Heat stress combined with lipopolysaccharide induces pulmonary microvascular endothelial cell glycocalyx inflammatory damage in vitro.

Heat stroke is a life-threatening disease with high mortality and complications. Endothelial glycocalyx (EGCX) is essential for maintaining endothelial cell structure and function as well as preventing the adhesion of inflammatory cells. Potential relationship that underlies the imbalance in inflammation and coagulation remains elusive. Moreover, the role of EGCX in heat stroke-induced organ injury remained unclear. Therefore, the current study aimed to illustrate if EGCX aggravates apoptosis, inflammation, and oxidative damage in human pulmonary microvascular endothelial cells (HPMEC). Heat stress and lipopolysaccharide (LPS) were employed to construct in vitro models to study the changes of glycocalyx structure and function, as well as levels of heparansulfate proteoglycan (HSPG), syndecan-1 (SDC-1), heparansulfate (HS), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, Von Willebrand factor (vWF), endothelin-1 (ET-1), occludin, E-selectin, vascular cell adhesion molecule-1 (VCAM-1), and reactive oxygen species (ROS). Here, we showed that heat stress and LPS devastated EGCX structure, activated EGCX degradation, and triggered oxidative damage and apoptosis in HPMEC. Stimulation of heat stress and LPS decreased expression of HSPG, increased levels of SDC-1 and HS in culture supernatant, promoted the production and release of proinflammation cytokines (TNF-α and IL-6,) and coagulative factors (vWF and ET-1) in HPMEC. Furthermore, Expressions of E-selection, VCAM-1, and ROS were upregulated, while that of occludin was downregulated. These changes could be deteriorated by heparanase, whereas they meliorated by unfractionated heparin. This study indicated that EGCX may contribute to apoptosis and heat stroke-induced coagulopathy, and these effects may have been due to the decrease in the shedding of EGCX.

Proteomic analysis of extracellular vesicles released from heat-stroked hepatocytes reveals promotion of programmed cell death pathway.

Liver injury is a common complication of severe heat stroke (HS). Extracellular vesicles (EVs) are part of a novel pathway mediating intercellular communication. Whether EVs are involved in the pathogenesis underlying HS-induced liver injury remains unknown. Here, we explored the role of hepatocyte EVs in HS-induced liver injury and their protein regulation patterns after HS induction. Isobaric tags for relative and absolute quantification technology (iTRAQ) and liquid chromatography-tandem mass spectrometry analysis identified changes in the proteomic profiles of hepatocyte-derived heat-stroked EVs, and we identified 53 up-regulated proteins. Bioinformatics analysis verified that the regulation of programmed cell death was the most significant altered pathway. To clarify the effect of HS hepatocyte-derived EVs in inducing hepatocyte-programmed death and injury, they were added to recipient hepatocytes and injected into mice. This treatment significantly induced the synthesis of apoptosis (caspase-3/8) and necroptosis-associated proteins [receptor-interacting protein 1 (RIP1), RIP3, and mixed lineage kinase domain-like protein]; moreover, it increased the numbers of apoptotic and necroptotic cells in hepatocytes and liver tissues and increased the levels of biochemical liver injury markers (alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase). Our study is the first comprehensive analysis of the hepatocyte-derived heat-stroked EV proteome confirming the induction of liver injury by Evs. We provide a novel explanation for the pathological mechanism underlying HS-induced liver injury.

Death Caused by Vaginal Injection of Hyaluronic Acid and Collagen: A Case Report.

