Asia-Pacific Association for the Study of the Liver published the guidelines on management of ascites in liver disease in May 2023， which introduces the diagnosis， differential diagnosis， and treatment of ascites， hyponatremia， hepatic hydrothorax， and hepatorenal syndrome in patients with liver cirrhosis and acute-on-chronic liver failure. This article summarizes the main recommendations in the guidelines， so as to provide a reference for the treatment of ascites in patients with liver diseases in China.

Background Chronic intermittent hypobaric hypoxia (CIHH) can effectively alleviate type 2 diabetes mellitus (T2DM). In this process, the underlying mechanism in its association with the epigenetic regulation of DNA methylation in the promoter regions of glucose metabolism key enzyme genes remains unclear yet. Objective To investigate the effects of CIHH on expression and promoter region methylation of key enzyme genes related to glucose metabolism in diabetes mice, and to explore the underlying mechanism by which CIHH regulates glucose metabolism. Methods Forty C57BL/6J male mice were divided randomly into a normobaric normoxic control (NN/CON) group, a chronic intermittent hypobaric hypoxia intervention control (CIHH/CON) group, a normobaric normoxic diabetic model (NN/DM) group, and a chronic intermittent hypobaric hypoxia intervention diabetic model (CIHH/DM) group. The mice in the NN/DM and the CIHH/DM groups were fed for 7 weeks with high-fat and high-sugar diet. Subsequently, these mice were intraperitoneally injected consecutively with 50 mmol·L⁻¹ streptozotocin (STZ) for 5 d at a dose of 40 mg·kg⁻¹ (body weight) per day to create T2DM model mice. The mice in the CIHH/DM and the CIHH/CON groups were intervened by simulating hypobaric hypoxia at 5000 m altitude for 6 h per day, while the mice in the NN/DM and the NN/CON groups were always placed in a normobaric normoxic environment. All mice were continuously treated for 4 weeks, and blood glucose were monitored during this period. After the CIHH intervention experiment, the glucose tolerance and insulin sensitivity of mice were evaluated. A set of indicators involved in key glycolytic enzymes glucokinase (GK) and pyruvate kinase (PK), as well as key gluconeogenic enzymes phosphoenolpyruvate carboxyl kinase (PEPCK) and glucose-6-phosphatase (G6P) were measured in the liver of mice, including enzyme activity, relative mRNA expression level, and DNA methylation level in the gene promoter regions. Results Compared with the mice in the NN/DM group, the blood glucose levels of the mice in the CIHH/DM group decreased after the 25^th day of the CIHH intervention (P<0.05). Regarding the diabetic glucose tolerance curves, the area under the curve (AUC) of the mice in the CIHH/DM group was lower than that of the NN/DM group (P<0.05). Compared with the mice in the NN/DM group, the mice in the CIHH/DM group showed that the serum insulin content and HOMA of insulin resistance index (HOMA-IRI) decreased (P<0.05), the enzyme activities of GK and PK increased and the relative mRNA expression levels of their genes were up-regulated (P<0.05), while the enzyme activities of PEPCK and G6P decreased and the relative mRNA expression levels of their genes were down-regulated (P<0.05) in liver. The average DNA methylation levels in the promoter regions of GK, PK, PEPCK, and G6P genes in liver of mice in each group were not significantly different (P>0.05), and their correlations with mRNA expression levels were also not statistically significant (P>0.05). Conclusion CIHH intervention may reduce blood glucose level, improve glucose tolerance, alleviate insulin resistance, and regulate the key enzyme activities of glucose metabolism and the relative mRNA expression of their corresponding genes in T2DM mice, but the above phenomena are not related to the DNA methylation levels in the promoter regions of these key enzymes.

