On June 16, 2023, National Disease Control and Prevention Administration of the People’s Republic of China, in collaboration with other ministries, formulated and issued the Action Plan to Accelerate the Elimination of Schistosomiasis in China (2023—2030). The implementation of this plan provides an important basis for achieving the targets set in the “Healthy China 2030” action plan and the implementation of the rural revitalization strategy. This paper describes the background, principles, targets, control strategies, safeguard measures and effectiveness evaluation of the plan, in order to guide the scientific and standardized implementation of actions for schistosomiasis elimination at the grassroots level, and facilitate the progress towards elimination of schistosomiasis in China with a high quality.

Objective:To investigate the clinical value of peripheral blood T lymphocytes in the diagnosis and prognosis of patients with hepatocellular carcinoma (HCC) recurrence after liver transplantation.Methods:The clinical and laboratory data of 50 HCC patients, who received liver transplantation and were followed up in the Liver transplantation Center of Beijing Youan Hospital from January 2014 to December 2016, were retrospectively analyzed. The differences on clinical laboratory indicators and five-year survival were compared between HCC recurrence group ( n=29) and non-recurrence group ( n=21). Spearman correlate analysis was used to analyze the correlation between clinical laboratory indicators and HCC recurrence after liver transplantation. Receiver operator characteristic (ROC) curve was used to analyze the diagnostic value of CD4+T lymphocytes in HCC recurrence after liver transplantation. Kaplan-Meier survival curve was used to compare the survival time of patients with different CD4+T lymphocytes levels post liver transplantation. Results:Compared to non-recurrence group, the level of alanine aminotransferase, aspartate aminotransferase, γ-glutamyltransferase, albumin, lymphocytes, alpha-fetoprotein, protein induced by vitamin K deficiency or antagonist-Ⅱ, CD3+, CD4+and CD8+T lymphocytes were significantly different (all P<0.05). The median recurrence time after liver transplantation was 13.0 (6.0, 24.0) months, and the mortality rate was 100%. The 5-year mortality rate was 0 in the non-recurrence group. During 5-year follow-up, the median survival time of patients in the HCC recurrence group was 18.0 (9.0, 36.0) months, which was significantly lower than that of non-recurrence group [60.0 (60.0, 60.0) months, ( P<0.05)]. Compared with non-recurrence group, the CD3+, CD4+, and CD8+T lymphocytes were significantly lower in the recurrence group (all P<0.05). Spearman correlate analysis showed that HCC recurrence after liver transplantation was negatively correlated with the CD3+, CD8+and CD4+T lymphocytes ( r=-0.43, -0.38, -0.44, all P<0.05). ROC analysis showed that CD4+T lymphocytes at cutoff of≤265.50 cells/μl was valuable for the diagnosis of HCC recurrence after liver transplantation (specificity 100%, sensitivity 48.30%). Survival curve analysis showed that the survival time was significantly lower in the CD4≤265.50 cells/μl group [15.0 (10.0, 36.8) months] than that in the CD4>265.50 cells/μl group [53.0 (19.5, 60.0) months] ( P<0.05). Conclusion:There is a significant negative correlation between CD4+T lymphocytes and HCC recurrence after liver transplantation. CD4+T lymphocytes at cutoff value of≤265.50 cells/μl is valuable for the clinical diagnosis and prognosis evaluation of HCC recurrence after liver transplantation.

