Objective To explore the influence of DaHuang on renal expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in diabetes mellitus rats. Methods After the DM rat model was made, 24 DM rats were selected randomly and divided into a model group (12 DM rats) and a Rhubarb group group were given pure water in equal amount every day. 8 weeks later, kidney was cut to make pathological slice and method of SP immunohistochemistry was adopted for staining. Observed the expression of ICAM-1 and VCAM-1. Result The renal expression of ICAM-1 and VCAM-1 in the rhubarb group and the model group were obviously increased compared with the normal group (P<0.05). The renal expression of ICAM-1 and VCAM-1 in the rhubarb group was obviously weaker than the normal group(P<0.05). Conclusion Rhubarb could obviously inhibit the renal expression of ICAM-1 and VCAM-1 in diabetes mellitus rats and protect kidney of diabetes mellitus rats.

Acute-On-Chronic Liver Failure ; blood ; pathology ; Case-Control Studies ; Cytochrome Reductases ; metabolism ; Humans ; Prospective Studies ; alpha-Fetoproteins ; metabolism

Objective To approach the mechanism and efficacy of regional intra-arterial infusion chemotherapy with the mixture of lipid emulsion-CDDP (LE-CDDP) for treatment of locally advanced pancreatic cancer. Methods Twenty-four health dogs were divided into four groups (group A, B, C, and D). The dosage of CDDP was used in 4 mg/kg/body weight for each animal The 20% LE, as a solvent, was used in the experimental animals with 2 ml/kg/ body weight (group A) and 1 ml/kg/bedy weight (group B), respectively. Normal sodium (NS) as a solvent was used as control with 2 ml/kg/bedy weight (group C) and 1 ml/kg/body weight (group D), respectively. The LE-CDDP mixture and the NS-CDDP mixture were infused into the proximal segment of splenic artery under the DSA, with transfemoral arterial approach. Blood samples were collected after infusion at 0,3,5,10,20,30,40,50,60 min and the tissues were obtained after the 60 min's blood sample was collected. Blood samples, absorbent gland in peripancreas, liver, spleen, kidney, heart, portal vein, the superior segment of jejunal and pancreas and parapancreatic tissues were obtained for CDDP concentration analysis and histopatholngic examination. Results The values of the area under curve (AUC), the incipient serum concentration ( C0 ) and the elimination half-life (t1/2 ) of the serum CDDP concentration-time curve in four groups were A (54. 5 ± 10.1)%,(2.6±0.5) mg/L, (16.7±3.6) min;B (18.3±6.0)%,(1.5±0.2) mg/L, (47.9 ± 11.1) min; C (116.7±20.6)%, (6.5±0.4) mg/L, (10.5±2.8) min and D (126.6±30.7)%, (5.5±0.4) mg/L, ( 10. 1±3. 1 ) min, respectively. There were significant difference among these four groups ( F(AUC) = 42. 42, F(C0) = 249. 61, F( t1/2 ) = 12. 48, P < 0. 01 ). The values of AUC and C0 in the group A were significantly lower than those in the group C (t(AUC) = 6. 64,t(C0) = 16. 34, P <0. 01 ), and the corresponding values in the group B being also significantly lower than those in the group D (t(AUC) = 8.49, t(C0) =22. 30, P<0. 01 ). The value t1/2 in the group A was significantly longer than that of in the group C ( t = 3.36, P < 0. 01 ), and that of group B was also significantly longer than that of group D ( t = 3.71, P <0. 01 ). The values of AUC and C0 in the group B were significantly lower than those in the group A (t(AUC) = 7. 57, t(C0) = 5.48, P < 0. 01 ), and the value t1/2 in the group B was significantly longer than that in the group A (t = 3.22, P < 0. 05 ). The concentrations of the left lobe and horn of pancreas were higher in the group B (0. 18, 0. 18 mg/L) than those in the group A (0. 05, 0. 05 mg/L) (t =2. 52, 2. 73, P < 0. 05). The tissue CDDP concentration of the right lobe of pancreas and spleen were no significant difference between group A ( 0. 11, 0. 29 mg/L ) and group B ( 0. 07, 0. 24 mg/L) ( P > 0. 05 ). Perivascular lymphocytic and neutrophilic infiltration, congestion and hemorrhage were found in the pancreas, parapancreatic absorbent gland, liver and spleen in the group A and group B. The micro-particles of intralipid were present in the capillary vessel of these tissues. No specific pathological changes were found in other groups and organs. Conclusions The regional intra-arterial infusion with LE-CDDP mixture could increase the pancreatic CDDP concentration, meanwhile, it also could decrease the serum CDDP concentration. The more of the CDDP concentration in the LE-CDDP mixture, the more CDDP concentration at the pancreatic tissue accordingly.