Objective To investigate the effects of hypothyroidism and drug intervention on the cognitive function of rat offspring through the establishment of a rat model of experimental hypothyroidism in pregnancy.Methods A to-tal of 20 SD female rats were randomly divided into control group(CON group)and hypothyroid group(PTU group).The hypothyroid model was established by propylthiouracil(PTU),the thyroid hormone levels of female mice were detected by electrochemiluminescence immunoassay,and the differences between the two groups were compared.After successful modeling,the male mice were mated in cages,and the hypothyroid group was randomly divided into no intervention group(group Ⅰ),first trimester intervention group(group Ⅱ)and second and third tri-mester intervention group(group Ⅲ).The Morris water maze(MWM)experiment was used to test the learning and memory ability of the rats.The morphological structure of hippocampal neurons,the expression of nucleoprotein(NeuN)and synapse-associated protein(SYN)in mature neurons were observed by hematoxylin-eosin staining(HE),Nissl staining and immunohistochemistry.Results ① Compared with the CON group,the female mice in the PTU group had a significant increase in TSH and a significant decrease in FT4(P＜0.05).② In the positio-ning navigation test,the evasion latency of the pups in each group was gradually shortened.On the 5th day,the in-cubation period of group Ⅰ was significantly longer than that of groups CON,Ⅱ,Ⅲ(P＜0.05).There was little change between groups Ⅱ and Ⅲ and CON groups(P＞0.05).③ The residence time of group Ⅱ was significantly different from that in group Ⅰ during the space exploration stage(P＜0.05).There was a significant difference be-tween the number of pups crossing the platform in group Ⅰ and groups CON,Ⅱ and Ⅲ(P＜0.05).④ There was no significant difference between HE staining and Nissl staining in hippocampal tissues of rats in each group.How-ever,compared with the CON group,the average absorbance of NeuN and SYN proteins in the hippocampus of mice in groups Ⅰ,Ⅱ and Ⅲ was significantly reduced(P＜0.05).Conclusion Hypothyroidism will have adverse effects on the cognitive function and hippocampal neuron development of pregnant rats,and the effects of interven-tion on the cognitive function of offspring at different stages of pregnancy are different,the earlier the intervention,the smaller the damage to cognitive function.

This study was designed to investigate the effects of wheat grain moxibustion on the immune function of mice immunosuppressed by cyclophosphamide,and to delve into the potential mechanisms by analyzing factors related to NF-κB signaling pathway.Sixty SPF-grade ICR mice were randomly allocated into four groups:blank group,model group,traditional Chinese medicine group and wheat grain moxibustion group,with 15 mice in each group.Immunosuppression was induced in mice of the model,traditional Chinese medicine and wheat grain moxibustion groups by intraperitoneal injection of cyclophosphamide at 80 mg/kg daily for three days,while mice of the blank group received an equivalent volume of saline.The traditional Chinese medicine group was treated with oral administration of Zhēn Qí Fú Zhèng granules,and the wheat grain moxibustion group was treated with wheat grain moxibustion at"Da Zhui,"bilateral"Zu San Li,"and bilateral"San Yin Jiao"once a day for seven consecutive days.After corresponding treatment,spleens were harvested from the mice of different groups for pathological examination,and enzyme-linked immunosorbent assay(ELISA)was utilized to measure the serum levels of IL-2,IL-4,TNF-α and IFN-γ.Additionally,Western blot analysis was conducted to assess the protein expression levels of IκBα and P-IκBα in spleen tissue.Compared with the blank group,mice in the model group exhibited poorer general conditions,significantly reduced white blood cell(WBC)count(P＜0.01),extensive damage in spleen tissue,significant decreases in serum IL-4 and IL-2 concentrations,increases in TNF-α and IFN-γ levels(P＜0.01),lower level of P-IκBα protein in spleen tissue(P＜0.01),and higher level of IκBα protein(P＜0.01).These changes mentioned above were reversed in mice of both the wheat grain moxibustion group and the traditional Chinese medicine group(P＜0.01).Compared to the traditional Chinese medicine group,on the last day of treatment,the wheat grain moxibustion group showed slightly higher WBC counts(P＜0.05),better tissue repair,and lower levels of IFN-γ(P＜0.01).In conclusion,wheat grain moxibustion can affect the activity of NF-κB signaling pathway by regulating the relative expression of IκBα and P-IκBα,and then regulate the immune response of the body,thus play a role in alleviating the immunosuppression caused by cyclophosphamide.

Cirrhosis is a severe disease caused by chronic inflammatory damage to the liver due to various factors,often complicated by portal hypertension.The primary causes of portal hypertension include increased intrahepatic vascular resistance and increased portal venous blood flow.Carvedilol,a third-generation non-selective beta-blocker(NSBB)with alpha-1 receptor-blocking role,is superior to traditional NSBBs in reducing portal pressure.It is believed that carvedilol significantly reduces hepatic venous pressure gradient(HVPG)through multiple mechanisms,prevents variceal bleeding,and extends patient survival.This paper reviews the mechanisms and clinical applications of carvedilol in the treatment of portal hypertension,focusing on its efficacy in the primary and secondary prevention of varices and its impact on the survival of cirrhotic patients with refractory ascites.

