Magnetic compression anastomosis for enteroenterostomy under peritonitis conditions in dogs.

BACKGROUND: The risk of complications and mortality are high after enteroenterostomy in severe peritonitic conditions. Magnetic compression anastomosis (MCA) is a sutureless technique of high efficacy and safety. The purpose of this study was to compare the efficacy of MCA for enteroenterostomy with stapled and hand-sewn techniques under peritonitic conditions. METHODS: The peritonitic conditions were created by puncturing the colon with a circular blade in 27 mongrel dogs. Eight hours later, the peritoneal cavity was washed with warm, sterilized normal saline solution. The animals were then randomly divided into three groups and underwent colonic anastomosis with MCA, stapled, or hand-sewn techniques, respectively. Animals were euthanized at 1, 2, and 4 w after the operation; anastomoses were compared on the basis of gross appearance and histology. RESULTS: All magnetic devices formed patent anastomoses without a leak. However, one stapled anastomosis and three hand-sewn anastomoses resulted in leaks. The anastomosis time was significantly less in the MCA group than that of the other two groups (P < 0.05). All magnetic devices were expelled naturally. The pathologic observation showed that the healing of anastomoses for MCA was smoother than that of the other two groups. CONCLUSION: MCA is a feasible, safe, and effective alternative for enteroenterostomy under peritonitic conditions in the canine model.

Combined administration of propranolol + AG490 offers better effects on portal hypertensive rats with cirrhosis.

BACKGROUND AND AIMS: AG490, the specific inhibitor of JAK2/STAT3 signaling, has been shown to decrease portal pressure, splanchnic hyperdynamic circulation and liver fibrosis in cirrhotic rats. Nonselective betablockers such as propranolol are the only drugs recommended in the treatment of portal hypertension. The aim of this study was to explore the combinative effect of treatment with propranolol and AG490 on portal hypertension. METHODS: Rats induced by common bile duct ligation were treated with vehicle, AG490, propranolol, or AG490 + propranolol for 2 weeks. Hemodynamics parameters were assessed. Expressions of phospho-STAT3 protein and its down-regulated cytokines in splanchnic organs were detected by ELISA or western blot. Lipopolysaccharide binding protein (LBP) and IL-6 were assessed by ELISA or western blot. Characterization of liver and mesentery was performed by histological analyses. RESULTS: Highly expressed phospho-STAT3 protein in cirrhotic rats could successfully be inhibited by AG490 or AG490 + propranolol treatments but not by propranolol alone. Both AG490 and propranolol significantly reduced portal pressure and hyperdynamic splanchnic circulation, and combination of AG490 and propranolol achieved an additive effect than with either drug alone. AG490, alone or in combination with propranolol, inhibited liver fibrosis, splenomegaly and splanchnic angiogenesis. Increased markers of bacterial translocation (LBP and IL6) were greatly reduced by propranolol but not by AG490. CONCLUSIONS: The combination of propranolol and AG490 caused a greater improvement of portal hypertension and might therefore offer a potentially promising therapy in the portal hypertension treatment.

Regulation of gene expression in Pseudomonas aeruginosa M18 by phenazine-1-carboxylic acid.

Phenazine-1-carboxylic acid (PCA), an environmentally compatible redox-active metabolite produced by Pseudomonas sp., has been found to effectively protect against various phytopathogens. The objective of this study was to discover whether PCA can also act as a signaling molecule that regulates gene expression in Pseudomonas aeruginosa M18. We constructed a series of PCA-producing mutant strains (high PCA, M18MSU1; low PCA, M18MS; and no PCA, M18MSP1P2) and analyzed their gene expression by using a custom microarray DNA chip. We found that the expression of PCA in both M18MSU1 and M18MS altered the expression of a total of 545 different genes; however, the higher level of PCA in M18MSU1 altered more genes (489) than did the lower level of PCA in M18MS (129). Of particular note, 73 of these genes were commonly regulated between the two mutants, indicating their importance in the downstream function of PCA. PCA molecules upregulated genes that function primarily in energy production, cell motility, secretion, and defense mechanisms and downregulated genes involved in transcription, translation, cell division, and gene expression in the prophage. We found that PCA worked to alter the expression of an efflux pump gene mexH through a SoxR-mediated mechanism; we further hypothesized that other pathways should also be affected by this interaction. Taken together, our results provide the first evidence of PCA-derived molecular responses at the transcriptional level. They also help to elucidate the future of genetically engineered P. aeruginosa strains for the production of PCA used in a number of applications.

