OBJECTIVE To study the effects of Hugan buzure formula （HBF） on intrahepatic cholestatic liver injury in rats and its potential mechanism. METHODS Rats were randomly divided into control group， model group， ursodeoxycholic acid （UDCA） group （positive control， 60 mg/kg ） and HBF low-dose， middle-dose and high-dose groups （HBF-L， HBF-M， HBF-H groups， 0.4， 0.8， 1.6 g/kg ）， with 6 rats in each group. The rats in each drug group were given the corresponding drug solution intragastrically， once a day， for 7 consecutive days. The rats in the control group and the model group were given equal volumes of water intragastrically. On the 5th day， except for the control group， the rats in other groups were single intragastrically administered with alpha-naphthyl isothiocyanate olive oil solution （100 mg/kg） to establish the model. After 48 h of modeling， the contents of liver function indexes （aspartate aminotransferase， alanine aminotransferase， alkaline phosphatase， total bile acid， total bilirubin， direct bilirubin） and oxidative stress indexes [malondialdehyde （MDA）， glutathione （GSH）， superoxide dismutase] in serum of rats were detected； the pathological changes of liver tissue were observed. The mRNA expressions of inflammation-related factors [tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）] and farnesoid X receptor （FXR） signaling pathway-related factors [FXR， small heterodimer partner （SHP）， multidrug resistance protein 2 （MRP2）， bile salt export pump （BSEP）， Na+-taurocholate cotransporting polypeptide （NTCP）， organic anion-transporting polypeptide 2 （OATP2） and cholesterol 7α-hydroxylase （CYP7A1）]， the expressions of FXR signaling pathway-related proteins （FXR， MRP2， BSEP， NTCP） and nuclear factor- κB p65 （NF- κB p65） in liver tissue were detected.RESULTS Compared with the model group， the contents of liver function indexes and the level of MDA in serum， the mRNA expressions of the above inflammation-related factors and CYP7A1， and the relative expression of NF-κB p65 in liver tissue were significantly decreased； the levels of GSH in serum， the mRNA expressions of FXR， SHP， MRP2， BSEP， NTCP and OATP2， and the relative expressions of FXR， MRP2， BSEP and NTCP in liver tissue were significantly increased （P＜0.05 or P＜0.01）； the pathological changes of liver tissue were significantly improved. Only some indexes in HBF-L group， HBF-M group and UDCA group were significantly reversed （P＜0.05 or P＜0.01）. CONCLUSIONS HBF can prevent intrahepatic cholestatic liver injury in rats， and the effects may be related to the activation of FXR signaling pathway and the reduction of inflammation and oxidative stress.

OBJECTIVE To study the protective effect of phenolic acid components from Salvia deserta Schang on the oxidative stress injury of human renal tubular epithelial cells HK -2 induced by high glucose and high fat . METHODS HK-2 cells were divided into control group ，model group ，canagliflozin group （positive control group ，15 μmol/L），purified product of phenolic acids from S. deserta Schang group （10.8 μg/mL），4 monomers group （salvianic acid ，protocatechuic aldehyde ，caffeic acid，rosmarinic acid ，50 μmol/L）. In addition to the control group ，cell injury model of high glucose and high fat was established in other groups （500 μmol/L palmitic acid+ 30 mmol/L glucose for 48 h）and cultured for 48 h. The cell apoptotic rate ，the contents of malondialdehyde （MDA）and glutathione （GSH），and the activity of superoxide dismutase （SOD）were detected in each group ； the expression levels of nuclear erythroid 2-related factor 2（Nrf2），Kelch-like ECH -associated protein 1（Keap1）protein，heme oxygenase-1（HO-1）and NADH ：quinone acceptor oxidoreductase 1（NQO1）were determined in above 5 groups（except for salvianic acid ，protocatechuic aldehyde ，caffeic acid ）. RESULTS Compared with control group ，the apoptotic rate of HK -2 cells in model group was increased significantly （P＜0.01）；the content of MDA was increased significantly （P＜0.01），while the content of GSH and the activity of SOD were decreased significantly ；protein expressions of Nrf 2，NQO1 and HO -1 2018D01C169） were significantly down -regulated（P＜0.01），while the protein expression of Keap 1 was up -regulated significantly （P＜0.01）. Compared with model group ， the apoptotic rate and the content of MDA were decreased significantly in administration groups（P＜0.01）；the content of GSH in administration groups and the activity of SOD in purified product of phenolic acids group，protocatechuic aldehyde group and rosmarinic acid group were increased significantly （P＜0.01）. The protein expressions of Nrf2，HO-1 and NQO 1 in purified product of phenolic acids group as well as the protein expression of Nrf 2 in rosmarinic acid group were up -regulated significantly （P＜0.01），while the protein expression of Keap 1 was down -regulated significantly in purified product of phenolic acids group and rosmarinic acid group （P＜0.01）. CONCLUSIONS The phenolic acids components from S. deserta Schang can relieve oxidative stress injury of renal tubular epithelial cells induced by high glucose and high fat ，the mechanism of which may be associated with activating Keap 1/Nrf2 signaling pathway and inhibiting oxidative stress response .

