Purpose To explore the predictive value of intravoxel incoherent motion quantitative parameters and pathological grading for the survival prognosis of patients with hepatocellular carcinoma(HCC)after surgery.Materials and Methods A retrospective analysis was performed on 65 patients with HCC who had complete imaging data and underwent radical surgery at the Fourth Hospital of Hebei Medical University from October 2018 to November 2019.All patients were followed up for a 5-year survival period.The receiver operating characteristic curve was used to determine the optimal cut-off values for intravoxel incoherent motion quantitative parameters,including standard apparent diffusion coefficient(sADC),diffusion coefficient(D),pseudo-diffusion coefficient(D*)and perfusion fraction(F).Univariate and multivariate Cox regression analyses were performed to select independent predictive factors affecting the overall survival time of HCC patients after surgery.Results Univariate Cox regression analysis showed that pathological grading(HR=1.588,95%CI 0.936-2.692,P=0.086),microscopic vascular invasion(HR=2.512,95%CI 1.308-4.823,P=0.006),neutrophil-to-lymphocyte ratio(HR=1.752,95%CI 1.000-3.068,P=0.050),sADC(HR=0.433,95%CI 0.235-0.796,P=0.007),D(HR=0.262,95%CI 0.121-0.565,P<0.001)and F(HR=2.268,95%CI 1.259-4.087,P=0.006)were all prognostic factors.Multivariate Cox regression analysis showed that pathological grade(grade Ⅲ and Ⅳ)was the independent risk factor for the survival prognosis of patients after HCC surgery(HR=1.748,95%CI 1.003-3.045,P=0.049);the D value>0.916×10-3 mm2/s was the independent protective factor for their survival prognosis(HR=0.249,95%CI 0.113-0.550,P<0.001).Conclusion The pathological grade(Ⅲ/Ⅳ)as an independent risk factor and higher D values as a protective factor are the independent predictors of survival and prognosis of patients with HCC after surgery,and the combination of the two can provide a reference for clinical prognosis assessment.

Purpose To explore the predictive value of intravoxel incoherent motion quantitative parameters and pathological grading for the survival prognosis of patients with hepatocellular carcinoma(HCC)after surgery.Materials and Methods A retrospective analysis was performed on 65 patients with HCC who had complete imaging data and underwent radical surgery at the Fourth Hospital of Hebei Medical University from October 2018 to November 2019.All patients were followed up for a 5-year survival period.The receiver operating characteristic curve was used to determine the optimal cut-off values for intravoxel incoherent motion quantitative parameters,including standard apparent diffusion coefficient(sADC),diffusion coefficient(D),pseudo-diffusion coefficient(D*)and perfusion fraction(F).Univariate and multivariate Cox regression analyses were performed to select independent predictive factors affecting the overall survival time of HCC patients after surgery.Results Univariate Cox regression analysis showed that pathological grading(HR=1.588,95%CI 0.936-2.692,P=0.086),microscopic vascular invasion(HR=2.512,95%CI 1.308-4.823,P=0.006),neutrophil-to-lymphocyte ratio(HR=1.752,95%CI 1.000-3.068,P=0.050),sADC(HR=0.433,95%CI 0.235-0.796,P=0.007),D(HR=0.262,95%CI 0.121-0.565,P<0.001)and F(HR=2.268,95%CI 1.259-4.087,P=0.006)were all prognostic factors.Multivariate Cox regression analysis showed that pathological grade(grade Ⅲ and Ⅳ)was the independent risk factor for the survival prognosis of patients after HCC surgery(HR=1.748,95%CI 1.003-3.045,P=0.049);the D value>0.916×10-3 mm2/s was the independent protective factor for their survival prognosis(HR=0.249,95%CI 0.113-0.550,P<0.001).Conclusion The pathological grade(Ⅲ/Ⅳ)as an independent risk factor and higher D values as a protective factor are the independent predictors of survival and prognosis of patients with HCC after surgery,and the combination of the two can provide a reference for clinical prognosis assessment.