Objective To investigate of effect and mechanism of honokiol against acute lung injury (ALI) induced by lipopolysaccharide (LPS).Methods Forty SPF BALB/c mice were randomly divided into 5 groups (N =8),normal control group,LPS group,low-and high-dose magnolol groups,and dexamethasone group.The mouse model of ALI was induced by LPS.After intraperitoneal injection of honokiol,we detected neutrophil count,concentration of albumin,and pulmonary myeloperoxidase (MPO) activity in bronchoalveolar lavage fluid (BALF)as well as alveolar permeability.We also detected the levels of malondialdehyde (MDA),protein carbonyl content(PCC),reactive oxygen species (ROS) and glutathione(CAT),and the activities of superoxide dismutase (SOD),catalase,glutathione peroxidase (GPx),and glutathione-S-transferase(GST) in lung tissue of mice.Results In the LPS group,the neutrophil count,albumin concentration,MPO activity and Evans blue (EB)content were increased (P ＜ 0.05),and anti-oxidase activity was decreased significantly (P ＜ 0.05).After treatment with honokiol,the neutrophil count,albumin concentration,MPO activity,EB content,and lipid peroxidation level were decreased significantly,and the activities of antioxidant enzymes were increased significantly (P ＜ 0.05).Conclusion Honokiol has protective effects against LPS-induced acute lung injury through inhibiting oxidative stress.

Objective To investigate the effects of peroxisome proliferator-activated receptor α( PPARα) on macrophage-mediated inflammatory responses with the interference of lipopolysaccharide and the possible mechanism.Methods The bone marrow stem cells were isolated from the femora of mice.The granulocyte-macrophage colony stimulating factor ( GM-CSF) was used to stimulate the in vitro differentiation from bone marrow stem cells into primary macrophages.An in vitro model with cultured cells expressing in-flammatory cytokines was established by treating the primary macrophages with lipopolysaccharide ( LPS) .A specific chemical agonist, Wy-14643, was used to activate PPARα. Autophagy inhibitors including 3-methyladenine (3-MA) and small interfering RNA against Atg7 ( Atg7 siRNA) were used to inhibit the autophagy.Western blot assay was performed to detect the expression of autophagy-related proteins ( Atg5, Atg7, Beclin-1 and LC3).The transcriptional levels of TNF-α, IL-1β, IL-6, Atg5, Atg7 and Beclin-1 were analyzed by qRT-PCR.Results Compared with the macrophages treated with LPS alone, those pretreated with various concentrations of Wy-14643 (10 μmol/L, 25 μmol/L and 50 μmol/L) showed inhibited ex-pression of proinflammatory cytokines ( TNF-α,IL-1βand IL-6) and enhanced expression of autophagy-relat-ed proteins (Atg5, Atg7 and Beclin-1) at mRNA level in a dose-dependent manner.The expression of auto-phagy-related proteins (Atg5, Atg7, Beclin-1 and LC3) by macrophages was promoted with the pretreatment of Wy-14643 as indicated by Western blot assay.The transcriptional levels of TNF-α, IL-1βand IL-6 were increased in Wy-14643 pretreated-macrophages after stimulation with 3-MA or Atg7 siRNA .Conclusion PPARαsuppressed the macrophage-mediated inflammatory responses by promoting autophagy, suggesting that the PPARα-autophagy pathway might be one of the signaling pathways regulating LPS induced-inflamma-tory responses.

Objective To analyze the role of cysteinyl aspartate specific proteinase-1 (caspase-1) in a mouse model of D-galactosamine (D-GalN) and lipopolysaccharide (LPS) induced acute liver failure (ALF) and to study the possible mechanism. Methods C57BL/ 6 mice were randomly divided into four groups including control group, Z-WEHD-FMK (caspase-1 inhibitor) treatment group, ALF model group and Z-WEHD-FMK-treated ALF group. The mouse model of ALF was established by intraperitoneally injec-ting the mice with D-GalN (450 mg/ kg) and LPS (10 μg/ kg). The damages in liver tissues were evaluated based on the histopathological examination and the levels of alanine transaminase (ALT) and aspartate trans-aminase (AST) in serum samples. Western blot assay was performed to analyze the expression of caspase-1 and the phosphorylation of glycogen synthase kinase 3β (GSK-3β). The qRT-PCR was used to measure the expression of inflammatory cytokines at transcriptional level. Results The expression of caspase-1 at both mRNA and protein levels were gradually increased during the development of ALF. Compared with the mice with ALF, those in the Z-WEHD-FMK-treated ALF group showed less severe liver damages on histopatholog-ical examination and decreased levels of ALT and AST in serum samples [ALT: (479. 2±39. 5) U/ L vs (998. 5±60. 4 ) U/ L, P<0. 05; AST: ( 478. 5±28. 6) U/ L vs ( 1 180. 7±91. 4) U/ L, P<0. 05]. The expression of TNF-α, IL-1β, IL-18 and IL-33 at transcriptional level were significantly suppressed in mice with ALF upon the Z-WEHD-FMK intervention. Results of the Western blot assay indicated that Z-WEHD-FMK suppressed the activities of GSK-3β by enhancing its phosphorylation. Conclusion This study demon-strated that caspase-1 could promote the activation of GSK-3β resulting in the development of inflammation responses and liver damages during the development of ALF in mice.

