Zerumbone attenuates the severity of acute necrotizing pancreatitis and pancreatitis-induced hepatic injury.

This paper investigated the potential effects of zerumbone pretreatment on an acute necrotizing pancreatitis rat model induced by sodium taurocholate. The pancreatitis injury was evaluated by serum AMY, sPLA2, and pancreatic pathological score. Pancreatitis-induced hepatic injury was measured by ALT, AST, and hepatic histopathology. The expression of I-κBα and NF-κB protein was evaluated by western blot and immunohistochemistry assay while ICAM-1 and IL-1ß mRNA were examined by RT-PCR. The results showed that AMY, sPLA2, ALT, and AST levels and histopathological assay of pancreatic and hepatic tissues were significantly reduced following administration of zerumbone. Applying zerumbone also has been shown to inhibit NF-κB protein and downregulation of ICAM-1 and IL-1ß mRNA. The present paper suggests that treatment of zerumbone on rat attenuates the severity of acute necrotizing pancreatitis and pancreatitis-induced hepatic injury, via inhibiting NF-κB activation and downregulating the expression of ICAM-1 and IL-1ß.

Exploration of the role and mechanism of all-trans retinoic acid on activation and oxidative stress of hepatic stellate cell / 药学实践与服务

Objective To explore the role and potential mechanisms of all-trans retinoic acid （ATRA） on activation and oxidative stress of hepatic stellate cell （HSC）. Methods Platelet-derived growth factor （PDGF-bb, 10 ng/ml） was applied to induce the activation of HSCs, which was then treated with ATRA at a dosage of 5 μmol/L for 48 h. The effects of ATRA on HSC activation were evaluated by detecting changes in cell growth viability and phenotypic marker expression. The effects of ATRA on HSC oxidative stress were evaluated by detecting changes in intracellular reactive oxygen species （ROS）, reduced glutathione （GSH） and malondialdehyde （MDA）, and the expression of antioxidant genes. The effects of ATRA on HSC autophagic activity were evaluated by detecting changes in autophagy marker expression and autophagic flow. Results Compared with the PDGF-bb group, the cell viability was significantly reduced in ATRA-treated HSCs （P<0.01）, as well as the expression of α-SMA and Collagen I. The intracellular levels of ROS and MDA were significantly reduced in ATRA-treated HSCs （P<0.01）, whereas the GSH level was significantly increased （P<0.01）. The expression levels of antioxidant genes （NRF2, HO-1, and ATF4）, were significantly higher in ATRA-treated HSCs than those in the normal ones under PDGF-bb condition （P<0.01）. Meanwhile, the expression of autophagy markers Beclin 1 and LC3 Ⅱ/I, and signal of autophagy flow in ATRA-treated HSCs were found to be significantly reduced （P<0.01）. Conclusion ATRA significantly inhibited PDGF-bb-induced HSC activation and reduced the level of oxidative stress and autophagic activity of HSCs, which had potential applications in the prevention and treatment of liver fibrosis.

Clinical study of intermediate frequency pulse electrical stimulation combined with traditional Chinese medicine directional drug penetration therapy in the treatment of lumbar spinal stenosis / 国际中医中药杂志

Objective:To evaluate the clinical efficacy of intermediate frequency pulse electrical stimulation combined with TCM directional drug penetration therapy in the treatment of patients with lumbar spinal stenosis.Methods:Randomized controlled trial. Totally 90 patients with lumbar spinal stenosis who were treated between July 2018 and December 2021 in the hospital were selected according to randomized controlled trial design, and they were divided into the two groups through the random number table method, with 45 cases in each group. The control group was given non-steroidal anti-inflammatory drugs+conventional intermittent traction + intermediate frequency pulse electrical stimulation, and the combined group was treated with TCM directional drug penetration therapy on the basis of the control group. Both groups were continuously treated for 1 month. The TCM syndromes were scored before and after treatment, and Visual Analogue Scale (VAS) was used to evaluate the pain degree. Japanese Orthopedic Association (JOA) and Oswestry Disability Index (ODI) were applied to assess the dysfunction degree and quality of life, and the clinical efficacy was assessed.Results:The total effective rate was 95.56% (43/45) in combined group and was 82.22% (37/45) in control group, with statistical significance ( χ2=4.05, P=0.044). The scores of lumbago pain, articular soreness, knee soreness and weakness and impaired activity and total score in combined group after treatment were lower than those in the control group ( t=18.40, 15.81, 15.40, 26.50, 59.575, P<0.01), and the JOA score was higher than that of the control group ( t=5.62, P<0.01), while the ODI score was lower than that of the control group ( t=9.43, P<0.01). The time-point effect and between-group effect of VAS score in combined group were lower than those in the control group with the extension of time ( F=240.00, 17.19, P<0.01), and there was an interaction effect between decrease and treatment method ( F=6.66, P<0.01). Conclusion:Intermediate frequency pulse electrical stimulation combined with TCM directional drug penetration therapy is helpful to relieve the pain, improve the lumbar dysfunction degree and enhance the quality of life and clinical efficacy in patients with lumbar spinal stenosis.

