Pulmonary delivery of siRNA against acute lung injury/acute respiratory distress syndrome

The use of small interfering RNAs (siRNAs) has been under investigation for the treatment of several unmet medical needs, including acute lung injury/acute respiratory distress syndrome (ALI/ARDS) wherein siRNA may be implemented to modify the expression of pro-inflammatory cytokines and chemokines at the mRNA level. The properties such as clear anatomy, accessibility, and relatively low enzyme activity make the lung a good target for local siRNA therapy. However, the translation of siRNA is restricted by the inefficient delivery of siRNA therapeutics to the target cells due to the properties of naked siRNA. Thus, this review will focus on the various delivery systems that can be used and the different barriers that need to be surmounted for the development of stable inhalable siRNA formulations for human use before siRNA therapeutics for ALI/ARDS become available in the clinic.

Effect of Xiao Qinglongtang on IL-33/ST2 Signaling Pathway in Mice with Allergic Rhinitis / 中国实验方剂学杂志

ObjectiveTo investigate the therapeutic effect of Xiao Qinglongtang （XQLT） on ovalbumin （OVA）-induced allergic rhinitis （AR） in mice and its effect on the interleukin-33 （IL-33）/suppression of tumorigenicity 2 （ST2） signaling pathway. MethodSeventy-two female BALB/c mice of SPF grade were randomly divided into a control group， a model group， a positive control group （loratadine， 2.05 mg·kg-1）， and low-， medium-， and high-dose （5.005，10.01，20.02 g·kg-1） XQLT groups. All mice except for those in the control group were sensitized by intraperitoneal injection of OVA solution， and the AR model was induced by intranasal drops of OVA solution. Thirty minutes before local intranasal drops， drugs were administered once， and mice in the control group and the model group received phosphate buffered saline （PBS） at 20 mL·kg-1 for 7 days. After the last intranasal drop of OVA solution， the times of sneezing and nasal rubbing of mice within 10 min was recorded. After drug administration for 7 days， blood samples were collected， and nasal bones of mice were decalcified for the preparation of pathological sections. The content of OVA-specific immunoglobulin E （OVA-sIgE）， interleukin-4 （IL-4）， interleukin-5 （IL-5）， and interleukin-13 （IL-13） was detected by enzyme-linked immunosorbent assay （ELISA） kits. Hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Giemsa staining were used to observe the pathological changes， goblet cell hyperplasia， and eosinophil infiltration of nasal mucosa， respectively. Western blot was used to detect the expression levels of IL-33， ST2， and IL-1 receptor accessory protein （IL-1RAP） in nasal mucosa. ResultCompared with the control group， the model group showed increased times of sneezing and nasal rubbing （P<0.01）， edema and thickening of nasal mucosa， goblet cell hyperplasia and eosinophil infiltration， increased serum levels of OVA-sIgE， IL-4， IL-5 and IL-13 （P<0.01）， and increased protein expression of IL-33， ST2， and IL-1RAP in nasal mucosa （P<0.05，P<0.01）. After drug administration， compared with the model group， the high-dose XQLT group showed reduced times of sneezing and nasal rubbing （P<0.01）， improved pathological conditions of nasal mucosa， reduced serum levels of OVA-sIgE， IL-4， IL-5， and IL-13 （P<0.01）， and declining protein expression of IL-33， ST2， and IL-1RAP in nasal mucosa （P<0.05，P<0.01）. ConclusionXQLT has a therapeutic effect on OVA-sensitized AR mice， and the mechanism may be related to the regulation of the IL-33/ST2 signaling pathway and Th2 inflammatory cytokine to reduce Th2 inflammatory response and alleviate nasal mucosal injury.

A review on integration methods for single-cell data / 生物医学工程学杂志

The emergence of single-cell sequencing technology enables people to observe cells with unprecedented precision. However, it is difficult to capture the information on all cells and genes in one single-cell RNA sequencing (scRNA-seq) experiment. Single-cell data of a single modality cannot explain cell state and system changes in detail. The integrative analysis of single-cell data aims to address these two types of problems. Integrating multiple scRNA-seq data can collect complete cell types and provide a powerful boost for the construction of cell atlases. Integrating single-cell multimodal data can be used to study the causal relationship and gene regulation mechanism across modalities. The development and application of data integration methods helps fully explore the richness and relevance of single-cell data and discover meaningful biological changes. Based on this, this article reviews the basic principles, methods and applications of multiple scRNA-seq data integration and single-cell multimodal data integration. Moreover, the advantages and disadvantages of existing methods are discussed. Finally, the future development is prospected.

