Analgesic mechanism of cinobufagin in rats with bone cancer pain / 中草药

Objective: To investigate the analgesic mechanism of cinobufagin in rats with bone cancer pain. Methods: Female SD rats meeting the conditions of pain threshold were selected to construct cancer-induced bone pain (CIBP) model. On the 7th day after modeling, the sham group and the model group were administrated by saline, while the treatment groups were administrated with the low, medium and high concentrations of cinobufagin for consecutive 7 d. The pain behavior (mechanical withdrawal threshold and thermal pain threshold) was tested before modeling and after modeling, and single injection of cinobufagin after 0.5, 1, 2, 4, 6, 8 and 24 h at the first day. The expression of MAPKs protein was detected by Western Blotting, and the content of spinal cytokines (IL-1β, TNF-α, MCP-1) was detected by ELISA. Results: The mechanical pain threshold and thermal pain threshold were significantly decreased in the model group, compared with the sham group (P 0.05). Protein levels of MAPKs were increased in the model group, while the levels of JNK and p38 were decreased in the cinobufagin group (P 0.05). ELISA results showed that cinobufagin significantly decreased the content of cytokines in the spinal cord, when compared with the model group (P < 0.05). Conclusion: Cinobufagin can inhibit the expression of MAPKs proteins in the spinal cord of the rat model with bone cancer pain, ultimately decrease the content of IL-1β, TNF-α, and MCP-1 to alleviate the pain during the process of cancer pain.

Expression and clinical significance of Flotillin-2 in gastric cancer tissues / 中国肿瘤生物治疗杂志

@# Objective: To investigate the expression of Flotillin-2 (Flot-2) protein in gastric cancer tissues and its relationship with clinicopathological features and prognosis of gastric cancer (GC) patients. Methods: 112 samples of gastric cancer tissue and the corresponding paracancerous tissue that resected at the gastrointestinal surgery department of the Second Affiliated Hospital of Nanchang University between January 2009 andApril 2010 were collected for this study. The expression of Flot-2 protein in tumor tissues was detected by immunohistochemistry. The survival data were analyzed by Kaplan-Meier and Log-Rank test, and the survival curve was plotted. Spearman correlation analysis was used to examine the relationship between Flot-2 protein expression and clinicopathological characteristics and prognosis of GC patients. Results: In gastric cancer tissues, Flot-2 was primary stained in cytoplasm. Level of Flot-2 was significantly higher in gastric cancer tissues compared with that in paracancerous tissues (53.57% vs 46.43%, P<0.05). Expression of Flot-2 in tumor tissues was significantly associated with tumor size, depth of invasion, lymph node metastasis, distant metastasis and AJCC stage (all P<0.01), but not with gender, age, differentiation degree and tumor location (P>0.05). Moreover, survival analysis showed that the overall survival of patients with low Flot-2 expression was significantly higher than that of the patients with high level (P<0.01). Cox regression analysis indicated that distant metastasis, AJCC stage and Flot-2 expression were the independent risk factors for the prognosis of GC patients. Conclusion: Flot-2 protein was highly expressed in gastric cancer tissues and closely correlated with the poor prognosis of GC patients; Flot-2 is an independent risk factor for GC prognosis and may be served as a potential therapeutic target for gastric cancer.

FXR expression is associated with the prognosis and pathological staging of patients with pancreatic cancer / 基础医学与临床

Objective To explore the correlation among farnesoid X receptor (FXR), clinical stage and survival time of patients with pancreatic cancer. Methods The total protein and mRNA were extracted from cultured 8 pan-creatic cancer cell lines,and the expression level of FXR in pancreatic cancer cells was detected by Western bolt and real-time PCR. We collected 5 cases of normal pancreatic tissue and 50 cases of pancreatic cancer tissues,and used immunohistochemistry method to detect FRX expression in normal pancreatic tissue and pancreatic cancer. Ac-cording to the different expression level of FXR,these 50 patients were divided into low expression group and high expression group, the correlation of clinical data and FRX expression level was analyzed. Furthermore, Kaplan-Meier and log-rank analysis of prognostic factors was assessed in a multivariable analysis using a Cox proportional hazards model. Results FXR was differently expressed in 8 pancreatic cancer cell lines and pancreatic cancer tis-sues. FXR was closely related to the pathological G stage of pancreatic cancer(P＜0.05). FXR and pathological G stage were significantly correlated with the patients' survival time. The survival time of the patients with high FXR expression was significantly longer than that of patients with low FXR expression (P＜0.05). Conclusions The expression of FXR is closely related to the pathological G stage in patients with pancreatic cancer. Both FXR expression and pathological G stage are independent prognostic factors in patients with pancreatic cancer.

