Ruthenium(v) terminal arylimido corroles: isolation, spectroscopic characterization and reactivity.

Terminal Ru(v)-imido species are thought to be as reactive to group transfer reactions as their Ru(v)-oxo homologues, but are less studied. With the electron-rich corrole ligand, relatively stable and isolable Ru(v)-arylimido complexes [Ru(tBu-Cor)(NAr)] (H3(tBu-Cor) = 5,15-diphenyl-10-(p-tert-butylphenyl)corrole, Ar = 2,4,6-Me3C6H2 (Mes), 2,6-(iPr)2C6H3 (Dipp), 2,4,6-(iPr)3C6H2 (Tipp), and 3,5-(CF3)2C6H3 (BTF)) can be prepared from [Ru(tBu-Cor)]2 under strongly reducing conditions. This type of Ru(v)-monoarylimido corrole complex with S = ½ was characterized by high-resolution ESI mass spectrometry, X-band EPR, resonance Raman spectroscopy, magnetic susceptibility, and elemental analysis, together with computational studies. Under heating/light irradiation (xenon lamp) conditions, the complexes [Ru(tBu-Cor)(NAr)] (Ar = Mes, BTF) could undergo aziridination of styrenes and amination of benzylic C(sp3)-H bonds with up to 90% product yields.

Impact of bariatric surgery on glucose and lipid metabolism and liver and kidney function in food-induced obese diabetic rats.

BACKGROUND: Obesity usually causes diabetes mellitus (DM) and is a serious danger to human health. Type 2 DM (T2DM) mostly occurs along with obesity. Foodborne obesity-induced DM is caused by an excessive long-term diet and surplus energy. Bariatric surgery can improve the symptoms of T2DM in some obese patients. But different types of bariatric surgery may have different effects. AIM: To investigate the effect of bariatric surgery on glucose and lipid metabolism and liver and kidney function in rats. METHODS: Male Sprague-Dawley rats aged 6-8 wk underwent Roux-en-Y gastric bypass surgery (RYGB), sleeve gastrectomy (SG), or gastric banding (GB). Glucose and insulin tolerance tests, analyses of biochemical parameters, histological examination, western blot, and quantitative real-time polymerase chain reaction were conducted. RESULTS: In comparison to the sham operation group, the RYGB, SG, and GB groups had decreased body weight and food intake, reduced glucose intolerance and insulin insensitivity, downregulated biochemical parameters, alleviated morphological changes in the liver and kidneys, and decreased levels of protein kinase C ß/ P66shc. The effect in the RYGB group was better than that in the SG and GB groups. CONCLUSION: These results suggest that RYGB, SG and GB may be helpful for the treatment of foodborne obesity-induced DM.

New insight of obesity-associated NAFLD: Dysregulated "crosstalk" between multi-organ and the liver?

Obesity plays a crucial role in the development of non-alcoholic fatty liver disease (NAFLD). However, the underlying mechanism for the pathogenesis of obesity-associated NAFLD remains largely obscure. Although the "multiple hit" theory provides a more accurate explanation of NAFLD pathogenesis, it still cannot fully explain precisely how obesity causes NAFLD. The liver is the key integrator of the body's energy needs, receiving input from multiple metabolically active organs. Thus, recent studies have advocated the "multiple crosstalk" hypothesis, highlighting that obesity-related hepatic steatosis may be the result of dysregulated "crosstalk" among multiple extra-hepatic organs and the liver in obesity. A wide variety of circulating endocrine hormones work together to orchestrate this "crosstalk". Of note, with deepening understanding of the endocrine system, the perception of hormones has gradually risen from the narrow sense (i.e. traditional hormones) to the broad sense of hormones as organokines and exosomes. In this review, we focus on the perspective of organic endocrine hormones (organokines) and molecular endocrine hormones (exosomes), summarizing systematically how the two types of new hormones mediate the dialogue between extra-hepatic organs and liver in the pathogenesis of obesity-related NAFLD.

miR-32-5p induces hepatic steatosis and hyperlipidemia by triggering de novo lipogenesis.

