Objective To evaluate the effects of different concentrations of chloroprocaine on KCNQ2/Q3 channel currents in HEK2936 cells.Methods Human embryonic kidney (HEK293) cells served as an expression system.KCNQ2 and KCNQ3 cDNAs and green fluorescent protein were transfected into HEK293 cells by using lipofectamine.The KCNQ2/Q3 currents were recorded by using the whole-cell patch-clamp technique.Part Ⅰ The transfected HEK293 cells were randomly divided into 4 groups (n =11 each):control group,and 1,10 and 100 mmol/L chloroprocaine groups.The KCNQ2/Q3 channel currents produced by different concentrations of chloroprocaine were recorded under different holding potentials (-40,0 and 40 mV) and the action time was 1 min.Part Ⅱ The transfected HEK293 cells were randomly divided into 2 groups (n =5 each):control group and 10 mmol/L chloroprocaine.The KCNQ2/Q3 channel currents were recorded under different holding potentials (-80-30 mV)and the action time was 1 min.Different test potentials were normalized and fitted to Boltzmann function,and KCNQ2/Q3 channel Ⅰ-Ⅴ curve was then obtained.The activation and deactivation currents were both fitted to a single exponential function and the time constants for current activation and for current deactivation were calculated.Results Part Ⅰ When the holding potential was 40,0 and-40 mV,the suppression rate of KCNQ2/Q3 channel currents in HEK293 cells was higher in 1,10 and 100 mmol/L chloroprocaine groups than in control group (P ＜0.05 or 0.01).Part Ⅱ Compared with control group,the time constant for the current activation at 0 mV of holding potential was prolonged,the time constant for the current deactivation was shortened when the holding potential was-80 mV,and the half-activation voltage of KCNQ2/Q3 channels was increased,the activation curve shifted to the depolarized potentials,and KCNQ2/Q3 channel Ⅰ-Ⅴ curve slope was decreased in 10 mmol/L chloroprocaine group (P ＜ 0.05).Conclusion Chloroprocaine concentration-dependently suppresses KCNQ2/Q3 channel currents in HEK2936 cells.The KCNQ2/Q3 channel is closed in advance due to KCNQ2/Q3 channel opening delay induced by chloroprocaine thus decreasing the activity of KCNQ2/Q3 channels.

ObjectiveTo systematically review the efficacy and safety of norepinephrine combined with albumin versus terlipressin combined with albumin in the treatment of type 1 hepatorenal syndrome (HRS1). MethodsPubMed, EMBASE, Medline, Cochrane Library, CNKI, Wanfang Data, and VIP were searched for comparative studies on norepinephrine combined with albumin versus terlipressin combined with albumin in the treatment of HRS1. Quality assessment was performed for articles. Related indicators were extracted, including hepatorenal syndrome (HRS) reversal rate, mortality rate, incidence of adverse events, mean arterial pressure, and renal function, and Review Manager 5.3 was used for data analysis. The chi-square test was used to determine the heterogeneity between studies. Odds ratio (OR) was used for the analysis of dichotomous variables, weighted mean difference (WMD) was used for the analysis of continuous variables, and 95% confidence interval (CI) was calculated for these two types of variables. ResultsA total of 6 randomized controlled trials which met the inclusion criteria were included, with a total sample size of 298 patients (149 patients in the norepinephrine+albumin group and 149 in the terlipressin+albumin group). The meta-analysis showed that there were no significant differences between the two groups in HRS reversal rate (OR=0.95, 95%CI: 0.6-1.49, P=0.81), mortality rate (OR=0.84, 95%CI: 0.51-1.41, P=0.51), incidence rate of adverse events (OR=042, 95%CI: 0.16-1.07, P=0.07), mean arterial pressure (standardized mean difference=0.05, 95%CI: -0.92 to 1.03, P=092), and renal function. ConclusionNorepinephrine combined with albumin has similar efficacy and safety as terlipressin combined with albumin in the treatment of HRS1, and terlipressin can be replaced by norepinephrine in clinical practice when necessary.

Objective To explore the effect of nucleos(t)ide analog (NA)antiviral treatment on the pathological differentiation of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC)and the prognostic factors of HCC.Methods Totally 127 patients with HBV-related HCC who were hospitalized and received partial hepatectomy in First Affiliated Hospital of Harbin Medical University from March 2007 to November 2013 were included in this study.Sixteen cases received antiviral treatment before operation and the remaining 111 cases had no history of NA treatment.The differences of histopathological grading were compared between the two groups.Twenty-nine patients received antiviral treatment for the first time after surgery,and the rest 82 patients did not.All these patients were followed up for survival and recurrence.Multivariate analysis was used to explore the prognostic factors for HCC.The categorical variables were analyzed byχ2 test or Fisher exact test.Survival rate was compared with Log-rank test. Univariate or multivariate Cox regression analysis was used to explore the related factors of survival. Results The proportions of well-,moderately- or poorly-differentiated HCC in patients with antiviral treatment before surgery were 18.75 %,68.75 % and 12.5 %,respectively.Whereas the proportions in those without treatment were 16.22%,66.67% and 17.11 %,respectively.There was no significant difference in histopathological grading of HCC between the two groups (χ2=0.224,P =0.885 ).The overall median survival time was 39 months.The 6-month,1-and 2-year survival rates were 91 .7%, 77.5 % and 59.3%,respectively.The 6-month,1- and 2-year survival rate of postoperative antiviral treatment were 96.3%,92.4% and 78.5 %,respectively,which were significantly higher than those of no antiviral treatment group (85 .9%,70.0% and 48.5 %,respectively;χ2= 6.967,P = 0.008 ). Univariate analysis showed that tumor number,size,portal vein transfer,AFP level,postoperative antiviral treatment,histopathological grading,TNM staging,BCLC staging,γ-GT and PTA were prognostic factors for postoperative HCC survival.Multivariate analysis showed that AFP level (HR=1 , 95 %CI :1 .0004—1 .002,P =0.004),postoperative antiviral treatment (HR =0.38,95 %CI :0.38—0.15 ,P =0.04)and BCLC stage (B vs A:HR=1 .55 ,95 %CI :0.76—3.18;C vs A:HR=3.63,95 %CI :1 .31 —10.09,P =0.04)were independent prognostic factors.Conclusions Preoperative antiviral treatment has no impact on the histopathological grading of HCC. BCLC stage, AFP level and postoperative antiviral treatment are independent prognostic factors for HBV-related HCC.

