Objective:To analyze the predictive value of von Willebrand factor (vWF) for venous thromboembolism (VTE) of patients in intensive care unit (ICU) by using propensity score matching (PSM).Methods:Patients admitted to ICU of the Second Affiliated Hospital of Kunming Medical University from December 2020 to June 2022 who stayed in ICU for ≥72 hours and underwent daily bedside vascular ultrasound screening were included. Baseline data such as age, gender, primary disease, and chronic comorbidities were collected. Coagulation indexes before admission to ICU and 24 hours and 48 hours after ICU admission were collected, including prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), international normalized ratio (INR), fibrinogen (Fib), fibrin monomer (FM), vWF, D-dimer, antithrombin Ⅲ (ATⅢ), etc. Patients were divided into VTE group and non-VTE group according to whether they had VTE or not [diagnosis of VTE: patients underwent daily ultrasound screening of bedside blood vessels (both upper and lower limbs, visceral veins), and those suspected of having thrombosis were confirmed by ultrasonographer or pulmonary angiography]. Using PSM analysis method, the VTE group was used as the benchmark to conduct 1 : 1 matching of age, whether there was malignant tumor, whether there was infection, whether there was diabetes, and coagulation indicators before admission to ICU. Finally, the cases with balanced covariates between the two groups were obtained. The risk factors of VTE were analyzed by multivariate Logistic regression analysis. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of vWF in the occurrence of VTE in critically ill patients.Results:A total of 120 patients were enrolled, of which 18 (15.0%) were diagnosed with VTE within 72 hours after admission to ICU, and 102 (85.0%) were not found to have thrombus in ICU. Before PSM, there were significant differences in age, gender, proportion of malignant tumor and infection, and coagulation indexes between VTE group and non-VTE group. After PSM, 14 pairs were successfully matched, and the unbalanced covariables between the two groups reached equilibrium. Multivariate Logistic regression analysis showed that vWF was an independent risk factor for VTE at 48 hours after ICU admission in critically ill patients [odds ratio ( OR) = 1.165, 95% confidence interval (95% CI) was 1.000-1.025, P = 0.004]. ROC curve analysis showed that the area under the ROC curve (AUC) of vWF at 48 hours after ICU admission for predicting VTE was 0.782, 95% CI was 0.618-0.945, P = 0.007. When the optimal cut-off value was 312.12%, the sensitivity was 67.7% and the specificity was 93.0%. Conclusion:Dynamic monitoring of vWF is helpful to predict the occurrence of VTE in ICU patients, and vWF at 48 hours after ICU admission has certain value in predicting the occurrence of VTE.

Objective To investigate the effect of spleen on hepatic macrophages mediated activation of hepatic stellate cells(HSCs)in mice with liver fibrosis.Methods Eighteen male C57BL/6 mice were randomly divided into three groups.Mice in Group A and Group B were injected intraperitoneally with CCl4 to establish liver fibrosis mouse model,while those in Group C were injected with corn oil as normal control.Four weeks later,mice with liver fibrosis received splenectomy(Spx)or sham operation(Sham),respectively.After continuous injection for 2 weeks,liver homogenates(L-Homo)were prepared and liver cells were isolated from the three groups.Expressions of IL-1β,IL-13,TGF-β,TNF-α,PDGF-β and VEGF in the liver homogenates of the three groups were detected by Luminex multifactor analysis.The expressions of these cytokines in liver macrophages(L-Mψ)and other non-parenchymal cells of Sham and Spx mice were analyzed by Real-time quantitative PCR(RT-qPCR)and flow cytometry.Macrophage cell line RAW264.7 or bone marrow-derived macrophages(BMDMs)were treated with liver homogenates from the Sham and Spx groups.Then the differently treated RAW264.7 cells were analyzed for mRNA expressions of cytokines and glutamine metabolism-related molecules by RT-qPCR,or transwell co-cultured with hepatic stellate cell line JS1.After co-culture,the survival and extracellular matrix expression of JS1 cells were analyzed.For comparison,Student's t test(between two groups)or one-way analysis of variance(among multiple groups)were used.Results Compared with normal control group,the concentrations of IL-1β,IL-13,TGF-β and TNF-α in the L-Homo of model group were significantly increased and showed higher levels in Sham group than in Spx group.Moreover,the hepatic macrophages were indicated as the major source of these cytokines.Consistently,macrophages treated with liver homogenate of Sham mice had increased expressions of IL-1β,TGF-β and TNF-α and glutaminase(GLS).After co-culture with macrophages treated with liver homogenate of Sham group rather than Spx group,JS1 expressed higher expressions of α-SMA and collagens.Conclusion The spleen is involved in regulating the secretion of cytokines by hepatic macrophages and enhancing their ability to activate hepatic stellate cells.