Cataract-causing mutation S228P promotes βB1-crystallin aggregation and degradation by separating two interacting loops in C-terminal domain

β/γ-Crystallins are predominant structural proteins in the cytoplasm of lens fiber cells and share a similar fold composing of four Greek-key motifs divided into two domains. Numerous cataract-causing mutations have been identified in various β/γ-crystallins, but the mechanisms underlying cataract caused by most mutations remains uncharacterized. The S228P mutation in βB1-crystallin has been linked to autosomal dominant congenital nuclear cataract. Here we found that the S228P mutant was prone to aggregate and degrade in both of the human and E. coli cells. The intracellular S228P aggregates could be redissolved by lanosterol. The S228P mutation modified the refolding pathway of βB1-crystallin by affecting the formation of the dimeric intermediate but not the monomeric intermediate. Compared with native βB1-crystallin, the refolded S228P protein had less packed structures, unquenched Trp fluorophores and increased hydrophobic exposure. The refolded S228P protein was prone to aggregate at the physiological temperature and decreased the protective effect of βB1-crystallin on βA3-crystallin. Molecular dynamic simulation studies indicated that the mutation decreased the subunit binding energy and modified the distribution of surface electrostatic potentials. More importantly, the mutation separated two interacting loops in the C-terminal domain, which shielded the hydrophobic core from solvent in native βB1-crystallin. These two interacting loops are highly conserved in both of the N- and C-terminal domains of all β/γ-crystallins. We propose that these two interacting loops play an important role in the folding and structural stability of β/γ-crystallin domains by protecting the hydrophobic core from solvent access.

Wnt3a enhances bone morphogenetic protein 9-induced osteogenic differentiation of C3H10T1/2 cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Bone morphogenetic protein 9 (BMP9) and Wnt/β-catenin signaling pathways are able to induce osteogenic differentiation of mesenchymal stem cells (MSCs), but the role of Wnt/β-catenin signaling pathway in BMP9-induced osteogenic differentiation is not well understood. Thus, our experiment was undertaken to investigate the interaction between BMP9 and Wnt/β-catenin pathway in inducing osteogenic differentiation of MSCs.</p><p><b>METHODS</b>C3H10T1/2 cells were infected with recombinant adenovirus expressing BMP9, Wnt3a, and BMP9+Wnt3a. ALP, the early osteogenic marker, was detected by quantitative and staining assay. Later osteogenic marker, mineral calcium deposition, was determined by Alizarin Red S staining. The expression of osteopotin (OPN), osteocalcin (OC), and Runx2 was analyzed by Real time PCR and Western blotting. In vivo animal experiment was carried out to further confirm the role of Wnt3a in ectopic bone formation induced by BMP9.</p><p><b>RESULTS</b>The results showed that Wnt3a enhanced the ALP activity induced by BMP9 and increased the expressions of OC and OPN, with increase of mineral calcium deposition in vitro and ectopic bone formation in vivo. Furthermore, we also found that Wnt3a increased the level of Runx2, an important nuclear transcription factor of BMP9.</p><p><b>CONCLUSION</b>Canonical Wnt/β-catenin signal pathway may play an important role in BMP9-induced osteogenic differentiation of MSCs, and Runx2 may be a linkage between the two signal pathways.</p>

Effect of Zhenwu Tang Granule on pressure-overloaded left ventricular myocardial hypertrophy in rats / 世界急诊医学杂志（英文）