Investigation and analysis of knowledge status and educational needs of caregivers for children with epilepsy / 中国实用护理杂志

Objective:To determine the level of epilepsy knowledge of caregivers for children with epilepsy and analyze its influencing factors, and investigate caregivers' educational needs and their acceptance for remote education, in order to provide reference for clinical telenursing education.Methods:From March to September 2022, 221 caregivers of epileptic children in the outpatient department and ward of neurology department of Xuzhou Children's Hospital were recruited by convenient sampling method for cross-sectional investigation. The status of caregivers' knowledge and educational needs were investigated by the general information questionnaire, epilepsy knowledge questionnaire, epilepsy knowledge needs questionnaire and telenursing acceptance questionnaire, and the influencing factors of knowledge level were analyzed by multiple linear regression.Results:The average score of epilepsy knowledge of caregivers was (15.68 ± 6.43) points. The course of disease, taking medicine on time, education background and monthly income of caregivers were the influencing factors of caregivers' knowledge level, and the difference was statistically significant ( P <0.05). 94.12% (208/221)- 96.38% (213/221) of the caregivers had high educational needs, and they had the highest demand for safety guidance during seizures. Caregivers' acceptance of remote education was moderate, ranging from 34.39% (76/221) to 71.95% (159/221). Conclusions:Caregivers' epilepsy knowledge needs to be improved. Medical institutions should formulate education plans according to the different characteristics of caregivers. Caregivers have a high demand for nursing knowledge, and medical staff should increase health education. Before giving health education based on remote nursing platform, we should fully understand the attitude of caregivers to the platform, so that they can master disease knowledge, strengthen their disease management ability, and improve the quality of life of children.

Applicability of three nutritional screening tools in patients with liver cirrhosis under the Global Leadership Initiative on Malnutrition criteria / 临床肝胆病杂志

Objective To investigate whether Royal Free Hospital Nutritional Prioritizing Tool (RFH-NPT) is more suitable than Nutritional Risk Screening 2002 (NRS-2002) in nutritional risk screening for patients with liver cirrhosis, as well as the applicability of subjective global assessment (SGA) in the nutritional assessment of patients with liver cirrhosis. Methods A total of 113 patients with liver cirrhosis who were hospitalized in Renmin Hospital of Wuhan University from August 2020 to June 2021 were enrolled. RFH-NPT and NRS-2002 were used for nutritional risk screening, and SGA was used for nutritional assessment. The results of these tools were compared with the Global Leadership Initiative on Malnutrition (GLIM) criteria, and sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for the three tools. The receiver operating characteristic (ROC) curve was plotted and the area under the ROC curve (AUC) was calculated for each screening tool, and the association between nutritional status and short-term prognosis was analyzed. The independent samples t -test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Spearman correlation analysis was used to analyze the correlation of GLIM criteria with NRS2002, RFH-NPT and SGA. Results According to the GLIM criteria, 69.9% of the patients were diagnosed with malnutrition, and RFH-NPT and NRS2002 screened out that 72.6% and 51.3%, respectively, of the patients had nutritional risk, while SGA assessment showed that 57.5% of the patients had malnutrition. Compared with NRS2002, RFH-NPT had a higher degree of correlation with the GLIM criteria ( r =0.764, P < 0.001), higher sensitivity (94.9%) and NPV (87.1%), and a better predictive value (AUC=0.872, 95% confidence interval [ CI ]: 0.786-0.957). Under the GLIM criteria, SGA had good specificity (88.2%) in the diagnosis of malnutrition in patients with liver cirrhosis, with fair sensitivity (77.2%), good correlation ( r =0.607, P < 0.001), and good predictive value (AUC=0.827, 95% CI : 0.744-0.911). Based on the GLIM criteria, SGA assessment, and RFH-NPT assessment, the patients with nutritional risk or malnutrition tended to have a longer length of hospital stay ( Z= -3.301, -2.812, and -3.813, all P < 0.05) and a higher rehospitalization rate ( χ 2 =3.957, 6.922, and 6.766, all P < 0.05). Based on the GLIM criteria and NRS2002 assessment, the patients with nutritional risk or malnutrition had a significant increase in mortality rate within 3 months ( χ 2 =4.511 and 0.776, both P < 0.05). Conclusion Under the GLIM criteria, RFH-NPT is more suitable than NRS2002 for nutritional risk screening of patients with liver cirrhosis, and SGA also has good applicability in nutritional assessment of patients with liver cirrhosis. In addition, GLIM criteria, SGA, and RFH-NPT are associated with the clinical outcome of patients.

The effect of h(1) calponin expression on gallstone formation in pregnancy.