With the expanding utilization of hyaluronic acid (HA) and collagen as cosmetic fillers in plastic and reconstructive surgery, complications due to their excessive use and/or irregular procedures warrant great caution. Recently, a fatal case occurred caused by a poorly regulated procedure of vaginal injection of HA and collagen. A 33-year-old female was admitted to the emergency department 3 hours after the operation with a chief complaint of dyspnea, which initiated 5 to 10 minutes after the operation. Her blood pressure remained low while dopamine pressor and fluid replacement were used. Computed tomography of the chest showed local exudation in the lower lobe of the left lung, enlargement of right atrium and ventricle, and uneven development of the bilateral inferior lobar artery with filling defects. Pulmonary computed tomography angiography and three-dimensional reconstruction showed continuous interruption of pulmonary artery branches of the posterior basal segment of the right lower lobe. Unfortunately, the clinical symptoms caused by vaginal injection aggravated rapidly and could not be effectively controlled. The patient died 9 hours after injection. Pulmonary complications after injection of cosmetic fillers are scarcely reported. Thus far, only 2 cases of HA-related pulmonary complications after vaginal injection have been described. The present case emphasizes that surgeons and other healthcare providers must be aware of the risk of serious pulmonary complications and even death associated with these 2 widely utilized injectable fillers. Level of Evidence: 5.

PI3K/AKT and CD40L Signaling Regulate Platelet Activation and Endothelial Cell Damage in Sepsis.

Platelets contribute to inflammation and their activation has been suggested as versatile effectors of sepsis. Activation of platelets promotes secretion of CD40L that induces sepsis and multiple organ dysfunction syndrome (MODS). However, the mechanisms regulate platelet-derived CD40L are not fully understood. Activation of PI3K/Akt pathway has been reported as a key component of sepsis, whereas the role of PI3K/Akt pathway in platelet-derived CD40L is unknown. In this study, we identified PI3K/Akt pathway as a key regulator of CD40L secretion by platelets. Significantly, inhibition of PI3K/Akt pathway by Ly294002 attenuated platelet activation and CD40L production. Moreover, PI3K/Akt pathway blocking suppresses vascular endothelial cells in vivo. Furthermore, the expression of biomarkers that represent the severity of sepsis, such as ICAM-1, VCAM-1, and E-selectin, was also suppressed by Ly294002. Altogether, our results confirm the pivotal role of PI3K/Akt pathway in sepsis and its inhibition might be a potential therapeutic target.

Xuebijing injection attenuates pulmonary injury by reducing oxidative stress and proinflammatory damage in rats with heat stroke.

The present study aimed to investigate the protective effect of Xuebijing injection (XBJ) on lung injury in heat-stroke rats and the underlying mechanisms. In total, 54 rats were randomly assigned to non-thermal, saline vehicle and XBJ groups. The rectal temperature (Tc), mean arterial pressure (MAP) and respiratory rate (RR) of the rats were recorded. The time-point of heat stroke and the time of survival were assessed, and indicators of arterial blood gas were regularly measured from 0 to 60 min. The concentration of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and IL-10 was also determined. At the end of the experiment, lung tissue was harvested for histopathological analysis. Inducible nitric oxide synthase (iNOS) and superoxide dismutase (SOD) expression was measured by immunohistochemistry. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was used to measure apoptosis. XBJ pretreatment prolonged the decline of clinical characteristics, as demonstrated by increases in Tc, MAP, RR and indicators in arterial blood gas in rats under heat stress. The time until heat stroke and the survival time in the Saline group were shorter than in rats treated with XBJ. The expression of iNOS in lung tissue and the concentration of TNF-α, IL-1ß and IL-10 in the bronchoalveolar lavage fluid of rats treated with saline was higher than in rats with XBJ pre-treatment. Contrarily, SOD expression in rats treated with saline was decreased compared with that in rats treated with XBJ. Moreover, the apoptotic rate in the lung tissues of rats with saline treatment was higher than that in rats treated with XBJ. In conclusion, XBJ delayed the development of heat stroke and increased the survival time in rats under heat-stress by ameliorating pulmonary failure and acute lung injury. The underlying mechanisms of this effect may be the reduction of inflammatory cytokines as well as attenuation of oxidative stress and apoptosis by XBJ.

Mesenteric Lymph Duct Ligation Alleviating Lung Injury in Heatstroke.

