Objective To study the effect of ketamine on L-type calcium currents (ICa-L) in guinea pig ventricular myocytes. Methods Adult guinea pigs of both sexes were anesthetized with pentobarbital. The hearts were immediately removed and ventricular myocytes were prepared by the technique described by Liu et al. The whole-cell patch clamp technique was used to study the ICa-L in isolated guinea pig ventricular myocytes. The changes in ICa-L produced by ketamine 100 ?mol?L-1 with different holding potentials or by different concentrations of ketamine with holding potential of + 10 mV were analyzed. Results Ketamine dose-dependently inhibited ICa-L evoked by a voltage step from a holding potential of - 40 mV to + 10 mV. The 4 concentrations of ketamine (100, 500, 1 000, 5 000 ?mol?L-1) reduced 1Ca-L by 28.7%?5.7% , 34.7%?1.4%, 58.7%?6.4% and 81.7%?6.7% respectively, with a mean IC50 concentration of 926.6 ?mol?L-1 . When the cells were exposed to ketamine 100 ?mol?L-1, the steady-state activation curve was not significantly affected, while the steady-state inactivation curve was shifted to more negative potentials.V1/2 decreased from ( - 14.8?0.8 ) mV to ( - 19.6?0.7) mV (P0.05) in control and drug-affected cells respectively. Ketamine slowed the rate of recovery from inactivation. Conclusion Ketamine can inhibit ICa-L in guinea pig ventricular myocytes in a concentration-dependent manner. This inhibitory effect of ketamine may explain its negative inotropic effect. Ketamine inhibits L-type calcium channel in its inactivated state.

Objective To determine the effect of cardiomyopeptidin on transient outward potassium current(I_(to) of rat ventricular myocytes and its action mechanism on the ion channels of myocardium.Methods Single ventricular myocytes of rats were obtained by enzymatic dissociation.The whole-cell patch-clamp recording technique was used to record the change of transient outward potassium current(I_(to) by different dosages of cardiomyopeptidin.Results Cardiomyopeptidin decreased I_(to) in a dose-dependent manner.Cardiomyopeptidin in dose of 10,50,100,250 and(500 mg/L) decreased I_(to %) by 4,13,22,32 and 38 respectively.Cardiomyopeptidin 50 mg/L moved the current density-voltage curve of I_(to) down,but the shape of the curve had no changes.Cardiomyopeptidin 50 mg/L did not change the steady state activation curve of I_(to).Conclusions Cardiomyopeptidin decreases the I_(to) of rat ventricular myocytes,which might be one of the mechanisms of its antiarrhythmic effect.

Objective To study the effect of ketamine on inward rectifier potassium currents(I_k1)in isolated rat ventricular myocytes using whole-cell patch clamp technique.Methods Adult Wistar rats of both sexes were anesthetized with pentobarbital.The hearts were removed and ventricular myocytes were prepared by the technique described by Liu et al.Whole-cell patch clamp technique was used to study I_(k1) in isolated rat ventricular myocytes The changes in I_(KI) produced by 100 ?mol?L~(-1) with different holding potentials or by different concentrations of ketamine with holding potential of-120 mV were analyzed.Results Ketamine 100 ?mol?L~(-1) inhibited the Ira without any significant effects on reverse potential (-50--60 mV)and the shape of the Ⅰ-Ⅴ curve.Ketamine inhibited I_(k1) evoked by a holding potential of-120 mV in a dose-dependent manner with a mean IC_(50) value of (162.3?8.4)?mol?L~(-1).Conclusion Ketamine significantly inhibits I_(k1) in ventricular myocytes. This may explain the prolonged duration of action potential of ventricular myocyte produced by ketamine.