Carcinoma renal de células claras: a propósito de un caso y revisión de la literatura / Renal clear cell carcinoma: case report and review of the literature

El carcinoma de células renales (CCR) es la lesión sólida más frecuente en el riñón y representa aproximadamente el 90% de los tumores renales malignos. Hay un predominio 1,5:1 de varones sobre las mujeres y su incidencia máxima tiene lugar entre los 60 y 70 años de edad. Este tipo de cáncer representa el 2%-3% de todos los cánceres y su incidencia máxima ocurre en los países occidentales. Se reporta un caso poco frecuente de CCR en una paciente femenina de 35 años de edad con una hematuria total, sin dolor, de 2 días de duración. El TAC abdomino-pélvico reveló una lesión ocupante de espacio de 15 x 12 x 10 cm aproximadamente, de aspecto neoproliferativo, con características heterogéneas de hipo e hiperdensidad, de 40 uH, neovascularización y realce al contraste, que compromete cáliz medio e inferior de riñón izquierdo, extensivo hasta pelvis renal. Se practicó nefrectomía radical izquierda. El estudio histopatológico reporta un carcinoma de células claras bien diferenciado de bajo grado, con márgenes libres y ganglios linfáticos sin MT. Paciente quien evoluciona satisfactoriamente en planificación de terapia adyuvante. Por el hecho de ser una presentación en un adulto joven, lo ideal es que el urólogo este en la capacidad de realizar el diagnóstico a la brevedad posible(AU)

Renal cell cancer (RCC) is the most common solid lesion in the kidney and accounts for approximately 90% of malignant renal tumors. There is a 1.5:1 male predominance and the highest incidence occurs between 60 and 70 years of age. RCC represents 2%-3% of all cancers and its highest incidence occurs in western countries. We report a rare case of a female patient of 35 years of age who has had pain free hematuria for two days. A contrasted abdominal/pelvic CT revealed a lesion of approximately 15 x 12 x 10 cm with neoproliferative appearance and heterogeneous features of hypo and hyperdensity of 40 uH, with neovascularization and contrast enhancement, compromising the middle and lower calyx of the left kidney extensive to renal pelvis. A left radical nephrectomy was performed. Histopathological study revealed a well-differentiated low grade clear cell carcinoma, with free margins and lymph nodes without metastasis. The patient has a satisfactory evolution and is awaiting adjuvant treatment. Due to the fact that the patient is a young adult, the urologist should be able to make the diagnosis as soon as possible(AU)

Renal Cell Carcinoma With Three Types Of Morphologies- A Rare Entity

Renal cell carcinomas(RCC) are the most common solid lesions of kidney with commonest subtype being clear cell type. Very few studies have reported synchronous presentation of three different morphological variants of RCC. We present a case of renal cell carcinoma in a 50 year old female presenting with renal mass. Microscopic examination showed presence of papillary, clear cell and collecting duct types of morphologies, which is a rare finding. Hence thorough sectioning and microscopic examination should be done to rule out possibility of simultaneous presence of different morphological varieties of RCC.

Effects of Hippo pathway on differentiation, proliferation, migration of bone marrow mesenchymal stem cells in vitro / 中华危重病急救医学