To explore the roles of mesenteric lymph on lung injury in heatstroke (HS), HS rat model was prepared in a prewarmed incubator. Vascular endothelium injury biomarkers (circulating endothelial cell [CEC] as well as von Willebrand factor [vWF] and thrombomodulin [TM]), proinflammatory factors (tumor necrosis factor-α [TNF-α], interleukin-1ß [IL-1ß], IL-6, and high mobility group box 1), and coagulant markers (activated partial thromboplastin time, prothrombin time, D-Dimer, and platelet count) were tested in HS and HS with mesenteric lymph duct ligation (LDL) rats. In addition, lung histopathology; arterial blood gas; Evans Blue dye (EBD) and protein lung permeability; intralung inflammatory parameters including bronchoalveolar lavage fluid (BALF) TNF-α, IL-1ß, and IL-6 levels; myeloperoxidase (MPO) activity; and vWF immune staining were analyzed. LDL prolonged HS onset time but not HS survival time. LDL significantly attenuated endothelial cell injury for decreased CEC counts as well as plasma vWF and TM concentrations; downregulated systemic inflammation for decreased plasma TNF-α, IL-1ß, IL-6, and high mobility group box 1 levels; and ameliorated coagulant disorders for decreased activated partial thromboplastin time, prothrombin time, and D-Dimer levels as well as increased platelet counts. LDL also significantly reduced acute lung pathological injury; improved lung function indexes including arterial blood PaO2, pH, PaCO2, and lactic acid; decreased BALF TNF-α, IL-1ß, and IL-6 levels and lung MPO activity; improved EBD and protein lung permeability; and inhibited lung vascular endothelium vWF expression. However, all of these parameters were not recovered to the normal states. In summary, LDL developed protection roles systemically and alleviated lung injury in HS rats which indicated that modulating mesenteric lymph flow may have some potential benefits in HS.

[Pretreatment with Xuebijing injection alleviates systemic inflammatory response induced by severe heat-stroke via ameliorating intestinal injury in rats].

OBJECTIVE: To observe the effect of Xuebijing injection pretreatment on systemic inflammatory response induced by severe heat-stroke, and to investigate the mechanism of alleviation of intestinal injury in rats. METHODS: Thirty-six healthy adult male Wistar rats with grade SPF were randomly assigned into three groups with randomized number method, namely sham group, severe heat-stroke model group, and Xuebijing pretreatment group ( XBJ group ), with 12 rats in each group. The animals were placed in a pre-warm chamber [ temperature ( 40±2 ) centigrade, humidity ( 65±5 )% ] in order to induce typical heat-stroke. The duration of heat-stress was 60 minutes, while the animals in sham group were exposed to ambient temperature of 25 centigrade. Arterial blood samples were collected at the beginning and the end of heat-stress, the concentrations of tumor necrosis factor-α( TNF-α), interleukins ( IL-1ß, IL-6 ), and lipopolysaccharide ( LPS ) in peripheral blood were determined by enzyme linked immunosorbent assay ( ELISA ). The intestinal tissues were harvested after heat-stress, and the pathological changes in intestine tissues were observed after hematoxylin-eosin ( HE ) staining and under optical microscope. The pathological injury scores were calculated. Immunohistochemistry was performed to determine inducible nitric oxide synthase ( iNOS ) expression in intestinal tissue. Apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling ( TUNEL ) staining. Western Blot was used to measure the tight junction protein occludin expression. RESULTS: The concentrations of TNF-α, IL-1ß, IL-6 and LPS in blood of the rats after heat-stress in model group were significantly higher than those of sham group [ TNF-α ( µg/L ): 443.00±110.10 vs. 98.36±44.61, IL-1ß ( µg/L ): 436.37±163.64 vs.64.24±16.15, IL-6 ( µg/L ): 342.70±92.42 vs. 54.40±13.22, LPS ( µg/L ): 0.68±0.22 vs. 0.09±0.02, all P < 0.01 ], but the levels of these parameters in XBJ group were significantly lower than those of model group [ TNF-α ( µg/L ): 340.45±68.57 vs. 443.00±110.10, IL-1ß ( µg/L ): 191.33±82.78 vs. 436.37±163.64, IL-6 ( µg/L ): 192.21±37.89 vs. 342.70±92.42, LPS ( µg/L ): 0.43±0.17 vs. 0.68±0.22, all P < 0.01 ]. Infiltration of inflammatory cells, necrosis and hemorrhage in intestinal mucosa were found in the intestine of heat-stroke animals in model group. The pathological lesions in XBJ group were milder than those of model group, with a decreased pathological injury score compared with model group ( 2.10±1.15 vs. 3.20±0.67, P < 0.01 ). The expression of iNOS and apoptosis of cells in intestinal tissue in model group were increased compared with that of sham group, but they were significantly less marked in XBJ group compared with model group [ iNOS ( adjusted A value ): 0.32±0.15 vs. 0.74±0.17, apoptotic index: 0.23±0.08 vs. 0.56±0.07, both P < 0.01 ]. The order of expression for occludin protein from high to low was sham group, XBJ group and model group ( A value was 0.96±0.25, 0.62±0.20, 0.33±0.11, respectively ). Furthermore, there was significant difference in the expression of occludin protein between model group and both XBJ group and sham group ( both P < 0.01 ). CONCLUSIONS: Xuebijing injection alleviates inflammation and endotoxemia produced by severe heat-stroke in rats. The mechanism may be related to amelioration of oxidative injury, apoptosis, and dysfunction of tight junction protein occludin expression.