Aim To develop a simple,rapid and ac-curate analysis method for determination of chiral ibu-profen in Beagle dog plasma.Method The plasma sample was submitted to liquid - liquid extraction u-sing hexane /isopropanol (95 ∶5,V/V),with ketopro-fen as the internal standard (IS).The separation was accomplished in a Lux 5u Cellulose-3 (250 mm·4.6 mm,5 μm)column,and the mobile phase consisted of methanol and a mixture of 1 mmol·L -1 ammonium acetate-methanol-formic acid (90 ∶1 0 ∶0.2,V/V/V) with the volume ratio of 82 ∶1 8 at a flow rate of 0.8 mL· min -1 .The mass spectrometer consisted of an ESI interface operating at negative ionization mode and the detection was performed using multiple reaction monitoring at the transitions of m /z 205.2 /1 61 .2 for ibuprofen and m /z 253.1 /209.2 for ketoprofen (IS). Method validation included the evaluation of the matrix effect, extraction recovery, linearity, lower LOQ, within-run and between-run precision,stability and di-lution effect.Results The calibration curve was line-ar across the concentration range of 0.2 ~50 mg·L -1 for each ibuprofen enantiomer with a lower LOQ of 0.2 mg·L -1 .The within-run and between-run precision (RSD%)was in the range 1 .01 % ~1 3.1 % for each ibuprofen.The pharmacokinetic parameters for orally single dose of (S +)and racemic ibuprofen in Beagle dogs were as follows: Cmax , T1 /2 , AUC(0-t) were (82.98 ±1 4.83 )mg·L -1 ,(3.21 7 ±0.7298)h, (362.0 ±58.67)h·mg·L -1 for (S +)ibuprofen and 70.62 /74.48 mg·L -1 ,1 .520 /5.432 h ,1 77.8 /649.6 h·mg·L -1 for (R -)/(S +)ibuprofen,re-spectively.Conclusions A simple,rapid,accurate, high sensitivity and repeatability method has been suc-cessfully developed,which can analyze the concentra-tions of (R -)/(S +)ibuprofen in Beagle dog plasma simultaneously.The method could be applied for the investigation of pharmacokinetics of ibuprofen enanti-omers in Beagle dogs.

Objective:To investigate the changes of directional connections of auditory and non-auditory in patients with noise-induced deafness (NID) by degree centrality (DC) and Granger causality analysis (GCA), and to explore the mode of brain function remodeling after NID.Methods:In October 2023, a total of 58 patients diagnosed with NID by the Occupational Diseases Department of Yantaishan Hospital of Yantai from 2014 to 2022 were collected as case group (NID group), and 42 healthy volunteers matched by gender, age and education level were selected as the control group (HC group). Resting state-functional magnetic resonance imaging (Rs-fMRI) was perfomed and PC analysis was performed. The brain regions with statistically significant differences in DC values between groups and the bilateral Heschl regions were extracted as regions of interest (ROI) for voxel-based whole brain GCA and correlation analysis.Results:Compared with HC group, the SOG.L DC value of NID group was lower, the connectivity values of SFGdor.L to SOG.L was increased, the connectivity value of PCL.L to SOG.L was decreased, the connectivity values of ORBmid.L, PCG.R and CUN. L/R to HES.L were increased, the connectivity value of SFGdor.L to HES.L was decreased, the connectivity value of HES.L to PCUN.L was decreased, the connectivity values of ORBsup.L and PCG.R to HES.R were increased, the connectivity value of HES.R to CUN.L was decreased ( P voxel level<0.01, P cluster level<0.05). The connectivity value of PCL.L to SOG.L was negatively correlated with the weighted value of the better whisper frequency ( P<0.05) . Conclusion:The NID patients have abnormal directional connectivity activity in multiple brain regions, such as auditory vision, executive control, somatosensory movement, and default mode network. It is suggested that hearing loss may cause complex neural remodeling between auditory and non-auditory centers.

