ObjectiveThis study aims to compare the modeling effects of submaxillary gland antigen and salivary gland antigen in the establishment of Sjögren syndrome (SS) mouse models, and to characterize the phenotypic and immunological features of these models in comparison with spontaneous SS-prone non-obese diabetic (NOD)/LtJ mice. MethodsAdult C57BL/6J mice (equal numbers of males and females) were immunized with submaxillary gland antigen or salivary gland antigen, respectively, combined with Freund's adjuvant to induce SS models. Mice immunized with phosphate-buffered saline (PBS) combined with Freund's adjuvant served as the control group. Immunization was induced via multiple subcutaneous injections in the back with antigen combined with Freund's complete adjuvant (FCA) on Days 1 and 7. A booster immunization was administered via multiple subcutaneous injections in the back with antigen combined with Freund's incomplete adjuvant (FIA) on Day 14. Female NOD/LtJ mice were used as the spontaneous SS model group, with ICR mice as the corresponding control strain for comparative analysis. Body weight, water intake, and salivary flow rate of mice were dynamically monitored for 4 weeks. At the end of the experiment, tissue and serum samples were collected, the weights of submaxillary glands, thymus, and spleen were measured, and organ indices (organ-to-body weight ratios) were calculated. Pathological morphological analysis of the submaxillary gland and spleen was performed with hematoxylin and eosin (HE) staining. Serum interleukin-17 (IL-17) level was detected using enzyme-linked immunosorbent assay (ELISA). Real-time quantitative polymerase chain reaction was used to detect the mRNA expression levels of SS type A (SSA) and SS type B (SSB) in submaxillary gland tissues. ResultsFemale mice in the submaxillary gland antigen group exhibited significantly increased water intake (P<0.05) and reduced salivary flow rate (P<0.05) compared with the female control group. No statistically significant differences were observed in the submaxillary gland index, thymus index and spleen index (P>0.05). Focal lymphocytic infiltration was observed in the submaxillary glands, and the splenic marginal zone was enlarged. Serum IL-17 levels were significantly increased (P<0.05). There was no significant difference in submaxillary gland SSA/SSB expression levels (P>0.05). Compared with the female control group, female mice in the salivary gland antigen group showed no statistically significant differences in water intake, salivary flow rate, submaxillary gland index, and spleen index (P>0.05), whereas the thymus index was significantly reduced (P<0.01). Mild inflammatory cell infiltration and glandular atrophy were observed in the submaxillary glands, and the splenic white pulp and marginal zone were slightly enlarged. Serum IL-17 levels and submaxillary gland SSB mRNA expression levels were significantly increased (P<0.01), whereas no significant change was observed in submaxillary gland SSA expression levels (P>0.05). Compared with the male control group, mild submaxillary gland atrophy was observed in male mice in the submaxillary gland antigen group, whereas no obvious changes were found in other modeling-related indicators (P>0.05). Compared with the ICR control group, NOD/LtJ model mice exhibited elevated water intake (P<0.05), significantly reduced salivary flow rate (P<0.01), no significant differences in the submaxillary gland index or spleen index (P>0.05), but a significantly increased thymus index (P<0.05). Marked focal infiltration was observed in the submaxillary glands, the splenic marginal zone was obviously enlarged, and serum IL-17 concentrations as well as submaxillary gland SSA/SSB expression levels were significantly increased (P<0.05). ConclusionSubmaxillary gland antigen and salivary gland antigen can induce SS-related features in female C57BL/6J mice. The SS-related phenotype is more pronounced in the submaxillary gland antigen group than in the salivary gland antigen group, but weaker than that in spontaneously SS-prone female NOD/LtJ mice. Immunization of male C57BL/6J mice with submaxillary or salivary gland antigens fails to induce an obvious SS phenotype.