BACKGROUND AND OBJECTIVES: MicroRNA-dependent regulation of hepatic lipid metabolism has been recognized recently as a key pathological mechanism contributing to the development of NAFLD. However, whether miR-32-5p (miR-32) plays a role in lipid metabolism or contributes to NAFLD remains unclear. METHODS AND RESULTS: A marked increase in miR-32 expression was observed in liver samples from patients and mice with NAFLD, as well as in palmitate-induced hepatocytes. Hepatocyte-specific miR-32 knockout (miR-32-HKO) dramatically ameliorated hepatic steatosis and metabolic disorders in high-fat diet-fed mice. Conversely, hepatic miR-32 overexpression markedly exacerbated the progression of these abnormalities. Further, combinational analysis of transcriptomics and lipidomics suggested that miR-32 was a key trigger for de novo lipogenesis in the liver. Mechanistically, RNA sequencing, luciferase assay and adenovirus-mediated downstream gene rescue assay demonstrated that miR-32 directly bound to insulin-induced gene 1 (INSIG1) and subsequently activated sterol regulatory element binding protein-mediated lipogenic gene programs, thereby promoting hepatic lipid accumulation and metabolic disorders. Notably, pharmacological administration of miR-32 antagonist significantly inhibited palmitate-induced triglyceride deposition in hepatocytes and markedly mitigated hepatic steatosis and metabolic abnormalities in obesity-associated NAFLD mice. CONCLUSION: miR-32 is an important checkpoint for lipogenesis in the liver, and targeting miR-32 could be a promising therapeutic approach for NAFLD treatment.

A Convergent, Modular Approach to Trifluoromethyl-Bearing 5-Membered Rings via Catalytic C(sp3 )-H Activation.

Trifluoromethyl-bearing 5-membered rings are prevalent in bioactive molecules, but modular approaches to these compounds by functionalization of robust C(sp3 )-H bonds in a direct and selective manner are extremely challenging. Herein we report the rhodium-catalyzed α-CF3 -α-alkyl carbene insertion into C(sp3 )-H bonds of a broad range of substrates to access 7 types of CF3 -bearing saturated 5-membered carbo- and heterocycles. The reaction is particularly effective for benzylic C-H insertion exerting good site-, diastereo- and enantiocontrol, and applicable to the synthesis of chiral CF3 analogues of bioactive molecules. Ruthenium α-CF3 -α-alkyl carbene complexes underwent stoichiometric reactions to give C-H insertion products, lending evidence for the involvement of metal α-CF3 -α-alkyl carbene species in the catalytic cycle. DFT calculations revealed that the π⋅⋅⋅π attraction and intra-carbene C-H⋅⋅⋅F hydrogen bond elucidate the origin of selectivity of the benzylic C-H insertion reactions.

Paracrine Regulation of Adipose Tissue Macrophages by Their Neighbors in the Microenvironment of Obese Adipose Tissue.

Obesity has recently been defined as a chronic low-grade inflammatory disease. Obesity-induced inflammation of adipose tissue (AT) is an essential trigger for insulin resistance (IR) and related metabolic diseases. Although the underlying molecular basis of this inflammation has not been fully identified, there is consensus that the recruited and activated macrophages in AT are the most important culprits of AT chronic inflammation. Adipose tissue macrophages (ATMs) are highly plastic and could be polarized from an anti-inflammatory M2 to proinflammatory M1 phenotypes on stimulation by microenvironmental signals from obese AT. Many efforts have been made to elucidate the molecular signaling pathways of macrophage polarization; however, the upstream drivers governing and activating macrophage polarization have rarely been summarized, particularly regulatory messages from the AT microenvironment. In addition to adipocytes, the AT bed also contains a variety of immune cells, stem cells, as well as vascular, neural, and lymphatic tissues throughout, which together orchestrate the AT microenvironment. Here, we summarize how the aforesaid neighbors of ATMs in the AT microenvironment send messages to ATMs and thus regulate its phenotype during obesity. Deciphering the biology and polarization of ATMs in the obese environment is expected to provide a precise immunotherapy for adipose inflammation and obesity-related metabolic diseases.