Objective:To identify whether splenectomy for treatment of hypersplenism has any impact on development of hepatocellular carcinoma(HCC) among patients with liver cirrhosis and hepatitis.Methods:Patients who underwent splenectomy for hypersplenism secondary to liver cirrhosis and portal hypertension between January 2008 and December 2012 were included from seven hospitals in China, whereas patients receiving medication treatments for liver cirrhosis and portal hypertension (non-splenectomy) at the same time period among the seven hospitals were included as control groups. In the splenectomy group, all the patients received open or laparoscopic splenectomy with or without pericardial devascularization. In contrast, patients in the control group were treated conservatively for liver cirrhosis and portal hypertension with medicines (non-splenectomy) with no invasive treatments, such as transjugular intrahepatic portosystemic shunt, splenectomy or liver transplantation before HCC development. All the patients were routinely screened for HCC development with abdominal ultrasound, liver function and alpha-fetoprotein every 3 to 6 months. To minimize the selection bias, propensity score matching (PSM) was used to match the baseline data of patients among splenectomy versus non-splenectomy groups. The Kaplan-Meier method was used to calculate the overall survival and cumulative incidence of HCC development, and the Log-rank test was used to compare the survival or disease rates between the two groups. Univariate and Cox proportional hazard regression models were used to analyze the potential risk factors associated with development of HCC.Results:A total of 871 patients with liver cirrhosis and hypertension were included synchronously from 7 tertiary hospitals. Among them, 407 patients had a history of splenectomy for hypersplenism (splenectomy group), whereas 464 patients who received medical treatment but not splenectomy (non-splenectomy group). After PSM,233 pairs of patients were matched in adjusted cohorts. The cumulative incidence of HCC diagnosis at 1,3,5 and 7 years were 1%,6%,7% and 15% in the splenectomy group, which was significantly lower than 1%,6%,15% and 23% in the non-splenectomy group ( HR=0.53,95% CI:0.31 to 0.91, P=0.028). On multivariable analysis, splenectomy was independently associated with decreased risk of HCC development ( HR=0.55, 95%CI:0.32 to 0.95, P=0.031). The cumulative survival rates of all the patients at 1,3,5,and 7 years were 100%,97%,91%,86% in the splenectomy group,which was similar with that of 100%,97%,92%,84% in the non-splenectomy group ( P=0.899). In total,49 patients (12.0%) among splenectomy group and 75 patients (16.2%) in non-splenectomy group developed HCC during the study period, respectively. Compared to patients in non-splenectomy group, patients who developed HCC after splenectomy were unlikely to receive curative resection for HCC (12.2% vs. 33.3%,χ2=7.029, P=0.008). Conclusion:Splenectomy for treatment of hypersplenism may decrease the risk of HCC development among patients with liver cirrhosis and portal hypertension.

