The present and future of quantum toxicology in China

This review introduced the concept of quantum toxicology,presented the adverse effects of light quantum on human being and recent developments in the study of quantum toxicology in China was also reported In the 70 s of last century,we began to apply quantum chemical calculation methods to study the mechanism of carcinogenesis,the anti-tumor mechanism of drugs and the structure-activity relationship of antitumor activity.In the future,we will use quantum mechanics,quantum biology,and quantum biochemistry to study the toxicity and mechanism of chemical compounds(include drugs).Quantum toxicology research is very important in environmental medicine and toxicology and should be paid attention.

Assessment of Acute Poisoning Cases in Emergency Department of the Provincial General Reference Hospital in Bukavu, DR-Congo

Background: Acute intoxications result from intentionally or accidentally taking a relatively significant amount of a chemical substance which triggers disturbances in the level of psychophysiological functions, the complications of which may lead to mental disorders, physical causalities, and death. Any acute intoxication mostly requires emergency care. Objective: To highlight the prevalence, history, clinical features, emergency treatment, and prediction of acute intoxication cases referred to the emergency services at the Provincial General Reference Hospital in Bukavu, DR-Congo. Methods: A retrospective cross-sectional study was conducted from January 2021 to October 2022 based on an analysis of patients’ medical files. Triage was performed among all-type of patient files recorded in the computerized hospital database Ebale-Sante to sort cases of intoxication. Results: During the observational period, 3966 emergency admissions were counted, of which 321 (8.09%) patients were identified as having acute intoxication. Among these, 100 files that containing sufficient information fit the quality criteria for this study’s analysis. The victims were infants, adolescents and adults aged 1 - 45 years, and 52% were female and 48% were male. Most cases were accidental and, occurred at home, and the victims were driven to the hospital within 2 - 24 hours. The substances consumed included household products, drugs, and herbs. Resuscitation care, antidotes and supportive symptomatic medications ensured that 85% were healed and 10% experienced sequelae;however, 5% died. Conclusion: Acute intoxication occurs in infants mostly accidentally though the ingestion of household products and medicines. Furthermore, suicide cases may occur in traumatized adolescents and discordant couples. People should be informed about how to store hazardous products (e.g.: drugs, household products and pesticides), which should not be available to children, to avoid unintentional poisoning. Special training in clinical toxicology is required to reduce treatment failure.

Identification of Key Blood Biomarkers Linking Di(2-ethylhexyl)Phthalate and Autoimmune Diseases in Adolescents Mice

Di(2-ethylhexyl)phthalate(DEHP)is a widely used plasticizer known for its reproductive developmental and immune system toxicity,mainly through esophagal,dermal,and respiratory exposure^([1-3]).Maternal exposure to DEHP during pregnancy can lead to adverse birth outcomes in offspring,including impacts on the thyroid system of adolescent offspring^([2-4]).

The Uptake and Distribution Evidence of Nano-and Microplastics in vivo after a Single High Dose of Oral Exposure

Objective Tissue uptake and distribution of nano-/microplastics was studied at a single high dose by gavage in vivo.Methods Fluorescent microspheres(100 nm,3μm,and 10μm)were given once at a dose of 200 mg/(kg∙body weight).The fluorescence intensity(FI)in observed organs was measured using the IVIS Spectrum at 0.5,1,2,and 4 h after administration.Histopathology was performed to corroborate these findings.Results In the 100 nm group,the FI of the stomach and small intestine were highest at 0.5 h,and the FI of the large intestine,excrement,lung,kidney,liver,and skeletal muscles were highest at 4 h compared with the control group(P<0.05).In the 3μm group,the FI only increased in the lung at 2 h(P<0.05).In the 10μm group,the FI increased in the large intestine and excrement at 2 h,and in the kidney at 4 h(P<0.05).The presence of nano-/microplastics in tissues was further verified by histopathology.The peak time of nanoplastic absorption in blood was confirmed.Conclusion Nanoplastics translocated rapidly to observed organs/tissues through blood circulation;however,only small amounts of MPs could penetrate the organs.