OBJECTIVE: To explore the effect of h(1) calponin mRNA expression on the biliary tract dynamics, and investigate the molecular mechanisms of gallstone formation in pregnancy. METHODS: This study was carried out in Renmin Hospital of Wuhan University, and in the Department of Molecular Biology and Biochemistry, Wuhan University School of Medicine, Wuhan, China from July to December 2004. Thirty female guinea pigs were divided randomly into 3 groups, the nonpregnant group (n=10) (group A), the 30 days of pregnancy group (n=10) (group B), and the 60 days of pregnancy group (n=10) (group C). Animal models of pregnancy were established on pregnant group guinea pigs through feeding animals with one cage according to female versus male as 4:1. The total cholesterol (TC), total bilirubin (TBiL), total bile acid (TBA) in the bile and the serum estradiol (E(2)), progesterone (Pg) levels were determined respectively. Expression levels of h(1) calponin mRNA in gallbladder smooth muscles and Oddi's Sphincter (OS) were evaluated using semiquantitative reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The concentration of TC, TBiL and the serum E(2) and Pg were more significantly increasing in group C than that in the other 2 groups. However, the concentration of TBA decreased gradually from group A to group C. Up-regulation of h(1) calponin gene expression was observed in the gallbladder smooth muscles in group C, but converse in OS. CONCLUSION: The h(1) calponin might play an important role in inducing dysfunction of extrahepatic biliary tract, bile stasis in gallbladder and gallstone formation in pregnancy.

Progress in One-carbon Metabolism and Tumor Therapy / 肿瘤防治研究

In recent years, it has already run into a common view that "tumor is a metabolic disease", and the reprogramming of tumor metabolism has become the focus of current research. One-carbon metabolism involves folate cycle, methionine cycle and trans-sulfuration pathway. By utilizing these three ways, one carbon unit can regulate tumor growth and proliferation with the production of pyrimidine, thymidine, s-adenosine, glutathione, etc. This paper mainly describes the production and utilization of one carbon unit in tumor, as well as the interaction between one carbon metabolism and tumor development, providing new ideas for studying the mechanism of one-carbon metabolism in tumorigenesis and the treatment of nutrients in tumor.

The role of macrophages in acute pancreatitis / 中华微生物学和免疫学杂志

Acute pancreatitis (AP) is a common and severe disease causing multiple organ dysfunction. With the deepening of research on AP pathogenesis, it has been found that macrophages play an important role in the initiation and progress of AP. The systemic innate macrophage populations, such as the pancreatic macrophages, Kupffer cells, peritoneal macrophages and pulmonary macrophages, can be activated by inflammatory mediators in different stages of pancreatitis, triggering inflammatory cascade reaction and systemic inflammatory response syndrome. This review focused on the recent progress in the role of macrophages in AP.

Progress in surfactant protein D-involved immune inflammatory responses / 中华微生物学和免疫学杂志

Surfactant protein D ( SP-D) is an important component of the surfactant family and ex-pressed in lung as well as many other organs. SP-D is a natural immune protein, which plays an important role in immune defense in lung tissues and in the regulation of inflammatory responses. Moreover, it also participates in immune inflammatory responses in other organs. This paper reviewed the function of SP-D in the regulation of immune inflammatory responses and its regulatory mechanisms in common diseases, and summarized the prospect of SP-D in disease treatment.

Combined aerobic and resistance exercise training for improving rehabilitation in spinal scoliosis / 中国实用护理杂志

Objective To explore the effect of combined aerobic and resistance exercise training on the quality of life, pain degree and hospital stay of spinal scoliosis patients. Methods A total of 112 patients were selected from January 2016 to March 2018, thereby assigning two groups randomly (56 cases). Patients in the control group was nursed by conventional training methods and traditional health education. The experimental group was added combined aerobic and resistance exercise training. The quality of life, pain degree on the first day of admission, 1 week, 1 month and 3 months after operation was evaluated by Scoliosis Research Society-22(SRS-22) and Visual Analogue Scale(VAS),the hospital stay was observed and compared between the two groups. Results There was no significant difference of SRS-22 score and VAS score on the first day of admission between the two groups (P>0.05). The score of VAS was 7(6.25,8.75), 4(3.25,5.00) points in 1 week, 1 month after operation in the experimental group, 8(7.00, 9.00), 5(3.00, 6.00) points in the control group, and there was significant difference between the two groups (Z=4.380, 3.318, P<0.01). The score of SRS-22 was (71.32±10.31), (65.96±6.01), (50.40±7.82) points in 1 week, 1 month, 3 months after operation in the experimental group, (74.64 ± 6.86), (68.16 ± 5.43), (66.42±7.65) points in the control group,and there was significant difference between the two groups (t=2.312, 1.286, 4.508, P<0.01 or 0.05). The hospital stay was (19.30±7.21) d in the control group, (16.70± 5.43) d in the experimental group, and there was significant difference between the two groups (t=1.321, P<0.05).Conclusions Combined aerobic and resistance exercise training is effective at decreasing the degree of pain in post operation, improving quality of life and shorting average of length of stay.