ObjectiveBy starting with the combination of Os Draconis， Bupleuri Radix， and Ostreae Concha， the role of mineral medicine Os Draconis in the combination of the Bupleuri Radix-containing tri-herbal medicines was preliminarily explored from the perspective of supramolecular system formation. Method① The appearance and Tyndall phenomenon of single decoction of Os Draconis， Bupleuri Radix， and Ostreae Concha， as well as co-decoction of Bupleuri Radix-Os Draconis， Bupleuri Radix-Os Draconis-Ostreae Concha， and Bupleuri Radix-Ostreae Concha were observed， and the average particle size， dispersion coefficient， and Zeta potential of suspension particles in each decoction were determined. The micromorphology of supramolecular structures was observed by scanning electron microscope （SEM）. ② The pH of different compatibility systems， liquid viscosity coefficient， liquid surface tension， freeze-dried powder yield rate， and other physical properties were determined， and the interaction of different compatibility systems was detected by infrared absorption spectroscopy （FTIR） and UV-visible spectrophotometry （UV-Vis）. ③ The composition and content difference of different compatible systems were determined by high-performance liquid chromatography （HPLC） and ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry （UPLC-Q-TOF-MS）. ResultCompared with the single decoction， the co-decoction had more obvious turbidity and Tyndall phenomenon. The particles in the co-decoction suspension were smaller and more evenly distributed， and the Zeta potential was reduced， indicating a more stable system. Under SEM， Bupleuri Radix was irregularly lamellar， and Bupleuri Radix-Os Draconis and Bupleuri Radix-Os Draconis-Ostreae Concha were mainly spherical nanoparticles. Bupleuri Radix-Ostreae Concha was irregularly lamellar， with a small number of spherical nanoparticles. The pH of the single decoction of Bupleuri Radix and co-decoction increased， and the viscosity coefficient increased. The liquid surface tension decreased. The freeze-dried powder yield rate of the Bupleuri Radix-Os Draconis co-decoction was the highest， followed by Bupleuri Radix-Ostreae Concha decoction and Bupleuri Radix-Os Draconis-Ostreae Concha decoction， and the yield rate of Bupleuri Radix single decoction was the lowest. The main change of FTIR was the stretching vibration of -OH， and the co-decoction moved to the low-frequency direction obviously. UV-Vis showed that the maximum absorption occurred at 295.8 nm for all groups， and the absorption intensity was different （Bupleuri Radix-Os Draconis>Bupleuri Radix-Os Draconis-Ostreae Concha>Bupleuri Radix-Ostreae Concha>Bupleuri Radix）. The components of Bupleuri Radix were used as the indexes， and the content of methanol extract determined by HPLC was higher than that of water extract， and the components of Bupleuri Radix single decoction were mainly saikosaponin a （SSa） and saikosaponin c （SSc）， which were slightly higher after co-decoction compatibility. UPLC-Q-TOF-MS could identify 37 compounds in both single decoction and co-decoction. ConclusionThe combination of Bupleuri Radix， Os Draconis， and Ostreae Concha can form a smaller， more uniform， and stable nano-sized supramolecular system， which is conducive to the dissolution of the main components of Bupleuri Radix， and the Os Draconis contributes the most in this process.

Objective To investigate the effect of Huangzhi oral liquid on ferroptosis and apoptosis of hepatocytes in acute hyperlipidemia mice based on abnormal lipid metabolism.Methods Forty SPF grade C57BL/6 mice were randomly assigned to the normal control group,the model group,Huangzhi oral liquid low-dose and high-dose groups,and fenofibrate group,with 8 mice in each group.All administration groups were given Huangzhi oral liquid and fenofibrate by gavage at corresponding doses,while the normal control group and the model group were given the same dose of distilled water for a period of 5 days.on the third day of administration,in addition to the normal control group,other groups were injected intramuscularly with Triton WR-1339 to establish a hyperlipidemia model.After the administration,the serum lipid levels and liver function in mice were detected.The pathological changes of liver were observed by HE staining and lipid accumulation was observed by oil red O staining.The iron content in liver tissues was detected by tissue iron assay kit.The changes in protein expression of ABCA1,ABCG5,LXRα,ASGR1,cleaved-PARP,cleaved-caspase 3,Bcl2,Bax,TFR1,SLC7A11,GCLM,GPX4 and FTH1 in liver were detected by Western Blot.Results Compared with the model group,Huangzhi oral liquid could reduce the lipid vacuoles in liver tissues,alleviate the degree of lipid degeneration,reduce the content of TC,TG,LDL-C,AST and ALT in serum,increase the content of HDL-C,increase the protein expression levels of ABCA1,ABCG5,LXRα,Bcl-2,SLC7A11,GCLM,GPX4 and FTH1 in mice liver tissues,reduce the protein expression levels of ASGR1,cleaved-PARP,cleaved-caspase 3,Bax and TFR1.Conclusion Huangzhi oral liquid can alleviate the abnormal lipid metabolism in acute hyperlipidemia mice,thus alleviates hepatocyte apoptosis and ferroptosis.

