Effectiveness of enhanced recovery after surgery in the perioperative management of patients with bone surgery in China.

BACKGROUND: Enhanced recovery after surgery (ERAS) was introduced in China in 2007. Over time, the scope of ERAS has expanded from abdominal surgery to orthopedics, urology and other fields. Continuous development and research has contributed to progress of ERAS in China. In 2019, to promote the application of ERAS in bone tumor surgery, we formed the "Consensus of Experts on Perioperative Management of Accelerated Rehabilitation in Major Surgery of Bone Tumors in China". AIM: To evaluate the effect of enhanced recovery after bone tumor surgery in perioperative management in China. METHODS: One hundred and seven patients who underwent bone tumor surgery at the Second Affiliated Hospital of Xi'an Jiaotong University between May 2019 and April 2021 were randomized into a study group (53 cases) and a control group (54 cases). The study group adopted the ERAS protocol and the control group adopted conventional care. Main outcome measures included postoperative length of stay (LOS), postoperative complications, mortality, and 30-d readmission rates. Secondary outcomes included postoperative visual analog scale (VAS) score of pain, number of blood transfusions, drainage volume in 24 h after operation, patient satisfaction 30 d after discharge, VAS score at 30 d after discharge, and daily standing walking time. RESULTS: There were no significant differences in the baseline data, clinical features and surgical site between the two groups. The LOS in the study group with the ERAS protocol was 7.72 ± 3.34 d compared with 10.28 ± 4.27 d in the control group who followed conventional care. The incidence of postoperative nausea and vomiting (PONV) in the study group was 19% and 37% in the control group. The VAS scores of pain on postoperative day 1 (POD1) and POD3 in the study group were 4.79 ± 2.34 and 2.79 ± 1.53 compared with 5.28 ± 3.27 and 3.98 ± 2.27 in the control group. The drainage volume in 24 h after the operation was 124.36 ± 23.43 mL in the study group and 167.43 ± 30.87 mL in the control group. The number of blood transfusions in the study group was also lower. The patient satisfaction rate was higher in the study group than in the control group. CONCLUSION: The ERAS protocol in the perioperative period of bone tumor surgery can decrease LOS, PONV, and postoperative pain, blood transfusion and 24-h drainage, improve patient satisfaction and accelerate recovery.

The Relationship between Blood Groups and Aortic Dissection.

BACKGROUND: Plenty of diseases have been found having associations with blood types, especially cardiovascular diseases. The purpose of this study was to clarify whether there is a relationship between blood groups and acute aortic dissection. We also further studied the distribution of blood groups in different types of acute aortic dissection. METHODS: A total of 291 patients diagnosed with acute aortic dissection from 2011 to 2018 were enrolled and analyzed retrospectively in this study. The control group consisted of 582 patients who received plastic surgery at West China hospital from 2011 to 2018. First, we analyzed the distribution of blood groups between the study group and the control group, including the ABO, Rh, O and non-O groups. Then, we further divided the study group into two groups by the type of acute aortic dissection to determine if there was difference in blood groups between the two types of acute aortic dissection. RESULTS: The analysis of the distribution of ABO blood groups (p = 0.302) and Rh blood groups (p = 0.502) did not reveal statistically significant differences. There were no statistically significant differences in the distributions of ABO blood groups and Rh blood groups in different types of acute aortic dissection. CONCLUSIONS: Our study did not prove the incidence of acute aortic dissection, or the type of acute aortic dissection had a relationship with common blood groups.

γ-Secretase inhibitor reduces immunosuppressive cells and enhances tumour immunity in head and neck squamous cell carcinoma.

Immune evasion is a hallmark feature of cancer, and it plays an important role in tumour initiation and progression. In addition, tumour immune evasion severely hampers the desired antitumour effect in multiple cancers. In this study, we aimed to investigate the role of the Notch pathway in immune evasion in the head and neck squamous cell carcinoma (HNSCC) microenvironment. We first demonstrated that Notch1 signaling was activated in a Tgfbr1/Pten-knockout HNSCC mouse model. Notch signaling inhibition using a γ-secretase inhibitor (GSI-IX, DAPT) decreased tumour burden in the mouse model after prophylactic treatment. In addition, flow cytometry analysis indicated that Notch signaling inhibition reduced the sub-population of myeloid-derived suppressor cells (MDSCs), tumour-associated macrophages (TAMs) and regulatory T cells (Tregs), as well as immune checkpoint molecules (PD1, CTLA4, TIM3 and LAG3), in the circulation and in the tumour. Immunohistochemistry (IHC) of human HNSCC tissues demonstrated that elevation of the Notch1 downstream target HES1 was correlated with MDSC, TAM and Treg markers and with immune checkpoint molecules. These results suggest that modulating the Notch signaling pathway may decrease MDSCs, TAMs, Tregs and immune checkpoint molecules in HNSCC.

