Objective To evaluate HSP90 levels in the diagnosis and staging of gastrointestinal tumors.Method Patients with gastrointestinal tumors hospitalized from 2014 January to 2015 April were enrolled in this study.Serum level of HSP90 was detected.Results The serum HSP90 level of cancer group(112 ± 74)was significantly higher than the control groups,the area under the ROC curve of HSP90's was 0.875 and the cut-off point was 63.63 with sensitivity of 76.1％ and specificity of 92.6％.The HSP90 level in gastric cancer group(135 ±73)ng/ml was the highest,in colon cancer group was (105 ± 60) ng/ml and in rectum cancer group was(79 ± 42)ng/ml (all P ＜ 0.05).Serum HSP90 levels in moderate and low differentiated adenocarcinoma were higher than well differentiated adenocarcinoma group (P ＜ 0.05).Serum HSP90 level was higher in tumors with submucosa and serosa infiltration (P ＜ 0.05).Those with lymphatic metastasis tend to have a higher serum HSP90 level than those without.Conclusion Serum HSP90 level has a good predictive value on gastrointestinal tumor diagnosis,and it is correlated with tumor staging and infiltration status.

Objective To investigate the optimal dose of apocynin to protect severe acute pancreatitis (SAP) and SAP caused intestinal injury in rats. Methods A total of 53 SPF male Wistar rats were randomly allocated into five groups:sham operation group (SO group, n=10), SAP group (n=12), low-dose apocynin group (25 mg/kg,n=11), medium-dose apocynin group (50 mg/kg, n=10) and high-dose apocynin group (100 mg/kg,n=10). SAP model was prepared by retrograde infusing 5%sodium taurocholate (1 mL/kg) into biliopancreatic duct of rat. At thirty minutes before modeling, apocynin was injected into rat to intervention. The survival condition was recorded at 12 h after modeling, and blood samples were obtained for detecting serum amylase (AMY), alanine aminotransferase (ALT) and creatinine (Cr). Pancreatic and ileal tissue samples were obtained for HE staining and pathological examination. Results Two rats died in SAP group and one died in low-dose apocynin group. The quantity of ascites, the levels of AMY, ALT, Cr and pancreatic and intestinal pathologic scores were significantly increased in SAP group than those in SO group (P<0.05). Except the levels of Cr and intestinal pathologic score, there was no significant difference between low-dose apocynin group and SAP group. The quantity of ascites ascites, levels of AMY, Cr and pancreatic and intestinal pathologic scores were significantly lower in medium-dose and high-dose apocynin groups than those in SAP group (P<0.05). The levels of ALT and Cr were significantly higher in high-dose apocynin group than those of medium-dose apocynin group (P<0.05). Conclusion Apocynin improves SAP symptoms and reduces SAP caused intestinal injury in rats, which may be related to the inhibition of NOX activity, and 50 mg/kg of apocynin is the optimal dose.

Objective To explore the value of plasma C-peptide levels in early prediction of type 2 diabetes mellitus with peripheral sensory neuropathy.Methods The vibration perception threshold,pain,temperature sensation,touch-pressure sensation,ankle reflex was detected in 500 eases of type 2 diabetes mellitus,and the patients were divided into 4 groups according to peripheral sensory nerve test results:normal group (159 cases),mildly abnormal group (120 cases),moderately abnormal group (121 cases) and severely abnormal group (100 cases).Fasting and 2-hour postprandial C-peptide levels were determined and analysed with peripheral sensory nerve changes.The receiver-operating characteristic (ROC) curve was used to find the best critical point for diagnosis of diabetic peripheral sensory neuropathy.Results The fasting C-peptide among 4 groups had no significant difference (F =1.632,P ＞0.05).Two-hour postprandial C-peptide from normal group to mildly abnormal group and then moderately abnormal group gradually increased [(1.110 ± 0.526),(1.324 ± 0.490),(1.573 ± 0.716) μ g/L],while 2-hour postprandial C-peptide in severely abnormal group was significantly decreased and lower than that in normal group,and there were significant differences (P＜ 0.05).The max Youden Index was 0.366 when 2-hour postprandial C-peptide was 1.173 μ g/L.Conclusions The fasting C-peptide might be not related to early diabetic peripheral sensory neuropathy,but 2-hour postprandial C-peptide might be closely related to early diabetic peripheral sensory neuropathy.It is helpful to detect the early diabetic peripheral sensory neuropathy if we can take a dynamical observation of 2-hour postprandial C-peptide.

