Proteomics-based evaluation of the mechanism underlying vascular injury via DNA interstrand crosslinks, glutathione perturbation, mitogen-activated protein kinase, and Wnt and ErbB signaling pathways induced by crotonaldehyde.

Crotonaldehyde (CRA)-one of the major environmental pollutants from tobacco smoke and industrial pollution-is associated with vascular injury (VI). We used proteomics to systematically characterize the presently unclear molecular mechanism of VI and to identify new related targets or signaling pathways after exposure to CRA. Cell survival assays were used to assess DNA damage, whereas oxidative stress was determined using colorimetric assays and by quantitative fluorescence study; additionally, cyclooxygenase-2, mitogen-activated protein kinase pathways, Wnt3a, ß-catenin, phospho-ErbB2, and phospho-ErbB4 were assessed using ELISA. Proteins were quantitated via tandem mass tag-based liquid chromatography-mass spectrometry and bioinformatics analyses, and 34 differentially expressed proteins were confirmed using parallel reaction monitoring, which were defined as new indicators related to the mechanism underlying DNA damage; glutathione perturbation; mitogen-activated protein kinase; and the Wnt and ErbB signaling pathways in VI based on Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and protein-protein interaction network analyses. Parallel reaction monitoring confirmed significant (p < 0.05) upregulation (> 1.5-fold change) of 23 proteins and downregulation (< 0.667-fold change) of 11. The mechanisms of DNA interstrand crosslinks; glutathione perturbation; mitogen-activated protein kinase; cyclooxygenase-2; and the Wnt and ErbB signaling pathways may contribute to VI through their roles in DNA damage, oxidative stress, inflammation, vascular dysfunction, endothelial dysfunction, vascular remodeling, coagulation cascade, and the newly determined signaling pathways. Moreover, the Wnt and ErbB signaling pathways were identified as new disease pathways involved in VI. Taken together, the elucidated underlying mechanisms may help broaden existing understanding of the molecular mechanisms of VI induced by CRA.

Integrative analysis of gene expression and DNA methylation through one-class logistic regression machine learning identifies stemness features in medulloblastoma.

Most human cancers develop from stem and progenitor cell populations through the sequential accumulation of various genetic and epigenetic alterations. Cancer stem cells have been identified from medulloblastoma (MB), but a comprehensive understanding of MB stemness, including the interactions between the tumor immune microenvironment and MB stemness, is lacking. Here, we employed a trained stemness index model based on an existent one-class logistic regression (OCLR) machine-learning method to score MB samples; we then obtained two stemness indices, a gene expression-based stemness index (mRNAsi) and a DNA methylation-based stemness index (mDNAsi), to perform an integrated analysis of MB stemness in a cohort of primary cancer samples (n = 763). We observed an inverse trend between mRNAsi and mDNAsi for MB subgroup and metastatic status. By applying the univariable Cox regression analysis, we found that mRNAsi significantly correlated with overall survival (OS) for all MB patients, whereas mDNAsi had no significant association with OS for all MB patients. In addition, by combining the Lasso-penalized Cox regression machine-learning approach with univariate and multivariate Cox regression analyses, we identified a stemness-related gene expression signature that accurately predicted survival in patients with Sonic hedgehog (SHH) MB. Furthermore, positive correlations between mRNAsi and prognostic copy number aberrations in SHH MB, including MYCN amplifications and GLI2 amplifications, were detected. Analyses of the immune microenvironment revealed unanticipated correlations of MB stemness with infiltrating immune cells. Lastly, using the Connectivity Map, we identified potential drugs targeting the MB stemness signature. Our findings based on stemness indices might advance the development of objective diagnostic tools for quantitating MB stemness and lead to novel biomarkers that predict the survival of patients with MB or the efficacy of strategies targeting MB stem cells.

Heat shock factor 1 in cancer-associated fibroblasts is a potential prognostic factor and drives progression of oral squamous cell carcinoma.