Self-Assembly of Molecular Trefoil Knots Featuring Pentadecanuclear Homoleptic AuI -, AuI /AgI -, or AuI /CuI -Alkynyl Coordination.

Metal-free and metal-containing molecular trefoil knots are fascinating ensembles that are usually covalently assembled, the latter requiring the rational design of di- or multidentate/multipodal ligands as connectors. In this work, we describe the self-assembly of pentadecanuclear AuI trefoil knots [Au15 (C≡CR)15 ] from monoalkynes HC≡CR (R=9,9-X2 -fluorenyl with X=nBu, n-hexyl) and [AuI (THT)Cl]. Hetero-bimetallic counterparts [Au9 M6 (C≡CR)15 ] (M=Cu/Ag) were self-assembled by reactions of [Au15 (C≡CR)15 ] with [Cu(MeCN)4 ]+ /AgNO3 and HC≡CR. The type of pentadecanuclear trefoil knots described herein is characterized by X-ray crystallography, 2D NMR and HR-ESI-MS. [Au9 Cu6 (C≡CR)15 ] is relatively stable in hexane; its excited state properties were investigated. DFT calculations revealed that non-covalent metal-metal and metal-ligand interactions, together with longer alkyl chain-strengthened inter-ligand dispersion interactions, govern the stability of the trefoil knot structures.

Direct photo-induced reductive Heck cyclization of indoles for the efficient preparation of polycyclic indolinyl compounds.

The photo-induced cleavage of C(sp2)-Cl bonds is an appealing synthetic tool in organic synthesis, but usually requires the use of high UV light, photocatalysts and/or photosensitizers. Herein is described a direct photo-induced chloroarene activation with UVA/blue LEDs that can be used in the reductive Heck cyclization of indoles and without the use of a photocatalyst or photosensitizer. The indole compounds examined display room-temperature phosphorescence. The photochemical reaction tolerates a panel of functional groups including esters, alcohols, amides, cyano and alkenes (27 examples, 50-88% yields), and can be used to prepare polycyclic compounds and perform the functionalization of natural product analogues in moderate to good yields. Mechanistic experiments, including time-resolved absorption spectroscopy, are supportive of photo-induced electron transfer between the indole substrate and DIPEA, with the formation of radical intermediates in the photo-induced dearomatization reaction.

Luminescent tungsten(vi) complexes as photocatalysts for light-driven C-C and C-B bond formation reactions.

The realization of photocatalysis for practical synthetic application hinges on the development of inexpensive photocatalysts which can be prepared on a large scale. Herein an air-stable, visible-light-absorbing photoluminescent tungsten(vi) complex which can be conveniently prepared at the gram-scale is described. This complex could catalyse photochemical organic transformation reactions including borylation of aryl halides, such as aryl chloride, reductive coupling of benzyl bromides for C-C bond formation, reductive coupling of phenacyl bromides, and decarboxylative coupling of redox-active esters of alkyl carboxylic acid with high product yields and broad functional group tolerance.

Transition-Metal-Free C(sp2 )-C(sp2 ) Cross-Coupling of Diazo Quinones with Catechol Boronic Esters.

A transition-metal-free C(sp2 )-C(sp2 ) bond formation reaction by the cross-coupling of diazo quinones with catechol boronic esters was developed. With this protocol, a variety of biaryls and alkenyl phenols were obtained in good to high yields under mild conditions. The reaction tolerates various functionalities and is applicable to the derivatization of pharmaceuticals and natural products. The synthetic utility of the method was demonstrated by the short synthesis of multi-substituted triphenylenes and three bioactive natural products, honokiol, moracin M, and stemofuran A. Mechanistic studies and density functional theory (DFT) calculations revealed that the reaction involves attack of the boronic ester by a singlet quinone carbene followed by a 1,2-rearrangement through a stepwise mechanism.

Solvent-Induced Cluster-to-Cluster Transformation of Homoleptic Gold(I) Thiolates between Catenane and Ring-in-Ring Structures.

