Objective To investigate the value of interleukin-6 (IL-6) combined with Model for End-stage Liver Disease (MELD) score in predicting the prognosis of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (HBV-ACLF). Methods A total of 86 patients with HBV-ACLF who were hospitalized in The First Affiliated Hospital of Soochow University from January 2015 to December 2018 were enrolled, and according to their survival status after follow-up for 90 days, they were divided into death group with 50 patients and survival group with 36 patients. ELISA was used to measure the serum level of IL-6, and a statistical analysis was performed for general information. The t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. A Pearson correlation analysis was performed for IL-6 and other variables; a binary logistic regression analysis was used to investigate the independent risk factors for the prognosis of patients with HBV-ACLF; the receiver operating characteristic (ROC) curve was used to assess the value of IL-6 combined with MELD score in predicting the prognosis of HBV-ACLF. Results There were significant differences between the death group and the survival group in hematocrit ( t =2.413), platelet count ( t =6.584), total bilirubin (TBil) ( t =-8.070), prothrombin time (PT) ( U =77.500), international standardized ratio ( U =102.000), HBV DNA ( t =-2.767), IL-6 ( t =-16.543), and MELD score ( t =-8.192), and the death group had a significantly higher level of IL-6 than the survival group (27.13±12.18 pg/mL vs 9.72±5.56 pg/mL, P < 0.001). The Pearson correlation analysis showed that IL-6 was positively correlated with TBil and PT ( r =0.579 and 0.681, both P < 0.001). The binary logistic regression analysis showed that IL-6 (odds ratio[ OR ]=1.480, 95% confidence interval [ CI ]: 1.196~1.833, P =0.007) and MELD score ( OR =1.128, 95% CI : 1.033~1.231, P < 0.001) were independent risk factors for the death of HBV-ACLF patients within 90 days. IL-6 combined with MELD score had an area under the ROC curve (AUC) of 0.891 (95% CI : 0.778~0.999), with a higher AUC than IL-6 (AUC=0.838, 95% CI : 0.687~0.989) or MELD score (AUC=0.783, 95% CI : 0.634~0.933). IL-6 combined with MELD score had a significantly higher value than IL-6 alone in predicting the prognosis of patients with HBV-ACLF ( Z =-2.257, P =0.024). Conclusion IL-6 combined with MELD score can be used as a good model for predicting the short-term prognosis of patients with HBV-ACLF.

ObjectiveTo investigate the value of interleukin-32 (IL-32) combined with Model for End-Stage Liver Disease (MELD) in predicting the prognosis of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (HBV-ACLF). MethodsA total of 92 patients with HBV-ACLF who were hospitalized in The First Affiliated Hospital of Soochow University from January 2015 to December 2018 were enrolled, and according to the follow-up results at 3 months after diagnosis, the patients were divided into survival group with 40 patients and death group with 52 patients. ELISA was used to measure the serum level of IL-32. Clinical data of the patients were collected, including age, sex, underlying diseases, major complications, white blood cell count (WBC), platelet count (PLT), hematocrit (HCT), total bilirubin (TBil), alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (Alb), serum creatinine (SCr), prothrombin time (PT), international normalized ratio (INR), and HBV DNA. The t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups; a Pearson correlation analysis was performed for IL-32 and other variables; a binary logistic regression analysis was performed to investigate the independent risk factors for the prognosis of patients with HBV-ACLF. The receiver operating characteristic(ROC) curve(AUC) was used to evaluate the value of IL-32 combined with MELD score in predicting the prognosis of patients with HBV-ACLF. The normal Z test was used for comparison of AUC. ResultsThere were significant differences between the two groups in HCT, PLT, TBil, SCr, PT, INR, HBV DNA, IL-32, and MELD score (all P＜0.05). IL-32 was positively correlated with TBil (r=0.952, P＜0.001) and MELD score (r=0850, P＜0.001). IL-32 (odds ratio ［OR］=1.137, 95% confidence interval ［CI］: 1040-1243, P=0.005) and MELD score (OR=1.055, 95% CI: 1.001-1.109, P=0.025) were independent risk factors for the death of HBV-ACLF patients. IL-32 combined with MELD score had the highest value in predicting the prognosis of patients with HBV-ACLF (AUC=0.992, 95% CI: 0.981-1000), with a significantly higher AUC than IL-32 (0.992 vs 0.984, Z=2.265, P＜0.05) and MELD score (0.992 vs 0877, Z=3182, P＜0.05). ConclusionBoth IL-32 and MELD score can predict the prognosis of patients with HBV-ACLF, and the combination of these two indicators has a better predictive value.

