Accumulating evidence has confirmed the links between transfer RNA (tRNA) modifications and tumor progression. The present study is the first to explore the role of tRNA methyltransferase 5 (TRMT5), which catalyzes the m1G37 modification of mitochondrial tRNAs in hepatocellular carcinoma (HCC) progression. Here, based on bioinformatics and clinical analyses, we identified that TRMT5 expression was upregulated in HCC, which correlated with poor prognosis. Silencing TRMT5 attenuated HCC proliferation and metastasis both in vivo and in vitro, which may be partially explained by declined extracellular acidification rate (ECAR) and oxygen consumption rate (OCR). Mechanistically, we discovered that knockdown of TRMT5 inactivated the hypoxia-inducible factor-1 (HIF-1) signaling pathway by preventing HIF-1α stability through the enhancement of cellular oxygen content. Moreover, our data indicated that inhibition of TRMT5 sensitized HCC to doxorubicin by adjusting HIF-‍1α. In conclusion, our study revealed that targeting TRMT5 could inhibit HCC progression and increase the susceptibility of tumor cells to chemotherapy drugs. Thus, TRMT5 might be a carcinogenesis candidate gene that could serve as a potential target for HCC therapy.
Humans ; Carcinoma, Hepatocellular/pathology* ; Cell Hypoxia ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Liver Neoplasms/pathology* ; Signal Transduction/genetics* ; tRNA Methyltransferases/metabolism*

Objective:To compare the efficacy and safety of ultrasound-guided percutaneous translumial septal myocardial ablation in dogs using laser and radiofrequency.Methods:Twelve healthy adult Beagle dogs (males or females) were randomly divided into two groups, namely, group laser and group radiofrequency (6 dogs each group). Under ultrasound guidance, laser fiber or radiofrequency ablation needle was respectively inserted into the basal and middle segments of the interventricular septa via the percutaneous transapical approach to perform ablation. The Beagle dogs received radiologic examination, laboratory tests and pathological detection before ablation, immediately after ablation, at 1 week after ablation, and at 1 month after ablation, respectively. The efficacy and safety of the two ablation procedures were compared.Results:All dogs survived after ablation. The peak gradient of LVOT decreased immediately after ablation using either laser or radiofrequency ( P<0.05), but it increased at 1 week after ablation than before ( P<0.05). At 1 month after ablation, no significant differences were found in the peak gradient of LVOT compared with that before surgery ( P<0.05). The interventricular septum thickness was increased immediately after ablation using either laser or radiofrequency than before ( P<0.05), but it decreased at 1 week and at 1 month after surgery than before ( P<0.05). The ablation zone using radiofrequency was slightly larger than that of using laser[(372.50±69.06)mm 3 vs (116.65±20.15)mm 3, P<0.001], and the surgical time of the former was significantly shorter than that of using laser [(56.00±3.22)s vs (260.00±65.39)s, P<0.05)]. Conclusions:Ultrasound-guided percutaneous translumial septal myocardial ablation is feasible, safe and effective using either laser or radiofrequency. Comparatively speaking, radiofrequency ablation is more simple and convenient.

Objective:To prepare ultrasound-responsive nanodroplets with block polymer PEG-PCL as shell and perfluoropentane (PFP) as core, and study the effects of mechanical index (MI) on contrast-enhanced imaging properties of nanodroplet.Methods:PEG-PCL micelles were first prepared by dialysis, and then the micelles were mixed with PFP for emulsification to obtain nanodroplets. The particle size and zeta potential of nanodroplets were measured, and the morphology of nanodroplets were observed using transmission electron microscope (TEM). The stability of nanodroplets after storage at 25 ℃ and 37 ℃ was investigated. The phase transition and contrast-enhanced imaging of nanodroplets in vitro under a series of mechanical index (MI) were studied using an ultrasound diagnostic instrument.Results:The particle size of the nanodroplets was (356.6±5.6)nm, and the zeta potential was -(7.30±0.14)mV. The nanodroplets were close to spherical under TEM and had a clear core-shell structure. The particle size and dispersion of the nanodroplets increased after storage at 37 ℃ and 25 ℃. For imaging in vitro, no acoustic signal were observed at 25 ℃ when the MI varied from 0.08 to 1.0. At 37 ℃, acoustic signals were observed when MI≥0.4, and the intensity was stronger for higher MIs.Conclusions:The contrast-enhanced imaging of nanodroplets are closely related to the MI, and a higher MI could induce the phase transition of more nanodroplets and produce stronger contrast enhancement. This study could provide basis for the application of polymeric nanodroplets in ultrasound diagnosis and targeted therapy.