Objective:To screen and identify differential proteins, analyze lipid metabolism-related proteins and pathways, and explore their functions and biological processes in liver tissue of patients with alcoholic liver disease using tandem mass tag (TMT) labeling technology.Methods:Liver tissues that met the inclusion criteria were collected. Eight samples from patients with alcoholic cirrhosis and three samples from the normal control group were screened out. The TMT technique was used to screen differential proteins, perform signaling pathway enrichment analysis, and analyze protein interaction networks to explore the biological processes involved in them.Results:Proteomic analysis identified 2 741 kinds of differentially expressed proteins in the two groups of data with statistical significance ( P < 0.05). The standard criteria of P < 0.05 and |log2(foldchange)| > 1 had screened out 106 kinds of differentially expressed proteins. Compared with the control group, the alcoholic liver disease group had 12 kinds of up-regulated proteins and 94 kinds of down-regulated proteins. Among them, there were 2 kinds of up-regulated differential proteins related to lipid metabolism and 14 kinds of down-regulated differential proteins. The results of bioinformatics analysis showed that these proteins were primarily involved in biological processes such as lipid transport, regulation of lipase activity, fatty acid binding, and cholesterol metabolism in lipid metabolism and also had a close link to signal pathways related to lipid metabolism such as peroxisome proliferator-activated receptor signaling pathways, cholesterol metabolism, triglyceride metabolism, and regulation of lipolysis in adipocytes. Conclusion:The 16 kinds of lipid metabolism-related differential proteins may be the key proteins in the pathogenesis of alcoholic liver disease.

Objective:To investigate the molecular mechanism of sorafenib against hepatocellular carcinoma.Methods:Sorafenib efficacy was screened and verified by the hepatocellular carcinoma patient-derived tumor xenograft (PDX) model. Veterinary B-mode ultrasonography and in vivo confocal laser scanning microscopy were used to observe PDX angiogenesis. Immunohistochemistry was used to observe the expression of proliferation and angiogenesis-related proteins in PDX tissue. Real-time quantitative PCR technology was used to observe the RUNX3 gene in PDX tissues. SPSS 17.0 statistical software was used for statistical analysis.Results:Four cases of PDX were used to screen the efficacy of sorafenib. PDX1 had a significant response to sorafenib, with an inhibition rate of 68.07%. Compared with the control group, sorafenib had significantly inhibited PDX1 relative tumor volume (5.76±2.14 vs. 11.71±2.87, P<0.05). Cell division index (39.50±7.72 vs. 67.10±9.14, P<0.05) and Ki67 expression (288.6±43.40 vs. 531.70±55.60, P<0.05) were significantly decreased. Veterinary B-mode ultrasonography showed evident blood flow signals in PDX1 tumors. In vivo confocal laser scanning microscopy results showed that sorafenib had significantly reduced the total vessel length (1573.00±236.21 vs. 2675.03±162.00, P<0.05) and area (11 145.33±1931.97 vs. 20 105.37±885.93, P<0.05)) of PDX1 tumors. Immunohistochemical results showed that sorafenib had significantly down-regulated the protein expressions of CD34 (27.55±3.76 vs. 45.47±5.57, P<0.05), VEGF (16.33±2.86 vs. 22.77±3.20, P<0.05) and MVD (38.75±6.01 vs. 55.50±8.61, P<0.05). Real-time PCR results showed that sorafenib had significantly up-regulated RUNX3 gene expression (2.14±0.71 vs. 1.00±0.36, P<0.05). However, there was a negative correlation between the expression of RUNX3 gene and the ratio of VEGF-positive cells in sorafenib group ( R2=0.509 7). Conclusion:Sorafenib may inhibit the PDX angiogenesis and the growth of hepatocellular carcinoma by regulating the RUNX3-VEGF pathway.

