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Gnathostoma doloresi is one of the neglected pathogens causing gnathostomiasis. Although this zoonotic parasite leads to significant socioeconomic concerns globally, little is known of its genetics and systematics. In the present study, we sequenced and characterized the complete mitochondrial (mt) genomes of G. doloresi isolates from China and Japan. The lengths of the mt genomes of the G. doloresi China and Japan isolates are 13,809 and 13,812 bp, respectively. Both mt genomes encode 36 genes, including 12 protein-coding genes (PCGs), 2 ribosomal RNA genes, and 22 transfer RNA genes. The gene order, transcription direction, and genome content are identical with its congener G. spinigerum. Phylogenetic analyses based on concatenated amino acid sequences of 12 PCGs by Bayesian inference (BI) indicated that G. doloresi are closely related to G. spinigerum. Our data provide an invaluable resource for studying the molecular epidemiology, phylogenetics, and population genetics of Gnathostoma spp. and should have implications for further studies of the diagnosis, prevention, and control of gnathostomiasis in humans and animals. [ABSTRACT FROM AUTHOR]

The objective of this meta-analysis was to evaluate the effects of repetitive transcranial magnetic stimulation (rTMS) for the treatment of depression in patients with Parkinson disease in order to arrive at qualitative and quantitative conclusions about the efficacy of rTMS. We included randomized controlled trials examining the effects of rTMS compared with sham-rTMS or selective serotonin re-uptake inhibitors (SSRIs). The quality of included studies was strictly evaluated. Data analyses were performed using the RevMan5.1 software. Eight studies including 312 patients met all inclusion criteria. The results showed that rTMS could evidently improve the HRSD score compared with sham-rTMS (p < 0.00001). However, we found similar antidepressant efficacy between rTMS and SSRIs groups in terms of HRSD and BDI score (p = 0.65; p = 0.75, respectively). Furthermore, patients who received rTMS could evidently show improvement on the unified Parkinson's disease rating scale (UPDRS), ADL score, and UPDRS motor score compared with sham-rTMS or SSRIs (p < 0.05, p = 0.05, respectively). The subgroup analysis by frequency of rTMS evidenced that the efficacy of low-frequency rTMS was superior to sham-rTMS (p < 0.0001) in terms of the outcome measure according to HAMD scale. Meanwhile, the high-frequency rTMS has the same antidepressant efficacy as SSRIs (p = 0.94). The current meta-analysis provided evidence that rTMS was superior to sham-rTMS and had similar antidepressant efficacy as SSRIs, and may have the additional advantage of some improvement in motor function. [ABSTRACT FROM AUTHOR]

The optimal treatment strategy for elderly patients with natural killer/T-cell lymphoma (NKTCL) remains to be established. A total of 63 elderly patients with newly diagnosed NKTCL were retrospectively reviewed. Among the patients with stage I-II disease, 58.3 % received radiotherapy (RT) ± chemotherapy, and 41.7 % received chemotherapy alone. Compared with chemotherapy alone, RT ± chemotherapy elicited a significantly higher overall response rate (ORR) (100 vs. 57.1 %, P < 0.001) and substantially prolonged 5-year overall survival (OS) (55.3 vs. 18.0 %, P < 0.001) in patients with stage I-II disease. Compared with other chemotherapeutic regimens, pegaspargase plus gemcitabine and oxaliplatin (PGEMOX)/L-asparaginase plus gemcitabine and oxaliplatin (GELOX) was associated with a significantly higher ORR (92.9 vs. 51.6 %, P = 0.009) and a significantly improved 5-year OS (78.6 vs. 23.9 %, P = 0.010) in patients with stage I-II disease. Nine patients with stage I-II disease who were treated with PGEMOX/GELOX followed by RT had an encouraging outcome (5-year OS 100 %, 5-year progression-free survival (PFS) 85.7 %), which was superior to that of patients receiving other regimens followed by RT. In conclusion, RT played an important role for elderly patients with early-stage NKTCL, and the PGEMOX/GELOX regimen was superior to other regimens. The combination of them may be a promising treatment option. [ABSTRACT FROM AUTHOR]

To assess the long-term use of l-dopa alone vs l-dopa-sparing therapy, as initial treatment, provides the most efficient long-term control of symptoms and best quality of life for people with early Parkinson's disease (PD). PubMed; Google scholar; Cochrane Central Register of Controlled Trials and the Web of Science were searched for randomised, placebo-controlled trials (RCTs) on l-dopa alone and l-dopa sparing as initial treatment in early PD patients. We used a random effects model rather than a fixed effects model because of this takes into account heterogeneity between multi-studies. Eleven RCTs were included. The results showed that l-dopa alone could evidently improve the UPDRS part I ( p = 0.005), part II ( p < 0.0001), part III ( p < 0.0001) and UPDRS total score ( p = 0.004) compared with l-dopa-sparing therapy in PD patients. Meanwhile, a reduced risk of dyskinesia ( p < 0.0001, RR = 1.88, 95 % CI 1. 37-2.59) and wearing-off phenomenon ( p < 0.00001, RR = 1.36, 95 % CI 1. 20-1.55) in patients treated initially with l-dopa-sparing therapy compared to l-dopa has been consistently reported. What is more, we found more patients on a l-dopa-sparing therapy were more than triple as likely to discontinue treatment prematurely due to adverse events than l-dopa treatment patients (43.7 vs 15.8 %). l-Dopa alone is the most effective medication available for treating the motor symptoms of PD patients, despite the greater incidence of involuntary movements. Meanwhile, more patients on dopamine agonists or MAOBI were more likely to discontinue treatment prematurely than l-dopa alone treatment patients within the long follow-up period. [ABSTRACT FROM AUTHOR]