Objective:To establish a rapid detection method for human astrovirus based on TaqMan-probe real-time fluorescent quantitative reverse transcription-polymerase chain reaction (RT-PCR).Methods:According to the conservative sequence of human astrovirus ORF1 b gene, we designed the amplification primers and specific fluorescent probe to establish the human astrovirus TaqMan real-time fluorescent quantitative RT-PCR rapid detection method. The specificity, sensitivity and stability of the method were evaluated. We also used this method to detect human astrovirus in clinical samples. Results:The established human astrovirus TaqMan real-time fluorescent quantitative RT-PCR detection method has good specificity and repeatability for human astrovirus, and the sensitivity can reach 10 2 copies/μl. After testing the clinical samples, the detection rate of human astrovirus by our method was 100%. Conclusions:The human astrovirus TaqMan real-time fluorescent quantitative RT-PCR detection method established in this study is simple, rapid, sensitive, specific and stable. It can be used for clinical human astrovirus detection and epidemiological investigation.

Injury monitoring is an important approach for injury control and is an important part of comprehensive disease monitoring. With the development of medical digitalization, an intelligent injury monitoring system has been created in Yinzhou District, Ningbo City, Zhejiang Province using artificial intelligence techniques based on Ningbo Municipal Health Information Platform and has been applied across the district since 2019. The manual card-reporting mode has been transformed to intelligent card-reporting mode in this system, which achieves functions of epidemiological analyses of the monitoring data, early warning of high-incidence injuries, classified management of injury and quality control of report cards. Nearly 300 thousand cards have been automatically reported since the system was online available since November 2022, and the epidemiological characteristics of injury were preliminarily understood, which provide data supports to early earning and interventions of injury. The intelligent injury monitoring system greatly improves the injury monitoring efficiency and card-reporting quality, and saves a large number of manpower and material resources, which provides a powerful technical support to widespread injury monitoring.

We reported a case of hypophysitis caused by a programmed death-1 ( PD-1) inhibitor. The patient was a 59-year-old female with metastatic malignant melanoma who participated in the phaseⅡclinical trial of a PD-1 inhibitor toripalimab. More than five months after the administration of toripalimab,she experienced fatigue, depression, nausea, and anorexia. Laboratory examinations showed mild hyponatremia, secondary adrenal insufficiency, and secondary hypothyroidism. MRI revealed the enlargement of her pituitary with obvious enhancement. The patient was diagnosed as hypophysitis caused by the PD-1 inhibitor and was given replacement therapy with physiological doses of corticosteroid and levothyroxine sodium. Her symptoms were then improved. MRI revealed that her pituitary size returned to normal after 8 weeks of treatment and remained stable during every 3-month follow-up. This case reminds us of the possibility of hypophysitis when patients suffere from fatigue and anorexia during the process of PD-1 inhibitor treatment. Correct diagnosis, proper therapy, and regular follow-up are important to ensure the patients' safety, and to improve their prognosis.

OBJECTIVETo investigate the protective mechanism of endoplasmic reticulum stress (ERS) inhibition against inflammation-induced acute liver injury using a mouse model.

METHODSMarrow-derived stem cells were isolated from mouse femur and used to derive macrophages for analysis in experimental inflammation conditions, established by exposure to LPS and consequent activation of TLR4. Tunicamycin, an ERS chemical inducer, was applied to interfere the inflammation model condition.Affect on the inflammation-related factor MAPK was detected by western blot, and affects on gene expression of inflammatory factors were measured by real-time quantitative PCR. Affect on TNFa was also measured by ELISA.

RESULTSExpression of TNFa, IL-6 and IL-1b was induced upon exposure to LPS, with the peak levels being reached at 4 hours of exposure (TNFa, 0.82+/-0.24; IL-1 b, 2.20+/-0.69; IL-6, 0.330+/-0.150). Tunicamycin significantly enhanced the LPS-induced up-regulation of TNFa, IL-6 and IL-1b expression (TNFa, 1.44+/-0.38, t=2.8, P<0.05; IL-1b, 16.063.40, t =7.93, P<0.05; IL-6, 31.1610.60, t=5.08, P<0.05). The tuniamycin treatment also enhanced the LPS-induced up-regulation of the protein expression of phospo-p38, phospho-JNK and phoshpo-ERK.

CONCLUSIONERS collaborates with LPS to promote the TLR4-mediated inflammatory response of macrophages, and this collaboration may be a pathogenic mechanism underlying progressive development of acute liver injury.

Animals ; Disease Models, Animal ; Endoplasmic Reticulum Stress ; Inflammation ; Interleukin-6 ; Lipopolysaccharides ; Liver ; Macrophages ; Mice ; Toll-Like Receptor 4 ; Up-Regulation