Posttranslational modifications of antibody products affect their stability,charge distribution,and drug activity and are thus a critical quality attribute.The comprehensive mapping of antibody modifications and different charge isomers(CIs)is of utmost importance,but is challenging.We intended to quanti-tatively characterize the posttranslational modification status of CIs of antibody drugs and explore the impact of posttranslational modifications on charge heterogeneity.The CIs of antibodies were fraction-ated by strong cation exchange chromatography and verified by capillary isoelectric focusing-whole column imaging detection,followed by stepwise structural characterization at three levels.First,the differences between CIs were explored at the intact protein level using a top-down mass spectrometry approach;this showed differences in glycoforms and deamidation status.Second,at the peptide level,common modifications of oxidation,deamidation,and glycosylation were identified.Peptide mapping showed nonuniform deamidation and glycoform distribution among CIs.In total,10 N-glycoforms were detected by peptide mapping.Finally,an in-depth analysis of glycan variants of CIs was performed through the detection of enriched glycopeptides.Qualitative and quantitative analyses demonstrated the dynamics of 24 N-glycoforms.The results revealed that sialic acid modification is a critical factor ac-counting for charge heterogeneity,which is otherwise missed in peptide mapping and intact molecular weight analyses.This study demonstrated the importance of the comprehensive analyses of antibody CIs and provides a reference method for the quality control of biopharmaceutical analysis.

Objective: To investigate the number and distribution of dendritic cells (DCs), macrophages and M2 macrophages in renal tissues of patients with IgA nephropathy (IgAN) and their correlation with clinicopathological parameters, and explore its role in the progression of IgAN. Methods: Renal tissue samples from 42 patients aged ≥18 years with IgAN were collected by kidney biopsy in Guangdong Provincial People's Hospital from January 2018 to June 2018. The patients were divided into different groups according to Oxford classification and Lee grade classification criteria. The distribution and number of DCs (CD209), macrophages (CD68) and M2 macrophages (CD68 and CD206) were detected by immunohistochemistry. Spearman correlation test was used to analyze the correlation between the number of DCs and macrophages in renal tissues and clinical pathological parameters. Results: The number of DCs in the glomeruli of the M1, T0 and C1 groups increased significantly compared with the M0, T1 and C0 groups, and the number of DCs in the renal interstitium of the T1 group increased significantly compared with the T0 group (all P<0.05). The number of glomerular macrophages in group C1 was significantly higher than that in group C0. The number of macrophages in S1, T1 and Lee IV-V tubulointerstitial groups was significantly higher than that in S0, T0 and Lee II-III groups (P<0.05). The number of M2 macrophages in the S1, T1 and Lee IV-V groups was significantly higher in the tubulointerstitial group than in the S0, T0 and Lee II-III groups (all P<0.05). The blood urea nitrogen, serum creatinine and 24 h urine protein levels in the T1 and Lee IV-V groups were significantly higher than those in the T0 and Lee II-III groups, and the serum albumin levels in the Lee IV-V group were significantly lower (all P<0.05). Spearman correlation analysis showed that the number of DCs in renal interstitium was positively correlated with the proportion of tubulointerstitial fibrosis. There were a positive correlation between the proportion of glomerular segmental sclerosis and tubulointerstitial fibrosis and renal interstitial macrophages and M2 macrophages. The number of M2 macrophages was positively correlated with serum creatinine and 24 h urine protein (both P<0.05). Conclusions The number of DCs and M2 macrophages in kidneys are positively correlated with the clinicopathological features of IgAN patients, which indicates that they may be associated with disease progression.