N-myc downstream-regulated gene 2 expression is associated with glucose transport and correlated with prognosis in breast carcinoma.

INTRODUCTION: N-myc downstream-regulated gene 2 (NDRG2), a novel tumour suppressor and cell stress-related gene, is involved in many cell metabolic processes, such as hormone, ion and fluid metabolism. We investigated whether NDRG2 is involved in any glucose-dependent energy metabolism, as well as the nature of its correlation with breast carcinoma. METHODS: The correlations between NDRG2 expression and glucose transporter 1 (GLUT1) expression in clinical breast carcinoma tissues were analysed. The effects of NDRG2 on glucose uptake were assessed in breast cancer cells and xenograft tumours. The consequences of NDRG2-induced regulation of GLUT1 at the transcription and translation levels and the interaction between NDRG2 and GLUT1 were examined. RESULTS: Data derived from clinical breast carcinoma specimens revealed that (1) patients with high NDRG2 expression had better disease-free survival and overall survival than those with low NDRG2 expression and (2) NDRG2 expression was negatively correlated with GLUT1 expression in these breast carcinoma tissues. NDRG2 inhibited glucose uptake by promoting GLUT1 protein degradation without affecting GLUT1 transcription in both breast cancer cells and xenograft tumours. In addition, NDRG2 protein interacted and partly colocalised with GLUT1 protein in cell cytoplasm areas. CONCLUSIONS: The results of our study support the notion that NDRG2 plays an important role in tumour glucose metabolism, in which GLUT1 is a likely candidate contributor to glucose uptake suppression and tumour growth. Targeting the actions of NDRG2 in cell glucose-dependent energy delivery may provide an attractive strategy for therapeutic intervention in human breast carcinoma.

Combination therapy with sorafenib and radiofrequency ablation for BCLC Stage 0-B1 hepatocellular carcinoma: a multicenter retrospective cohort study.

OBJECTIVES: The objective of this study was to evaluate the efficacy of combined therapy using Sorafenib and radiofrequency ablation (RFA) with curative intent for all detectable lesions in patients with Barcelona Clinic Liver Cancer (BCLC) Stage 0-B1 hepatocellular carcinoma (HCC). METHODS: One hundred and twenty-eight patients with HCC from 12 centers were enrolled in this retrospective study; 64 patients who received Sorafenib plus RFA (Sorafenib-RFA) were compared with a control group treated with RFA alone. The two patient groups were selected with a predefined criterion and matched in terms of their clinical and tumor characteristics at baseline. The primary end point of the study was the incidence of post-RFA HCC recurrence. Secondary end points were overall survival (OS) and treatment toxicity. RESULTS: During a median follow-up of 134.1 weeks, 49 patients died and 79 survived. The 1-, 2-, and 3-year cumulative incidences of post-RFA recurrence were 40.5%, 62.9%, and 74.5%, respectively, in the Sorafenib-RFA group, and 62.8%, 85.4%, and 92.7%, respectively, in the RFA group. The 1-, 2-, 3-, and 4-year OS rates were 85.6%, 64.0%, 58.7%, and 50.3%, respectively, in the Sorafenib-RFA group, and 80.7%, 47.2%, 30.9%, and 30.9%, respectively, in the RFA group. Thus, the Sorafenib-RFA group exhibited better survival than the RFA alone group. CONCLUSIONS: Combined therapy with Sorafenib-RFA was associated with a lower incidence of post-RFA recurrence and better OS than RFA alone in patients with BCLC Stage 0-B1 HCC. Although these findings suggest that Sorafenib and RFA is safe and effective for the treatment of early HCC, prospective and randomized controlled trials are needed to validate them.

Phenazine-1-carboxylic acid production in a chromosomally non-scar triple-deleted mutant Pseudomonas aeruginosa using statistical experimental designs to optimize yield.