Immunoregulatory Effects of Ethyl-acetate Fraction of Extracts from Tetrastigma Hemsleyanum Diels et. Gilg on Immune Functions of ICR Mice

Objective To evaluate the effects of ethyl-acetate fraction （EAF） of extracts from Tetrastigma hemsleyanum Diels et. Gilg （TDG） on immune functions of ICR mice. Methods ICR mice were exposed to different doses of EAF for 15 or 30 days and then their immune functions were analyzed, including ConA-induced splenic lymphocyte transformation, SRBC- induced delayed type hypersensitivity response, serum hemolysin analysis, antibody-producing cells, peritoneal macrophage phagocytized chicken red blood cells, natural killer cell activity, and serum level of cytoldnes. Results EAF of extracts from TDG at different doses had various effects on immune functions of ICR mice. As compared with the controls, it increased the mouse spleen lymphocyte transformation induced by ConA, the left-hind voix pedis thickness and the number of plague forming cells （PFCs） at the dose of 1.82 mg/mL, 5.48 mg/mL, and 9.12 mg/mL, respectively; increased the ink clearance ability at the dose of 0.91 mg/mL, 1.82 mg/mL, 5.48 mg/mL, and 9.12 mg/mL, respectively; increased the phagocytosis index of mononuclear-macrophages and production of serum interferon-gamma （IFN-？） at the dose of 5.48 mg/mL; and could promote the production of serum tumor necrosis factor-alpha （TNF-α） at the dose of 9.12 mg/mL. Conclusion EAF of extracts from TDG can regulate mouse immune functions in vivo.

Effectiveness of probiotics in irritable bowel syndrome:Updated systematic review with meta-analysis

AIM:To investigate the efficacy of probiotics in irritable bowel syndrome(IBS) patients.METHODS:Pub Med,Cochrane library,Scopus,Google Scholar,and Clinicaltrial.gov databases were searched for literature published between September 2007 and December 2013.The applied Mesh terms were "probiotics," "irritable bowel syndrome," and "irritable bowel syndrome treatment." The collected data contained24 clinical trials,of which 15 were eligible for meta-analysis and nine were reviewed systematically.All studies were randomized placebo-controlled trials in patients with IBS that investigated the efficacy of probiotics in IBS improvement.The Jadad score was used to assess the methodological quality of trials.The quality scale ranges from 0 to 5 points,with a score ≤ 2 indicating a low quality report,and a score of ≥3 indicating a high quality report.Relative risk(RR),standardized effect size,and 95%CI were calculated using the Der Simonian-Laird method.The Cochran Q test was used to test heterogeneity with P < 0.05.Funnel plots were constructed and Egger's and BeggMazumdar tests were performed to assess publication bias.RESULTS:A total of 1793 patients were included in the meta-analysis.The RR of responders to therapies based on abdominal pain score in IBS patients for two included trials comparing probiotics to placebo was 1.96(95%CI:1.14-3.36;P = 0.01).RR of responders to therapies based on a global symptom score in IBS patients for two included trials comparing probiotics with placebo was 2.43(95%CI:1.13-5.21;P = 0.02).For adequate improvement of general symptoms in IBS patients,the RR of seven included trials(six studies) comparing probiotics with placebo was 2.14(95%CI:1.08-4.26;P = 0.03).Distension,bloating,and flatulence were evaluated using an IBS severity scoring system in three trials(two studies) to compare the effect of probiotic therapy in IBS patients with placebo,the standardized effect size of mean differences for probiotics therapy was-2.57(95%CI:-13.05--7.92).CONCLUSION:Probiotics reduce pain and symptom severity scores.The results demonstrate the beneficial effects of probiotics in IBS patients in comparison with placebo.