Heat shock factor 1 (HSF1) is highly expressed in various malignancies and is a potential modulator of tumor progression. Emerging evidence suggests that HSF1 activation in stromal cells is closely related to poor patient prognosis. However, the role of HSF1 in oral squamous cell carcinoma (OSCC) remains elusive. We aimed to investigate the function of HSF1 in cancer-associated fibroblasts (CAFs) of the tumor microenvironment (TME) and in tumor development. In the present study, we found that HSF1 was highly expressed in both CAFs and tumor cells, and was significantly correlated with poor prognosis and overall survival. Moreover, HSF1 overexpression in CAFs resulted in a fibroblast-like phenotype of Cal27 cells, induced epithelial-mesenchymal transition (EMT), and promoted proliferation, migration and invasion in Cal27 cells. HSF1 knockdown attenuated features of CAFs and reduced EMT, proliferation, migration and invasion in Cal27 cells. Furthermore, HSF1 in CAFs promoted tumor growth in nude mice. Taken together, these data suggest that HSF1 expression in CAFs drive OSCC progression, and could serve as an independent prognostic marker of patients with OSCC. Thus, HSF1 is a potent mediator of OSCC malignancy.

Synthesis and evaluation of tetrahydroquinolin-2(1H)-one derivatives as novel anti-pancreatic cancer agents via targeting autophagy.

Pancreatic cancer is one of the most deadly neoplasm with a 5-year survival rate of less than 6% owing to its remarkable tolerance to nutrient starvation, and new drugs and treatment strategies are urgently needed. During a project aiming at discovery of anticancer agents, we performed a structure modification on polycyclic polyprenylated acylphloroglucinols (PPAPs) skeleton, and discovered that PPAP rearranged to a tetrahydroquinolin-2(1H)-one feature. Here, series of tetrahydroquinolin-2(1H)-one derivatives were designed, synthesized and evaluated against a highly metastatic human pancreatic cancer cell line (PANC-1), and the structure-activity relationship was also discussed. Among them, derivative 11k showed the most potent inhibitory activity with an IC50 value of 4.9 µM under nutrient-deprived condition. In contrast, all these derivatives exhibited low cytotoxicity against PANC-1 cells under normal nutrient condition, suggesting that the derivatives appeared to allow alternative tumor cell death mechanisms, and led to less toxicity. Further evaluations demonstrated that 11k decreased colony formation and induced the apoptosis of PANC-1 under nutrient-deprived condition in a concentration dependent manner. In in vivo study, 11k significantly suppressed the tumor development and weight in nude mice. Preliminary mechanism research revealed that 11k clearly downregulated LC3-II expression and increased the level of p62, two key autophagy markers and critical signals for pancreatic tumor growth and progression. Our current findings demonstrated that 11k might be a promising candidate for the new chemotherapeutic molecule of pancreatic cancer, and deserve further study.

NR4A1 retards adipocyte differentiation or maturation via enhancing GATA2 and p53 expression.

Nuclear receptor subfamily 4 group A member 1 (NR4A1) is an orphan nuclear receptor with diverse functions. It has been reported that NR4A1, as a transcriptional activator, is implicated in glucose and lipid metabolism. The aim of this study was to investigate the regulatory role of NR4A1 in adipogenesis and explore the underlying mechanisms. Quantitative real-time PCR and Western blotting were used to analyse the expression of genes involved in synthesis and mobilization of fats in vivo and in vitro. Dual-luciferase reporter assay was conducted to study the regulatory mechanisms of NR4A1. Our data from in vivo study confirmed that NR4A1 knockout (KO) mice fed with high-fat diet were more prone to obesity, and gene expression levels of PPARγ and FAS were increased in KO mice compared to controls; our data from in vitro study showed that NR4A1 overexpression in 3T3-L1 pre-adipocytes inhibited adipogenesis. Moreover, NR4A1 enhanced GATA binding protein 2 (GATA2) expression, which in turn inhibited peroxisome proliferator-activated receptor γ (PPARγ); NR4A1 inhibited sterol regulatory element binding transcription factor 1 (SREBP1) and its downstream gene fatty acid synthase (FAS) by up-regulating p53. NR4A1 inhibits the differentiation and lipid accumulation of adipocytes by enhancing the expression of GATA2 and p53.

Decrease in phosphorylated ERK indicates the therapeutic efficacy of a clinical PI3Kα-selective inhibitor CYH33 in breast cancer.

