Post-radiation survival time in hepatocellular carcinoma based on predictors for CT-determined, transarterial embolization and various other parameters

AIM: In this retrospective study of unresectable hepatocellular carcinoma (HCC), we have investigated the efficacy of CT-derived parameters, laboratory measurements, clinical assessment and associated transarterial embolization (TAE) as predictors of post-radiotherapy survival time. METHODS: Sixty-six patients diagnosed with unresectable HCC that had undergone radiotherapy at two medical university hospitals in Taipei were enrolled in the study. Using multivariant analysis, pre-treatment parameters including tumor number and CT confirmation of PVT and ascites were compared. Multivariant analysis was also used for comparison of the mean pretreatment values for laboratory measurements, including alpha-fetoprotein, direct/total bilirubin and GOT/GPT levels, and clinical history of chronic hepatitis across the three survival-time categories. The x2 was used to test the significance of the relationship between survival time and TAE procedure. The P values for the above tests were deemed statistically significant where P<0.05. RESULTS: Portal vein thrombosis (P= 0.032) and ascites (P><0.05) were negative predictors of post-radiation survival time. Low-grade liver cirrhosis (A or B), lower tumor volume and low levels of AFT, GOT/GPT, and total bilirubin were predictors of longer post-radiation survival time (P<0.05). CONCLUSION: The CT and clinical and laboratory assessment provide a reference for, and enable estimation of, probable survival times in HCC patients after radiotherapy. Tumor volume, severity of liver cirrhosis, status with respect to portal vein thrombosis and ascites and AFT, GOT/GPT and total bilirubin values were significant predictors of survival in this study.

The relationship between level of plasma D-dimer and survival time in metastatic gastric cancer patients

Objective:The principal purpose of this study was to determine the relationship between level of plasma D-dimer and survival time in metastatic gastric cancer patients.Methods:We retrospectively collected the data of plasma D-dimer in metastatic gastric cancer patients admitted in our Department (Department of Oncology,The Affiliated Changzheng Hospital,The Second Military Medical University,Shanghai,China) from October 2006 to October 2008 and analyzed the relationship between level of plasma D-dimer and survival time along with other clinicopathologic parameters.Results:A total of 82 patients were studied in our research,52 were males and 30 females,and the mean age was 57 years.The 48 cases had a normal plasma D-dimer level (<300μg/L) and 34 had a high plasma D-dimer level (≥300μg/L).In the normal and high plasma D-dimer level groups,the mean survival times were 10.9 (95% CI:9.8-12.2) months and 6.8(95% CI:4.4-7.6) months respectively,and the difference was statistically significant.Conclusion:Metastatic gastric cancer patients with high plasma D-dimer level had significantly shorter survival time than those with normal plasma D-dimer level.Level of plasma D-dimer can be referred as a potential predictor in metastatic gastric cancer patients.

Studies on the Relationship between Neuroendocrine Cellular Differentiation in Gastric Cancers and Post-operative Survival Time

OBJECTIVE To examine the ultrastructure of gastric cancer ceils by the electron microscope, in order to assess the relationship between neuroendocrine differentiation and post-operative survival time. METHODS NSE, Syn and CgA immunohistochemical labeling was conducted in 168 cases with a common-type of gastric cancer. Electron microscopy was performed in 80 cases with positive immunohistochemical labeling. These cases were followed-up for over 5 years and the post-operative survival data analyzed. RESULTS Neuroendocrine granules were found by electron microscopy in 39 cases. The rate of neuroendocrine differentiation found was 23% （39/168）, using routine diagnostic criteria and electron microscopy （REM）. The post-operative survival time of gastric cancer patients with neuroendocdne differentiation was significantly shorter （P=-0.0032） compared to those without neuroendocrine differentiation. CONCLUSION It is of significant clinical importance to determine if the neuroendocrine cells are differentiated in gastdc cancers. The gastric cancer patients with neuroendocrine differentiation have a shorter post-operative survival time and a poorer prognosis. Electron microscopy is a reliable method of providing a diagnosis.