We constructed a non-scar triple-deleted mutant Pseudomonas aeruginosa to improve phenazine-1-carboxylic acid (PCA) yield and then optimized the culture conditions for PCA production. Using a non-scar deletion strategy, the 5'-untranslated region of the phz1 gene cluster and two genes, phzM and phzS, were knocked out of the P. aeruginosa strain M18 genome. The potential ability for high-yield PCA production in this triple-deleted mutant M18MSU1 was successfully realized by using statistical experimental designs. A 2(5-1) fractional factorial design was used to show that the three culture components of soybean meal, corn steep liquor and ethanol had the most significant effect on PCA production. Using a central composite design, the concentration of the three components was optimized. The maximum PCA production was predicted to be 4,725.1 mg/L. With the optimal medium containing soybean meal 74.25 g/L, corn steep liquor 13.01 g/L and ethanol 21.84 ml/L, a PCA production of 4,771.2 mg/L was obtained in the validation experiments, which was nearly twofold of that before optimization and tenfold of that in the wild-type strain. This non-scar triple-deleted mutant M18MSU1 may be a suitable strain for industrial production of this biologically synthesized fungicide due to its high PCA production, presumed safety, thermal adaptability and cost-effectiveness.

CRP­1 promotes the malignant behavior of hepatocellular carcinoma cells via activating epithelial­mesenchymal transition and Wnt/ß­catenin signaling.

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. It has been reported that cysteine rich protein 1 (CRP-1) is dysregulated in several types of human cancer; however, its role in HCC is poorly understood. Therefore, the current study aimed to investigate the role of CRP-1 in HCC. Western blotting and reverse transcription-quantitative PCR results showed that CRP-1 was upregulated in HCC cell lines. Furthermore, for in vitro experiments, CRP-1 was knocked down and overexpressed in the HCC cell lines Hep 3B2.1-7 and BEL-7405, respectively. c-Myc and proliferating cell nuclear antigen upregulation, and cleaved caspase 3 and poly(ADP-ribose) polymerase downregulation suggested that CRP-1 silencing could inhibit the proliferation and colony-forming ability of HCC cells, and induce apoptosis. In addition, CRP-1 overexpression promoted the malignant behavior of HCC cells and induced epithelial-mesenchymal transition (EMT), as verified by E-cadherin downregulation, and N-cadherin and vimentin upregulation. Additionally, CRP-1 overexpression promoted the nuclear translocation of ß-catenin, and activated the expression of cyclin D1 and matrix metalloproteinase-7. Furthermore, inhibition of Wnt/ß-catenin signaling, following cell treatment with XAV-939, an inhibitor of the Wnt/ß-catenin signaling pathway, abrogated the effects of CRP-1 on enhancing the proliferation and migration of HCC cells. These findings indicated that the regulatory effect of CRP-1 on HCC cells could be mediated by the Wnt/ß-catenin signaling pathway. Overall, CRP-1 could promote the proliferation and migration of HCC cell lines, partially via promoting EMT and activating the Wnt/ß-catenin signaling pathway.

Different methods of vaginal preparation before cesarean delivery to prevent postoperative infection: a systematic review and network meta-analysis.