BACKGROUND:In the perspective of traditional Chinese medicine, few studies have focused on the compound preparations though there are many investigations. The present study was undertaken to investigate the effect of Zhenwu Tang Granule on chronic pressure-overloaded left ventricular hypertrophy in rats. METHODS:The study was performed at the laboratory of Guangzhou Institute of Respiratory Disease. Male SD rats were divided randomly into 3 groups:sham operation group (n=8), operation group (n=15) and traditional Chinese medicine (TCM) group (n=15).The model of myocardial hypertrophy was made by gradually constricting the abdominal aorta. Sixteen weeks later, cardiac ultrasonography was performed in all groups in order to ascertain post-operational left ventricular (LV) hypertrophy. And Zhenwu Tang Granule was added at a dose of 12 g/kg in the mixed feedstuff for 8 weeks in the TCM group. In the 24th week, weight, structure as well as function of the heart in each group were measured by high-frequency ultrasonography, and Masson's staining was performed on the cardiac muscles. Meanwhile, total collagen volume fraction (CVF-T) and non-coronary vessel collagen volume fraction (CVF-NV) were analyzed. RESULTS:There was an increase in the weight of the heart in the operation group, with the left ventricule dominated (P<0.05). The heart was enlarged, with diastolic interventricular septal distance (IVSd) and left ventricular posterior wal distance (LVPWd) dominated (P<0.01).There was a significant decrease in the cardiac function (P<0.05). The weight (P<0.01) and volume of the heart decreased in the TCM group compared with the operation group, with IVSd and systolic left ventricular posterior wal dominated (P<0.01). And the cardiac function was improved (P<0.05). Significant interstitial and col agen hyperplasia was shown in the operation group based on pathological analysis, and various improvements were proved in the TCM group, i.e. there was a significant decrease in CVF-T and CVF-NV (P<0.01) compared with the operation group; but no difference (P>0.05) was found when compared with the pseudo-operation group. CONCLUSION:Zhenwu Tang Granule could reduce the weight and volume of the heart, improve the cardiac function, inhibit hyperplasia of collagen, and reverse myocardial hypertrophy in rats with pressure-overloaded left ventricular hypertrophy.

MRI Findings of Primary CNS Lymphoma in 26 Immunocompetent Patients

OBJECTIVE: To record the MR imaging features of primary central nervous system lymphoma (PCNSL) and compare these features in monofocal and multifocal disease. MATERIALS AND METHODS: Twenty-one cases of monofocal disease were compared to five cases of multifocal disease. All patients were examined by non-enhanced and contrast-enhanced MRI. Tumor location, tumor size, signal intensity, enhancement characteristics, age distribution, peritumoral edema, cystic changes, and the presence of calcifications were assessed. The MRI features were compared between the monofocal and multifocal disease cases. RESULTS: The 26 cases, including both the monofocal and multifocal cases, exhibited 37 lesions. Contrast-enhanced images showed variable enhancement patterns: homogeneous enhancement (33 lesions), ring-like enhancement (2), and 'open-ring-like' enhancement (2). The 'notch sign' was noted in four of 33 homogeneously enhancing lesions. One case of hemorrhage and three cases of cystic formation were observed. Intra-tumoral calcification was not found. The frontal lobe, the corpus callosum and the basal ganglia were commonly affected in both the monofocal and multifocal groups. Tumor size differed significantly between the two groups (t = 3.129, p 0.05) and the signal characteristics (p > 0.05) between the two groups. CONCLUSION: Our data show that PCNSL has a variable enhancement pattern on MR images. We first reported two lesions with an 'open-ring' enhancement as well as four cases with a 'notch sign'. Monofocal PCNSL cases typically have larger sized tumors with mild or moderate enhancement.

Comparative Study on 16-slice CT Coronary Angiography vs Conventional Coronary Angiography-A Report of 38 Cases / 华中科技大学学报（医学）（英德文版）