The objective of this study was to prepare a biodegradable poly (DL-lactide) injectable gel of tinidazole. The formulation parameters evaluated in this study included polymer molecular weight, polymer concentration, solvent and drug loading, and orthogonal design was used to optimize the formulation. The preferable formulation was that 30% (w/w) poly(DL-lactide) (MW is 5 700) dissolved in 70% (w/w) N-methyl-2-pyrrolidone with 4%-6% (w/w) tinidazole.
Delayed-Action Preparations ; Drug Carriers ; chemistry ; Gels ; Lactic Acid ; chemistry ; Polyesters ; Polymers ; chemistry ; Technology, Pharmaceutical ; methods ; Tinidazole ; administration & dosage

Objective To retrospectively analyze the setup error in radiotherapy of somal tumors and body metastases using the ExacTrac X-ray portal image,and to evaluate the feasibility and effectiveness of 6D setup error correction in body radiotherapy.Methods The translational and rotational setup errors were calculated by registering the bony structures on the ExacTrac X-setup images to that of the digitally reconstructed setup images,and the corresponding residual errors were calculated together.Results The translational and rotational setup errors in the x (left-right),y (superior-inferior),z (anterior-posterior) and Rx (sagittal),Ry (transverse),Rz (coronal) directions were(2.27±2.02) mm,(4.49±2.52) mm,(2.27± 1.37) mm and (1.02 ± 0.73) °,(0.67 ± 0.68) °,(0.76 ± 0.84) °,respectively.The residual translational and rotational setup errors in the x(r),y(r),z(r) and Rx(r),Ry(r),Rz(r) directions were(0.27±0.48)mm,(0.37±0.45)mm,(0.22±0.30)mm and (0.17±0.33)°,(0.14±0.34)°,(0.16± 0.28) ° respectively.Conclusions Besides the translational setup errors,a certain amount of rotational setup errors exist in radiotherapy of somal tumors and body metastases.By using the 6D setup error correction of the ExacTrac system,a translational less than 0.4 mm and rotational setup errors less than 0.2° could be achieved.

Objective:To investigate the workflow, efficacy and safety of MR-Linac in liver malignancies.Methods:Clinical data of 15 patients with hepatocellular carcinomas (HCC) or liver metastases treated with MR-Linac between November 2019 and July 2021 were retrospectively analyzed. The workflow of MR-Linac was investigated and image identification rate was analyzed. Patients were followed up for response and toxicity assessment.Results:Fifteen patients (6 HCC, 8 liver metastases from colorectal cancer, 1 liver metastasis from breast cancer) were enrolled. A total of 21 lesions were treated, consisting of 10 patients with single lesion, 4 patients with double lesions and 1 patient with triple lesions. The median tumor size was 2.4 cm (0.8-9.8 cm). The identification rate for gross tumor volume (GTV) in MR-Linac was 13/15. Although GTV of two patients were unclearly displayed in MR-Linac images, the presence of adjacent blood vessel and bile duct assisted the precise registration. All the patients were treated with stereotactic body radiation therapy (SBRT). For HCC, the median fraction dose for GTV or planning gross tumor volume (PGTV) was 6 Gy (5-10 Gy) and the median number of fractions was 9(5-10). The median total dose was 52 Gy (50-54 Gy) and the median equivalent dose in 2 Gy fraction (EQD 2Gy) at α/ β= 10 was 72 Gy (62.5-83.3 Gy). For liver metastases, the median fraction dose for GTV or PGTV was 5 Gy (5-10 Gy) and the median number of fractions was 10(5-10). The median total dose was 50 Gy (40-50 Gy) and the median EQD 2Gy at α/ β=5 was 71.4 Gy (71.4-107.1 Gy). At 1 month after SBRT, the in-field objective response rate (ORR) was 8/13 and the disease control rate was 13/13. At 3-6 months after SBRT, the in-filed ORR was increased to 6/6. During the median follow-up of 4.0 months (0.3-11.6), 4-month local progression-free survival, progression-free survival and overall survival were 15/15, 11/15 and 15/15, respectively. Toxicities were mild and no grade 3 or higher toxicities were observed. Conclusions:MR-Linac provides a platform with high identification rates of liver lesions. Besides, the presence of adjacent blood vessel and bile duct also assists the precise registration. It is especially suitable for liver malignancies with promising local control and well tolerance.