[Correlation of kidney injury and inflammatory response in rats with classic severe heatstroke].

OBJECTIVE: To investigate the temporal features of renal injury in rats with severe heat stroke (SHS) and their relationship with inflammatory response. METHODS: Fifty-six male Wistar rats were randomly divided into normal control group and SHS for 0, 2, 6, 24, 48, 72 hours group (SHS-0, 2, 6, 24, 48, 72 h groups), with 8 rats in each group. Rats were placed in an artificial climate chamber [ temperature (39.5±0.2) centigrade, humidity (60±5)% ] to induce SHS model, and the criterion for successful model reproduction was the onset of lowering peak systolic blood pressure ( SBP ). Then the rats were transferred to room temperature (23.0±0.2) centigrade after successful reproduction of the model. The rats of normal control group were kept in room temperature of (23.0±0.2) centigrade. Heart blood and renal tissue samples were harvested, and the levels of serum creatinine (SCr) and blood urea nitrogen (BUN) were determined by automatic biochemistry analyzer. The levels of myeloperoxidase (MPO), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in renal tissue specimens were determined by enzyme linked immunosorbent assay (ELISA). The changes in histopathology in kidney were observed with light microscopy, and Paller scores were used to assess the degree of renal injury. RESULTS: Compared with normal control group, the levels of SCr and BUN in serum, and MPO, TNF-α and IL-6 in the renal tissue homogenate were significantly increased in SHS-6 h group [SCr (µmol/L): 174.0±27.0 vs. 68.0±11.3, BUN (mmol/L): 12.6±2.3 vs. 4.3±1.2, MPO: (203.0±38.0)% vs. (100.0±1.4 )%, TNF-α: (121.0±16.0)% vs. (100.0±1.4 )%, IL-6: (118.0±19.0)% vs. (100.0±1.3)%, all P < 0.05], and they peaked at 24 hours [SCr (µmol/L): 489.0±96.0 vs. 68.0±11.3, BUN (mmol/L): 19.3±5.7 vs. 4.3±1.2, MPO: (511.0±41.0)% vs. (100.0±1.4)%, TNF-α: (399.0±47.0)% vs. (100.0±1.4)%, IL-6: (473.0±56.0)% vs. (100.0±1.3)%, all P < 0.01], then declined to the normal levels at 72 hours. Under light microscopy, tissue edema and necrosis of renal tubules were found, and leukocyte infiltration was found to be most profuse at 24 hours, then they returned to normal levels at 72 hours. Paller scores in SHS-6 h group were significantly higher than those of the normal control group (75.45±9.70 vs. 14.23±3.26, P < 0.01), and it peaked at 24 hours (186.00±14.25 vs. 14.23±3.26, P < 0.01), followed by a gradual lowering, back to normal level at 72 hours. CONCLUSIONS: The results suggest that progressive renal damage occurred in the rats with SHS within 24 hours, and it was accompanied with elevated levels of MPO, TNF-α and IL-6 in the kidney homogenate, suggesting that inhibition of neutrophil activation and the release of IL-6, TNF-α may protect the SHS associated renal injury.