NOTCH1 inhibition enhances the efficacy of conventional chemotherapeutic agents by targeting head neck cancer stem cell.

Cancer stem cells (CSCs) are considered responsible for tumor initiation and chemoresistance. This study was aimed to investigate the possibility of targeting head neck squamous cell carcinoma (HNSCC) by NOTCH1 pathway inhibition and explore the synergistic effect of combining NOTCH inhibition with conventional chemotherapy. NOTCH1/HES1 elevation was found in human HNSCC, especially in tissue post chemotherapy and lymph node metastasis, which is correlated with CSCs markers. NOTCH1 inhibitor DAPT (GSI-IX) significantly reduces CSCs population and tumor self-renewal ability in vitro and in vivo. Flow cytometry analysis showed that NOTCH1 inhibition reduces CSCs frequency either alone or in combination with chemotherapeutic agents, namely, cisplatin, docetaxel, and 5-fluorouracil. The combined strategy of NOTCH1 blockade and chemotherapy synergistically attenuated chemotherapy-enriched CSC population, promising a potential therapeutic exploitation in future clinical trial.

Donor-antigen Inoculation in the Testis Promotes Skin Allograft Acceptance Induced by Conventional Costimulatory Blockade via Induction of CD8 + CD122+ and CD4 + CD25+ Regulatory T Cells.

BACKGROUND: Immune responses are somewhat suppressed in immune privileged sites, including the testes, which provide a preexisting opportunity to prolong allograft survival. Previous studies have shown that intratesticular islet allografts enjoy extended survival even without any immunosuppression. However, it is unknown if testicular immune privilege can be exploited to prolong the survival of a solid allograft, including the skin, because it is impractical to implant a solid tissue in human testes. METHODS: To immunize recipient mice, splenocytes from BALB/c mice were injected into the testis of C57BL/6 recipients 1 week before skin transplantation. CD8 + CD122+ and CD4 + FoxP3+ regulatory T [Treg] cells were quantified by fluorescence-activated cell sorting. RESULTS: Although donor-antigen inoculation alone did not delay skin allograft rejection, it significantly extended the allograft survival when combined with CD40/CD40L or B7/CD28 costimulatory blockade and further induced long-term skin allograft acceptance when both costimulatory pathways were blocked. Similarly, donor-antigen inoculation suppressed alloreactive T cell proliferation in draining lymph nodes of skin recipients in the presence of the same costimulatory blockade. Interestingly, donor-antigen inoculation via intratesticular injection increased CD8 + CD122+, but not CD4 + FoxP3+, Treg numbers after transplantation. However, both CD8 + CD122+ and CD4 + CD25+ Treg cells induced by donor-antigen inoculation and the costimulatory blockade were more potent in suppression than that induced without the inoculation. Depletion of CD8+ or CD25+ T cells largely abrogated long-term skin allograft survival induced by donor-antigen inoculation and the costimulatory blockade. CONCLUSIONS: Intratesticular inoculation with donor antigens promotes long-term skin allograft survival induced by conventional costimulatory blockade via the induction of both CD8 + CD122+ and CD4 + CD25+ Treg cells.

STAT3 blockade enhances the efficacy of conventional chemotherapeutic agents by eradicating head neck stemloid cancer cell.

Signaling transducer and activator 3 (STAT3) and cancer stem cells (CSCs) have garnered huge attention as a therapeutic focus, based on evidence that they may represent an etiologic root of tumor initiation and radio-chemoresistance. Here, we investigated the high phosphorylation status of STAT3 (p-STAT3) and its correlation with self-renewal markers in head neck squamous cell carcinoma (HNSCC). Over-expression of p-STAT3 was found to have increased in post chemotherapy HNSCC tissue. We showed that blockade of p-STAT3 eliminated both bulk tumor and side population (SP) cells with characteristics of CSCs in vitro. Inhibition of p-STAT3 using small molecule S3I-201 significantly delayed tumorigenesis of spontaneous HNSCC in mice. Combining blockade of p-STAT3 with cytotoxic drugs cisplatin, docetaxel, 5-fluorouracil (TPF) enhanced the antitumor effect in vitro and in vivo with decreased tumor sphere formation and SP cells. Taken together, our results advocate blockade of p-STAT3 in combination with conventional chemotherapeutic drugs enhance efficacy by improving CSCs eradication in HNSCC.