Objective:To identify whether splenectomy for treatment of hypersplenism has any impact on development of hepatocellular carcinoma(HCC) among patients with liver cirrhosis and hepatitis.Methods:Patients who underwent splenectomy for hypersplenism secondary to liver cirrhosis and portal hypertension between January 2008 and December 2012 were included from seven hospitals in China, whereas patients receiving medication treatments for liver cirrhosis and portal hypertension (non-splenectomy) at the same time period among the seven hospitals were included as control groups. In the splenectomy group, all the patients received open or laparoscopic splenectomy with or without pericardial devascularization. In contrast, patients in the control group were treated conservatively for liver cirrhosis and portal hypertension with medicines (non-splenectomy) with no invasive treatments, such as transjugular intrahepatic portosystemic shunt, splenectomy or liver transplantation before HCC development. All the patients were routinely screened for HCC development with abdominal ultrasound, liver function and alpha-fetoprotein every 3 to 6 months. To minimize the selection bias, propensity score matching (PSM) was used to match the baseline data of patients among splenectomy versus non-splenectomy groups. The Kaplan-Meier method was used to calculate the overall survival and cumulative incidence of HCC development, and the Log-rank test was used to compare the survival or disease rates between the two groups. Univariate and Cox proportional hazard regression models were used to analyze the potential risk factors associated with development of HCC.Results:A total of 871 patients with liver cirrhosis and hypertension were included synchronously from 7 tertiary hospitals. Among them, 407 patients had a history of splenectomy for hypersplenism (splenectomy group), whereas 464 patients who received medical treatment but not splenectomy (non-splenectomy group). After PSM,233 pairs of patients were matched in adjusted cohorts. The cumulative incidence of HCC diagnosis at 1,3,5 and 7 years were 1%,6%,7% and 15% in the splenectomy group, which was significantly lower than 1%,6%,15% and 23% in the non-splenectomy group ( HR=0.53,95% CI:0.31 to 0.91, P=0.028). On multivariable analysis, splenectomy was independently associated with decreased risk of HCC development ( HR=0.55, 95%CI:0.32 to 0.95, P=0.031). The cumulative survival rates of all the patients at 1,3,5,and 7 years were 100%,97%,91%,86% in the splenectomy group,which was similar with that of 100%,97%,92%,84% in the non-splenectomy group ( P=0.899). In total,49 patients (12.0%) among splenectomy group and 75 patients (16.2%) in non-splenectomy group developed HCC during the study period, respectively. Compared to patients in non-splenectomy group, patients who developed HCC after splenectomy were unlikely to receive curative resection for HCC (12.2% vs. 33.3%,χ2=7.029, P=0.008). Conclusion:Splenectomy for treatment of hypersplenism may decrease the risk of HCC development among patients with liver cirrhosis and portal hypertension.

Objective To investigate the changes of the regional homogeneity(ReHo)values of spontaneous brain activity in patients with idiopathic trigeminal neuralgia (ITN).Methods Left ITN (LITN)group (n=23)and the healthy control (HC)group (n=33)underwent resting-state functional magnetic resonance imaging(rs-fMRI)scans.The changes of ReHo values between the two groups were compared.Results Compared with HC group,LITN group yielded increased ReHo values in bilateral nucleus accumbens,bilateral caudate nucleus,right putamen, right precentral gyrus (M1),right supplementary motor area (SMA)and right anterior insula (P<0.01).Conclusion The rs-fMRI shows abnormal ReHo values of brain activity in several regions in ITN patients.The regions are related to pain processing-motion,emotion and endogenous regulation.The suggest that brain involves the developing and regulating mechanism of ITN as an importment factor.

Objective To investigate the value of MRI in analyzing relationship between compression site of the vascular compression and the facial pain area in patients with primary trigeminal neuralgia (PTN).Methods MRI data of 123 patients with unilateral PTN were retrospectively analyzed,including imaging of three-dimensional-time of flight MRA (3D TOF MRA) sequence,three-dimensional-fast imaging employing steady state acquisition sequence and contrast-enhanced 3D TOF MRA sequence.Neurovascular conflict (NVC) sites were divided into 8 sites according to the sectional anatomy of trigeminal nerve,and the relations between topography of pain and site of NVC were analyzed in 60 PTN patients with a single offending vessel and a single site of NVC.Distance (d) from the root entry point to the site of NVC,the length (L) of cisternal segment of the trigeminal nerve were both measured,and d/L was calculated in 123 patients with 206 NVC points.Results Of 60 patients with single offending vessel and single site of NVC,95.00％ (57/60) sites of NVC matched to topography of pain,5.00％ (3/60) did not,whereas NVC points with d/L≤1/4 accounted for 58.33％ (35/ 60),d/L≤1/2 accounted for 85.00％ (51/60).Among 206 NVC points,the meand was (2.50±1.35)mm,and NVC points with d/L≤1/4 accounted for 44.66％ (92/206),d/L≤1/2 accounted for 74.27％ (153/206).Conclusion MRI is helpful to detecting the offending vessels in PTN patients through judging relationship between the topography of pain and the site of NVC,as well as measuring the distance from the root entry point to the site of NVC.