PI3Ks are frequently hyper-activated in breast cancer and targeting PI3Kα has exhibited promising but variable response in preclinical and clinical settings. CYH33 is a novel PI3Kα-selective inhibitor in phase I clinical trial. We investigated the efficacy of CYH33 against breast cancer and explored potential predictive biomarkers. CYH33 potently restrained tumor growth in mice bearing human breast cancer cell xenografts and in R26-Pik3caH1047R;MMTV-Cre transgenic mice. CYH33 significantly inhibited proliferation of a panel of human breast cancer cells, while diversity in sensitivity has been observed. Cells harboring activating PIK3CA mutation, amplified HER2 were more responsive to CYH33 than their counterparts. Besides, cells in HER2-enriched or luminal subtype were more sensitive to CYH33 than basal-like breast cancer. Sensitivity to CYH33 has been further revealed to be associated with induction of G1 phase arrest and simultaneous inhibition of Akt and ERK. Sensitivity of patient-derived xenograft to CYH33 was also positively correlated with decrease in phosphorylated ERK. Taken together, CYH33 is a promising PI3Kα inhibitor for breast cancer treatment and decrease in ERK phosphorylation may indicate its efficacy, which provides useful clues for rational design of the ongoing clinical trials.

Dual roles of QOA-8a in antiosteoporosis: a combination of bone anabolic and anti-resorptive effects.

Osteoporotic treatments have largely depended on antiresorptive or anabolic drugs; but the former also suppresses new bone formation, and the latter only includes human parathyroid hormone. There is no drug that has a dual effect to inhibit bone resorption and to stimulate bone formation simultaneously. Here, we report a small molecule, a quinoxaline derivative of oleanolic acid (QOA-8a) that plays such dual roles in osteoblasts and osteoclasts in the treatment of osteoporosis. Osteoclast differentiation was induced by incubation of primary mouse bone marrow-derived macrophages in the presence of RANKL and M-CSF, treatment with QOA-8a dose-dependently inhibited the osteoclast formation with an IC50 value of 0.098 µmol/L. QOA-8a also directly acted on osteoblasts, and stimulated new bone formation in murine calvarial bones in vitro and in vivo. In an OVX rat model, administration of QOA-8a (1, 5 mg·kg-1·d-1, po) for 16 weeks effectively prevented OVX-induced bone loss, accompanied by decreased serum levels of the bone resorption marker CTX-1 and increased serum levels of osteoblast marker N-MID-OT. Meaningfully, our preliminary study revealed that QOA-8a down-regulated the ERK1/2 signal in osteoclasts and up-regulated the signal in osteoblasts. QOA-8a showed dual functions in both animal and human osteoclastogenesis and osteoblastogenesis. Our results demonstrate that QOA-8a might serve as a lead compound with a dual function of bone anabolic and anti-resorptive effects in the development of anti-osteoporosis agents.

The polycystic ovary syndrome-associated gene Yap1 is regulated by gonadotropins and sex steroid hormones in hyperandrogenism-induced oligo-ovulation in mouse.