Role of hypoxia-inducible factor-1α and CD146 in epidermal growth factor receptor-mediated angiogenesis in salivary gland adenoid cystic carcinoma.

Adenoid cystic carcinoma (AdCC) of the salivary gland in the head and neck is characterized by indolent yet persistent growth, multiple local recurrences and early hematogenous metastasis. Considering the possible association between the epidermal growth factor receptor (EGFR) signaling pathway and angiogenesis in various types of cancer and the overexpression of EGFR in AdCC, it is reasonable to examine the correlation between angiogenesis and the EGFR signaling pathway in this carcinoma. In the present study, the expression of EGFR, CD31, CD146 and hypoxia­inducible factor­1α (HIF­1α) were evaluated by immunohistochemical staining with tissue microarray containing normal salivary gland (NSG), pleomorphic adenoma (PMA) and AdCC tissues. Pearson's correlation coefficient was conducted to demonstrate the correlation between EGFR, CD31, CD146 and HIF­1α. To determine their similarity and intimacy, hierarchical analysis was performed with Cluster 3.0 and then visualized using TreeView software. Immunohistochemical results of tissue microarrays were quantified, revealing that the expression of EGFR, CD146 and HIF­1α increased in AdCC compared with in PMA and NSG tissues. The association between the expression of EGFR and CD31 was significant and positive. The expression of CD146 and HIF­1α was positively correlated with EGFR and CD31, respectively. These findings suggest that the EGFR signaling pathway has a vital role in AdCC progression and may be associated with HIF­1α­mediated angiogenesis. These results may enhance our understanding of the mechanism underlying AdCC progression and provide potential clinical therapeutic strategies based on the inhibition of EGFR.

Notch signaling induces epithelial-mesenchymal transition to promote invasion and metastasis in adenoid cystic carcinoma.

Epithelial-mesenchymal transition (EMT) is considered to have pivotal roles in the invasive and metastatic of Adenoid cystic carcinoma (AdCC) which is marked by local infiltration and distant metastasis. Notch signaling abnormity has been implicated as important molecular events in recent next generation sequencing studies of AdCC, but the detail is still unclear. This study was designed to investigate the expression of Notch signaling pathway and its relation with EMT program in AdCC. We constructed custom-made Tissue microarray (TMA) to evaluate the immunoreactivity of Notch signaling and EMT program and found that Notch signaling increase consecutively from NSG, PMA to AdCC, suggesting Notch signaling pathway may be associated with human AdCC progression. Then, we carried out Pearson correlation analysis and showed a close correlation of Notch signaling and EMT progression. When blocking Notch signaling pathway with γ-secretase inhibitor DAPT, EMT progression was decreased and migration and invasion ability were declined. Collectively, these findings suggest the vital roles of Notch signaling pathway in AdCC progression through their relationship with EMT progress. Targeting Notch signaling may provide further understanding of the mechanism of invasion and metastasis of AdCC as well as potential clinical therapeutics.

Epidermal growth factor receptor inhibition reduces angiogenesis via hypoxia-inducible factor-1α and Notch1 in head neck squamous cell carcinoma.

Angiogenesis, a marker of cancer development, affects response to radiotherapy sensibility. This preclinical study aims to understand the receptor tyrosine kinase-mediated angiogenesis in head neck squamous cell carcinoma (HNSCC). The receptor tyrosine kinase activity in a transgenic mouse model of HNSCC was assessed. The anti-tumorigenetic and anti-angiogenetic effects of cetuximab-induced epidermal growth factor receptor (EGFR) inhibition were investigated in xenograft and transgenic mouse models of HNSCC. The signaling transduction of Notch1 and hypoxia-inducible factor-1α (HIF-1α) was also analyzed. EGFR was overexpressed and activated in the Tgfbr1/Pten deletion (2cKO) mouse model of HNSCC. Cetuximab significantly delayed tumor onset by reducing tumor angiogenesis. This drug exerted similar effects on heterotopic xenograft tumors. In the human HNSCC tissue array, increased EGFR expression correlated with increased HIF-1α and micro vessel density. Cetuximab inhibited tumor-induced angiogenesis in vitro and in vivo by significantly downregulating HIF-1α and Notch1. EGFR is involved in the tumor angiogenesis of HNSCC via the HIF-1α and Notch1 pathways. Therefore, targeting EGFR by suppressing hypoxia- and Notch-induced angiogenesis may benefit HNSCC therapy.