OBJECTIVE: Precesarean vaginal antisepsis can benefit pregnant women with ruptured membranes. However, in the general population, recent trials have shown mixed results in reducing postoperative infections. This study aimed to systematically review clinical trials and summarize the most suitable vaginal preparations for cesarean delivery in preventing postoperative infection. DATA SOURCES: We searched PubMed, Web of Science, Cochrane Library, SinoMed databases, and the ClinicalTrials.gov clinical trials registry for randomized controlled trials and conference presentations (past 20 years, 2003-2022). Reference lists of previous meta-analyses were searched manually. In addition, we conducted subgroup analysis on the basis of whether the studies were conducted in developed or developing countries, whether the membranes were ruptured, and whether patients were in labor. STUDY ELIGIBILITY CRITERIA: We included randomized controlled trials comparing vaginal preparation methods for the prevention of postcesarean infection with each other or with negative controls. METHODS: Two reviewers independently extracted data and assessed the risk of bias and the certainty of the evidence. The effectiveness of prevention strategies was assessed by frequentist-based network meta-analysis models. The outcomes were endometritis, postoperative fever, and wound infection. RESULTS: A total of 23 trials including 10,026 cesarean delivery patients were included in this study. Vaginal preparation methods included 19 iodine-based disinfectants (1%, 5%, and 10% povidone-iodine; 0.4% and 0.5% iodophor) and 4 guanidine-based disinfectants (0.05% and 0.20% chlorhexidine acetate; 1% and 4% chlorhexidine gluconate). Overall, vaginal preparation significantly reduced the risks of endometritis (3.4% vs 8.1%; risk ratio, 0.41 [0.32-0.52]), postoperative fever (7.1% vs 11.4%; risk ratio, 0.58 [0.45-0.74]), and wound infection (4.1% vs 5.4%; risk ratio, 0.73 [0.59-0.90]). With regard to disinfectant type, iodine-based disinfectants (risk ratio, 0.45 [0.35-0.57]) and guanidine-based disinfectants (risk ratio, 0.22 [0.12-0.40]) significantly reduced the risk of endometritis, and iodine-based disinfectants reduced the risk of postoperative fever (risk ratio, 0.58 [0.44-0.77]) and wound infection (risk ratio, 0.75 [0.60-0.94]). With regard to disinfectant concentration, 1% povidone-iodine was most likely to simultaneously reduce the risks of endometritis, postoperative fever, and wound infection. CONCLUSION: Preoperative vaginal preparation can significantly reduce the risk of postcesarean infectious diseases (endometritis, postoperative fever, and wound infection); 1% povidone-iodine has particularly outstanding effects.

The feasibility and safety of the brachial artery approach in the treatment of hepatic artery infusion chemotherapy: a retrospective study.

Background: Compared to hepatic artery infusion chemotherapy (HAIC) treatment through the femoral artery (TFA), the brachial artery (TBA) is more flexible and easier for patients to accept. However, the feasibility of TBA has not been studied yet. This study aims to evaluate the feasibility and safety of HAIC via the TBA. Methods: We retrospectively reviewed the medical records of 63 patients with primary liver cancer who were treated with HAIC via TBA. In this study, a total of 163 HAIC procedures were performed via the left brachial artery pathway, and each patient underwent an average of 2.59 procedures. One patient received 5 treatments, 18 patients received 4 treatments, 15 patients received 3 treatments, 12 patients received 2 treatments, and 17 patients received 1 treatment. The main evaluation indicators were the technical success rate and complication rate. Results: The main technical success rate was 99.4% (162/163). No patient required conversion to the femoral artery (TFA) access. All the complications were minor and occurred in 11 patients (6.75%). Subcutaneous ecchymosis occurred in 3 (1.84%) patients, arterial thrombosis in 2 patients (1.23%), and catheter displacement in 6 patients (3.68%). No serious complications occurred. Conclusions: TBA pathway is feasible and safe for HAIC treatment of liver cancer patients. More research is needed in the future to confirm whether TBA is superior to other pathways.

Potential candidates for liver resection in liver-confined advanced HCC: a Chinese multicenter observational study.

Background: Advanced hepatocellular carcinoma (HCC) is characterized as symptomatic tumors [performance status (PS) score of 1-2], vascular invasion and extrahepatic spread, but patients with PS1 alone may be eliminated from this stage. Although liver resection is used for liver-confined HCC, its role in patients with PS1 alone remains controversial. Therefore, we aimed to explore its application in such patients and identify potential candidates. Methods: Eligible liver-confined HCC patients undergoing liver resection were retrospectively screened in 15 Chinese tertiary hospitals, with limited tumor burden, liver function and PS scores. Cox-regression survival analysis was used to investigate the prognostic factors and develop a risk-scoring system, according to which patients were substratified using fitting curves and the predictive values of PS were explored in each stratification. Results: From January 2010 to October 2021, 1535 consecutive patients were selected. In the whole cohort, PS, AFP, tumor size and albumin were correlated with survival (adjusted P<0.05), based on which risk scores of every patient were calculated and ranged from 0 to 18. Fitting curve analysis demonstrated that the prognostic abilities of PS varied with risk scores and that the patients should be divided into three risk stratifications. Importantly, in the low-risk stratification, PS lost its prognostic value, and patients with PS1 alone achieved a satisfactory 5-year survival rate of 78.0%, which was comparable with that PS0 patients (84.6%). Conclusion: Selected patients with PS1 alone and an ideal baseline condition may benefit from liver resection and may migrate forward to BCLC stage A.