Objective To investigate the value of cytokines in bile combined with clinical indices in predicting the degree of liver injury after liver transplantation. MethodsA total of 16 patients undergoing liver transplantation who were hospitalized in Center of Organ Transplantation, The Affiliated Hospital of Qingdao University, from January to December 2018 were enrolled, and according to the level of alanine aminotransferase (ALT) on day 1 after surgery, the patients were divided into mild liver injury (ALT ＜500 U/L) group with 10 patients and severe liver injury (ALT ＞500 U/L) group with 6 patients. Bile samples were collected on days 1, 3, 5, and 7 after surgery, and MILLIPLEX assay was used to measure the levels of 17 cytokines. R software was used to perform principal component analysis (PCA) of bile cytokines and clinical indices and gene ontology (GO) enrichment analysis of bile cytokines. The two-independent-samples t-test was used for comparison of normally distributed continuous data between two groups; The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. A Spearman correlation analysis was performed to evaluate the correlation between clinical indices and bile cytokines. ROC curve analysis was used to evaluate the predictive value of cytokines in bile and clinical indices for liver injury after liver transplantation. ResultsCompared with the mild liver injury group, the severe liver injury group had significantly higher expression levels of bile Fractalkine (Z=-2.828, P=0.003), soluble CD40 ligand (sCD40L) (Z=-2.850, P=0.008), interleukin-4 (Z=-2.398, P=0.017), CXCL10 (Z=-2.475, P=0.023), and macrophage inflammatory protein-1α (Z=-1844, P=0.043). The correlation analysis showed that on day 1 after liver transplantation, aspartate aminotransferase, ALT, and lactate dehydrogenase were positively correlated with the levels of several cytokines in bile (all P＜0.05). The area under the ROC curve of Fractalkine, sCD40L and AST were 0.933 (0.812-1.000), 0.833 (0.589-1.000) and 0.917 (0.779-1.000), respectively, suggesting that AST and Fractalkine and sCD40L in bile on the first day after liver transplantation have significant predictive value for liver injury. The results of PCA showed that bile cytokines combined with clinical indices on day 1 after liver transplantation could better distinguish the patients with mild liver injury from those with severe liver injury. GO analysis showed that bile cytokines were associated with positive feedback regulation of external stimulus, cell chemotaxis, receptor ligand activity, cytokine activity, and cytokine-cytokine receptor interaction. ConclusionFractalkine and sCD40L in bile can predict the degree of liver injury after liver transplantation.

The diagnosis of insomnia includes not only complaints of dissatisfaction with sleep quantity or quality, but also accomplished with daytime dysfunction.Cognitive impairment is one of the daytime dysfunction that insomnia patients often complain about, but the objective measures of cognitive function have no obtained consistent results.Executive functions consist of three core areas, including inhibitory control, working memory and cognitive flexibility.Executive functions represent advanced cognitive processes and are related to daily activities and academic achievement.Executive functions are sensitive to insufficient sleep.However, the relationship between insomnia and executive functions has not attracted enough attention, and it is unclear whether insomnia is related to impairment of executive functions.This article reviews the influence of insomnia on executive functions.The potential mechanism and the role of hyperarousal on executive functions impairment in patients with insomnia is also discussed.

Objective:To construct apoptosis-stimulating of p53 protein 2 (ASPP2) gene knockout mice using diethylnitrosamine (DEN)-induced liver cancer model to study the biological functions of ASPP2.Methods:The sgRNA oligonucleotides were constructed, and ASPP2 knockout mice were prepared with the CRISPR/Cas9 system. PCR and sequencing methods were used to identify the genotypes of F0 and F1 generations and their progeny. DEN was used to induce ASPP2+/- mice to establish liver cancer model.Results:PCR and sequencing results showed that ASPP2 gene was successfully knocked out in F0 generation mice. The genotype of F1 generation mice was accorded with ASPP2+/- and had obtained stable heredity. The success rate of DEN-induced liver cancer model (7/8 and 3 / 8) of ASPP2 + /-mice obtained by self-hybridization of F1 generation was significantly higher than that of wild-type mice.Conclusion:ASPP2 knockout mice were successfully constructed based on the CRISPR/Cas9 system. The success rate of DEN-induced liver cancer model of ASPP2 knockout mice was significantly higher than that of the wild-type mice.

