[Pay attention to the futile recanalization management of patients with acute ischemic stroke].

Vascular recanalization therapy has been proven to be one of the most effective treatments for acute ischemic stroke (AIS) worldwide. Recently, the neurological functions have dramatically improved for AIS patients receiving endovascular thrombectomy, especially after the issue and promotion of evidence from different clinical studies. But nearly 50% of the patients had unfavorable clinical outcome even after successful recanalization [modified thrombolysis in cerebral infarction (mTICI)≥2b/3], which was termed as"futile recanalization". The mechanisms are complex, which may be related to poor collateral circulation, microthrombus and small artery reocclusion. The most significant pathophysiological change is brain tissue hypoperfusion although complete opening of the large artery, known as"no-reflow phenomenon". Therefore, it is urgent to manage the complications after vascular recanalization, such as hemorrhagic transformation, hyperperfusion syndrome, vascular re-occlusion, and even surgery-related complications (arterial dissection, contrast-induced encephalopathy), and future research is warranted to focus on the strategy of drugs with multi-target protection combined with vascular recanalization treatment. The current article covers the review, original research and case report focusing on this topic, aiming to raise clinical questions and call for more contribution to explore the mechanism and potential therapeutic strategy of futile recanalization, and thus provides more selections on the improvement of clinical outcome for AIS patients.

[Attention should be paid to futile recanalization after endovascular treatment in acute ischemic stroke].

With the accumulation of research evidence and clinical experience, an increasing number of patients benefit from vascular recanalization therapies. Although successful recanalization of the occluded artery has been achieved, neurological deficits persist after endovascular treatment, which defined as"futile reperfusion". Compared with the successful recanalization, successful reperfusion predicts final infarct size and clinical outcome more accurately. At present, the known influencing factors of futile reperfusion include older age, female, high baseline National Institute of Health stroke scale (NIHSS) score, hypertension, diabetes, atrial fibrillation, reperfusion treatment strategy, large infarction core volume, and collateral circulation status. The incidence of futile reperfusion in China is significantly higher than that in western population. However, few studies focused on its mechanism and influencing factors. To date, many clinical studies have attempted to reduce the occurrence of futile recanalization regarding antiplatelet therapy, blood pressure management and treatment process improvement. However, only one effective measure has been achieved in blood pressure management: systolic blood pressure control below 120 mmHg (1 mmHg=0.133 kPa) should be avoided after successful recanalization. Therefore, future studies are warranted to promote the establishment and maintenance of collateral circulation, as well as neuroprotective therapy.

[Safety and effectiveness of emergency stenting for acute anterior circulation large artery disease].

Objective: To explore the safety and effectiveness of early stent implantation in patients with acute anterior circulation large artery disease. Methods: Patients were recruited from the RESCUE-RE study (a registration study for Critical Care of Acute Ischemic Stroke After Recanalization). Patients who were diagnosed with acute ischemic stroke within 24 hours of onset and given endovascular treatment after consultation from July 2018 to May 2019 from 18 sub-centers nationwide were retrospectively enrolled. According to whether the stents were placed during the operation, the patients were divided into two groups: stenting group and non-stenting group. The baseline between the two groups was matched by propensity score. The matching variables included age, sex, baseline National Institutes of Health Stroke Scale (NIHSS) score, baseline Glasgow Coma Scale (GCS) score, history of stroke, smoking and onset to hospital time. The primary clinical outcome was 90-day good neurological outcome [defined as modified Rankin score (mRS) 0-2]. Secondary outcomes include 90-day mortality, 24-hour re-occlusion of the responsible artery, and symptomatic intracranial hemorrhage. The differences in clinical endpoints between the two groups were compared. Result: A total of 899 patients with acute anterior circulation artery stenosis or occlusion were included in the study, with a mean age of(66±12)years,and 532(59.18%) were male. There were 193 patients in the stenting group and 706 patients in the non-stenting group. After the baseline data between the two groups were matched by propensity score, 169 patients were enrolled in each of two groups respectively. After matching, the proportion of patients in the stenting group with etiological diagnosis of large atherosclerosis [82.53% (137/166) vs 55.69% (93/167)] and the proportion of patients with previous history of hypertension [63.31% (107/169) vs 47.93% (81/169)] in the stenting group were higher than those in the non-stenting group (both P<0.05). While the proportion of patients in the non-stenting group with cardiogenic embolism [37.73%(63/167) vs 11.45%(19/166)]and the proportion of patients with atrial fibrillation [18.93% (32/169) vs 10.65%(18/169)]was higher(all P<0.05). In the stenting group, the time from onset to recanalization was longer[519 (408, 620)min vs 469 (365, 690)min], and the proportion of general anesthesia [50.89% (86/169) vs 35.50% (60/169)] was higher in the stenting group(both P<0.05). In addition, in the stenting group, the proportion of patients receiving mechanical thrombectomy[67.46% (114/169) vs 88.76% (150/169)] and arterial thrombolysis [2.37% (4/169) vs 18.93% (32/169)] was lower than non-stenting group during the operation, while the proportion of patients receiving balloon dilation [53.85% (91/169) vs 13.61% (23/169)]was higher(both P<0.05). The proportion of patients in stent group receiving antiplatelet drugs before operation was higher [13.46% (21/169) vs 8.70% (14/169)](both P<0.05). In terms of clinical outcome, compared with the non-stenting group, the proportion of patients in the stenting group with good neurological function in 90 days was lower [44.79% (73/169) vs 56.36% (93/169)], and the proportion of death at 90 days was higher[15.98% (27/169) vs 8.88% (15/169)] (both P<0.05). There was no significant difference between the two groups in 24-hour re-occlusion[8.88% (15/169) vs 9.47% (16/169)] and symptomatic intracranial hemorrhage[5.92% (10/169) vs 4.76% (8/169)](both P>0.05). Conclusion: For patients with acute anterior circulation artery disease, early stent therapy may increase the proportion of patients with adverse neurological outcomes.