Potential of the ellagic acid-derived gut microbiota metabolite–Urolithin A in gastrointestinal protection

Urolithin A(UA)is a metabolic compound generated during the biotransformation of ellagitannins by the intestinal bacteria.The physiologically relevant micromolar concentrations of UA,achieved in the plasma and gastrointestinal tract(GI)after consumption of its dietary precursors,have been revealed to offer GI protection.The health benefit has been demonstrated to be principally related to anticancer and anti-inflammatory effects.UA has been shown to possess the capability to regulate multiple tumor and inflammatory signaling pathways and to modulate enzyme activity,including those involved in carcinogen biotransformation and antioxidant defense.The purpose of this review is to gather evidence from both in vitro and in vivo studies showing the potential of UA in GI protection alongside suggested mechanisms by which UA can protect against cancer and inflammatory diseases of the digestive tract.The data presented herein,covering both studies on the pure compound and in vivo generated UA form its natural precursor,support the potential of this metabolite in treatment interventions against GI ailments.

Changes of CREB in rat hippocampus, prefrontal cortex and nucleus accumbens during three phases of morphine induced conditioned place preference in rats

Objective: To investigate the changes in CREB (cAMP response element binding protein) in hippocampus, PFC (prefrontal cortex) and NAc (nucleus accumbens) during three phases of morphine induced CPP (conditioned place preference) in rats, and to elucidate the role of CREB during the progress of conditioned place preference. Methods: Morphine induced CPP acquisition, extinction and drug primed reinstatement model was established, and CREB expression in each brain area was measured by Western Blot methods. Results: Eight alternating injections of morphine (10 mg/kg) induced CPP, and 8 d saline extinction training that extinguished CPP. CPP was reinstated following a priming injection of morphine (2.5 mg/kg). During the phases of CPP acquisition and reinstatement, the level of CREB expression was significantly changed in different brain areas. Conclusion: It was proved that CPP model can be used as an effective tool to investigate the mechanisms underlying drug-induced reinstatement of drug seeking after extinction, and that morphine induced CPP and drug primed reinstatement may involve acti-vation of the transcription factor CREB in several brain areas, suggesting that the CREB and its target gene regulation pathway may mediate the basic mechanism underlying opioid dependence and its drug seeking behavior.

Combined Effect of Fluoride and Arsenate on Gene Expression of Osteoclast Differentiation Factor and Osteoprotegerin

Objective To study the combined effect of fluoride and arsenate on the expression of SD rat osteoblastic osteoclast differentiation factor （ODF） mRNA and osteoprotegerin （OPG） mRNA. Methods Osteoblasts were obtained by enzymatic isolation from newborn SD rats. A factorial experiment was performed. Osteoblasts were exposed to NaF （0.5 mmolF/L, 4 molF/L） and Na3AsH2 （12.5 μmolAs/L and 200 μmolAs/L） separately or F plus As and cultured for 48 h. The gene expression of osteoblastic ODF and OPG was observed by RT-PCR. Results The expression ofODF mRNA increased in F0.5, F4 groups compared with control group and two groups of F0.As200, F,As200 compared with As200 group, and decreased significantly in groups of F4As12.5, F0.5As200, and F4As200. The expression of OPG rnRNA decreased in groups of F4, As200, F4As12.5, F0.5As200, and F4As200. Conclusion The joint effect of fluoride and arsenate on the gene expression of ODF is antagonistic, while the combined effect on the gene expression of OPG is synergistic. F4, F4As12.5, and F0.5As200 promote bone resorption of rat osteoclasts, whereas F0.5As12.5 inhibits osteolytic effect of rat osteoclasts.