ObjectiveTo investigate the serum level of ceruloplasmin in patients with different stages and etiologies of liver diseases. MethodsA total of 1077 patients with liver diseases who were hospitalized in Department of Hepatology, The First Hospital of Jilin University, from January 2012 to January 2018 were enrolled, and the serum level of ceruloplasmin was analyzed for the patients with different liver diseases. The Kruskal-Wallis H test was used to compare the level of ceruloplasmin between the patients with virus-related liver diseases with different liver functional states, and a Spearman correlation analysis was used to investigate the correlation of ceruloplasmin with other biomarkers. ResultsIn the Wilson’s disease group, 97.6% (41/42) of the patients had a serum ceruloplasmin level of ＜0.2 g/L and 881% (37/42) had a level of ＜0.1 g/L. In the non-Wilson’s disease group, 24.3% (251/1035) of the patients had a ceruloplasmin level of ＜0.2 g/L and 0.2% had a level of ＜0.1 g/L. There was a significant difference in the serum level of ceruloplasmin between the patients with virus-related liver diseases with different liver functional states, and the patients with chronic viral hepatitis, severe viral hepatitis, and viral hepatitis cirrhosis had a significantly lower level than those with acute viral hepatitis and virus-related liver cancer (P=0005, P＜0.001, P=0.001, P=0.027, P＜0.001, and P=0.001). In the patients without Wilson’s disease, serum ceruloplasmin was positively correlated with albumin and prealbumin (r=0.068 and 0.091, both P＜0.05) and was negatively correlated with prothrombin time (r=-0.297, P＜0.05). ConclusionCeruloplasmin often decreases significantly in patients with Wilson’s disease, with a slight reduction in patients with other types of liver diseases. For these patients, it should be determined whether the reduction in ceruloplasmin is caused by hepatocyte injury or the presence of Wilson’s disease.

Objective: To explore the relationship between serum complement 1q (C1q) and C1q/tumor necrosis factor-related protein 1 (CTRP1) levels in patients with coronary atherosclerotic heart disease (CHD) and their clinical value. Methods: Case-control study.115 patients with CHD who were hospitalized in the Department of Cardiology of Ningxia Medical University General Hospital from January 2018 to November 2018 were selected as the case group, including 72 males and 43 females, aged 35-82 years, average (59.96±9.49) years old. There were three subgroups: stable angina group (SAP, n=12), unstable angina group (UA, n=69), and acute myocardial infarction group (AMI, n=34). The control group was selected from 43 healthy subjects in the same period, including 21 males and 22 females, aged 23-71 years, with an average of (45.00±10.66) years old. Serum C1q and CTRP1 levels were tested by immunoturbidimetry and ELISA, and other biochemical indicators such as triglyceride (TG) and total cholesterol (CHOL) were detected.Multiple linear regression was used to analyze the influence of various factors on C1q level. ROC curve and area under the curve (AUC) to explore the diagnostic value of C1q and CTRP1. Results: The C1q level in the CHD group (184.06±31.05) mg/L was higher than that in the control group (122.22±28.18) mg/L (t=-11.405, P<0.001). The AMI group (192.80±34.08) mg/L was significantly higher than the SAP group (169.17±27.13) mg/L (t=-2.328, P=0.021).The CTRP1 level in the CHD group [241.85(79.38)] ng/ml was lower than that in healthy control group [292.7(67.64)] ng/ml (Z=-3.64, P<0.001). Group B with higher Gensini score (t=3.672, P<0.001) and group C (t=2.529, P=0.013) had higher C1q levels than group A.After adjusting for the effects of age, sex and other indicators, C1q levels were correlated with HDL-C (β=-0.582, P<0.001),CHOL (β=0.384,P<0.001) and systolic blood pressure (β=0.142,P=0.038). The ROC curve shows that when the CHD is diagnosed, the sensitivity of C1q level >150.82 mg/L is 87%,the specificity is 88.4%, and the AUC is 0.942. The corresponding sensitivity and specificity of CTRP1 <281.80 ng/ml are 76.5% and 60.5% respectively, and the AUC is 0.688. The AUC obtained by combined predictors was 0.944, and the sensitivity and specificity were 89.6% and 86.0% respectively. When AMI is diagnosed, C1q level >178.3 mg/L, corresponding sensitivity and specificity are 70.6% and 66.1%, the AUC is 0.726, CTRP1 has no diagnostic value. Conclusions Serum C1q levels in patients with CHD are elevated, and AMI patients are higher than SAP patients; C1q may be a potential marker reflecting the severity of coronary artery disease; there is no significant correlation between serum C1q and CTRP1 in CHD patients.

