Factors influencing the efficacy of residual thyroid clearance with 131I for the first time after surgery in patients with differentiated thyroid cancer / 中国医师杂志

Objective:To explore the influencing factors of residual thyroid clearance with 131I after surgery in patients with differentiated thyroid cancer (DTC). Methods:A retrospective analysis was conducted on the clinical data of 100 DTC patients admitted to the Hunan Provincial People′s Hospital from January 2018 to February 2021 who underwent 131I treatment for the first time. The success rates of first thyroidectomy using different doses of 131I, different pathological types, and different treatment times were compared, and logistic regression analysis was conducted to investigate the influencing factors of the efficacy of first postoperative 131I thyroidectomy in DTC patients. Results:A total of 54 patients successfully cleared residual thyroid, 46 patients failed to clear residual thyroid, and the success rate of clearing residual thyroid was 54%. The success rates of first clearance of residual thyroid in patients with 131I doses of 80 mCi, 90 mCi, and 100 mCi were 37.50%(12/32), 52.78%(19/36), and 71.88%(23/32), respectively, with statistically significant differences among the groups ( P<0.05); The success rates of first removal of residual thyroid in patients with follicular carcinoma, mixed papillary follicular carcinoma, and papillary carcinoma were 65.71%(23/35), 39.13%(9/23), and 52.38%(22/42), respectively. There was no statistically significant difference between the groups ( P>0.05); The success rates of first removal of residual thyroid in the group1 of patients (treatment time<3 months), the group2 of patients (treatment time 3-12 months), and the group3 of patients (treatment time>12 months) were 68.09%(32/47), 44.44%(16/36), and 35.30%(6/17), respectively. There was no statistically significant difference between the groups ( P>0.05); There was no statistically significant difference in the success rate of clearing residual thyroid in DTC patients of different genders, ages, pathological stages, and thyroid stimulating hormone (TSH) levels (all P>0.05); The difference in the success rate of clearing residual thyroid in DTC patients with different metastatic conditions and stimulating thyroid globulin (sTg) was statistically significant (all P<0.05); sTg, postoperative lymph node metastasis, and postoperative distant metastasis were independent risk factors for the efficacy of residual thyroid clearance in DTC patients for the first time after surgery (all P<0.05). Conclusions:The influencing factors for the efficacy of the first 131I in removing residual thyroid include differences in 131I dosage, presence or absence of metastatic lesions during treatment, Tg levels, etc. Reducing Tg levels is an important factor in improving remission rate, and controlling lymph nodes and distant metastasis is a key factor for the successful efficacy of the first 131I in removing residual thyroid.

Effect of bergapten on glucose and oxygen deprivation induced PC12 cell injury by regulating long non-coding RNA opioid receptor gene expression / 解剖学报

Objective To study whether bergapten (BG) protects PC12 cells from oxygen-glucose deprivation (OGD) induced cell injury by regulating long non-coding RNA (lncRNA) opioid receptor gene (Oprm1) expression. Methods PC12 cells were divided into control (Con) group, OGD group, OGD+ low concentration BG (BG-L) group, OGD+medium concentration BG (BG-M) group, OGD + high concentration BG (BG-H) group, OGD + pcDNA group, OGD+pcDNA-Oprm1 group, OGD+BG+si-NC group, OGD+BG+si-Oprm1 group. The malondialdehyde (MDA) content, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were measured by the kits. Cell apoptosis rate was analysed by flow cytometry. The expression level of Oprm1 was analysed by Real-time PCR. Results Compared with the Con group, the apoptosis rate and MDA content of PC12 cells in OGD group increased significantly, whereas Oprm1 expression, SOD and GSH-Px activity decreased significantly (P < 0. 05). Compared with the OGD group, the apoptosis rate and MDA content of PC12 cells in the OGD + BG-L group, OGD + BG-M group, OGD + BG-H group were significantly reduced, whereas the Oprm1 expression, SOD and GSH-Px activities increased significantly (P < 0. 05). Compared with the OGD+pcDNA group, the apoptosis rate and MDA content of the PC12 cells in the OGD+pcDNA-Oprm1 group reduced significantly, whereas the SOD and GSH-Px activities increased significantly (P<0. 05). Compared with the OGD+BG+si-NC group, the apoptosis rate and MDA content of PC12 cells in the OGD+BG+si-Oprm1 group increased significantly, whereas the SOD and GSH-Px activities decreased significantly (P < 0. 05). Conclusion Bergapten may alleviate OGD-induced PC12 cell injury, which is correlated to the up-regulation of lncRNA Oprm1 expression.

Establishment of lectin-ELISA for sialylated fetuin-A and its diagnostic value in primary hepatocellular carcinoma / 中华检验医学杂志