Objective To explore the effects of Hippo pathway on differentiation, proliferation, and migration of bone marrow mesenchymal stem cells (BMSCs) in vitro. Methods BMSCs of C57BL/6 mice were identified using fluorescence-activated cellsorting analysis and the capabilities of osteogenic, chondrogenic and adipogenic differentiation were evaluated. The differentiation of BMSCs to typeⅡalveolar epithelial cells (AECⅡ) was induced by indirect co-culture with mouse lung epithelial cells (MLE-12) and small airway epithelial cell growth medium (SAGM). The Hippo pathway was regulated by 2-deoxy-D-glucose (2-DG) and 9E1, the effects of 2-DG and 9E1 on the expression of BMSCs surface proteins (SPB, SPC and SPD) mRNA and pro-SPC protein were detected by real time quantitative polymerase chain reaction (qRT-PCR) and Western Blot. The effect of Hippo pathway on differentiation of BMSCs to AECⅡ cells was evaluated. The effect of Hippo pathway on the proliferation of BMSCs was evaluated by methyl thiazolyl tetrazolium (MTT) assay (intervention of 0.1, 0.5, 1.0, 5.0 mmol/L 2-DG). The scratch test and Transwell chamber test were used to analyze the effect of Hippo pathway on migration ability of BMSCs to conditioned medium of acute respiratory distress syndrome (ARDS) lung tissue. Results 2-DG could activate Hippo pathway in a dose-dependent manner and promote the differentiation to AECⅡ and proliferation of BMSCs, the maximum effects were observed after 5 mmol/L of 2-DG treatment [SPB mRNA (2-ΔΔCT): 2.42±0.28 vs. 1.89±0.11, SPC mRNA (2-ΔΔCT): 8.06±0.68 vs. 6.59±0.79, SPD mRNA (2-ΔΔCT): 6.45±0.37 vs. 5.27±0.28, pro-SPC/β-actin: 5.80±1.86 vs. 4.93±1.18, proliferation rate:(145.46±18.18)% vs. (98.91±4.36)%, all P < 0.05], but 9E1 could reverse those effects through inhibition of Hippo pathway [SPB mRNA (2-ΔΔCT): 1.32±0.17 vs. 1.89±0.11, SPC mRNA (2-ΔΔCT): 3.91±0.34 vs. 6.59±0.79, SPD mRNA (2-ΔΔCT): 3.38±0.25 vs. 5.27±0.28, pro-SPC/β-actin: 2.48±0.17 vs. 4.93±1.18, proliferation rate: (80.00±7.27)% vs. (98.91±4.36)%, all P < 0.05]. The ability of horizontal migration [wound healing: (27.17±3.53)% vs. (52.45±6.52)%, P < 0.05] and homing BMSCs to conditioned medium of ARDS lung tissue [cell count (fold, relative to control): 2.77±0.21 vs. 1.90±0.19, P < 0.05] were increased after activation of Hippo pathway by 2-DG treatment, but those effects were reversed after inhibition of Hippo pathway by 9E1 treatment [wound healing: (79.89±8.42)% vs. (52.45±6.52)%, cell count (fold, relative to control): 1.69±0.13 vs. 1.90±0.19, both P < 0.05]. Conclusion Activation of Hippo pathway could enhance differentiation of BMSCs to AECⅡ, promote proliferation and ability of horizontal migration and homing BMSCs to conditioned medium of ARDS lung tissue in vitro.

Effect of overexpression of microRNA-21-5p on early apoptosis of typeⅡalveolar epithelial cells in rats with hyperoxic acute lung injury / 中华危重病急救医学