STUDY QUESTION: What is the physiological function of Yes-associated protein-1 (Yap1), a susceptibility gene for polycystic ovary syndrome (PCOS), in ovarian granulosa cells (GCs)? SUMMARY ANSWER: Physiologically, steroid sex hormones stimulate follicle growth by activating YAP1; however, the preovulatory inhibition of YAP1 activity in GCs is a prerequisite of LH actions. WHAT IS KNOWN ALREADY: PCOS is a common gynecologic and endocrine disease with multiple short and long-term consequences. Many PCOS patients suffer anovulation caused by hyperandrogenism, but its etiology remains unclear. STUDY DESIGN, SIZE, DURATION: To study the effect of acute hyperandrogenism on ovulation, we injected pregnant mare serum gonadotrophin (PMSG)-primed (44 h) pubertal mice with dihydrotestosterone (DHT), the major biologically active form of androgen, in a superovulation assay. We investigated if YAP1 is regulated by testosterone and if it is potentially involved in follicle development and ovulation. Cultured primary GCs were subjected to Yap1 depletion by RNA interference and Yap1 overexpression by adenoviral infections. PARTICIPANTS/MATERIALS, SETTING, METHODS: Female mice at postnatal day (PD)-21~23 were analyzed to avoid the complexity of ovarian functions associated with estrous cycles and endogenous surges of gonadotropins. Immature mice were injected intraperitoneally with five IU PMSG to stimulate preovulatory follicle development followed 44 h later with five IU hCG to stimulate ovulation. For DHT treatments, female mice at PD23 were injected intraperitoneally with five IU PMSG followed 44 h later with five IU hCG alone (as control) or five IU hCG plus 100 µg DHT, which was dissolved in 0.1 ml DMSO. Methods of gene expression detection used include immunohistochemistry, immunofluorescence, Western blotting and quantitative PCR. More than three biological and technical replicates were included in each experiments. MAIN RESULTS AND THE ROLE OF CHANCE: we provide novel evidence in a mouse model that YAP1 is required for proliferation of ovarian GCs, but is down-regulated by LH through the extracellular-regulated kinase-1/2 (ERK1/2) cascade. Acute hyperandrogenism blocks LH actions and causes oligo-ovulation by activating YAP1. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Results shown were obtained only in mouse, and need to be further confirmed in human samples. WIDER IMPLICATIONS OF THE FINDINGS: These findings not only elucidated the role of YAP1 in maintaining normal ovarian functions, but also link the YAP1 deregulation to the pathogenesis of PCOS. STUDY FUNDING AND COMPETING INTEREST(S): This study is funded by the National Key Research and Development Program of China (2016YFC1000600 and 2017YFSF1001500) and National Natural Science Foundation of China (31528016, 31371449 and 31671558). The authors have no competing interests.

STMN1 Promotes Progesterone Production Via StAR Up-regulation in Mouse Granulosa Cells.

Stathmin 1 (STMN1) is a biomarker in several types of neoplasms. It plays an important role in cell cycle progression, mitosis, signal transduction and cell migration. In ovaries, STMN1 is predominantly expressed in granulosa cells (GCs). However, little is known about the role of STMN1 in ovary. In this study, we demonstrated that STMN1 is overexpressed in GCs in patients with polycystic ovary syndrome (PCOS). In mouse primary GCs, the overexpression of STMN1 stimulated progesterone production, whereas knockdown of STMN1 decreased progesterone production. We also found that STMN1 positively regulates the expression of Star (steroidogenic acute regulatory protein) and Cyp11a1 (cytochrome P450 family 11 subfamily A member 1). Promoter and ChIP assays indicated that STMN1 increased the transcriptional activity of Star and Cyp11a1 by binding to their promoter regions. The data suggest that STMN1 mediates the progesterone production by modulating the promoter activity of Star and Cyp11a1. Together, our findings provide novel insights into the molecular mechanisms of STMN1 in ovary GC steroidogenesis. A better understanding of this potential interaction between STMN1 and Star in progesterone biosynthesis in GCs will facilitate the discovery of new therapeutic targets in PCOS.

Reconstruction of abdominal wall defects using small intestinal submucosa coated with gelatin hydrogel incorporating basic fibroblast growth factor.

PURPOSE: To construct a new biomaterial-small intestinal submucosa coated with gelatin hydrogel incorporating basic fibroblast growth factor, and to evaluate the new biomaterials for the reconstruction of abdominal wall defects. METHODS: Thirty six Sprague-Dawley rats were used in the animal experiments and randomly divided into three groups. The new biomaterial was constructed by combining small intestinal submucosa with gelatin hydrogel for basic fibroblast growth factor release. Abdominal wall defects were created in rats, and repaired using the new biomaterials (group B), compared with small intestinal submucosa (group S) and ULTRAPROTM mesh (group P). Six rats in each group were sacrificed at three and eight weeks postoperatively to examine the gross effects, inflammatory responses, collagen deposition and neovascularization. RESULTS: After implantation, mild adhesion was caused in groups B and S. Group B promoted more neovascularization than group S at three weeks after implantation, and induced significantly more amount of collagen deposition and better collagen organization than groups S and P at eight weeks after implantation. CONCLUSION: Small intestinal submucosa coated with gelatin hydrogel incorporating basic fibroblast growth factor could promote better regeneration and remodeling of host tissues for the reconstruction of abdominal wall defects.

