Atractylenolide-I covalently binds to CYP11B2, selectively inhibits aldosterone synthesis, and improves hyperaldosteronism

Hyperaldosteronism is a common disease that is closely related to endocrine hypertension and other cardiovascular diseases. Cytochrome P450 11B2 (CYP11B2), an important enzyme in aldosterone (ALD) synthesis, is a promising target for the treatment of hyperaldosteronism. However, selective inhibitors targeting CYP11B2 are still lacking due to the high similarity with CYP11B1. In this study, atractylenolide-I (AT-I) was found to significantly reduce the production of ALD but had no effect on cortisol synthesis, which is catalyzed by CYP11B1. Chemical biology studies revealed that due to the presence of Ala320, AT-I is selectively bound to the catalytic pocket of CYP11B2, and the C8/C9 double bond of AT-I can be epoxidized, which then undergoes nucleophilic addition with the sulfhydryl group of Cys450 in CYP11B2. The covalent binding of AT-I disrupts the interaction between heme and CYP11B2 and inactivates CYP11B2, leading to the suppression of ALD synthesis; AT-I shows a significant therapeutic effect for improving hyperaldosteronism.

Clinicopathological features of liposarcoma of the extremities: analysis of 14 cases / 肿瘤研究与临床

Objective:To investigate the clinicopathological characteristics, diagnosis and differential diagnosis of liposarcoma of the extremities.Methods:Fourteen patients with atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL), dedifferentiated liposarcoma (DDL) and myxoid liposarcoma (ML) in Beijing Tiantan Hospital of Capital Medical University from March 2002 to December 2019 were collected. Fluorescence in situ hybridization (FISH) and immunohistochemical staining were used to detect the MDM2 gene amplification and expressions of S-100, CDK4 and MDM2 proteins in tumor tissues. The characteristics of different types of liposarcoma were comprehensively analyzed combined with clinical data and histopathological characteristics.Results:The age of 14 patients was (55.6±16.7) years old, with 10 males and 4 females. There were 2 cases of ALT/WDL, 6 cases of DDL, and 6 cases of ML. Immunohistochemistry showed that S-100 was positive in all patients and the patterns were scattered, partial and extensive. CDK4 and MDM2 were positive in both ALT/WDL and DDL, and weakly expressed in ML (4 cases). Vimentin was positive in all patients. MDM2 gene amplification was detected in 2 cases of ALT/WDL and 6 cases of DDL.Conclusion:Liposarcoma has a high incidence and obvious morphological diversity, accurate diagnosis is critical to the prognosis and treatment of the tumor.

Pelvic serous carcinoma of female:a clinicopathogical analysis of 20 cases / 临床与实验病理学杂志

Purpose To study the clinicopathological and immunohistochemical features, carcinogenesis and differential diagnosis of female pelvic serous carcinoma. Methods The clinical data, macroscopic and microscopic features and immunostaining results of 20 patients with pelvic serous carcinoma were studied, and some associated literatures were reviewed. Results 20 cases of PSC aged from 23 to 87, with the mean age being 58. 9. PSC may occur in fallopian tube, ovary and peritoneum, while they were referred to hospital because of abdominal distention, abdominal pain or pelvic mass. The tumor often invasive pelvic organs diffusely when they were diag-nosed, so, the primary site were difficultly determined. Usually, the primary focus of serous carcinoma of fallopian tube is small and easily planted in pelvic. The patients with ovarian serous carcinoma or peritoneal serous carcinoma had serous tubal intraepithelial car-cinoma at the mean time. Conclusions The tubal epithelial cells may be the major source of PSC. About the specimen of PSC, we need check the fallopian tube carefully to determine the primary site, and make differential diagnosis with peritoneal malignant mesothe-lioma and metastatic carcinoma from other sites than pelvic when it diffusely invasive peritoneum.

