To study the immunoregulatory effects of lycorine on mice infected with Toxoplasma gondii(T.gondii),BALB/c mice were treated with 20 mg/kg lycorine solution after peritoneal in-fection with T.gondii RH strain.The serum and spleen of mice were collected at the 1st,3rd,5th and 7th day,respectively,and the spleen index of mice was calculated.The proportion of T lympho-cyte subtypes and NK cells were detected in mice by flow cytometry,and the changes of cytokine levels in mice were measured using ELISA kit,so as to evaluate the immunomodulatory effect of lycorine on mice infected with T.gondii.At the same time,the heart,liver,spleen,lungs,and kid-neys of mice were collected at the 7th day,and the pathological changes of the mouse organs were observed through pathological tissue sections,and the amount of the parasite in the liver,lung,kid-ney,and brain of the mice was detected by fluorescence quantitative PCR.The results showed that the survival time of the mice treated with lycorine was significantly extended,and the survival rate reached 80％.The spleen index of mice treated with lycorine was lower than that of the control group.Lycorine up-regulates the ratio of the CD4+T lymphocytes and NK cells in the spleen of mice infected with T.gondii,and helps to improve the ability of mice to resist T.gondii infection.Lycorine can up-regulate the levels of anti-inflammatory cytokine IL-4 and down-regulate the lev-els of pro-inflammatory factors IFN-γ,IL-1β,and IL-9 in serum of mice infected with T.gondii,which is conducive to reducing the damage of inflammatory response and enhancing the ability of anti-T.gondii infection.In addition,lycorine can alleviate the pathological damage of T.gondii to the liver,lungs,spleen,and kidneys of mice,and significantly reduce the amount of the parasite in the lung of mice.The results showed that lycorine could up-regulate the proportion of immune cells CD4+T lymphocytes and NK cells,inhibit the inflammatory response of mice infected with T.gondii,reduce the pathological damage of mice organs,and enhance the ability of mice to resist T.gondii infection,which is expected to become a novel anti-T.gondii drug.

To study the immunoregulatory effects of lycorine on mice infected with Toxoplasma gondii(T.gondii),BALB/c mice were treated with 20 mg/kg lycorine solution after peritoneal in-fection with T.gondii RH strain.The serum and spleen of mice were collected at the 1st,3rd,5th and 7th day,respectively,and the spleen index of mice was calculated.The proportion of T lympho-cyte subtypes and NK cells were detected in mice by flow cytometry,and the changes of cytokine levels in mice were measured using ELISA kit,so as to evaluate the immunomodulatory effect of lycorine on mice infected with T.gondii.At the same time,the heart,liver,spleen,lungs,and kid-neys of mice were collected at the 7th day,and the pathological changes of the mouse organs were observed through pathological tissue sections,and the amount of the parasite in the liver,lung,kid-ney,and brain of the mice was detected by fluorescence quantitative PCR.The results showed that the survival time of the mice treated with lycorine was significantly extended,and the survival rate reached 80％.The spleen index of mice treated with lycorine was lower than that of the control group.Lycorine up-regulates the ratio of the CD4+T lymphocytes and NK cells in the spleen of mice infected with T.gondii,and helps to improve the ability of mice to resist T.gondii infection.Lycorine can up-regulate the levels of anti-inflammatory cytokine IL-4 and down-regulate the lev-els of pro-inflammatory factors IFN-γ,IL-1β,and IL-9 in serum of mice infected with T.gondii,which is conducive to reducing the damage of inflammatory response and enhancing the ability of anti-T.gondii infection.In addition,lycorine can alleviate the pathological damage of T.gondii to the liver,lungs,spleen,and kidneys of mice,and significantly reduce the amount of the parasite in the lung of mice.The results showed that lycorine could up-regulate the proportion of immune cells CD4+T lymphocytes and NK cells,inhibit the inflammatory response of mice infected with T.gondii,reduce the pathological damage of mice organs,and enhance the ability of mice to resist T.gondii infection,which is expected to become a novel anti-T.gondii drug.