Objective To evaluate the value of proteinuria in predicting acute kidney injury (AKI) after cardiac surgery in elderly patients.Methods To retrospectively analyze the perioperative clinical data of elderly patients (age 60 or older)undergone cardiac surgery with cardiopulmonary bypass at Guangdong General Hospital from January 2005 to December 2010.Target patients were divided into two groups according to AKI defined by the KDIGO criteria.Data for those two groups were examined by single-factor analysis,and then logistic regression analysis was used to further determine independent factors of AKI after cardiac surgery.Results Among 848 elderly patients,AKI occurred in 524(61.8％) participants,including 39.2％(n=332)at AKI stage 1,16.6％ (n =141) at AK I stage 2,and 6.0 ％ (n=51) at AKI stage 3.A total of 15.9 ％ of patients(n=135) had preoperative proteinuria,including 12.4 ％ (n =106) with mild proteinuria,and 3.5 ％ (n =30) with heavy proteinuria.Logistic regression analysis showed that proteinuria was correlated with postoperative AKI.With the increase of proteinuria,the risk of AKI also increased,and the OR values of mild and severe proteinuria were 1.758 (1.020-3.029) and 4.758 (1.326-17.077),respectively.Conclusions Preoperative proteinuria may predict the occurrence of AKI after cardiac surgery in elderly patients.There is a gradual increase in the risk of AKI as proteinuria becomes more severe.Early institution of therapeutic interventions may be used in elderly patients with preoperative proteinuria undergoing cardiac surgery to attenuate the risk of AKI.

BACKGROUND:Magnesium alloy is a material that is easily degradable and has good mechanical properties.OBJECTIVE:To study the effects of the two kinds of magnesium aloy materials (AM50 and WE43) on proliferation and morphology of human umbilical vein endothelial cells.METHODS: Human umbilical vein endothelial cells at logarithmic phase were cultured in 100%, 50%, 10% extracts of AM50 and WE43 or directly seeded on the surface of AM50 and WE43 for 24 hours to study the morphological effect of magnesium alloys on the cells. Human umbilical vein endothelial cells cultured routinely served as negative controls. Relative growth rate of the cells was detected at 12, 24, 48 hours after culture. Cell morphology was observed using immunofluorescence staining at 24 hours after culture, and pH and element levels in the cell supernatant were measured.RESULTS AND CONCLUSION: (1) AM50 and WE43 extracts showed no effects on the proliferation of human umbilical vein endothelial cells in comparison with the negative control group. (2) Compared with the negative control group, reduced area of human umbilical vein endothelial cells was found on the surface of AM50 or WE43 alloy by the immunofluorescent staining, and the cytoskeleton of the cytoplasm was blurred. However, after 24 hours of culture, morphological changes of the cells cultured in 10%, 50% and 100% AM50 or WE43 extracts were consistent with those cultured routinely. The cytoskeleton of the cytoplasm was clearly visible. (3) Compared with the negative control group, the pH values of 100% AM50 and WE43 extract groups were significantly upregulated, and the level of magnesium element was also increased remarkably. In summary, AM50 and WE43 alloys possess good cytocompatibility with human umbilical vein endothelial cells, and have no influence on the cell proliferation and growth.

Objective:To determine expression levels of ubiquitin C-terminal hydrolase-L1 (UCH-L1) and serum glial fibrillary acidic protein (GFAP) in patients with acute cerebral infarction and their clinical significance.Methods:A total of 80 patients with acute cerebral infarction in Chongqing Cancer Hospital from January 2014 to February 2016 were enrolled as an observation group.Another 80 healthy people served as a control group.The expression levels of UCH-L1 and GFAP in the 2 groups were detected.Results:Sensibility and specificity for UCH-L1 and GFAP were 75.0％,87.5％ and 81.3％,90.0％,respectively.Receiver operating characteristic curve areas of UCH-L1 and GFAP were 0.670 and 0.757,respectively.There were no significant significance in age,gender,drinking,smoke,diabetes,and hyperlipidemia in the 2 groups (P＞0.05).High blood pressure rate in the observation group was higher than that in the control group (P＜0.05).Spearson/Pearson analysis showed that serum UCH-L1 and GFAP levels were positively correlated with hypertension,but they were negatively correlated with sex,age,diabetes,hyperlipidemia,alcohol consumption,smoking,and other factors.General data at different time in the observation group was not statistically different (P＞0.05).The expression levels of UCH-L1 and GFAP in the observation group was higher than that in the control group (P＜0.05).UCH-L1 and GFAP levels at different time in the 2 groups were not statistically different (P＞0.05).UCH-L1 and GFAP levels in the light,medium,and heavy groups were higher than those in the control group (P＜0.05),while UCH-L1 and GFAP levels in the medium and heavy groups were higher than those in the light group (P＜0.05).There was significant difference between levels of UCH-L1 or GFAP and infarction size at different time in the observation group (P＜0.05).The results of Pearson correlation analysis showed that the levels of serum UCH-L1 and GFAP were positively correlated (r=0.634,P=0.001).Conclusion:The levels of serum UCH-L1 and GFAP are significantly increased at the early stage of acute cerebral infarction,and they have a certain correlation with the severity of cerebral infarction,which can provide a basis for early clinical diagnosis and treatment.