Objective To investigate the effects and mechanisms of poly adenosine diphosphate (ADP)-ribose polymerase inhibitor 3-aminobenzamide (3-AB) on kidney injury in rates with severe acute pancreatitis (SAP).Methods Fifty-six male Wistar rats were divided into the sham operation (SO) group,SAP (3,6,12 hours) groups,and 3-AB + SAP (3,6,12 hours) groups,and there were 8 rats in each group.SAP model was established by retrograde injection of 5％ sodium taurocholate into the biliopancreatic duct.Rats in the 3-AB + SAP group were infused with 3-AB (20 μg/g) via femoral vein 30 minutes before SAP model establishment.The serum amylase,kidney function and renal myeloperoxidase (MPO) were determined,and pathological scores of pancreatic and renal tissues were evaluated under light microscope.Renal poly ADP-ribose formation,intercellular adhesion molecules-1 (ICAM-1) and P-selectin expression were detected by the Western blot.All data were analyzed using the analysis of variance or t test.Renal injury grading was analyzed using the Kruskal-Wallis nonparametric test.Results The levels of serum amylase of SAP 3,6,12 groups were (3806 ± 229)U/L,(4898 ± 295) U/L and (5726 ± 372) U/L,which were significantly higher than (2785 ± 160) U/L,(3241 ± 198) U/L and (3953 ± 249) U/L of the 3-AB + SAP groups (t =3.652,4.672,4.407,P ＜ 0.05).The levels of blood urea nitrogen were (11.6 ± 0.8) mmol/L,(19.3 ± 1.3) mmol/L and (29.6 ± 2.1) mmol/L,which were higher than (7.5 ± 0.5) mmol/L,(10.5 ± 0.7) mmol/L and (21.6 ± 1.5) mmol/L of the 3-AB + SAP groups.There were significant differences in the levels of blood urea nitrogen between the SAP group and the 3-AB + SAP group at the 6 and 12 hours (t =3.836,6.849,P ＜0.05).The levels of creatinine of the SAP 3,6,12 hours groups were (48.7 ±3.1) μmol/L,(58.3 ±3.7) μmol/L and (75.9 ±5.4) μmol/L,which were higher than (40.7 ±2.6)μmol/L,(43.2 ± 2.6) μmol/L and (53.4 ± 3.2) μmol/L of the 3-AB + SAP groups.There were significant differences in the levels of creatinine between the SAP group and the 3-AB + SAP group at the 6 and 12 hours (t =3.279,3.073,P ＜ 0.05).The renal MPO activity of the SAP 3,6,12 hours groups were (0.69 ± 0.06) U/g,(1.07 ± 0.09)U/g and (1.42 ±0.13)U/g,which were higher than (0.57 ±0.05)U/g,(0.75 ±0.06)U/g and (0.89 ± 0.07) U/g of the 3-AB + SAP groups.There were significant differences in the renal MPO activity between the SAP group and the 3-AB + SAP group at the 6 and 12 hours (t =3.066,4.012,P ＜ 0.05).The pancreatic pathological scores of the SAP 3,6 and 12 hours group were 6.50 ± 0.53,9.06 ± 0.66 and 11.75 ± 0.89,which were significantly higher than 4.25 ± 0.31,6.06 ± 0.51 and 7.57 ± 0.59 of the 3-AB + SAP group (t =3.631,3.598,5.147,P ＜ 0.05).The structure of the kidney was normal in the SO group.Congestive changes were observed in glomerulus of kidney,the renal tubular epithelial cell was necrosed,and luminal narrowing or occlusion,hemorrhage in the intercellular substance and inflammatory cell infiltration were observed in the SAP 12 hours group.The pathological changes of the 3-AB + SAP 12 hours group were significantly slighter (P ＜ 0.05).The relative expressions of poly ADP-ribose,ICAM-1 and P-selectin of the SO group were 1.00 ±0.21,1.00 ±0.18,1.00 ± 0.16,which were significantly lower than 3.83 ± 0.63,5.42 ± 0.83,3.71 ± 0.48 of the SAP 12 hours group (t =6.955,23.107,10.352,P ＜ 0.05).The relative expressions of poly-ADP-ribose,ICAM-1 and P-selectin of the 3-AB + SAP 12 hours group were 1.94 ± 0.36,2.35 ± 0.35,2.11 ± 0.29,which were significantly lower than SAP 12 hours group (t =3.977,12.115,5.012,P ＜ 0.05).Conclusions Poly ADP-ribose polymerase inhibitor 3-AB protects kidney from injury in the experimental SAP rats.Poly ADP-ribose polymerase inhibitor 3-AB functions by suppressing the ICAM-1 and P-selectin expression and reducing neutrophil infiltration.

