Objective To study the effects of total extracts of Averrhoa carambola L.( Oxalidaceae ) roots ( TEACLR ) in hyperlipidemia rats. Methods Sixty SD rats ( male and female in half ) were subjected to induction of hyperlipidemia by high -fat diet for established hyperlipi-demia rat model and were divided into the following groups:blank group, model group, positive control group ( simvastatin 2.5 mg? kg-1? d -1 orally) , TEACLR high, middle and low doses groups.Hyperlipidemia rats were treated with TEACLR, at doses of 1200, 600 and 300 mg? kg-1? d-1 for 5 weeks by gavages, respectively.After 5-week of treatment with drugs, blood sample and liver were collected for determi-nation.Results In contrast to the model group, TEACLR could reduce the contents of cholesterol, triglyceride, low-density lipoprotein, alka-line phosphatase in rat serum and liver malondialdehyde reduced obvious-ly [ ( 2.48 ±0.43 ) , ( 0.86 ±0.44 ) , ( 0.86 ±0.43 ) mmol? L-1 and (165.55 ±71.71 ) U? L-1 , ( 1.38 ±0.42 ) nmol? prot-1 , respective-ly] .The level of high -density lipoprotein and glutathione elevated evidently [(1.67 ±0.32)mmol? L-1,(3.43 ±0.78)nmol? prot -1]. Liver coefficient was significantly lowered ( 2.92 ±0.03 ) .TEACLR middle dose group could reduce the contents of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) obviously[(38.91 ±10.47),(99.91 ±30.74) U? L-1 ].TEACLR high dose group could increase the contents of superoxide dismutase evidently(24.44 ±3.13) nmol? prot -1 .Comparison with blank group and positive control group, there was no significant difference in TEACLR middle dose group.Conclusion TEACLR is proven to be able to decrease the level of hyperlipidemia markedly, which might be used as an effective therapeutic agent for hyperlipidemia and fatty liver.

Objective To establish a model of acoustically evoked short latency negative response (ASNR) in guinea pigs, a model of profound hearing loss with normal saccular functions, and verify the correlation between ASNR and vestibular evoked myogenic potential (VEMP). Methods Thirty-two healthy guinea pigs were employed in the experiment, which were randomly divided into control group ( 16subjects) and deafened group (16 subjects). Each animal experienced auditory and vestibular tests including auditory brainstem response ( ABR), VEMP and caloric test. A quick treatment was employed for deafened group consisting of a subcutaneous injection of kanamycin at a dose of 400 mg/kg followed by a jugular vein injection of ethacrynic acid at a dose of 40 mg/kg one hour later. The animals were received ABR, VEMP and caloric test 7 - 10 days following the drug administration. The deafened group was further divided into ASNR group and non-ASNR group, based on the presence of ASNR. Results In deafened group, five subjects died postoperatively, 11 subjects (22 ears) provided full data, ASNR was elicited in eight ears (36.4%), the threshold was 120- 130 dB SPL with mean of (124.4 ±4.96) dB SPL. Its latency range was 1.75 - 2. 60 ms with mean of ( 2. 15 ± 0. 27 ) ms. The mean latency of threshold was (2. 34 ±0. 18) ms. All eight ASNR ears presented with VEMP. The VEMP threshold, positive and negative potential latencies proved no statistical difference (P ＞ 0. 05 ) between ASNR group and control group.Significant difference was detected between the VEMP presence of ASNR group and non-ASNR group ( P =0. 002). There was no statistically significant correlation between VEMP and caloric test neither between ASNR and caloric test in deafened group. Conclusions This study evoked ASNR in an ototoxicity guinea pig model which has profound hearing loss with normal saccular functions. The presence of ASNR correlated with VEMP, however, not correlated with caloric test, suggesting that ASNR and VEMP are both originated from the saccule.

Osteosarcoma is suggested to be caused by genetic and molecular alterations that disrupt osteoblast differentiation. Recent studies have reported that transmembrane protein 119 (TMEM119) contributes to osteoblast differentiation and bone development. However, the level of TMEM119 expression and its roles in osteosarcoma have not yet been elucidated. In the present study, TMEM119 mRNA and protein expression was found to be up-regulated in osteosarcoma compared with normal bone cyst tissues. The level of TMEM119 protein expression was strongly associated with tumor size, clinical stage, distant metastasis and overall survival time. Moreover, gene set enrichment analysis (GSEA) of the Gene Expression Omnibus (GEO) GSE42352 dataset revealed TMEM119 expression in osteosarcoma tissues to be positively correlated with cell cycle, apoptosis, metastasis and TGF-β signaling. We then knocked down TMEM119 expression in U2OS and MG63 cells using small interfering RNA, which revealed that downregulation of TMEM119 could inhibit the proliferation of osteosarcoma cells by inducing cell cycle arrest in G0/G1 phase and apoptosis. We also found that TMEM119 knockdown significantly inhibited cell migration and invasion, and decreased the expression of TGF-β pathway-related factors (BMP2, BMP7 and TGF-β). TGF-β application rescued the inhibitory effects of TMEM119 knockdown on osteosarcoma cell migration and invasion. Further in vitro experiments with a TGF-β inhibitor (SB431542) or BMP inhibitor (dorsomorphin) suggested that TMEM119 significantly promotes cell migration and invasion, partly through TGF-β/BMP signaling. In conclusion, our data support the notion that TMEM119 contributes to the proliferation, migration and invasion of osteosarcoma cells, and functions as an oncogene in osteosarcoma.
Apoptosis ; Bone Cysts ; Bone Development ; Cell Cycle ; Cell Cycle Checkpoints ; Cell Movement ; Dataset ; Down-Regulation ; Gene Expression ; In Vitro Techniques ; Neoplasm Metastasis ; Oncogenes ; Osteoblasts ; Osteosarcoma* ; RNA, Messenger ; RNA, Small Interfering ; Up-Regulation*