Objective:To investigate the changes of directional connections of auditory and non-auditory in patients with noise-induced deafness (NID) by degree centrality (DC) and Granger causality analysis (GCA), and to explore the mode of brain function remodeling after NID.Methods:In October 2023, a total of 58 patients diagnosed with NID by the Occupational Diseases Department of Yantaishan Hospital of Yantai from 2014 to 2022 were collected as case group (NID group), and 42 healthy volunteers matched by gender, age and education level were selected as the control group (HC group). Resting state-functional magnetic resonance imaging (Rs-fMRI) was perfomed and PC analysis was performed. The brain regions with statistically significant differences in DC values between groups and the bilateral Heschl regions were extracted as regions of interest (ROI) for voxel-based whole brain GCA and correlation analysis.Results:Compared with HC group, the SOG.L DC value of NID group was lower, the connectivity values of SFGdor.L to SOG.L was increased, the connectivity value of PCL.L to SOG.L was decreased, the connectivity values of ORBmid.L, PCG.R and CUN. L/R to HES.L were increased, the connectivity value of SFGdor.L to HES.L was decreased, the connectivity value of HES.L to PCUN.L was decreased, the connectivity values of ORBsup.L and PCG.R to HES.R were increased, the connectivity value of HES.R to CUN.L was decreased ( P voxel level<0.01, P cluster level<0.05). The connectivity value of PCL.L to SOG.L was negatively correlated with the weighted value of the better whisper frequency ( P<0.05) . Conclusion:The NID patients have abnormal directional connectivity activity in multiple brain regions, such as auditory vision, executive control, somatosensory movement, and default mode network. It is suggested that hearing loss may cause complex neural remodeling between auditory and non-auditory centers.

Objective Knowledge-motivation-psychological model was set up and tested through structural equation model to provide evidence on HIV prevention related strategy in Men who have Sex with Men (MSM).Methods Snowball sampling method was used to recruit a total of 550 MSM volunteers from two MSM Non-Governmental Organizations in Urumqi,Xinjiang province.HIV prevention related information on MSM was collected through a questionnaire survey.A total of 477 volunteers showed with complete information.HIV prevention related Knowledge-motivationpsychological model was built under related experience and literature.Relations between knowledge,motivation and psychological was studied,using a ‘structural equation model’ with data from the fitting questionnaires and modification of the model.Results Structural equation model presented good fitting results.After revising the fitting index:RMSEA was 0.035,NFI was 0.965 and RFI was 0.920.Thereafter the exogenous latent variables would include knowledge,motivation and psychological effects.The endogenous latent variable appeared as prevention related behaviors.The standardized total effects of motivation,knowledge,psychological on prevention behavior were 0.44,0.41 and 0.17 respectively.Correlation coefficient of motivation and psychological effects was 0.16.Correlation coefficient on knowledge and psychological effects was-0.17 (P＜0.05).Correlation coefficient of knowledge and motivation did not show statistical significance.Conclusion Knowledge of HIV and motivation of HIV prevention did not show any accordance in MSM population.It was necessary to increase the awareness and to improve the motivation of HIV prevention in MSM population.

Objective To understand the human papilloma virus (HPV) infection status in men who have sex with men (MSM) recruited from gay bathhouses and HIV voluntary counseling and testing (VCT) clinics in Urumqi,Xinjiang Uygur autonomous region,and identify the associated risk factors.Methods A total of 200 MSM aged ≥≥ 18 years were recruited by using the "snowballing" sampling method from gay bathhouses and VCT clinics in Urumqi during March-May,2016.The MSM recruited completed questionnaires after filling in the informed consent form.The information about their demographic characteristics and sexual behaviors were collected,and anal swabs were collected from them for HPV genotyping.Results The overall HPV infection rate was 54.0％.The HPV infection rate was 66.7％(74/111) in MSM from gay bathhouses and 38.2％(34/89) in MSM from VCT clinics and the high risk type HPV infection rate was 39.6％ (44/111) in MSM from gay bathhouses and 14.6％(13/89) in MSM from VCT clinics,the differences were significant (x2=16.112,P＜0.05;x2=15.190,P＜0.05).Multiple logistic regression analysis indicated that the major risk factors for HPV infection included activity in gay bathhouse (OR=3.732,95％CI:1.950-7.141) and anal sexual behavior (OR=2.555,95％ CI:1.329-4.912).Conclusion The prevalence of HPV in MSM from gay bathhouses was higher than that in MSM from VCT clinics,indicating that close attention should be paid to the behavior intervention in MSM.