Objective To investigate the ultrastructure and function changes of the thyroid parafollicular cell in ANP rats and to study the possible mechanism of hypocalcemia during ANP.Methods Thirty-two male Wistar rats were randomly divided into 4 groups:sham operation group ( SO group) and ANP 3,6,12 h groups.ANP model was induced by retrograde injection of 5％ sodium taurocholate into the biliopancreatic duct. The serum levels of amylase,lipoidase,calcitonin and Ca2+ were measured.The pathological changes in pancreatic tissue were observed.The ultrastructure changes of thyroid parafollicular cell were observed.ResultsThe serum levels of amylase,lipoidase,calcitonin and Ca2+ were (4025 ±579)U/L,(8272 ± 794) U/L,(383.6 ± 64.5) pg/ml,(2.41 ± 0.12) mmol/L at 6h in ANP group,which were significantly higher than those in SO group [ ( 1063 ± 129 ) U/L,( 55 ± 18 ) U/L,( 143.1 ± 42.2 ) pg/ml,(2.97 ±0.12 ) mmol/L ( P ＜0.05 ) ].Under the electron-microscopy,the nucleus of thyroid parafollicular cells shrinked and mitochondrial proliferation and endoplasmic reticulum fusion appeared.After 6 h,all the organelle reduced and disappeared,and only small amount of secretory granules remained.Conclusions Changes in the structure and function of the thyroid parafollicular cells occur in rats of ANP,and they induce the development of hypocalcemia.

Objective To evaluate the protection of 3-aminobenzamide (3-AB),an inhibitor of Poly (ADP-ribose) polymerase (PARP),on severe acute pancreatitis associated adenohypophysis injury in rats.Method Forty Wistar rats were randomly divided into 4 groups:sham operation group (SO group,n=8),SAP group (n=12),3-AB pretreatment group (n =12),drug control group (n =8).The bilepancreatic duct was cannulated through the duodenum and SAP model was induced by a standardized pressure-controlled retrograde infusion of 5％ sodium taurocholate (0.1 ml/100 g) into the bile-pancreatic duct.In 3-AB group,3-AB (20 mg/kg) was administered via femoral vein 30 min prior to the operation;other procedures were identical to SAP group.In SO group,pancreas was flipped several times only.In drug control group,3-AB (20 mg/kg) was administered via femoral vein 30 min prior to the operation.Serum amylase,lipase were measured.Pancreas and pituitary tissue were taken for pathological examination under light microscope.PARP and NF-κB antibodies for adenohypophysis immunohistochemical stains.Adenohypophysis cell was observed under electronic microscope.Result Serum amylase,lipase and pancreas pathological scores were significantly higher in 3-AB group compared with SO group (P ＜ 0.05),but lower than that in SAP group (P ＜ 0.05).Adenohypophysis pathological injury was less severe in 3-AB group.Expressions of PARP and NF-κB in adenohypophysis cells were significantly higher in 3-AB group compared with SO group,but lower than that in SAP group (P ＜ 0.05).Ultrastructural change of thyrotroph cell was relieved in 3-AB group.No significant difference was observed between SO group and drug control group in PARP and NF-κB expression nor adenohypophysis pathological injury.Conclusions 3-AB exerts the protective effect against acute pancreatitis associated adenohypophysis injury by inhibition of PARP and NF-κB.

