Objective:To establish a method for the determination of 2-amino-5-chloro-N, 3-dimethylbenzamide in blood by ultra-performance liquid chromatography-quadrupole-orbitrap high resolution mass spectrometry (UPLC-Q-Orbitrap HRMS) .Methods:In October 2022, 200 μl of blood samples were taken and 800 μl of acetonitrile was added. The samples were centrifuged at 3500 r/min (with a centrifugation radius of 6.6 cm) for 15 minutes. The supernatant was detected in the positive ion target tandem mass spectrometry (Target MS 2) mode and quantified by the external standard method. Methodological validation was also carried out for the established method. Results:The working curve of 2-amino-5-chloro-N, 3-dimethylbenzamide showed good linearity in the concentration range of 2.07-165.44 μg/L, with a correlation coefficient ( r) of 0.9994. The intra-day and inter-day relative standard deviations ( RSD) for the detection of 2-amino-5-chloro-N, 3-dimethylbenzamide were 2.6%-3.0% and 3.1%-3.5%, respectively. Analytical accuracy of 2-amino-5-chloro-N, 3-dimethylbenzamide quantification ranged from 101.0 % to 108.4 %, and the limit of detection and limit of quantification were 0.11 μg/L and 0.36 μg/L, respectively. The blood samples were able to be stored at -20 ℃ for at least 7 days. Conclusion:The UPLC-Q-Orbitrap HRMS determination method is sensitive, efficient and accurate, and can be used for the determination of 2-amino-5-chloro-N, 3-dimethylbenzamide in blood.

ObjectiveTo investigate the therapeutic efficacy， influencing factors， and safety of a treatment regimen based on coblopasvir hydrochloride capsules/sofosbuvir tablets in patients with chronic hepatitis C virus （HCV） infection in a real-world setting. MethodsA total of 253 patients who attended The Third People’s Hospital of Kunming from September 1， 2021 to May 31， 2024 were enrolled， among whom there were 86 patients with compensated liver cirrhosis （CLC group） and 167 patients with chronic hepatitis C （CHC group）. The patients were treated with coblopasvir hydrochloride capsules （60 mg）/sofosbuvir tablets （400 mg） with or without ribavirin tablets for 12 weeks， and they were followed up for 12 weeks after drug withdrawal. The primary outcome measures were the rate of sustained virologic response at week 12 after treatment （SVR12） and safety， and the secondary outcome measures were the changes in liver function， renal function， blood routine， and liver stiffness measurements （LSM） after 4 weeks of treatment， after 12 weeks of treatment， and at 12 weeks after drug withdrawal. The independent-samples t test and the Mann-Whitney U test were used for comparison of continuous data between two groups， and the Friedman test was used for comparison between multiple groups， while the Bonferroni method was used for paired comparison within each group； the chi-square test was used for comparison of categorical data between two groups. The Logistic analysis was used to investigate related influencing factors. ResultsThe 253 patients with chronic HCV infection had a mean age of 49.38±8.65 years， and there were 151 male patients （59.7%）. Of all patients， 33.99% （86/253） had liver cirrhosis， 25.69% （65/253） had hypertension， 10.67% （27/253） had HIV infection， 8.70% （22/253） had diabetes， 3.95% （10/253） had liver cancer， 1.98% （5/253） had chronic hepatitis B， and 7.91% （20/253） were treatment-experienced patients. As for genotype distribution， 2.77% （7/253） had genotype 1， 12.65% （32/253） had genotype 2， 66.01% （167/253） had genotype 3， 16.60% （42/253） had genotype 6， and 1.98% （5/253） had unknown genotype. The patients had an overall SVR12 rate of 92.09%， with an SVR12 rate of 93.02% in the CLC group and 91.02% in the CHC group. The multivariate logistic regression analysis showed that age （odds ratio ［OR］=1.086， 95% confidence interval ［CI］： 1.007 — 1.170， P=0.032） and HCC （OR=9.178， 95%CI： 1.722 — 48.912， P=0.009） were independent influencing factors for sustained virologic response. Compared with baseline data， the CLC group had significant reductions in alanine aminotransferase （ALT） （χ²=107.103， P0.05）， aspartate aminotransferase （AST） （χ²=90.602， P0.05）， and LSM （χ²=42.235， P0.05） after 12 weeks of treatment， while the CHC group had significant reductions in total bilirubin （χ²=15.113， P0.05）， ALT （χ²=202.237， P0.05）， AST （χ²=161.193， P0.05）， and LSM （χ²=37.606， P0.05）. The incidence rate of serious adverse events was 1.58%， and none of the patients withdrew from drug therapy； the patients with such events were relieved after active symptomatic treatment. The incidence rate of all adverse events was 23.72%， among which fatigue （17.39%） and nausea （2.37%） were the most common adverse events， and these events often disappeared within 2 weeks or were gradually relieved after symptomatic treatment. ConclusionCoblopasvir hydrochloride capsules/sofosbuvir tablets with or without ribavirin tablets has good efficacy and safety in the treatment of chronic HCV infection.