NADPH oxidase participates in pancreatic injury in rats with acute hypertriglyceridemic pancreatitis by regulating Akt/GSK3 β pathway / 中华急诊医学杂志

Objective To investigate the aggravation of pancreatic tissue injury in rats with acute hypertriglyceridemic pancreatitis and the possible role of NADPH oxidase(NOX).Methods Thirty SPF rats were randomly(random number)divided into five groups: N group,H group,NLAP group,HLAP group and HAPO group.AMY,TG,TC and FFA levels were detected.The pathological changes of pancreas were observed under light microscope and the ultrastructural changes of pancreatic acinar cells were observed by TEM.Serum levels of MDA,SOD,LM-1β,TNF-α and LDH were detected.The expression of NOX4,p-Akt and p-GSK3β in pancreas was detected by immunofluorescence,and the expression of NF-κB and TNF-α in pancreas was detected by immunohistochemistry.Results Intraperitoneal injection of P-407 could significantly increase the levels of serum TG,TC and FF A in rats.After acute pancreatitis induced by L-Arg,the levels of serum AMY in the NLAP and HLAP groups were significantly increased,while Apocynin could significantly decrease the level of serum AMY.Compared with the NLAP group,the pathological injury of pancreatic tissue in the HLAP group was more serious,the level of inflammatoty mediators was significantly increased,and the cell necrosis was more serious.After inhibiting NOX,the activation of Akt/GSK3β pathway was regulated and the pancreatic injury was improved.Conclusion In HTGP,NOX aggravates pancreatic injury by regulating the activation of Akt/GSK3 β pathway.Inhibition of NOX expression can play a protective role in pancreas injury of HTGP..

Effects of p38MAPK inhibitor on fetal lung injury in a rat model of acute pancreatitis in late pregnancy / 中华急诊医学杂志

Objective To investigate the effect and underlying mechanisms of p38 mitogenactivated protein kinase inhibitor SB203580 on fetal lung injury in a rat model of acute pancreatitis in late pregnancy.Methods Twenty-four pregnant Sprague-Dawley rats in last gestation were randomly(random number) divided into the SO group,APILP group,and SB203580 treatment (SB) group.APILP model was induced by retrograde injection of 5％ sodium taurocholate into the biliary-pancreatic duct.SB203580 administration (10 mg/kg body weight,intraperitoneal injection) was performed 0.5 h before surgery.All the rats in the SO and APILP groups received intraperitoneal injection of equivoluminal solvent at the same time point.Animals were sacrificed at 12 h after the induction of APILP,then the blood and tissue samples were harvested.Serum levels of AMY and TNF-α were analyzed.Histopathological changes of maternal pancreas and fetal lung were observed and evaluated.The expression and location of NF-κB in fetal lungs were detected by immunohistochemistry and MPO expression in fetal lungs was examined by immunofluorescence.The expression ofp-p38MAPK,p38MAPK,TNF-α and ICAM-1 was determined by Western blot.One-way ANOVA and Tukey's multiple comparison tests were used for statistical analysis.Results The levels of AMY and TNF-α in maternal serum were markedly increased after APILP [(7871.3±623.5) vs (1 915.3±452.3),(193.8±25.4) vs (107.0±±13.3),(P＜0.05)].Obvious pathological changes presented in matemal pancreas and fetal lung after the attack of APILP,and their pathological scores were significantly higher than those of the SO group [(12.44±1.08) vs (1.56±0.56),(2.50±0.53) vs (0.88±0.64),(P＜0.05)].The number of NF-κB and MPO positive cells in fetal lungs were significantly higher than those in the SO group [(150.63±34.58) vs(29.50±8.80),(53.38±8.30) vs (11.75±3.33);P＜0.05)].In addition,the expression and nuclear translocation were pervasive in fetal lungs in the APILP group.Furthermore,the levels of p-p38MAPK [(0.6367±0.0386) vs (0.2282±0.0220)],TNF-α [(0.6313±0.0395) vs (0.0725±0.0076)],ICAM-1 [(0.8958±0.0776) vs (0.1372±0.0388)] and HMGB1 [(0.6478±0.0209) vs (0.2825±0.0533)] expression in fetal lungs were significantly increased after the establishment of APILP model (P＜0.05).However,with the pre-administration of SB203580,the pathological scores of matemal pancreases (9.38±1.58) and fetal lungs (1.63±0.52) were decreased significantly (P＜0.05),as well as the levels of AMY (4162.1±642.1) and TNF-α (139.6±21.1) in maternal serum (P＜0.05).The number of NF-κB (93.00±18.88) and MPO (27.38±4.75) positive cells in fetal lungs were dramatically reduced (P＜0.05) and fewer nuclear translocation was observed in the SB group.Interestingly,the expression levels of p-p38MAPK (0.2578±0.0170),TNF-α (0.3240±0.0326),ICAM-1 (0.4177±0.0823) and HMGB1 (0.4923±0.0457) in fetal lungs were markedly decreased with the treatment of SB203580 (P＜0.05).Conclusions P38MAPK and its downstream inflammatory signaling pathway were involved in the process of APILP-related fetal lung injury;SB203580 administration could significantly attenuate fetal lung injury induced by APILP,which may be closely related to the inhibition of p38MAPK phosphorylation and inflammatory cascade caused by the activation of downstream signal pathways.