To investigate the effect of overexpression of microRNA-21-5p (miR-21-5p) on early apoptosis of type Ⅱalveolar epithelial cells (AECⅡ) in rats with hyperoxic acute lung injury (HALI). Methods The Sprague-Dawley (SD) rats were randomly divided into four groups: control group (CON group), hyperoxia group (H group), overexpression group (OE group) and empty vector group (EV group), with 20 rats in each group. HALI animal model was made by inhaling high concentration oxygen (oxygen concentration ≥90%); CON group was arranged to inhale room air. The miR-21-5p adeno-associated virus-6 (AAV-6) overexpression vectors or empty vectors were dripped into the lungs of OE group and EV group through tracheal tube, respectively. The hyperoxia model was prepared after 3 weeks of feeding. At 0, 24, 48 and 60 hours after making model, 5 rats were selected to detect lung injury parameters:oxygenation index (OI), respiratory index (RI), wet/dry ratio (W/D), pathological injury score of lung tissue; real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of miR-21-5p in AECⅡ, and flow cytometry was used to detect the early apoptotic rate of AECⅡ. Results ① The lung injury parameters: in H group, the OI gradually decreased with time, but the RI, lung W/D ratio and pathological score increased gradually with time, the difference between CON group was statistically significant at 24 hours [OI (mmHg, 1 mmHg = 0.133 kPa):336.04±5.79 vs. 400.22±19.70, RI: 0.20±0.02 vs. 0.10±0.06, lung W/D ratio: 5.04±0.09 vs. 4.85±0.09, lung tissue pathological score: 0.13±0.01 vs. 0.07±0.01, all P < 0.05]. It indicated that HALI model could be successfully established by inhaling high concentration oxygen continuously. ② The expression of miR-21-5p: the miR-21-5p was gradually increased in H, OE and EV groups, and the expression of miR-21-5p was significantly higher than that in CON group at 24, 48 and 60 hours. Compared with H group, the expression of miR-21-5p was significantly increased further in OE group at 0, 24, 48 and 60 hours (2-ΔΔCt: 3.75±0.11 vs. 0.98±0.14, 3.98±0.12 vs. 1.18±0.13, 4.28±0.18 vs. 1.49±0.06, 4.66±0.12 vs. 1.80±0.12, all P < 0.05). ③ The early apoptosis of AECⅡ: the early apoptosis rate gradually increased with time in H, OE and EV groups, and the early apoptosis of AECⅡ was significantly higher than that in CON group at 24, 48 and 60 hours. Compared with H group, the early apoptosis rate was significantly decreased in OE group at 24, 48 and 60 hours [(1.22±0.63)% vs. (2.84±0.59)%, (5.76±0.18)% vs. (13.10±2.01)%, (29.48±0.48)% vs. (49.04±1.36)%, all P < 0.05]. ④ There was no significant difference in the expression of miR-21-5p and the early apoptosis of AECⅡ cells between EV group and H group at each time point. Conclusion Overexpression of miR-21-5p could inhibit the early apoptosis of AECⅡ in rats with HALI.

Cell-Type Identification in the Autonomic Nervous System / 神经科学通报·英文版

The autonomic nervous system controls various internal organs and executes crucial functions through sophisticated neural connectivity and circuits. Its dysfunction causes an imbalance of homeostasis and numerous human disorders. In the past decades, great efforts have been made to study the structure and functions of this system, but so far, our understanding of the classification of autonomic neuronal subpopulations remains limited and a precise map of their connectivity has not been achieved. One of the major challenges that hinder rapid progress in these areas is the complexity and heterogeneity of autonomic neurons. To facilitate the identification of neuronal subgroups in the autonomic nervous system, here we review the well-established and cutting-edge technologies that are frequently used in peripheral neuronal tracing and profiling, and discuss their operating mechanisms, advantages, and targeted applications.

Effect of heme oxygenase-1 on the apoptosis of type Ⅱ alveolar epithelial cells in rats with hyperoxia-induced acute lung injury / 中华危重病急救医学