The Cellular Toxicity of PM_(2.5) Emitted from Coal Combustion in Human Umbilical Vein Endothelial Cells

Objective To explore the relationship between different components of fine particulate matter（PM2.5） emitted from coal combustion and their cytotoxic effect in the vascular endothelial cells. Methods Coal-fired PM2.5 was sampled using a fixed-source dilution channel and flow sampler. The sample components were analyzed by ion chromatography and inductively coupled plasma atomic emission spectroscopy（ICP-AES）. The PM2.5 suspension was extracted using an ultrasonic water-bath method and then human umbilical vein endothelial cells（EA.hy926） were treated with various concentrations of the PM2.5 suspension. Cell proliferation, oxidative DNA damage, and global DNA methylation levels were used to measure the cellular toxicity of PM2.5 emitted from coal combustion. Results Compared to other types of coal-fired PM2.5 preparations, the PM2.5 suspension from Yinchuan coal had the highest cytotoxicity. PM2.5 suspension from Datong coal had the highest toxic effect while that from Yinchuan coal had the lowest. Exposure to coal-fired PM2.5 from Jingxi coal resulted in lower 8-hydroxy-2’-deoxyguanosine（8-OHd G） levels. At the same dose, PM2.5 emitted from coal combustion could produce more severe DNA impairment compared to that produced by carbon black. Cell survival rate was negatively correlated with chloride and potassium ions content. The 5-methylcytosine（5-m C） level was positively correlated with Mn and negatively correlated with Zn levels. The 8-OHd G% level was positively correlated with both Mn and Fe. Conclusion PM2.5 emitted from coal combustion can decrease cell viability, increase global DNA methylation, and cause oxidative DNA damage in EA.hy926 cells. Metal components may be important factors that influence cellular toxicity.

Interventions of natural and synthetic agents in inflammatory bowel disease, modulation of nitric oxide pathways

Inflammatory bowel disease(IBD)refers to a group of disorders characterized by chronic inflammation of the gastrointestinal(GI)tract.The elevated levels of nitric oxide(NO)in serum and affected tissues;mainly synthesized by the inducible nitric oxide synthase(iNOS)enzyme;can exacerbate GI inflammation and is one of the major biomarkers of GI inflammation.Various natural and synthetic agents are able to ameliorate GI inflammation and decrease iNOS expression to the extent comparable with some IBD drugs.Thereby,the purpose of this study was to gather a list of natural or synthetic mediators capable of modulating IBD through the NO pathway.Electronic databases including Google Scholar and PubMed were searched from 1980 to May 2018.We found that polyphenols and particularly flavonoids are able to markedly attenuate NO production and iNOS expression through the nuclear factorκB(NF-κB)and JAK/STAT signaling pathways.Prebiotics and probiotics can also alter the GI microbiota and reduce NO expression in IBD models through a broad array of mechanisms.A number of synthetic molecules have been found to suppress NO expression either dependent on the NF-κB signaling pathway(i.e.,dexamethasone,pioglitazone,tropisetron)or independent from this pathway(i.e.,nicotine,prednisolone,celecoxib,β-adrenoceptor antagonists).Co-administration of natural and synthetic agents can affect the tissue level of NO and may improve IBD symptoms mainly by modulating the Toll like receptor-4 and NF-κB signaling pathways.

Effects of extracellular vesicles from mesenchymal stem cells on oxygen-glucose deprivation/reperfusioninduced neuronal injury

BACKGROUND: Small extracellular vesicles (sEVs) from bone marrow mesenchymal stemcells (BMSCs) have shown therapeutic potential for cerebral ischemic diseases. However, themechanisms by which BMSC-derived sEVs (BMSC-sEVs) protect neurons against cerebral ischemia/reperfusion (I/R) injury remain unclear. In this study, we explored the neuroprotective effects ofBMSC-sEVs in the primary culture of rat cortical neurons exposed to oxygen-glucose deprivation andreperfusion (OGD/R) injury.METHODS: The primary cortical neuron OGD/R model was established to simulate the processof cerebral I/R in vitro. Based on this model, we examined whether the mechanism through whichBMSC-sEVs could rescue OGD/R-induced neuronal injury.RESULTS: BMSC-sEVs (20 μg/mL, 40 μg/mL) significantly decreased the reactive oxygenspecies (ROS) productions, and increased the activities of superoxide dismutase (SOD) and glutathioneperoxidase (GPx). Additionally, BMSC-sEVs prevented OGD/R-induced neuronal apoptosis in vivo, asindicated by increased cell viability, reduced lactate dehydrogenase (LDH) leakage, decreased terminaldeoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining-positivecells, down-regulated cleaved caspase-3, and up-regulated Bcl-2/Bax ratio. Furthermore, Westernblot and flow cytometry analysis indicated that BMSC-sEV treatment decreased the expression ofphosphorylated calcium/calmodulin-dependent kinase II (p-CaMK II)/CaMK II, suppressed the increaseof intracellular calcium concentration ([Ca2+]i) caused by OGD/R in neurons.CONCLUSIONS: These results demonstrate that BMSC-sEVs have signifi cant neuroprotectiveeff ects against OGD/R-induced cell injury by suppressing oxidative stress and apoptosis, and Ca2+/CaMK II signaling pathways may be involved in this process.

