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Background/Aims@#Existing hepatocellular carcinoma (HCC) prediction models are derived mainly from pretreatment or early on-treatment parameters. We reassessed the dynamic changes in the performance of 17 HCC models in patients with chronic hepatitis B (CHB) during long-term antiviral therapy (AVT). @*Methods@#Among 987 CHB patients administered long-term entecavir therapy, 660 patients had 8 years of follow-up data. Model scores were calculated using on-treatment values at 2.5, 3, 3.5, 4, 4.5, and 5 years of AVT to predict threeyear HCC occurrence. Model performance was assessed with the area under the receiver operating curve (AUROC). The original model cutoffs to distinguish different levels of HCC risk were evaluated by the log-rank test. @*Results@#The AUROCs of the 17 HCC models varied from 0.51 to 0.78 when using on-treatment scores from years 2.5 to 5. Models with a cirrhosis variable showed numerically higher AUROCs (pooled at 0.65–0.73 for treated, untreated, or mixed treatment models) than models without (treated or mixed models: 0.61–0.68; untreated models: 0.51–0.59). Stratification into low, intermediate, and high-risk levels using the original cutoff values could no longer reflect the true HCC incidence using scores after 3.5 years of AVT for models without cirrhosis and after 4 years of AVT for models with cirrhosis. @*Conclusions@#The performance of existing HCC prediction models, especially models without the cirrhosis variable, decreased in CHB patients on long-term AVT. The optimization of existing models or the development of novel models for better HCC prediction during long-term AVT is warranted.
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Objective: Tourette syndrome (TS) is a group of childhood-onset chronic neuropsychiatric disorders characterized by tics, i.e., repetitive, sudden, and involuntary movements or vocalizations, which is often associated with various psychopathological and/or behavioral comorbidities, including attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), anxiety, depression, and sleep disorders and have a worse prognosis. The mechanism of TS is still not clear. The relationship between immune activation, neuroinflammation, and neuropsychiatric disorders has attracted much attention in the past two decades. To explore the underlying mechanism in TS, the relationship between neuroinflammation and behavioral alterations in TS rats was investigated in this study. Methods: A total of 36 Sprague-Dawley male rats were divided into three groups randomly as follows: the TS, control (CON), and drug intervention groups. The TS rat group was treated with haloperidol (Hal) (the TS + Hal group). The TS rat model was established using 3,3-iminodipropionitrile (IDPN), which is a well-known animal model of TS. The behavioral syndromes, brain tissue cytokines, like interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α), and microglial activation of the three groups were assessed. Results: The behavioral scores of rats in the TS group and the TS + Hal group were higher than those in the CON group (P < 0.05), but the scores of behavioral tests in the TS + Hal group were lower than those in the TS group (P < 0.05). The levels of IL-6 and TNF-α in the rat brain tissue were significantly higher in the TS group than in the CON group (P < 0.05), while no significant differences were found between the CON group and the TS + Hal group (P > 0.05). The microglia was significantly activated in the TS group and slightly activated in the TS + Hal group, which was considerably less than that in the TS group. Conclusion: The IDPN-induced TS rats had significant neuroinflammation in the brain, and the interaction between dopamine (DA) dysregulation and immune dysfunction may play a vital role in the pathogenic mechanisms of TS.
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The papain-like protease (PLpro) in coronavirus is one of key cysteine proteases responsible for the proteolytic processing of viral polyproteins, and plays an important role in dysregulation of host immune response. PLpro is a promising therapeutic target with a major challenge in inhibitor design due to the restricted S1/S2 sites for two consecutive glycine of substrates. Here we reported the discovery of two activators of the SARS-CoV-2 PLpro from a biochemical screening, and the identification of the unique residue, C270, as an allosteric and covalent regulation site for the activators. This site was also specifically modified by glutathione oxidized, resulting in the S-glutathionylation and activation of the protease. Furthermore, one compound was found to allosterically inhibit the protease by covalent binding to this crucial site. Together, these results elucidated an unrevealed molecular mechanism for allosteric modulation of the proteases activity, and provided a new strategy for discovery of allosteric inhibitors of the SARS-CoV-2 PLpro.