[Analysis of efficacy and factors influencing sequential combination therapy with tenofovir alafenamide fumarate after treatment with entecavir in chronic hepatitis B patients with low-level viremia].

Objective: To observe the efficacy and factors influencing sequential or combined tenofovir alafenamide fumarate (TAF) after treatment with entecavir (ETV) in patients with chronic hepatitis B (CHB) with low-level viremia (LLV). Methods: 126 CHB cases treated with ETV antiviral therapy in the Department of Infectious Diseases of the First Affiliated Hospital of Nanchang University from January 2020-September 2022 were retrospectively collected. Patients were divided into a complete virologic response (CVR) group (n = 84) and a low-level viremia (LLV) group (n = 42) according to the HBV DNA level during treatment. Clinical characteristics and laboratory indicators of the two groups at baseline and 48 weeks were analyzed by univariate analysis. Patients in the LLV group were divided into three groups according to their continued antiviral treatment regimen until 96 weeks: continued use of ETV as a control group; replacement of TAF as a sequential group; and combination of ETV and TAF as a combined group. The data of the three groups of patients were analyzed by one-way analysis of variance for 48 weeks. HBV DNA negative conversion rate, HBeAg negative conversion rate, alanine aminotransferase (ALT), creatinine (Cr), and liver stiffness test (LSM) were compared among the three groups after 96 weeks of antiviral treatment. Multivariate logistic regression was used to analyze the independent factors influencing the occurrence of HBV DNA non-negative conversion in LLV patients at 96 weeks. Receiver operating characteristic curve (ROC) was used to evaluate the effectiveness of predicting the occurrence of HBV DNA non-negative conversion in LLV patients at 96 weeks. Kaplan-Meier was used to analyze the cumulative negative rate of DNA in LLV patients, and the Log-Rank test was used for comparison. HBV DNA and HBV DNA negative conversion rates during treatment were observed dynamically. Results: Univariate analysis showed statistically significant differences in age, BMI, HBeAg positivity rate, HBV DNA, HBsAg, ALT, AST, and LSM at baseline between the CVR group and the LLV group (P < 0.05). Univariate analysis of variance revealed no statistically significant difference among the three groups of LLV patients at 48 weeks (P > 0.05). HBV-DNA negative conversion rate in the sequential group and the combination group was significantly higher than that in the control group after 96 weeks of treatment (88.89% vs. 41.18%, 85.71% vs. 41.18%, χ (2) = 10.404, P = 0.006). HBeAg negative conversion rate was higher than that of the control group, with no statistically significant difference (P > 0.05).Compared with the control group, ALT, Cr, and LSM in the sequential group and the combined group were equally improved to varying degrees, with a statistically significant difference (P < 0.05). Subsequent use of ETV and HBV DNA at 48 weeks were independent risk factors for HBV DNA positivity at 96 weeks in LLV patients (P < 0.05). The AUC of HBV DNA at 48 weeks was 0.735 (95%CI: 0.578 ~ 0.891), the cut-off value was 2.63 log(10) IU/ml, and the sensitivity and specificity were 76.90% and 72.40%, respectively. DNA conversion rate was significantly lower in LLV patients receiving 48-week ETV and 48-week HBV DNA≥2.63 log10 IU/mL than in patients receiving sequential or combined TAF and 48-week HBV DNA < 2.63 log(10) IU/mL. HBV DNA negative conversion rates in the sequential group and combined group at 72 weeks, 84 weeks, and 96 weeks were higher than those in the control group during the period from 48 weeks to 96 weeks of continuous treatment, and the differences were statistically significant (P < 0.05). Conclusion: Sequential or combined TAF antiviral therapy could more effectively improve the 96-week CVR rate, as well as hepatic and renal function, and alleviate the degree of hepatic fibrosis in CHB patients with LLV following ETV treatment. Subsequent use of ETV and HBV DNA load at 48 weeks were independent predictors of HBV DNA positivity at 96 weeks in LLV patients.