Beneficial effect of butyrate, Lactobacillus casei and L-carnitine combination in preference to each in experimental colitis

AIM: To investigate the beneficial effect of the combination of butyrate, Lactobacillus casei, and L-carnitine in a rat colitis model.

Evaluation of gastric lavage efficiency and utility using a rapid quantitative method in a swine paraquat poisoning model

BACKGROUND:Gastric lavage(GL)is one of the most critical early therapies for acute paraquat(PQ)poisoning;however,details of the treatment protocol remain to be established.METHODS:A rapid quantitative method involving sodium dithionite testing was developed.It was validated for the determination of the PQ concentrations in gastric juice and eluate samples from a swine acute PQ poisoning model with early or delay GL,or without.The vital signs,laboratory testing,and PQ plasma concentrations were collected for therapeutic effect evaluation.RESULTS:The reaction conditions of the test were optimized for two types of samples.Early GL at one hour(H1)could improve the signs and symptoms after acute PQ poisoning at 24 hours(H24).In contrast,GL at 6 hours(H6)could only partially relieve the vital signs.The H1 GL group effectively reduced the peak of the plasma PQ concentration.In addition,the PQ concentrations in the plasma and the gastric juice were significantly decreased in both the GL groups as compared to the untreated group at H24.Moreover,there was no significant difference in the washing efficiencies calculated from the total eluates between the two GL groups.However,the washing efficiency of the first 10 L eluate is superior to that of the additional 10 L eluate.CONCLUSION:GL only at early stage may it benefit PQ poisoning in an animal model.The currently used 20 L GL volume may need to be reduced in view of the low washing efficiency in the later 10 L eluate.The rapid quantitative method can be used for gastric juice sample and has a certain value for clinical GL practices.

Induction of clinical response and remission of inflammatory bowel disease by use of herbal medicines:A meta-analysis

AIM:To evaluate the efficacy and tolerability of herbal medicines in inflammatory bowel disease(IBD)by conducting a meta-analysis.METHODS:Electronic databases were searched for studies investigating efficacy and/or tolerability of herbal medicines in the management of different types of IBD.The search terms were:"herb"or"plant"or"herbal"and"inflammatory bowel disease".Data were collected from 1966 to 2013(up to Feb).The"clinical response","clinical remission","endoscopic response","endoscopic remission","histological response","histological remission","relapse","any adverse events",and"seriousadverse events"were the key outcomes of interest.We used the Mantel-Haenszel,Rothman-Boice method for fixed effects and DerSimonian-Laird method for random-effects.For subgroup analyses,we separated the studies by type of IBD and type of herbal medicine to determine confounding factors and reliability.RESULTS:Seven placebo controlled clinical trials met our criteria and were included(474 patients).Comparison of herbal medicine with placebo yielded a significant RR of 2.07(95%CI:1.41-3.03,P=0.0002)for clinical remission;a significant RR of 2.59(95%CI:1.24-5.42,P=0.01)for clinical response;a non-significant RR of 1.33(95%CI:0.93-1.9,P=0.12)for endoscopic remission;a non-significant RR of 1.69(95%CI:0.69-5.04)for endoscopic response;a non-significant RR of 0.64(95%CI:0.25-1.81)for histological remission;a non-significant RR of 0.86(95%CI:0.55-1.55)for histological response;a non-significant RR of 0.95(95%CI:0.52-1.73)for relapse;a non-significant RR of 0.89(95%CI:0.75-1.06,P=0.2)for any adverse events;and a non-significant RR of 0.97(95%CI:0.37-2.56,P=0.96)for serious adverse events.CONCLUSION:The results showed that herbal medicines may safely induce clinical response and remission in patients with IBD without significant effects on endoscopic and histological outcomes,but the number of studies is limited to make a strong conclusion.