Objective Toexplore the application value of diffusion tensor imaging (DTI) in evaluating evaluation offunctional changes of the in patients with primary trigeminal neuralgia caused (PTN) by neurovascular compression. Methods 40 unilateral PTN patients and 40 healthy volunteers were enrolled in ourstudy.They allAll patients underwent the general sequences and DTI ,and then to measured the ADC and FA values of the trigeminal nerves. Results (1) Compared with contralateral side (0.408 ± 0.054)and bilateral sides in control group(0.423 ± 0.057), FA value of the ipsilateral side in PTN group(0.330 ± 0.056) was significant lower (P< 0.05)compared with the contralateral side (0.408 ± 0.054) and bilateral sides in control group (0.423 ± 0.057).The ADC value of ipsilateralside (2.052 ± 0.473)× 10-3 mm2/s was significantly higher (P < 0.05) thancompared withthe contralateral side (1.541 ± 0.266) ×10-3 mm2/s and bilateral sides in control group(1.431 ± 0.308) ×10-3 mm2/s. (2) An There's a nnegative correlation was found (r = -0.613,P < 0.001) between the loss of FA and the increase of ADC (r = -0.613,P < 0.001). Conclusion DTI could be used to evaluate the changes of neuratrophy and demyelination ,so it canmight be used of in diagnosis and treatment of PTNin further way.

OBJECTIVETo investigate the efficacy and safety of antiviral treatment in patients with hepatitis C virus (HCV) infection and decompensated cirrhosis and determine the effects of virological response on long-term prognosis.

METHODSSixty-six consecutive,interferon (IFN)-na(i)ve patients with HCV infection and decompensated cirrhosis were enrolled in this prospective study. All patients were given a 48-to 72-week course of IFN plus ribavirin (RBV) combined therapy,with a low accelerating dosage regimen using either:pegylated (PEG)-IFNa-2b at 1.0-1.5 mug/kg/week,PEG-IFNa-2a at 90-180 mug,or standard IFN-a-2b at 3MU,every other day.RBV was given at 800 to 1000 mg/day. All patients were routinely monitored for adverse drug reactions and virological response.Effects of treatments on patient survival were assessed by Kaplan-Meier analysis.

RESULTSAt the end of treatment,74.2% of patients were HCV RNA-negative,with 45.5% having achieved sustained virological response and 28.8% having relapsed;the remaining 25.7% of patients showed non-virological response (NVR). Among the patients with HCV genotype 1, 65.9% achieved end-of-treatment virological response (ETVR) and 34.1% achieved SVR;among the patients with HCV genotype 2,90.9% achieved ETVR and 68.2% achieved SVR. The positive and negative predictive values of early virological response (EVR) for ETVR were 95.7% and 75.0% respectively, and for SVR were 65.2% and 100% respectively. Compared with baseline,patients who achieved ETVR had better liver function,as evidenced by changes in levels of total bilirubin,alanine aminotransferase and albumin,as well as prothrombin activity and Child-Pugh score (t =4.564,11.486,2.303,2.699,3.694 respectively, all P less than 0.05).Compared with the NVR patients, the ETVR patients had lower risk of hepatic decompensation and hepatocellular carcinoma, and had improved survival (x2=18.756,6.992,7.580, respectively, all P less than 0.05).Twelve (18.2%) patients experienced serious adverse events,with 10 requiring premature treatment withdrawal and 2 dying.

CONCLUSIONAntiviral treatment for patients with HCV infection and decompensated cirrhosis using interferon in a low accelerating dosage regimen in combination with ribavirin is feasible.Patients who achieved ETVR had significantly improved long-term prognosis.