Objective:To establish a lectin enzyme-linked immunosorbent assay (lectin-ELISA) for the dection of sialylated fetuin-A and to explore the clinical diagnostic value of sialylated fetuin-A in hepatocellular carcinoma (HCC).Methods:From January 2017 to December 2020, 300 HCC patients and 160 disease controls, including 36 liver cirrhosis subgroups and 124 chronic hepatitis B subgroups, were collected from Shanghai Eastern Hepatobiliary Surgery Hospital. At the same time, 100 healthy subjects were collected as healthy controls. Lectin-ELISA method for detecting sialylated fetuin A was established based on the principle that Sambucus nigra lectin (SNA) can recognize the structure of α-2, 6-linked sialic acid residues. Differences between groups were compared using t-test or analysis of variance. Logistic regression method was used to establish the multi-index joint detection model, and receiver operating characteristic curve (ROC) was used to evaluate the efficacy of single index and joint detection model in the diagnosis of HCC.Results:A lectin-ELISA method for the detection of serum Sia-fetuin A was established. The linear regression coefficient of the system was 0.978 5, and the precision evaluation and interference experiments were in line with the clinical detection requirements. Using this method to detect serum Sia-fetuin A levels in each group, the levels of HCC group, disease control group and healthy control group were 1.362±0.310, 1.199±0.370, 1.086±0.420, respectively, and the three groups decreased in turn. The areas under the curve of Sia-fetuin A, α-fetoprotein, and their combined detection models for differential diagnosis of HCC were 0.790, 0.809, and 0.860, respectively. The diagnostic model had a sensitivity of 79.3% (238/300) and a specificity of 95.0% (247/260). Among the 300 patients in the HCC group, 138 (46%) patients were negative for serum AFP (<20 μg/L), and their serum Sia-fetuin A level was 1.364±0.305. Combining the disease control group and the healthy control group into the non-Cancer group, the serum Sia-fetuin A level was 1.146±0.381. The serum level of Sia-fetuin A in AFP-negative HCC patients was higher than that in non-HCC group ( t=6.134, P<0.001). The areas under the curve of Sia-fetuin A and the combined diagnostic model for the diagnosis of AFP-negative HCC were 0.776 and 0.919, respectively. The combined diagnostic model had a sensitivity of 93.4% (129/138) and a specificity of 77.3% (201/260). Conclusion:Serum Sia-fetuin A and combined determination model can provide a new auxiliary diagnostic index for AFP-negative HCC.

Value of multi-glycan in the auxiliary diagnosis of dual-phenotype hepatocellular carcinoma / 临床肝胆病杂志

Objective To investigate the expression of multi-glycan in serum of patients with dual-phenotype hepatocellular (DPHCC) and its clinical significance. Methods Serum samples were collected from 65 patients with DPHCC, 80 patients with primary hepatocellular carcinoma (HCC), and 120 patients with liver cirrhosis (LC) who were treated in Mengchao Hepatobiliary Hospital of Fujian Medical University from June 2019 to December 2020. DNA sequencer-aided fluorophore-assisted carbohydrate electrophoresis was used to measure the expression of N-glycan in serum, The measurement data of normal distribution were compared by t -test between the two groups and analysis of variance between multiple groups; The measurement data with non normal distribution were compared by Mann-Whitney U test between the two groups and Kruskal-Wallis H test between multiple groups, the chi-square test was used for comparison of categorical data between groups.The logistic regression method was used to establish the common index model. The efficacy of AFP, PIVKA - Ⅱ, CEA, CA19-9 and multi glycan in the diagnosis of DPHCC was evaluated by receiver operating characteristic (ROC) curve, and the area under ROC curve (AUC) was compared by Z test. Results There was a significant difference in multi-glycan between the DPHCC group and the HCC group ( P < 0.001), while there were no significant differences in AFP, PIVKA-Ⅱ, CEA, CA19-9, and SUM between the two groups ( P =0.924, 0.084, 0.442, 0.924, and 0.206). Multi-glycan had an area under the ROC curve (AUC) of 0.775, which was significantly higher than that of AFP (0.507), PIVKA-Ⅱ (0.584), CEA (0.537), CA19-9 (0.505), and SUM (0.561), and multi-glycan had a sensitivity of 69.23%, which was increased compared with the other 5 items. There were significant differences in multi-glycan, AFP, PIVKA-Ⅱ, CA19-9, and SUM between the DPHCC group and the LC group (all P < 0.001), but there was no significant difference in CEA between the two groups ( P =0.14). Multi-glycan had an AUC of 0.780, which was also higher than that of AFP (0.767), PIVKA-Ⅱ (0.743), CEA (0.566), CA19-9 (0.689), and SUM (0.713), and multi-glycan had a sensitivity of 89.23%, which was increased compared with the other five items. Conclusion Multi-glycan can be used as one of the indicators for the auxiliary diagnosis of DPHCC.

The expression and clinical value of CHI3L1 in hepatocellular carcinoma / 中华检验医学杂志

Objective:To investigate the clinical management value of chitinase 3-like 1 protein(CHI3L1) in hepatocellular carcinoma (HCC) by studying the expression of CHI3L1 in peripheral blood, liver cancer and paired adjacent non-tumor tissues.Methods:Retrospective study. From 2013 to 2017, 405 patients with HCC in Third Affiliated Hospital of Naval Medical University were enrolled into the study. Meanwhile, 112 patients with liver cirrhosis (LC), 114 health subjects were included as disease and health controls. CHI3L1 in peripheral blood was detected by ELISA kit. Tissues array was made by collecting 90 pairs of tumor tissues and matched paracancer tissues, from HCC patients who were conformed by pathology. The expression of CHI3L1 in HCC tissues was analyzed by immunohistochemistry. Differences between independent groups were tested by Mann-Whitney U test or Kruskal Wallis H test, Pearson correlation analysis was used for analyzing the relationship between two subjects, and matched rank sum test was used for cancer tissue and adjacent tissue comparison. Results:The median (quartile) of CHI3L1 protein in LC group, HCC group and NC group was 195.8 (103.3,330.4) μg/L,118.2 (74.9,201.0) μg/L,46.8 (30.7,66.4) μg/L independently. The protein level of CHI3L1 in LC group was significantly higher than that in HCC group and health control group ( Z=5.186,12.928, P<0.001). HCC group was significantly higher than that in health control group ( Z=10.788, P<0.001). The level of CHI3L1 in HCC group was not related to whether liver cirrhosis was accompanied ( Z=-0.286, P=0.775). The level of serum CHI3L1 was positively correlated with noninvasive fibrosis markers (HA, PⅢNP, Ⅳ-C, FIB-4 index) ( r=0.202,0.159,0.299 and 0.221, P<0.05) and negatively correlated with ALB( r=-0.326, P<0.05) while positively correlated with AST and PT( r=0.138, 0.160, P<0.05). Positively correlation was observed between CHI3L1 and tumor size ( r=0.284, P<0.001). CNLC stage [CHI3L1 level in advanced group125.2(81.9,228.5)μg/L was higher than that in early group112.0(70.2,169.2)μg/L ( Z=-2.326, P=0.018)], but no correlation with microvascular invasion( Z=-1.531) and tumor capsule(χ 2=0.818, P>0.05). In 73 cases of HCC tissues, the positive rate of CHI3L1 was 78% (57/73) in cancer tissues and 83%(61/73) in paired adjacent non-tumor tissues. The staining intensity score of paracancer tissue 1.5(1.5,2.5) was higher than that of cancer tissue 1.5(1.5,2.0)( Z=-2.053, P=0.040). Conclusions:The tissue source of CHI3L1 protein in HCC includes cancer tissue and paracancerous tissue. The detection of serum CHI3L1 level is helpful to evaluate tumor load assessment and disease stratification management in HCC.