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Objective:To observe the clinical effect of Perampanel on the add-on therapy in children with drug-resistant epilepsy.Methods:Clinical data of children with drug-resistant epilepsy treated with add-on therapy of Perampanel in the Department of Pediatrics, Fujian Medical University Union Hospital from January to June 2020 were retrospectively analyzed, aiming to assess the therapeutic efficacy of Perampanel on the add-on therapy of drug-resistant epilepsy.The self-control effective rate of Perampanel before and after treatment were counted.Results:A total of 20 cases of 2-12 year-old children with drug-resistant epilepsy were collected, including 14 males and 6 females.Their mean age, age of onset and course of disease were (5.82±2.39) years, (3.41±1.96) years and (2.40±1.48) years, respectively.Among them, 1 case had simple partial seizures, 7 cases had complex partial seizures, 1 case had generalized seizures and 5 cases had epilepsy syndromes, there were 6 cases with undetermined seizure attack.After 3-month add-on therapy of Perampanel, 4 cases of children with drug-resistant epilepsy were seizure-free, 8 cases had the reduced frequency of seizure for 50% or more, 2 cases had the reduced duration of seizure, 1 case had the reduced severity of seizure, while 4 cases did not respond to perampanel and 1 case was aggravated.Based on the criteria of reduced frequency of seizure for more than 50%, the therapeutic efficacy of add-on therapy of Perampanel achieved 60% in children with drug-resistant epilepsy.Conclusions:The third generation of anti-seizure medication Perampanel can effectively reduce the frequency of seizure, especially in the elder children and those with certain epilepsy syndromes.
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Objective:To investigate the correlation of OCA2 gene rs4778137 single nucleotide polymorphism with the prognosis of early breast cancer patients receiving epirubicin-based regimen chemotherapy.Methods:The data of 152 patients with early breast cancer who received epirubicin combined with cyclophosphamide and docetaxel (EC-T regimen) chemotherapy in the First People's Hospital of Ziyang from April 2010 to January 2013 were retrospectively analyzed. OCA2 gene rs4778137 single nucleotide polymorphism of peripheral venous blood before chemotherapy was detected. The follow-up was up to April 2017, recurrence and disease-free survival (DFS) were analyzed. DFS of patients with different rs4778137 locus genotype in patients with different estrogen receptor (ER)/progesterone receptor (PR) expressions, human epithelial factor receptor 2 (HER2) expressions and Ki-67 positive index were analyzed.Results:The median follow-up time was 60 months (28-80 months). There were 2 cases of lost follow-up and 26 cases of recurrence. Among 150 patients with follow-up results, 68 cases (45.33%) of rs4778137 genotype were CC genotype, 47 cases (31.33%) of GC genotype and 35 cases (23.33%) of GG genotype. There were significant differences in N staging, HER2 expression and ER/PR expression among patients with or without recurrence ( χ2 value was 5.79, 6.08 and 6.05; P value was 0.016, 0.014 and 0.014, respectively). The 5-year DFS rate of 150 breast cancer patients was 82.2%, and there was no significant difference in DFS among patients with different rs4778137 locus genotype ( χ2 = 2.35, P = 0.167). Cox regression analysis showed that N staging and ER/PR expression were independent influencing factors of DFS in breast cancer patients (all P < 0.05). Among 71 ER/PR-negative patients, there was a statistically significant difference in DFS of patients with different rs4778137 locus genotype ( χ2 = 6.52, P = 0.030). Among 79 ER/PR-positive patients, 60 HER2-positive patients and 90 HER2-negative patients, 118 cases with Ki-67 positive index >14% and 32 cases with Ki-67 positive index≤14%, there were no statistically significant differences in DFS of patients with different rs4778137 locus genotype (all P > 0.05). Conclusions:The DFS of ER/PR-negative patients with early breast cancer who received epirubicin-based regimen chemotherapy is correlated with OCA2 gene rs4778137 single nucleotide polymorphism. Patients with GG genotype at rs4778137 locus have better prognosis.
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The clinical data of patients with hepatocellular carcinoma who underwent anatomical hepatectomy at the Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University from June 2021 to January 2022 were retrospectively analyzed. Of 4 patients, there were 3 males and 1 female, aged (52.0±3.7) years. These patient underwent anatomical hepatectomy using the " target territory hepatic artery dye-injection" method. There were 2 patients with right hemi liver tumors with portal vein tumor thrombus, and 1 patient with a right anterior section tumor which involved the ventral segment of right anterior branch of portal vein. One patient had a left hemi liver tumor with portal vein tumor thrombus. The surgical operations were right hemihepatectomy combined with thrombectomy of portal vein in 2 patients, right anterior sectionectomy in 1 patient, and left hemihepatectomy combined with thrombectomy of portal vein in 1 patient. There were no postoperative complications including bile fistula or bleeding. The "Target territory hepatic artery dye-injection" method could be used in appropriate by selected patients.