Organocatalytic asymmetric conjugate addition of 3-monosubstituted oxindoles to (E)-1,4-diaryl-2-buten-1,4-diones: a strategy for the indirect enantioselective furanylation and pyrrolylation of 3-alkyloxindoles.

An asymmetric conjugate addition of 3-monosubstituted oxindoles to a range of (E)-1,4-diaryl-2-buten-1,4-diones, catalyzed by commercially available cinchonine, is described. This organocatalytic asymmetric reaction affords a broad range of 3,3'-disubstituted oxindoles that contain a 1,4-dicarbonyl moiety and vicinal quaternary and tertiary stereogenic centers in high-to-excellent yields (up to 98%), with excellent diastereomeric and moderate-to-high enantiomeric ratios (up to 99:1 and 95:5, respectively). Subsequently, cyclization of the 1,4-dicarbonyl moiety in the resultant Michael adducts under different Paal-Knorr conditions results in two new kinds of 3,3'-disubstituted oxindoles--3-furanyl- and 3-pyrrolyl-3-alkyl-oxindoles--in high yields and good enantioselectivities. Notably, the studies presented here sufficiently confirm that this two-step strategy of sequential conjugate addition/Paal-Knorr cyclization is not only an attractive method for the indirect enantioselective heteroarylation of 3-alkyloxindoles, but also opens up new avenues toward asymmetric synthesis of structurally diverse 3,3'-disubstituted oxindole derivatives.

Prognostic impact of Metadherin-SND1 interaction in colon cancer.

The interaction between Metadherin (MTDH) and Staphylococcal nuclease homology domain containing 1 (SND1) is involved in tumorigenesis and tumor progression of several human malignancies. However, its roles in colon cancer are still unclear. To investigate the clinical value of MTDH and SND1 expression in colon cancer. Immunohistochemical staining was performed to detect the expression of MTDH and SND1 using human colon cancer and their corresponding non-cancerous colon tissues from 196 patients' biopsies. Positive expression of MTDH and SND1 were both increased in colon cancer tissues compared to paired non-cancerous colon tissues. There was a positive correlation between MTDH and SND1 expression in colon cancer tissues (r = 0.86, p < 0.001). In addition, their positive expression were both significantly associated with nodal status (both p = 0.02), pathological stage (p = 0.006 and 0.008, respectively) and differentiation (both p = 0.03). Moreover, the overall survival in colon cancer patients with positive expression of MTDH and SND1 were significantly shorter than those without their expression (both p = 0.01). Furthermore, multivariate Cox regression analysis suggested that positive expression of MTDH and SND1 was an independent poor prognostic predictor in colon cancer. Our data suggest that the increased expression of MTDH and/or SND1 is closely related to carcinogenesis, progression, and prognosis of colon cancer. The co-expression of MTDH/SND1 may be a novel distinctive marker to benefit us in prediction of the prognosis in colon cancer.

Immunohistochemical evidence of the prognostic value of hedgehog pathway components in primary gallbladder carcinoma.

PURPOSE: The activation of hedgehog (Hh) pathways has been studied extensively in many malignant tumors to elucidate their clinical diagnostic and prognostic utilities. However, their roles in primary gallbladder carcinoma (GBC) remain poorly understood. This study was conducted to clarify the immunoreactivity and prognostic value of Hh pathway components in GBC. METHODS: Levels of sonic hedgehog (Shh), its receptor, Patched (Ptch1), and its downstream transcription factor, Gli1 protein, were measured by immunohistochemistry in 93 specimens from patients with GBC. We analyzed the correlations between the expression of these factors and clinicopathological features, including prognosis. RESULTS: Among the 93 GBC specimens, 76 (81.7%), 70 (75.3%) and 66 (70.0%) were positive for Shh, Ptch1 and Gli1 expression, respectively. Expressions were significantly correlated with stage, lymph node metastasis, venous invasion, hepatic infiltration and lymphatic invasion (all P < 0.05). Patients with positive staining for Shh, Ptch1 and Gli1 had significantly lower survival rates than patients with negative staining. The expression patterns of Shh, Ptch1 and Gli1 were all associated with a malignant behavior risk category in GBC. CONCLUSIONS: To our knowledge, this is the first report to define the role of the Hh pathway in GBC. Shh, Ptch1 and Gli1 are frequently expressed in GBC and associated with poorer survival. Thus, high expressions of Shh, Ptch1 and Gli1 proteins could serve as auxiliary parameters for predicting the malignant behavior of GBC.