The value of core fucosylated alpha 2 macroglobulin in the diagnosis of hepatocellular carcinoma / 中华检验医学杂志

Objective To investigate the core fucosylated alpha 2-macroglobulin(LCA-α2M) level in patients with hepatocellular carcinoma (HCC), liver cirrhosis (LC) and chronic hepatitis B (CHB), and explore its diagnostic value in HCC. Methods A total of 193 HCC patients,104 LC patients and 71 HC patients in Shanghai Eastern Hepatobiliary Surgery Hospital and 45 CHB patients in Changzheng Hospital from January 2013 to December 2016 were included for retrospective study. The method for detecting LCA-α2M was set up, and then the levels of serum α2M and LCA-α2M in each group were detected. The diagnostic value of LCA-α2M for HCC was evaluated by receiver operating characteristic (ROC) analysis. Result The level of LCA-α2M/α2M × 100(LCA-α2M％) was significantly higher in HCC patients[31.25(26.61-35.42)] than that in LC patients [26.00(22.30-30.64)], CHB patients[26.23 (23.86-31.86)] and healthy controls[20.29(17.35-22.60)] (H values were 5.626, 3.388 and 10.942, respectively, P<0.05). The area under the receiver operating characteristic curve (AUC) of LCA-α2M％for identifying HCC was 0.768 (0.725-0.808). Combined α-fetoprotein(AFP) and LCA-α2M％, the area under the ROC curve was 0.890(0.856-0.919). For AFP negative HCC patients, the sensitivity of LCA-α2M％was 77.42％(24/31). Conclusion LCA-α2M％ has some values in assistant diagnosis of HCC, and could improve the detection of AFP negative HCC patients.

Role of GALAD serological model in the clinical diagnosis of primary hepatocellular carcinoma / 中华检验医学杂志

Objective To explore the value of GALAD model, including gender, age, AFP, AFP-L3 and DCP in diagnosis of primary hepatocellular carcinoma and prediction of microvascular invasion (MVI). Methods Using retrospective study method, 5919 patients with primary hepatocellular carcinoma (HCC) who received radical operation from January 2015 to December 2018 in Eastern Hepatobiliary Surgery Hospital were enrolled into study group. At the same time, 1745 patients with benign liver diseases (BLDs) were enrolled into control group. The concentration of DCP was detected by Lumipulse G1200 automatic immune analyzer, and the concentration of AFP was detected by Cobas e601 automatic immune analyzer. AFP-L3 was detected by affinity adsorption centrifugation. The non-parametric Mann Whitney test was used to compare the difference between two groups. The chi square test was used to compare the rates. The diagnostic value of single serological marker and GALAD model for primary hepatocellular carcinoma was analyzed. The predictive effect of GALAD model on MVI of primary hepatocellular carcinoma was evaluated. Results Compared with single serum marker, the diagnostic value of GALAD model is higher. When the cutoff value is-0.33, the diagnostic sensitivity, specificity and accuracy reach to 91.9％(5440/5919), 86.8％ (1515/1745) and 90.7％ (6955/7664), respectively. The area under the curve can reach 0.960 [95％CI (0.955-0.964)]. Compared with no MVI (MO) group, the value of GALAD model in MVI low-risk group (M1), MVI high-risk group (M2) and MVI (M1+2) were significantly higher (Z values were-12.517,-22.883,-21.655, P<0.05), Galad model predicts MVI (M2) in high risk group, AUC was 0.717 [95％CI (0.701-0.733)] (M0 ratio M2). Conclusion GALAD model has better diagnostic performance in primary hepatocellular carcinoma and has certain predictive value for microvascular invasion.

Role of GALAD serological model in the clinical diagnosis of primary hepatocellular carcinoma / 中华检验医学杂志

Objective@#To explore the value of GALAD model, including gender, age, AFP, AFP-L3 and DCP in diagnosis of primary hepatocellular carcinoma and prediction of microvascular invasion (MVI).@*Methods@#Using retrospective study method, 5 919 patients with primary hepatocellular carcinoma (HCC) who received radical operation from January 2015 to December 2018 in Eastern Hepatobiliary Surgery Hospital were enrolled into study group. At the same time, 1 745 patients with benign liver diseases (BLDs) were enrolled into control group. The concentration of DCP was detected by Lumipulse G1200 automatic immune analyzer, and the concentration of AFP was detected by Cobas e601 automatic immune analyzer. AFP-L3 was detected by affinity adsorption centrifugation. The non-parametric Mann Whitney test was used to compare the difference between two groups. The chi square test was used to compare the rates. The diagnostic value of single serological marker and GALAD model for primary hepatocellular carcinoma was analyzed. The predictive effect of GALAD model on MVI of primary hepatocellular carcinoma was evaluated.@*Results@#Compared with single serum marker, the diagnostic value of GALAD model is higher. When the cutoff value is -0.33, the diagnostic sensitivity, specificity and accuracy reach to 91.9% (5 440/5 919), 86.8% (1 515/1 745) and 90.7% (6 955/7 664), respectively. The area under the curve can reach 0.960 [95%CI (0.955-0.964)]. Compared with no MVI (MO) group, the value of GALAD model in MVI low-risk group (M1), MVI high-risk group (M2) and MVI (M1+2) were significantly higher (Z values were-12.517, -22.883, -21.655, P<0.05), Galad model predicts MVI (M2) in high risk group,AUC was 0.717 [95%CI (0.701-0.733)] (M0 ratio M2).@*Conclusion@#GALAD model has better diagnostic performance in primary hepatocellular carcinoma and has certain predictive value for microvascular invasion.