OBJECTIVE： To analyze the current status and trend of opioids consumption in China， and to provide reference for rational use of opioids. METHODS： Purchasing data on five opioids as fentanyl， morphine， pethidine， oxycodone and hydromorphone， were extracted from the database of the Medicine Economic Information Network from 2014 to 2016. Drug consumption was measured by the daily dose per million population （unit： S-DDD）， and the consumption amount of all opioids and different dosage forms （including oral dosage form， injection and other form） in China and different districts were analyzed and compared. RESULTS： The consumption amount of five opioids increased from 69.62 S-DDD in 2014 to 78.64 S-DDD in 2016. The consumption amount of hydromorphone and oxycodone showed an upward trend， while the consumption amount of morphine was basically unchanged， and the consumption amount of fentanyl and pethidine showed a downward trend. The consumption amount of oral dosage form increased from 39.77 S-DDD in 2014 to 45.61 S-DDD in 2016， the consumption amount of the injection increased from 20.74 S-DDD in 2014 to 24.23 S-DDD in 2016， and the consumption amount of other form decreased from 9.11 S-DDD in 2014 to 8.81 S-DDD in 2016. The consumption amount of oral dosage form was around twice that of injection， with the gap expanding yearly. Regionally， the consumption amount of five opioids in the eastern region was the highest， followed by the western region， and the lowest but the highest growth rate in the central region from 2014 to 2016 （in 2016， consumption amount of eastern， western and central regions were 94.04， 67.90， 63.78 S-DDD， with increase rate of 8.50％， 11.77％， 16.17％， compared with 2014）. Morphine was the most widely used drug in all regions， followed by fentanyl； in the eastern and central regions， the use of oral and injection dosage form increased year by year； in western region， the use of oral dosage forms increased while that of injection decreased year by year. CONCLUSIONS： The opioids consumption in China is increasing overall， with regional differences. Nonetheless， the overall consumption is still low. On the premise of strict supervision， it is necessary to take measures to promote the rational use of opioids in different areas.

Objective To investigate the effect of acupuncture-rehabilitation therapy on the neurological function and the expression of cleaved-caspase-8, cleaved-caspase-3 and cellular inhibitor of apoptosis 1 (cIAP1) in ischemic penumbra of rats with cerebral ischemia. Methods A total of 90 male Sprague-Dawley rats were randomly divided into sham group, model group, acupuncture group, rehabilitation group and acupuncture-rehabilitation group. Each group was divided into three days, seven days and 14 days subgroups (n=6). The cerebral ischemia model was established with the modified Koizumi suture method. The sham group and the model group received no treatment. The acupuncture group received cluster needling of scalp acupuncture, the rehabilitation group received treadmill training, and the acupuncture-rehabilitation group received both acupuncture and treadmill training. Three days, seven days and 14 days after modeling, their neurological function was assessed with modified Neurological Severity Score (mNSS) and Rota-rod test, and the expression of cleaved-caspase-8, cleaved-caspase-3 and cIAP1 protein in cerebral ischemic penumbra were detected with Western blotting. Results Compared with the model group, the mNSS scores decreased, the retention time of Rota-rod test increased, the expression of cleaved-caspase-8, cleaved-caspase-3 protein decreased and the expression of cIAP1 protein increased in each treatment group at each time point (P<0.05). Compared with the other two treatment groups, the mNSS scores further decreased, the retention time further increased, the expression of cleaved-caspase-8, cleaved-caspase-3 protein further decreased, and the expression of cIAP1 protein further increased (P<0.05) seven days and 14 days after modeling in the acupuncture-rehabilitation group.Conclusion Acupuncture-rehabilitation therapy can improve the neurological function in rats with cerebral ischemia, that is better than the simple acupuncture or exercise, which may relate to the inhibition of caspase-8 and caspase-3 protein activation, and promotion of cIAP1 protein expression, to inhibit the apoptotic caspases cascade reaction.