OBJECTIVE: To investigate the high risk factors of failure of autologous arteriovenous fistula (AVF) in hemodialysis patients. METHODS: A retrospective study was conducted, patients with maintenance hemodialysis (MHD) undergoing AVF admitted to General Hospital of Western Theater Command from January 2021 to December 2022 were enrolled, including 107 patients with normal AVF and 168 patients with AVF dysfanction. According to the causes of AVF failure, the patients were divided into AVF stenosis group (n = 103) and AVF thrombosis group (n = 65). Age, gender, body mass index (BMI) and comorbidities (hypertension, diabetes, coronary heart disease) and other clinical data of all patients were collected. Hemoglobin, hematocrit, white blood cell count, neutrophil count, lymphocyte count, platelet count, C-reactive protein (CRP), high density lipoprotein, low density lipoprotein, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) within 1 month of AVF use in normal dialysis patients and 1 week before AVF failure. Multivariate Logistic regression was used to analyze the independent risk factors of AVF dysfuction in MHD patients. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of risk factors on AVF dysfuction in MHD patients. RESULTS: (1) There were significant differences in age, BMI, hypertension, hemoglobin, hematocrit, PLR and CRP [age (years): 56.94±14.32, 58.83±14.05, 51.57±13.19; BMI (kg/m²): 22.83±3.10, 21.27±4.98, 23.35±2.72; hypertension: 93.20%, 64.62%, 86.92%; hemoglobin (g/L): 110.82±22.16, 88.70±24.00, 87.95±23.45; hematocrit: 0.350±0.069, 0.282±0.076, 0.275±0.071; PLR: 197.35±113.59, 192.55±138.25, 162.12±73.25; CRP (mg/L): 10.01±4.02, 8.18±5.42, 3.17±1.30, all P < 0.05], among AVF stenosis group, AVF thrombosis group and AVF normal group, there were statistically significant differences no statistically significant difference was found in other indexes among three groups. (2) Multivariate Logistic regression analysis showed that hypertension [odds ratio (OR) = 4.849, 95% confidence interval (95%CI) was 1.278-18.397, P = 0.020], elevated CRP levels (OR = 2.104, 95%CI was 1.533-2.888, P = 0.000) were associated with AVF stenosis. Elevated CRP levels (OR = 1.984, 95%CI was 1.442-2.730, P = 0.000) was an independent risk factor for AVF thrombosis. Analysis of ROC curve showed that the area under the curve (AUC) of AVF dysfunction predicted by CRP was 0.712, 95%CI was 0.637-0.786, P = 0.000; CRP cut-off value was 1.8 mg/L, the sensitivity was 67.0%, the specificity was 83.7%. CONCLUSIONS Elevated CRP is an independent risk factor for AVF failure in hemodialysis patients, which can be used to predict the occurrence of AVF failure.
Humans ; Retrospective Studies ; Constriction, Pathologic ; Renal Dialysis/adverse effects* ; Lymphocytes ; C-Reactive Protein ; Risk Factors ; Hypertension ; Hemoglobins ; Thrombosis ; ROC Curve ; Prognosis

Radiotherapy is widely used in the treatment of primary and metastatic malignant tumors. It is traditionally believed that the killing effect of radiotherapy on tumor is based on the direct or indirect damage of ionizing radiation to DNA. In recent years, the anti-tumor role and mechanism of anti-tumor immune response induced by ionizing radiation have captivated widespread attention and achieved significant progress. Among them, Cyclic GMP-AMP synthase (cGAS)-stimulator of interference genes (STING) pathway is considered to be one of the key regulatory hubs. cGAS is a cytoplasmic DNA receptor that can bind to tumor-derived double-stranded DNA and activate the downstream STING, thereby activating anti-tumor immune response of the host. In view of the latest progress in this field, the important role and potential mechanism of cGAS-STING pathway in radiotherapy immune effect were mainly summarized, and the application prospect of targeting cGAS-STING pathway in radiotherapy sensitization was explored.