Salvianolic acid B exerts anti-hepatic fibrosis-carcinoma effect via mediation of pSmad3C/pSmad3L / 中国药理学通报

Aim To observe the effect of Salvianolic-aid B ( Sal B ) on the progression of hepatic fibrosis-carcinoma in mice induced by diethylnitrosamine ( DEN ) and investigate the mechanism of Sal B in-volved in the shift between pSmad 3 C/p21-mediated tumor suppressive signaling and pSmad 3L/PAI-1/c-Myc-mediated pro-fibrogenic/oncogenic signaling . Methods A total of 100 male Kunming mice were randomly grouped , DEN-induced hepatic fibrosis-car-cinoma model of mice was established , which was in-tragastrically treated by Sal B with two dosages ( 15 , 30 mg · kg -1 ) and colchicine with one dosage ( 0.2 mg· kg -1 ) , respectively.The mice were sacrificed at 12th week or 16th week after the start of DEN adminis-tration.Pathological changes of livers in each group were assessed by liver biopsy , hematoxylin-eosin ( HE ) staining and Van Gieson ( VG ) staining .The protein expressions of pSmad3C, pSmad3L, p21, plas-minogen activator inhibitor-1 ( PAI-1 ) and c-Myc in liver tissues were assayed by Western blot .Results In the normal control group , the surface of mouse liver was smooth and soft , and the structure of the hepatic lobule was intact.In the DEN alone group, at 12th week, the surface of mouse liver was rough and hard , the hepatic lobule was encysted or separated by colla-gen bundles, and pseudolobules emerged.At 16th week, the surface of mouse liver in the DEN alone group was rough with some nodules. HE and VG staining showed that the hepatocytes of nodules with obvious atypia and hyperchromatic nuclei were veri-fied.However, these pathological changes were evi-dently improved in Sal B treatment groups compared with the DEN group , which was proved by reductive cirrhotic nodules and alleviative fibrosis at 12th week, and decreasing cancerous nodes and ameliorative dif-ferentiation via Sal B treatment at 16th week.Western blot results showed that the protein expression of pS-mad3C, pSmad3L, PAI-1 were less, and c-Myc ex-pression was scarcely found in normal group; in DEN alone group, at 12th week, the protein expression of pSmad3C had no significant change , while the protein levels of pSmad3L, PAI-1, p21 were up-regulated, and at 16th week, the protein expressions of pS-mad3C, pSmad3L, p21, PAI-1 and c-Myc increased. In Sal B treatment group, the expressions of p21 and pSmad3C increased significantly , pSmad3L and PAI-1 protein levels markedly decreased at 12th week, the expression of pSmad3C increased obviously , p21 was almost unchanged , and the expression of pSmad 3L, PAI-1 and c-Myc were significantly reduced at 16th week .Conclusions Sal B could delay the progression of hepatic fibrosis-carcinoma in mice induced by DEN , and the mechanism may involve mediating the shift of pSmad3C/p21 and pSmad3L/PAI-1/c-Myc signaling.

Compound Astragalus and Salvia miltiorrhiza extract exerts anti-tumor activity by intervening the interaction of microRNA-145/microRNA-21 and Smad3C/3L phos-phorylation in hepatocellular carcinoma / 中国药理学与毒理学杂志

OBJECTIVBE To investigate the intervention of compound Astragalus and Salvia milt-iorrhiza extract (CASE) consisted of astragalosides, astragalus polysaccharides and salvianolic acids on the interaction of microRNA-145/microRNA-21 (miR-145/miR-21) and Smad3C/3L phosphorylation (pSmad3C/pSmad3L) down-stream of transforming growth factor-β (TGF-β)/mitogen activated protein kinase (MAPK) signaling in hepatocellular carcinoma (HCC) progression by in vitro and in vivo experi-ments. METHODS In HepG2 cells and xenografts of nude mice, antagomir/agomir and plasmids of Smad3C/3L phosphorylation site mutation (Smad3 3S-A/Smad3 EPSM) were used to intervene miR-145/miR-21 and pSmad3C/pSmad3L expression respectively,then incorporative CASE treatment. Cell proliferation, migration, apoptosis, tumor growth and histopathologic characteristics of xenografts, relevant proteins of TGF-β/Smad pathway and miR-145/miR-21 were evaluated.RESULTS CASE up-regulated miR-145 while down-regulated miR-21, inhibited cell proliferation,migration and tumor growth, accelerated cell apoptosis in HepG2 cells respectively transfected with Smad3 WT, Smad3 EPSM,Smad3 3S-A plasmids in cultured dishes and xenografts of nude mice,the above effects were more evident in HepG2 cells with increased pSmad3C.In TGF-β1-stimulated HepG2 cells and xenografts of nude mice, CASE antagonized the facilitating effects of miR-145 antagomir/miR-21 agomir on cell migration,proliferation,tumor growth and inhibiting effects of miR-145 antagomir/miR-21 agomir on cell apoptosis; CASE increased miR-145 down-regulated by miR-145 antagomir and decreased miR-21 up-regulated by miR-21 agomir,reduced protein level of pSmad3L and their proteins including TβRⅡ, pERK1/2, pJNK1/2 and pp38 while elevated pSmad3C expression. CONCLUSION These results suggest that pSmad3C/pSmad3L maybe interact with miR-145/miR-21 in HCC progression,which may be one of important molecular mechanisms of CASE's anti-HCC effects.