A COMPARATIVE STUDY ON THERAPEUTIC RESPONSE AND SURVIVAL TIME OF PATIENTS WITH MULTIPLE MYELOMA TREATED WITH MODIFIED VMCP REGIMEN

Therapeutic response and survival time or 43 patients with multiple myeloma treated with modified VMCP(Vincristine,Melphalan, Cyelophosphamide and perdnisone;mVMCP)multidrug regimen are analyzed,and compared with those of 41 patients treated with VACP, M2, MP and other regimens.Therapeutic response to mVMCP regimen was better than that to other combination regimens(83. 5% VS 60.9%;P< 0.01).The median remission duration in patients responding to mVMCP was longer than that to other regimens(18.7 vs 12.2 mouths;P<0.001).But the survival time of two groups of responders was not signifficautly different(32. 5 vs 34.1 mouths; P>0.5).The prognostic significance of various pretreatment characteristics was evaluated in term of therapeutic response.The bone status and renal function had a significant inverse correlation with the survival time of patients responding to chemotherapy.Our data indicate that the patients with MM treated by mean or mVMCP regimen can obtain a better response in early treatment and maintain a longer remission duration as well as a better performance status. although the regimen can not prolong the patients survival time.

Systemic review of the robustness of randomized controlled trials for the treatment of cholangiocarcinoma in three domains: survival-inferred fragility index, restricted mean survival time, and the spin effect

Background:The vast majority of patients with cholangiocarcinoma(CC)have advanced disease at diagnosis and are candidates for palliative treatment only.The robustness of the randomized controlled trials regarding the treatment of CC are assessed.Methods:A systematic review of all randomized control trials(RCT)of treatments for both intra-and extrahepatic CC between 2010 and 2020 was performed.The survival-inferred fragility index(SIFI;the minimum number of reassignments of the best survivors between arms that would overturn the statistical outcomes)was calculated.In addition,the gain,or loss,in survival in RCTs was evaluated by the restricted mean survival time(RMST)difference.Finally,the level of spin i.e.,misrepresentation of study outcomes,was measured in inconclusive studies to assess distorted reporting strategies.Results:Out of 6,167 studies retrieved,11 could be retained for full text revision(7 with both intra-and extrahepatic CC,3 with peri-hilar CC,and 1 with peri-hilar or distal CC).Only 3 studies included resected patients(2 with both intra-and extrahepatic CC and 1 with peri-hilar or distal CC).Nine studies investigated systemic chemotherapy(including 3 after surgical resection),one study evaluated photodynamic therapy,and another investigated the use of an endoscopically inserted stent in the biliary tract.The median SIFI was−2[interquartile range(IQR):−6.25,−0.25]across all studies.Overall,the median RMST difference was 0.56 months(IQR:0.10,0.95).Finally,for inconclusive studies,the level of spin was high,moderate,and low in respectively 12.5%,25%,and 62.5% of the studies.Conclusions:RCTs of CC showed a low degree of robustness with a frequent proportion of associated spin.

Joint modeling of longitudinal proportional measurements and survival time with a cure fraction

In cancer clinical trials and other medical studies, both longitudinal measurements and data on a time to an event(survival time) are often collected from the same patients. Joint analyses of these data would improve the efficiency of the statistical inferences. We propose a new joint model for the longitudinal proportional measurements which are restricted in a finite interval and survival times with a potential cure fraction. A penalized joint likelihood is derived based on the Laplace approximation and a semiparametric procedure based on this likelihood is developed to estimate the parameters in the joint model. A simulation study is performed to evaluate the statistical properties of the proposed procedures. The proposed model is applied to data from a clinical trial on early breast cancer.