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ObjectiveTo investigate the association of liver stiffness measurement (LSM) and serum biochemical parameters with hepatic steatosis, liver inflammation, and liver fibrosis in patients with nonalcoholic steatohepatitis (NASH). MethodsA total of 520 patients with NASH who were treated in The Fifth Medical Center of Chinese PLA General Hospital from January 2007 to December 2018 were enrolled, and according to body mass index (BMI) with a cut-off value of 28 kg/m2, the patients were divided into obese group with 151 patients and non-obese group with 369 patients. All patients underwent liver biopsy, and LSM was measured within 3 days before biopsy. Serum biochemical parameters and general clinical data were collected before liver biopsy, and the noninvasive indices aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 (FIB-4) were calculated. The t-test was used for comparison of normally distributed continuous between groups, the nonparametric Mann-Whitney U test was used for comparison of non-normally distributed continuous between groups; the chi-square test was used for comparison of categorical data between groups. A Spearman rank correlation analysis was also performed. ResultsAlanine aminotransferase (ALT), aspartate aminotransferase, LSM, controlled attenuation parameter (CAP), spleen length, and APRI gradually increased with the increase in BMI (all P＜0.05). The Spearman correlation analysis showed that LSM, ALT, BMI, and CAP were positively correlated with the degree of hepatic steatosis (r=0.263, 0.327, 0.184, and 0.452, all P＜0.05); LSM, ALT, and CAP were positively correlated with the degree of liver inflammation (r=0.357, 0.278, and 0.121, all P＜0.05); LSM, ALT, BMI, and CAP were positively correlated with the degree of liver fibrosis (r=0.500, 0.216, 0.248, and 0.101, all P＜0.05); age was negatively correlated with the degree of hepatic steatosis, liver inflammation, and liver fibrosis (r=-0.344, -0.129, and -0.163, all P＜0.05). ConclusionLSM, CAP, ALT, and age are significantly correlated with the degree of liver inflammation, liver fibrosis, and hepatic steatosis in NASH patients, and therefore, they can be used in noninvasive diagnostic and predictive models to access the severity of liver injury.
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Objective:To analyze the influencing factors of prognosis of early mixed signet ring cell carcinoma (SRCC) of the stomach with signet ring cell ratio less than 50%.Methods:The clinical data of 110 patients with SRCC who underwent radical resection of gastric cancer in the First People's Hospital of Ziyang from January 2014 to December 2016 were retrospectively analyzed. The postoperative pathology was confirmed as mixed SRCC of the stomach with signet ring cell ratio less than 50%. The patients were followed up, and the end point of the follow-up was all-cause death. The prognostic influencing factors of SRCC patients were analyzed.Results:The median follow-up time was 32.5 months (0.9-70.0 months), with the median overall survival (OS) time of 40.0 months (7.0-61.0 months) and the 3-year OS rate of 46.5%. Kaplan-Meier survival analysis showed that the 3-year OS rate of age ≥60 years, male, upper stomach, tumor diameter ≥5 cm, invasion of the gastric wall, lymph node metastasis, and vascular invasion of mixed SRCC of the stomach patients was 34.3%, 31.1%, 30.0%, 33.3%, 40.7%, 28.9%, 37.5%, respectively, which was all lower than that of those with age <60 years old, female, lower stomach, tumor diameter <5 cm, non-invasive whole stomach wall, no lymph node metastasis, no vascular invasion (57.6%, 57.5%, 52.9%, 57.6%, 56.7%, 74.6%, 62.3%), and there was no statistically significant difference (all P < 0.05). Cox multivariate results showed that age ≥60 years old ( OR = 1.225, 95% CI 1.089-3.481, P = 0.003), lymph node metastasis ( OR = 1.077, 95% CI 1.059-2.674, P = 0.034), invasion of the whole stomach wall ( OR = 1.342, 95% CI 1.117-7.225, P = 0.002), and vascular invasion ( OR = 1.104, 95% CI 1.087-2.541, P = 0.018) were independent factors affecting OS of mixed SRCC of the stomach. Conclusion:Mixed SRCC of the stomach patients with signet ring cell ratio less than 50% featured by advanced age, lymph node metastasis, invasion of the full thickness of the stomach wall, and vascular invasion have a poor prognosis.