Objective To evaluate the role of remimazolam in lipopolysaccharide(LPS)-induced M1 microglial polarization and its relationship with Toll-like receptor 4(TLR4).Methods BV2 mi-croglia cells were randomly divided into 5 groups(n=20):control group,LPS group(1 μg/ml for 24 h),remimazolam+LPS group(remimazolam group,pretreated with 100 μg/ml remimazolam for 20 min followed by LPS),remimazolam+LPS+Neoseptin-3 group(agonist group,50 pmol Neoseptin-3 dissolved in DMSO),and remimazolam+LPS+DMSO group(agonist control group).The contents of TNF-α and IL-1β in the supernatant were detected by ELISA.The expres-sion of M1 microglia markers,inducible nitric oxide synthase(iNOS)and TLR4 at mRNA.Immu-nofluorescence staining was employed to identify the location of iNOS.Results When compared to the control group,the contents of TNF-α and IL-1β in the supernatant and the expression of iNOS[(14.757±0.986)％vs(1.561±0.08)％]and TLR4 at mRNA and protein levels were sig-nificantly higher in the other four groups(P＜0.05).Remimazolam treatment reversed the increa-ses of the TNF-α and IL-1β contents in the supernatant and mRNA and protein expression of iNOS[(3.767±0.364)％vs(14.757±0.986)％]and TLR4 induced by LPS(P＜0.05).In addi-tion,remimazolam agonist Neoseptin-3 restored the effects of LPS on above molecules[iNOS:(6.827±0.642)％vs(3.767±0.364)％,all P＜0.05].But,there were no statistical differences in above molecules between the agonist group and agonist control group(P＞0.05).Conclusion The mechanism by which remimazolam inhibits LPS-induced M1 microglial polarization is related to down-regulation of TLR4 expression.

Objective To evaluate the role of remimazolam in lipopolysaccharide(LPS)-induced M1 microglial polarization and its relationship with Toll-like receptor 4(TLR4).Methods BV2 mi-croglia cells were randomly divided into 5 groups(n=20):control group,LPS group(1 μg/ml for 24 h),remimazolam+LPS group(remimazolam group,pretreated with 100 μg/ml remimazolam for 20 min followed by LPS),remimazolam+LPS+Neoseptin-3 group(agonist group,50 pmol Neoseptin-3 dissolved in DMSO),and remimazolam+LPS+DMSO group(agonist control group).The contents of TNF-α and IL-1β in the supernatant were detected by ELISA.The expres-sion of M1 microglia markers,inducible nitric oxide synthase(iNOS)and TLR4 at mRNA.Immu-nofluorescence staining was employed to identify the location of iNOS.Results When compared to the control group,the contents of TNF-α and IL-1β in the supernatant and the expression of iNOS[(14.757±0.986)％vs(1.561±0.08)％]and TLR4 at mRNA and protein levels were sig-nificantly higher in the other four groups(P＜0.05).Remimazolam treatment reversed the increa-ses of the TNF-α and IL-1β contents in the supernatant and mRNA and protein expression of iNOS[(3.767±0.364)％vs(14.757±0.986)％]and TLR4 induced by LPS(P＜0.05).In addi-tion,remimazolam agonist Neoseptin-3 restored the effects of LPS on above molecules[iNOS:(6.827±0.642)％vs(3.767±0.364)％,all P＜0.05].But,there were no statistical differences in above molecules between the agonist group and agonist control group(P＞0.05).Conclusion The mechanism by which remimazolam inhibits LPS-induced M1 microglial polarization is related to down-regulation of TLR4 expression.