The abnormal lipid levels caused by disorders of lipid metabolism are important factors leading to various diseases such as cardiovascular and cerebrovascular damage .Studies found that monitoring blood lipid levels can provide evidences for the early diagnosis of cardiovascular and cerebrovascular diseases, assessing the risks of cardiovascular and cerebrovascular diseases , and evaluation of the therapeutic effects. The commonly used lipid markers for the diagnosis of clinical cardiovascular and cerebrovascular diseases are the four routine blood lipids , such as total cholesterol ( TC) , total triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL).The application of other blood lipid markers including apolipoprotein A (ApoA), apolipoprotein B (ApoB), non high density lipoprotein cholesterol (non-HDL-C), and lipoprotein a[Lp (a)]in the diagnosis and treatment of cardiovascular and cerebrovascular diseases have also been reported .

Objective To evaluate the effect of controlled hypotension at the beginning of reperfusion on ischemia-reperfusion (I/R) injury of the liver in patients undergoing hepatectomy.Methods Forty ASA Ⅱ or Ⅲ patients (aged 30-60 years and weighing 40-70 kg) undergoing elective partial hepatectomy for liver cancer were randomly divided into two groups (n =20 each):normal blood pressure group (control group,group C) and controlled hypotension group (group H).In group C,normal blood pressure was maintained during reperfusion,while in group H,controlled hypotension (the mean arterial blood pressure (MAP) was maintained at 60-70 mm Hg) was performed for 10 minutes since the beginning of reperfusion.Hepatic portal was occluded during operation.Venous blood samples were taken before hepatic ischemia (T0,baseline) and after 15 minutes of ischemia (T1) and after 25 minutes of reperfusion (T2) for determination of plasma levels of endothelin (ET),nitric oxide (NO),tumor necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1).Results I/R of the liver led to significant increases in plasma levels of ET,TNF-α and IL-1 and a decrease in plasma level of NO at T1,2 as compared with the baseline values at T0 in both groups.Plasma levels of ET,TNF-α and IL-1 were significantly lower while plasma level of NO was significantly higher at T2 in group H than in group C.Conclusion Controlled hypotension for 10 minutes in the initial stage of reperfusion can attenuate I/R-induced injury to the liver in patients undergoing hepatectomy through balancing ET with NO and inhibiting inflammation responses.

Objective To evaluate the effect of controlled hypotension at the beginning of reperfusion on ischemia-reperfusion (I/R) injury of the liver in patients undergoing hepatectomy. Methods Forty ASA Ⅱ or Ⅲ patients aged 30-60 yr weighing 40-70 kg undergoing elective partial hepatectomy for liver cancer were randomly divided into 2 groups ( n = 20 each): group C normal BP and group H controlled hypotension. Hepatic portal was occluded during operation. In group C normal BP was maintained during reperfusion while in group H controlled hypotension (MAP was maintained at 60-70 mm Hg) was performed for 10 min since the beginning of reperfusion.Venous blood samples were taken before hepatic ischemia (T0 ,baseline) and at 15 min of ischemia (T1) and 25 min of reperfnsion (T2 ) for determination of plasma endothelin (ET), nitric oxide(NO), TNF-α and IL-1 concentrations. Results I/R of the liver led to significant increase in plasma ET, TNF-α and IL-1 concentrations and decrease in plasma NO concentration at T1,2 as compared with the baseline values at T0 in both groups. Plasma ET,TNF-α and IL- 1 concentrations were significantly lower while plasma NO concentration was significantly higher at T2 in group H than in group C. Conclusion Ten minutes controlled hypotension in the initial stage of reperfusion can attenuate I/R-induced injury to the liver in patients undergoing hepatectomy by balancing ET with NO and inhibiting inflammation response.