Objective:To explore the diagnostic value of serum C-C chemokine ligand 5 (CCL5) in assessing the degree of liver fibrosis in patients with metabolic-associated fatty liver disease (MAFLD).Methods:71 MAFLD patients who visited the Department of Integrated Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, and underwent liver biopsy histopathology examinations between October 2021 and June 2023 were selected for diagnostic testing. Simultaneously, 71 healthy subjects who underwent physical examinations at the physical examination center of the hospital were selected as the control group. Serum CCL5 levels were detected using an enzyme-linked immunosorbent assay (ELISA). Routine blood tests, liver and kidney function tests, and other tests were conducted to analyze the expression level of CCL5 and its correlation with the above indicators. The aspartate aminotransferase/platelet ratio index (APRI) and fibrosis 4 index (FIB-4) were calculated. SPSS 26.0 software was used for statistical analysis. The area under the receiver operating characteristic curve (ROC) was used to evaluate the diagnostic efficacy of CCL5 for the degree of liver fibrosis in MAFLD. The combined diagnostic efficacy of APRI and FIB-4 was further analyzed for the degree of liver fibrosis in MAFLD.Results:The expression level of serum CCL5 gradually increased with the increase in liver fibrosis stage in patients with MAFLD, and the difference was statistically significant ( P<0.05). The AUC value of serum CCL5 for diagnosing significant liver fibrosis in MAFLD patients was 0.775, with a sensitivity of 65.7%, a specificity of 80.6%, and an optimal cutoff value of 49.845 ng/ml. The CCL5 and FIB-4 combination had the highest diagnostic value for significant liver fibrosis in patients with MAFLD, with an AUC of 0.802, a sensitivity of 91.4%, and a specificity of 61.1%. Conclusion:CCL5 has a high diagnostic value for significant liver fibrosis in MAFLD patients. Therefore, it is expected to become a non-invasive diagnostic marker for assessing the degree of liver fibrosis in MAFLD patients.

The incidence of non-alcoholic fatty liver disease (NAFLD) is increasing year by year, and it has become a serious public health problem that threatens human health.NAFLD patients can progress from simple steatosis to non-alcoholic steatohepatitis (NASH), liver fibrosis, and even cirrhosis without intervention. Therefore, early diagnosis and treatment are particularly important.Liver biopsy is the gold standard for diagnosing NAFLD, but its limitations such as invasion, bleeding, and high cost limit its widespread clinical application. There is an urgent need for sensitive and convenient non-invasive diagnostic methods to achieve early diagnosis and treatment of NAFLD.This article provides a review of the progress in serological diagnostic methods for NAFLD both domestically and internationally in recent years.

Objective:This study aimed to evaluate the diagnostic value of serum Golgi protein 73(GP73) alone and GP73 combined with liver stiffness measurement (LSM), aspartate aminotransferase/platelet ratio index (APRI), and 4-factor-based fibrosis index (FIB4) in diagnosing liver fibrosis in patients with chronic liver disease of different etiologies.Methods:A diagnostic test. A total of 68 patients who underwent liver biopsy in the Department of Traditional and Western Medical Hepatology of the Third Hospital of Hebei Medical University from October 2019 to December 2020 were selected to detect serum GP73 levels. iLivTouch was used to assess liver stiffness measurement (LSM). In addition, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total bilirubin (TBil), direct bilirubin (DBil), triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL) levels, and peripheral platelet (PLT) counts were assayed. The correlation between GP73 and the above indexes was assessed, and APRI and FIB-4 were calculated. SPSS 21.0 statistical software was used for statistical analysis. The area under the receiver operating characteristic curve was calculated to evaluate diagnostic efficacy of GP73 in identifying hepatic fibrosis stages. Furthermore, the difference between GP73 and liver stiffness, as well as APRI and FIB4 in diagnosing significant fibrosis was assessed.Results:Based on liver biopsy, 13, 18, 17, and 20 cases were diagnosed as stages S0-1, S2, S3, and S4, respectively. The AUC of GP73 diagnosing hepatic fibrosis stage S≥3 and S=4 were 0.806 and 0.844 at cut-off points of 2.06 and 3.27 μg/L, and the sensitivity and specificity were 93.5%, 61.5%, 90.0%, 70.3%, respectively. In addition, GP73 levels were positively correlated with the degree of liver fibrosis ( r=0.547, P<0.001). Conclusions:The efficacy of serum GP73 level in diagnosing the degree of liver fibrosis in patients with chronic liver disease from different causes was significantly higher than that of APRI, FIB4, and LSM. The combination of GP73 and FIB4 can further improve the accuracy of diagnosis of liver fibrosis staging S≥3 and S=4, which is a reliable serological marker for the diagnosis of fibrosis in patients with chronic liver disease.