Glycosylation and biomarkers in primary liver cancer / 中华检验医学杂志

Primary liver cancer (PLC) is the second leading cause of cancer death in China,and is one of the most serious threats to people's health.Early diagnosis and treatment can significantly improve the prognosis of PLC.Abnormal glycosylation is reported to be closely related to the genesis and development of malignant tumors.With the advent of modern proteomic and glycomic methodologies,several alterations in fucosylation,sialylation,and glycan branching have been observed in serum of patients with PLC.Altered glycosylation profiles,glycosyltransferases and glycosylated proteins could be screened and used as potential serum markers for early diagnosis,progression monitoring and prognosis evaluation of PLC.

Clinical analysis of the application of autologous blood transfusion in neurosurgery of primary hospital / 中国医师进修杂志

Objectives To observe the clinical significance and application value of autologous blood transfusion in neurosurgery of primary hospital. Methods Four hundred and fourteen patients who underwent the neurosurgery operation and were subjected to intraoperative blood transfusion were selected, among whom 97 patients were subjected to autologous blood transfusion (observation group), and 317 patients were subjected to heterogenous blood transfusion (control group). The condition of intraoperative blood transfusion, changes of hemoglobin and hematocrit, blood transfusion related cost were compared between 2 groups. Results There were no statistical differences in operation time, infusion volume, rate of transfusion related complications and postoperation hemoglobin, hematocrit between observation group and control group (P>0.05). The patients in control group were infused with 189 000 ml, and the transfusion liquid volume proportion of total blood transfusion was 79.22%(189 000/238 580);13 patients in observation group were used the heterogenous blood transfusion with 5 400 ml, and the transfusion liquid volume proportion of total blood transfusion was 10.30%(5 400/52 430). Eighty-six patients (88.66%, 86/97) in observation group performed autologous blood collection and transfusion, the volume of autologous collection was 80 650 ml, and the volume of transfusion was 47 020 ml. Eleven patients in observation group did not perform autologous blood transfusion, among whom 6 patients was because of operational and mechanical reasons, and 5 patients performed collection but did not transfuse. The cost of heterogenous concentrated suspension red blood cell over 6 U was significantly higher than the cost of disposable material and injection of autologous blood:(2 287.06 ± 243.52) yuan vs. (1 595.08 ± 133.95) yuan, and there was statistical difference (P<0.05). The rate of heterogenous concentrated suspension red blood cell 6 U in control group was 14.83%(47/317), and the rate of over 6 U was 6.62%(21/317). Conclusions The autologous blood transfusion is safe and effective, and it is worth popularizing in neurosurgery of primary hospital. But in the process of its application, it is necessary to strengthen the user′s operating skills and ensure the quality of autologous blood transfusion.

A comparative study on preoperative ICGR15 dye excretion detection and liver function indexes in patients with primary liver cancer / 中华检验医学杂志

Objective To study the correlation between preoperative dye exclusion test and liver function in patients with primary hepatic carcinoma.Methods This was a cross sectional survey.A total of 192 cases of primary liver cancer patients were recruited from May 2014 to March 2015 at the Second Military Medical University Affiliated Eastern Hepatobiliary Surgery Hospital.Hereinto, 160 cases were male and 32 females, the male to female ratio was 5: 1.The age of the patients ranged from 26 to 72 years old, and the average age was 50.5 years old.ICG 15 minutes retention rate of ICG clearance test was determined by PDD method in 192 cases of primary liver cancer patients.ICGR15 value was stratified into three stages: ICGR15 ＜ 10％ , ICGR1510％-20％ , and ICGR15 ＞ 20％.The ICGR15 stage of patients with different ChildPugh grades was analyzed.The biological liver function indexes of patients were simultaneous detected including TBIL, TBA, TP, ALB, PA, ALT, AST, PT-INR, HA, LN, Ⅲ, Ⅳ, APRI, PLT etc.The correlations of ICGR15 and biological indexes of liver function were analyzed using Spearman nonparametric correlation analysis.Results (1) ICGR15 was positively correlated with Child-Pugh grade (r =0.477, P ＜ 0.01) in the 192 cases of HCC.The hierarchical analysis showed that there were significant differences between ICGR15 and different Child-Pugh grades (P ＜ O.05).(2) Child-Pugh classification and ICGR15 comparison further showed that, ICGR15 increased with Child-Pugh grade.While ICG plasma clearance rate (ICGK) and effective hepatic blood flow (EHBF) reduced (P ＜ 0.05).(3) The correlation analysis between ICGR15 and biological indexes of liver function showed that: ICGR15 was positively correlated with TBIL,TBA, ALT, AST, AFU, GGT, PT-INR, HA, LN, Ⅲ, Ⅳ and APRI index [(AST/ULN) × 100/ PLT (× 109/L)] (r =0.422, 0.389, 0.219, 0.301, 0.219, 0.244, 0.325, 0.652,0.403, 0.523, 0.519, 0.434, P ＜ 0.05);and was negatively correlated with TP, ALB, PA, SOD, WBC, PLT (r =-0.290,-0.532, 0.546, 0.531, 0.256, 0.327, P＜ 0.05).Conclusions ICGR15 as a indicator for liver reserved and dynamic function can comprehensively reflect the liver reserve function is associated with the existing Child-Pugh grades and liver function biochemical indexes.Therefore, ICGR15 could be served as a sensitive index reflecting the preoperative liver reserve function.