Objective To investigate the changes of poly-ADP-ribose polymerase (PARP) and NF kappa B (NF-κB) in adenohypophysis in rat model of severe acute pancreatitis (SAP),and their role in the mechanism of adenohypophysis injury in SAP.Methods Forty Wistar rats were randomly (random number) divided into 5 groups:the sham operation group (SO group,n =8),SAP 1 h,3 h,6 h and 12 h groups (n =8 in each group).SAP model was induced by retrograde injection of 5％ sodium taurocholate into the biliopancreatic duct.Serum levels of amylase,lipase and ascites were measured.After sacrifice of experiment rats,pancreas and adenohypophysis tissues were taken for pathological examination under light microscope.Adenohypophysis cells were observed under electronic microscopy as well.PARP and NF-κB expressions in adenohypophysis cell was studied by using immunohistochemisty assay.Results After modelling,serum levels of amylase,lipase and ascites in SAP group increased gradually,which were higher than those in SO group (P ＜ 0.05).Adenohypophysis cell swelling and partial necrosis were observed under light microscope.As the time prolonged,their nuclei became dark and pyknotic more and more,and the endoplasmic reticulum and mitochondrial swelling in adenohypophysis cells were observed under electronic microscopy.The expressions of PARP and NF-κB in SAP group increased gradually,which were higher than those in SO group.Conclusions Significant pathological and ultrastructural injuries were observed in adenohypophysis cells in severe acute pancreatitis.These changes might correlate with PARP and NF-κB signaling pathway.

Objective To explore the effects of rosiglitazone (ROSI),a PPAR-γ ligand,on hyperlipidemia with severe acute pancreatitis (SAP) in the rat model induced by sodium taurocholate injected into intra-bile-pancreatic duct and explore their underlying mechanism.Methods A total of 120 male SD rats were randomly divided into two groups,and eighty rats were fed with high fat diet for two weeks to induce experimental hyperlipemia and the rest received normal diet.The rats fed with normal diet were divided into two groups:sham operation group (SO group,n =20) and SAP group (n =20).The hyperlipidemic rats were randomly divided into four groups:sham operation hyperlipidemia rats group (HL group,n =20),hyperlipidemia with acute pancreatitis group (HAP group,n =20),ROSI prevention group (HR group,n =20) and antagonist group (HRI group,n =20).Rats of SAP group and HAP group were induced by a retrograde infusion of 5％ sodium tauroholate into bile-pancreatic duct,whereas the rats in SO group and HL group were induced by saline instead; rats in HR group were administered ROSI (10 mg/kg) intra-peritoneally 1 hour prior to sodium taurocholate; rats in HRI group were administered GW9662 (0.3 mg/kg) intraperitoneally 30 min prior to ROSI.Rats from each group were sacrificed by exsanguination 12 h after the induction of pancreatitis.Blood samples were taken from all animals to measure serum amylase (AMY),total cholesterol (TC),triglycerides (TG).The severity of pancreatitis was evaluated by histological score of pancreatic injury.The level of nuclear factor (NF)-KB p65 protein in pancreas was measured by immunohistochemistry.The levels of intercellular adhesion molecule (ICAM-1) protein and tumor necrosisfactor-α (TNF-α) protein were detected by using Western blot analysis.Results The serum levels of TC and TG in HL group and HAP group were significantly higher than those in SO group and SAP group (10.86 ± 1.47,10.42±0.95vs.1.72±0.13; 1.24±0.28,1.36±0.13 vs.0.61 ±0.12,0.54±0.08; all P＜ O.05).Compared with SAP group,the levels of serum AMY,the pancreas pathological score,the levels of NF-KB p65,ICAM-1 and TNF-α in pancreas in the HAP group were significantly higher in HAP group (P ＜ 0.05).Compared with the HAP group and HRI group,HR group significantly decreased the levels of serum AMY,TC and TG; pancreas pathological score; the levels of NF-KB p65,ICAM-1 and TNF-α in pancreas significantly decreased in HR group (2006.9 ± 331.9 vs.6501.9 ± 3771.0,5892.2 ± 474.3 ; 4.36 ± 0.99 vs.10.42 ±0.95,11.08 ± 1.05; 0.58 ±0.12 vs.1.36 ±0.13,1.58 ±0.12; all P ＜0.05),but there were no statistically significant differences in those biomarkers between HAP group and HRI (P ＞ 0.05).Conclusions Our study demonstrated that hyperlipidemia aggravated the severity of sodium taurocholateinduced severe acute pancreatitis and ROSI exerted anti-hyperlipidemic effect and anti-inflanmatory effect against hyperlipidemia rats with sodium taurocholate-induced severe acute pancreatitis.