Effects of p38MAPK inhibitor on fetal lung injury in a rat model of acute pancreatitis in late pregnancy / 中华急诊医学杂志

Objective@#To investigate the effect and underlying mechanisms of p38 mitogen-activated protein kinase inhibitor SB203580 on fetal lung injury in a rat model of acute pancreatitis in late pregnancy.@*Methods@#Twenty-four pregnant Sprague-Dawley rats in last gestation were randomly(random number) divided into the SO group, APILP group, and SB203580 treatment (SB) group. APILP model was induced by retrograde injection of 5% sodium taurocholate into the biliary-pancreatic duct. SB203580 administration (10 mg/kg body weight, intraperitoneal injection) was performed 0.5 h before surgery. All the rats in the SO and APILP groups received intraperitoneal injection of equivoluminal solvent at the same time point. Animals were sacrificed at 12 h after the induction of APILP, then the blood and tissue samples were harvested. Serum levels of AMY and TNF-α were analyzed. Histopathological changes of maternal pancreas and fetal lung were observed and evaluated. The expression and location of NF-κB in fetal lungs were detected by immunohistochemistry and MPO expression in fetal lungs was examined by immunofluorescence. The expression of p-p38MAPK, p38MAPK, TNF-α and ICAM-1 was determined by Western blot. One-way ANOVA and Tukey's multiple comparison tests were used for statistical analysis.@*Results@#The levels of AMY and TNF-α in maternal serum were markedly increased after APILP [(7 871.3±623.5) vs (1 915.3±452.3), (193.8±25.4) vs (107.0±13.3), (P<0.05)]. Obvious pathological changes presented in maternal pancreas and fetal lung after the attack of APILP, and their pathological scores were significantly higher than those of the SO group [(12.44±1.08) vs (1.56±0.56), (2.50±0.53) vs (0.88±0.64), (P<0.05)]. The number of NF-κB and MPO positive cells in fetal lungs were significantly higher than those in the SO group [(150.63±34.58) vs(29.50±8.80), (53.38±8.30) vs (11.75±3.33); P<0.05)]. In addition, the expression and nuclear translocation were pervasive in fetal lungs in the APILP group. Furthermore, the levels of p-p38MAPK [(0.6367±0.0386) vs (0.2282±0.0220)], TNF-α [(0.6313±0.0395) vs (0.0725±0.0076)], ICAM-1 [(0.8958±0.0776) vs (0.1372±0.0388)] and HMGB1 [(0.6478±0.0209) vs (0.2825±0.0533)] expression in fetal lungs were significantly increased after the establishment of APILP model (P<0.05). However, with the pre-administration of SB203580, the pathological scores of maternal pancreases (9.38±1.58) and fetal lungs (1.63±0.52) were decreased significantly (P<0.05), as well as the levels of AMY (4162.1±642.1) and TNF-α (139.6±21.1) in maternal serum (P<0.05). The number of NF-κB (93.00±18.88) and MPO (27.38±4.75) positive cells in fetal lungs were dramatically reduced (P<0.05) and fewer nuclear translocation was observed in the SB group. Interestingly, the expression levels of p-p38MAPK (0.2578±0.0170), TNF-α (0.3240±0.0326), ICAM-1 (0.4177±0.0823) and HMGB1 (0.4923±0.0457) in fetal lungs were markedly decreased with the treatment of SB203580 (P<0.05).@*Conclusions@#P38MAPK and its downstream inflammatory signaling pathway were involved in the process of APILP-related fetal lung injury; SB203580 administration could significantly attenuate fetal lung injury induced by APILP, which may be closely related to the inhibition of p38MAPK phosphorylation and inflammatory cascade caused by the activation of downstream signal pathways.

NADPH oxidase participates in pancreatic injury in rats with acute hypertriglyceridemic pancreatitis by regulating Akt/GSK3 β pathway / 中华急诊医学杂志

