The comparative safety of biological treatment in patients with axial spondylarthritis: a meta-analysis of randomized controlled trials with placebo.

OBJECTIVE: To evaluate the comparative safety of biological treatment in patients with axial spondyloarthritis (axSpA) enrolled in randomized controlled trials (RCTs) with placebo. MATERIALS AND METHODS: Studies were systematically retrieved from the Web of Science, PubMed, Cochrane Library, and Embase databases. The last search was performed on 8 June 2020. The primary outcome measures were adverse events (AEs), serious AEs, infection, serious infection, and discontinuation due to AEs. This study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: A total of twenty-two trials, including 2599 participants treated with biologics and 1547 participants treated with placebo, met the inclusion criteria. There was a significantly higher risk of infection, AEs, and discontinuation due to AEs in the biologics groups compared to the placebo groups [risk ratio (RR) = 1.38, 95% confidence interval (95% CI) = 1.22-1.57, p < 0.01; RR = 1.17, 95% CI = 1.10-1.25, p < 0.01; and RR = 1.72, 95% CI = 1.03-2.87, p = 0.04, respectively], and low heterogeneity was found among the included studies (I2 = 0%, p = 0. 49; I2 = 29%, p = 0.10; and I2 = 0%, p = 0.79, respectively). The risk of serious infection and serious AEs was not significantly different between axSpA patients treated with biologics and those treated with placebo [RR = 1.62, 95% CI = 0.54-4.90, p = 0.39 and RR = 1.17, 95% CI = 0.79-1.73, p = 0.44]. Low heterogeneity was found among the included studies (I2 = 0%, p = 0.94 and I2 = 0%, p = 0.69). The subgroup analyses based on tumour necrosis factor inhibitors and interleukin antagonists did not yield significant differences. CONCLUSIONS: This meta-analysis is the first comprehensive assessment of the safety of various biological agents in axSpA patients. The use of biological agents in axSpA is generally safe and tolerable.

LncRNA TTN-AS1 contributes to gastric cancer progression by acting as a competing endogenous RNA of miR-376b-3p.

Long noncoding RNAs (lncRNAs) were reported to participate in the progression of gastric cancer (GC). However, litter is known about the biological functions of TTN antisense RNA 1 (TTN-AS1) in GC. Using qRT-PCR examination, we found that TTN-AS1 was expressed at a higher level in GC tissues and cell lines compared to the normal controls. Kaplan-Meier analysis of GC patients revealed the negative correlation between TTN-AS1 expression and the overall survival. To detect the biological function of TTN-AS1 in GC, we silenced TTN-AS1 to perform loss-of-function assays. The experimental results revealed that knockdown of TTN-AS1 obviously inhibited GC cell proliferation, induced cell apoptosis and impaired cell migration and invasion. In mechanism, TTN-AS1 was located in the cytoplasm of GC cells, indicating the post-transcriptional regulation of TTN-AS1 on gene expression. Bioinformatics analysis revealed the potential binding relation between TTN-AS1 and miR-376b-3p as well as between miR-376b-3p and KLF12. Mechanism experiments such as luciferase reporter assay and RNA pull-down assay demonstrated the interaction between TTN-AS1 and miR-376b-3p as well as between miR-376b-3p and KLF12 in GC cells. At last, rescue assays certified that miR-376b-3p and KLF12 involved in TTN-AS1-mediated GC progression. Similarly, the role of TTN-AS1-miR-376b-3p-KLF12 axis in GC progression was analyzed and validated. Taken together, we concluded that TTN-AS1 might function as a novel potential therapeutic target in the treatment of gastric cancer.

In vitro induction and differentiation of newborn guinea pig hippocampus neural stem cells into cells resembling inner hair cells, using artificial perilymph.

OBJECTIVE: To investigate whether artificial perilymph can induce neural stem cells, derived from the hippocampus of newborn guinea pigs, to differentiate into inner ear hair cells, in vitro. METHODS: Primary neural stem cells derived from the hippocampus of newborn guinea pigs were incubated in medium containing either 10 per cent fetal bovine serum or 5, 10 or 15 per cent artificial perilymph, for three weeks. Differentiated cells were identified using immunofluorescence, Western blot and scanning electron microscopy. RESULTS: Both fetal bovine serum and artificial perilymph induced the neural stem cells to differentiate into cells with hair-cell-specific antibodies. CONCLUSION: Neural stem cells can survive in both fetal bovine serum and artificial perilymph, and within these media can differentiate into cells with hair-cell-specific antibodies. This provides an experimental basis for transplantation of neural stem cells into the inner ear.