Inhibition of survivin reduces HIF-1α, TGF-ß1 and TFE3 in salivary adenoid cystic carcinoma.

In the present study, we explored the expression and correlation of survivin with HIF-1α, TGF-ß1 and TFE3 in adenoid cystic carcinoma (AdCC). The expression of survivin, HIF-1α, TGF-ß1 and TFE3 was assessed by immunohistochemical staining of a tissue microarray containing tissue samples of normal salivary gland (NSG), pleomorphic adenoma (PA) and AdCC. Correlation analysis of these proteins revealed that increased survivin expression was associated with the overexpression of HIF-1α (P<0.001, r = 0.5599), TGF-ß1 (P<0.001, r = 0.6616) and TFE3 (P<0.001, r = 0.7747). The expression of survivin, HIF-1α, TGF-ß1 and TFE3 was not correlated with the pathological type of human AdCC (P>0.05). Selective inhibition of survivin by YM155 and siRNA significantly reduced human SACC-83 cell proliferation, with the corresponding decrease in expression of HIF-1α, TGF-ß1 and TFE3. The data indicate that the overexpression of survivin in AdCC is related to HIF-1α, TGF-ß1 and TFE3. We hypothesize from these findings that the inhibition of survivin may be a novel strategy for neoadjuvant chemotherapeutic and radiosensitive treatment of AdCC.

CD163+ tumor-associated macrophages correlated with poor prognosis and cancer stem cells in oral squamous cell carcinoma.

Tumor-associated macrophages (TAMs) play an important role in the progression and prognostication of numerous cancers. However, the role and clinical significance of TAM markers in oral squamous cell carcinoma (OSCC) has not been elucidated. The present study was designed to investigate the correlation between the expression of TAM markers and pathological features in OSCC by tissue microarray. Tissue microarrays containing 16 normal oral mucosa, 6 oral epithelial dysplasia, and 43 OSCC specimens were studied by immunohistochemistry. We observed that the protein expression of the TAM markers CD68 and CD163 as well as the cancer stem cell (CSC) markers ALDH1, CD44, and SOX2 increased successively from the normal oral mucosa to OSCC. The expressions of CD68 and CD163 were significantly associated with lymph node status, and SOX2 was significantly correlated with pathological grade and lymph node status, whereas ALDH1 was correlated with tumor stage. Furthermore, CD68 was significantly correlated with CD163, SOX2, and ALDH1 (P < 0.05). Kaplan-Meier analysis revealed that OSCC patients overexpressing CD163 had significantly worse overall survival (P < 0.05). TAM markers are associated with cancer stem cell marker and OSCC overall survival, suggesting their potential prognostic value in OSCC.

Clinical significance of Keap1 and Nrf2 in oral squamous cell carcinoma.

Oxidative stress has been reported to play an important role in progression and prognostication in various kinds of cancers. However, the role and clinical significance of oxidative stress markers Keap1 and Nrf2 in oral squamous cell carcinoma (OSCC) has not been elucidated. This study aimed to investigate the correlation of oxidative stress markers Keap1 and Nrf2 expression and pathological features in OSCC by using tissue microarray. Tissue microarrays containing 17 normal oral mucosa, 7 oral epithelial dysplasia and 43 OSCC specimens were studied by immunohistochemistry. The association among these proteins and pathological features were analyzed. Expression of oxidative stress markers Keap1, Nrf2, and antioxidants PPIA, Prdx6, as well as CD147 was found to increase consecutively from normal oral mucosa to OSCC, and the Keap1, Nrf2, PPIA, Prdx6, CD147 expression in OSCC were significantly higher when compared to normal oral mucosa. Expression of Keap1, Nrf2 in tumors was not found to be significantly associated with T category, lymph node metastases, and pathological grade. Furthermore, we checked the relationship among these oxidative stress markers and found that Keap1 was significantly correlated with Nrf2, Prdx6 and CD147. Significant relationship between Nrf2 and Prdx6 was also detected. Finally, we found patients with overexpression of Keap1 and Nrf2 had not significantly worse overall survival by Kaplan-Meier analysis. These findings suggest that ROS markers are associated with carcinogenesis and progression of OSCC, which may have prognostic value and could be regarded as potential therapeutic targets in OSCC.

[Expression of RANKL/OPG in male mandible of different ages].