[Investigation and analysis of occupational hazard factors in different industries in Tongliao City].

Objective: To investigate the occupational hazard factors of different industries in Tongliao City, and to provide scientific basis for the prevention and control of occupational disease in Tongliao City. Methods: In July 2021, the detection data of coal dust, silica dust, cement dust, benzene, noise and other occupational hazard factors, as well as the occupational health examination data of workers in various positions of 104 enterprises in different industries in Tongliao City were cllected and anylazed. χ(2) test was used to analyze the results of chest radiography of workers in different age groups. Results: A total of 104 enterprises were investigated, and the median time-weighted average concentration (C(TWA)) of coal dust, silic a dust, cement dust and benzene in contact with test posts were 0.94, 0.30, 0.70 and 0.95 mg/m(3), respectively. The median 8 h equivalent sound level (L(EX, 8 h)) of noise was 74.1 dB (A) . The over standard rates of silica dust, cement dust and noise contact positions were 10.83% (16/240) , 7.14% (2/28) and 0.48% (3/628) , respectively. The differences of chest X-ray examination of coal dust and silica dust workers in different working ages were statistically significant (χ(2)=218.50, 531.80, P<0.001) . The difference of hearing threshold of noise workers with different working age was statistically significant (χ(2)=1290.00, P<0.001) . The rates of leukopenia and neutropenia were 41.90% (44/105) and 20.95% (22/105) in benzene exposed workers. The positive rate of brucella exposure workers was 1.33% (1/75) for tiger red plate agglutination test and 3.23% (3/93) for tube agglutination test. Conclusion: Silica dust, cement dust and noise exceed the standard in some posts and places in the Tongliao City, and some workers are infected with Brucella. In the future, we can focus on monitoring noise-generating posts, strengthen supervision and implement prevention and control measures to reduce the incidence of occupational diseases.

[The association between stress hyperglycemia ratio and outcome of patients with acute ischemic stroke undergoing endovascular treatment].

Objectives: To investigate the correlation between stress hyperglycemia ratio (SHR) and outcomes in patients with acute ischemic stroke treated with endovascular treatment. Methods: In a multicenter registration study for RESCUE-RE (a registration study for critical care of acute ischemic stroke after recanalization), eligible patients with large vessel occlusion stroke within 24 hours after onset who received endovascular treatment between July 2018 and May 2019 were enrolled. SHR was calculated as the fasting glucose concentration divided by the estimated average glucose concentration and then categorized into four groups according to the quartiles (group Q1, group Q2, group Q3 and group Q4). The primary outcome was poor neurological outcomeat day 90 fromstroke onset [defined as modified Rankin scale (mRS) of 3-6]. Secondary outcomes included early neurological deterioration (END), death within 3 months after stroke onset, and symptomatic intracranial hemorrhage.Multivariable logistic and Cox regression modelswere used to assess the correlation between quartiles of SHR and prognosis in patients with endovascular treatment. Results: A total of 592 patients were enrolled in the study, with a mean age of (63±12) years, and 68.07% were male.The median National Institute of Health stroke scale(NIHSS) score on admission was15(11, 20), and the median SHR was 1.23 (1.07, 1.47), with SHR<1.07 in group Q1, 1.07≤SHR<1.23 in group Q2, 1.23≤SHR<1.47 in group Q3 and SHR≥1.47 in group Q4, respectively. The rate of complete recanalization was lower in group Q4 than that of group Q1 (70.27% vs 83.67%, P=0.026). After fully adjusted for potential covariates, the risk of poor neurological outcome at day 90 from stroke onset in group Q4 was 2.38 folds that of group Q1(adjusted OR= 2.38, 95%CI: 1.57-3.57,P=0.003). The risk of death within 3 months of patients in group Q4 was 1.80 times that of the patients in group Q1, but the difference was not statistically significant(adjusted HR=1.80, 95%CI: 0.90-3.62, P=0.098). Conclusion: Higher SHR was correlated with poor neurological outcome at 3 months in large artery occlusion related acute ischemic stroke patients receiving endovascular therapy.

[A multicenter randomized prospective study of concurrent chemoradiation with 60 Gy versus 50 Gy for inoperable esophageal squamous cell carcinoma].