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Hepatitis C virus (HCV) is one of leading causes for chronic liver diseases, the treatment area has been changed rapidly since direct acting antiviral agents (DAAs) were approved to treat patients with chronic HCV infection. To cure hepatitis in 2030 is the goal set by World Health Organization. However, globally, especially in China, there are still many difficulties needing to be resolved on the cure road of chronic hepatitis C, such as large patient population, high percentage of untreated patients, nonstandard DAA treatment, low efficacy of special groups, and resistance-associated variants in baseline, etc. This comment will focus on the new demands for HCV related clinical examinations for DAA treatment, so as to improve the treatment effectiveness and to help achieve the goal of eliminating viral hepatitis .
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Objective To investigate the appropriate age of primary and secondary school students for cardiopulmonary resuscitation (CPR) training.Methods A total of 437 students aged 9-15 years at 3 to 6 grade in the primary schools or 1 to 2 grade in the secondary schools were selected from 2 Yuyao primary and secondary schools by stratified random sampling between March 2017 and January 2018.The numbers of students with the age of 9,10,11,12,13,14 and 15 y were 61,62,66,64,63,63 and 58,respectively.All students received chest compression training provided by Yuyao emergency department People's Hospital according to the 2015 Cardiopulmonary Resuscitation Guidelines.The training included 30 min theoretic teaching and 6 min practice in the simulator.The quality of chest compression performed by students was assessed;the depth,rate,position and retention of chest compression were recorded.Results The mean depth of chest compression in the students aged 9-15 years was 3.8,4.1,4.6,5.1,5.2,5.6 and 5.6 cm,respectively;the accuracy rate was 24.6％(14/61),25.8％ (16/62),50.2％ (33/66),70.5％ (45/64),79.4％(50/63),88.9％(56/63) and 91.4(53/58),respectively.Compared with the students aged 9-11 years,the mean depth of chest compression was significantly increased and accuracy rate was significantly improved in the students aged 12-15 years (Compared with 9-y students,t=-8.936,-9.502,-10.640 and-11.370;x2=35.019,47.599,63.013 and 65.671;compared with 10-y students,t=-6.927,-8.179,-10.70 and-11.047;x2=24.977,35.967,50.916 and 52.727;compared with 1 1-y students,t=-3.095,-4.177,-6.785 and-6.995;x2=5.586,12.114,22.786 and 24.870;all P＜0.05).The mean rate of chest compression was 110-116/min and its accuracy rate was 86.4％-95.2％;the accuracy rate of chest compression position was 90.9％-96.8％ in all students,there were no significant differences among the 7 groups.The mean retention rate of chest compression in the 7 groups was 81.3％(122/150),67.3％(101/150),64.7％ (94/150),48.0％(72/150),48.7％(73/150),33.3％(50/150) and 27.3％(41/150),respectively.Compared with the students aged 9-11 years,the mean retention rate of chest compression was significantly decreased in the students aged 12-15 years (compared with the 9-y students,x2=36.472,35.179,70.64 and 119.92;compared with 10-y students,x2=11.483,10.728,34.682 and 72.150;compared with 11-y students,x2=6.528,5.927,25.855 and 59.11;all P＜0.05).Correlation analysis showed that the depth (r=0.96,0.89,0.91 and 0.86;P＜0.01) and retention rate (r=-0.99,-0.90,-0.93 and-0.86;all P＜0.01) of chest compression were significantly associated with the age,body weight,height and body mass index of students.Conclusion The students with an age of 12 years or more are able to effectively perform chest compression;thus,12 years and above might be the appropriate age for CPR training.
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Objective To investigate the effects of the third-generation mechanical chest compressor on outcomes of cardiopulmonary resuscitation in patients with out-of-hospital cardiac arrest.Methods The patients with out-of-hospital cardiac arrest from October 2015 to September 2017 in the Yuyao peoples' hospital were included and divided randomly into 2 groups:manual chest compression group and mechanical chest compression group.The duration of resuscitation,the rate of restoration of spontaneous circulation (ROSC),4-h survival rate and the rate of survival getting to hospital discharge with favorable neurological status of two groups were analyzed.Results A total of 95 patients with out-of-hospital cardiac arrest were included.The rate of ROSC and 4-h survival was significantly increased in the mechanical chest compression group compared with the manual chest compression group (P＜0.05).There was no remarkable difference in the duration of resuscitation and the rate of survival getting to hospital discharge with favorable neurological status between 2 groups.Conclusions The thirdgeneration mechanical chest compressor significantly improves the rate of ROSC and the shout-term survival in patients with out-of-hospital cardiac arrest.