Objective To investigate the effect of heme oxygenase-1 (HO-1) on the apoptosis of type Ⅱalveolar epithelial cells (AEC-Ⅱ) in rats with hyperoxia-induced acute lung injury (HALI). Methods Twenty-four healthy male Sprague-Dawley (SD) rats were randomly divided into 4 groups (n = 6): control group, HALI group, HO-1 group, and HO-1 inhibition group. The control group was fed in the room air; the HALI group was fed in the hyperoxia box (the oxygen concentration was more than 90%, the temperature was kept at 25-27 ℃, the humidity was maintained at 50%-70%, and the CO2concentration was less than 0.5%); the HO-1 group was fed in the hyperoxia box after HO-1 (0.2 μmol/L) treatment; and the HO-1 inhibition group was fed in the hyperoxia box after treatment with zinc protoporphyrin Ⅸ (20 μmol/L). After 48 hours of hyperoxia treatment, rats were sacrificed, left upper lung tissue was stained with hematoxylin-eosin (HE) and the pathological changes of lung tissue were observed under light microscope. The ratio of wet/dry weight (W/D) was measured in the lower left lung. AECⅡ was extracted from the right lung tissue, the apoptosis rate was detected by flow cytometry, and the expressions of apoptosis-related proteins Bcl-2 and caspase-3 were detected by Western Blot. Results ①It was shown by light microscopy that the lung tissue structure of the control group was clear. In HALI group and HO-1 inhibitor group, the lung tissue structure was disordered, alveolar wall was broken and fused into pulmonary alveoli, alveolar septum was obviously swollen and widened, a large number of inflammatory cells infiltrated, and edema fluid and inflammatory cells appeared in alveolar cavity. The pathological changes of lung tissue in HO-1 group were significantly less than those in HALI group. ② Compared with the control group, the lung W/D ratio, the apoptosis rate of AECⅡand the expression of Bcl-2 protein in the HALI group and the HO-1 inhibitor group were significantly increased, and the expression of caspase-3 was significantly decreased [lung W/D ratio: 4.61±0.41 vs. 3.68±0.45, apoptosis rate of AECⅡ: (42.44±0.93) % vs. (24.74±0.64) %, Bcl-2 (integral absorbance): 0.72±0.18 vs. 0.41±0.12, caspase-3 (integral absorbance): 1.32±0.32 vs. 1.81±0.69, all P < 0.05]. Compared with the HALI group, the lung W/D ratio, the apoptosis rate of AECⅡ, the expression of Bcl-2 protein in HO-1 group were significantly decreased, and the expression of caspase-3 was significantly increased [lung W/D ratio: 3.82±0.28 vs. 4.61±0.41, apoptosis rate of AECⅡ: (26.67±1.58) % vs. (42.44±0.93) %, Bcl-2 (integral absorbance): 0.39±0.08 vs. 0.72±0.18, caspase-3 (integral absorbance): 1.78±0.46 vs. 1.32±0.32, all P < 0.05]. There was no significant difference between HO-1 inhibitor group and HALI group. Conclusions HO-1 can reduce the apoptosis rate of AECⅡin rats with HALI, which may be related to the expressions of apoptosis related proteins Bcl-2 and caspase-3.

Changes of Alternative Splice Variant of the SRSF12 by Cisplatin in Multiple Cells / 昆明医科大学学报

Objective To detect the changes of mRNA isoforms in multiple cancer cell lines with dose of cisplatin. Methods Total RNA of the cells treated by cisplatin were abstracted 24 h after the treatment. mRNA isoforms of SRSF12 gene were detected by semiquantitative RT-PCR. The ratios of mRNA isoforms were analyzed by gel image software and statistical analysis. Results Under the cisplatin treatment, 2 mRNA isoforms of SRSF12 were detected in five cells except Caski cells,their ratios and relative mRNA levels were changed. With the increase of dose of cisplatin, the ratio of isoform-a was slightly increased; but the ratio of isoform-b was different, the changes were not obvious in the A549 and 293FT cells, the weaker expression was expressed in the H1299 and C33A cells, and the two isoforms were gradually weakening in the Siha cells. Conclution Under the cisplatin treatment in multiple cancer cells, the expression of SRSF12 shows tissue-specific and cell type-specific patterns .

Laminar Distribution of Neurochemically-Identified Interneurons and Cellular Co-expression of Molecular Markers in Epileptic Human Cortex / 神经科学通报·英文版

Inhibitory GABAergic interneurons are fundamental elements of cortical circuits and play critical roles in shaping network activity. Dysfunction of interneurons can lead to various brain disorders, including epilepsy, schizophrenia, and anxiety. Based on the electrophysiological properties, cell morphology, and molecular identity, interneurons could be classified into various subgroups. In this study, we investigated the density and laminar distribution of different interneuron types and the co-expression of molecular markers in epileptic human cortex. We found that parvalbumin (PV) and somatostatin (SST) neurons were distributed in all cortical layers except layer I, while tyrosine hydroxylase (TH) and neuropeptide Y (NPY) were abundant in the deep layers and white matter. Cholecystokinin (CCK) neurons showed a high density in layers IV and VI. Neurons with these markers constituted ~7.2% (PV), 2.6% (SST), 0.5% (TH), 0.5% (NPY), and 4.4% (CCK) of the gray-matter neuron population. Double- and triple-labeling revealed that NPY neurons were also SST-immunoreactive (97.7%), and TH neurons were more likely to express SST (34.2%) than PV (14.6%). A subpopulation of CCK neurons (28.0%) also expressed PV, but none contained SST. Together, these results revealed the density and distribution patterns of different interneuron populations and the overlap between molecular markers in epileptic human cortex.