In situ HYBRIZATION STUDY ON GAP-43mRNA EXPRESSION DURING NERVE INJURE / 解剖学报

Objective To study GAP\|43mRNA expression during nerve injure and regeneration. Methods Rat sciatic nerve was crushed then, in situ hybridization technique was used to explore GAP\|43mRNA expressions in spinal cord and dorsal root ganglion (DRG). Results The neurons of spinal cord and DRG were detected to have GAP\|43 hybridization sinal by 2 days after sciatic nerve lesion. At later times(4,7 and 14 days postsurgery) the anterior horn motor neurons and DRG cells showed an increase in the number of GAP\|43mRNA positive neurons, followed by a significant rise in their content of GAP\|43mRNA. The number of GAP\|43mRNA positive neurons was decreased by 30 days postinjure, and was nearly nomal 60 days postinjure.Conclusion GAP\|43mRNA expression was increased during peripheral nerve injure and regeneration. The study showed that GAP\|43 may play a key role in nerve regeneration. [

Diagnostic Value of HRCT in Primary Sjgren’s Syndrome / 实用放射学杂志

Objective To study the HRCT appearances and diagnostic value of primary Sjgren’s syndrome ( pSS ) . Methods CT images of 12 cases of pSS were retrospectively analyzed . Results CT and HRCT scans showed pulmonary interstitial diseases in different degree mainly localized periphery of lung in all cases,the ground-glass opacity and interlobular septal thickening were preliminary features of pSS.Conclusion The ground-glass opacity of lung is active preliminary features of pSS,while the honeycombed lung is final feature of pSS.HRCT can help to determine the stage of pSS,and to estimate the prognosis in patients with pSS.

CT Diagnosis of the Lobaris Bronchial Intraluminal Cancer / 实用放射学杂志

Objective To summarize the CT signs and clinic characteristics to improve the CT diagnoses ability on the lobar bronchial intraluminal cancer and provide a well comprehension for it.Methods To study the clinical symptom and CT presentation in 7 cases with the lobar bronchial intraluminal cancer which had been confirmed by bronchoscopy and pathologic exam.Results 3 cases were in right superior lobaris bronchus,1 case in right middle lobaris bronchus,3 cases in left superior lobaris bronchus.Obstructive pneumonia were found in 7 cases.Obstructive atelestasis in 5 cases.The nodules or emboluses within lobaris bronchus were showed by CT in all cases and the obstructive signs on each patient in its degrees. Conclusion To get the CT diagnosis of the lobar bronchial cancer is easily be delayed. But if pay attention and keep it a close combination with clinic, the early diagnosis will be attained on time.

EFFECTS OF PROTEIN KINASE C SUBTYPE IN THE GROWTH OF PRIMARY CULTURED NEURONS / 解剖学报

Objective To study the role of different subtypes of PKC in the neurite outgrowth of primary cultured neurons from embryonic rat spinal cord. Methods We observed the expression and distribution of protein kinase C(?、?Ⅰ、?Ⅱ、? subtypes) by using immunohistrochemical technique in the neurite outgrowth of the primary cultured neurons from the embryonic rat spinal cord by means of computer image analysis system to measure the lengths of neurites and the areas of bodies. Results The areas of the cultured neuronal bodies increased and the neurites prolonged while the expression of the four subtypes of PKC gradually increased before 7div(day in vitro )during primary cultured neurons growth. The expression both in bodies and neurites of neurons decreased after 7div and the processes gradually shrinked and at the same time bubbles appeared inside the bodies. Relative assay demonstrated that ?Ⅱ subtype was most relative to the outgrowth of neurites( r =0 73, P

THE ANATOMY AND CLINICAL SIGNIFICANCE OF THE TERMINAL SEGMENT OF THE SUPERFICIAL MIDDLE CEREBRAL VEIN——WITH TWO VARIANT DURAL VENOUS SINUSES / 解剖学报

The superficial middle cerebral veins (SMCV) of 50 human heads were dissectedunder the operating microscope (10?).There were 122 terminal braches of the SMCV in the specimens and the typesof their drainage can be divided into four:type 1 (41.00%)—drains into the caver-nous sinus;type 2 (24.60%)—drains into the variant venous sinus in the lateralwall of the cavernous sinus;type 3(28.70%)—drains into the variant venous sinus inthe dura of the middle cranial fossa;type 4(5.70%)—drains into other dural venoussinuses.Type 1 may be considered as normal and the others as variant.The two variant dural venous sinuses reported are respectively located in thelateral wall of the cavernous sinus,named“the lateral wall sinus of the cavernoussinus”,and in the dura of the middle cranial fossa,named the“variant sinus ofthe middle cranial fossa”.The former occurred 27% in the specimens and the later25%.We have discussed about the drainage of the SMCV and two variant dural ven-ous sinuses on the embryonic basis and the clinical practice.