Background::With an increasing number of patients with hematological malignancies being treated with umbilical cord blood transplantation (UCBT), the correlation between immune reconstitution (IR) after UCBT and graft-versus-host disease (GVHD) has been reported successively, but reports on double-negative T (DNT) cell reconstitution and its association with acute GVHD (aGVHD) after UCBT are lacking.Methods::A population-based observational study was conducted among 131 patients with hematological malignancies who underwent single-unit UCBT as their first transplant at the Department of Hematology, the First Affiliated Hospital of USTC, between August 2018 and June 2021. IR differences were compared between the patients with and without aGVHD.Results::The absolute number of DNT cells in the healthy Chinese population was 109 (70-157)/μL, accounting for 5.82 (3.98-8.19)% of lymphocytes. DNT cells showed delayed recovery and could not reach their normal levels even one year after transplantation. Importantly, the absolute number and percentage of DNT cells were significantly higher in UCBT patients without aGVHD than in those with aGVHD within one year ( F = 4.684, P = 0.039 and F = 5.583, P = 0.026, respectively). In addition, the number of DNT cells in the first month after transplantation decreased significantly with the degree of aGVHD increased, and faster DNT cell reconstitution in the first month after UCBT was an independent protective factor for aGVHD (HR = 0.46, 95% confidence interval [CI]: 0.23-0.93; P = 0.031). Conclusions::Compared to the number of DNT cells in Chinese healthy people, the reconstitution of DNT cells in adults with hematological malignancies after UCBT was slow. In addition, the faster reconstitution of DNT cells in the early stage after transplantation was associated with a lower incidence of aGVHD.

Objective:To evaluate the clinicopathologic characteristics and outcomes of HIV-negative plasmablastic lymphoma (PBL) .Methods:Medical records of 15 patients diagnosed with HIV-negative PBL in Changhai Hospital between January 2013 and August 2019 were reviewed, and clinicopathologic characteristics and outcomes were analyzed.Results:Median age was 59 years (range: 17-69) . All patients had extranodal involvement. According to the Cotswolds-modified Ann Arbor staging system, 1 (6.7%) , 2 (13.3%) , 3 (20.0%) , and 9 (60.0%) patients were classified as at Ⅰ,Ⅱ,Ⅲ and Ⅳ, respectively. Plasmablast and immunoblast proliferations were typical manifestations of PBL. Immunohistochemical staining showed tumor cells were diffusely positive for plasma cell markers CD38, CD138, and Mum-1, while negative for B cell markers CD20, CD10, PAX-5, and BCL-6. Median Ki-67 index was 80% (70%-90%) . Epstein-Barr virus-encoded RNA (EBER) expression was detected in 3 patients, and 1 of them was positive. All patients received chemotherapy, 80% combined with bortezomib as the first line, and responses were observed in 8 patients (6 complete and 2 partial responses) . Median progression-free survival (PFS) and overall survival (OS) were 6.8 (95% CI 2.5-11.1) months and 17.9 (95% CI 5.6-30.2) months, the 3-year PFS and OS rates were 21.2% (95% CI 1.4%-56.8%) and 38.5% (95% CI 12.0%-65.0%) , respectively. Conclusion:HIV-negative PBL with high invasiveness is extremely prone to extranodal involvement and most patients were at the advanced stage. Patients receiving an intensive therapy combined with bortezomib and bridged autologous stem cell transplantation may improve long-time survival.