Reconstruction of abdominal wall defects using small intestinal submucosa coated with gelatin hydrogel incorporating basic fibroblast growth factor

To construct a new biomaterial-small intestinal submucosa coated with gelatin hydrogel incorporating basic fibroblast growth factor, and to evaluate the new biomaterials for the reconstruction of abdominal wall defects. Thirty six Sprague-Dawley rats were used in the animal experiments and randomly divided into three groups. The new biomaterial was constructed by combining small intestinal submucosa with gelatin hydrogel for basic fibroblast growth factor release. Abdominal wall defects were created in rats, and repaired using the new biomaterials (group B), compared with small intestinal submucosa (group S) and ULTRAPROTM mesh (group P). Six rats in each group were sacrificed at three and eight weeks postoperatively to examine the gross effects, inflammatory responses, collagen deposition and neovascularization. After implantation, mild adhesion was caused in groups B and S. Group B promoted more neovascularization than group S at three weeks after implantation, and induced significantly more amount of collagen deposition and better collagen organization than groups S and P at eight weeks after implantation. Small intestinal submucosa coated with gelatin hydrogel incorporating basic fibroblast growth factor could promote better regeneration and remodeling of host tissues for the reconstruction of abdominal wall defects.

[Application of fat clearance technique in pathologic staging for colon cancer].

OBJECTIVE: To evaluate whether the use of fat clearance technique improves the accuracy of staging for colon cancer. METHODS: Between June 2007 and December 2008, surgical specimens of 91 patients with colon cancer were procured. Between June 2007 and January 2008, routine technique for lymph node harvest including visualization and tactile sensation was used in 45 patients (conventional group), while lymph nodes of 46 patients between February 2008 and December 2008 were examined using fat clearance technique(fat clearance group). RESULTS: The mean of lymph nodes harvested was 32.7 using fat clearance technique, significantly higher than that(15.3) of the conventional group(P<0.01). The mean positive lymph nodes was 2.7 and 1.8 in the two groups, respectively, with a statistically significant difference(P<0.05). There were more stage III( colon cancer in the postoperative staging than that in the preoperative staging using fat clearance technique (31 vs.19, P<0.05), while there was no difference in stage III( colon cancer between postoperative staging and preoperative staging using conventional method (21 vs.19, P>0.05). CONCLUSIONS: Fat clearance technique significantly increases number of lymph node retrieval and positive nodes, therefore the accuracy of postoperative staging is improved.

[The influence of lymph nodes detection on pathological staging in rectal cancer].

OBJECTIVE: To investigate the influence of lymph nodes detection on the pathological staging in rectal cancer specimens. METHODS: From January 2007 to June 2008, 75 patients with rectal cancer who underwent total mesorectal excision were randomly divided into two groups: conventional group (n = 39), in which lymph nodes were detected by sight and palpation; fat clearance group (n = 36), in which lymph nodes were harvested after the specimens immersed in a fat clearance solution for 24 hours. The lymph node number harvested was compared between the two groups, and metastasis of the lymph nodes and its impact on the pathologic staging was analyzed in the two groups. RESULTS: A total of 75 patients (42 male and 33 female, the average age was 53.2 years) were enrolled in this study. In the conventional group, a mean of 14.4 lymph nodes (range, 8 - 27) was detected, and was significantly less than that in fat clearance group (mean 36.2, range, 18 - 62) (t = 5.800, P < 0.05). The tumor invasion was classified as T1 in 4 cases and 5 cases, T2 in 9 cases and 6 cases, T3 in 24 cases and 22 cases and T4 in 2 cases and 3 cases in conventional group and fat clearance group, respectively. No significant difference was found in T classification between the two groups (Z = 0.160, P = 0.850). The mean number of metastatic lymph nodes harvested in conventional group was 1.5, and it was 3.2 in the fat clearance group (Z = 3.500, P < 0.05). According to the regional lymph nodes, patients classified as N0, N1 and N2 were 20, 12, 7 cases in conventional group, and were 9, 14, 13 cases in the fat clearance group, respectively; and there was significant difference between the two groups (Z = 2.410, P = 0.016). CONCLUSIONS: The variation of the number of harvested lymph nodes in surgical specimens from rectal cancer after total mesorectal excision is great. The metastasis of mesorectal lymph nodes is not only associated with the tumor staging, but also related to the number of harvested lymph nodes. It is questionable that 12 lymph nodes is currently seen as enough to evaluate the pathologic staging for rectal cancer.