Cancer biomarkers and their clinical application for hepatocellular carcinoma diagnosis / 中华检验医学杂志

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China because of high incidence of hepatitis B virus (HBV) infection.HCC is diagnosed at a late stage in most of the cases; therefore the prognosis of patients with HCC is generally poor.Early diagnosis and surgical treatment are of great clinical desirable to improve prognosis of HCC.Tumor marker is an effective means for early diagnosis,prognosis assessment and recurrence monitoring.In addition to alpha fetoprotein (AFP),Lens culinaris agglutinin-reactive AFP (AFP-L3),des-γ-carboxy prothrombin (DCP),glypican-3,N-glycome markers,candidate-susceptibility genes,microRNAs and several other biomarkers have been revealed as potential HCC markers and will be applied in clinical laboratory gradually.In this review,the efficacies of novel HCC markers and their possible implications for clinical application are described.

Effect of ulinastatin on oxidative stress and nuclear factor E2-related factor 2 expression in the lung tissues of acute hydrogen sulfide intoxicated rats / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the dynamic changes of oxidative stress and nuclear factor-E2 related factor 2 (Nrf2) expression in the lung tissues of acute hydrogen sulfide (H2S) intoxicated rats and intervention effects of ulinastatin (UTI).</p><p><b>METHODS</b>A total of 96 SD rats of clean grade were divided randomly into four groups: normal control group (n = 8), UTI control group (n = 8), H2S -intoxicated model group (n = 40), and UTI treatment group (n = 40). The H2S-intoxicated model group and UTI treatment group were exposed to H2S (283.515 mg/m3) by inhalation for 1h, then UTI treatment group was intraperitoneally exposed to UTI at the dose of 10(5) U/kg for 2 h. H2S-intoxicated model group and UTI treatment group were sacrificed at 2, 6, 12, 24 and 48 h after exposure, respectively. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione (GSH) in the rat lung tissues were measured. The expression levels of Nrf2 mRNA in the rat lung tissues were detected. Pathological changes of rat lung tissues were observed under a light microscope and the lung injury scores were evaluated.</p><p><b>RESULTS</b>Compared with control group, the pulmonary SOD, CAT and GSH levels at 2,6 and 12 h after exposure and the pulmonary GSH-Px levels at 2, 6, 12 and 24 h after exposure in H2S-intoxicated model group significantly decreased (P < 0.05 or P < 0.01). The levels of pulmonary MDA at 2, 6, 12 and 24 h after exposure in H2S-intoxicated model group were significantly higher than those in normal control group (P < 0.01). As compared with H2S -intoxicated model group, the pulmonary GSH-Px activities at 6 and 12 h after exposure, the pulmonary CAT activities at 2, 6 and 12 h after exposure, the pulmonary GSH levels at 2, 6, 12 and 24 h after exposure and the pulmonary SOD activities at 2, 6, 12, 24 and 48 h after exposure in UTI treatment group significantly increased (P < 0.05 or P < 0.01), the pulmonary MDA levels at 2, 6 and 12 h after exposure in UTI treatment group significantly decreased (P < 0.01). The expression levels of Nrf2 mRNA at 2, 6, 12, 24 h after exposure in H2S-intoxicated model group were 0.314 +/- 0.011, 0.269 +/- 0.010, 0.246 +/- 0.011 and 0.221 +/- 0.018, respectively, which were significantly higher than those (0.149 +/- 0.012) in control group (P < 0.01). As compared with H2S-intoxicated model group, the expression levels (0.383 +/- 0.017, 0.377 +/- 0.014, 0.425 +/- 0.017, 0.407 +/- 0.011 and 0.381 +/- 0.010) of Nrf2 mRNA at 2, 6, 12, 24 and 48 h after exposure in UTI treatment group significantly increased (P < 0.01). The lung injury at 24 h after exposure in H2S-intoxicated model group was higher than that in UTI treatment group. Histopathological examination showed that the scores of lung injury at 12, 24 and 48 h after exposure in UTI treatment group was significantly lower than those in H2S-intoxicated model group (P < 0.01).</p><p><b>CONCLUSION</b>Oxidative stress and Nrf2 activation may be the important factors in rat lung injury induced by H2S-intoxicated, UTI may reduce the rat lung injury and protect the rat lung from damage induced by H2S by inhibiting ROS, improving the imbalance in redox and up-regulating Nrf2 mRNA expression.</p>

Effects of hemoperfusion on oxidative stress, matrix metalloproteinases and their inhibitors in acute paraquat poisoning rabbits / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To observe the effects of hemoperfusion on oxidative stress status and the levels of matrix metallo proteinase (MMP-2, MMP-9), tissue inhibitor of metalloproteinase (TIMP-1) in lungs, livers and kidneys in paraquat poisoning rabbits, and to explore the mechanism of therapeutic effects induced by HP on acute paraquat poisoning.</p><p><b>METHODS</b>Seventy eight rabbits were randomly divided into normal control group (N group, n=6), exposure groups (PQ group, n=24), hemoperfusion treatment group (HP treatment group, n= 24) and blank control group (HP group, n=24). The PQ, HPQ and HP groups were divided into 4 observation time groups (1, 3, 7 and 21 d). N group was exposed to 5 ml normal saline and PQ group was exposed to 50 mg/kg PQ by oral gavage. In 1 h after PQ exposure, HPQ group was exposed to the activated carbon hemoperfusion for 2 h. The content or activity of MDA, SOD and GSH-Px in lungs, livers and kidneys were detected, the expression levels of MMP-2, MMP-9 and TIMP-1 were measured with immunohistochemical SP method for all groups.</p><p><b>RESULTS</b>The contents of MDA in lungs, livers and kidneys of PQ and HPQ groups decreased and the activities of SOD and GSH-Px in lungs, livers and kidneys of PQ and HPQ groups increased with observation time. The expression levels of MMP-2, MMP-9 and TIMP-1 in PQ and HPQ groups enhanced on the first day, PQ group was most obvious. Along with the observation time extended, all kinds of positive expression were still high. Compared with normal control group, the activities of serum SOD and GSH-Px in PQ and HPQ groups declined significantly, but the contents of serum MDA increased; the expression levels of MMP-2, MMP-9 and TIMP-1 in lung, liver and kidney tissues increased obviously, the ration between MMP-9 and TIMP-1 significantly increased (P < 0.05). Compared with PQ group, the activities of SOD and GSH-Px in HPQ group significantly increased, the content of MDA declined, the expression levels of MMP-2, MMP-9 and TIMP-1 in lung, liver and kidney tissues declined obviously, the ration between MMP-9 and TIMP-1 significantly declined, but higher than N group, the differences were statistically significant (P < 0.05).</p><p><b>CONCLUSION</b>The oxidative stress and MMPs may be involved in the pathogenesis of tissue injuries induced by paraquat. The treatment with HP could obviously reduce oxidative stress and the expression levels of MMP-2, MMP-9 and TIMP-1, enhance the ration between MMP-9 and TIMP-1. So HP treatment could play a role in rescuing the PQ poisoning and protecting the organs function.</p>