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Objective To evaluate the effectiveness and safety of direct-acting antiviral agents (DAA) treatment in Chinese chronic hepatitis C (CHC) patients with genotype (GT) 1b HCV infection in a real world setting .Methods The consecutive GT1b CHC Chinese patients treated with sofosbuvir (SOF) plus daclatasvir (DCV) (n＝62) or SOF plus ledipasvir (LDV) (n＝171) were enrolled from July 2014 to December 2016 at 302 Military Hospital of China .The treatment duration for all the patients was 12 weeks .All the clinical parameters were measured at baseline and then 4-weekly till 12 weeks after the end-of-treatment (EOT ).Baseline clinical characteristics ,treatment efficacy ,safety and tolerance were compared .Serum HCV RNA concentration was detected by means of COBAS TaqMan assay with a lower detection limit of 15 IU/mL ,and liver stiffness was measured using FibroScan?.Sustained virologic response (SVR) was defined as HCV RNA under the lower limit of quantification 12 weeks after EOT (SVR12).Students′t-test ,pearson χ2 test ,Spearman rank correlation analysis and Fisher exact test were used for comparison between groups when appropriate .Results Among 233 patients ,173 cases had baseline HCV RNA level ≥ 6 .0 lg IU/mL and 97 cases hade liver stiffness measurement (LSM )≥17.5 kPa.The baseline liver inflamation ,liver fibrosis ,and HCV RNA load of patients in the two groups were not significantly different (all P＞0 .05).The HCV RNA of all the 233 patients was undetectable at the end of 12-week treatment ,while 2 patients relapsed after 12 weeks of EOT with the overall SVR12 of 99.1% .HCV RNA decline was significantly faster in patients with lower LSM than those with higher LSM (ρ＝0 .233 ,P＝0 .001) ,and SVR12 was higher in those with lower LSM .In terms of other clinical characteristics of SOF+DCV and SOF+LVD groups ,alanine transaminase declined from (68 .0 ± 60 .1) and (70 .1 ± 56 .1) U/L to (21 .1 ± 10 .9) U/L and (15 .3 ± 9 .5) U/L ,respectively ,total bilirubin declined from (21 .3 ± 17 .3) and (18 .2 ± 14 .0) μmol/L to (13 .2 ± 6 .7) and (10 .2 ± 4 .6) μmol/L , respectively ,AFP declined from 19 .6 (10 .6 ,62 .3) and 15 .0 (12 .0 ,25 .0) μg/L to 6 .5(4 .5 ,18 .7) and 7 .8(5 .3 ,15 .4) μg/L ,respectively ,LSM declined from 17 .6 (8 .9 ,25 .4) and 15 .7 (7 .8 ,23 .9) kPa to 13.9(6 .5 ,21 .4) and 9 .1(5 .6 ,19 .9) kPa ,respectively ,serum album elevated form (37 .5 ± 5 .8) and (38 .7 ± 5 .5) g/L to (41 .3 ± 4 .7) and (42 .8 ± 5 .1) g/L ,respectively ,platelet elevated from (120.9 ± 78 . 2)×109/L and (136 .6 ± 65 .8 )× 109/L to (139 .5 ± 71.8 )× 109/L and (149 .7 ± 71.4 )× 109/L , respectively .Reports of adverse events were low in both groups .Conclusions Both SOF + DCV and SOF/LDV therapy are highly effective with ＞ 98% of SVR12 and reduce LSM value significantly with good safety for CHC GT1b Chinese patients .
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Acute myeloid leukemia (AML),the most common disease in acute leukemia,is a highly heterogeneous invasive hematological disease.The t(8;21)(q22;q22) translocation is the most common chromosomal translocation in AML,generating AML1-ETO fusion gene and encoding AML1-ETO fusion protein.This article summarizes the two-hit hypothesis in AML occurrence,the pathogenesis of t(8;21)AML,all features involved in t(8;21)AML,and the function of the components in AML1-ETO fusion protein,providing important basic information for the treatment and prognosis of t(8;21)AML.Meanwhile,this article also summarizes the progress of next generation sequencing technique in leukemia,providing a new technique for the accurate therapy of (8;21)AML.