Identifying optimal therapies in patients with advanced hepatocellular carcinoma: a systematic review and network meta-analysis.

Background: Recently, increasing literature has been reported on optimal therapies in patients with advanced hepatocellular carcinoma (HCC) and many therapeutic modalities have been proposed to improve the survival rate. However, the results are not consistent due to different research protocols, small sample sizes and different study endpoints and there is no standard treatment protocol has been defined. Therefore, it is very important to explore the optimal bonding mode and to evaluate the efficacy and safety of the optimal sequential therapy for those patients. Methods: We searched available databases through January 2020 for relevant studies. The main outcome measure was 1-year overall survival (OS) and overall response rate (ORR); the secondary outcome measure was a composite of toxic effects retrieved grade 3 or 4 adverse events (AEs) from all included studies. Statistical analyses were conducted using STATA version 15 and GeMTC package in the R statistical software. Results: After a detailed review, 8 randomized controlled trials (RCTs) and 20 retrospective studies involving 3,675 advanced HCC patients were included for network meta-analysis. Indirect comparisons showed that hepatic arterial infusion chemotherapy (HAIC) plus radiofrequency ablation (RFA) was highest probability of obtaining the best OS rate of 1 year [surface under the cumulative ranking (SUCRA), 0.95] and ORR (SUCRA, 0.86) when compared with other potential optimal therapies and which had ranked the first in all treatment regimens, followed by HAIC (SUCRA, 0.75). Direct and indirect comparison of 1-year OS and ORR with all treatment regimens each other showed that for all treatment regimens, patients showed significant clinical benefit when compared with transcatheter arterial chemoembolization (TACE) or sorafenib alone. However, the incidence of treatment-related AEs of grade 3 or 4 occurred in patients who have received targeted drug sorafenib therapy (SUCRA, 0.51) compared with other interesting regimens. Conclusions: HAIC may be a valuable therapeutic strategy for advanced HCC patients to prevent recurrence and metastasis after RFA, as well as in improving patient prognosis and quality of life. Meanwhile, HAIC combined with RFA is a safe and effective treatment in patients with advanced HCC, and this combination therapy can significantly prolong 1-year survival rate when compared with other optimal sequential therapies. Trial registration: This study is registered with PROSPERO, number CRD42020176149.

Identify optimal HAP series scores for unresectable HCC patients undergoing TACE plus sorafenib: A Chinese multicenter observational study.

Background: Hepatoma arterial-embolization prognostic (HAP) series scores have been proposed for prognostic prediction in patients with unresectable hepatocellular carcinoma (uHCC) undergoing transarterial chemoembolization (TACE). However, their prognostic value in TACE plus sorafenib (TACE-S) remains unknown. Here, we aim to evaluate their prognostic performance in such conditions and identify the best model for this combination therapy. Methods: Between January 2012 and December 2018, consecutive patients with uHCC receiving TACE-S were recruited from 15 tertiary hospitals in China. Cox regression analyses were used to investigate the prognostic values of baseline factors and every scoring system. Their prognostic performance and discriminatory performance were evaluated and confirmed in subgroup analyses. Results: A total of 404 patients were enrolled. In the whole cohort, the median follow-up period was 44.2 (interquartile range (IQR), 33.2-60.7) months, the median overall survival (OS) time was 13.2 months, and 336 (83.2%) patients died at the end of the follow-up period. According to multivariate analyses, HAP series scores were independent prognostic indicators of OS. In addition, the C-index, Akaike information criterion (AIC) values, and time-dependent area under the receiver operating characteristic (ROC) curve (AUC) indicated that modified HAP (mHAP)-III had the best predictive performance. Furthermore, the results remained consistent in most subsets of patients. Conclusion: HAP series scores exhibited good predictive ability in uHCC patients accepting TACE-S, and the mHAP-III score was found to be superior to the other HAP series scores in predicting OS. Future prospective high-quality studies should be conducted to confirm our results and help with treatment decision-making.