Objective To study the effect of radiofrequency ablation (RFA) with sublethal temperature on the production of liver cancer stem cells (LCSCs) and on the expression of LCSCs-related transcriptional factors.Methods Mouse hepl-6 hepatoma cell line and clinical samples of patients with hepatocellular carcinoma (HCC) were used to test the expressions of LCSCs-related markers and transcriptional factors.Results Different temperatures were used to stimulate Hep1-6 cells,and it was proved that the temperature of 45℃ was a sublethal temperature that could not induce cell death.Flow cytometry testing showed that treatment with 45℃ could obviously increase CD13+,CD44+,CD90 and CD133+ Hep1-6 cells,suggesting that treatment with 45℃ could increase the production of above mentioned types of LCSCs in hep1-6 cells.Real-time quantitative polymerase chain reaction (RT-qPCR) assay indicated that the temperature of 45℃could cause significant increase in CD13,CD90 and CD133 mRNA.In all 5 HCC patients,CD13 mRNA in the recurrent HCC lesions was remarkably increased,CD133 mRNA was increased in 4 patients with recurrent HCC,and CD90 mRNA was increased in only one patient with recurrent HCC.Flow cytometry testing revealed that CD13+ LCSCs were strikingly increased in 4 recurrent HCC patients,while CD133+LCSC was increased in only one patient,suggesting that more close correlation existed between the increase of CD13+ LCSCs and the temperature of 45℃.RT-qPCR assay showed that in 4 recurrent HCC patients with increased CD13+ LCSC,the Sox2 and Stat2 among 13 LCSCs-related transcriptional factors were obviously increased.Flow cytometry testing showed that 45℃ treatment also increased the expression of Sox2 and Stat1 mRNA in Hep1-6 cells.Finally,Sox2 and Stat1 could be knockdown by siRNAs,indicating that both Sox2 and Stat1 transcriptional factors were involved in 45℃-induced production of CD13+ LCSCs in Hep1-6 cells.Conclusion In RFA therapy,the use of sublethal temperature of 45℃ can increase CD13+LCSCs,which is related to the promotion of Sox2 and Stat1 expression.The results of this study can be used for reference in the research of liver cancer recurrence.

Objective To observe the therapeutic effect of oral use of Yibai Tongfeng Pills for the treatment ofgouty arthritis with damp-heat obstruction. Methods One hundred and sixteen gouty arthritis patients were randomized into treatment group (N = 62) and control group (N = 54). The treatment group was treated with Yibai Tongfeng Pills orally, and the control group was treated with oral use of Colchicine Tablets and Sodium Bicarbonate Tablets at acute stage and with oral use of Benzbromarone Tablets at remission stage. Twelve weeks constituted one treatment course. Clinical efficacy of the two groups was evaluated after treatment, and the changes of C-reactive protein(CRP), white blood cell(WBC) and uric acid(UA) levels in the blood of the two groups were observed before and after treatment. Results (1) The total effective rate of the treatment group was 93.55%and that of the control group was 83.33%, the difference being significant(P<0.05).(2) After treatment, the scores of syndrome manifestations of the two groups were obviously decreased(P < 0.05 compared with those before treatment), and the decrease in the treatment group was superior to that in the control group(P<0.05) . (3) After treatment, CRP, WBC and UA levels in the blood of the two groups were much improved(P < 0.05 compared with those before treatment), and the improvement of CRP in the treatment group was superior to that in the control group(P<0.05), while the differences of the improvement of WBC and UA between the two groups were insignificant (P > 0.05). Conclusion Yibai Tongfeng Pills are effective for the treatment of gouty arthritis with damp-heat obstruction by improving syndrome manifestations and rapidly decreasing CRP level.

Aim Toanalyzethekeyqualityandestablishmeth-ods for essential quality control of human recombinant ASPP2 adenovirus.Methods TheviralstructuralgeneofE2Bandtar-get gene of ASPP2 were identified by PCR;The number of virus particles was measured by UV-SDS methods;Infectious titer was determined by TCID50 assay;Target protein of ASPP2 was ob-served by Western blot assay;The biological effects of recombi-nant adenovirus on liver cancer cells were evaluated by MTT as-say;A549 cells were used to check replication of the competent adenovirus(RCA)by the observation of the cytopathic effect. Results PCRanalysisofE2BandASPP2wasinconsistent with theoretical values;Particle numbers of virus were 5. 6 × 1012 VP/mL,infectious titer was 2 ×1011 IU/mL and specific activity was 3. 5%;ASPP2 protein expression could be detected when cells were infected with virus for 24 h;Growth inhibition of liver cancer cells could be found by adding recombinant ASPP 2 adenovirus;The level of RCA was less than 1 RCA/3. 0 ×1010 VP,in line with the standards of China Food and Drug Adminis-tration(SFDA).Conclusion Thequalitycontrolmethodswere established aiming at key characters of human recombinant AS-PP2 adenovirus,which may provide foundations for its quality standard and future applications.