Risk evaluation of splenic hilar lymph node metastasis and survival analysis of patients with advanced gastric cancer

Background:There is no consensus regarding the influence of prophylactic no.10 lymph node(LN)dissection in patients with advanced gastric cancer(AGC).We aimed to evaluate whether patients with AGC could benefit from no.10 LN dissection and to explore the clinicopathological indicators of no.10 LN metastasis.Methods:We analyzed the data of 218 patients with AGC who underwent standard D2 lymphadenectomy(SD2;n=108)or modified D2 lymphadenectomy(MD2;n=110)between January 2017 and January 2021.In addition,we examined factors influencing no.10 LN metastasis in the SD2 group.Results:Differentiation,tumor location,and no.4 positive LNs were significantly correlated with no.10 LN metastasis(P<0.05).Borrmann classification,differentiation,depth of invasion,LN metastasis(N),and tumor size were found to correlate with survival in univariate analyses.Age,sex,extent of gastrectomy,tumor location,and extent of lymphadenectomy were not associated with survival(P>0.05).The median survival times were 72.23 and 68.56months for the SD2 andMD2 groups,respectively(P=0.635).Postoperative major morbidity and mortality rates were 37.96%and 3.70%in the SD2 group,and 23.64%and 1.82%in the MD2 group,respectively.Conclusions:Based on our findings,prophylactic no.10 lymphadenectomy may be recommended in patients with AGC who exhibit positive no.4 LN status,poor differentiation,and tumors located on the greater curvature.

Prognostic prediction models for postoperative patients with stageⅠtoⅢcolorectal cancer based on machine learning

BACKGROUND Colorectal cancer(CRC)is characterized by high heterogeneity,aggressiveness,and high morbidity and mortality rates.With machine learning(ML)algorithms,patient,tumor,and treatment features can be used to develop and validate models for predicting survival.In addition,important variables can be screened and different applications can be provided that could serve as vital references when making clinical decisions and potentially improving patient outcomes in clinical settings.AIM To construct prognostic prediction models and screen important variables for patients with stageⅠtoⅢCRC.METHODS More than 1000 postoperative CRC patients were grouped according to survival time(with cutoff values of 3 years and 5 years)and assigned to training and testing cohorts(7:3).For each 3-category survival time,predictions were made by 4 ML algorithms(all-variable and important variable-only datasets),each of which was validated via 5-fold cross-validation and bootstrap validation.Important variables were screened with multivariable regression methods.Model performance was evaluated and compared before and after variable screening with the area under the curve(AUC).SHapley Additive exPlanations(SHAP)further demonstrated the impact of important variables on model decision-making.Nomograms were constructed for practical model application.RESULTS Our ML models performed well;the model performance before and after important parameter identification was consistent,and variable screening was effective.The highest pre-and postscreening model AUCs 95%confidence intervals in the testing set were 0.87(0.81-0.92)and 0.89(0.84-0.93)for overall survival,0.75(0.69-0.82)and 0.73(0.64-0.81)for disease-free survival,0.95(0.88-1.00)and 0.88(0.75-0.97)for recurrence-free survival,and 0.76(0.47-0.95)and 0.80(0.53-0.94)for distant metastasis-free survival.Repeated cross-validation and bootstrap validation were performed in both the training and testing datasets.The SHAP values of the important variables were consistent with the clinicopathological characteristics of patients with tumors.The nomograms were created.CONCLUSION We constructed a comprehensive,high-accuracy,important variable-based ML architecture for predicting the 3-category survival times.This architecture could serve as a vital reference for managing CRC patients.

Loss of heterozygosity for chromosomes 16q in Wilms tumors predicts outcomes:A meta-analysis