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Objective To analyze the virulence genes expression and drug resistance situation of type three secretion system (TTSS) of pseudomonas aeruginosa in Zhongshan area to provide a basis for clinical anti-infection treatment .Methods Seventy-six clinically isolated strains of Pseudomonas aeruginosa were collected from the Zhongshan Municipal People′s Hospital from July to September 2016 .Four virulence genes exoU ,exoS ,exoT and exoY were isolated from the strains by PCR .The Vitek2 Compact au-tomatic microbiological identification instrument was used to detect the sensitivity of antibacterial drugs .The enumeration data were processed with chi-square test .Results The detection rates of gene exoS and exoY were highest ,which were 52 .6% (40/76) and 63 .2% (48/76) respectively ;genotype exoU(-)exoS(+ )exoT (-)exoY(+ ) were predominant and accounted for 59 .26% .The positive rates of 4 virulence genes had no statistical difference between the multiple resistant and non-multiple resistant strains of pseudomonas aeruginosa .The resistance rates in the TTSS positive group to 13 kinds of drugs were commonly lower than those in the TTSS negative group ,the difference was statistically significant .Conclusion The geographic difference exists in virulence genes carrier of pseudomonas aeruginosa .The virulence genes carrying situation in both the multiple resistant and non-multiple resistant strains of pseudomonas aeruginosa is similar .
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Objective@#To investigate the methods for qualitative pathological assessment of dynamic changes in liver fibrosis/cirrhosis after antiviral therapy in patients with chronic hepatitis B (CHB), since antiviral therapy can partially reverse liver fibrosis and cirrhosis caused by hepatitis B and semi-quantitative, rather than qualitative, pathological assessment is often used for the research on liver fibrosis regression.@*Methods@#Previously untreated CHB patients with liver fibrosis and cirrhosis were enrolled, and liver biopsy was performed before treatment and at 78 weeks after the antiviral therapy based on entecavir. The follow-up assessment was performed once every half a year. Based on the proportion of different types of fibrous septum, we put forward the new qualitative criteria called P-I-R classification (predominantly progressive, predominantly regressive, and indeterminate) for evaluating dynamic changes in liver fibrosis. This classification or Ishak fibrosis stage was used to evaluate the change in liver fibrosis after treatment and Ishak liver inflammation score was used to evaluate the change in liver inflammation after treatment.@*Results@#A total of 112 CHB patients who underwent liver biopsy before and after treatment were enrolled, and among these patients, 71 with an Ishak stage of ≥3 and qualified results of live biopsy were included in the final analysis. Based on the P-I-R classification, 58% (41/71) were classified as predominantly progressive, 29% (21/71) were classified as indeterminate, and 13% (9/71) were classified as predominantly regressive; there were no significant differences between the three groups in alanine aminotransferase, aspartate aminotransferase, albumin, HBeAg positive rate, HBV DNA, and liver stiffness (P < 0.05). After treatment, the proportion of predominantly progressive, indeterminate, or predominantly regressive patients changed to 11% (8/71), 11% (8/71), and 78% (55/71), respectively. Among the 35 patients who had no change in Ishak stage after treatment, 72% (25/35) were classified as predominantly regressive and had certain reductions in the Laennec score, percentage of collagen area, and liver stiffness.@*Conclusion@#This new P-I-R classification can be used to assess the dynamic changes in liver fibrosis after antiviral therapy in CHB patients.