PURPOSE: To investigate the relationship between male osteoporosis and the expression of receptor activator of NF-κB ligand(RANKL) and osteoprotegerin(OPG)-mRNA in male mandible at different ages. METHODS: Between May 2008 and January 2009, bone tissues of the mandible were collected as the experimental material from 46 patients suffering from jaw facial deformity and extraction. The patients with periodontist, systemic disorder and smoking as well as drinking were excluded.They were divided into three groups: young group, whose age was 10-29 years old ;middle age group, whose age was 30-59 years old; aged group, whose age was 60-89 years old. The expression of RANKL mRNA and OPG mRNA was examined by real-time PCR. The data was analyzed using ANOVA followed by least significant difference (LSD) test with SPSS16.0 software package. RESULTS: (1)Compared with the young group, RANKL mRNA level in mandible was 2.1-fold and 5.3-fold higher in the middle age and aged groups, respectively, whereas OPG mRNA level was 3.3-fold and 4.8-fold higher in middle age and aged groups, respectively. RANKL and OPG were positively correlated with age.(2)The ratio of RANKL/OPG in middle age group was lower than that of young group and old group,respectively. CONCLUSIONS: (1)The expression of RANKL and OPG increases with age remarkably.(2)Bone formation of the mandible is activated in middle aged group. The formation is over absorption.(3)Bone formation of the mandible in aged group is at low level. Bone absorption exceeds bone formation.

[Migratory and chemoattractant responses of mesenchymal stem cells to oxidative stress injury of endothelial cell in vitro].

OBJECTIVE: To investigate the possibilities of human mesenchymal stem cells (hMSCs) migrating toward the oxidative stress injuries of endothelial cells. METHODS: hMSCs were isolated and cultured from human marrow in vitro and the multipotential differentiation of P3 hMSCs identified by specific medium induced to differentiate into osteoblasts, adipocytes and endothelial cells. And the marker antigen of P3 hMSCs was detected by flow cytometry (FCM) and immunohistochemistry. Then a cellular model of hMSCs migrating toward the oxidative stress injuries of endothelial cells was created, i. e. 1 x 10(5) hMSCs were seeded in Transwell upper chamber, indirectly co-cultured with ECV-304 cells seeded in the Transwell inferior chamber and was injured by adding 3% H2O2 into the medium (final concentration of 0.01 ml/ml) for 1 h, the injured ECV-304 cells + hMSCs group (n = 8), as experimental group, and in the mean time, hMSCs indirectly co-cultured with uninjured ECV-304 cells in Transwell chamber, ECV-304 cells + hMSCs group (n = 8) and hMSCs monoculture group (n = 8) in Transwell chamber as control groups. After a 12-h culture in all groups, the migrating hMSCs in Transwell upper chamber were HE-stained and counted under an inverted phase contrast microscope. To understand the reason why hMSCs migrated to the oxidative stress injured endothelial cells, ELISA was employed to measure the concentration of monocyte chemoattractant protein-1 (MCP-1) and vascular cell adhesion molecule-1 (VCAM-1) of cellular supernatant in ECV-304 cells with H2O2 1-h treating group (H2O2 treatment group) or without H2O2 treating group (control group). RESULTS: The multipotential differentiation experiment demonstrated that the cultured P3 hMSCs can be induced to differentiate in vitro into osteoblasts, adipocytes and endothelial cells. And the expressions of CD29, CD44, CD90 and CD106 were positive in hMSCs while CD31, CD34, CD45 and CD49b negative by using FCM and immunohistochemistry. And the effects of hMSCs upon in vitro movement toward oxidative stress injuries of ECV-304 cells were averaged (8. 00 +/- 0.22) cells/HP in the injured ECV-304 cells + hMSCs group, significantly higher than those of the ECV-304 cells + hMSCs group [(0.20 +/- 0.05) cells/HP, P < 0.01] and the hMSCs monoculture group [(0.00 +/- 0.00) cells/HP, P < 0.01). The concentrations of MCP-1 and VCAM-1 in cellular supernatant of the H2O2 treatment group were significantly higher than those of the control group [(69.2 +/- 3.5) ng/ml vs (62.5 +/- 3.6) ng/ml, P < 0.05; (114.0 +/- 7.5) ng/ml vs (97.2 +/- 5.0) ng/ml, P < 0.01]. CONCLUSIONS: The oxidative stress injuries of endothelial cells chemoattracted the hMSCs toward the injured site and its mechanism may be correlated with releasing a certain concentration of chemoattractant factor to result in the elevations of MCP-1 and VCAM-1 by oxidative stress injury.