The prognosis of advanced stage natural killer/T-cell lymphoma (NKTCL) remains relatively disappointing, and the optimal treatment strategy for this disease has yet to be discovered. Seventy-three patients with Ann Arbor stage III or IV NKTCL were retrospectively reviewed. The treatment efficacies of asparaginase-containing and asparaginase-absent chemotherapy regimens were compared, and the effects of postchemotherapeutic radiotherapy were explored. The overall response rate (ORR) of the asparaginase-containing regimens was marginally higher than that of the asparaginase-absent regimens (56.5 vs 32.6 %, P = 0.057). However, no significant difference was observed in 2-year overall survival (OS) (38.3 vs 22.7 %, P = 0.418) or 2-year progression-free survival (PFS) (25.4 vs 14.9 %, P = 0.134) between the asparaginase-containing and asparaginase-absent groups. Postchemotherapeutic radiotherapy was associated with a significantly prolonged survival (2-year OS 57.5 vs 14.5 %, P < 0.001; 2-year PFS 46.3 vs 8.4 %, P < 0.001) and was an independent predictor of both OS and PFS. Radiotherapy significantly improved the prognosis among the patients who exhibited complete or partial remission after initial chemotherapy (2-year OS 81.5 vs 40.2 %, P = 0.002; 2-year PFS 65.6 vs 23.4 %, P = 0.008) but failed to provide a significant survival advantage among those who experienced stable or progressive disease after initial chemotherapy. In conclusion, the use of asparaginase did not significantly improve survival for the treatment of patients with stage III/IV NKTCL. Postchemotherapeutic radiotherapy provided additional prognostic benefits to patients who responded well to the initial chemotherapy, which requires further validation in future prospective studies using larger sample sizes. [ABSTRACT FROM AUTHOR]

Notch signalling pathway plays an essential role in the development of cochlea, which inhibits the proliferation of hair cells. Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol in green tea, which presents strong antioxidant activation and has been applied for anti-cancer and anti-inflammatory. In this study, we treated the cochlear explant cultures with EGCG and found that EGCG can protect cochlear hair cells from ototoxic drug gentamicin. We demonstrated that EGCG could down-regulate the expression of Notch signalling pathway target genes, such as Hes1, Hes5, Hey1 and Hey5. However, the Notch pathway ligands such as Delta1, Jag1 and Jag2 were not affected by EGCG. To further illustrate the mechanism of recover cochlear hair cells, we demonstrated that EGCG inhibited the activity of γ-secrectase to suppress Notch signalling pathway and promoted the proliferation and regeneration of hair cells in the damaged cochlea. Our results suggest for the first time the role of EGCG as an inhibitor of the Notch signalling pathway, and support its potential value in hearing-impaired recovery in clinical therapy. [ABSTRACT FROM AUTHOR]

Aim:Potassium 2-(1-hydroxypentyl)-benzoate (dl-PHPB) is a new drug candidate for ischemic stroke. The aim of this study was to investigate the effects of dl-PHPB on memory deficits and long-term potentiation (LTP) impairment in animal models of Alzheimer's disease.Methods:The expression of NMDA receptor subunits GluN1 and GluN2B in the hippocampus and cortex of APP/PS1 transgenic mice were detected using Western blot analysis. Memory deficits of the mice were evaluated with the passive avoidance test. LTP impairment was studied in the dentate region of Aβ1-42-injected rats and APP/PS1 transgenic mice.Results:APP/PS1 transgenic mice showed significantly lower levels of GluN1 and p-GluN2B in hippocampus, and chronic administration of dl-PHPB (100 mg·kg−1·d−1, po) reversed the downregulation of p-GluN2B, but did not change GluN1 level in the hippocampus. Furthermore, chronic administration of dl-PHPB reversed the memory deficits in APP/PS1 transgenic mice. In the dentate region of normal rats, injection of dl-PHPB (100 μmol/L, icv) did not change the basal synaptic transmission, but significantly enhanced the high-frequency stimulation (HFS)-induced LTP, which was completely prevented by pre-injection of APV (150 μmol/L, icv). Chronic administration of dl-PHPB (100 mg·kg−1·d−1, po) reversed LTP impairment in Aβ1-42-injected normal rats and APP/PS1 transgenic mice.Conclusion:Chronic administration of dl-PHPB improves learning and memory and promotes LTP in the animal models of Alzheimer's disease, possibly via increasing p-GluN2B expression in the hippocampus. [ABSTRACT FROM AUTHOR]