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Objective To investigate the effects of limb ischemic post-conditioning (LIpostC) alone or its combination with therapeutic hypothermia (TH) on systemic inflammatory response and lung injury after cardiac arrest (CA) and resuscitation. Methods Twenty-one healthy male pigs weighing (37±2) kg were randomly divided into 3 groups (n = 7 each): control group, LIpostC group, and LIpostC+TH group. The animal model was established by 10 minutes of untreated CA and then 5 minutes of cardiopulmonary resuscitation (CPR).Coincident with the start of CPR, LIpostC was induced by four cycles of 5 minutes of limb ischemia followed by 5 minutes of reperfusion in the LIpostC and LIpostC+TH groups. After successful resuscitation, TH was implemented by surface cooling to reach a temperature of 32-34℃ until 4 hours post-resuscitation, followed by a re-warming rate of 1 ℃/h for 4 hours in the LIpostC+TH group. Normal temperature was maintained in the control and LIpostC groups. The resuscitation outcomes in each group were recorded during CPR. At 15 minutes prior to CA (baseline) and during 4 hours post-resuscitation, the level of arterial lactate was measured and PaO2/FiO2 was calculated, and extra-vascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI) were measured meanwhile by a PiCCO monitor. At 15 minutes prior to CA (baseline) and during 24 hours post-resuscitation, the levels of serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were measured by enzyme linked immunosorbent assay (ELISA). Results Six animals in each group were successfully resuscitated. Coronary perfusion pressure (CPP), duration of resuscitation, number of shocks and epinephrine dosage during CPR were not statistically significant among the three groups. The baseline of arterial lactate, PaO2/FiO2, EVLWI, PVPI and cytokines prior to CA were also not statistically significant among the three groups. The levels of serum TNF-α and IL-6 after resuscitation were gradually increased in all the three groups; however, the values of TNF-αand IL-6 were significantly lower in the LIpostC and LIpostC+TH groups than that in the control group, and they were further decreased in the LIpostC+TH group when compared to the LIpostC group [TNF-α (ng/L): 305±22 vs. 343±26 at 4 hours, 350±29 vs. 389±18 at 24 hours; IL-6 (ng/L): 239±14 vs. 263±19 at 24 hours, all P < 0.05]. The levels of lactate reached the peak at 2 hours post-resuscitation and then gradually decreased in all the three groups; it finally returned to the baseline in the LIpostC and LIpostC+TH groups, which was markedly lower than that in the control group (mmol/L: 1.4±0.7, 1.2±0.3 vs. 3.1±1.7, both P < 0.05). During 4 hours post-resuscitation, PaO2/FiO2 was significantly higher and EVLWI and PVPI were markedly lower in the LIpostC and LIpostC+TH groups than that in the control group; additionally, PaO2/FiO2 and EVLWI were further improved in the LIpostC+TH group than the LIpostC group [4-hour PaO2/FiO2 (mmHg, 1 mmHg = 0.133 kPa): 391±26 vs. 361±20; 4-hour EVLWI (mL/kg): 10.1±1.5 vs. 12.1±1.2, both P < 0.05]. Conclusion LIpostC can be used to alleviate systemic inflammatory response and lung injury after porcine CA and CPR, and its combination with TH further enhanced its protective effects.
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Objective To establish a human HepG2 cell growth model under the low oxygen environment induced by cobalt chloride in order to observe the impacts of human HepG2 cell proliferation,cellular cycles and apoptosis,namely cellular growth conditions,under the low oxygen environment induced by cobalt chloride with different concentrations and to study the HepG2 cell growth mechanism under the low oxygen environment induced by cobalt chloride.Methods The human HepG2 cells in the logarithmic phase were randomized grouping as control group and CoCl2 experimental group with different concentrations (50 μm/L,100 μm/L,150 μm/L and 200 μm/L).① HepG2 cell proliferation was tested by MTT assay to calculate cell's suppression rate and draw HepG2 cell growth inhibition curves.② The move ability of HepG2 cells was observed by scratch test.③ The cellular apoptosis and periodic changes were detected using the flow cytometer Annexin-V FITC/PI double-staining and PI single staining methods.④HepG2 cell's Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and Bcl-2 protein expression were detected by Western Blot.Results ① The test results obtained via MTT assay showed that CoCl2 suppressed the human HepG2 cell proliferation within a certain amount of time and concentration and presented a time-dose dependent relation.② Scratch damage trial suggested that the cobalt chloride suppressed the HepG2 cell migration and wound repair capacity and presented a concentration dependent relation.③ Flow cytometer' s test results revealed that the apoptosis rates (％) in control group and experimental group with different concentrations (50 μm/L,100 μm/L,150 μm/L and 200 μm/L) were 3.42,7.74,13.07,20.56,28.53 and 44.45 (P ＜0.05),respectively.The apoptosis rate of the experimental group was significantly increased compared with the control group,as well as showing a concentration dependency.The results of cellular cycles revealed that the cobalt chloride significantly suppressed the HepG2 cell's periodic changes along with increases of concentration,as well as blocked the cell cycle staying in phase G1,thereby suppressing cell proliferation.④Western Blot test:Compared with the control group,the Bcl-2 protein expression was significantly decreased in the experimental group after treatment of cobalt chloride with different concentrations.Conclusion Within a certain range,CoC12-indiuced low oxygen environment can suppress the human HepG2 cell proliferation and healing migration capacity,induce apoptosis and present a time-dose dependent relation.The mechanism is likely associated with decreases of Bcl-2 protein expression.
