Advances in treatment and prognosis of MiT family translocated renal cell carcinoma / 中华泌尿外科杂志

MiT family translocation renal cell carcinoma mainly includes Xp11.2/TFE3 gene fusion-related renal cell carcinoma (TFE3 RCC)and t(6; 11)/TFEB gene fusion-related renal cell carcinoma(TFEB RCC), which is rare and there is no standard treatment plan yet, and the prognosis is still controversial. For localized lesions, surgery is the first choice for treatment, and systemic treatment such as targeted drugs and immune checkpoint inhibitors can be combined when there is metastasis. The application of gene testing provides the basis for personalized treatment. TFE3 RCC is highly invasive and has a poor prognosis, while TFEB RCC usually has a biological behavior of inertia and a better prognosis.

Nuciferine protects against high-fat diet-induced hepatic steatosis and insulin resistance via activating TFEB-mediated autophagy-lysosomal pathway

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis and insulin resistance and there are currently no approved drugs for its treatment. Hyperactivation of mTOR complex 1 (mTORC1) and subsequent impairment of the transcription factor EB (TFEB)-mediated autophagy-lysosomal pathway (ALP) are implicated in the development of NAFLD. Accordingly, agents that augment hepatic TFEB transcriptional activity may have therapeutic potential against NAFLD. The objective of this study was to investigate the effects of nuciferine, a major active component from lotus leaf, on NAFLD and its underlying mechanism of action. Here we show that nuciferine activated ALP and alleviated steatosis, insulin resistance in the livers of NAFLD mice and palmitic acid-challenged hepatocytes in a TFEB-dependent manner. Mechanistic investigation revealed that nuciferine interacts with the Ragulator subunit hepatitis B X-interacting protein and impairs the interaction of the Ragulator complex with Rag GTPases, thereby suppressing lysosomal localization and activity of mTORC1, which activates TFEB-mediated ALP and further ameliorates hepatic steatosis and insulin resistance. Our present results indicate that nuciferine may be a potential agent for treating NAFLD and that regulation of the mTORC1-TFEB-ALP axis could represent a novel pharmacological strategy to combat NAFLD.

Animal history: an interview with Professor Harriet Ritvo / História dos animais: uma entrevista com a professora Harriet Ritvo

Abstract It was in the 1980s that a new field in historical studies began to emerge, the animal history, or more specifically the history of human-animal relations. Harriet Ritvo - an eminent American historian and Emeritus Professor at Massachusetts Institute of Technology - is a pioneer in this field. Her career has been dedicated, among other activities, to researching, writing, teaching and lecturing on the subject. In this interview, Professor Ritvo talks about aspects of her academic trajectory, as well as important features of animal history, such as interactions between this area and other fields in which she also works: environmental history, the history of science and the history of technology.

Resumo Na década de 1980 começou a surgir um novo campo nos estudos históricos, a história dos animais, ou, mais especificamente, a história das relações entre os seres humanos e os animais. Harriet Ritvo - eminente historiadora norte-americana e professora emérita do Massachusetts Institute of Technology - é pioneira nessa área. Sua carreira tem sido dedicada à pesquisa, à escrita, ao ensino e à apresentação de palestras sobre o assunto. Nesta entrevista, Ritvo fala sobre aspectos de sua trajetória acadêmica e também sobre importantes questões da história dos animais, tais como as interações dessa área com outros campos nos quais ela também atua: história ambiental, história da ciência e história da tecnologia.

Two Cases of Chloromethylisothiazolinone and Methylisothiazolinone-associated Toxic Lung Injury

Previous animal studies have not conclusively determined the association between exposure to humidifier disinfectants (HDs) containing 5-chloro-2-methyl-4-isothiazolin-3-one (CMIT) and/or 2-methyl-4-isothiazolin-3-one (MIT) and development of HD-associated lung injuries. Nonetheless, patients exposed to HDs containing only CMIT and/or MIT showed clinically similar lung injuries to those exposed to HDs containing polyhexamethylene guanidine (PHMG) or oligo (2-[2-ethoxy]ethoxyethyl) guanidinium chloride (PGH). Here, we report twin sisters with lung injuries associated with exposure to CMIT/MIT-containing HDs. At 6 months of age, a younger twin sister presented with the 3-day history of cough, sputum, and respiratory difficulty. Chest radiography revealed multiple patchy consolidation and ground-glass opacities with pneumothorax and pneumomediastinum. Thoracostomy was performed due to pneumothorax at admission and she was discharged at 11 days of hospitalization. At 5 years of age, multiple tiny nodules and faint centrilobular ground-glass opacities were observed with the small pneumatocele. The elder sister visited a tertiary hospital due to dyspnea at 12 months of age. Chest radiography showed consolidation, pneumomediastinum, and pulmonary interstitial emphysema. There was no response to the administration of immunosuppressant drugs and antifibrotic agents. At 5 years of age, chest CT revealed ground-glass opacity and multiple tiny centrilobular ground-glass opacities nodules in both lungs with exercise intolerance.

