Liver diseases constitute a major healthcare burden globally, including acute hepatic injury resulted from acetaminophen overdose, ischemia-reperfusion or hepatotropic viral infection and chronic hepatitis, alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC). Attainable treatment strategies for most liver diseases remain inadequate, highlighting the importance of substantial pathogenesis. The transient receptor potential (TRP) channels represent a versatile signalling mechanism regulating fundamental physiological processes in the liver. It is not surprising that liver diseases become a newly explored field to enrich our knowledge of TRP channels. Here, we discuss recent findings revealing TRP functions across the fundamental pathological course from early hepatocellular injury caused by various insults, to inflammation, subsequent fibrosis and hepatoma. We also explore expression levels of TRPs in liver tissues of ALD, NAFLD and HCC patients from Gene Expression Omnibus (GEO) or The Cancer Genome Atlas (TCGA) database and survival analysis estimated by Kaplan-Meier Plotter. At last, we address the therapeutical potential and challenges by pharmacologically targeting TRPs to treat liver diseases. The aim is to provide a better understanding of the implications of TRP channels in liver diseases, contributing to the discovery of novel therapeutic targets and efficient drugs.

BACKGROUND: Based on reported results of three large cardiovascular outcome trials (CVOTs) of glucagon-like peptide 1 receptor agonists (GLP-1 RAs), we aimed to investigate the overall effect of GLP-1 RAs on major adverse cardiovascular events (MACEs) and to identify subpopulations exhibiting the greatest cardiovascular (CV) benefit. METHODS: Three CVOTs reporting effects of long-acting GLP-1 RAs were included: LEADER (liraglutide), SUSTAIN-6 (semaglutide), and EXSCEL (exenatide once weekly). In all studies, the primary endpoint was three-point MACE, comprising CV death, non-fatal myocardial infarction, and non-fatal stroke. Overall effect estimates were calculated as hazard ratios and 95% confidence intervals (CIs) using the random-effects model; subgroup analyses reported in the original studies were similarly analyzed. RESULTS: Overall, statistically significant risk reductions in MACE and CV death were observed. Subgroup analysis indicated a significant racial difference with respect to CV benefit (P for interaction <0.001), and more substantial risk reductions were observed in subjects of African origin (relative risk [RR], 0.78; 95% CI, 0.60 to 0.99) and in Asians (RR, 0.35; 95% CI, 0.09 to 1.32). However, post hoc analysis (Bonferroni method) revealed that only Asians exhibited a significantly greater CV benefit from treatment, compared with white subjects (P<0.0001). CONCLUSION: Long-acting GLP-1 RAs reduced risks of MACE and CV deaths in high-risk patients with type 2 diabetes mellitus. Our findings of a particularly effective reduction in CV events with GLP-1 RA in Asian populations merits further exploration and dedicated trials in specific populations.
Asian Continental Ancestry Group ; Cardiovascular Diseases ; Diabetes Mellitus, Type 2 ; Glucagon-Like Peptide 1 ; Humans ; Incretins ; Myocardial Infarction ; Stroke

With the development of information technology,the concept of smart healthcare has gradually come to the fore.Smart healthcare uses a new generation of information technologies,such as the internet of things (IoT),big data,cloud computing,and artificial intelligence,to transform the traditional medical system in an all-round way,making healthcare more efficient,more convenient,and more personalized.With the aim of introducing the concept of smart healthcare,in this review,we first list the key technologies that support smart healthcare and introduce the current status of smart healthcare in several important fields.Then we expound the existing problems with smart healthcare and try to propose solutions to them.Finally,we look ahead and evaluate the future prospects of smart healthcare.