ObjectiveTo investigate the role of coagulation function parameters and platelet indices in thrombotic events in patients with hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF). MethodsA total of 56 patients with HBV-ACLF who were hospitalized in The First Affiliated Hospital of Soochow University from January 2015 to December 2019 were enrolled and divided into thrombotic complication (TC) group with 24 patients and non-thrombotic complication (NTC) group with 32 patients. A retrospective analysis was performed for their general clinical data on admission, and the patients were observed in terms of the changes in coagulation function, platelet count (PLT), and the platelet function-related index mean platelet volume (MPV) on days 1-7 after admission. The t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. A repeated measures analysis of variance was used to compare coagulation markers within and between groups at different time points. ResultsOn admission, the TC group had a significantly younger age than the NTC group ［31.5 (29.0-34.0) years vs 48.5 (36.0-50.7) years, Z=-2.637, P=0.008］. On the day of admission, there was no significant difference in MPV between the TC group and the NTC group (P ＞0.05), while on days 2-7 after admission, there was a significant difference in MPV between the two groups (t=-2.696、-2.742、-2.894、-4.174、-3.945、-4.716,all P ＜0.01). In the TC group, MPV reached the peak value on day 5 of admission, with a mean value of 13.90±1.12 fl, which was higher than the range of normal values. On admission, all patients had a mean prothrombin time (PT) of 28.8±7.2 s, a mean activated partial thromboplastin time (APTT) of 50.5±8.7 s, and a mean international normalized ratio (INR) of 2.6±0.7, which were higher than normal values; all patients had a mean fibrinogen (Fb) level of 1.16±0.3 g/L and a mean PLT of (107.7±26.5)×109/L, which were lower than normal values. There were no significant differences in PT, APTT, Fb, INR, and PLT between the TC group and the NTC group (all P ＞0.05). ConclusionCoagulation disorder in patients with liver failure is more of a low-equilibrium state, which is complex and heterogeneous and requires individualized treatment. For patients with HBV-ACLF, the development of thrombotic events may be more associated with platelet function than PLT or conventional coagulation markers.

Objective:To explore the significance of the clinical target volume (CTV) dose optimization in the upper and middle neck in protecting the laryngopharynx, anterior and posterior rings during intensity-modulated radiotherapy (IMRT) and multimodal imaging system for nasopharyngeal carcinoma.Methods:Clinical data of 298 nasopharyngeal carcinoma patients admitted to Jiangsu Cancer Hospital from 2016 to 2018 were retrospectively analyzed. According to the following five strategies of CTV dose optimization in the upper and middle neck: group A, complete optimization of bilateral cervical lymph nodes (CLNs), that is, the CTV doses of bilateral CLNs were 50.4 Gy; group B, complete optimization of unilateral CLNs, that is, the CTV dose of unilateral CLNs was 50.4 Gy and the contralateral CLNs was 60 Gy; group C, incomplete optimization of bilateral CLNs, that is, the CTV doses of bilateral CLNs were 50.4 Gy, while the suspicious positive CLNs were selectively boosted to 60 Gy; group D, incomplete optimization of unilateral CLNs, that is, the CTV dose of unilateral CLNs was 50.4 Gy and the suspicious positive CLNs were selectively boosted to 60 Gy, and the CTV dose of contralateral side was 60 Gy; group E: no optimization, that is, the CTV doses of bilateral CLNs were 60 Gy.Results:Among 298 patients, 215 patients received dose optimization and 83 cases did not receive dose optimization. In the dose optimization schemes, 114 cases were assigned in group A, 36 cases in group B, 60 cases in group C and 5 cases in group D. The median (range) follow-up time was 28.5(6.0-46.3) months. The overall survival rate was 95.6%, the progression-free survival rate was 84.2% and the locoregional control rate of CLNs was 98.0%. Local relapse of CLNs occurred in six patients, including 1 case of retropharyngeal lymph node, 4 cases of Ⅱ area and 1 case of Ⅳ area. The P values of average dose of laryngopharynx in group A, group B, group C and group D compared with that in group E were<0.001, 0.016, 0.001 and 0.572, respectively. The P values of the average dose of the anterior ring in group A, group B, group C and group D compared with that in group E were<0.001, 0.011, <0.001 and 0.805, respectively. The P values of the average dose of the posterior ring in group A, group B, group C and group D compared with that in group E were<0.001, 0.004, <0.001 and 0.252, respectively.Conclusions:Combined with the metastatic rules of CLNs and multimodal imaging system, it is safe to optimize the CTV dose of the upper and middle neck during IMRT in nasopharyngeal carcinoma patients, which can significantly reduce the doses of laryngopharynx, anterior and posterior rings, thereby providing evidence for reducing the CTV dose in the upper and middle neck.