Objective:To investigate the risk factors of invasive fungal disease after haploid hematopoietic stem cell transplantation in children with acute leukemia.Methods:Four hundred and two children (median age 10 years) with acute leukemia, undergoing haplo-HSCT at this institutute from January 2016 to December 2020,were analyzed retrospectively according to the diagnosis criteria of IFD. The basic information and preoperative indicators of the children were collected, including gender, age, primary disease, remission status of primary disease, and previous IFD history. Postoperative indicators were collected, including long-term granulocyte deficiency time, high-dose glucocorticoids, using CD25 monoclonal antibody, acute and chronic graft-versus-host disease. Count data are expressed as example (%), and comparisons between groups are made using the continuously multifactorial corrected Chi-square test or Fisher exact probability method. Logistic regression model was used to analyze the risk factors of IFD after haplo-HSCT in children.Results:Among 402 cases, 250 were male and 152 were female. The median age at transplantation was 10 years, and the age range was 9 months to 17 years 7 months. Before transplantation, 390 cases achieved complete remission of the primary disease, 9 cases had partial remission, and 3 cases had no remission. The implantation time of neutrophils ranged from +10 to 24 days, with a median time of 12 days. IFD occurred in 17 cases (4.2%), of which 3 cases (0.7%) were proven IFD and 14 cases (3.5%) were probable IFD. IFD occurred from 13 to 275 days after transplantation, with a median time of 30 days. The lungs were the most common site of infection (88.2%,15/17). The multivariate Logistic regression analysis showed that age >10 years old ( P=0.046, odds ratio =3.05, 95% confidence interval: 1.02~9.13), the use of high-dose corticosteroids ( P=0.005, odds ratio =7.72, 95% confidence interval: 1.85~32.20) were risk factors for IFD after haplo-HSCT in children. Conclusions:IFD is an important complication after haplo-HSCT in children with acute leukemia. Age >10 years and the use of high-dose corticosteroid are risk factors for IFD after haplo-HSCT in children with acute leukemia.