Traumatic brain injury (TBI) remains a major cause of death and disability worldwide. Increasing evidence indicates that TBI is an important risk factor for neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and chronic traumatic encephalopathy. Despite improved supportive and rehabilitative care of TBI patients, unfortunately, all late phase clinical trials in TBI have yet to yield a safe and effective neuroprotective treatment. The disappointing clinical trials may be attributed to variability in treatment approaches and heterogeneity of the population of TBI patients as well as a race against time to prevent or reduce inexorable cell death. TBI is not just an acute event but a chronic disease. Among many mechanisms involved in secondary injury after TBI, emerging preclinical studies indicate that posttraumatic prolonged and progressive neuroinflammation is associated with neurodegeneration which may be treatable long after the initiating brain injury. This review provides an overview of recent understanding of neuroinflammation in TBI and preclinical cell-based therapies that target neuroinflammation and promote functional recovery after TBI.
Age Factors ; Animals ; Brain ; immunology ; Brain Injuries, Traumatic ; complications ; therapy ; Cell- and Tissue-Based Therapy ; methods ; Exosomes ; Extracellular Vesicles ; physiology ; Female ; Humans ; Inflammation ; etiology ; Lymphatic System ; physiology ; Male ; Neuroprotective Agents ; Sex Characteristics

Objective: To verify the safety and efficacy of IONTRIS particle therapy system (IONTRIS) in clinical implementation. Methods: Between 6.2014 and 8.2014, a total of 35 patients were enrolled into this trial: 31 males and 4 females with a median age of 69 yrs (range 39-80). Ten patients had locally recurrent head and neck tumors after surgery, 4 cases with thoracic malignancies, 1 case with hepatocellular carcinoma, 1 case with retroperitoneal sarcoma, and 19 cases with non-metastatic prostate carcinomas. Phantom dose verification was mandatory for each field before the start of radiation. Results: Twenty-two patients received carbon ion and 13 had proton irradiation. With a median follow-up time of 1 year, all patients were alive. Among the 16 patients with head and neck, thoracic, and abdominal/pelvic tumors, 2, 1, 12, and 1 cases developed complete response, partial response, stable disease, or disease progression, respectively. Progression-free survival rate was 93.8% (15/16). Among the 19 patients with prostate cancer, biological-recurrence free survival was 100%. Particle therapy was well tolerated in all 35 patients. Twenty-five patients (71.4%) experienced 33 grade 1 acute adverse effects, which subsided at 1 year follow-up. Six (17.1%) patients developed grade 1 late adverse effects. No significant change in ECOG or body weight was observed. Conclusions IONTRIS is safe and effective for clinical use. However, long term follow-up is needed to observe the late toxicity and long term result.

Objective: To investigate in vitro antioxidant and anti-inflammatory activities of Korean blueberry (Vaccinium corymbosum L.).
Methods:Total phenolic and flavonoid contents of the Korean blueberry water and ethanol extracts were determined before determining the potential of the extracts as antioxidant. Antioxidant activity of the extracts was determined by following some well established methods for free radical scavenging such as 2,2-diphenyl-picrylhydrazyl hydrate, 1,2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonicacid), free radical induced DNA damage, superoxide dismutase-like and catalase assay etc. Furthermore, 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan and nitric oxide assay were performed to determine the anti-inflammatory activity of the extracts.
Results:Total phenolic contents were found (115.0±3.0) and (4.2±3.0) mg GAE/100 g fresh mass for both extracts, respectively and flavonoid contents were (1942.8±7.0) and (1292.1±6.0) mg CE/100g fresh mass for water and ethonal extracts, respectively. Both the extracts displayed significant scavenging activity of some radicals such as 2,2-diphenyl-picrylhydrazyl hydrate (IC50 at 1.8 mg/mL and 2.05 mg/mL, respectively), 1,2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonicacid) (IC50 at 1.5 mg/mL and 1.6 mg/mL, respectively) and nitrite (IC50 at 1.7 mg/mL and 1.5 mg/mL, respectively)etc. The extracts were found to prevent inflammation as well by reducing nitric oxide production and cytotoxicity in cell.
Conclusions:The findings suggest that the fresh Korean blueberry could be used as a source of natural antioxidants and anti-inflammatory agents.