BACKGROUND The research findings suggest that the prognosis of children with Wilms tumor(WT)is affected by various factors.Some scholars have indicated that loss of heterozygosity(LOH)on chromosome 16q is associated with a poor prognosis in patients with WT.AIM To further elucidate this relationship,we conducted a meta-analysis.METHODS This meta-analysis was registered in INPLASY(INPLASY2023100060).We systematically searched databases including Embase,PubMed,Web of Science,Cochrane,and Google Scholar up to May 31,2020,for randomized trials reporting any intrapartum fetal surveillance approach.The meta-analysis was performed within a frequentist framework,and the quality and network inconsistency of trials were assessed.Odds ratios and 95%CIs were calculated to report the relationship between event-free survival and 16q LOH in patients with WT.RESULTS Eleven cohort studies were included in this meta-analysis to estimate the relationship between event-free survival and 16q LOH in patients with WT(I^(2)=25%,P<0.001).As expected,16q LOH can serve as an effective predictor of eventfree survival in patients with WT(risk ratio=1.95,95%CI:1.52–2.49,P<0.001).CONCLUSION In pediatric patients with WT,there exists a partial correlation between 16q LOH and an unfavorable treatment prognosis.Clinical detection of 16q chromosome LOH warrants increased attention to the patient’s prognosis.

Study on Preservation of Boar Semen and Bacteria Contamination in Kandal Province

The breeding program is progressing steadily,with increasing the awareness among farmers regarding the its critical role in improving productivity,promoting rapid growth,enhancing disease resistance,and boosting household income.At the same time,the dissemination of AI(Artificila Insemination)technique among farmers has been active and effective.For the application of the AI,the quality of boar semen is extended in BTS(Belts Ville Thawing Solution)for more longer preservation period.The study purpose is to evaluate sperm survival time and bacterie contamination in boar semen.Six boars with different breed around 3 years old were used for this study as two Durocs,two Landraces and two Yorkshires.In evaluation sperm survival time in extender on each boar was designed by CRD(Completely Randomized Design)and calculating the survival time of spermatozoa was done after semen dilution and the sperm mobility was determined.The experimental BTS compositions are glucose,sodium bicarbonate acid,trisodium citrate,ethylenediaminetetraacetic acid,potassium chloride and distill water.In the same time,eighteen sample semen ware collected and used for detection of bacterial contamination.The results showed that the survival time of spermatozoa with its straight mobility more than 50%between the commercial BTS and BTS-KH was from 52 to 56 h.They are not significantly different(p>0.05).And the total survival time of spermatozoa was from 92 to 98 h,they are also not significantly different(p>0.05).The survival time of spermatozoa with its straight mobility more than 50%between the Yorkshire,Landrace and Duroc was 55 h 5 min,54 h 25 min and 50 h 18 min respectively.They are significantly different(p>0.05).The total survival time of spermatozoa between the commercial BTS and BTS-KH was 97 h 19 min,91 h 29 min and 92 h 26 min respectively.They are also not significantly different(p>0.05).The main bacteria isolated from the diluted semen were gram-negative bacteria,Escherichia coli 27.78%was contaminated with an average 6.4×106 CFU/mL,and the family Pseudomonaceae was 11.11%with 8.3×106 CFU/mL.In conclusion,the comparative results of the survival time of spematozoa during the breeding period(t=0.5)between the breeds and extender are similar.For bacteria contamination isolate from the semen all breeds may be due to direct and environmental factors.It is a rainy season with heavy rains that can cause infections.

5-hydroxymethyl-2-furfural prolongs survival and inhibits oxidative stress in a mouse model of forebrain ischemia

In the present study, we hypothesized that 5-hydroxymethyl-2-furfural could attenuate ischemic brain damage by reducing oxidative injury. Thus, mice were subjected to bilateral common carotid artery occlusion to establish a model of permanent forebrain ischemia. The mice were intraperitoneally injected with 5-hydroxymethyl-2-furfura130 minutes before ischemia or 5 minutes after ischemia. The survival time of mice injected with 5-hydroxymethyl-2-furfural was longer compared with untreated mice. The mice subjected to ischemia for 30 minutes and reperfusion for 5 minutes were intraperitoneally injected with 5-hydroxymethyl-2-furfural 5 minutes prior to reperfusion, which increased superoxide dismutase content and reduced malondialdehyde content, similar to the effects of Edaravone, a hydroxyl radical scavenger used for the treatment of stroke. These findings indicate that intraperitoneal injection of 5-hydroxymethyl-2-furfural can prolong the survival of mice with permanent forebrain ischemia. This outcome may be mediated by its antioxidative effects.