[Open total extraperitoneal herniorrhaphy for inguinal hernia via a ventral midline incision].

OBJECTIVE: To discuss the operation skills and evaluate the effects of open total extraperitoneal herniorrhaphy for inguinal hernia via a ventral midline incision. METHODS: From June 2008 to December 2009, 106 patients with inguinal hernia received open total extraperitoneal herniorrhaphy via a ventral midline incision, the clinical data were analyzed retrospectively. RESULTS: Of the patients, 86 cases were male, 20 were female, the mean age was 60.2 years (range, 21 - 86 years). The mean operation time was (32.6 ± 10.5) minutes. The postoperative hospital stay was (2.3 ± 0.7) days. Intra-operative peritoneal perforation occurred in 2 cases. Four cases experienced urine retention and seroma happened in 2 cases, 6 cases suffered early surgical-site pain, and all of the complications were cured with conservative treatment. Three cases developed scrotal hydrocele. No neuralgia or incisional infection occurred in this group. During a 3- to 22-months follow-up period (mean, 10.2 months), no patient complained of discomfort or foreign body sensation in the inguinal area. Two cases recurred 2 and 11 months after the surgery, respectively; the recurrence rate was 1.9%, the two patients healed after reoperation. CONCLUSIONS: Open total extraperitoneal herniorrhaphy operation via a ventral midline incision is a safe, effective and convenient technique for inguinal hernia with few postoperative complications. This method is worth popularizing.

[Comparison of fat clearance and fat lucidification in examining rectal cancer specimen].

OBJECTIVE: To compare fat clearance and fat lucidification in the examination of rectal cancer specimen, and to study the distribution pattern of lymph nodes in rectal cancer specimen. METHOD: Between January 2007 and December 2007, sixty-four cases undergone total mesorectal excision were divided into two groups. The fat clearance technique was used to examine the specimens in one group, while fat lucidification was used in the other. The total number and the number of metastatic lymph nodes between two groups were compared, as well as the time for processing specimens and that for dissecting the lymph nodes. RESULTS: An average of 37.4 lymph nodes were detected with fat clearance, in which 3.3 lymph nodes were metastatic; while an average of 36.2 nodes were detected with fat lucidification, in which 3.2 were metastatic. There were no significant differences in either the total number or the number of metastatic lymph nodes. The time for processing specimens in the fat lucidification group was 28 hours, while in the fat clearance group was 72 hours. The time for specimen processing was significantly shorter in the fat lucidification group (P<0.05). The mean time for dissecting lymph nodes in the fat clearance group was 2.1 hours, while in the fat lucidification group was 2.0 hours, the difference was not statistically significant. CONCLUSION: When processing rectal cancer specimens with the fat lucidification technique can result in the similar number of lymph nodes compared to the fat clearance technique, with significantly shorter specimen processing time. The spatial position of the lymph nodes is better preserved using the fat lucidification technique, which may help study the distribution pattern of the normal and metastatic lymph nodes.

Randomized trial on the application of biofragmentable anastomosis ring in intestinal anastomosis.

BACKGROUND: The biofragmentable anastomosis ring (BAR) is a simple alternative device to create intestinal anastomosis. Our study was designed to evaluate the clinical value of BAR in intestinal anastomosis. METHODS: A total of 167 patients performed intestinal anastomosis from January 2002 to February 2006 were randomized to BAR group (n = 82) and manual suture group (n = 85) as control. They were equally allocated to the two groups regarding sex, age, site of anastomosis, emergent or elective surgery and contaminant diseases. The results of postoperative complications and recovery were recorded in each group. RESULTS: Eighty-seven intraperitoneal BAR anastomoses were completed in 82 patients. Two and one postoperative deaths were recorded in BAR and suture group, respectively, no deaths were directly related to anastomotic technique. In suture group, anastomotic leakage and early bleeding both occurred in two patients respectively, no anastomotic bleeding occurred in BAR group, one patient in BAR group developed enterocutaneous fistulae. Perioperative bleeding, operation time and length of hospitalization were similar in two groups (P > 0.05). Time for return of bowel function was significantly shortened in BAR group than that in suture group (P < 0.05). CONCLUSION: The BAR appears to be a standard, easy, safe and effective alternative either in elective or emergent intraperitoneal intestinal anastomotic surgery.