OBJECTIVETo calculate the actual expenditures in a county of Dehong prefecture, Yunnan province, China by using the method of National AIDS Spending Assessment (NASA) in 2010.

METHODSData were collected through NASA data collection form based on adapted NASA classification in the county of Dehong prefecture from October to December, 2011, and complemented by semi-structured interview with 16 well trained programmatic and financial representatives in 8 spending units. Data were entered in Resource Tracking Software (RTS) V 2009.3.0, and SPSS 13.0 was used for data processing and analysis.

RESULTSThe NASA estimations showed that the county spent a total of ¥16 235 954 on HIV/AIDS in 2010. Public funds constituted 96.3% of the total expenditure (¥15 630 937), followed by Global Fund which accounted for 3.0% (¥484 585) and private sources which accounted for 0.7% (¥120 432). Findings based on NASA categories showed that AIDS spendings were mainly on 4 areas, and expenditure on Care & Treatment was ¥12 401 382 (76.4% of total expenditure), followed by Prevention which accounted for 14.3% (¥2 325 707), Program Management & Administration which accounted for 7.8% (¥1 268 523) and human resources which accounted for 1.5% (¥240 342). The most beneficial population group was People Living with HIV (PLHIV), accounting for 84.7% of total expenditure. (¥13 753 428), followed by 4.8% for high risk population, including female sex workers and their partners (¥297 333), injection drug users and their partners (¥293 143), men having sex with men and their partners (¥185 136) and 1.5% (¥241 429) for the general population.

CONCLUSIONThe local funds for HIV/AIDS in this county was insufficient. The local government should increase corresponding funds based on central government funding. Care and treatment was the first spending priority in the county and the investment of prevention services needs to be increased. Prevention and treatment and care should be combined to ensure the effectiveness of comprehensive prevention and treatment of AIDS.

Acquired Immunodeficiency Syndrome ; economics ; prevention & control ; China ; Financing, Government ; economics ; Health Expenditures ; Humans ; Outcome and Process Assessment (Health Care) ; Surveys and Questionnaires

BACKGROUNDPreconditioning with remifentanil confers cardioprotection. Since Ca(2+) overload is a precipitating factor of injury, we determined the effects of remefentanil on intracellular Ca(2+) ([Ca(2+)](i)) and its transients induced by electrical stimulation and caffeine, which reflects Ca(2+) handling by Ca(2+) handling proteins, in rat ventricular myocytes.

METHODSFreshly isolated adult male Sprague-Dawley rat myocytes were loaded with Fura-2/AM and [Ca](i) was determined by spectrofluorometry. Remifentanil at 0.1 - 1000 microg/L was administered. Ten minutes after administration, either 0.2 Hz electrical stimulation was applied or 10 mmol/L caffeine was added. The [Ca(2+)](i), and the amplitude, time resting and 50% decay (t(50)) of both transients induced by electrical stimulation (E [Ca(2+)](i)) and caffeine (C [Ca(2+)](i)) were determined.

RESULTSRemifentanil (0.1 - 1000.0 microg/L) decreased the [Ca(2+)](i) in a dose-dependent manner. It also decreased the amplitude of both transients dose-dependently. Furthermore, it increased the time to peak and t(50) of both transients dose-dependently.

CONCLUSIONRemifentanil reduced the [Ca(2+)](i) and suppressed the transients induced by electrical stimulation and caffeine in rat ventricular myocytes.

Animals ; Caffeine ; pharmacology ; Calcium ; metabolism ; Calcium Signaling ; drug effects ; Cells, Cultured ; Electric Stimulation ; Male ; Myocytes, Cardiac ; drug effects ; metabolism ; Piperidines ; pharmacology ; Rats ; Rats, Sprague-Dawley

BACKGROUNDBifurcation angles may have an impact on the clinical outcomes of crush stenting. We sought to compare high (> or = 60 degrees ) with low (< 60 degrees ) bifurcation angle in patients who underwent either classical or double kissing (DK) crush stenting for bifurcation lesions from the DKCRUSH-1 data base.