Construction of a clinical survival prognostic model for middle-aged and elderly patients with stage III rectal adenocarcinoma

BACKGROUND Nomograms for prognosis prediction in colorectal cancer patients are few,and prognostic indicators differ with age.AIM To construct a new nomogram survival prediction tool for middle-aged and elderly patients with stage III rectal adenocarcinoma.METHODS A total of 2773 eligible patients were divided into the training cohort(70%)and the validation cohort(30%).Optimal cutoff values were calculated using the X-tile software for continuous variables.Univariate and multivariate Cox proportional hazards regression analyses were used to determine overall survival(OS)and cancer-specific survival(CSS)-related prognostic factors.Two nomograms were successfully constructed.The discriminant and predictive ability and clinical usefulness of the model were also assessed by multiple methods of analysis.RESULTS The 95%CI in the training group was 0.719(0.690-0.749)and 0.733(0.702-0.74),while that in the validation group was 0.739(0.696-0.782)and 0.750(0.701-0.800)for the OS and CSS nomogram prediction models,respectively.In the validation group,the AUC of the three-year survival rate was 0.762 and 0.770,while the AUC of the five-year survival rate was 0.722 and 0.744 for the OS and CSS nomograms,respectively.The nomogram distinguishes all-cause mortality from cancer-specific mortality in patients with different risk grades.The time-dependent AUC and decision curve analysis showed that the nomogram had good clinical predictive ability and decision efficacy and was significantly better than the tumor-node-metastases staging system.CONCLUSION The survival prediction model constructed in this study is helpful in evaluating the prognosis of patients and can aid physicians in clinical diagnosis and treatment.

Is there utility for fluorine-18-fluorodeoxyglucose positron-emission tomography scan before surgery in breast cancer? A 15-year overall survival analysis

BACKGROUND The prognostic value of preoperative fluorine-18-fluorodeoxyglucose positronemission tomography(18 F-FDG PET)scan for determining overall survival(OS)in breast cancer(BC)patients is controversial.AIM To evaluate the OS predictive value of preoperative PET positivity after 15 years.METHODS We performed a retrospective search of the Universitair Ziekenhuis Brussel patient database for nonmetastatic patients who underwent preoperative PET between 2002-2008.PET positivity was determined by anatomical region of interest(AROI)findings for breast and axillary,sternal,and distant sites.The prognostic role of PET was examined as a qualitative binary factor(positive vs negative status)and as a continuous variable[maximum standard uptake value(SUVmax)]in multivariate survival analyses using Cox proportional hazards models.Among the 104 identified patients who received PET,36 were further analyzed for the SUVmax in the AROI.RESULTS Poor OS within the 15-year study period was predicted by PET-positive status for axillary(P=0.033),sternal(P=0.033),and combined PET-axillary/sternal(P=0.008)nodes.Poor disease-free survival was associated with PET-positive axillary status(P=0.040)and combined axillary/sternal status(P=0.023).Cox models confirmed the long-term prognostic value of combined PETaxillary/sternal status[hazard ratio(HR):3.08,95%confidence interval:1.42-6.69].SUVmax of ipsilateral breast and axilla as continuous covariates were significant predictors of long-term OS with HRs of 1.25(P=0.048)and 1.54(P=0.029),corresponding to relative increase in the risk of death of 25%and 54%per SUVmax unit,respectively.In addition,the ratio of the ipsilateral axillary SUVmax over the contralateral axillary SUVmax was the most significant OS predictor(P=0.027),with 1.94 HR,indicating a two-fold relative increase of mortality risk.CONCLUSION Preoperative PET is valuable for prediction of long-term survival.Ipsilateral axillary SUVmax ratio over the uninvolved side represents a new prognostic finding that warrants further investigation.