Protective effects of 2,4-dihydroxybenzophenone against acetaminophen-induced hepatotoxicity in mice

AIM:To examine the effects of 2,4-dihydroxybenzophenone(BP-1),a benzophenone derivative used as an ultraviolet light absorbent,on acetaminophen(APAP)induced hepatotoxicity in C57BL/6J mice.METHODS:Mice were administered orally with BP-1 at doses of 200,400 and 800 mg/kg body weight respectively every morning for 4 d before a hepatotoxic dose of APAP(350 mg/kg body weight) was given subcutaneously.Twenty four hours after APAP intoxication,the serum enzyme including serum alaine aminotransferase(ALT),aspartate aminotransferase(AST),lactate dehydrogenase(LDH) were measured and liver histopathologic changes were examined.RESULTS:BP-1 administration dramatically reduced serum ALT,AST and LDH levels.Liver histopathological examination showed that BP-1 administration antagonized APAP-induced liver pathological damage in a dose-dependent manner.Further tests showed that APAP-induced hepatic lipid peroxidation was reduced significantly by BP-1 pretreatment,and glutathione depletion was ameliorated obviously.CONCLUSION:BP-1 can effectively protect C57BL/6J mice from APAP-induced hepatotoxicity,and reduction of oxidative stress might be part of the protection mechanism.

Apoptosis of human colon carcinoma HT-29 cells induced by ceramide

AIM： To investigate the effect of exogenous ceramideinduced apoptosis on human colon carcinoma HT-29 cells. METHODS： Light microscope, transmission electron microscope and fluorescence microscope were used to observe the morphology change of apoptosis in HT-29 cells. Agarose gel electrophoresis was performed to detect the DNA fragment. Mitochondrial function was detected by MTT assay, mRNA expression of Bcl-2 family gene members was determined by reverse transcription polymerase chain reaction （RT-PCR） assay. RESULTS： After C2-ceramide treatment, typical characteristics of apoptosis, such as nuclear chromatin breakage, apoptotic body and DNA ladder, could be observed. After exposure to 50μmol/L C2-ceramide for 12 and 24 h, cell apoptosis was 64.1% and 81.3% respectively, which had a time-and dose-effect relationship. Mitochondrial function started to decrease from 6 h after exposure to ceramide. Meanwhile, ceramide up-regulated or down-regulated the mRNA expression of Bcl-2 family gene members. CONCLUSION： Ceramide induces apoptosis of human colon carcinoma HT-29 cells by affecting the expression of Bcl-2 family gene members and impacting the mitochondrial function.

Nafamostat mesylate attenuates the pathophysiologic sequelae of neurovascular ischemia