Objective: To determine whether 60 Gy is superior to standard 50 Gy for definitive concurrent chemoradiation(CCRT) in esophageal squamous cell carcinoma (ESCC) using modern radiation technology in a phase Ⅲ prospective randomized trial. Methods: From April 2013 to May 2017, 331 patients from 22 hospitals who were pathologically confirmed with stage ⅢA-ⅣA ESCC were randomized to 60 Gy or 50 Gy with random number table. Total of 305 patients were analyzed, including 152 in 60 Gy group and 153 in 50 Gy group. The median age was 63 years, 242(79.3%) males and 63(20.7%) females. The median length of primary tumor was 5.6 cm. The clinical characteristics between two groups were comparable. All patients were delivered 2 Gy per fraction, 5 fractions per week. Concurrent weekly chemotherapy with docetaxel (25 mg/m(2)) and cisplatin (25 mg/m(2)) and 2 cycles consolidation chemotherapy with docetaxel (70 mg/m(2)) and cisplatin (25 mg/m(2), d1-3) were administrated. The primary endpoint was local/regional progression-free survival (LRPFS). The data were compared with Pearson chi-square test or Fisher's exact test. Results: At a median follow-up of 27.3 months, the disease progression rate was 37.5% (57/152), 43.8% (67/153) in the high and standard-dose group, respectively (χ(2)=1.251, P=0.263). The 1, 2, 3-year LRPFS rate was 75.4%, 56.8%, 52.1% and 74.2%, 58.4%, 50.1%, respectively (HR: 0.95, 95%CI: 0.69-1.31, P=0.761). The 1, 2, 3-year overall survival rate was 84.1%, 64.8%, 54.1% and 85.4%, 62.9%, 54.0%, respectively (HR: 0.98, 95%CI: 0.71-1.38, P=0.927). The 1, 2, 3-year progression-free survival rate was 70.8%, 54.2%, 48.5% and 65.5%, 51.9%, 45.1%, respectively (HR: 0.93, 95%CI: 0.68-1.26, P=0.621). The incidence rates in toxicities between the two groups were similar except for higher rate of severe pneumonitis in high dose group (χ(2)=11.596, P=0.021). Conclusions: The efficacy in disease control is similar between 60 Gy and 50 Gy using modern radiation technology concurrent with chemotherapy for ESCC. The 50 Gy should be recommended as the regular radiation dose with CCRT for ESCC.

[Mutation of RAS gene in follicular-differentiated thyroid tumors and its significance].

Objective: To investigate the frequency and clinical significance of RAS mutation in thyroid tumors with follicular differentiation. Methods: The samples and clinical data of 207 patients with thyroid follicular-differentiated tumors were collected at Shunyi Region Hospital of Beijing from January 2000 to December 2017, including 60 cases of follicular variant of papillary thyroid carcinoma (FVPTC), 42 cases of classical papillary thyroid carcinoma (CPTC), 26 cases of follicular thyroid carcinoma (FTC), 40 cases of follicular adenoma (FTA) and 39 cases of adenomatoid hyperplasia. BRAF V600E mutations were detected using immunohistochemical staining. FVPTC was divided into BRAF-like (BRAF V600E mutant) and RAS-like (without BRAF V600E mutant). Real-time fluorescence quantitative polymerase chain reaction was used to detect the RAS mutation in RAS-like FVPTC, CPTC, FTC, FTA and adenomatoid hyperplasia. The genetic differences in RAS mutation and their correlation with clinicopathological features were analyzed. Results: The average age of patients with benign and malignant tumors in thyroid with follicular differentiation was 53.2 years and 47.7 years, respectively. In these patients, 42 were male and165 were female. Most of the tumors had a maximum diameter of less than 4 cm, and rarely spread to the surrounding tissues of thyroid and were at early stage (stages Ⅰ and Ⅱ). The diameter of tumors in FTC was significantly larger than that in RAS-like FVPTC and CPTC groups (P<0.01). Peripheral thyroid invasion was rare in the RAS-like FVPTC, CPTC and FTC groups, but the clinical stage of FTC was more advanced than that of RAS-like FVPTC group (P<0.01) or CPTC group (P<0.01). The real-time fluorescence quantitative PCR showed that the RAS mutation rate in FTC was the highest (61.5%), significantly higher than that in others (P<0.01). The RAS mutation rate in CPTC was the lowest (4.8%), while those in RAS-like FVPTC, FTA and adenomatous hyperplasia were similar (about 15%). The Spearman rank correlation analysis showed that the RAS mutation was not correlated with age, sex or tumor size in benign lesions (FTA and adenomatous hyperplasia), nor was it associated with age, sex, tumor size, lymph node metastasis, spreading of tumors to thyroid and clinical stage in malignant tumors (RAS-like FVPTC, CPTC and FTC). Conclusions: RAS mutation can occur in both benign and malignant thyroid tumors with follicular differentiation, in which the incidence is the highest in FTC. Both morphologic and immunohistochemical changes should be taken into account. The molecular genetics of RAS-like FVPTC is similar to FTA and adenomatous hyperplasia. RAS gene mutation appears not to be a prognostic factor for thyroid diseases.