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Objective To evaluate the effectiveness of regional electrocardiographic consultation network for primary medical institutions.Methods A distance electrocardiographic ( ECG ) consultation center was established in Yuyao People′s Hospital in September 2012, which was connected to 56 regional primary medical through internet.The online consultation was provided by ECG specialists in the center for general practitioners in regional primary health care institutions.Additionally, the ECG training course was also conducted monthly for general practitioners.The 2-year data of ECG consultation were retrospectively reviewed and the effectiveness of the consultation network was evaluated.Results During the past two years, 86 593 electrocardiograms were uploaded by primary medical institutions, in which 3 976 were required for consultation. The monthly number of electrocardiograms sent by general practitioners was increased from 3 269 ±290 in the first year to 3 947 ±376 in the second year ( P<0.01 ) .However, the requirements of ECG consultation were not significantly different between two years.Compared to the first year, the rates of consultation requirements, misdiagnosis and missed diagnosis for ECGs of atrial and ventricular premature beats, atrial fibrillation, supraventricular tachycardia, left and right bundle branch blocks,ⅠandⅡdegree atrioventricular blocks and myocardial infarction were significantly decreased ( all P<0.05) in the second year;meanwhile there was a tendency towards the reduction for ECGs of atrial flutter and Ⅲ degree atrioventricular block in the second year.Conclusion The regional electrocardiographic consultation network is effective to improve the capability of primary medical institutions in electrocardiographic diagnosis.
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Objective To investigate the clinical application of Glissonean pedicle transection method in hepatocellular carcinoma. Methods We analyzed the clinical data of 232 cases of hepatocellular carcinoma underwent hepatic resection in our department from April 2009 to April 2013. Eighty-nine cases underwent hepatic resection by Glissonean pedicle transection method, and 143 cases underwent Pringle maneuver. Results There was no significant differences in the operation time and blood loss between the two groups (P > 0.05). However, the postoperative hospital stay time and the postoperative complications in group A were better than those in group B(P0.05). Conclusion Glissonean pedicle transection method has many advantages including effectively preventing the intraoperative bleeding, maximally reserving the remaining of liver function, decreasing the rate of tumor spread and metastasis. Meanwhile, it is a safe and effective technique for hepatectomy without dissection of the hepatic artery, portal vein and bile duct in the hepatoduodenal ligament.
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Objective To evaluate the efficacy of pegylated interferon ( PegIFN ) α-2a plus ribavirin ( RBV) therapy for chronic hepatitis C ( CHC) in non-responders, and to investigate the related influencing factors.Methods A prospective, open, multicenter and randomized study was conducted.A total of 81 CHC non-responders were recruited from 10 clinical centers during February 2009 to November 2011.Patients were randomly assigned into two groups:group A (n=37) was given PegIFNα-2a plus RBV treatment for 72 weeks and group B (n=44) was given PegIFNα-2a plus RBV treatment for 96 weeks.Both groups were followed up for 24 weeks after treatment.Virological responses in two groups were observed, and treatment efficacies among patients with different genotypes, and among those with different previous treatment were compared.SAS software was used for statistical analysis.Results Fifty-two patients ( 28 from group A and 24 from group B) completed the study in total.The rates of rapid virological response ( RVR) , complete early virological response ( cEVR ) , end of treatment viral response ( ETVR ) and sustained virological response (SVR) in group A were 25.0% (7/28), 60.7% (17/28), 67.9%(19/28) and 60.7%(17/28), respectively; while those in the group B were 41.7% (10/24), 70.8%(17/24), 70.8%(17/24) and 70.8% (17/24), respectively; and there were no significant differences between two groups (P>0.05).SVR was observed in 82.9%(29/35) of patients with CC genotype of IL-28B, which was higher than that in patients with other genotypes ( 3/13 ) , and the difference was of statistical significance (P0.05).The rates of RVR, cEVR, ETVR and SVR in patients who were previously treated with IFN were 36.4%(12/33), 81.8%(27/33), 81.8%(27/33) and 75.8%(25/33), and the rates of cEVR, ETVR and SVR were higher than those in patients who were previously treated with PegIFN (P0.05).Adverse events occurred in 38 patients (46.9%), but no severe ones were observed. Conclusion The efficacy of PegIFNα-2a plus RBV therapy for CHC in non-responders is satisfactory, which may influenced by IL-28B genotypes and previous treatment.