Objective:To establish a method for the determination of 2-amino-5-chloro-N, 3-dimethylbenzamide in blood by ultra-performance liquid chromatography-quadrupole-orbitrap high resolution mass spectrometry (UPLC-Q-Orbitrap HRMS) .Methods:In October 2022, 200 μl of blood samples were taken and 800 μl of acetonitrile was added. The samples were centrifuged at 3500 r/min (with a centrifugation radius of 6.6 cm) for 15 minutes. The supernatant was detected in the positive ion target tandem mass spectrometry (Target MS 2) mode and quantified by the external standard method. Methodological validation was also carried out for the established method. Results:The working curve of 2-amino-5-chloro-N, 3-dimethylbenzamide showed good linearity in the concentration range of 2.07-165.44 μg/L, with a correlation coefficient ( r) of 0.9994. The intra-day and inter-day relative standard deviations ( RSD) for the detection of 2-amino-5-chloro-N, 3-dimethylbenzamide were 2.6%-3.0% and 3.1%-3.5%, respectively. Analytical accuracy of 2-amino-5-chloro-N, 3-dimethylbenzamide quantification ranged from 101.0 % to 108.4 %, and the limit of detection and limit of quantification were 0.11 μg/L and 0.36 μg/L, respectively. The blood samples were able to be stored at -20 ℃ for at least 7 days. Conclusion:The UPLC-Q-Orbitrap HRMS determination method is sensitive, efficient and accurate, and can be used for the determination of 2-amino-5-chloro-N, 3-dimethylbenzamide in blood.

Objective:To investigate the differences of white matter diffusion properties between vulnerable and resistant individuals to continuous attention after sleep deprivation.Methods:According to the psychomotor vigilance test performance before and after sleep deprivation, the participants were divided into the vulnerable group( n=24) and resistant group( n=25). All participants underwent diffusion tensor imaging (DTI) scans.Tract based spatial statistics(TBSS) was used to compare fractional anisotropy(FA), mean diffusivity(MD), axial diffusivity(AD), radial diffusivity(RD) maps between the two groups.Spearman correlation analysis was conducted by SPSS 24.0 to investigate the relationships between the altered DTI metrics and PVT task performance. Results:(1) Compared with resistant group, FA value of vulnerable group decreased in the body of corpus callosum(x, y, z=-8, 9, 25, t=-7.855), right superior longitudinal fasciculus(x, y, z=-39, -7, 26, t=-6.252), bilateral anterior limb of internal capsule(x, y, z=-13, 8, 13, t=-5.235; x, y, z=12, 8, 3, t=-5.024) and right posterior thalamic radiation(x, y, z=-26, -56, 17, t=-5.469)(TFCE corrected, P<0.05, cluster size≥50 voxel). (2) Compared with resistant group, MD value of vulnerable group increased in the body of corpus callosum(x, y, z=-3, -6, 26, t=7.613), right superior longitudinal fasciculus(x, y, z=-31, -19, 38, t=5.314), bilateral anterior limb of internal capsule(x, y, z=-16, 7, 8, t=6.898; x, y, z=15, 5, 7, t=6.652), splenium of corpus callosum(x, y, z=27, -53, 17, t=6.541), and AD value increased in the right superior longitudinal fasciculus(x, y, z=-33, -19, 39, t=4.892), splenium of corpus callosum(x, y, z=-22, -49, 21, t=5.450), genu of corpus callosum(x, y, z=4, 26, 0, t=4.332), as well as RD value increased in the right superior corona radiata(x, y, z=-17, 1, 33, t=7.558), body of corpus callosum(x, y, z=4, -8, 26, t=6.699), right anterior limb of internal capsule(x, y, z=-12, 7, 3, t=5.212) (TFCE corrected, P<0.05, cluster size≥50 voxel). (3) Correlational analysis revealed that the negative correlations were found between PVT task performance and the FA value in the