Preliminary study on clinicopathological features of renal mucinous tubular and spindle cell carcinoma北大核心CSCD

Objective: To explore the clinicopathological features and prognosis of mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney in order to improve the understanding of the tumor. Methods: The clinical and pathological information of 15 patients with MTSCC in 7 hospitals were retrospectively collected and analyzed from July 2010 to July 2018. The sections were reviewed by two high-seniority pathologists. The EnVision two-step immunohistochemical staining technique was used to detect the expressions of villin, cytokeratin 7 (CK7), epithelial membrane antigen (EMA), alpha-methylacyl-CoA racemase (AMACR), transducin-like enhancer of split 1 (TLE1), hepatocyte nuclear factor-1p (HNF-1p)and kidney specific calcium binding protein (Ksp-cadherin). The fluorescence in situ hybridization (FISH) was used to detect the synovial sarcoma translocation (SYT)-synovial sarcoma X chromosome breakpoint (SSX) fusion gene in the patients with sarcomatoid changes and positive immunohistochemical staining of TLE1. Finally, the prognostic data of all patients and the relevant literature were reviewed. Results: Among 15 patients with MTSCC, seven of the patients were male and the other eight were female, with an average age of 62 years (ranging from 48 to 75 years). The tumors were found by chance in 12 patients during physical examination, and the other 3 patients developed clinical symptoms such as frequent urine pain or hematuria, including 1 patient with a history of renal calculi for 15 years. The cut surface of tumor is firm and grey or yellow. Except for 2 cases, the majority of tumors were well-circumscribed. Microscopically, 1 case showed neoplastic necrosis, 13 cases showed a mixture of mucinous stroma, tubules and spindle cells, 1 case was mainly composed of spindle cells and mucus, and 1 case was mainly composed of tubule and mucus. Some tumors were with obvious clear cytoplasmic changes, and two cases were accompanied by sarcomatoid differentiation. The immunohistochemical results showed that the positive rates of villin, CK7, EMA, AMACR, TLE1, HNF-1 p and Ksp-cadherin were 20.0% (3/15), 80.0% (12/15), 93.3% (14/15), 80.0% (12/15), 20.0% (3/15), 20.0% (3/15), 93.3% (14/15) and 13.3% (2/15), respectively; the result of FISH excluded synovial sarcoma. Eight patients were followed up wihout other treatment after operation. Bone metastasis occurred in half a year after operation in one patient with follow-up information, while no evidence of local recurrence or distant metastases was identified in the other 7 patients until now. Conclusion: A few cases of MTSCC can metastasize and belong to malignant tumors. The positive expressions of AMACR, CK7 and villin in some cases suggests that the tumor has both proximal and distal renal tubular origins. The positive expression of HNF-ip is correlated with the histological characteristics of MTSCC clear cytoplasm. © 2019 by TUMOR. All rights reserved.     

Astrocyte morphology: Diversity,plasticity, and role in neurological diseases

Astrocytes are the most abundant glial cells in the central nervous system (CNS) and participate in synaptic, circuit, and behavioral functions. The well‐developed protoplasmic astrocytes contain numerous processes forming well‐delineated bushy territories that overlap by as little as 5% at their boundaries. This highly complex morphology, with up to approximately 80% of the cell's membrane constituted by fine processes with dimensions on the tens of nanometer scale and high surface area to volume ratios, comes in contact with synapses, blood vessels, and other glial cells. Recent progress is challenging the conventional view that astrocytes are morphologically homogeneous throughout the brain; instead, they display circuit‐ and region‐specific morphological diversity that may contribute to the heterogeneous astrocyte‐neuron spatiotemporal interplay in different brain areas. Further, the fine structure of astrocytes is found to be highly plastic and activity‐dependent. We are beginning to understand how astrocyte structural plasticity contributes to brain functions. The change/loss of astrocyte morphology, traditionally known as a hallmark for reactive astrogliosis, is a common pathological feature in many neurological disorders. However, recent data suggest the fine structural deficits preceding reactive astrogliosis may drive disease progression. This review summarizes recent advances in astrocyte morphological diversity, plasticity, and disease‐related deficits.     

Synthesis and antitumor activity of novel podophyllotoxin derivatives against multidrug-resistant cancer cells

Seven novel 4β-N-substituted podophyllotoxin derivatives with indole rings were prepared and evaluated for cytotoxicity against human cancer cell lines HeLa, KB, KBV, K562, and K562/AO2. Most of them demonstrated improved antitumor activity and weak multidrug resistance compared to the drugs currently available.     

Mycophenolic acid derivative 118 improves outcome of skin grafts by suppressing IL-17 production

Aim:

To investigate the effects and underlying mechanisms of 118, a novel derivative of mycophenolic acid, in a murine allogeneic skin graft model.