Objective@#To investigate the aggravation of pancreatic tissue injury in rats with acute hypertriglyceridemic pancreatitis and the possible role of NADPH oxidase (NOX).@*Methods@#Thirty SPF rats were randomly (random number)divided into five groups: N group, H group, NLAP group, HLAP group and HAPO group. AMY, TG, TC and FFA levels were detected. The pathological changes of pancreas were observed under light microscope and the ultrastructural changes of pancreatic acinar cells were observed by TEM. Serum levels of MDA, SOD, IL-1β, TNF-α and LDH were detected. The expression of NOX4, p-Akt and p-GSK3β in pancreas was detected by immunofluorescence, and the expression of NF-κB and TNF-α in pancreas was detected by immunohistochemistry.@*Results@#Intraperitoneal injection of P-407 could significantly increase the levels of serum TG, TC and FFA in rats. After acute pancreatitis induced by L-Arg, the levels of serum AMY in the NLAP and HLAP groups were significantly increased, while Apocynin could significantly decrease the level of serum AMY. Compared with the NLAP group, the pathological injury of pancreatic tissue in the HLAP group was more serious, the level of inflammatory mediators was significantly increased, and the cell necrosis was more serious. After inhibiting NOX, the activation of Akt/GSK3β pathway was regulated and the pancreatic injury was improved.@*Conclusion@#In HTGP, NOX aggravates pancreatic injury by regulating the activation of Akt/GSK3 β pathway. Inhibition of NOX expression can play a protective role in pancreas injury of HTGP..

Experimental study on the mechanism of glycogen synthase kinase-3β inhibitor on acute kidney injury of acute necrotizing pancreatitis in rats / 中华危重病急救医学

Objective To explore the protective mechanism of glycogen synthase kinase-3β(GSK-3β) inhibitor TDZD-8 on acute necrotizing pancreatitis (ANP) associated kidney injury in rats. Methods SPF male Wistar rats were randomly divided into four groups (n = 20): sham operation group (Sham group), ANP model group, TDZD-8 intervention group and TDZD-8 control group. The rat ANP model was prepared by retrograde injection of 5% sodium taurocholate into the bile duct; the same volume of normal saline was injected into the pancreatic duct of the Sham group. The TDZD-8 intervention group and the TDZD-8 control group were injected with GSK-3β inhibitor TDZD-8 (1 mL/kg) via the femoral vein 30 minutes before the model or sham operation; the ANP model group and the Sham group were injected equal volume of 10% dimethyl sulfoxide (DMSO). Rats in each group were sacrificed at 12 hours after operation to measure the serum amylase (AMY), blood lipase (LIPA), serum creatinine (SCr) and blood urea nitrogen (BUN) levels and to observe the pathological changes of pancreatic tissues and kidney tissues. Ultrastructural change of renal cells was analyzed by transmission electron microscopy. Serum interleukin-1β (IL-1β) and interleukin-6 (IL-6) levels were evaluated by enzyme linked immunosorbent assay (ELISA). The activation of nuclear factor-κB p65 (NF-κB p65) was evaluated by immunohistochemistry assay. The protein expressions of GSK-3β, phospho-GSK-3β (Ser 9), tumor necrosis factor -α (TNF-α), inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1) and interleukin-10 (IL-10) in the kidney were determined by Western Blot. Results Compared with the Sham group, the serum and inflammatory factors levels of the ANP model group were significantly increased, the pathological damage of the pancreas and kidney tissues were severe, the histopathological score was significantly increased, the expression of NF-κB p65 was enhanced in the nucleus of the kidney tissue, and the expressions of GSK-3β, TNF-α, ICAM-1 and iNOS were significantly enhanced, and the expressions of p-GSK-3β(Ser 9) and IL-10 were significantly attenuated. Compared with the ANP model group, TDZD-8 pretreatment significantly reduced serum and inflammatory factor levels in the ANP model group [AMY (kU/L): 5.60±0.30 vs. 10.07±0.34, LIPA (U/L): 1 111.0±110.8 vs. 2 375.0±51.1, SCr (μmol/L): 47.38±1.48 vs. 72.50±2.43, BUN (mmol/L): 17.6±1.0 vs. 26.0±1.0, IL-1β (ng/L):195.90±5.50 vs. 332.40±38.29, IL-6 (ng/L): 246.10±26.74 vs. 385.30±32.19, all P < 0.01]; pathological damage of pancreas and kidney tissue (histopathological score: 7.1±0.4 vs. 12.1±0.3, 301.2±7.5 vs. 433.5±13.8, both P < 0.01) and ultrastructural damage of renal cells were alleviated; the expression of NF-κB p65 in the nucleus was significantly decreased; the expression of p-GSK-3β(Ser 9) was significantly increased, and blocking GSK-3β activity could inhibit the expressions of TNF-α, ICAM-1, iNOS and increase the expression of IL-10, while the expression of GSK-3β in renal tissues was not statistically significant. There were no significant differences between the TDZD-8 control group and the Sham group. Conclusions Blockade of GSK-3βactivity by TDZD-8 exerts the protective effect against kidney injury by inhibiting the inflammation signaling pathway in ANP. It can alleviate histopathological and ultrastructural changes in kidney injury, which protection mechanism is mediated by NF-κB and its related inflammatory mediators.