[Experimental study on recombinant human platelet-derived growth factor gel in a diabetic rat model of cutaneous incisal wound healing].

OBJECTIVE: To investigate the effect of recombinant human platelet-derived growth factor (rhPDGF-BB) on cutaneous incisal wound healing in diabetic rats and this factor does-effect relationship. METHODS: Thirty Wistar diabetic rats were used in this study. Four full-thickness skin wounds of 2.54 cm(2) were incised in the back of each rat. The wounds were divided into five groups: three groups were treated with different dosage of rhPDGF-BB gel (14.0 microg/cm(2) wound, 7.0 microg/cm(2) wound, 3.5 microg/cm(2) wound), other two groups were treated with vehicle or untreated, respectively. rhPDGF-BB gel was topically applied to the wounds from 1 to 14 days. The wound healing effect was assessed by the measurements of the wound area, subcutaneous chamber and histological changes of each group. RESULTS: On 14 days, the wounds of the three groups treated with rhPDGF-BB contracted to (0.22+/-0.30)cm(2), (0.05+/-0.06)cm(2), (0.32+/-0.32)cm(2), respectively. The area of the middle dosage groups was significantly smaller than those treated with vehicle 0.23+/-0.22 cm(2) (P<0.05) and untreated (0.22+/-0.25) cm(2) (P<0.05). On 7 days, the subcutaneous chambers of the three treated groups contracted to (0.04+/-0.03)ml, (0.02+/-0.02)ml, (0.06+/-0.03)ml, and there was a statistic significance when comparing middle dosage group with vehicle group (0.06+/-0.03) ml (P<0.05) and untreated group (0.07+/-0.05 ml (P<0.05). As for histological examination, much more granulation formation was shown in the wound bed in middle dosage group than that in other four groups on 7 days, and some of the wounds treated with middle dosage were healing on 14 days. CONCLUSION: It suggested that topical application of rhPDGF-BB might improve wound healing in diabetic rats. The effective dosage of rhPDGF-BB is 7.0 microg/cm(2) wound.

[Characteristics of epidermal growth factor and its receptor expression in dermal chronic ulcers].

OBJECTIVE: To investigate the expression and location of epidermal growth factor (EGF) and its receptor (EGFR) in dermal chronic ulcers and normal skin in order to explore their influence on ulcer formation. METHODS: The expression intensity and distribution of EGF and EGFR were detected with pathological method and immunohistochemistry method in 8 cases of dermal ulcers, 8 cases of edge of ulcer and 8 cases of normal skin. RESULTS: The Positive signals of EGF could be found in epidermal cells, endothelial cells and some fibroblasts; EGFR was principally located in the cytoplasm and cellular membrane of these cells mentioned above in normal skin. From normal skin, edge of ulcer to ulcerative tissues, the protein contents of EGF and EGFR were decreased progressively. In ulcerative tissues, EGF was mostly distributed in monocytes and macrophages while EGFR was chiefly sited in monocytes. When compared with normal skins, the protein expression of EGF and EGFR was notably reduced in ulcerative tissues (both P<0.01). The positive cellular ratios of two proteins were reduced to (7.1+/-5.2) % and (8.8+/-5.5) % of those in normal skin respectively (all P<0.01). CONCLUSION: The formation of dermal chronic ulcers is closely associated with the reduction of EGF and EGFR protein expression which may lead to binding obstruction between EGF and its receptor.

[Expression of protooncogene c-jun, p38 and proliferating cell nuclear antigen in intestinal epithelial cells in rats different development stages].

OBJECTIVE: To investigate the expression characteristics of protooncogene c-jun and its related gene p38 in different developmental intestinal epithelial cells in rats, and to explore their biological roles in the intestinal wound healing after injury. METHODS: Immunohistochemical techniques were used to detect the expressions of c-jun, p38 and proliferating cell nuclear antigen (PCNA). RESULTS: The positive expression of c-jun in intestinal epithelial cells at the early development stage (from E14 d to P28 d) was much stronger and more extensive than that in mature rats, and migrated from bottom to top of villus with epithelial cellular development. The positive expression of PCNA was similar with c-jun during the same time, but the distinction between them was location of their expression. The expression of c-jun in mature rat only lay in the top of villus, while the expression of PCNA was limited to intestinal crypts. The expression of p38 during stages of development and mature, mainly was in mitogenic cells. CONCLUSION: The results indicate that the strong expression of tumor gene c-jun at the early development and mature stages of intestinal epithelial cells at the special region is related to cellular differentiation, and p38 is probable correlate with cellular mitogenesis.