Vascular endothelial cell injury partly induced by mesenteric lymph in heat stroke.

Animal models have shown that mesenteric lymph plays important roles in the pathogenesis of endothelium injury in many critical ill states. Gut-derived septicemia and endothelium injury are the two key pathogenesis of heat stroke (HS); however, it is unclear whether mesenteric lymph is cytotoxic to endothelium in HS. HS rat models were prepared in a prewarmed incubator. Mesenteric lymph, collected pre-, during, and post-HS, was analyzed for biological activity on human umbilical vein endothelial cell (HUVEC) in vitro. The effect of HS lymph on the production of von Willebrand factor (vWF), thrombomodulin (TM), and IL-6 by HUVEC was investigated. In vivo, vascular endothelium injury biomarkers, circulating endothelial cell (CEC), as well as serum soluble vWF and TM were tested in rats of HS and HS with mesenteric lymph duct ligation (HS-LDL). HS but not heat stroke sham mesenteric lymph-injured endothelial cells showed significantly increased HUVEC cytotoxicity and enhanced HUVEC monolayer permeability as well as elevated levels of vWF and TM production by HUVEC. IL-6 production by HUVEC was augmented by HS lymph in vitro. The effects of HS lymph on IL-6 production had a time course resembling that of the toxic effects of HS lymph on HUVEC. In vivo, when compared with HS rats, decreased CEC counts as well as lower serum vWF and TM concentrations were detected in HS-LDL rats. HS mesenteric lymph is probably harmful to vascular endothelium, which indicates that the modulation of mesenteric lymph may have some potential benefits to HS.

Xuebijing injection alleviates liver injury by inhibiting secretory function of Kupffer cells in heat stroke rats.

OBJECTIVE: To evaluate the effects of Xuebijing (XBJ) injection in heat stroke (HS) rats and to investigate the mechanisms underlying these effects. METHODS: Sixty anesthetized rats were randomized into three groups and intravenously injected twice daily for 3 days with 4 mL XBJ (XBJ group) or phosphate buffered saine (HS and Sham groups) per kg body weight. HS was initiated in the HS and XBJ groups by placing rats in a simulated climate chamber (ambient temperature 400C, humidity 60% ). Rectal temperature, aterial pressure, and heart rate were monitored and recorded. Time to HS onset and survival were determined, and serum concentrations of tumor necrosis factor (TNF)-alpha interleukin (IL)-1beta, IL-6, alanine-aminotransferase (ALT), and aspartate-aminotransferase (AST) were measured. Hepatic tissue was harvested for pathological examination and electron microscopic examination. Kupffer cells (KCs) were separated from liver at HS initiation, and the concentrations of secreted TNF-a, IL-beta and IL-6 were measured. RESULTS: Time to HS onset and survival were significantly longer in the XBJ than in the HS group. Moreover, the concentrations of TNF-alpha, IL-1beta, IL-6, ALT and AST were lower and liver injury was milder in the XBJ than in the HS group. Heat-stress induced structural changes in KCs and hepatic cells were more severe in the HS than in the XBJ group and the concentrations of TNF-alpha, IL-beta and IL-6 secreted by KCs were lower in the XBJ than in the HS group. CONCLUSION: XBJ can alleviate HS-induced systemic inflammatory response syndrome and liver injury in rats, and improve outcomes. These protective effects may be due to the ability of XBJ to inhibit cytokine secretion by KCs.

HMGB1 activity inhibition alleviating liver injury in heatstroke.