Objective:To explore the molecular genetics of myeloid neoplasms in elderly patients.Methods:High-throughput DNA sequencing was performed to detect 49 target gene mutations in 26 patients with acute myeloid leukemia(AML)and 51 patients with myelodysplastic syndrome(MDS). Genomic DNA-PCR and Sanger sequencing were used to detect the mutations of CALR gene exon 9, NMP1 gene exon 12, FLT3-ITD and the two functional domains, TAD and BZIP, in CEBPA.Results:(1)Of the 77 patients enrolled, the overall incidence of gene mutations was 91.0%(71/77), with an average of 2 mutations per patient and an incidence of 42.9% for the coexistence of 3 or more gene mutations(33/77), and the most common genetic mutations were NPM1, U2AF1, RUNX1, TET2, ASXL1, TP53, DNMT3A, IDH2, BCOR, and FLT3-ITD, and the incidence of other genetic mutations was<10%.(2)The incidence of double gene mutations in the AML group was significantly higher than that in the MDS group, and the incidence of≥3 gene mutations in the MDS group was higher than that in the AML group( P<0.05). The AML group was associated with significantly higher incidences of NPM1, FLT3-ITD, and CEBPA double mutations and lower incidences of BCOR and ASXL1 mutations than those in the MDS group(all P<0.05). Functional classification showed that tyrosine kinase receptor gene mutations mainly occurred in the AML group( P=0.004), while chromatin modified gene mutations mainly occurred in the MDS group( P=0.007). (3)Fifty-one cases with MDS were followed up and 9 cases developed leukemia transformation with an average transformation time of 6.5 months during the period, and the conversion rate of patients with RUNX1 and U2AF1 mutations was 44.4%, which was higher than that of other gene mutations. Conclusions:Elderly patients with myeloid neoplasms have unique gene mutation profiles.The types and frequencies of common myeloid tumor gene mutations are different in AML and MDS, and some gene mutations in patients with MDS are related to leukemia transformation.