Objective To establish a model of ototoxicity in guinea pigs with acoustically evoked short latency negative response (ASNR) and verify the responsible organ of ASNR based on microscopic characteristics of basal membranes,saccules,utricles and ampulla canalis semicircularis of the inner ear.Methods Total of 45 guinea pigs were employed in the experiment,which were randomly divided into the control group (15 subjects,30 ears) and the deafened group (30 subjects,60 ears). Each animal experienced auditory brainstem response ( ABR ). A quick treatment was employed for deafened group consisting of a subcutaneous injection of kanamycin at a dose of 400 mg/kg followed by jugular vein injection of ethacrynic acid at a dose of 40 mg/kg one hour later.The animals were performed ABR test from 7 to 10 days after the drug administration.The deafened group was further divided into ASNR group and non-ASNR group based on the presence of ASNR.All the guinea pigs were sacrificed after ABR tests.The Corti organ,macula sacculi,macula utriculi and crista ampullaris were observed by light microscope.Results In the deafened group (60 ears),3 subjects died postoperatively,27 subjects (54 ears) provided full data.ASNR was elicited in 19 ears (35.2％,19/54 ),the thresholds of ASNR were from 110 to 125 dBSPL with average of ( 121.7 ±4.5)dBSPL ASNR latency ranges were 1.80-2.08 ms,the average latency of thresholds were ( 1.93 ±0.07) ms.The stretched preparation results:overall hair-cell density of macula saccule,macula utriculi and crista ampullaris decreased in order of normal eontrol group,ASNR group and non-ASNR group.There was no difference between the normal group and ASNR group for cell density of macula saccule.Apart from this,statistical differences were found among other groups.Conclusions The present study evoked ASNR in an olotoxicity guinea pig model which was profound hearing loss with normal saccular function and normal saccular hair cell density.It suggested that ASNR originates from the saccule and have no relation with cochlear,utricle and semicircular canal according to morphological study.

Background: Prospective real-life data on the safety and effectiveness of rituximab in Chinese patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) are limited. This real-world study aimed to evaluate long-term safety and effectiveness outcomes of rituximab plus chemotherapy (R-chemo) as first-line treatment in Chinese patients with DLBCL or FL. Hepatitis B virus (HBV) reactivation management was also investigated. Methods: A prospective, multicenter, single-arm, noninterventional study of previously untreated CD20-positive DLBCL or FL patients receiving first-line R-chemo treatment at 24 centers in China was conducted between January 17, 2011 and October 31, 2016. Enrolled patients underwent safety and effectiveness assessments after the last rituximab dose and were followed up for 3 years. Effectiveness endpoints included progression-free survival (PFS) and overall survival (OS). Safety endpoints were adverse events (AEs), serious AEs, drug-related AEs, and AEs of special interest. We also reported data on the incidence of HBV reactivation. Results: In total, 283 previously untreated CD20-positive DLBCL and 31 FL patients from 24 centers were enrolled. Three-year PFS was 59% (95% confidence interval [CI]: 50-67%) for DLBCL patients and 46% (95% CI: 20-69%) for FL patients. For DLBCL patients, multivariate analyses showed that PFS was not associated with international prognostic index, tumor maximum diameter, HBV infection status, or number of rituximab treatment cycles, and OS was only associated with age >60 years (P < 0.05). R-chemo was well tolerated. The incidence of HBV reactivation in hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative/hepatitis B core antibody-positive patients was 13% (3/24) and 4% (3/69), respectively. Conclusions: R-chemo is effective and safe in real-world clinical practice as first-line treatment for DLBCL and FL in China, and that HBV reactivation during R-chemo is manageable with preventive measures and treatment. Trial Registration ClinicalTrials.gov, NCT01340443; https://clinicaltrials.gov/ct2/show/NCT01340443.
Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; China ; Cyclophosphamide ; administration & dosage ; Doxorubicin ; administration & dosage ; Female ; Follow-Up Studies ; Humans ; Lymphoma, Follicular ; drug therapy ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; Male ; Middle Aged ; Prospective Studies ; Rituximab ; therapeutic use ; Vincristine ; administration & dosage