Cell-type specific examination of central amygdala dopamine receptor 2 expressing neurons as a translational target for pharmacological enhancement of extinction / 中国药理学与毒理学杂志

Behavioral and molecular characterization of cell- type specific populations governing fear learning and behavior is a promising avenue for the rational identification of potential therapeutics for fear-related disorders. Identification of cell-type specific changes in neuronal translation following fear learning allows for targeted pharmacological intervention during fear extinction learning, mirroring possible treatment strategies in humans. Here we identify the central amygdala (CeA) Drd2-expressing population as a fear-supporting population that is molecularly distinct from other, previously identified fear-supporting CeA populations. Sequencing of actively translating transcripts of Drd2 neurons identifies mRNAs that are differentially regulated following fear learning including Npy5r, Rxrg, Sst5r, Fgf3, ErbB4, Fkbp14, Dlk1,Ssh3 and Adora2a. Direct pharmacological manipulation of NPY5R, RXR, and ADORA2A confirms their importance in fear behavior and validates the present approach of identifying pharmacological targets for the modulation of emotional learning.

Unicentric Castlemans disease involving central nervous system – plasma cell type: A rare entity.

Castleman’s disease (CD) is a rare disease primarily involving lymph nodes and lymphatic system. Other synonyms used for the Casleman's disease are giant lymph node hyperplasia, and angio- follicular lymph node hyperplasia (AFH). CD is not a true cancer and is a lympho-proliferative disorder which means there is an abnormal overgrowth of cells of the lymphatic system that is similar in many ways to lymphomas (cancers of lymph nodes). Even though CD is not officially a true cancer, one form of this disease (known as multi-centric Castleman’s disease) acts very much like lymphoma. In fact we can call it as premalignant condition as many people with this disease eventually develop lymphomas. Multi-centric CD is more common in people infected with HIV. In recent years, it’s become clear that another virus, known as human herpesvirus-8 (HHV-8) or Kaposi sarcoma herpes virus (KSHV), is often found in the lymph node cells of people with multi-centric CD. In fact, HHV-8 is found in the lymph nodes of nearly all CD patients who are HIV positive. We present a case of unicentric plasma cell type of Castleman' s disease involving central nervous system ( CNS) or brain perenchyam in a young male patient which is a rare occurrence.

A Gene and Neural Stem Cell Therapy Platform Based on Neuronal Cell Type-Inducible Gene Overexpression

PURPOSE: Spinal cord injury (SCI) is associated with permanent neurological damage, and treatment thereof with a single modality often does not provide sufficient therapeutic outcomes. Therefore, a strategy that combines two or more techniques might show better therapeutic effects. MATERIALS AND METHODS: In this study, we designed a combined treatment strategy based on neural stem cells (NSCs) introduced via a neuronal cell type-inducible transgene expression system (NSE::) controlled by a neuron-specific enolase (NSE) promoter to maximize therapeutic efficiency and neuronal differentiation. The luciferase gene was chosen to confirm whether this combined system was working properly prior to using a therapeutic gene. The luciferase expression levels of NSCs introduced via the neuronal cell type-inducible luciferase expression system (NSE::Luci) or via a general luciferase expressing system (SV::Luci) were measured and compared in vitro and in vivo. RESULTS: NSCs introduced via the neuronal cell type-inducible luciferase expressing system (NSE::Luci-NSCs) showed a high level of luciferase expression, compared to NSCs introduced via a general luciferase expressing system (SV::Luci-NSCs). Interestingly, the luciferase expression level of NSE::Luci-NSCs increased greatly after differentiation into neurons. CONCLUSION: We demonstrated that a neuronal cell type-inducible gene expression system is suitable for introducing NSCs in combined treatment strategies. We suggest that the proposed strategy may be a promising tool for the treatment of neurodegenerative disorders, including SCI.