MiT family translocation renal cell carcinoma:imaging findings in 15 patients / 复旦学报（医学版）

Objective To analyze the imaging findings in MiT family translocation renal cell carcinoma (RCC) for the better understanding on the rare tumor combined with its clinicopathological features.Methods Fifteen patients with MiT family translocation RCC were analyzed retrospectively including 14 cases of Xp11.2 RCC and 1 case of t(6;11) RCC.Tumor location,size,capsule sign,hemorrhage,cystic change,calcification,density,signal features and enhancement pattern were evaluated.Results Four men and ten women aged from 14 to 42 years old (mean age of 26 years old) were diagnosed as Xp1 1.2 RCC.Most of the tumors (n =12) were located in renal medulla and most of the tumors (n =11) were 4 cm or more in diameter.There were 8 cases with hemorrhage.They were always well-defined (n =11) and all heterogeneous.Additionally,we could find calcification (a half of the number) typically distributed on CT.The tumor density was grater on plain CT (n =8) and the signal intensive was slightly high on T1WI (n-6) and low or slightly low on T2WI (n =9) than renal cortex.All of the cases were slightly or moderately persistent enhancement on DCE CT and MRI.The imaging features of the male patient with t(6;11)RCC was similar with Xp11.2 RCC apart from the diameter of 16 cm.Conclusions MiT family translocation RCC should be considered when a young patient presents with a relatively huge and well-defined renal tumor with an obviously heterogeneous features,annular calcification and persistent enhancement.It is difficult to distinguish Xp11.2 RCC and t(6,11) RCC,but size maybe play a hinting role in discriminate them.

A posição do psicanalista em um espaço de acolhimento para pequenas crianças e seus pais: da sustentação simbólica à constituição subjetiva / The position of psychoanalysts in a welcoming place for young children and their parents: from symbolic support to subjective constitution / La position du psychanalyste dans un lieu d'accueil enfants-parents: du support symbolique à la constitution subjective / La postura del psicoanalista en un espacio de acogida para niños pequeños y sus padres: de la sustentación simbólica a la constitución subjetiva

Partindo de um questionamento sobre as especificidades da clínica psicanalítica com bebês, o presente artigo discute a posição do psicanalista em um espaço de acolhimento para crianças pequenas e seus pais. Conclui que ele opera pela sustentação simbólica da função materna e propõe uma torção no que concerne à noção de prevenção, concebendo-a como o acompanhamento que participa da instauração do processo de constituição psíquica do bebê.

Based on examination of the specificities of psychoanalytic clinics for babies, this paper discusses the position of psychoanalysts in a welcoming place for young children and their parents. It concludes that the latter operates through symbolic support to maternity, and proposes a twist referring to the notion of prevention - seeing it as monitoring that participates in the process of babies' psychic constitution.

A partir d'un questionnement sur les spécificités de la clinique psychanalytique avec des bébés, cet article traite de la position du psychanalyste dans un lieu d'accueil enfants-parents. Il conclut que celui-ci opère à travers le support symbolique de la fonction maternelle et propose une torsion de la notion de prévention, conçue comme l'accompagnement qui participe à la mise en place du processus de constitution psychique du bébé.

A partir de un cuestionamiento acerca de las especificidades de la clínica psicoanalítica con bebés, este artículo discute la postura del psicoanalista en un espacio de acogida para niños pequeños y sus padres. Se concluye que el psicoanalista actúa a través de la sustentación simbólica de la función materna y propone un giro con respecto al concepto de la prevención, concibiéndola como el seguimiento que participa en la instauración del proceso de constitución psíquica del bebé.

Basierend auf der Erforschung der spezifischen Aspekte der psychoanalytischen Klinik mit Kleinkindern beschreibt dieser Artikel die Stellung des Psychoanalytikers in einer Anlaufstelle für Kleinkinder und ihre Eltern. Wir kommen zum Schluss, dass der Psychoanalytiker die mütterliche Funktion symbolisch unterstützt und schlagen vor, das Konzept der Prävention abzuändern und es als Begleitung zu verstehen, als Teil der Erstellung des Prozesses der psychischen Konstitution des Kleinkindes.