Nafamostat mesylate,an apparent soi-disant panacea of sorts,is widely used to anticoagulate patients undergoing hemodialysis or cardiopulmonary bypass,mitigate the inflammatory response in patients diagnosed with acute pancreatitis,and reverse the coagulopathy of patients experiencing the commonly preterminal disseminated intravascular coagulation in the Far East.The serine protease inhibitor nafamostat mesylate exhibits significant neuroprotective effects in the setting of neurovascular ischemia.Nafamostat mesylate generates neuroprotective effects by attenuating the enzymatic activity of serine proteases,neuroinflammatory signaling cascades,and the endoplasmic reticulum stress responses,downregulating excitotoxic transient receptor membrane channel subfamily 7 cationic currents,modulating the activity of intracellular signal transduction pathways,and supporting neuronal survival brain-derived neurotrophic factor/TrkB/ERK1/2/CREB,nuclear factor kappa B.The effects collectively reduce neuronal necrosis and apoptosis and prevent ischemia mediated disruption of blood-brain barrier microarchitecture.Investigational clinical applications of these compounds may mitigate ischemic reperfusion injury in patients undergoing cardiac,hepatic,renal,or intestinal transplant,preventing allograft rejection,and treating solid organ malignancies.Neuroprotective effects mediated by nafamostat mesylate support the wise conduct of randomized prospective controlled trials in Western countries to evaluate the clinical utility of this compound.

Association between polymorphisms of the APOBEC3G gene and chronic hepatitis B viral infection and hepatitis B virusrelated hepatocellular carcinoma

AIM to determine the relationship between five A3 G gene single nucleotide polymorphisms and the incidence of hepatitis B virus(HBV) infection and hepatocellular carcinoma(HCC). METHODS this association study was designed as a retrospective study, including 657 patients with chronic HBV infection(CHB) and 299 healthy controls. All subjects were ethnic Han Chinese. Chronic HBV-infected patients recruited between 2012 and 2015 at the First Hospital of Jilin University(Changchun) were further classified into HBV-related HCC patients(n = 287) and non-HCC patients(n = 370). Frequency matching by age and sex was performed for each group. Human genomic DNAwas extracted from whole blood. Gene polymorphisms were identified using a mass spectroscopic method.RESULTS there were no significant differences between the genotype and allele frequencies of the rs7291971, rs5757465 and rs5757463 A3 G gene polymorphisms, and risk of CHB and HBV-related HCC. the AG genotype and G allele for rs8177832 were significantly related to a decreased risk of CHB(OR = 0.67, 95%CI: 0.47-0.96; OR = 0.69, 95%CI: 0.50-0.95, respectively) and HCC(OR = 0.53, 95%CI: 0.34-0.84; OR = 0.58, 95%CI: 0.39-0.87, respectively). A significant relationship was found between rs2011861 computed tomography, tt genotypes and increased risk of HCC(OR = 1.69, 95%CI: 1.02-2.80; OR = 1.82, 95%CI: 1.08-3.06, respectively). Haplotype analyses showed three protective and four risk haplotypes for HCC. Also, one protective haplotype was found against CHB.CONCLUSION this study indicates that the A3 G rs8177832 polymorphism is associated with a decreased risk of CHB infection and HCC, while the rs2011861 polymorphism is associated with an increased risk of HCC.

Effect of glycine site/NMDA receptor antagonist MRZ2/576 on the conditioned place preference and locomotor activity induced by morphine in mice

Objective: To study the effect of glycine site/NMDA (N-methyl-D-aspartate) receptor antagonist MRZ2/576 on the conditioned place preference (CPP) and locomotor activity induced by morphine in mice. Methods: Different doses (1.25, 2.5 and 5 mg/kg, i.p.) of MRZ2/576 were used to evaluate the effect of MRZ2/576 on the acquisition and expression of CPP induced by morphine (5 mg/kg) in mice. In addition, we examined the locomotor activity of mice in conditioning and testing phase of CPP paradigm. Results: MRZ2/576 alone could not establish place preference, but a 5 mg/kg dose of MRZ2/576 could block both acquisition and expression of morphine-induced CPP. In testing phase of CPP, there was no statistical difference for locomotor activity between the groups; injection of MRZ2/576 showed a dose-dependent decrease of locomotor activity on both control and morphine-treated mice, especially 5 mg/kg of MRZ2/576 significantly suppressed the locomotor activity of mice. Conclusion: Based on the present results, we assume that MRZ2/576 can antagonize the rewarding effect of morphine, suggesting that this glycine site/NMDA receptor antagonist could be used to treat addictions due to its light side effect profile.