Alanine Transaminase ; Antiviral Agents ; therapeutic use ; Carcinoma, Hepatocellular ; Drug Therapy, Combination ; Genotype ; Hepacivirus ; genetics ; Hepatitis C ; diagnosis ; drug therapy ; Humans ; Interferon-alpha ; therapeutic use ; Kaplan-Meier Estimate ; Liver Cirrhosis ; drug therapy ; virology ; Liver Neoplasms ; Polyethylene Glycols ; therapeutic use ; Prospective Studies ; Recombinant Proteins ; therapeutic use ; Ribavirin ; therapeutic use ; Treatment Outcome

ObjectiveTo investigate the effect of splenectomy on cellular immune function of patients with hepatitis C virus (HCV) related cirrhotic portal hypertension.MethodsTwelve patients with HCV-related cirrhotic portal hypertension undergoing splenectomy + pericardial devascularization in the Second Affiliated Hospital of Xi'an Jiaotong University between December 2011 and December 2013 were enrolled in this prospective study. Among the 12 patients, 4 were males and 8 were females withthe average age of (55±8) years old. Moreover, 12 healthy people were enrolled in the control group. The informed consents of all patients were obtained and the local ethical committee approval had been received. Percentage of natural killer (NK) cell, natural killer T (NKT) cell, CD4+ cell, CD8+T cell and CD4+/CD8+ ratio in peripheral blood before and 2, 6 weeks after splenectomy were observed. The comparison on different lymphocyte subsets was conducted using Wilcoxon rank-sum test.ResultsThe percentage of CD3-CD56+CD16+ NK cell 6 weeks after splenectomy was 7.7%, which was signiifcantly higher than 6.2% before splenectomy (T=1.992,P<0.05). And the percentage of CD56dim NK cell 2 and 6 weeks after splenectomy was respectively 94.9% and 96.4%, which was signiifcantly higher than 87.9%before splenectomy (T=2.747, 2.201;P<0.05). The percentage of CD56bright NK cell 2 and 6 weeks after splenectomy was respectively 3.8% and 2.4%, which was signiifcantly lower than 9.2% before splenectomy (T=2.747, 2.201;P<0.05). The percentage of CD3+CD56+ NKT cell 2 and 6 weeks after splenectomy was respectively 7.3% and 7.0%, which was significantly higher than 6.5% before splenectomy (T=2.275, 1.572;P<0.05). Percentage of CD4+ T cell 2 weeks after splenectomy was 41.7%, which was signiifcantly lower than 45.7% before splenectomy (T=3.059,P<0.05), and further decreased to 26.7% 6 weeks after splenectomy (T=2.201,P<0.05), while percentage of CD8+ T cell increased from 21.1% before splenectomy to 24.8% 2 weeks after splenectomy (T=2.432,P<0.05), and further increased to 35.3% 6 weeks after splenectomy (T=1.992,P<0.05). The CD4+/CD8+ ratio before splenectomy was 2.0 and decreased to 1.4 and 0.8 respectively 2 and 6 weeks after splenectomy (T=2.981, 1.992;P<0.05).ConclusionThe cellular immune function of patients with HCV related cirrhotic portal hypertension after splenectomy improves signiifcantly.

OBJECTIVETo predict and identify B-cell linear epitopes of hepatitis B e antigen (HBeAg).

METHODSThe B-cell linear epitopes of HBeAg were predicted using the software provided by NCBI Database and Immune Epitope Database (IEDB) and synthesized by a solid-phase method followed by conjugation with keyhole limpet hemocyanin (KLH). The KLH conjugates were used for immunization of New Zealand white rabbits, and the immune response of the rabbits was monitored by direct ELISA using a bovine serum albumin conjugate of the predicted epitopes. RESULTS Four new B-cell linear epitopes of HBeAg were identified, namely (1)MDIDPYKEFG(10), (37)LYREALESPEHCSP(50), (74)SNLEDPAS(81) and (127)RTPPAYRPPNAPIL(140). The rabbits immunized with the KLH conjugate showed an antibody titer over 1:512 000. The antisera of B-cell linear epitopes collected could specifically react with HBeAg as shown by ELISA.

CONCLUSIONFour B-cell linear epitopes of HBeAg have been confirmed using bioinformatics methods, which provides new evidence for further functional studies of HBeAg in hepatitis B.

Animals ; Computational Biology ; Epitopes, B-Lymphocyte ; immunology ; Hepatitis B e Antigens ; immunology ; Hepatitis B virus ; immunology ; Rabbits