[Study on the tectology change of rectum wall above the hemorrhoids].

OBJECTIVE: To investigate the histomorphological characteristics and its significance of rectum wall above hemorrhoids. METHODS: Tissues of rectum wall above hemorrhoids were obtained after stapled hemorrhoidopexy from 21 patients with grade III-IV internal hemorrhoids. Seven macroscopically normal rectal tissues collected from upper rectal cancer patients without a history of hemorrhoids served as control. Masson trichrome staining was performed for detecting smooth muscles and collagen in the tissues. The expression of type III collagen was detected by using immunohistochemical staining in the two groups. RESULTS: Morphological abnormalities, such as fragment, rupture, disorganization were found in smooth muscle of proximal rectal tissues above the piles, and it was statistically different from the distal rectal tissues above the piles and control tissues (all P < 0.05). Moreover, hyperplasia of type III collagen in both muscularis mucosa and rectum wall in tissues above hemorrhoids were observed, no such changes was found in the control tissues. CONCLUSIONS: The range of pathological changes in hemorrhoids is beyond the anal cushions. The pathological changes of the smooth muscle and the type III collagen in the tissues above the piles are the pathological basis of hemorrhoids.

[Use of local or epidural anesthesia in inguinal hernia repair: a randomized trial].

OBJECTIVE: To investigate the efficacy and safety of local anesthesia and epidural anesthesia in tension-free repair of inguinal hernia. METHODS: Between January 2004 and December 2006, 269 patients underwent inguinal hernia repair were randomly divided into two groups, receiving local anesthesia (143 cases) and epidural anesthesia (126 cases). The clinical data from the two groups were analyzed retrospectively. RESULTS: The operation time, ambulation time, length of hospital stay and cost of hospitalization in local anesthesia group were significantly less than those in epidural anesthesia group (P < 0.05). No significant differences were found in intra-operative use of ancillary sedation drugs, postoperative recovery situation, pain scores and operation-correlated complications between the two groups. The occurrence of postoperative anaesthetic complication rate was also significantly lower in local anesthesia group (P < 0.05). One case of recurrence occurred in each group during postoperative follow-up period. CONCLUSION: Tension-free inguinal hernia repair under local anesthesia is a simple, safe, economical, effective procedure and superior to epidural anesthesia.

[Study on intra-abdominal pressure in indirect inguinal hernia patients].

OBJECTIVE: To investigate intra-abdominal pressure (IAP) and its changes in patients with indirect inguinal hernia and non-hernia diseases. METHODS: Supine IAP (SIAP), supine Valsava IAP (SVIAP), orthostatic IAP (OIAP) and orthostatic Valsava IAP (OVIAP) were measured by intra-vesicle pressure measurement in 19 indirect inguinal hernia patients and 20 non-hernia patients, respectively. The differences of IAP between orthostatic and supine position in quiescent condition (OSIAPD), before and after taking Valsava maneuver in supine position (SVIAPD) or in orthostatic position (OVIAPD), orthostatic and supine position when taking Valsava maneuver (OSVIAPD) were compared between the two groups. RESULTS: There was no significant differences in SIAP, OIAP, SVIAP, OSIAPD, SVIAPD between the two groups (P > 0.05). While patients with indirect inguinal hernia had higher OVIAP (P < 0.05). Significant differences in OVIAPD and OSVIAPD was found between the two groups (P < 0.05). CONCLUSIONS: The etiology of indirect inguinal hernia were related to orthostatic position, increasing IAP and changes of anatomic structures. The IAP is prone to elevated in patients with indirect inguinal hernia.