Intestinal flora plays an important role in the process of human health and disease conversion. It not only participates in a number of physiological processes in the host, but also affects the central nervous system (CNS) -related diseases, which may involve in neurotransmitter, immune, endocrine, metabolites, etc. Intestinal dysbacteriosis plays a role in the development of CNS diseases, such as ischemic brain injury, Parkinson's disease, Alzheimer's disease, multiple sclerosis, hepatic encephalopathy, and mental disorders, etc. Fecal microbes transplantation, exercise training, acupuncture and Tuina therapy can improve the intestinal flora balance, which may be potential for the treatment and prevention of some nervous system diseases.

Gut microbiota, as a "microbial organ" in human body, has important physiological functions and participates in regulating body's homeostasis and health. Exercise can improve metabolism and immune regulation of body by promoting the composition and structure of gut microbiota, and even affects interaction of the "microbiota-gut-brain axis". This article reviewed the effects of various functions of gut microbiota on body and relationship between gut microbiota and exercise.

Objective To explore the effect of Taijiquan on motor function and depression in patients with post-stroke depression. Meth-ods From January to October, 2015, 60 stroke patients with depression were randomly divided into control group (n=30) and Taijiquan group (n=30). Both groups accepted routine rehabilitation, while Taijiquan group accepted another training of six actions from simplified Taijiquan. They were assessed with Fugl-Meyer Assessment (FMA), Barthel Index (BI) and Hamilton Depression Rating Scale (HAMD) be-fore, and four and eight weeks after treatment. Results The scores of FMA and BI increased more in Taijiquan group than in the control group after treatment (t>2.351, P<0.05), while the score of HAMD decreased more (t>2.169, P<0.05). Conclusion Taijiquan can relieve the depression and improve the motor and activities of daily living in patients with post-stroke depression.

Objective To explore the effects of acupuncture-rehabilitation therapy on neurological function recovery and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway activation after permanent focal cerebral ischemia in rats. Methods Ninty male Sprague-Dawley rats were divided into five groups, namely sham group, model group, acupuncture group, rehabilitation group and acupunc-ture-rehabilitation group, and 18 in each group. Each group was further divided into 3 days, 7 days and 14 days subgroups (n=6). Their mid-dle cerebral arteries were occluded except those of sham group. The sham and model groups accepted no treatment, while the acupuncture group accepted cluster needling of scalp acupuncture, rehabilitation group accepted treadmill training, and the acupuncture-rehabilitation group accepted both acupuncture and treadmill training. They were assessed with modified Neurologic Severity Score (mNSS) 3, 7 and 14 days after modeling, while the expression of ERK1/2 and p-ERK1/2 were determined with Western blotting. Results The neurologic severi-ty score reduced in all three treatment groups (P<0.05) compared with that of the model group at every time point, and was the least in the acupuncture-rehabilitation group (P<0.05) 7 and 14 days after modeling among the treatment groups. Meanwhile, the expression of p-ERK1/2 increased in all three treatment groups (P<0.05), and was the most in the acupuncture-rehabilitation group (P<0.05), as well as the rate of (p- ERK1/2)/(ERK1/2) (P<0.05). Conclusion Acupuncture- rehabilitation therapy can promote the neurological function recovery, which may be associated with activation of ERK1/2 signaling pathway.

Objective To investigate the effect of electroacupuncture or exercise preconditioning on neurological function after focal ce-rebral infarction in rats and the possible mechanism. Methods A total of 24 male Sprague-Dawley rats were randomly divided into model group (n=6), sham group (n=6), exercise preconditioning group (n=6) and electroacupuncture preconditioning group (n=6). The model group and the sham group did not accept any treatment, while the exercise preconditioning group and the electroacupuncture precondition-ing group accepted treadmill training and electroacupuncture for two weeks, respectively. Their middle cerebral arteries were occluded with modified Longa's approach, except the sham group that was ligated the same arteries but did not result in infarction. They were evaluated with Neurologic Severity Scores (NSS) 24 hours after modeling, and the laminin expression in the ischemic area was detected with Western blotting. Results There was no neurological deficit in the sham group. The NSS was lower in both preconditioning groups than in the model group (P<0.05), but was not significant different between preconditioning groups (P>0.05). The expression of laminin was the most in the sham group, and was more in both preconditioning groups than in the model group (P<0.05), but was not significant different between pre-conditioning groups (P>0.05). Conclusion Preconditioning with exercise or electroacupuncture can both reduce the neurological deficits in rats after focal cerebral infarction, which may associate with the protection of laminin from inhibition in early stage.