Supramolecular ensembles adopting ring-in-ring structures are less developed compared with catenanes featuring interlocked rings. While catenanes with inter-ring closed-shell metallophilic interactions, such as d10 -d10 AuI -AuI interactions, have been well-documented, the ring-in-ring complexes featuring such metallophilic interactions remain underdeveloped. Herein is described an unprecedented ring-in-ring structure of a AuI -thiolate Au12 cluster formed by recrystallization of a AuI -thiolate Au10 [2]catenane from alkane solvents such as hexane, with use of a bulky dibutylfluorene-2-thiolate ligand. The ring-in-ring AuI -thiolate Au12 cluster features inter-ring AuI -AuI interactions and underwent cluster core change to form the thermodynamically more stable Au10 [2]catenane structure upon dissolving in, or recrystallization from, other solvents such as CH2 Cl2 , CHCl3 , and CH2 Cl2 /MeCN. The cluster-to-cluster transformation process was monitored by 1 H NMR and ESI-MS measurements. Density functional theory (DFT) calculations were performed to provide insight into the mechanism of the "ring-in-ring⇌ [2]catenane" interconversions.

Clinical significance of Stathmin1 expression and epithelial-mesenchymal transition in curatively resected gastric cancer.

In our previous study, it was demonstrated that the Stathmin1 (STMN1) is overexpressed in gastric cancer (GC) and that its high expression level is associated with tumor invasion and metastasis. Epithelial-mesenchymal transition (EMT) has also been shown to be critically involved in GC invasion and metastasis. Certain studies have indicated that STMN1 may serve an important role in the EMT process. However, the association between STMN1 expression and EMT-associated markers, as well as clinicopathological characteristics of patients with GC, remains unclear. The aim of the present study was to investigate the clinicopathological significance and prognostic value of STMN1 and EMT-associated markers in GC. The expression of STMN1 and the EMT-associated proteins E-cadherin (E-Cad) and vimentin (VIM) were analyzed by immunohistochemistry in GC and adjacent non-tumorous tissues. Associations between the expression of these markers and clinicopathological parameters were analyzed. The association between STMN1 expression and EMT-associated markers was investigated in the GC cell lines BGC-803 and SGC-7901. The results revealed that STMN1 was expressed in 63.5% of the 167 GC tissues, which was significantly higher than the percentage observed in the adjacent non-tumorous tissues (P=0.003). The STMN1 expression was demonstrated to be positively associated with the VIM levels (P=0.001) and negatively associated with the E-Cad levels (P=0.022) in GC tissues. The STMN1 expression was associated with Lauren's Classification, invasion depth, lymph node metastasis and pathological Tumor-Node-Metastasis (pTNM) stage (P<0.05). In the univariate analyses, the high E-Cad expression was a positive prognostic indicator for overall survival, whereas the high STMN1 and VIM expression was a negative indicator. COX multiple regression analysis demonstrated that the pTNM stage [hazard ratio (HR) 1.912, 95% confidence interval (CI): 1.282-2.851, P=0.001] and E-Cad expression (HR 0.403, 95% CI: 0.249-0.650, P=0.000) were independent prognostic factors. It was also revealed that the expression level of E-Cad decreased, while the expression level of VIM increased by depleting STMN1 levels in GC cells. The present results suggest that the aberrant expression of STMN1 may promote tumor progression through EMT in GC.

Antioxidant Activity of Water Extract from Fermented Mycelia of Cordyceps sobolifera (Ascomycetes) in Caenorhabditis elegans.

This research aimed to evaluate the potential of Cordyceps sobolifera in mycelial biomass production via liquid culture and to assay the safety and determine the antioxidative and antiaging activities of Caenorhabditis elegans. A C. sobolifera isolate was cultured using the one-factor-at-a-time method to illustrate its carbon and nitrogen requirements. To assess safety, we determined the lethality, locomotion behavior, and reproduction of C. elegans cultured on a mycelial water extract (MWE) containing nematode growth medium (NGM). To investigate antiaging activity, C. elegans treated with MWE was incubated on NGM plates. The lethality was recorded throughout the whole life cycle. To identify antioxidant activity, C. elegans treated with MWE was exposed to paraquat, causing superoxide conditions. The results showed that C. sobolifera was favored by glucose and peptone as carbon and nitrogen sources, respectively. MWE was considered to be safe, as no abnormal behaviors were observed in C. elegans. Compared with nematodes pretreated with no MWE but with water instead, MWE at 1.0 mg/mL significantly prolonged the mean lifespan of C. elegans by 24%. We observed an obvious dose-effect relation between concentration and mean lifespan. The effective antioxidant activity was recorded at the high concentration of MWE. These findings demonstrate the potential antiaging and antioxidant properties of C. sobolifera as functional food and dietary supplement.