BACKGROUND: Heatstroke is generally considered as a sepsis-like syndrome induced by hyperthermia leading to multiorgan dysfunction. High-mobility group box 1 (HMGB1) has recently been identified as a mediator of systemic inflammation leading to multiorgan dysfunction in sepsis and nonsepsis. Elevation of plasma HMGB1 in heatstroke has been suggested in experimental models and clinical patients. By far, whether HMGB1 could be a potential therapeutic target in heatstroke is unknown. The objectives of this study are to use HMGB1 monoclonal antibody to specifically inhibit the activity of extracellular HMGB1 and to observe the possible protection of liver injury in a rat heatstroke model. METHODS: After treatment with neutralizing antibodies to HMGB1, rats were exposed to a high-temperature and high-humidity environment. At the time of heatstroke onset, the plasma and liver cytoplasm HMGB1 levels were detected by enzyme-linked immunosorbent assay. The histopathology of liver tissue was observed under light microscopy and transmission electron microscopy. Plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were determined using the commercially available kits. Plasma tumor necrosis factor-α, interleukin-1ß (IL-1ß), and IL-6 were determined using enzyme-linked immunosorbent assay kits. RESULTS: HMGB1 levels in plasma and liver cytoplasm were both elevated in heatstroke rats, which were both associated with increased plasma ALT and AST levels. Histopathologic results showed that HMGB1 monoclonal antibody pretreatment could obviously alleviate the pathologic impairments of heatstroke rats. HMGB1 monoclonal antibody pretreatment could also downregulate plasma AST and ALT levels in heatstroke rats. Plasma tumor necrosis factor-α, IL-1ß, and IL-6 levels in heatstroke rats were elevated, which could be significantly suppressed by HMGB1 antibody pretreatment. CONCLUSION: HMGB1 could be a potentially effective treatment target in heatstroke. The pathogenic mechanism of heatstoke is complicated, which needs comprehensive prevention and treatment.

Curative effect of Xuebijing injection on severe pulmonary contusion.

OBJECTIVE: To investigate the curative effects of Xuebijing (XBJ) injection, a Chinese patent medicine, on severe pulmonary contusion (PC). METHODS: Sixty-three patients with PC were randomized to conventional therapy plus XBJ injection (n = 33) or conventional therapy alone (n = 30). Between groups differences in corticosteroid treatment, immune regulation therapy, hemofiltration, infusion volume, transfusion volume and antibiotic period were measured, as were intensive care unit (ICU)-free time, ventilation time, 28-day mortality rate and incidence of ventilation-associated pneumonia (VAP). Serum concentrations of procalcitonin (PCT), tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, and IL-10, white blood cell (WBC) counts and percentages of human leukocyte antigen DR/ CD14+ (HLA-DR/CD14+) peripheral blood mononuclear cells were compared. Markers of ventilation were determined by blood gas analysis and ventilator parameters. RESULTS: WBC counts and serum concentrations of PCT, TNF-alpha, IL-6 and IL-10 were reduced significantly more quickly, and CD14+ percentage was increased significantly earlier, in the XBJ group than in the control group (P < 0.05 each).The level of ventilation and oxygenation index were ameliorated earlier in the XBJ than in the control group (P < 0.05). XBJ treatment significantly reduced ICU-free time, ventilation time and incidence of VAP (P < 0.05 each), but had no effect on 28-day mortality rate CONCLUSION: XBJ treatment can shorten ICU-free and ventilation times and reduce the incidence of VAP, improving outcomes in patients with severe PC. XBJ may act by regulating inflammation and immunity, alleviating systemic inflammatory response syndrome induced by trauma.

[Screening and identifying differentially expressed proteins in LST-R1 cells].