Role of Toll-like receptor 4 and NOD-like receptor 3 inflammasome in liver injury of acute necrotizing pancreatitis rats with obesity / 中华胰腺病杂志

Objective To investigate the role of Toll-like receptor 4 ( TLR4 ) and NOD-like receptor 3 (NLRP3)inflammasome in the liver injury of acute necrotizing pancreatitis (ANP) rat with obesity. Methods Twenty-four SD rats were randomly divided into normal group, ANP group, obesity group and obesity ANP group. The obesity rat model was established by continuously feeding high fat diet and the ANP model was induced by retrograde infusion of 5％ sodium taurocholate into the biliopancreatic duct. Rats were killed at 12 h after model establishment, and automatic biochemical immune analyzer were used for detecting serum AMY, LIP, ALT, AST, TG and TC. Pathological changes of pancreas and liver tissue samples were observed by miscroscopy and pathological score was recorded. The levels of MPO, CD68 , TLR4, NLRP3 and IL-1βin liver tissue were detected by immunofluorescence, and NF-κB and caspase-3 in liver tissue were detected by immunohistochemistry. Results The serum ALT and AST in obesity ANP group were significantly increased than those in ANP group (233. 00 ± 34. 44 U/L vs 102. 83 ± 8. 90 U/L,388. 00 ± 41. 60 U/L vs 282. 00 ± 21. 06 U/L);and liver pathologic score was also significantly higher than ANP group (6. 66 ± 1. 21 vs 3. 33 ± 1. 03);and CD68 + /TLR4 +, CD68 + /NLRP3 +, TLR4 + /NLRP3 +, MPO, NF-κB, IL-1β and caspase-3 level were all greatly higher in obesity ANP than those in ANP group, respectively (24. 16 ± 1. 47 vs 6. 66 ± 1. 21, 25. 00 ± 2. 60 vs 7. 00 ± 1. 41, 14. 16 ± 1. 47 vs 5. 50 ± 1. 04, 35. 33 ± 6. 88 vs 20. 83 ± 2. 48, 58. 80 ± 6. 75 vs 37. 63 ± 2. 96, 50. 00 ± 2. 36 vs 35. 00 ± 2. 82, 66. 00 ± 4. 04 vs 55. 00 ± 2. 60); and all the differences were statistically significant (all P<0. 05). Conclusions Liver injury was more severe in ANP rats with obesity, which may be related to the fact that obesity may enhance the activation of TLR4/NLRP3 signal pathway and result in the release of more inflammatory factors.

The role of Toll-like receptor 4 in acute pancreatitis / 中华危重病急救医学

Toll-like receptors (TLRs) is a kind of pattern recognition receptor which widely exists on the cell membrane. It is a natural immune system component which can regulate the inflammatory response of the body participating in the signal transduction of cells and play an important role in the endogenous immune response. But the excessive inflammatory reaction initiated by TLRs can make the immune function of the body unbalanced and damage the function of many organs. The earliest discovered TLR4 is a transmembrane protein, almost express in all kinds of cell. Lots of study show it is closely related to the occurrence and development of acute pancreatitis (AP). The role and mechanism of TLR4 in AP will be reviewed in this article.

The expression and role of Caspase3, Caspase12 and CHOP in pituitary tissues of rats with acute necrotizing pancreatitis / 中华内分泌外科杂志

Objective To observe the pathological changes of pituitary tissue in rats with acute necrotizing pancreatitis and to explore the mechanism of pituitary tissue injury in rats.Methods 24 SD rats were randomly divided into normal group (N group,n=8),sham operation group (SO group,n=8),and acute necrotizing pancreatitis group (ANP group,n=8).ANP model was established by retrograde injection of 5％ sodium taurocholate into the biliopancretic duct.The serum levels of amylase(AMY) and lipase (LIP) were detected by automatic biochemical.The serum levels of growth hormone (GH),adrenocorticotropic hormone (ACTH),thyroid stimulating hormone (TSH) and follicle-stimulating hormone (FSH) were measured by radioimmunoassay.The pathological changes of pancreatic tissue and pituitary tissue were observed by the light microscope.The expression of Casepase3,Caspasel2 and CHOP in pituitary tissue were determined by immunohistochemical method.Results Compared to SO group,the serum levels of AMY(8679.16±307.60) U/L and LIP(9376.83±380.92) U/L were significantly higher in ANP group (P＜0.05).The serum levels of ACTH (0.92±0.41) pg/ml,TSH (0.14±0.06) pg/ml,and FSH (2.01±0.38) pg/ml were significantly lower in ANP group(P＜0.05).The expression of Caspse 3 (65.66±7.58),Caspase12(70.66±4.76) and CHOP(143.16±19.05) in pituitary tissue were significantly increased in ANP group (P＜0.05).The pancreatic injury was more severe in ANP group under light microscope (P＜0.05).The degree of hyperemia of pituitary tissue of ANP group was aggravated.Conclusion Pathological changes occur in rat pituitary tissues and endoplasmic reticulum stress injury plays a role in pituitary injury during ANP.