ObjectiveTo investigate the association between mean platelet volume (MPV) and prognosis of hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) and the value of MPV in prognostic evaluation. MethodsA retrospective analysis was performed for the clinical data of 37 patients with hepatitis B cirrhosis, 44 patients with HBV-ACLF, and 27 patients with chronic hepatitis B, who were admitted to Department of Infectious Diseases, The First Affiliated Hospital of Soochow University, from January 2015 to December 2019, as well as 24 individuals who underwent physical examination during the same period of time. Related clinical data included sex, age, total bilirubin (TBil), creatinine (Cr), blood urea nitrogen (BUN), albumin (Alb), blood ammonia (NH3), routine blood test results, Model for End-Stage Liver Disease (MELD) score, and blood coagulation parameters. According to prognosis, the patients with HBV-ACLF patients were divided into improvement group with 19 patients and non-improvement group with 25 patients, and the patients were followed up for 3 months. The Kruskal-Wallis H test was used for comparison between multiple groups, and the Wilcoxon rank sum test was used for comparison within each group， the Mann-Whitney U test was used for comparison between two groups； a binary logistic regression analysis was used to investigate the independent influencing factors for prognosis, and the receiver operating characteristic (ROC) curve was used to predict the accuracy of variables. ResultsThere were significant differences in MPV, platelet count, prothrombin time (PT), international normalized ratio (INR), Alb, BUN, TBil, and MELD score between the liver cirrhosis group, the HBV-ACLF group, the chronic hepatitis group, and the healthy group (χ2=39.031， 75.837, 59.894, 56.033, 22.760, 83.353 and 70.299, all P＜0.001). Further comparison of MPV between two groups showed that the HBV-ACLF group had a significantly higher MPV than the healthy group and the chronic hepatitis group (Z=9.076 and 4.435, both corrected P＜0.001), and the liver cirrhosis group had a significantly higher MPV than the healthy group (Z=2.646, corrected P=0.049). For the patients with HBV-ACLF, there were significant differences in MPV, age, PT, INR, and MELD score between the improvement group and the non-improvement group (Z=-3.710， -2.726， -2.678， -2.322 and -2.610, all P＜0.05), and further binary logistic regression analysis showed that MPV (odds ratio ［OR］=1.175, 95% confidence interval ［CI］: 1.067-2.756, P=0.026) and MELD score (OR=1.643, 95% CI: 1.021-2.644, P=0.041) were independent influencing factors for the prognosis of HBV-ACLF. MPV alone, MELD score alone, and MPV combined with MELD score had an area under the ROC curve of 0.742, 0.731, and 0.791, respectively, in predicting the prognosis of HBV-ACLF, and MPV combined with MELD score had relatively high sensitivity (0.72) and specificity (0.895). ConclusionMPV is an independent influencing factor for the prognosis of HBV-ACLF and has a good value in predicting prognosis. MPV combined with MELD score has advantages over MPV or MELD score alone in predicting the prognosis of HBV-ACLF.

Objective:To investigate the feasibility of cationic antimicrobial peptide cathelicidin-PY(PY) therapy through a mouse model of acute liver failure.Methods:The ability of different concentrations of antimicrobial peptide PY to neutralize endotoxin / lipopolysaccharide (LPS) in vitro was detected by Limulus Amebocyte Lysate (LAL) assay. Cell counting kit-8 (CCK-8) was used to detect the toxic effect of different concentrations of antimicrobial peptide PY on mouse monocyte macrophages (RAW264.7). An in vitro hemolysis experiment was used to evaluate the activity of antimicrobial peptide PY on healthy human erythrocytes. D-galactosamine combined with LPS- induced mouse model of acute liver failure was constructed. The antimicrobial peptide PY effect on survival rate of mouse model was observed. HE staining was used to observe the pathological changes of liver tissue. Immunohistochemistry and Western blotting were used to detect the expression of apoptosis-associated protein caspase-3. Intra-group comparisons were performed using t-test and analysis of variance. χ2 test was used for the comparison of rates. Results:An in vitro experiment showed that the endotoxin neutralization rate was higher at very low dose (0.01 μmol/L), and exceeded 70% at medium-dose (10-40 μmol/L), and the difference between groups with different concentration was statistically significant ( F = 569.22, P < 0.05). Medium-dose antimicrobial peptide PY had strong endotoxin neutralizing effect, low cytotoxicity and hemolytic activity. Moreover, in vivo experiments showed that the degree of liver injury and survival rate of mouse model was significantly improved with the medium-dose of antimicrobial peptide PY. Immunohistochemistry results showed that the expression of caspase-3 in the liver tissue was significantly depleted in the medium-dose group than that of the liver failure group, and the results were consistent with protein immunoblotting testing. Conclusion:Antimicrobial peptide PY possesses a strong ability to neutralize endotoxin and few toxic side effects. A specific dose of antimicrobial peptide PY can attenuate hepatocyte apoptosis and significantly improve the survival rate of animal model, and thus provides a new idea for the liver failure treatment.