BACKGROUND & OBJECTIVE: Colorectal laterally spreading tumor (CLST) rarely invades deeply but always laterally spreads along the colorectal mucosa, therefore, CLST could be used as a comparative model in studying the invasion and metastasis of colorectal cancer (CRC). This study was to identify differentially expressed proteins between a CLST cell line LST-R1 and two colorectal carcinoma cell lines SW480 and LoVo using proteomic technology. METHODS: Total proteins of LST-R1, SW480 and LoVo cells were isolated by two-dimensional electrophoresis (2-DE). Differentially expressed protein spots were analyzed with Melanie 3 software. The peptide mass fingerprints (PMFs) of differently expressed proteins were analyzed by MALDI-TOF mass spectrum. Subsequently matched proteins were searched through protein databases. RESULTS: Using pH4-7 IPG gels with 250 microg protein loading, the numbers of protein spots in 2-DE maps were 1285+/-51 in LST-R1 cells, 1184+/-47 in SW480 cells, and 1124+/-54 in LoVo cells; when with 150 microg protein loading, the numbers were 989, 935 and 893, respectively. The distribution and levels of these proteins in 2-DE maps of LST-R1, SW480 and LoVo cells were analogical which indicated CLST also expresses the protein profile of common colorectal tumors. In 2-DE maps, 96+/-7 differential protein spots were detected between LST-R1 cells and SW480 cells with 50+/-6 only expressed or obviously over-expressed in LST-R1 cells and 47+/-5 in SW480 cells; 108+/-10 differential protein spots were detected between LST-R1 cells and LoVo cells with 56+/-8 only expressed or obviously over-expressed in LST-R1 cells and 52+/-11 in LoVo cells. Nineteen differentially expressed proteins were identified among LST-R1, SW480 and LoVo cells. CONCLUSION: Nineteen differentially expressed proteins are possibly involved in laterally spreading of CLST and adhesion and invasion of CRC.

[Expression of tissue inhibitor of metalloproteinase-1 in colorectal carcinoma and its clinical implications].

OBJECTIVE: To investigate the expression and clinical implication of tissue inhibitor of metalloproteinase-1 (TIMP-1) in colorectal carcinoma. METHODS: TIMP-1 expression in 54 colorectal carcinoma was observed by SP immunohistochemical method, and the results were analyzed in relation to the clinical data of patients. RESULTS: TIMP-1 was localized on the membrane and in the cytoplasm of the enteric epithelial cells, and its expression rate was 100% in normal tissue but only 59.6% (31/52) in colorectal carcinoma tissues. In addition, the expression rate of TIMP-1 was higher in the tumor tissues without lymph node metastasis than in tissues with lymph node metastasis (P<0.05). CONCLUSION: The expression of TIMP-1 is inversely correlated to lymph node metastasis of colorectal carcinoma, and decreased TIMP-1 expression may play a role in the progression of colorectal carcinoma.

[Endoscopic and histopathological features of serrated adenoma of large intestine:an analysis of 71 cases].

OBJECTIVE: To explore the endoscopic and histopathological morphology of large intestinal serrated adenomas (SA). METHODS: The endoscopic and pathological data of 71 SA patients, diagnosed in the Digestive Endoscopy Center, Nanfang Hospital from January 2002 to July 2005, were analyzed retrospectively. RESULTS: Forty-seven of the 71 serrated adenomas were protruded (sessile 23, semipedunculated 5, pedunculated 23) and 24 were superficial (flat 16, laterally spreading 8). The mean sizes of the protruded and superficial SA were 10.5 mm and 16.6 mm, respectively, and both of them were frequently located in the sigmoid and rectum. Histopathologically, SA contained tubular glands in 53, tubulovillous glands in 9 and villous glands in 9 cases. Mild dysplasia was found in 47 SAs, moderate dysplasia in 22 SAs, and canceration foci in 2 SAs. The dysplasia of SAs (<10 mm) was significantly better than that of SAs (>or= 10 mm) (P< 0.01). Most IV and III L pit SAs presented villous glands (64%) and tubular glands (68%), respectively. 40% of hyperplastic polyps-like SAs, composed of tubular glands,showed II pit pattern. Atypia in II pit SAs was similar to that in IIIL pit SAs, but was worse than that in IV pit SAs. CONCLUSION: Polyps with II pit pattern possibly are SAs sometimes. SA with the common characters of neoplastic polyps,should be regarded as a new potential precancerous lesion.