Objective To observe the value of B1 corrected T1 mapping for distinguishing pathological types and differentiation degrees of lung cancers.Methods A total of 74 lesions in 65 patients with lung cancers were prospectively enrolled,including 49 poorly differentiated lesions and 25 moderately or well differentiated ones,i.e.42 adenocarcinomas,14 squamous cell carcinomas and 18 small cell lung cancers(all poorly differentiated).B1 corrected T1 mapping was performed,ROI(ROI1 and ROI2)were delineated using 2 methods,and T1 values of different pathological types and differentiation degrees lung cancers were compared.The receiver operating characteristic(ROC)curves were drawn,and the areas under the curve(AUC)were calculated.Results Significant differences of T1 values were found among different pathological types of lung cancer(all P＜0.05),as well as between small cell lung cancer and the rest 2 types of lung cancer(both P＜0.05).There were significant differences of T1 values between poorly differentiated and moderately well differentiated lung cancer(squamous cell carcinoma+adenocarcinoma)(both P＜0.05).Taken ROI1 T1 value=1 524.21 ms as the cut-off value,the AUC of T1 value for distinguishing poorly differentiated and moderately well differentiated lung cancer(squamous cell carcinoma+adenocarcinoma)was 0.698,with sensitivity of 64.50％and specificity of 76.00％.Taken ROI2 T1 value=1 630.68 ms as the cut-off value,the AUC of T1 value was 0.676,with sensitivity of 54.80％and specificity of 80.00％.Conclusion B1 corrected T1 mapping was helpful for distinguishing pathological types and differentiation degrees of lung cancers.

Objective To evaluate the application value of golden angle radial sparse parallel(Grasp)sequence in contrast-enhanced MRI of liver.Methods The imaging data of 30 patients who underwent gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid contrast-enhanced MRI of liver were collected.With the same equipment,images were collected by Grasp sequence and breath-hold sequence separately,with an interval of less than 3 months.The subjective and objective scores of the late arterial phase and portal venous phase images were evaluated.Results There were no significant differences in all subjective scores of the late arterial phase and portal venous phase images between the two sequences(P＞0.05).The signal-to-noise ratio(SNR)of the late arterial phase images in the Grasp sequence was lower than that in the breath-hold sequence(148.4±52.8 vs 195.6±68.4),and the difference was statistically significant(P＜0.01).Although the SNR of the portal venous phase in the Grasp sequence was lower than that in the breath-hold sequence,the difference was not statistically significant(P＞0.05).There was no statistical difference in the other objective scores between the two sequences(P＞0.05).Conclusion The image quality of Grasp sequence in contrast-enhanced MRI of liver can meet the diagnositic requirements,and it is suitable for patients with poor breath-hold capacity,which has important application value.

Objective:To evaluate the relationship between glutathione S-transferase μ1 (GSTM1) and the apoptosis signal-regulating kinase 1 (ASK1)-c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK) signaling pathway during therapeutic hypothermia-induced reduction of cerebral ischemia-reperfusion injury (CIRI) in rats.Methods:One hundred clean-grade healthy male Sprague-Dawley rats, aged 8 weeks, weighing 260-280 g, were divided into 5 groups ( n=20 each) using a random number table method: sham operation group (S group), cerebral ischemia-reperfusion group (I/R group), therapeutic hypothermia group (H group), GSTM1 inhibitor+ therapeutic hypothermia group (IH group), and GSTM1 inhibitor + ASK1 inhibitor + therapeutic hypothermia group (IAH group). CIRI model was developed by occlusion of the left middle cerebral artery for 2 h, followed by restoration of the blood flow. A nylon thread was inserted into the internal carotid artery and advanced cephalad until resistance was met. The brain temperature was maintained at 36-37 ℃ during surgery. In H group, the head and neck were wiped with 75% alcohol immediately after reperfusion, and the brain temperature was maintained at 32-33℃ for 3 h, and the rest procedures were the same as those previously described in I/R group. In IH group, GSTM1 inhibitor itaconic acid 8.6 mg/kg was intraperitoneally injected at 24 and 1 h before developing the model, and the rest procedures were the same as those previously described in H group. In IAH group, ASK1 inhibitor selonsertib 10 mg/kg was given orally once a day for 4 consecutive days starting from 4 days before developing the model, and the rest procedures were the same as those previously described in IH group. Modified Neurological Severity Score (mNSS) was assessed at 24 h of reperfusion, then the rats were sacrificed and brains were harvested for microscopic examination of brain infarction, neuronal morphology (using HE staining) and for determination of the expression of GSTM1, ASK1, phosphorylated ASK1 (p-ASK1), JNK, phosphorylated JNK (p-JNK), p-38 MAPK and phosphorylated p-38 MAPK (p-p38 MAPK) (by Western blot) and neuronal apoptosis (by TUNEL assay). The percentage of the infarct size was calculated using TTC staining. The apoptosis rate was calculated. Results:Compared with S group, the mNSS, apoptosis rate of neurons, percentage of the cerebral infarct size, p-ASK1/ASK1 ratio, p-JNK/JNK ratio and p-p38 MAPK/p38 MAPK ratio were significantly increased, and the expression of GSTM1 was down-regulated in I/R group ( P<0.05). Compared with I/R group and IH group, the mNSS, apoptosis rate of neurons, percentage of the cerebral infarct size, p-ASK1/ASK1 ratio, p-JNK/JNK ratio and p-p38 MAPK/p38 MAPK ratio were significantly decreased, the expression of GSTM1 was up-regulated ( P<0.05), and the neuronal injury was significantly attenuated in H group. Compared with IH group, the mNSS, apoptosis rate of neurons, percentage of the cerebral infarct size, p-ASK1/ASK1 ratio, p-JNK/JNK ratio and p-p38 MAPK/p38 MAPK ratio were significantly decreased ( P<0.05), no significant change was found in GSTM1 expression ( P>0.05), and the neuronal damage was significantly attenuated in IAH group. Conclusions:The mechanism by which therapeutic hypothermia alleviates CIRI is related to up-regulating the expression of GSTM1 and inhibiting the activation of the ASK1-JNK-p38 MAPK signaling pathway in rats.