Adolescentes exibicionistas: a busca de um olhar / Exhibitionistic teenage girls: wanting to be seen / Adolescentes exhibitionnistes: à la recherche d'un regard / Adolescentes exhibicionistas: la búsqueda por una mirada

Este artigo reflete sobre adolescentes autoras de ato infracional, adotando como ponto de partida a fala habitual da instituição que as acolhia - Fundação de Atendimento Socioeducativo do Pará -, segundo a qual o trabalho com adolescentes do sexo feminino é mais difícil. Buscando respostas para essa formulação emblemática, a partir de entrevistas psicológicas com cinco adolescentes em conflito com a lei, verificou-se que essa dificuldade se associava à exposição que as adolescentes faziam dos genitais no cotidiano institucional, colocando em questão alguns aspectos da sexualidade feminina.

This article discusses female juvenile offenders, taking as its starting point the habitual discourse of the institution where they were detained - Fundação de Atendimento Socioeducativo do Pará. According to staff members, it is more difficult to treat female patients. Seeking answers to this emblematic formulation, and based on psychological interviews with five juvenile offenders, we found that this difficulty was associated with the fact that such girls often exposed their genital areas during their institutional routines. This brings up certain aspects of female sexuality.

Cet article propose une réflexion sur les jeunes-filles adolescentes auteurs d'infractions en prenant comme point de départ le discours habituel de l'institution qui les accueillit - la Fundação de Atendimento Socioeducativo do Pará - selon laquelle le travail avec les jeunes filles adolescentes est plus difficile. Pour découvrir ce qui mène à cette formulation emblématique, nous avons réalisé des entretiens psychologiques avec cinq adolescentes en conflit avec la loi et nous avons constaté que cette difficulté est associée au fait que ces adolescentes exposent leurs organes génitaux dans la routine institutionnelle, ce qui met en question certains aspects de la sexualité féminine.

Este artículo presenta una reflexión sobre adolescentes autoras de acto infracional, adoptando como punto de partida el discurso habitual de la institución que las amparaba,la Fundação de Atendimento Socioeducativo de Pará, según la cual el trabajo con adolescentes del sexo femenino sería más difícil. Buscando respuestas para esta formulación emblemática, a partir de las entrevistas psicológicas con cinco adolescentes en conflicto con la ley, se verificó que esta dificultad estaba asociada a la exposición que las adolescentes hacían de sus genitales en la rutina institucional, cuestionando algunos aspectos de la sexualidad femenina.

A Comparative Evaluation of the Performances of Anti-MIT3, Anti-gp210, and Anti-sp100 Antibodies for the Diagnosis of Primary Biliary Cirrhosis

BACKGROUND: Anti-mitochondrial antibody (AMA) is a serological hallmark of primary biliary cirrhosis (PBC). AMAs are detected by an immunofluorescence assay (IF), which is subject to errors. We evaluated the diagnostic performances of the AMA ELISA test (the anti-MIT3 antibody) and PBC-associated antinuclear antibody (ANA) tests (the anti-gp210 and anti-sp100 antibodies). METHODS: AMA, anti-gp210, and anti-sp100 were measured in the sera of 130 subjects including patients for whom the AMA test was requested with the clinical suspicion of PBC, patients with other autoimmune diseases, and those undergoing health check-ups. AMA was detected by both IF and ELISA (anti-MIT3 antibodies), and anti-gp210 and anti-sp100 were detected by ELISA. The diagnostic performances of the anti-MIT3, anti-gp210, and anti-sp100 were compared with that of the AMA IF test. Associations between the presence of anti-sp100 or anti-gp210 and the diagnosis and biochemical abnormalities of PBC were investigated. RESULTS: The area under the curve of anti-MIT3 for the diagnosis of PBC was 0.934 (95% confidence interval, 0.877-0.970), and the agreement between anti-MIT3 and AMA IF was 93.8% (kappa, 0.82). The sensitivities of anti-MIT3 and AMA IF were both 100%, and the specificities were 83.1% and 81.4%, respectively, whereas the sensitivities of anti-gp210 and anti-sp100 were 41.7% and 16.7%, and their specificities were 94.9% and 97.5%, respectively. The presence of anti-gp210 was associated with the diagnosis of PBC (P=0.0001), but that of anti-sp100 was not. CONCLUSIONS: The diagnostic performance of anti-MIT3 is comparable to that of AMA IF. Anti-gp210 seems to be complementary to AMA for the diagnosis of PBC.

Role of reverse transcriptase polymerase chain reaction for the diagnosis of human rabies.