Expression of high mobility group protein B1 in the lungs of rats with sepsis / 世界急诊医学杂志（英文）

BACKGROUND: Vibrio vulnificus inside the body could activate the NF-κB signaling pathway and initiate the inflammatory cascade. The lung is one of the earliest organs affected by sepsis associated with acute lung injury. High mobility group protein B1 (HMGB1) is an important late-acting pro-inflammatory cytokine involving in the pathophysiology of sepsis. It is also involved in the injury process in the lung, liver and intestine. There has been no report on the involvement of HMGB1 in Vibrio vulnificus sepsis-induced lung injury. METHODS: Sixty rats were randomly divided into a normal control group (group A,n=10) and a Vibrio vulnificus sepsis group (group B,n=50). Sepsis was induced in the rats by subcutaneous injection of Vibrio vulnificus (concentration 6×108 cfu/mL, volume 0.1 mL/100g)) into the left lower limbs. The rats in group B were sacrificed separately 1, 6, 12, 24, and 48 hours after the infection. Their lungs were stored as specimens, lung water content was measured, and lung pathology was observed under a light microscope. The expressions of the HMGB1 gene and protein in the lungs were detected by RT-PCR and Western blot. Data were analyzed with one-way analysis of variance (ANOVA) and the LSD method for pair-wise comparison between the two groups.P<0.05 was considered statistically significant. RESULTS: Compared to group A (0.652±0.177), HMGB1 mRNA expression in the lungs of group B was significantly higher at 0 hour (1.161±0.358,P=0.013), 24 hours (1.679±0.235,P=0.000), and 48 hours (1.258±0.274,P=0.004) (P<0.05), and peaked at 24 hours. Compared to group A (0.594±0.190), HMGB1 protein expression at 6 hours (1.408±0.567,P=0.026) after infection was significantly increased (P<0. 05), and peaked at 24 hours (2.415±1.064,P=0.000) after infection. Compared to group A (0.699±0.054), lung water content was significantly increased at 6 hours (0.759±0.030,P=0.001),12 hours (0.767±0.023,P=0.000), 24 hours (0.771±0.043,P=0.000) and 48 hours (0.789±0.137,P=0.000) after infection (P<0.05). Compared to group A, pathological changes at 12 hours in group B indicate marked pulmonary vascular congestion, interstitial edema and inflammatory infiltration. Alveolar cavity collapse and boundaries of the alveolar septum could not be clearly identified. CONCLUSION:Vibrio vulnificus sepsis can lead to injury in rat lungs, and increased HMGB1 expression in lung tissue may be one of the mechanisms for injury from Vibrio vulnificus sepsis.

The effects of NF-E2-related factor-2 prompter polymorphism on alcoholic liver disease with Vibrio vulnificus sepsis / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the influence of genetic polymorphism in NF-E2-related factor-2 (nrf2) gene promoter locus at 336 in alcoholic liver disease (ALD) with Vibrio vulnificus (VV) sepsis.</p><p><b>METHODS</b>Through the simple random sampling method, C57B6 male mice were divided into normal feeding group (group A, 10 mice), alcoholic liver disease group (group B, 10 mice), normal feeding group infected with VV through intraperitoneal injection (group C, 8 mice), alcoholic liver disease group infected with VV (group D, 110 mice). Through gene sequencing method, nrf2 gene promoter 336 polymorphism in D group was analyzed and grouped into: non-mutation group (336T) (group D1, 7 mice) and mutation group (336C) (group D2, 10 mice). Through RT-PCR, Western-blotting and ELISA method, expressions of nrf2, tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), high mobility group protein 1 (HMGB(1)) gene and protein of liver were measured. The pathological changes in liver were recorded with light microscope.</p><p><b>RESULTS</b>After infected with VV for 48 hours for A, B, C, D1, D2 group, the expression medians of nrf2 mRNA in liver were 0.115, 0.173, 0.211, 0.764, 0.352, respectively (χ(2) = 40.64, P < 0.05), the expression medians of IL-10 mRNA in liver were 0.338, 0.637, 1.002, 1.825, 1.403, respectively (χ(2) = 41.05, P < 0.05), the expression medians of TNF-α mRNA in liver were 0.140, 0.254, 0.372, 0.399, 0.699, respectively (χ(2) = 38.16, P < 0.05), the expression medians of HMGB(1) mRNA in liver were 0.230, 0.410, 0.668, 0.508, 1.021, respectively (χ(2) = 31.45, P < 0.05). After infected with VV 48 hours for mice in A, B, C, D1, D2 group, the expression medians of nrf2 protein in liver were 0.908, 1.461, 2.061, 3.982, 2.243, respectively (χ(2) = 33.72, P < 0.05), the expression medians of IL-10 protein in liver were 13.97, 22.54, 30.14, 57.98, 41.53, respectively (χ(2) = 37.31, P < 0.05), the expression medians of TNF-α protein in liver were 114.07, 142.94, 175.44, 174.60, 266.11, respectively (χ(2) = 32.29, P < 0.05), the expression medians of HMGB(1) protein in liver were 2.01, 6.05, 9.62, 6.24, 12.89, respectively (χ(2) = 36.94, P < 0.05). Compared with group A, there were large amount of fat drops, fatty changes in group B, inflammatory cell infiltration, disorder of hepatic cell in group C, and extension of hepatic duct and vein, edema of liver cells and disorder of hepatic cells in group D.</p><p><b>CONCLUSION</b>The nrf2 gene promoter of T336C mutation in C57B6 mouse of ALD can significantly decrease the expression of nrf2, and intensify organ inflammation and damage when they were infected by VV.</p>