Objective:To evaluate the role of glutathione S-transferase μ1 (GSTM1) expression in mild hypothermia-induced mitigation of cerebral ischemia-reperfusion (I/R) injury and the relationship with microglial polarization.Methods:Eighty clean-grade healthy male Sprague-Dawley rats, aged 8 weeks, weighing 260-280 g, were divided into 4 groups ( n=20 each) using a random number table method: sham operation group (S group), cerebral I/R group (I/R group), mild hypothermia group (H group), and GSTM1 inhibitor + mild hypothermia group (IH group). The rat model of cerebral I/R injury was prepared using the filament occlusion method. The filament was removed to restore blood flow after the left middle cerebral artery was blocked for 2 h, and the rats′ brain and rectal temperature were maintained at 36-37 ℃ during the period. The vessels were only isolated and ligated without occlusion in S group. In H group, the entire body was wiped with 75% ethanol immediately after removing the filament, and the brain and rectal temperatures were maintained at 32-33 ℃ for 3 h, and the other procedures were the same as those previously described in I/R group. In IH group, GSTM1 inhibitor itaconic acid 8.6 mg/kg was intraperitoneally injected at 24 and 1 h before developing the model, and the other procedures were the same as those previously described in H group. Neurological deficits were evaluated using a modified neurological severity score (mNSS) at 24 h of reperfusion, and then the animals were sacrificed and the brains were removed for observation of cerebral infarction (by TTC staining) and for determination of the expression of GSTM1, M1-type microglial marker inducible nitric oxide synthase (iNOS), and M2-type microglial marker arginase-1 (Arg-1) (by Western blot), expression of GSTM1, iNOS and Arg-1 mRNA (quantitative real-time polymerase chain reaction) and contents of interleukin-6 (IL-6), IL-10, tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β) (by enzyme-linked immunosorbent assay). Results:Compared with S group, the mNSS and percentage of cerebral infarct size were significantly increased, and the expression of iNOS and Arg-1 protein and mRNA was up-regulated, the expression of GSTM1 and mRNA was down-regulated, and the contents of IL-6, TNF-α, IL-10 and TGF-β were increased in the other three groups ( P<0.05). Compared with I/R group and IH group, the mNSS and percentage of cerebral infarct size were significantly decreased, and the expression of iNOS protein and mRNA was down-regulated, the expression of Arg-1 protein and mRNA and GSTM1 was up-regulated, the contents of TNF-α and IL-6 were decreased, and the contents of TGF-β and IL-10 were increased in H group ( P<0.05). Conclusions:Up-regulated expression of GSTM1 is involved in mild hypothermia-induced mitigation of cerebral I/R injury, which is associated with inhibition of microglial polarization toward the M1 phenotype and promotion of polarization toward the M2 phenotype.