Amino-indanol-catalyzed asymmetric Michael additions of oxindoles to protected 2-amino-1-nitroethenes for the synthesis of 3,3'-disubstituted oxindoles bearing α,ß-diamino functionality.

An organocatalytic asymmetric Michael addition reaction of 3-substituted oxindoles to protected 2-amino-1-nitroethenes has been developed. The reaction is catalyzed by a simple and readily available amino-indanol derivative and affords the desired products in very high yields (up to 99%) with excellent diastereoselectivities (up to >99:1) and very good enantioselectivities (up to 90%). Significantly, this study provides a general catalytic method for the construction of 3,3'-disubstituted oxindoles bearing α,ß-diamino functionality as well as vicinal chiral quaternary/tertiary stereocenters. The potential utility of the protocol also had been demonstrated by gram-scale reaction and the versatile conversion of product. Furthermore, On the basis of the comprehensive experimental results and the absolute configuration of one of the Michael adducts, a work model was also proposed to explain the origin of asymmetric induction.

Catalytic asymmetric 1,6-Michael addition of arylthiols to 3-methyl-4-nitro-5-alkenyl-isoxazoles with bifunctional catalysts.

An enantioselective 1,6-Michael addition reaction of arylthiols to a wide range of 3-methyl-4-nitro-5-alkenyl-isoxazoles catalyzed by readily available Takemoto's thiourea catalyst has been developed. This reaction provides a useful catalytic method for the synthesis of optically active chiral sulfur compounds bearing a 4-nitroisoxazol-5-yl moiety in high to excellent yields (up to 97%) and high enantioselectivities (up to 91% ee). Significantly, the potential utilities of the protocol had been further demonstrated by gram-scale reaction and the versatile conversions of some resulting products into other functionalized and useful compounds.

Identification of high-risk stage II and stage III colorectal cancer by analysis of MMP-21 expression.

BACKGROUND: The expression of matrix metalloproteinase-21 (MMP-21) has been shown to be elevated in some solid tumor and thought to enhance tumor invasion and metastasis ability. In the present study, we investigated the expression of MMP-21 and its association with prognosis in stage II and III colorectal cancer. METHODS: MMP-21 expression was investigated in 286 cases of colorectal cancer by immunohistochemistry assay. Statistical analysis was utilized to evaluate the association of MMP-21 expression with clinicopathological characters and overall survival of patients with stage II and III colorectal cancer. RESULTS: MMP-21 expression was significantly higher in colorectal cancer, compared with that in normal epithelial tissue. And it also correlated with tumor invasion, lymph node metastasis, and distant metastasis of colorectal cancer. MMP-21 was also proved to be an independent prognostic factor in patients with stage II as well as stage III colorectal cancer. However, no correlations between MMP-21 expression and patients' age, sex, tumor location, or differentiation status were detected. CONCLUSION: These results suggested the potential role of MMP-21 in the invasion and metastasis process of human colorectal cancer. It could also be a novel molecular marker to predict prognosis of patients with stage II and stage III colorectal cancer.

Correlation between MMP1-PAR1 axis and clinical outcome of primary gallbladder carcinoma.