Effects of RNA interference targeting four different genes on the growth and proliferation of nasopharyngeal carcinoma CNE-2Z cells.

To explore the effects of RNA interference targeting four different genes (VEGF, C-myc, Survivin, hTERT) on the growth and proliferation of nasopharyngeal carcinoma (NPC) CNE-2Z cells. Fluorescein-labeled short-hairpin (sh)RNA plasmids together and separately targeting VEGF, C-myc, Survivin and hTERT were built and respectively called plasmid-shVEGF-shC-myc-shSurvivin-shhTERT, plasmid-shVEGF, plasmid-shC-myc, plasmid-shSurvivin, plasmid-shhTERT. These plasmids were respectively transfected into human NPC CNE-2Z cells and xenograft tumors in nude mice. The expression of plasmids in NPC CNE-2Z cells and xenograft tumors was observed. Cell proliferation was detected with MTT assay. The mRNA and protein expression were determined by real-time PCR and western blot, respectively. The effects of plasmids on the biological behavior of CNE-2Z cells were observed with transwell invision chamber models. Apoptosis was determined with flow cytometer. The inhibitory effect of plasmids on xenograft tumors was observed in nude mice. The plasmid containing four different shRNAs could significantly inhibit CNE-2Z cell proliferation and decrease invasion ability in vitro compared with plasmids with each single shRNA (P<0.05). The plasmid containing four different shRNAs could simultaneously downregulate VEGF, C-myc, surviving, hTERT mRNA and protein expression in the CNE-2Z cells. The multiple gene shRNA could more significantly induce cell apoptosis than each single shRNA, respectively (P<0.05). The combinative silencing of these four genes had a better inhibitory effect on xenograft tumors than the silencing of each single shRNA (P<0.05). RNA interference targeting multiple genes can effectively inhibit NPC proliferation and induce apoptosis, which provides an experiment basis for NPC gene therapy.

First Report of a Soft Rot of Banana in Mainland China Caused by a Dickeya sp. (Pectobacterium chrysanthemi).

Banana is one of the most important fruit crops grown in China (2). A severe outbreak of a soft rot of banana occurred in Guangzhou, China from 2009 to 2010. The disease was characterized by an odorous soft rot of the center of the rhizome. The rot progressed up the pseudostem, destroying the growing point and causing internal decay and often accompanied by vascular discoloration. Yellowing and wilting of the leaves were also characteristic symptoms. A survey of three areas of production of Musa sapientum (cv. ABB) covering 10 ha in Guangzhou revealed that 82% of the fields were affected at an incidence ranging from 20 to 40%. Forty-five bacterial isolates were obtained from lesions on plants sampled from these fields by surface-sterilizing symptomatic tissue in 0.3% NaOCl for 10 min, rinsing the tissue sections three times in sterile water, and plating the sections on nutrient agar. Three representative isolates selected randomly were all gram negative, caused a soft rot of potato disks, utilized malonate, tested positive for phosphatase production, and tested negative for acid production from palatinose, glucopyranoside, and trehalose. A Biolog similarity index of 0.803 indicated that the three isolates had a high similarity to the Biolog reference strain of Pectobacterium chrysanthemi (Version 4.2, Biolog Inc., Hayward, CA). The 16S rDNA sequence (GenBank Accession No. 1321085) of each of the three isolates was determined (1). When compared with sequences in GenBank, the highest degree of sequence similarity was with P. chrysanthemi AF373199. On the basis of a phylogenetic tree of the sequences, the three bacterial isolates are related to Pectobacterium (100% bootstrap values). On the basis of two diagnostic methods, the three isolates were identified as P. chrysanthemi. However, according to Samson et al. (3), they are a Dickeya sp. Additional genetic comparisons with type strains will be needed for the strains to be assigned to a known species of Dickeya. Pathogenicity of each of the three strains on M. sapientum (cv. ABB) was confirmed by injecting 60 40-day-old seedlings each with 5 ml of a suspension of the isolate (108 CFU/ml) into the rhizome. Sixty plants of the same cultivar injected with sterile water served as the control treatment. After 48 h, yellowing and wilting of the leaves, similar to symptoms observed on field plants, were observed on all inoculated seedlings for each of the three bacterial strains. There were no symptoms on the control plants. Koch's postulates were fulfilled by reisolating bacteria from lesions on the leaves of inoculated seedlings. The reisolates were identical to the inoculated strains in biochemical characteristics. Bacteria characteristic of the inoculated strains were not reisolated from the control plants. To our knowledge, this is the first report of a Dickeya sp. causing soft rot of banana in mainland China. References: (1) W. S. Kaneshiro et al. Plant Dis. 92:1444, 2008. (2) Y. P. Ke et al. China Trop. Agric. 1:14, 2008. (3) R. Samson et al. Evol. Microbiol. 55:1415, 2005.