Objective:To investigate the efficacy and diagnostic accuracy of changes in cytokine levels before and after non-biological artificial liver (referred to as ABL) treatment in patients with acute-on-chronic liver failure (ACLF) in order to establish a basis for treatment timing selection and short-term (28d) prognosis.Methods:90 cases diagnosed with ACLF were selected and divided into a group receiving artificial liver treatment (45 cases) and a group not receiving artificial liver treatment (45 cases). Age, gender, first routine blood test after admission, liver and kidney function, and procalcitonin (PCT) of the two groups were collected. The 28-day survival of the two groups was followed-up for survival analysis. The 45 cases who received artificial liver therapy were further divided into an improvement group and a deterioration group according to the clinical manifestations before discharge and the last laboratory examination results as the efficacy evaluation indicators. Routine blood test, coagulation function, liver and kidney function, PCT, alpha fetoprotein (AFP), β-defensin-1 (HBD-1), 12 cytokines and other indicators were analyzed and compared. A receiver operating characteristic curve (ROC curve) was used to analyze the diagnostic efficacy of the short-term (28 d) prognosis and an independent risk factors affecting the prognosis of ACLF patients. According to different data, Kaplan-Meier method, log-rant test, t-test, Mann-Whitney U test, Wilcoxon rank-sum test, χ2 test, Spearman rank correlation analysis and logistic regression analysis were used for statistical analysis. Results:The 28-day survival rate was significantly higher in ACLF patients who received artificial liver therapy than that of those who did not receive artificial liver therapy (82.2% vs. 61.0%, P<0.05). The levels of serum HBD-1, alpha interferon (IFN-α) and interleukin-5 (IL-5) after artificial liver treatment were significantly lower in ACLF patients than those before treatment ( P<0.05), while liver and coagulation function were significantly improved compared with those before treatment ( P<0.05), and there was no statistically significant difference in other serological indexes before and after treatment ( P＞0.05). Before artificial liver treatment, serum HBD-1 and INF-α levels were significantly lower in the ACLF improvement group than in the deterioration group ( P<0.05) and were positively correlated with the patients' prognosis (deteriorating) ( r=0.591, 0.427, P<0.001, 0.008). The level of AFP was significantly higher in the improved ACLF group than that in the deterioration group ( P<0.05), and was negatively correlated with the prognosis (deteriorating) of the patients ( r=-0.557, P<0.001). Univariate logistic regression analysis showed that HBD-1, IFN-α and AFP were independent risk factors for the prognosis of ACLF patients ( P=0.001, 0.043, and 0.036, respectively), and that higher HBD-1 and IFN-α levels were associated with lower AFP level and a deteriorating prognosis. The area under the curve (AUC) of HBD-1, IFN-α, and AFP for short-term (28d) prognostic and diagnostic efficacy of ACLF patients was 0.883, 0.763, and 0.843, respectively, and the sensitivity and specificty was 0.75, 0.75, and 0.72, and 0.84, 0.80, and 0.83, respectively. The combination of HBD-1 and AFP had further improved the diagnostic efficiency of short-term prognosis of ACLF patients (AUC=0.960, sensitivity and specificity: 0.909 and 0.880 respectively). The combination of HBD-1+IFN-α+AFP had the highest diagnostic performance, with an AUC of 0.989, sensitivity of 0.900, and specificity of 0.947. Conclusion:Artificial liver therapy can effectively improve the clinical symptoms and liver and coagulation function of patients with ACLF; remove cytokines such as HBD-1, IFN-α, and IL-5 in patients with liver failure; delay or reverse the progression of the disease; and improve the survival rate of patients. HBD-1, IFN-α, and AFP are independent risk factors affecting the prognosis of ACLF patients, which can be used as biological indicators for evaluating the short-term prognosis of ACLF patients. The higher the level of HBD-1 and/or IFN-α, the higher the risk of disease deterioration. Therefore, artificial liver therapy should be started as soon as possible after the exclusion of infection. In diagnosing the prognosis of ACLF, HBD-1 has higher sensitivity and specificity than IFN-α and AFP, and its diagnostic efficiency is greatest when combined with IFN-α and AFP.

Objective To investigate the clinical and pathological features of children with glycogen storage disease (GSD). Methods A retrospective analysis was performed for ten children with GSD who were admitted to the Third Hospital of Hebei Medical University and The Fifth Medical Center of Chinese PLA General Hospital from January 2002 to January 2022, based on medical history, liver biochemistry, and liver biopsy, and population characteristics, clinical manifestations, biochemical parameters, and liver histopathological characteristics were compared and analyzed. Results All ten children had developmental retardation and a short stature, with the manifestations of abnormal liver function, mild weakness, poor appetite, yellow urine, and yellow eyes, and four children had hepatosplenomegaly. Among the ten children, six had the clinical manifestations of hypoglycemia, and one had bilateral gastrocnemius hypertrophy and positive Gower sign. Two children had positive CMV IgG. Liver histopathological manifestations included diffuse enlargement of hepatocytes, light cytoplasm, and small nucleus in the middle like plant cells, with or without fibrous tissue proliferation. Conclusion Most patients with GSD have developmental retardation and abnormal aminotransferases, and liver pathological examination shows specific pathological features.

Nonalcoholic steatohepatitis (NASH) has become the second leading cause of hepatitis and can further progress to liver fibrosis, liver cirrhosis, and even liver cancer; however, the detailed pathogenesis of NASH remains unclear, and there is still a lack of effective therapeutic drugs. MicroRNAs (miRNAs) are a class of non-coding, post-transcriptionally regulated, and highly conserved small RNAs in the body and play an important role in a variety of liver diseases. This article mainly reviews the role of miRNAs in the development and progression of NASH.

Patients with liver cirrhosis are prone to infection due to various reasons such as weakened immunity and intestinal bacteria translocation. Among them, bacterial infections are the most common and are the main cause for liver failure progression, leading to increased mortality, while fungal infections, mainly caused by Candida mycoderma bacteria (Candida), are usually related to delayed diagnosis. Therefore, high vigilance, timely diagnosis and treatment of infection are important means to improve the treatment effectiveness in patients with end-stage liver disease. This paper focuses on the main characteristics and treatment methods of bacterial and fungal infections in patients with liver cirrhosis.