OBJECTIVE: Matrix metalloprotease-1 and protease-activated receptor-1 axis plays an important role in many cancers, with activation often associated with poor survival. The aim of the present study was to determine whether the immunohistochemical detection of matrix metalloprotease-1 and protease-activated receptor-1 could provide useful information as novel therapeutic or prognostic factors in primary gallbladder carcinoma. METHODS: Eighty-six gallbladder carcinoma tissues were evaluated by immunohistochemistry for matrix metalloprotease-1 and protease-activated receptor-1 expressions. The association of matrix metalloprotease-1 and protease-activated receptor-1 expressions with clinicopathological characteristics and the univariate survival analysis for the influence of matrix metalloprotease-1 and protease-activated receptor-1 expressions on the overall survival were analyzed. RESULTS: Matrix metalloprotease-1 and protease-activated receptor-1 immunoreactivities were observed in 62 (72.1%) and 59 (68.6%) of the 86 gallbladder carcinoma cases, respectively. The tumors with the positive expressions of matrix metalloprotease-1 (P= 0.007) and protease-activated receptor-1 (P= 0.01) more frequently showed lymph node metastasis, respectively. In addition, the tumors with the positive expressions of matrix metalloprotease-1 and protease-activated receptor-1 tended to show a deeper invasion depth (P= 0.006 and 0.008, respectively) and more frequent lymphovascular invasion (both P= 0.01). The Kaplan-Meier survival curves demonstrated that patients with the positive expressions of matrix metalloprotease-1 and protease-activated receptor-1 had a significantly shorter survival time than those patients with their negative expression (both P= 0.02). CONCLUSIONS: A subset of gallbladder carcinoma cases revealed the overexpression of matrix metalloprotease-1 and protease-activated receptor-1, which was associated with a progressive pathological feature and an aggressive clinical course. Therefore, matrix metalloprotease-1 and protease-activated receptor-1 expressions may be predictors for a poor prognosis in patients with gallbladder carcinoma. This is the first report describing about the involvement of matrix metalloprotease-1 and protease-activated receptor-1 axis in gallbladder carcinoma.

Comparison between Child-Pugh score and Albumin-Bilirubin grade in the prognosis of patients with HCC after liver resection using time-dependent ROC.

BACKGROUNDS: The Child-Pugh score is a scoring system used to measure liver function and predict postoperative outcomes in patients with hepatocellular carcinoma (HCC). Recently, the Albumin-Bilirubin (ALBI) grade has been proposed for the evaluation of hepatic reserve function in HCC. This study aimed to assess and compare the capability of ALBI grade and Child-Pugh score in predicting overall survival (OS). METHODS: A total of 196 consecutive HCC patients who treated with hepatectomy were enrolled in this retrospective study. The prognostic values of ALBI grade and Child-Pugh score in predicting postoperative OS were respectively estimated using the Kaplan-Meier method and time-dependent receiver operating curves (ROC). Univariate and multivariate Cox regression analyses were performed to investigate the prognostic factors for OS. RESULTS: Stratified by the Albumin-Bilirubin (ALBI) system, there were 81 (41.3%) patients with grade 1 and 115 (58.7%) patients with grade 2. The cumulative 1-, 3-, 5-year OS rates in patients with ALBI-1 were 82.7%, 51.5% and 35.5%, respectively. For patients with ALBI-2, the cumulative 1-, 3-, 5-year OS rates were 57.6%, 19.4% and 0%, respectively. Based on the Child-Pugh classification, 136 (69.4%) patients had a score of 5, and 60 (30.6%) patients had a score of 6. Patients with Child-Pugh-A5 showed a better OS than those with Child-Pugh-A6, with respective OS at 1, 3 and 5 years (72.7%, 29.2%, 20.3% vs. 53.9%, 21.1%, 0%, Log-rank P<0.001). Besides, the ALBI grade revealed two prognostic groups within Child-Pugh-A5 (P<0.001), while the Child-Pugh score did not distinguish ALBI-2 in different prognostic groups (P=0.705). The multivariate analysis indicated that both ALBI grade and Child-Pugh score could significantly stratify the patients with different OS [hazard ratio (HR), 3.088 and 1.783; 95% confidence interval (CI), 1.985 to 4.805 and 1.272 to 2.731; P<0.001 and P=0.032 for ALBI grade and Child-Pugh score, respectively]. Additionally, time-dependent ROC analysis in the entire cohort proved that the ALBI grade had a better discriminatory ability than the Child-Pugh score in predicting survival, especially for long-term outcomes. According to the subgroup analyses, the ALBI grade had a better discriminatory ability and survival prediction accuracy in overall subsets than the Child-Pugh score for the prediction of OS. CONCLUSIONS: ALBI grade supplied better prognostic performance and distribution of liver function than Child-Pugh score in stratifying prognosis for HCC patients treated by hepatectomy. These results declared that ALBI grade could be an alternative liver function grading system for stratification in patients with HCC.