Survival and Its Predictors among Tuberculosis Patients on Treatment in Selected Health Centers of Addis Ababa, Ethiopia: A Retrospective Cohort Study

Tuberculosis is one of the leading causes of morbidity and mortality globally. Although different strategies have been designed and implemented to combat it, it has continuously increased in the past five years, resulting in 10 million new cases and 1.6 million deaths. This study aims to estimate survival and predictors among tuberculosis patients on treatment in selected health centers in Addis Ababa, Ethiopia. The study employed a retrospective cohort design where data were collected by reviewing medical records of tuberculosis patients who were registered from May 2016 to May 2017 on treatment in 20 selected health centers in Addis Ababa. Independent predictors were identified, and the strength of association between dependent and independent predictors was determined using the Weibull regression model. Before computing Weibull regression analysis, Cox proportional assumption, model diagnosis, and fitness were checked. The hazard ratio was calculated to indicate the strength of association. Of 371 TB patients, about 136 (36.7%) died during the treatment period. Most TB deaths occurred during the intensive phase, and the overall estimated median survival time was 157 days. In the multivariable Weibull model, age (HR = 0.98), baseline weight (HR = 0.96, P = 0.03), tuberculosis treatment phase (continuation phase, HR = 0.48), and tuberculosis type (pulmonary negative TB, HR = 19.92) were found to be independent predictors of time to death of tuberculosis patients. Finally, the study concluded that the survival time to death of the patients is high. The health care providers should give special attention and follow up for pulmonary negative and underweight TB patients.

Comparison of Cox proportional hazards model,Cox proportional hazards with time-varying coefficients model,and lognormal accelerated failure time model:Application in time to event analysis of melioidosis patients

Objective:To compare the prognostic factors of mortality among melioidosis patients between lognormal accelerated failure time(AFT),Cox proportional hazards(PH),and Cox PH with time-varying coefficient(TVC)models.Methods:A retrospective study was conducted from 2014 to 2019 among 453 patients who were admitted to Hospital Sultanah Bahiyah,Kedah and Hospital Tuanku Fauziah,Perlis in Northern Malaysia due to confirmed-cultured melioidosis.The prognostic factors of mortality from melioidosis were obtained from AFT survival analysis,and Cox’s models and the findings were compared by using the goodness of fit methods.The analyses were done by using Stata SE version 14.0.Results:A total of 242 patients(53.4%)survived.In this study,the median survival time of melioidosis patients was 30.0 days(95%CI 0.0-60.9).Six significant prognostic factors were identified in the Cox PH model and Cox PH-TVC model.In AFT survival analysis,a total of seven significant prognostic factors were identified.The results were found to be only a slight difference between the identified prognostic factors among the models.AFT survival showed better results compared to Cox's models,with the lowest Akaike information criteria and best fitted Cox-snell residuals.Conclusions:AFT survival analysis provides more reliable results and can be used as an alternative statistical analysis for determining the prognostic factors of mortality in melioidosis patients in certain situations.

An Adaptive Approach for Hazard Regression Modeling

Regression models for survival time data involve estimation of the hazard rate as a function of predictor variables and associated slope parameters. An adaptive approach is formulated for such hazard regression modeling. The hazard rate is modeled using fractional polynomials, that is, linear combinations of products of power transforms of time together with other available predictors. These fractional polynomial models are restricted to generating positive-valued hazard rates and decreasing survival times. Exponentially distributed survival times are a special case. Parameters are estimated using maximum likelihood estimation allowing for right censored survival times. Models are evaluated and compared using likelihood cross-validation (LCV) scores. LCV scores and tolerance parameters are used to control an adaptive search through alternative fractional polynomial hazard rate models to identify effective models for the underlying survival time data. These methods are demonstrated using two different survival time data sets including survival times for lung cancer patients and for multiple myeloma patients. For the lung cancer data, the hazard rate depends distinctly on time. However, controlling for cell type provides a distinct improvement while the hazard rate depends only on cell type and no longer on time. Furthermore, Cox regression is unable to identify a cell type effect. For the multiple myeloma data, the hazard rate also depends distinctly on time. Moreover, consideration of hemoglobin at diagnosis provides a distinct improvement, the hazard rate still depends distinctly on time, and hemoglobin distinctly moderates the effect of time on the hazard rate. These results indicate that adaptive hazard rate modeling can provide unique insights into survival time data.