Background & objectives: Traditionally, rabies diagnosis is made by demonstration of rabies viral antigen by direct immunofluorescence (DIF) and mouse inoculation test (MIT). The present study was carried out to evaluate the role of reverse transcriptase-polymerase chain reaction (RT-PCR) in comparison with these conventional techniques for the diagnosis of rabies. Methods: Skin biopsies, corneal impression smears and saliva sample were collected ante-mortem and brain tissue and CSF were collected post-mortem from ten clinically suspected rabies patients. DIF, Seller staining, MIT and RT-PCR were performed on the patients’ samples for the diagnosis of rabies. The ability of RT-PCR to detect rabies virus earlier as compared to other assays was tested both for reference virus as well as clinical isolates. Results: All samples taken ante-mortem were negative for DIF test. Six of 10 post-mortem brain tissues of the clinically suspected patients were positive both by RT-PCR and MIT, of these six, five were positive by DIF test and four were positive by Seller stain. RT-PCR could detect the rabies virus earlier as compared to DIF, both from clinical isolates and fixed rabies virus. Interpretation & conclusions: The present results showed 100 per cent sensitivity and specificity of RT-PCR as compared to 83.3 per cent of DIF and 66.7 per cent of Sellers stain for diagnosis of rabies. RT-PCR also detected rabies viral infection earlier as compared to conventional tests and can also be used on ante-mortem samples. Thus, the present study shows the usefulness of RT-PCR as an alternative to MIT for the confirmation of rabies diagnosis.

Research Status and Developing Trends of the Electrical Impedance Imaging by Magnetic Means / 中国医学物理学杂志

Purpose: To obtain more precise Electrical Impedance Tomography, the conductivity imaging which utilizes the in-formation of magnetic field has been developed as new approaches of EIT. Methods: Analysing the basic theory and develop-ing status of MIT, MD-EIT and MREIT, the Electrical Impedance Imaging by magnetic means was proved to have more bright applicational prospect. Results: Based on different imaging methods, the Electrical Impedance Imaging by magnetic means can give more accurate conductivity distributions. Conclusions: The Electrical Impedance Imaging will be used more widely by magnetic means.

Mitoxantrone inhibits growth of melanoma by increasing expression of calreticulin / 中国肿瘤生物治疗杂志

Objective: To investigate the effect of mitoxantrone (MIT) on calreticulin (CRT) expression in B16 cells, and to observe the immune effect of B16-membrane antigen vaccine highly expressing CRT on B16 tumor-bearing mice. Methods: The expression of CRT on membrane of B16 cells was detected by immunofluorescence after treatment with different concentrations of MIT. B16-implanted mouse model was established, and the growth of B16-implanted tumors and CRT expression in B16-implanted tumor tissues were observed after treatment with different concentrations of MIT. Membrane antigen vaccines from both normal B16 cells and MIT-treated B16 cells were prepared, and mice were immunized before B16 cell implantation. The infiltration of immune cells into B16 tumor tissues and the ratios of CD4~+ and CD8~+ T cells in the spleen of B16 tumor-bearing mice were examined by immunohistochemistry and flow cytometry, respectively. Results: Flow cytometry results showed that MIT dose-dependently increased CRT expression on B16 cell membrane, with CRT expression in control and high dosage MIT groups being (29.40±3.57)% and (72.20±2.94)% (P<0.05), respectively. MIT also increased CRT expression in B16 tumor tissues, with those in the control and high dosage MIT groups being 3.21±1.37 and 9.17±1.06 (P<0.05), respectively. MIT effectively inhibited the growth of B16 tumors (P<0.05). Compared with normal B16 cell membrane antigen vaccine, the vaccine highly expressing CRT increased the numbers of DCs and T cells in B16 tumors tissues and the ratios of CD4~+ and CD8(+) T cells in the spleen (P<0.05). Conclusion: MIT can increase CRT expression on membrane of B16 cells. B16-membrane antigen vaccine highly expressing CRT can enhance the infiltration of DCs and T cells in melanoma, thus improving the immune effect of B16-membrane antigen vaccine.

Diverse effects of two kinds of PI3K inhibitors on drug-resistant human breast cancer MCF-7/MIT cells / 肿瘤

Objective:To investigate the reversing effect of phosphatidylinositol 3-kinase (PI3K) inhibitors, LY294002(LY) and wortmannin (Wort), on the drug resistance of mitoxantrone (MIT)-resistant human breast cancer MCF-7/MIT cells. Methods:Drug-resistant MCF-7/MIT cells were treated with LY or Wort combined with MIT. Cell viability and proliferation were measured using the MTT assay and morphological changes were recorded by microscopy. Intracellular accumulation of MIT in MCF-7/MIT cells was detected by flow cytometry. Mitochondrial membrane potential was determined by rhodamine 123 staining. Cell cycle was examined by propidium iodide staining. Results:LY significantly enhanced the cytotoxicity of MIT to MCF-7/MIT cells. In LY and MIT cotreated cells, the percentage of cells arrested at S and G2/M phases and the mitochondrial membrane potential decreased significantly compared with single LY- or MIT-treated cells. The mechanism was related with increased accumulation of MIT in MCF-7/MIT cells induced by LY. While Wort, another PI3K inhibitor, did not significantly enhance the cytotoxic effects of MIT.Conclusion: The PI3K inhibitor significantly enhances the sensitivity of MCF-7/MIT cells to MIT.