Objective:To evaluate the effects of remimazolam on gastrointestinal motor function in the patients undergoing gastrointestinal endoscopy.Methods:A total of 262 American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ patients, aged 18-64 yr, with body mass index of 18-28 kg/m 2, scheduled for elective gastrointestinal endoscopy from May 2022 to August 2022, were divided into 2 groups ( n=131 each) using a random number table method: remimazolam group (group R) and propofol group (group P). The patients in group R received intravenous remimazolam 0.20-0.25 mg/kg, and patients in group P received intravenous propofol 1.5-2.0 mg/kg. The gastrointestinal endoscopy was performed when the patients′ Modified Observer′s Assessment of Alertness/Sedation scores ≤3. During fasting before gastrointestinal preparation, before gastrointestinal endoscopy and while leaving the post-anesthesia care unit (PACU), the concentrations of serum motilin and gastrin were measured by enzyme-linked immunosorbent assay, the intestinal peristalsis rating assessed by the endoscopist during the examination was recorded, the occurrence of hypotension and hypoxemia during the examination and occurrence of abdominal distension, abdominal pain, and nausea and vomiting during stay in PACU were recorded. Results:Compared with group P, the intestinal peristalsis rating was significantly increased, the serum motilin and gastrin concentrations were increased while leaving PACU, the incidence of hypotension and hypoxemia was decreased during the examination, and the incidence of abdominal distention was decreased during stay in PACU in group R ( P<0.05). Conclusions:Remimazolam has a milder inhibitory effect on secretion of gastrointestinal hormones than propofol in the patients undergoing gastrointestinal endoscopy and is helpful for the recovery of gastrointestinal motility.

Objective:To evaluate the relationship between hippocampal miR-3065-5p and insulin-like growth factor-1/phosphatidylinositol 3-kinase/protein kinase B(IGF-1/PI3K/Akt)signaling pathway in a mouse model of perioperative neurocognitive disorder (PND).Methods:Eighty clean-grade healthy male C75BL/6 mice, aged 12-14 weeks, weighing 20-30 g, were divided them into 4 groups ( n=20 each) using the random number table method: control group (C group), PND group, miR-3065-5p agonist group (Ag group) and miR-3065-5p agonist negative control group (Ag-NC group). PND model was prepared by internal fixation of tibial fracture under anesthesia with 1.5% isoflurane. Two days before developing the model, miR-3065-5p agomir 2 μl was injected into the lateral ventricle in Ag group, miR-3065-5p agomir negative control 2 μl was injected into the lateral ventricle in Ag-NC group. Morris water maze test and open field test were performed at 7 days after surgery. The mice were sacrificed after the end of test, and hippocampal tissues were obtained for determination of the expression of miR-3065-5p, IGF-1 mRNA and Bcl-2 mRNA (by quantitative real-time polymerase chain reaction) and expression of IGF-1, phosphorylated Akt (p-Akt), phosphorylated glycogen synthase kinase-3β (p-GSK3β) and Bcl-2 (by Western blot). Results:There was no significant difference in each parameter in the open field test among the four groups ( P>0.05). Compared with group C, the postoperative escape latency was significantly prolonged, the percentage of time of stay at the target quadrant was decreased, the number of crossing the original platform was reduced, the expression of miR-3065-5p was up-regulated, and the expression of IGF-1 mRNA, Bcl-2 mRNA, IGF-1, p-Akt, p-GSK3β and Bcl-2 was down-regulated in the other three groups ( P<0.05). Compared with PND group and Ag-NC group, the postoperative escape latency was significantly prolonged, the percentage of time of stay at the target quadrant was decreased, the number of crossing the original platform was reduced, the expression of miR-3065-5p was up-regulated, and the expression of IGF-1 mRNA, Bcl-2 mRNA, IGF-1, p-Akt, p-GSK3β and Bcl-2 was down-regulated in Ag group ( P<0.05). Conclusions:Up-regulation of miR-3065-5p can inhibit the activation of IGF-1/PI3K/Akt signaling pathway, which might be one of the mechanisms of PND developed in mice.