Methods:

Skin grafts were conducted by grafting BALB/c donor tail skin into C57BL/6 skin beds (allograft) or by grafting female C57BL/6 donor tail skin into female C57BL/6 skin beds (syngraft). The mice were treated with the derivative 118 (40 mg·kg⁻¹·d⁻¹, po) for 13 d (3 d before and 10 d after transplantation). Skin grafts, splenocytes and graft-infiltrated lymphocytes were isolated and examined ex vivo. The effects of the derivative 118 on naive CD4⁺ T cell differentiation were examined in vitro.

Results:

Treatment with the derivative 118 dramatically increased the survival rate of murine allogeneic skin grafts. Flow cytometric analysis and H&E staining showed that the derivative significantly decreased inflammatory cell infiltration into the grafts. The levels of the chemokines CXCL1, CXCL2, CCL7, and CCL2 were reduced in the derivative 118-treated grafts. Additionally, the derivative 118 significantly suppressed the IL-17 levels in the grafts but did not affect the differentiation of systemic helper T cells in the murine allogeneic skin graft model. Furthermore, IL-23p19 expression was suppressed in the grafts from the derivative 118-treated group, which might be due to decreases in TLR4 and MyD88 expression. Finally, the derivative 118 did not exert direct influences on helper T cell differentiation in vitro.

Conclusion:

Treatment with the mycophenolic acid derivative 118 improves murine allogeneic skin grafts by decreasing IL-23 expression and suppressing local IL-17 secretion in the grafts, rather than directly inhibiting Th17 differentiation.     

浅论食品药品检测实验室之质量监督

目的提高食品药品检测实验室对质量监督工作的重视程度,促进质量管理体系的持续改进。方法从质量监督的内容、质量监督的实施和质量监督的意义等方面,对食品药品检测实验室质量监督工作进行分析探讨。结果与结论有效的实施质量监督,是保证食品药品检测实验室质量管理体系持续改进的重要手段之一。     

Preclinical factors affecting the pharmacokinetic behaviour of tanshinone IIA,an investigational new drug isolated from Salvia miltiorrhiza for the treatment of ischaemic heart diseases

Tanshinone IIA (TSIIA) is a major active triterpenoid isolated from Salvia miltiorrhiza. The purposes of this study were to investigate various preclinical factors that determined the pharmacokinetics of TSIIA. After oral dosing at 6.7, 20, and 60 mg kg^?1, TSIIA was detected mainly as glucuronidated conjugate (TSIIAG) with only small amounts of the unchanged in the plasma. TSIIA was predominantly excreted into the bile and faeces as TSIIAG, and urine to a minor extent. The C_max and AUC_0?t of TSIIAG after i.p. administration were significantly lower than those after intragastric administration. The plasma concentration–time profiles of TSIIA following oral dosing of TSIIA showed multiple peaks. The C_max and AUC_0?t of TSIIA and its glucuronides in rats with intact bile duct were significantly lower than those of rats with bile duct cannulation. Studies from the linked-rat model and intraduodenal injection of bile containing TSIIA and its metabolites indicate that TSIIA glucuronides underwent hydrolysis and the aglycone was reabsorbed from the gut and excreted into the bile as conjugates. TSIIA had a wide tissue distribution, with a very high accumulation in the lung, but very limited penetration into the brain and testes. TSIIA was metabolized by rat CYP2C, 3A and 2D, as ticlopidine, ketoconazole and quinidine all inhibited TSIIA metabolism in rat liver microsomes. Taken collectively, these findings indicate that multiple factors play important roles in determining the pharmacokinetics of TSIIA.     

Brain Disposition and Catalepsy After Intranasal Delivery of Loxapine: Role of Metabolism in PK/PD of Intranasal CNS Drugs

Purpose

To elucidate the role of metabolism in the pharmacokinetics and pharmacodynamics of intranasal loxapine in conscious animals.

Methods

At pre-determined time points after intranasal or oral loxapine administration, levels of loxapine, loxapine metabolites, and neurotransmitters in rat brain were quantified after catalepsy assessments (block test and paw test). Cataleptogenicity of loxapine was also compared with its metabolites.

Results

Intranasally administered loxapine was efficiently absorbed into systemic circulation followed by entering brain, with t_max ≤15 min in all brain regions. Oral route delivered minimal amounts of loxapine to plasma and brain. Brain AUC_0–240min values of 7-hydroxy-loxapine were similar after intranasal and oral administration. Intranasal loxapine tended to induce less catalepsy than oral loxapine, although statistical significance was not reached. The catalepsy score was positively and significantly correlated with the striatal concentration of 7-hydroxy-loxapine, but not with loxapine. 7-hydroxy-loxapine was more cataleptogenic than loxapine, while the presence of loxapine tended to reduce rather than intensify 7-hydroxy-loxapine-induced catalepsy. The increases in striatal dopamine turnover were comparable after intranasal and oral loxapine administration.

Conclusions

The metabolite 7-hydroxy-loxapine, but not loxapine, was the main contributor to the catalepsy observed after intranasal and oral loxapine treatment. Intranasal route could effectively deliver loxapine to brain.