Effects of Magnetic Field on the Quality of Chicken Semen Stored at Low Temperature

[ Objective] The study aimed to explore the effects of magnetic treatment on the quality of chicken semen stored at low temperature. [ Method] 5 ml fresh chicken semen was divided into five groups equally, each of which was diluted at the volume ratio 1：4. With the group without magnetic treatment as the control, the other four groups were magnetized for 6, 12, 24 and 48 min in the self-made magnetizer, respectively. Subsequently, all the five groups were stored at 2 -4 ℃, and the sperm motility, survival time, survival index and deformity rate were observed regularly. [ Result] Comparing with the control group, the magnetic groups showed higher sperm motilities and effective survival indices as well as lower deformity rates. The effective survival index of the group magnetized for 24 min was the highest and increased by 7.75% in con- trast to the control. [ Conclusion] Magnetic treatment can effectively enhance the quality of chicken semen stored at low temperature.

Delayed ethyl pyruvate therapy attenuates experimental severe acute pancreatitis via reduced serum high mobility group box 1 levels in rats

AIM： To investigate the effect of delayed ethyl pyruvate （EP） delivery on distant organ injury, survival time and serum high mobility group box 1 （HMGB1） levels in rats with experimental severe acute pancreatitis （SAP）. METHODS： A SAP model was induced by retrograde injection of artificial bile into the pancreatic ducts of rats. Animals were divided randomly into three groups （n = 32 in each group）： sham group, SAP group and delayed EP treatment group. The rats in the delayed EP treatment group received EP （30 mg/kg） at 12 h, 18 h and 30 h after induction of SAP. Animals were sacrificed, and samples were obtained at 24 h and 48 h after induction of SAP. Serum HMGB1, aspartate arninotransferase （AST）, alanine arninotransferase （ALT）, blood urea nitrogen （BUN）, and creatinine （Cr） levels were measured. Lung wet-to-dry-weight （W/D） ratios and histological scores were calculated to evaluate lung injury. Additional experiments were performed between SAP and delayed EP treatment groups to study the influence of EP on survival times of SAP rats. RESULTS： Delayed EP treatment significantly reduced serum HMGB1 levels, and protected against liver, renal and lung injury with reduced lung W/D ratios （8.22 ±0.42 vs 9.76 ± 0.45, P 〈 0.01）, pulmonary histological scores （7.1 ± 0.7 vs 8.4 ± 1.1, P 〈 0.01）, serum AST （667 ± 103 vs 1 368 ± 271, P 〈 0.01）, ALT （446 ± 91 vs 653 ± 98, P 〈 0.01） and Cr （1.2 ± 0.3 vs 1.8 ± 0.3, P 〈 0.01） levels. SAP rats had a median survival time of 44 h. Delayed EP treatment significantly prolonged median survival time to 72 h （P 〈 0.01）. CONCLUSION： Delayed EP therapy protects against distant organ injury and prolongs survival time via reduced serum HMGBllevels in rats with experimental SAP. EP may potentially serve as an effective new therapeutic option against the inflammatory response and multiple organ dysfunction syndrome （MODS） in SAP patients.

Ethyl pyruvate protects against experimental acute-on-chronic liver failure in rats