Prolonged overall survival in gastric cancer patients after adoptive immunotherapy.

AIM: To assess the efficacy of immunotherapy with expanded activated autologous lymphocytes (EAALs) in gastric cancer. METHODS: An observational study was designed to retrospectively analyze the clinical data of 84 gastric cancer patients, of whom 42 were treated by EAAL immunotherapy plus conventional treatment and another 42 only received conventional treatment (control group). EAALs were obtained by proliferation of peripheral blood mononuclear cells from patients followed by phenotype determination. Clinical data including age, gender, clinical stage, chemotherapeutic regimens, hospitalization, surgical, radiotherapy, and survival data were collected along with EAAL therapy details and side effects. Patients were followed and the relationship between treatment and overall survival (OS) data obtained for the immunotherapy and control groups were compared retrospectively. The safety of EAAL immunotherapy was also evaluated. RESULTS: After in vitro culture and proliferation, the percentages of CD3+, CD3+CD8+, CD8+CD27+, CD8+CD28+, and CD3+CD16+/CD56+ cells increased remarkably (P < 0.05), while the percentages of CD3+CD4+, CD4+CD25+, and CD3-CD16+/CD56+ (natural killer cells) were overtly decreased (P < 0.05); no significant change was observed in CD4+CD25+CD127- cells (P = 0.448). Interestingly, OS in the immunotherapy group was significantly higher than that in the control group, with 27.0 and 13.9 mo obtained for the two groups, respectively (P = 0.028, HR = 0.573, 95%CI: 0.347-0.945). These findings indicated a 42.7% decrease in the risk of death. In addition, we found that clinical stage and application of EAAL immunotherapy were independent prognostic factors for gastric cancer patients. Indeed, the OS in stage IIIc and IV patients that had received surgery was prolonged after EAAL immunotherapy (P < 0.05). Importantly, in vitro induction and proliferation of EAAL were easy and biologically safe. CONCLUSION: Overall, EAAL adoptive immunotherapy might prolong the OS in gastric cancer patients.

PAHs in sediment cores at main river estuaries of Chaohu Lake: implication for the change of local anthropogenic activities.

In the present study, 28 polycyclic aromatic hydrocarbons (PAHs) were investigated in four sediment cores collected from the main river estuaries of Chaohu Lake, one of the severely polluted lakes in China. The results indicate that elevated concentrations of total PAHs (Σ28PAH) were found in the samples from the estuary of Nanfei River (ENF), considering BaP-based total toxicity equivalent (TEQ-BaP) and toxic unit (TU) results; there are potential adverse environmental implications. The total organic carbon (TOC) played an important role on the accumulation of PAHs at ENF and the estuary of Tongyang River (ETY). The predominant PAHs are high molecular weight (HMW) homologous for all samples; as a result, industrial wastewater from a steel company is expectedly the key source of PAHs in ENF, while coke consumption would be the important source of PAHs at other three sampling sites. Vertical distribution of PAHs in the sediment cores could be explained by the local social and economic activities. Furthermore, a minor variation of PAH composition in the sediment core could be justified by the stable structure of energy consumption in the Anhui Province. These results justify the need for further enhancement of industrial wastewater treatment and development of renewable energies which are the key factors on the control of PAH pollution in China.

Prognostic value of number of examined lymph nodes in patients with node-negative gastric cancer.