The clinical application of 16-slice CT coronary angiography (CTCA) and the impact of plaques differently characterized on assessing coronary artery stenosis were evaluated. Thirty-eight patients with coronary artery disease diagnosed by conventional coronary angiography (CAG) un- derwent 16-slice CTCA (collimation: 16×0.75 mm; rotation time: 420 msec; kernel: 35f; effective current: 500 mAs; tube voltage: 120 kV). The interval between CTCA and CAG was within one month. CTCA was evaluated by consensus of two independent experienced radiologists unknowing CAG findings. Original images, maximum intensity projections and multiplanar reconstructions were used to assess coronary artery stenosis. For a determined plaque an attenuation value≥130 HU was considered as calcified, and ＜130 HU noncalcified. The plaques were then classified into significant calcification (extensive calcification), medium calcification (small isolated calcification) and noncal- cification. The diagnostic accuracy of 16-slice CTCA findings as well as to detect ≥50% stenoses caused by plaques was evaluated respectively regarding CAG as the standard of reference. In com- parison with CAG findings, the sensitivity, specificity, positive and negative predictive value derived from CTCA for mild stenosis (＜50%) were 72.7%, 38.5%, 50%, 62.5%, respectively; for moderate stenosis (50%-75%) 82.4%, 72.7%, 70%, 84.2%, resepctively; and for severe coronary stenosis (＞75%) 85%, 90.5%, 81%, 92.7% respectively. With the increase of stenoses degree, the value of CTCA was greater. For the classification of the plaque calcification with ≥50% stenosis CTCA at- tained the sensitivity, specificity, positive and negative predictive value for severe calcificatoin 73.3%, 22.2%, 61.1% and 33.3%, respectively; for moderate calcification 70%, 55.6%, 63.6% and 62.5%, respectively; for noncalcification 93.8%, 85.7%, 93.8% and 85.7% respectively. CTCA was restricted in assessing coronary artery stenosis in the presence of calcification, but CTCA value was much im-proved in assessing non-calcified stenosis. It was concluded that 16-slice CTCA could provide useful information about coronary artery stenosis, especially for severe stenosis (≥50%) and non-calcified plaque. Since CTCA is a noninvasive technique, it may be useful in screening coronary artery dis-ease.

Expression of P33ING1 in stomach cancer and its clinical significance / 第二军医大学学报

Objective:To discuss the pathological relationship between P33ING1 and stomach cancer and its clinical significance. Methods: In 71 cases of stomach cancer specimen, twelve cases of gas tric mu cous membrane atypical hyperplasia tissues and 18 cases of normal gastric mucous membrane tissue（as control）,the expression of P33ING1 were detected b y EnVision immunohistochemical method,while the expression of P53 and Bcl -2 in stomach cancer were also detected. Results: P33IN G1 expression in mucous membrane atypical hyperplasia group and control group was positive, the expression in stomach cancer group was extremely low(62.0%，44 /71), significantly different from the other 2 groups(P<0.01).P33ING1 expression in stomach cancer was related to the tumor growth, lymph node meta s tasis and tumor polarization (P<0.01), P53 expression was related to tumor s ize, growth and lymph node metastasis (P<0.01). Bcl-2 expression was relate d to lymph node metatasis and tumor polarization.The expression of P33ING1 was related to that of P53 in stomach cancer(P<0.05),while had no relation with that of Bcl-2.Conclusion:P33ING1 may play an importa nt role in the occurrance and development of stomach cancer.It's very important to detect the expression of P33ING1 and P53 simultaneously.

Expression of P33ING1 in stomach cancer and its clinical significance / 第二军医大学学报

Objective:To discuss the pathological relationship between P33ING1 and stomach cancer and its clinical significance. Methods: In 71 cases of stomach cancer specimen, twelve cases of gas tric mu cous membrane atypical hyperplasia tissues and 18 cases of normal gastric mucous membrane tissue（as control）,the expression of P33ING1 were detected b y EnVision immunohistochemical method,while the expression of P53 and Bcl -2 in stomach cancer were also detected. Results: P33IN G1 expression in mucous membrane atypical hyperplasia group and control group was positive, the expression in stomach cancer group was extremely low(62.0%，44 /71), significantly different from the other 2 groups(P<0.01).P33ING1 expression in stomach cancer was related to the tumor growth, lymph node meta s tasis and tumor polarization (P<0.01), P53 expression was related to tumor s ize, growth and lymph node metastasis (P<0.01). Bcl-2 expression was relate d to lymph node metatasis and tumor polarization.The expression of P33ING1 was related to that of P53 in stomach cancer(P<0.05),while had no relation with that of Bcl-2.Conclusion:P33ING1 may play an importa nt role in the occurrance and development of stomach cancer.It's very important to detect the expression of P33ING1 and P53 simultaneously.