Effects of low molecular weight heparin in the treatment of venous thromboembolism in patients with gastrointestinal cancer.

This study aimed to observe the safety and effectiveness of different dosing regimens of low molecular weight heparin in the prevention of venous thromboembolism (VTE) and to provide a guideline for the treatment of individualized VTE prophylaxisin patients with postoperative gastrointestinal tumors. Forty patients with high risk for VTE after surgery for gastrointestinal tumors treated in Hongqi Hospital of Mudanjiang Medical University in the period October 2016 to May 2017 were included in the study. The patients were randomly divided into two groups, group A that included 24 patients treated with low molecular weight heparin (LMWH) 5000 IU every 12 hours, and group B comprised of 16 patients treated with LMWH 5000IU every 24 hours. On the seventh day post-surgery anti-Xa activity values reached effective anticoagulation (>0.5 IU/mL) in both groups. In group A, there was one case of anti-Xa activity exceeding 1.0 IU/mL, but no bleeding complications occurred. Using LMWH 5000 IU subcutaneous injection every 12 hours could also prevent postoperative VTE of gastrointestinal tumor, but the risk of bleeding complications is higher compared with 24-hour administration. Monitoring of plasma D-dimer within 7 days after gastrointestinal surgery did not show a great value for VTE monitoring. This study demonstrated that subcutaneous injection of LMWH can prevent VTE after gastrointestinal tumor surgery and provide a new alternative for VTE prevention.

Differential expression and analysis of target regulation of microRNAs in alcohol-dependent rats.

This study analyzed the differential expression of miRNAs related to alcohol dependence in rats undergoing continued consumption and withdrawal. Furthermore miRNAs were sought and evaluated for potential use as biomarkers for diagnosis. This study used Exiqon miRCURYTM LNA miRNA microarray on alcohol-dependent and normal rats for the expression of microRNAs in perfluorinated compounds, and the stem-loop qPCR method to validate its expression in brain tissue. We forecast the relevant target genes of differentially expressed miRNA and drew the regulatory network. Comparison of the differential expression between brain tissue and plasma was carried out and the correlation and analyzed.65 miRNA with differential expression with threshold of 1.5 were screened out; among them, most miRNA with differential expression in the dependent group had relatively high expression values. The target genes were found with great confidence: PIK3CA, MAPK, NTF, BDNF, NGFR, IGF-1, and the pair consisting of miRNA- mRNA. Among the three groups, the expression levels of miR-101b (F=8.12, P less than0.05) showed significant difference; no significant difference was found in the expression levels of miRNA in plasma among the groups (F=1.23, P>0.05). No consistency was shown in the changing trend of miRNA in PFC and plasma (r= -.004, p>0.05). The genetic regulatory network of neurotrophic factors, its receptors and the protein kinases that influence metabolism may mediate the incidence of alcohol-dependence. There is a lack of conformity between the expression of miR-101b in the prefrontal cortex and the plasma.

[The association of lipid profile and bleeding in patients with minor stroke or transient ischemic attack on antiplatelet therapy: subgroup analysis of CHANCE].

Objective: Abnormalities of lipid profile were considered as risk factors of hemorrhage after ischemic stroke. We aimed to determine the relationship between lipid levels and bleeding in minor stroke or transient ischemic attack (TIA) patients receiving antiplatelet therapy. Methods: Serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglyceride were tested in a subgroup of 3 044 consecutive patients from Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial. Patients were randomized to clopidogrel plus aspirin group or single aspirin group. The primary endpoint was any bleeding within 90 days. The secondary endpoint was severe bleeding according to the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) definition. Cox proportional hazards models were used to assess the associations of lipid levels and outcomes. Results: A total of 59 (1.9%) bleeding events occurred at 90 days. High-density lipoprotein cholesterol (adjusted HR=2.16; 95%CI 1.17-4.00, P=0.014) and age (adjusted HR=1.04; 95%CI 1.01-1.06, P=0.006) were significantly associated with any bleeding. High-density lipoprotein cholesterol was also associated with severe bleeding (adjusted HR=3.05; 95%CI 1.39-6.68, per 1 mmol/L increase). No correlations between outcomes and levels of total cholesterol, low-density lipoprotein cholesterol and triglyceride were found. There was no interaction of any lipid component level with randomized antiplatelet therapy. Conclusions: Elevated high-density lipoprotein cholesterol is independently associated with any bleeding and severe bleeding in the patients with acute minor stroke or high-risk TIA on antiplatelet therapy.