Objective To investigate the expression of helper T cells (Th)17/regulatory T cells (Treg) balance associated factors in rheumatoid arthritis (RA) patients and their correlation with serum midkine (MK).Methods A total of 60 RA patients were divided into active RA patients (n=32) and inactive RA patients group (n=28).MK level in sera was detected by enzyme linked immunosorbent assay (ELISA) in 60 patients with RA and 30 healthy controls (HCs).The fraction of CD4+CD25+FOXP3+ Treg cells and IL-17+CD4+ Th17 cells in RA patients and healthy controls were determined by flow cytometry (FCM), and the expreasion of Foxp3, RORγt, Signal transducer and activator of transcription (STAT) 3 and STAT5 mRNA were detected with real-time polymerase chain reaction (PCR).Results were evaluated using ANOVA followed by q tests for comparisons of Th17 population between active RA patients, inactive RA patients and HCs, t test was used for comparing of Foxp3, RORγt, STAT3, STAT5 mRNA between RA group and HCs.The correlations between serum MK concentration and peripheral Treg cells, Th17 cells, Foxp3, RORγt, STAT3, STAT5 mRNA were analyzed by Pearson's correlation analysis.Results The percentages of Treg cells from active RA patients, inactive RA patients and HCs were significantly different (F=129.6, P＜0.01), the percentages of Treg cells of active RA patients [(1.41±1.05)％] were lower than that of the inactive RA patients [(3.6±1.6)％;q =7.92, P＜0.05] and healthy group [(7.7±1.7)％;q=22.45, P＜0.05], and there was significant difference between healthy group and inactive RA group (q=14.53, P＜0.05).The percentages of Th17 cells of the three groups were also significantly different (F=36.3, P＜0.01),the percentage of Th17 cells of active RA patients [(1.84±1.01)％] was significantly higher than that of inactive RA patients [(0.71±0.28)％;q=9.59, P＜0.05] and healthy group (0.53±0.16)％ [(P＜0.05;q=1 1.10, P＜0.05], there was no significant difference between the inactive RA group and healthy group (q=1.51, P＞0.05).The expression of RORγt and STAT3 mRNA in RA patients was higher than that of healthy controls (t=5.84, P＜0.01;t=4.52, P＜0.01).The expression of Foxp3 and STAT5 mRNA in RA patients were lower than healthy controls (t=6.01, P＜0.01;t=2.18, P＜0.05).Serum MK values were correlated with STAT5 (r=-0.55, P＜0.01), but not with Foxp3, RORγt, STAT3 mRNA or the percentage of Treg/Th17 cells.Conclusion Serum MK expression and the percentage of Th17 cells increase, while the percentage of Treg cells decrease in RA patients.Serum MK values are negatively correlated with STAT5 mRNA which is associated with Th17/Treg balance.This may be important in the pathogenesis of RA.

Objective To understand the epidemiological characteristics of patients with advanced schistosomiasis in Hunan Province,so as to provide the evidence for formulating the advanced schistosomiasis prevention strategies and measures. Meth-ods The data of advanced schistosomiasis patients were collected and analyzed retrospectively with the cross section research method and description method in Hunan Province,2012. Results There were 5 722 advanced schistosomiasis patients in Hu-nan Province,and among them,4 112 patients were male(71.86%),and 1 610 were female(28.14%). Totally 5 311 patients came from the schistosomiasis endemic areas(92.82%)and 411 patients from non-schistosomiasis endemic areas(7.18%). The prevalence rate of advanced schistosomiasis was 8.46/10 000. The mean age of advanced schistosomiasis patients was 60.30 ± 11.63 years,and the youngest was 17 years old and the oldest 92 years old. In the age composition of advanced schistosomiasis pa-tients,the greatest number of cases was in the 60-70 years age group (32.72%). There were 3 595 cases of ascites type (62.83%),2107 cases of splenomegaly type(36.82%),11 cases of dwarf type(0.16%),and 11 cases of colon proliferation type (0.35%). Conclusion The prevalence rate of advanced schistosomiasis is relatively stable in Hunan Province,and the age of the patients showed an old aging trend. The salvation of advanced schistosomiasis patients in non-endemic areas should be strength-ened.

Amino Acid Sequence ; Genes, Bacterial ; Hydrogen Peroxide ; pharmacology ; Molecular Sequence Data ; Mutation ; genetics ; Mycobacterium ; drug effects ; genetics ; growth & development ; Peptides ; chemistry ; metabolism ; Stress, Physiological ; drug effects