AIM: To elucidate the potential impact of examined lymph nodes (eLNs) on long-term survival of node-negative gastric cancer patients after curative surgery. METHODS: A total of 497 node-negative gastric cancer patients who underwent curative gastrectomy between January 2000 and December 2008 in our center were enrolled in this study. Patients were divided into 4 groups according to eLNs through cut-point analysis. Clinicopathological features were compared between ≤ 15 eLNs group and > 15 eLNs group and potential prognostic factors were analyzed. The Log-rank test was used to assess statistical differences between the groups. Independent prognostic factors were identified using the Cox proportional hazards regression model. Stratified analysis was performed to investigate the impact of eLNs on patient survival in each stage. Overall survival was also compared among the four groups. Finally, we explored the recurrent sites associated with eLNs. RESULTS: Patients with eLNs > 15 had a better survival compared with those with eLNs ≤ 15 for the entire cohort. By the multivariate survival analysis, we found that the depth of invasion and the number of eLNs were the independent predictors of overall survival (OS) of patients with node-negative gastric cancer. According to the cut-point analysis, T2-T4 patients with 11-15 eLNs had a significantly longer mean OS than those with 4-10 eLNs or 1-3 eLNs. Patients with ≤ 15 eLNs were more likely to experience locoregional and peritoneal recurrence than those with > 15 eLNs. CONCLUSION: Number of eLNs could predict the prognosis of node-negative gastric cancer, and dissection of > 15 eLNs is recommended during lymphadenectomy so as to improve the long-term survival.

[Significance of No.14v lymph node dissection for advanced gastric cancer undergoing D2 lymphadenectomy].

OBJECTIVE: To elucidate the necessity of No.14v lymph node dissection in D2 lymphadenectomy for advanced gastric cancer. METHODS: Clinicopathological data of 131 cases of advanced gastric cancer receiving D2 or D2+ plus No.14v lymph node dissection were reviewed retrospectively. Clinicopathological factors associated with No.14v lymph node metastasis were analyzed and prognostic value of No.14v lymph node metastasis was evaluated. RESULTS: Of the 131 patients, 24 (18.3%) had positive No.14v lymph node. The incidence of 14v metastasis was associated with tumor location, tumor size, depth of invasion, N staging, TNM staging, No.1, No.6, and No.8a lymph nodes metastasis. Tumor location and N staging were independent risk factors for No.14v metastasis (all P<0.05). The 5-year survival rate was 8.3% and 37.8% in patients with and without No.14v metastasis respectively. The difference was statistically significant (P<0.01). Multivariate analysis revealed that metastasis of No.14v was an independent prognostic factor for advanced gastric cancer after D2 lymphadenectomy (P=0.029, RR=1.807, 95%CI:1.064-3.070). CONCLUSIONS: For advanced middle and lower gastric cancers, especially those with larger size, serosa invasion and possibility of No.6 lymph node metastasis, it is necessary and feasible to remove the No.14v lymph node.

Overexpression of stathmin 1 is associated with poor prognosis of patients with gastric cancer.

Recently, stathmin 1 has been proposed to function as an oncogene based on some relevant studies in multiple types of human cancers. However, the role of stathmin 1 in gastric cancer carcinogenesis has not been elucidated yet. The aim of this study was to investigate the expression of stathmin 1 as well as its association with overall survival of gastric cancer patients. The expression of stathmin 1 was detected by real-time quantitative reverse transcription polymerase chain reaction and Western blotting in gastric cancer and adjacent nontumor tissues. In addition, stathmin 1 expression was analyzed by immunohistochemistry in paraffin samples from 210 primary gastric cancer patients. The expression levels of stathmin 1 mRNA and protein in gastric cancer tissues were both significantly higher than those in adjacent nontumor tissues. In addition, the expression of stathmin 1 is correlated with Lauren's classification, depth of invasion, lymph node metastases, and tumor node metastasis (TNM) stage (all P < 0.05). Univariate analysis showed that high stathmin 1 expression was associated with poor prognosis in gastric cancer patients (P = 0.040). Multivariate analysis demonstrated that only lymph node metastasis and TNM stage were the independent prognostic indicators for gastric cancer. Stathmin 1 expression status is not an independent prognostic factor for patients with gastric cancer. Further subgroup analysis revealed that stathmin 1 expression was significantly correlated with prognosis in diffuse type gastric cancer. This research showed that the stathmin 1 overexpression might play an important role in the pathogenesis and subsequent progression of gastric cancer. Stathmin 1 could also be a potential therapeutic target in gastric cancer, especially for diffuse type gastric cancer.