[Difference of one year death and stroke recurrence in ischemic stroke patients with anterior and posterior circulation intracranial atherosclerosis].

Objective: To explore the differences of one year death and stroke recurrence between ischemic stroke patients with intracranial atherosclerotic stenosis or occlusion of anterior circulation and those of posterior circulation. Methods: All the patients were from the Chinese Intracranial Atherosclerosis Study (CICAS), between October 2007 and June 2009; patients with extracranial stenosis or occlusion, patients without acute infarction by diffusion weighted image, and patients with intracranial atherosclerosis of both anterior and posterior circulation were excluded.All the enrolled patients were divided into three groups: no significant intracranial atherosclerosis group (n=964), anterior circulation intracranial atherosclerosis group (n=440), posterior circulation intracranial atherosclerosis group (n=233). One year outcome was evaluated by any cause of death and stroke recurrence. Results: Of the 1 637 patients, 30 cases were died and 58 cases had stroke recurrence within one year.Compared with : no significant intracranial atherosclerosis group, adjusted hazard ratio (95% confidence interval) of one-year death for anterior and posterior circulation intracranial atherosclerosis group were 1.349 (0.311-5.851), 4.542 (1.227-16.813), respectively.Adjusted hazard ratio (95% confidence interval) of one year stroke recurrence were 1.663 (0.620-4.460) and 2.464 (0.935-6.493), respectively. Conclusions: Ischemic stroke patients with intracranial atherosclerosis of posterior circulation has higher risk of one year death. One year stroke recurrence risk for patients with intracranial atherosclerosis of anterior and posterior circulation needs to be further evaluated.

[Effect of dopamine on intracerebral glutamate uptake ability in rats with minimal hepatic encephalopathy and the pathogenesis of minimal hepatic encephalopathy].

Objective: To investigate the effect of dopamine (DA) on the glutamate (Glu) uptake ability of neural cells, as well as its effect on cognitive impairment in rats with minimal hepatic encephalopathy (MHE) via related pathways. Methods: A total of 45 Sprague-Dawley rats were randomly divided into control group, MHE model group, and DA intervention model group, with 15 rats in each group. The rats in the MHE model group were given intraperitoneal injection of thioacetamide (TAA), those in DA intervention model group were given intraventricular injection of DA, and those in the control group were given intraperitoneal injection of physiological saline, with a frequency of twice a week for 8 weeks. Cerebral microdialysis was used to measure the change in the content of Glu in the brain in MHE rats and rats with DA intervention; RT-PCR and Western blotting were used to measure the relative mRNA and protein expression of trace amine-associated receptor 1 (TAAR1) and excitatory amino acid transporter 2 (EAAT2); the changes in the expression of EAAT2 and extracellular Glu level were measured after intracerebroventricular injection of TAAR1 siRNA and TAAR1 plasmid in MHE rats and rats with DA intervention. One- way analyses of variance for comparison among different groups were performed, categorical data between groups were compared using nonparametric tests. Results: Compared with the control group, the MHE model group had significant increases in the content of DA in liver tissue, plasma, and brain tissue (4.90 ± 0.13 ng/g vs 1.20 ± 0.13 ng/g, P < 0.05; 16.32 ± 1.01 pmol/ml vs 5.50 ± 0.82 pmol/ml, P < 0.05; 732.45 ± 78.85 ng/g vs 387.00 ± 23.36 ng/g, P < 0.05). There was a significant increase in the extracellular Glu level within 40-120 minutes after intracerebral injection of DA in the DA intervention model group. Compared with the control group, the MHE model group and the DA intervention model group had a significant increase in the relative protein expression of TAAR1 (3.72 ± 0.50/4.18 ± 0.43 vs 0.96 ± 0.40, both P < 0.05) and a significant reduction in the expression of EAAT2 (0.46 ± 0.16/0.51 ± 0.20 vs 0.92 ± 0.11, P = 0.013 and 0.036). Compared with the model group treated with empty vector, the MHE model group and the DA intervention model group had a significant increase in the relative protein expression of EAAT2 after TAAR1 siRNA intervention (0.86±0.142 vs 0.56 ± 0.060, P = 0.028; 0.99 ± 0.056 vs 0.43 ± 0.098, P = 0.0010) and a significant reduction in the extracellular Glu level in the brain at 60-120 minutes after injection, while after TAAR1 plasmid intervention, the MHE model group and the DA intervention model group had a significant reduction in the relative protein expression of EAAT2 (0.20 ± 0.040 vs 0.48 ± 0.08, P = 0.006; 0.24 ± 0.05 vs 0.54 ± 0.07, P = 0.004) and a significant increase in the extracellular Glu level in brain at 60-100 minutes after injection. Conclusion: DA interacts with TAAR1 in brain tissue to induce extracellular accumulation of Glu, thus leading to the disorder of the TAAR1-EAAT2 signaling pathway in brain tissue and ultimately injuring the cognitive function of MHE rats.