Objective To investigate the protective effects of poly-ADP-ribose polymerase inhibitor 3-aminobenzamide (3-AB) on lung injury in rats with severe acute pancreatitis (SAP) and to explore the mechanisms.Methods Thirty-six Wistar rats were randomly (random number) divided into three groups (n =12 for each group),namely sham operation (SO) group,SAP group and 3-AB-treated group.The model of SAP-associated lung injury was established by retrograde injection of 5％ sodium taurocholate (STC) into the biliopancreatic duct.In the treated group,3-AB in dose of 10 mg/kg was administered twice by intravenous injection 30 min before and 30 min after STC infusion.The survival rats were sacrificed 12hours after SAP modeling,and the serum amylase,lung wet/dry ratio and myeloperoxidase (MPO) activity were determined,and pathological scores of pancreas and lung tissue were evaluated under light microscope.Expressions of interleukin (IL) -1 β and IL-6 mRNA,tumor necrosis factor α (TNF-α) and inter-cellular adhesion molecule-1 (ICAM-1) protein were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot,respectively. Results The serum amylase level,lung wet/dry ratio and MPO activity,IL-1β and IL-6 mRNA expressions,TNF-α and ICAM-1 protein levels were dramatically increased in SAP group ( P ＜ 0.05 ).Treatment with 3-AB significantly reduced these biomarkers in 3-AB group than in SAP group (P ＜ 0.05 ).Conclusions Poly-ADP-ribose polymerase inhibitor 3-AB exerts the protective and therapeutic effects on lung injury associated with severe acute pancreatitis through inhibiting intrapulmonary MPO activity and down-regulating the expressions of IL-1 β and IL-6 mRNA as well as the levels of TNF-α,and ICAM-1.

Objective:To investigate the clinical value of peripheral monocyte and neutrophil count in predicting the response of patients with metastatic non-small cell lung cancer (mNSCLC) to immunosuppressive checkpoint inhibitors (ICI).Methods:The clinical data of 34 adult mNSCLC patients who received nafulizumab or pabolizumab in Danzhou People's Hospital of Hainan Province from January 2017 to March 2019 were retrospectively analyzed. The correlation of the demographic characteristics, clinical data, hematological examination results in the first two weeks before the treatment and two weeks after ICI treatment with prognosis was recorded and observed.Results:The baseline mean monocyte count [(0.52±0.09)×10 9/L vs. (0.60±0.12)×10 9/L] and neutrophil count [(4.27±0.87)×10 9/L vs.(5.39±1.02)×10 9/L] of patients with ICI reaction were lower than those of patients without ICI reaction, and the differences were statistically different ( t = -2.572, -2.727, all P < 0.05). However, there was a negative correlation between the monocyte count of the patients who responded to ICI and the reaction time ( r = -0.507, P < 0.05). The median reaction time in patients with monocyte count >0.70×10 9/L was shorter than that in patients with monocyte count ≤0.70×10 9/L (8 weeks vs. 12 weeks, χ2=4.162, P = 0.041). There was no correlation between monocyte count and time of reaction duration, progression of free survival (PFS) and overall survival (OS) ( r = -0.214, 0.182, 0.232, all P > 0.05). The decrease rate of neutrophil count in response group was higher than that in non-response group (22% vs. 2%, P < 0.05). After the first administration, cutoff value of neutrophil count was 4.2×10 9/L; the response rate of patients with neutrophil count ≤ 4.2×10 9/L was higher than that of patients with neutrophil count > 4.2×10 9/L [86.7% (13/15) vs. 36.8% (7/19), χ2=6.657, P < 0.05]. Conclusion:Peripheral blood monocyte and neutrophil count can predict the response to ICI therapy in patients with mNSCLC.