Inhibition of cell proliferation and arrest of cell cycle progression by blocking chloride channels in human laryngeal cancer cell line Hep-2.

Chloride channel (ClC) is involved in normal physiological processes and pathology of various diseases. Although it is recognized that blockade of ClC inhibits the cell proliferation, it is not well understood the potential function of ClC in laryngeal cancer. In this study, we investigated the effect of the ClC inhibitor on cell proliferation, cell cycle progression in human laryngeal cancer cell line Hep-2, as well as the effect on the phosphorylation levels of ERK1/2 and AKT1. In this study crystal violet method was used to study the effect of the ClC inhibitor, 5-nitro-2-(3-phenylpropylamino) benzoic acid, NPPB, on Hep-2 cell proliferation. The impaction of the inhibitor on the cell cycle distribution was investigated by the flow cytometry (FCM). Western blot was performed to measure the phosphorylation levels of ERK1/2 and AKT1. Our data indicated ClC played an important role in Hep-2 cell proliferation and cell cycle. NPPB inhibited Hep-2 cell proliferation when compared with the controls. Blockade of ClC arrested cell cycle progression and suppressed the phosphorylation of ERK1/2 and AKT1 in Hep-2 cells by inhibition of cell proliferation by CIC inhibitor (NPPB) could be through arresting cell cycle progression, which is probably by suppressing phosphorylation of ERK1/2 and AKT1.

[The first branchial fistula: an analysis of 16 cases].

OBJECTIVE: To discuss how to improve the level of diagnosis and treatment about the first branchial fistula. METHOD: 16 cases with the first branchial fistula were analyzed retrospectively. RESULT: Of all the patients underwent surgery, 14 cases were free from disease postoperatively within 0.5 years follow-up, 2 patients underwent re-operation because of recurrence. CONCLUSION: Knowing about the disease fully, selecting proper surgical incision and possessing skilled surgical technique is important to improve the level of diagnosis and treatment about the first branchial fistula.

[Quantitative assay of telomerase activity in head and neck squamous cell carcinoma].

OBJECTIVE: To detect and quantify telomerase activity in tissues from head and neck squamous cell carcinoma (HNSCC), and to explore whether the levels of telomerase activity can be a useful marker for cancer risk assessment in HNSCC. METHOD: The levels of telomerase activity of 55 fresh specimens obtained from 25 patients with HNSCC were detected by the method of telomeric repeat scintillation radioactive count, including 25 primary tumors, 7 samples of neck metastases and 23 corresponding normal tissues as control. In 7 patients, both primary and metastatic tumors were obtained. The levels of telomerase activity were determined with a liquid scintillation counter. The basic principle of the technique is that a G-rich oligonucleotide strand of telomeric sequence is used as primer, 3H-dTTPs are incorporated into the products while telomerase elongates the primers, and then free 3H-dTTPs are removed by rinsing step, finally radioactive count per minute (cpm) of products is detected, and the levels telomerase activity can be evaluated according to the value (cpm). RESULT: 1. The levels of telomerase activity (cpm) in tissues with HNSCC were significantly higher than those in the normal tissues (P < 0.05); 2. The levels of telomerase activity in the primary tumors were higher than those of their neck metastases, but the difference was not statistical significance (P > 0.05); 3. The levels of telomerase activity in the neck metastases were remarkably higher than those in the normal tissues (P < 0.05). CONCLUSION: 1. Detection of telomerase activity in HNSCCs can be a useful marker for cancer assessment. 2. To quantify telomerase activity may have clinical diagnostic value for HNSCC. 3. The levels of telomerase activity in the metastatic lymph nodes were higher.