[Depletion of GP73 inhibits invasion and metastasis of hepatocellular carcinoma cells].

Objective: To explore the in vitro and in vivo effect of GP73 on the proliferation, invasion and metastasis in hepatocellular carcinoma. Methods: GP73 gene was knocked out using CRISPR/Cas9 gene editing system in H22 and HepG2 cells, and stable knock out strains were constructed. The knockout efficiency was measured by western blot. Colony formation assay was used to detect the effect of GP73 on long-term survival ability. Cells were then highly synchronized in G(1) phase upon treatment with cell synchronization reagents (mimosine), and the percentage of cells in G(2)/M phase at different time points was detected by flow cytometry. The invasive and metastasis abilities of hepatocellular carcinoma cells were detected by Transwell™ assay. Furthermore, the tumor formation abilities in vivo were examined using subcutaneous xenograft models. Results: The stable knock out strains of GP73 in H22 and HepG2 cells were successfully established via puromycin selection. The number of colonies of GP73 knock out groups in HepG2 and H22 cells 10 days after transfection were 400±70 and 248±60, respectively. They were significantly lower than those in the control groups (980±40 and 1 100±50, respectively; P<0.01). In addition, GP73 knockout slowed down the cell cycle progression. Moreover, the cell numbers that had migrated to the underside of the filters were 312±50 and 305±49 in the GP73 knockout groups of HepG2 and H22 cells, respectively, significantly lower than 1 540±87 and 1 270±86 in the controls (P<0.01). For transwell invasion assay, the cell number that had invaded into the underside of the filters were 230±47 and 238±54 in the GP73 knockout groups of HepG2 and H22 cells, respectively, significantly lower than 648±74 and 596±63 in the controls(P<0.01). Furthermore, the tumor volume of GP73 knockout group was (70±170) mm(3,) significantly smaller than (1 200±110)mm(3) of the control guoup (P<0.01). Conclusions: GP73 knockout decreases the proliferation, invasive and migratory abilities of HepG2 and H22 cells in vitro and in vivo. GP73 may contribute to tumorigenesis of hepatocellular carcinoma.

Preoperative serum α-fetoprotein and prognosis after hepatectomy for hepatocellular carcinoma.

BACKGROUND: While the majority of studies report that a raised serum α-fetoprotein (AFP) level before operation is associated with a high risk of recurrence and death in patients who undergo hepatectomy for hepatocellular carcinoma (HCC), results are conflicting. The aim of this study was to assess the prognostic value of AFP. METHODS: Serum AFP levels were measured in patients with hepatitis-associated HCC who underwent hepatectomy between 1995 and 2012. Kaplan-Meier and multivariable analyses were performed to identify risk factors for overall and disease-free survival. Univariable and multivariable Cox proportional hazards regression was used to evaluate the predictive value of AFP. Receiver operating characteristic (ROC) curves were generated to identify the AFP level that had the highest accuracy in discriminating between survivors and non-survivors. RESULTS: Some 376 patients with hepatitis B virus (HBV)-associated HCC were included in the study. The overall survival rate was 58·8 per cent in patients with an AFP level of 400 ng/ml or less compared with 40·4 per cent for those with a level exceeding 400 ng/ml (P = 0·001). AFP concentration above 400 ng/ml was an independent risk factor for shorter disease-free and overall survival after surgery. ROC analysis indicated that the optimal cut-off values for AFP varied for different subtypes of HCC. The sensitivity and specificity were lower with areas under the ROC curve of less than 0·600. An AFP level greater than 400 ng/ml was not sensitive enough to predict the prognosis in patients with an HCC diameter smaller than 3 cm. CONCLUSION: A serum AFP level above 400 ng/ml predicts poor overall and recurrence-free survival after hepatectomy in patients with HBV-associated HCC. AFP is not a strong prognostic marker given its poor discriminatory power, with low sensitivity and specificity.

[Technical advancement improves survival in patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving definitive radiotherapy].