Objective:To explore the clinical characteristics and establish a corresponding prognostic scoring model in patients with early-stage clinical features of hepatitis B-induced acute-on-chronic liver failure (HBV-ACLF).Methods:Clinical characteristics of 725 cases with hepatitis B-related acute-on-chronic hepatic dysfunction (HBV-ACHD) were retrospectively analyzed using Chinese group on the study of severe hepatitis B (COSSH). The independent risk factors associated with 90-day prognosis to establish a prognostic scoring model was analyzed by multivariate Cox regression, and was validated by 500 internal and 390 external HBV-ACHD patients.Results:Among 725 cases with HBV-ACHD, 76.8% were male, 96.8% had cirrhosis base,66.5% had complications of ascites, 4.1% had coagulation failure in respect to organ failure, and 9.2% had 90-day mortality rate. Multivariate Cox regression analysis showed that TBil, WBC and ALP were the best predictors of 90-day mortality rate in HBV-ACHD patients. The established scoring model was COSS-HACHADs = 0.75 × ln(WBC) + 0.57 × ln(TBil)-0.94 × ln(ALP) +10. The area under the receiver operating characteristic curve (AUROC) of subjects was significantly higher than MELD, MELD-Na, CTP and CLIF-C ADs( P < 0.05). An analysis of 500 and 390 cases of internal random selection group and external group had similar verified results. Conclusion:HBV-ACHD patients are a group of people with decompensated cirrhosis combined with small number of organ failure, and the 90-day mortality rate is 9.2%. COSSH-ACHDs have a higher predictive effect on HBV-ACHD patients' 90-day prognosis, and thus provide evidence-based medicine for early clinical diagnosis and treatment.

Objective To study the clinical efficacy of transnasal transsphenoidal surgery in acromegaly caused by pituitary adenoma and the clinical characteristics of patients achieved early biochemical remission after surgery. Methods Thirty-three patients with acromegaly caused by pituitary adenoma, admitted to and underwent transnasal transsphenoidal surgery in our hospital from September 2014 to June 2017, were chosen in our study. Clinical data and treatment efficacy of these patients were analyzed retrospectively. The patients were divided into biochemical remission group and non-biochemical remission group according to serum growth hormone (GH) trough value and insulin-like growth factor-1 (IGF-1) levels after oral glucose tolerance test (OGTT) 3 months after surgery, and endocrinology test results of the two groups were compared. Results Thirty-three acromegaly patients underwent microscopic transnasal pituitary surgery. For these patients, 24 achieved total resection, two achieved subtotal resection, 5 achieved massive resection, and two achieved partial resection. Patients were followed up for an average of 13.2 (3-36) months. At 3 months after surgery, blood sugar of two patients with diabetes were restored to normal level; reduction or restoration of hypertension was observed in most patients with preoperative hypertension (81.8％ , 9/11); improvement of cardiac hypertrophy or cardiac enlargement was observed in about 1/3 patients with preoperative cardiac organic changes; heart enlargement was improved in 4 patients; one patient had normal sinus arrhythmia. The average interventricular septum thickness of the patients after surgery was significantly reduced as compared with that before surgery ([8.36±1.56] mm vs. [9.22±1.24] mm, P<0.05). The early biochemical remission was achieved in 19 patients (57.6％); as compared with the 14 patients failed to achieve early biochemical remission, those patients achieved early biochemical remission had significantly smaller adenoma diameters and volumes, lower percentages of patients with degrees of adenoma packaging internal carotid artery<135° and Knosp grading 0-2, and higher extent of surgical resection, lower IGF-1 level at one week and three months after surgery, lower GH level one, two and three d, one week and three months after surgery, and lower GH trough value after OGTT before surgery, one week and 3 months after surgery, with significant differences (P<0.05). Conclusions Transsphenoidal surgery is effective treatment for acromegaly caused by pituitary adenoma. Most patients could achieve biochemical remission three months after surgery. And the surgery could help in improving the cardiovascular complications of patients. The patients who are able to achieve early biochemical remission may have the features of smaller adenoma, lower GH trough value after OGTT before and one week after surgery, and lower GH and IGF-1 levels after surgery.

Pituitary adenomas are common benign intracranial tumors;however,some pituitary adenomas are invasive.Recent studies on the invasive pituitary adenomas have mainly focused on genomics,proteomics,and imaging.Although there are few studies on metabolites and magnetic resonance (MR) signs of pituitary adenomas,these studies can aid in understanding the metabolism of tumor cells and relevant imaging characteristics.This paper reviews the research progress on MR imaging evaluation and metabolites in invasive pituitary adenomas.