Effects of hemoperfusion on plasma concentration and histopathological changes in paraquat poisoning rabbits / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To observe the effects of hemoperfusion on plasma concentration and histopathological changes in paraquat (PQ) poisoning rabbits.</p><p><b>METHODS</b>Sixteen rabbits were randomly divided into exposure group (PQ group, n = 8) and hemoperfusion plus PQ exposure group (HPQ group, n = 8). HPQ group were given hemoperfusion in 45 min after exposure to PQ. The plasma PQ concentrations at 0.5, 1.0, 1.5, 2.0, 3.0, 6.0, 12.0, 24.0, 48.0 and 72.0 hours after exposure were measure in 2 groups. The histopathological changes of lung, liver and kidney were examined, the behavior changes and the survival number of 7 days were observed.</p><p><b>RESULTS</b>The poisoning symptoms of HPQ group were generally better than those of PQ group, in each group six animals survived for 7d. The plasma PQ concentrations at 1.0, 1.5, 2.0, 3.0, 6.0, 12.0, 24.0, 48.0, 72.0 h after exposure in HPQ group were significantly lower than those in PQ group (P < 0.05 or P < 0.01). In HPQ group, the plasma PQ peak concentration [(5.01 ± 0.15] µg/L], area under the curve [(54.03 ± 5.31) mg×h(-1)×L(-1)] and PQ half-life time [(16.29 ± 3.26) h] after treatment of HP were significantly lower than those [(11.97 ± 0.75) µg/L, (141.40 ± 10.10) mg×h(-1)×L(-1) and (31.16 ± 9.85) h] in PQ group (P < 0.05). The apparent volume of distribution and PQ clearance rate in HPQ group were significantly higher than those in PQ group (P < 0.05). Congestion, edema, cell infiltration and other pathological changes were found in lung, liver and kidney in PQ group under the light microscope, which were significantly more severe than those in HPQ group. The pathologic scores of lung tissue, liver and renal tubular damage on the 1st, 3rd, 7th days after exposure in HPQ group were significantly lower than those in PQ group (P < 0.05).</p><p><b>CONCLUSION</b>When acute PQ poising, rabbits appeared the quick absorption, high toxicity and long half-life time of PQ. The early hemoperfusion can effectively remove the toxicant in plasma and reduce the pathological injury in major organs, which may be beneficial for further treatment.</p>

Intervention effect of dimercaptopropansulfonate sodium on central toxic induced by bromoxynil in vivo / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>to investigate the changes of γ-aminobutyric acid (GABA) and glutamate (Glu) in the cerebral cortex following acute bromoxynil intoxication in mice and the protective effect of sodium dimercaptopropane sulfonate (Na-DMPS).</p><p><b>METHODS</b>30 ICR mice were randomly divided into blank control group (10), exposure group (10) and Na-DMPS protection group (10). The levels of GABA and Glu in the cerebral cortex were measured by RP-HPLC. The glutamine (Gln) level and the glutamine synthetase (GS), glutamate decarboxylation enzyme (GAD), γ-aminobutyric acid transaminase (GABA-T) activity in the cerebral cortex were determined by UV colorimetric.</p><p><b>RESULTS</b>compared with the control group [GABA: (3.41 ± 0.12) micromol/g, Glu (14.00 ± 0.16) micromol/g, Gln (1.25 ± 0.19) micromol/g, GAD (13.50 ± 0.25) micromol × g(-1) × h(-1), GABA-T (25.51 ± 0.21) micromol × g(-1) × h(-1), GS(142.19 ± 1.31) U/mg pro], the level of GABA [(3.14 ± 0.14) micromol/g] was decreased (P < 0.05), whereas the level of Glu [(17.54 ± 0.40) micromol/g] and Gln [(3.35 ± 0.27) micromol/g] were increased (P < 0.05), the activity of GAD [(11.93 ± 0.15 micromol × g(-1) × h(-1)], GABA-T [(24.15 ± 0.22) micromol × g(-1) × h(-1)], GS [(140.75 ± 1.01) U/mg pro] was decreased (P < 0.05) in acute intoxication group; Compared with the acute intoxication group, the level of GABA [(3.52 ± 0.30) micromol/g] was increased (P < 0.05), whereas the level of Glu [(14.20 ± 0.32) micromol/g] and Gln [(1.32 ± 0.17) micromol/g] were decreased (P < 0.05), the activity of GAD [(13.01 ± 0.45 micromol × g(-1) × h(-1)], GABA-T [(25.19 ± 0.26) micromol × g(-1) × h(-1), GS [(142.35 ± 1.20) U/mg pro] was increased (P < 0.05); In contrast, the levels of GABA, Glu, Gln and the activity of GAD, GABA-T, and GS in Na-DMPS protection group were not significantly different in comparison with control group (P > 0.05).</p><p><b>CONCLUSION</b>the central toxic effects of mice with acute bromoxynil intoxication may be related to the changes of GABA and Glu content in the cerebral cortex;Na-DMPS can protect mice from bromoxynil-induced central toxic effects and GABA and Glu abnormal change in the cerebral cortex.</p>