OBJECTIVE: This study aimed to evaluate the impact of technical advancement of radiation therapy in patients with LA-NSCLC receiving definitive radiotherapy (RT). METHODS: Patients treated with definitive RT (≥50 Gy) between 2000 and 2010 were retrospectively reviewed. Overall survival (OS), cancer specific survival (CSS), locoregional progression-free survival (LRPFS), distant metastasis-free survival (DMFS) and progression-free survival (PFS) were calculated and compared among patients irradiated with different techniques. Radiation-induced lung injury (RILI) and esophageal injury (RIEI) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events 3.0 (NCI-CTCAE 3.0). RESULTS: A total of 946 patients were eligible for analysis, including 288 treated with two-dimensional radiotherapy (2D-RT), 209 with three-dimensional conformal radiation therapy (3D-CRT) and 449 with intensity-modulated radiation therapy (IMRT) respectively. The median follow-up time for the whole population was 84.1 months. The median OS of 2D-RT, 3D-CRT and IMRT groups were 15.8, 19.7 and 23.3 months, respectively, with the corresponding 5-year survival rate of 8.7%, 13.0% and 18.8%, respectively (P<0.001). The univariate analysis demonstrated significantly inferior OS, LRPFS, DMFS and PFS of 2D-RT than those provided by 3D-CRT or IMRT. The univariate analysis also revealed that the IMRT group had significantly loger LRPFS and a trend toward better OS and DMFS compared with 3D-CRT. Multivariate analysis showed that TNM stage, RT technique and KPS were independent factors correlated with all survival indexes. Compared with 2D-RT, the utilization of IMRT was associated with significantly improved OS, LRPFS, DMFS as well as PFS. Compared with 3D-CRT, IMRT provided superior DMFS (P=0.035), a trend approaching significance with regard to LRPFS (P=0.073) but no statistically significant improvement on OS, CSS and PFS in multivariate analysis. The incidence rates of RILI were significantly decreased in the IMRT group (29.3% vs. 26.6% vs.14.0%, P<0.001) whereas that of RIET rates were similar (34.7% vs. 29.7% vs. 35.3%, P=0.342) among the three groups. CONCLUSIONS: Radiation therapy technique is a factor affecting prognosis of LA-NSCLC patients. Advanced radiation therapy technique is associated with improved tumor control and survival, and decreased radiation-induced lung toxicity.

[An analysis and literature review of two cases of autoimmune encephalitis with GABAB receptor antibodies].

Autoimmune encephalitis with GABAB receptor antibodies has been rarely reported. Two cases of GABAB receptor antibodies encephalitis were presented here.Epilepsy was the onset symptom, followed by declined consciousness and frequent seizures. Fever was presented in the whole course of the disease. Myorhythmia of the two hands and pilomotor seizures were shown in the later course of the disease. No specificity was demonstrated in electroencephalograms and magnetic resonance imaging. Sensitive response was shown to the first-line immunotherapy.

HBx mutants differentially affect the activation of hypoxia-inducible factor-1α in hepatocellular carcinoma.

BACKGROUND: Mutations in HBx gene are frequently found in HBV-associated hepatocellular carcinoma (HCC). Activation of hypoxia-inducible factor-1α (HIF-1α) contributes to HCC development and progression. Wild-type HBx has been demonstrated to activate HIF-1α, but the effect of HBx mutations on HIF-1α has not been elucidated. METHODS: HBx mutations were identified by gene sequencing in 101 HCC tissues. Representative HBx mutants were cloned and transfected into HCC cells. Expression and activation of HIF-1α were analysed by western blot and luciferase assays, respectively. The relationship between HBx mutants and HIF-1α expression in HCC tissues was also evaluated. RESULTS: The dual mutations K130M/V131I enhanced the functionality of HBx as they upregulated the expression and transcriptional activity of HIF-1α. The C-terminal truncations and deletion mutations, however, weakened the ability of HBx to upregulate HIF-1α. Meanwhile, the C-terminus was further found to be essential for the stability and transactivation of HBx. In the HCC tissues, there was a positive association between the HBx mutants and HIF-1α expression. CONCLUSION: Different mutations of HBx exert differentiated effects on the functionality of HIF-1α, however, the overall activity of HBx mutants appears to increase the expression and transcriptional activity of HIF-1α.

Acoustic radiation force impulse elastography for non-invasive assessment of disease stage in patients with primary biliary cirrhosis: A preliminary study.

AIM: To investigate the diagnostic performance of the acoustic radiation force impulse (ARFI) elastography for the assessment of primary biliary cirrhosis (PBC) stage. MATERIALS AND METHODS: Sixty-one patients with PBC in which liver biopsy and ARFI elastography measurements were performed in the same session were included in the study. The diagnostic performance of ARFI elastography for predicting the PBC stage was determined from the area under receiver operating characteristics (AUROC) curve analysis. RESULTS: ARFI elastography correlated significantly with histological stage (r = 0.74, p < 0.001) in patients with PBC. The AUROC of ARFI elastography for predicting histological stage equal to or higher than II, III, and equal to IV were 0.83, 0.93, and 0.91, respectively. The optimal cut-off values of ARFI elastography were 1.51 m/s, 1.79 m/s, and 2.01 m/s for PBC stage equal to or higher than II, III, and equal to IV, respectively. CONCLUSION: ARFI elastography is an acceptable and powerful technique for quantitative assessment of PBC stage.