[Prognosis analysis of 310 patients with pathological stage pN3 gastric cancer].

OBJECTIVE: To investigate the clinicopathological characteristics and prognostic factors of patients with pathological stage pN3 gastric cancer. METHODS: A retrospective study of 310 patients with histologically confirmed pN3 stage gastric cancer undergoing radical gastrectomy from January 2000 to December 2006 in our department was performed. The Kaplan-Meier method was used to analyze the survival. Log-rank test and Cox regression model were carried out for univariate and multivariate analyses. RESULTS: All the patients were followed up for 2 to 103 (mean 35.7) months. The overall 5-year survival rate was 14.6%. There were 201 cases with stage pN3a and 109 cases with stage pN3b, and the 5-year survival rates were 16.8% and 10.3% respectively (P=0.013). Univariate analysis showed that tumor location, Borrmann type, depth of tumor invasion, surgical method, metastatic lymph node ratio, and pN stage were associated with postoperative survival (all P<0.05). The multivariate analysis revealed that depth of tumor invasion, surgical method and metastatic lymph node ratio were independent prognostic factors, while the pN stage was not. The difference of 5-year survival rate between pN3a and pN3b subgroups was significant in pT4a patients (16.1% vs. 12.8%, P=0.001), while such difference was not significant in pT4b patients (8.6% vs. 3.1%, P=0.137). CONCLUSIONS: Prognosis of patients with pN3 stage gastric cancer after radical resection is poor. Depth of tumor invasion and surgical method are independent prognostic factors for pN3 stage gastric cancer. Metastatic lymph node ratio is valuable to predict the prognosis of pN3 stage patients. The pN3 staging of the 7th UICC provides a more accurate prediction of prognosis.

[Changes of lymphocyte subsets before and after chemotherapy in colorectal carcinoma patients].

OBJECTIVE: To investigate the change of lymphocyte subsets before and after chemotherapy in colorectal carcinoma patients. METHODS: Twenty-one peripheral blood lymphocyte subsets from 62 colorectal carcinoma patients before and after FOLFOX4(including oxaliplatin, 5-fluorouracil and leucovorin) , FOLFRI(including irinotecan, 5-fluorouracil and leucovorin) , or XELOX(including oxaliplatin and capecitabine) regimen chemotherapy were examined by flow cytometry.The differences of these lymphocyte subsets were analyzed. RESULTS: After chemotherapy, the percentages of CD3(+), CD3(+)CD8(+), CD29(+), CD4(+)CD29(+), and CD4(+)CD25(+) cells in peripheral blood of colorectal carcinoma patients increased significantly, while the percentages of CD19(+) and human leukocyte antigen(locus) DR(HLA-DR) (+) cells decreased significantly(P<0.05) .The results of subgroup analysis showed that the patients' CD3(+)CD8(+) and CD4(+)CD25(+) cells increased significantly, CD19(+) and HLA-DR(+) cells decreased significantly after FOLFOX4 regimen chemotherapy(P<0.05) ;CD3(+)CD8(+) cells increased significantly and CD19(+) cells decreased significantly after XELOX regimen chemotherapy(P<0.05) ;while after FOLFRI regimen chemotherapy, there were no significant changes in all 21 lymphocyte subsets(P>0.05) . CD3(+), CD3(+)CD8(+), memory T lymphoctye(45RO(+)) , and CD4(+)CD45RO(+) cells increased significantly(P<0.05) in patients who received no more than 4 cycles of chemotherapy. However, in patients that received 5 to 8 cycles and more than 9 cycles chemotherapy, we only found significant decrease of HLADR(+) cells and significant increase of CD29(+) cells, respectively(P<0.05) . CONCLUSIONS: The humoral immunity is attenuated after chemotherapy in colorectal carcinoma patients. FOLFOX4 may suppress the cellular immunity.Chemotherapy that is less than 4 cycles will strengthens the cellular immunity by modulating body immunity arrangement;however, along with the increase of chemotherapy cycles, the cellular immunity gradually declines in these patients.