1, 25 (OH)2-Vitamin-D3 attenuates Th17-related cytokines expression in peripheral blood mononuclear cells in patients with early-diagnosed rheumatoid arthritis / 中华内科杂志

Objective To investigate the effects of 1,25-dihydroxyvitamin D3 [1,25 (OH) 2D3] on T helper cell type 17 (Th17) cytokines and therapeutic mechanism in patients with rheumatoid arthritis (RA).Methods Peripheral blood mononuclear cells (PBMCs) from healthy donors and RA patients were collected.The PBMCs were stimulated with anti-CD3/anti-CD28 monoclonal antibodies in the absence or presence of 1,25(OH)2D3 and methotrexate (MTX).After co-culture,the serum levels of Th17 cytokines interleukin (IL)-17,IL-6,tumour necrosis factor alpha (TNFα) were analyzed by cytometric bead array (CBA).The level of IL-22 was analyzed by enzyme-linked immunosorbent assay (ELISA).The independent samples t test and one-way analysis of variance (ANOVA) were used for statistical analysis.Results The levels of cytokines IL-17,TNFα,IL-6 and IL-22 in RA group were significantly higher than those in the control group[(43 ± 6) ng/L,(5.91 ± 2.53) ng/L,(16.6 ± 12.0) ng/L,(51 ± 17) ng/L vs (21 ±3)ng/L,(2.63 ±0.27) ng/L,(4.2 ±2.3) ng/L,(22 ± 14) ng/L].Each of the three different 1,25 (OH) 2 D3 doses inhibited secretion of IL-17 [(533 ± 47) pg/ml,(426 ± 55) pg/ml,(319 ± 86) pg/ml],TNFα[(424 ± 82) pg/ml,(382 ± 79) pg/ml,(326 ± 87) pg/ml],and IL-6 [(5 513 ± 3 429) pg/ml,(4 555 ±3 157)pg/ml,(3 748 ± 1 919)pg/ml]in RA group (P ＜0.05),yet no statistical difference was found in IL-22 secretion with a trend of decrease after treatment of 1,25 (OH)2D3.Three different doses of MTX inhibited secretion of IL-17 [(452 ± 50) pg/ml,(372 ± 67) pg/ml,(315 ± 104) pg/ml] and TNFα [(319 ± 74) pg/ml,(292 ± 59) pg/ml,(266 ± 64) pg/ml] in RA group (P ＜ 0.05).However,levels of IL-6 and IL-22 were not affected after treated with MTX.Conclusion Our data indicated that 1,25 (OH)2D3 may play as an immune modulating agent to suppress Th17 cell cytokines.Supplement of vitamin D has the effective potential to treat patients with RA or other Th17 cell mediated autoimmune disorders.

Plasma Cell Type of Castleman's Disease Involving Renal Parenchyma and Sinus with Cardiac Tamponade: Case Report and Literature Review

Castleman's disease is an uncommon disorder characterized by benign proliferation of the lymphoid tissue that occurs most commonly in the mediastinum. Although unusual locations and manifestations have been reported, involvement of the renal parenchyma and sinus, and moreover, manifestations as cardiac tamponade are extremely rare. Here, we present a rare case of Castleman's disease in the renal parenchyma and sinus that also accompanied cardiac tamponade.

Castleman's Disease of the Renal Sinus Presenting as a Urothelial Malignancy: A Brief Case Report

Castleman's disease is a rare benign lymphoproliferative disorder that frequently affects lymph nodes of the mediastinal thorax and the neck. It very rarely affects the renal sinus. We report a case of Castleman's disease arising in the renal sinus in a 64-year-old man. The patient visited the hospital with the chief complaint of hematuria. Abdominal computed tomography revealed a homogeneous mass in the sinus of the left kidney, radiologically interpreted as a malignant urothelial tumor. Subsequently, nephroureterectomy was performed, after which microscopic examination of the specimen revealed a diffuse lymphoproliferative lesion with reactive lymphoid follicles of various sizes and prominent plasma cell infiltration of interfollicular spaces, highlighted by immunohistochemical staining for CD138. The lesion was diagnosed as Castleman's disease of the plasma cell type. Although preoperative diagnosis of Castleman's disease is difficult and the incidence is exceedingly rare, it should be considered in the differential diagnosis of renal sinus tumors.