METHODSThere were 212 patients with 220 lesions, some with low-angle (n = 138) and some with high-angle (n = 74). Angiography was indexed at 8-month after procedure. Primary endpoint was the occurrence of major adverse cardiac events (MACEs), defined as cardiac death, myocardial infarction and target lesion revascularization (TLR). Secondary endpoint included late lumen loss, the rate of restenosis, and final kissing balloon inflation (FKBI).

RESULTSAt 8 months, clinical follow-up was 100%; angiographic follow-up was 75% in the low-angle group and 83.3% in the high-angle group. There were no significant differences in the FKBI between the high-angle group (91.43%) and the low-angle group (82.39%). In the high angle group, there was a significant difference in contrast volume used (P = 0.005) but no significant difference in acute gain, minimum lumen diameter (MLD), late loss and diameter stenosis in the pre-bifurcation segment, post-bifurcation segment or side branch. When lesions were assigned into with-(n = 133) and without-FKBI (n = 42), significant side-branch late loss was seen in the group without-FKBI ((0.65 +/- 0.49) mm vs (0.47 +/- 0.62) mm, P = 0.02), with a resultant greater restenosis rate (37.68% vs 18.32%, P = 0.001). No difference was detected in the MACE free survival rate between the high and low angle groups (82.39% vs 82.36%, P = 0.84). The rate of stent thrombosis tended to be higher in the lower-angle group although there was no significant difference (P = 0.38). The TLR free survival rate was 87.2% in the with-FKBI group vs 73.5% in the without-FKBI group (P = 0.001). Cox regression analysis showed that the independent predictors for target vessel revascularization were the side branch stent MLD post stenting (hazard ratios (HR) 1.028, 95% CI 2.357 - 16.233, P = 0.002), lack of FKBI (HR 4.910, 95% CI 4.706 - 8.459, P = 0.001) and unsatisfactory kissing (HR 3.120, 95% CI 2.975 - 5.431, P = 0.001).

CONCLUSIONSBifurcation angles do not influence the clinical outcome of crush stenting. Successful final kissing balloon inflation, regardless of bifurcation angles, can predict TLR.

Aged ; Angioplasty, Balloon, Coronary ; methods ; Asian Continental Ancestry Group ; ethnology ; Coronary Angiography ; methods ; Coronary Stenosis ; ethnology ; pathology ; therapy ; Drug-Eluting Stents ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; ethnology ; pathology ; therapy ; Stents ; Treatment Outcome

Objective To determine independent factors correlated with clinical effects of DK crush and classical crush technique with drug-eluting stents on bifurcation lesions.Methods 311 patients with bifurcation lesions were randomized to classical(C,n=156)or double kissing(DK)crush(n=155)stent implantation group.The primary endpoints included major adverse cardiac events(MACE).Results Final kissing balloon inflation(FKBI)success rate was 76%in C and 100%in DK groups(P＜0.001).Dkcrush procedure was characterized by lower unsatisfactory FKBI rate(27.6%VS.6.3%,P＜0.01).Clinical follow-up was available in 100%and angiographic follow-up in 82%patients.The overall restenosi srate was 32.3%in C and 20.3%in DK groups(P=0.01).respectively.Cumulative 8-month MACE was 35.9%in without-FKBI and 19.7%in with-FKBI sub-groups,and 11.4%in DK group(P=0.02).The incidence of stent thrombosis was 3.2%in C group (5.1%without VS.1.7%with FKBI)and 1.3%in Dkgroup(P＞0.05).The predictive factors of MACE included minimal side branch stent lumen diameter and lack of DK crush technique.Conclusion DK crush technique is an alternative of double stenting techniquesin terms of improvement of restenosis and clinical outcomes.