OBJECTIVE To optimize the extraction technology of volatile components from Wuyao decoction. METHODS On the basis of single factor investigation ，the extraction technology of volatile components from Wuyao decoction was optimized and validated by Box-Behnken design-response surface technology using the contents of bomyl acetate ，cyperotundone，α-cyperone， ligustilide and dehydrocostuslactone ， extraction rate of volatile oil as indexes ， with extraction time ， soaking time and liquid-material ratio as factors. On this basis ，the extraction state of the decoction was quantified. RESULTS The optimal extraction technology was as followed ：the ratio of liquid -material was 13∶1（mL/g），soaking time was 0.5 h，and the extraction time was 6 h in the boiling state. The comprehensive scores of the three validation experiments were 0.948 7，0.948 4 and 0.948 6 respectively （RSD＝0.02％，n＝3），and the deviation from the predicted value （0.947 9）was no more than 1％. The boiling state of the decoction in 180 ℃ oil bath was taken as the sudden boiling state. CONCLUSIONS The optimized extraction technology is stable and feasible.

Objective To investigate the expressions of ATPase family AAA domain-containing protein 2 (ATAD2) and β-catenin,and to analyze their correlations with clinicopathological features and prognostic significance in patients with hepatocellular carcinoma (HCC).Methods The HCC tissues of 40 patients were tested by real-time PCR to study the expressions of ATAD2 and β-catenin.Real-time PCR and Western blot were performed to detect the proteins and mRNA levels of ATAD2,APC,β-catenin and wnt signaling pathway downstream.The HCC tissues of 80 patients and 20 peritumoral tissues were tested by immunohistochemistry (IHC).The cumulative survival-rate was analyzed by the Kaplan-Meier method,and univariate and multivariate were analyzed by the Cox proportional hazards model.Results ISH:The positive rates of ATAD2 and β-catenin were 65.0％ and 55.0％,respectively.These rates were significantly higher than those in the peritumoral tissues (30.0％ and 25.0％,respectively).The ATAD2 expression was related to tumor size (P ＜ 0.05),metastasis (P ＜ 0.05),serum AFP level (P ＜ 0.05) and TNM stag ing (P ＜ 0.05).The β-catenin expression was only significantly related to metastasis (P ＜ 0.05).Correlation analysis showed that the ATAD2 expression was positively related to the β-catenin expression (Pearson =0.578,P ＜ 0.01,R2 =0.3607,Spearman =0.495).This positive relationship was also found in the remaining 4 cell lines except the SK-hep1.Depleting ATAD2 up-regulated APC and down-regulated β-catenin protein and mRNA expression.Univariate and multivariate analyses showed that ATAD2 and β-catenin expressions,tumor size,metastasis,serum AFP,and TNM staging were poor prognostic factors for HCC,and ATAD2 and β-catenin expressions,metastasis,serum.AFP were independent prognostic factors.Patients whose ATAD2 and β-catenin were both positive had worse survival than those with only one positive expression or both negative expressions (P ＜ 0.05).Depleting ATAD2 down-regulated survivin,cyclinD1,c-myc,MMP7,Vimentin in wnt signaling pathway and EMT related proteins.Conclusions ATAD2 and β-catenin expressions were positively related in patients with HCC.Abnormal expressions between ATAD2 and β-catenin might participate in the wnt signaling pathway.

Objective To explore the influence of sodium oxamate on the radiaosensitivity of hypoxic nasopharyngeal carcinoma CNE2 cells. Methods The production of lactate and angiotensin Ⅱ in CNE2 with or without sodium oxamate treatment was detected by lactate assay kit and angiotensin Ⅱ ELISA kit. Cell growth of hypoxic CNE2 with or without sodium oxamate treatment was measured in vitro by MTT method. Radiosensitivity of hypoxic CNE2 with or without sodium oxamate treatment was tested by clone formation assay. Results Lactate and angiotensin Ⅱ production of CNE2 cells treated with sodium oxalate was inhibited. Sodium oxalate inhibited the proliferation of hypoxic CNE2 cells. The radiosensitivity of hypoxic CNE2 cells treated with sodium oxalate was largely improved. Conclusions Sodium oxalate inhibits the proliferation of CNE2 cells in hypoxic condition and significantly enhances the radiosensitivity of hypoxic CNE2 cells. The mechanism may be involved in its inhibiting of angiotensinⅡproduction.