The effects of different GSK-3β inhibitors and dose-response relationship in severe acute pancreatitis associated kidney injury in rats / 中华急诊医学杂志

Objective To observe the dose-response relationship of the GSK-3β inhibitor TDZD-8 in severe acute pancreatitis (SAP) associated kidney injury in rats. In order to identify the most effective class of GSK-3β inhibitor and its effective and reasonable safe dose in SAP associated kidney injury model in rats by comparing three kinds of frequently-used GSK-3β inhibitor TDZD-8, lithium chloride (LiCL), SB216763 in this model. Methods Totally 96 SPF male Wistar rats were randomly(random number) divided into 8 groups (n=12): sham operation group (SO group), severe acute pancreatitis group (SAP group), TDZD-8 pretreatment groups (TD group, marked TD1, TD2, TD3 and TD4 group, respectively) at different dosage (0.25, 0.5, 1.0 and 2.0 mg/kg), LiCL pretreatment groups (L group, 40 mg/kg), and SB216763 pretreatment group (SB group, 1 mg/kg). SAP model was induced by retrograde infusion of 5％ sodium taurocholate into the biliopancreatic duct. Rats in each group were sacrificed at 12 h after operation. Then the mortality, quantity of ascites, serum AMY, Cr, BUN and ALT were recorded, and the pathological changes of pancreatic tissues and kidney tissues were observed. Results Compared with the SO group, the levels of ascites, serum AMY, Cr, BUN, ALT and pancreatic and renal pathologic score in the SAP group were all significantly increased (P<0.05). Compared with the TD1 group, quantity of ascites, serum AMY, Cr, BUN,ALT and pancreatic tissue pathological grading were reduced in different degrees in the TD2, TD3 and TD4 groups with statistically significant difference (P<0.05); ALT values were reduce in different degrees in the TD2 and TD3 groups as compared with the SAP group (P<0.05), while ALT value in the TD4 group was similar to that in the SAP group; compared with the TD2 group, all the indexes in the TD3 group were significant better (P<0.05); Compared with TD3 group (the best group in TD group), the levels of ascites and serum ALT in the L group and SB group had no significant difference (P>0.05), but the levels of AMY, Cr, BUN, ALT, pancreatic and renal pathologic score were significantly reduced in the TD3 group than those in the L and SB groups (P<0.05); compared with the SB group, the values of Cr, BUN, pancreatic and renal pathologic score in the L group were lower (P<0.05). GSK-3βprotein expression in all groups showed no obvious difference (P>0.05), while p-GSK-3β ser9 protein expression in the SAP group was lower than that in the SO group (P<0.05), and p-GSK-3β ser9 protein expression in the TD3, L and SB groups were stronger than that in the SAP group. Among them, p-GSK-3βser9 protein expression was highest in the TD3 group, followed by the L group, finally the SB group, and the differences were statistically significant (P<0.05). Conclusions Among the three different GSK-3βinhibitors, TDZD-8 is the most effective GSK-3β inhibitor for SAP associated with kidney injury in rats. The GSK-3β inhibitor TDZD-81 mg/kg administered intravenously is safe, effective and optimal dosage for attenuating the severity of severe acute pancreatitis associated with kidney injury.

The risk factors affecting early recurrence and survival after surgical resection of hepatocellular carcinoma / 介入放射学杂志

Objective To analyze the risk factors that affect the early recurrence (recurrence occurring within 3 months after surgical resection) of hepatocellular carcinoma (HCC), and to discuss the risk factors influencing the survival after hepatectomy. Methods The clinical data of 257 HCC patients, who were admitted to authors' hospital during the period from January 1, 2007 to March 31, 2014 to receive cTACE within 3 months after surgical resection of hepatocellular carcinoma, were retrospectively analyzed. According to DSA findings (lipiodol CT scan was performed in part of patients with undetermined diagnosis), the patients were divided into recurrence group and non-recurrence group. By using univariate analysis and multiple logistic regression analysis, the correlation of the clinical and pathological data with the early recurrence was analyzed. The patients were followed up, the survival time was recorded. The relationship between patient's clinical data and postoperative survival was evaluated. Results ① Of the 257 patients, early recurrence was detected in 150 patients (58. 4％, recurrence group) and no recurrence was observed in 107 patients (41. 6％, non-recurrence group). ②The presence of satellite nodules and the integrity of tumor encapsulation were two independent factors associated with the postoperative residual lesions. ③The maximum diameter of the tumor, Edmondson grade and the vascular cancer thrombus were the independent risk factors affecting survival. ④The median survival time of patients in recurrence group was markedly shortened than that of patients in non-recurrence group (39 months vs. 93 months). Conclusion The early recurrence (within 3 months after resection) of hepatocellular carcinoma is associated with the presence of satellite nodules and the integrity of tumor encapsulation. The survival of patients after hepatectomy is related to the maximum diameter of the tumor, Edmondson grade and the vascular cancer thrombus. The median survival time in patients having early recurrence is significantly shortened than that in patients having no early recurrence. (J Intervent Radiol, 2018, 27: 215-222)