right superior longitudinal fasciculus( r=-0.492, P<0.001), right anterior limb of internal capsule( r=-0.510, P<0.001), right posterior thalamic radiation( r=-0.502, P<0.001) and body of corpus callosum( r=-0.464, P<0.001). The positive correlations were found between PVT task performance and the MD value in the body of corpus callosum( r=0.500, P<0.001), right superior longitudinal fasciculus( r=0.499, P<0.001), splenium of corpus callosum( r=0.462, P<0.001), right anterior limb of internal capsule( r=0.471, P<0.001), and AD value in right superior longitudinal fasciculus( r=0.643, P<0.001), as well as RD value in right superior corona radiate( r=0.498, P<0.001) (Bonferroni corrected, P<0.003). Conclusion:Differences in the microstructural characteristics of white matter fiber tracts in specific brain regions may constitute the potential neuropathological basis for the phenotypes of vulnerable and resistant individuals to continuous attention after sleep deprivation.

Objective To observe the effect of 3D-Slicer combined with sina software assisted minimally invasive neuroendoscopic surgery for hypertensive intracerebral hemorrhage,and investigate the application value of 3D-Slicer combined with sina software in the preoperative localization of minimally invasive neuroendoscopic surgery.Methods From July 2015 to October 2017,38 consecutive patients with supratentorial hypertensive intracerebral hemorrhage admitted to Shunde Hospital,Guangzhou University of Chinese Medicine were enrolled retrospectively.According to the different treatment methods,they were divided into an endoscopic group and a puncture group (n =19 in each group).The endoscopic group was treated with 3D-Slicer combined with sina software for neuroendoscopic hematoma removal,and the puncture group was treated with the hematoma minimally invasive soft-channel puncture and drainage under the CT localization.The effect of 3D-Slicer combined with sina software in the preoperative localization of hypertensive intracerebral hemorrhage by the minimally invasive surgery was evaluated by comparing the hematoma clearance of the first and third day of the two groups of patients after procedure,puncture to the preset position success,postoperative rebleeding,postoperative complications,and good prognosis at 3 months after procedure.Results The clearance rate of hematoma at the first day after operation in the endoscopic group was significantly higher than that in the puncture group ([90 ± 10]％ vs.[46 ± 16]％;t =2.348,P ＜ 0.05).The success of the puncture to the preset position was better than that in the puncture group (19/19 vs.14/19;x2 =5.758,P =0.016),and postoperative rebleeding rate was lower than that in the puncture group (0 vs.4/19;x2 =4.471,P =0.034).There were significant differences.There was no significant difference in postoperative infection complications between the two groups (all P ＞ 0.05).The prognosis of the endoscopic group was good in 17 patients within 3 months after procedure,and the prognosis was good in 11 patients in the puncture group.The good prognosis in the endoscopic group was better than that in the puncture group (x2 =4.866,P =0.027).Conclusion The effect of 3D-Slicer combined with sina software assisted minimally invasive neuroendoscopic surgery for hypertensive intracerebral hemorrhage was better than the hematoma minimally invasive soft-channel puncture and drainage under the CT localization,and the 3D-slicer combined with sina software can provide rapid and accurate preoperative localization for minimally invasive neuroendoscopic surgery of hypertensive intracerebral hemorrhage.