AIM： To investigate the protective effects of ethyl py- ruvate （EP） on acute-on-chronic liver failure （ACLF） in rats. METHODS： An ACLF model was established in rats, and animals were randomly divided into normal, mod- el and EP treatment groups. The rats in EP treatment group received EP （40 mg/kg） at 3 h, 6 h, 12 h and 24 h after induction of ACLF. Serum endotoxin, high mobility group box-1 （HMGB1）, alanine transaminase （ALT）, tumor necrosis factor-α （TNF-α）, interferon-α （IFN-γ）, interleukin （IL）-10 and IL-18 levels, changes of liver histology and HMGB1 expressions in liver tis- sues were detected at 48 h after induction of ACLF. The effects of EP on the survival of ACLF rats were also observed.RESULTS： Serum levels of endotoxin （0.394 ± 0.066 EU/mL vs 0.086±0.017 EU/mL, P 〈 0.001）, HMGB1 （35.42±10,86 μg/L vs 2.14 ± 0.27 μg/L, P 〈 0.001）, ALT （8415.87 ± 3567.54 IU/L vs 38.64 ± 8.82 IU/L, P 〈 0.001）, TNF-α （190.77 ± 12.34 ng/L vs 124.40 ± 4.12 ng/L, P 〈 0.001）, IFN-γ （715.38 ± 86.03 ng/L vs 398.66 ± 32.91 ng/L, P 〈 0.001）, IL-10 （6.85 ± 0.64 ng/L vs 3.49 ± 0.24 ng/L, P 〈 0.001） and IL-18 （85.19 ±3.49 ng/L vs 55.38 ±1.25 ng/L, P 〈 0.001） were significantly increased, and liver tissues presented se- vere pathological injury in the model group compared with the normal group, Howeverr EP administration significantly improved hepatic histopathology and re- duced the serum levels of endotoxin （0.155±0.045 EU/mL vs 0.394 ± 0.066 EU/mL vs P 〈 0.001） and in- flammatory cytokines （11.13 ± 2.58 μg/L vs 35.42 ± 10.86 μg/L for HMGB1, 3512.86 ± 972.67 IU/L vs 8415.87 ± 3567.54 IU/L for ALT, 128.55 ± 5.76 ng/L vs 190.77 ± 12.34 ng/L for TNF-α 438.16 ± 38.10 ng/L vs 715.38 ± 86.03 ng/L for IFN-γ 3.55 ± 0.36 ng/L vs 6.85 ± 0.64 ng/L for IL-10, and 60.35 ± 1.63 ng/L vs 85.19 ± 3.49 ng/L for IL-18, respectively, P 〈 0.001）, and the levels of HMGB1 in liver tissues re- gardless of treatment time after induction of ACLF. EP treatment at the four time points prolonged the me- dian survival time of ACLF rats （60 h） to 162 h, 120 h, 102 h and 78 h, respectively （χ2 = 41.17, P 〈 0.0001）. CONCLUSION： EP administration can protect against ACLF in rats, and is a potential and novel therapeutic agent for severe liver injury.

Combined MELD and blood lipid level in evaluating the prognosis of decompensated cirrhosis

AIM: To evaluate the prognostic value of the combined model for end-stage liver disease (MELD) and blood lipid level in patients with decompensated cirrhosis. METHODS: A total of 198 patients with decompensated cirrhosis were enrolled into the study. The values of triglyceride (TG), cholesterol (TC), high density lipoproteins (HDL) and low density lipoprotein (LDL) of each patient on the fi rst day of admission were retrieved from the medical records, and MELD was calculated. All the patients were followed up for 1 year. The relationship between the change of blood lipid level and the value of MELD score was studied by analysis of variance. The prognostic factors were screened by multivariate Cox proportional hazard model. Draw Kaplan-Meier survival curves were drawn. RESULTS: Forty-f ive patients died within 3 mo and 83 patients died within 1 year. The levels of TG, TC, HDL and LDL of the death group were all lower than those of the survivors. The serum TG, TC, HDL and LDL levels were lowered with the increase of the MELD score. Multivariate Cox proportional hazard model showed that MELD ≥18 and TC ≤2.8 mmol/L were independent risk factors for prognosis of decompensated cirrhosis. Survival analysis showed that MELD ≥18 combined with TC ≤ 2.8 mmol/L can clearly discriminate between the patients who would survive and die in 1 year. CONCLUSION: MELD ≥18 and TC ≤2.8 mmol/L are two important indexes to predict the prognosis of patients with decompensated cirrhosis. Their combination can effectively predict the long-term prognosis of patients with decompensated cirrhosis.