VARIATION ANALYSIS OF HPV16 CELL-TYPE-SPECIFIC ENHANCER IN CERVICAL CARCINOMA / 药物分析学报

Objective To investigate the cell-type-specific enhancer (CTSE) in HPV16 and its variation in cervical carcinoma. Methods CTSEs were detected by polymerase chain reaction (PCR) in 58 cervical carcinoma from Shaanxi province; in addition variation of CTSEs was analyzed through single-strand conformation polymorphisms (SSCP). Results HPV16 CTSEs were detectable in 34 of 58 (57%) specimens and mutant rate was 41%(14/34) and the main mutations of chosen randomly variant CTSE (CTSEv) happened at YY1 binding sites in addition to glucocoticoid response elements (GRE). Conclusion CTSE in some specimens of Shaanxi province was obviously different from that in HPV16 wild type and variant CTSE might affect the transcriptional regulation of LCR on viral P97, which regulates over-expression of viral oncogenes in cervical carcinoma.

Ileal Mesenteric Castleman's Disease

Castleman's disease is a rare disorder characterized by tumorous masses that may develop in the lymph node tissue throughout the body. Most common location is mediastinum, but it can also affect retroperitoneum, neck, pelvis, and/or axilla. It may exceptionally affect extranodal sites like striated muscle, thoracic wall, lungs, skull, larynx, and/or vulva. The presentation is varied and diagnosis is difficult. There are two main types of Castleman's disease: hyaline-vascular type and plasma cell type. The hyaline vascular type accounts for approximately 90% of the cases. Most individuals exhibit no symptoms of this form of the disorder or they may develop non-cancerous growths in the lymph nodes. The plasma cell type is often associated with fever, weight loss, skin rash, early destruction of red blood cells, leading to unusually low levels of circulating red blood cells (hemolytic anemia), and/ or abnormally increased amounts of certain immune factors in the blood (hypergammaglobulinemia). We here report a case of Castleman's disease of ileal mesentery in 30-years old female patient. Abdominal mass, 4.7x3.6 cm in size, was completely removed from ileal mesentery without complication, and confirmed histologically mesenteric Castleman's disease of the mixed type.

Ultramorphology and histology of the Polistes versicolor (Oliver) (Vespidae) thorax salivary gland compared with other Hymenoptera / Ultramorfologia e histologia da glândula salivar do tórax de Polistes versicolor (Olivier) (Vespidae), comparada com a de outros Hymenoptera

The salivary system of the Hymenoptera consists of the mandible, hypopharynx and thoracic salivary glands. It is very important because it is related to various aspects of the life of the insects, such as pheromone production, feeding the young, food digestion and nest building. Adult Polistes versicolor (Olivier) individuals were dissected, the thoracic salivary glands removed and processed for scanning electronic microscopy and histological examination. The P. versicolor thoracic salivary gland presents alveolar secretory units, consists of pseudoacines and does not have a reservoir. Four types of cells are present in the gland. The T1 and T2 cells make up the pseudoacines and differ mainly by the many secretory vessels in T2. There is a cluster of T3 cells at the base of the gland duct collectors, also with secretory characteristics. The secretion produced in the pseudoacines is conducted by canals and ducts to the outside, and the latter are made of T4 cells. The comparison of these characteristics with those of different Hymenoptera species, already studied, showed that the thoracic salivary gland cannot be used as a single comparison factor in evolutionary studies.

O sistema salivar dos Hymenoptera é constituído pelas glândulas mandibulares, hipofaríngeas e salivares do tórax. É de grande importância por estar relacionado a diversos aspectos da vida destes insetos, como produção de feromônios, alimentação da cria, digestão dos alimentos e construção do ninho. Indivíduos adultos de Polistes versicolor (Olivier)foram dissecados, as glândulas salivares do tórax retiradas e processadas para exames com microscopia eletrônica de varredura e histológico. A glândula salivar do tórax de P. versicolor apresenta as unidades secretoras alveolares, sendo constituída por pseudoácinos e não apresenta reservatório. Quatro tipos de células estão presentes na glândula. As células T1 e T2, constituem os pseudoácinos e, diferem entre si, principalmente, pelo grande número de vesículas secretoras em T2. Na base dos dutos coletores da glândula há um agrupamento de células T3, também com características secretoras. A secreção produzida nos pseudoácinos é conduzida por canalículos e dutos ao exterior, sendo os últimos constituídos por células T4. A comparação dessas características com as de diferentes espécies de Hymenoptera, já estudadas, demonstrou que as glândulas salivares do tórax não podem ser utilizadas como único fator de comparação em estudos evolutivos.