metastatic carcinoma, 2 cases of lymphoma diagnosed as lymphoproliferation and recommended for biopsy, 1 case suggestive of malignant tumor without further classification, and 2 cases microscopically characterized and recommended for lymph node biopsy.Compared with the results of the biopsy, FNAC achieved a 99.3%coincidence rate of qualitative diagnosis (432/425), with a misdiagnosis rate of 1.6%(7/435). Conclusion FNAC plays a very important role in the initial identification of the nature of lymph node lesions and the type of tumors.Practiced puncture skills and intimate knowledge about the histopathological features, diagnostic criteria, and differential diagnosis of the lymphatic system disorders are essential for improving the diagnostic accuracy of FNAC .