Synthesis of pyrrolo(spiro-[2.3']-oxindole)-spiro-[4.3"]-oxindole via 1,3-dipolar cycloaddition of azomethine ylides with 3-acetonylideneoxindole.

A series of novel dispirooxindole derivatives, 3-acetyl-5-phenyl-pyrrolo(spiro-[2.3']-1'-benzyl-oxindole)-spiro-[4.3"]-1"-benzyl-oxindoles, were synthesized via 1,3-dipolar cycloaddition of the azomethine ylide with 3-acetonylideneoxindole in high regioselectivities and yields. An unusual regioselectivity was observed in this 1,3-dipolar cycloaddition, leading to the construction of novel dispirooxindole skeleton. The substituent effects on the regioselectivity were also investigated.

[Analysis of the prognosis of 111 patients with gastric cancer or adenocarcinoma of the esophagogastric junction combined with pleural or abdominal effusion].

OBJECTIVE: To explore the prognostic factors in patients with gastric cancer (GC) or adenocarcinoma of the esophagogastric junction (AEG) combined with malignant pleural and/or abdominal effusion. METHODS: Clinicopathological data of 111 GC or AEG patients with malignant pleural and/or abdominal effusion treated in our hospital from January 2001 to December 2010 were retrospectively analyzed. RESULTS: The median survival time for the whole group of 111 patients was 6 months. Effusion disappeared in 12 patients, was reduced in 36 cases, with no changes in 15 cases, and increased in 48 patients. The effusion control rate was 56.8%. Effusion was better controlled in female patients, with simple abdominal ascites, Karnovsky performance scores ≥ 80, with no liver metastases, effusion at initial diagnosis, and effective response to systemic chemotherapy.Univariate analysis showed that patients of female sex, Karnovsky performance scores ≥ 80, effusion present at initial diagnosis, simple abdominal ascites, minimal volume of effusion, absence of liver metastasis, control of effusion, initial treatment with effusions and effective response to systemic chemotherapy, normal hemoglobin, albumin, direct and indirect bilirubin levels showed better prognosis (all P < 0.05). Multivariate analysis showed that liver metastases, control of effusions were independent prognostic factors in patients with gastric cancer and adenocarcinoma of the esophagogastric junction (all P < 0.05). CONCLUSIONS: Female patients, simple abdominal ascites, KPS scores ≥ 80, ascites at initial diagnosis, no liver metastases and effective systemic chemotherapy seem to have a better control of the malignant effusion. Patients with no liver metastases and effective control of effusion have a longer survival time.

[In vitro effect of N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide on differentiation from human adipose-derived mesenchymal stem cells to endothelial cells].

OBJECTIVE: To explore the effect of N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide(W7) on the differentiation from human adipose-derived mesenchymal stem cells (hADSCs) to endothelial cells. METHODS: hADSCs were cultured with serum-free differential medium containing 40 ng/ml vascular endothelial growth factor (VEGF) and 10ng/ml basic fibroblast growth factor (bFGF). Cells were divided into control group (differential medium without W7), high-dose group (containing 30 µmol/L W7), medium-dose group (containing 20 µmol/L W7), and low-dose group ( containing 10 µmol/L W7). The hADSCs were cultured for 8 days, and then the changes in the phenotypes of von Willebrand factor (vWF) and vessel-selective cadherin (VE-Cadherin) were detected by flow cytometry (FCM). The intracellular Ca(2+) labeled with Fluo-3 was detected by laser confocal microscopy. After hADSCs planting on Matrigel, their angiogenic potentials were observed under the inverted phase contrast microscope, and the expression of extracellular regulated kinase (ERK) and phosphorylated extracellular regulated kinase (p-ERK) were evaluated by Western blot. RESULTS: After the hADSCs were cultured for 8 days, compared with the control group, the expressions of vWF and VE-Cadherin significantly increased along with the decrease of W7 level and the intracellular Ca(2+) also significantly increased (Pü0.01). Lumina-like vascular structure was formed in W7 treatment groups, but not in the blank control group. Compared with the blank control group, the expression of ERK showed no significant in W7 treatment groups (high-, medium-, and low-dose groups)(P>0.05); however, along with the decrease of W7 levels, the expression of p-ERK significantly increased(P<0.05). CONCLUSION: W7 in proper levels can effectively induce the differentiation from hADSCs to endothelium by increasing the intracellular Ca(2+) level and thus activating the ERK/MAPK pathway.

Synthesis of Fullerenes from a Nonaromatic Chloroform through a Newly Developed Ultrahigh-Temperature Flash Vacuum Pyrolysis Apparatus.

The flash vacuum pyrolysis (FVP) technique is useful for preparing curved polycyclic aromatic compounds (PAHs) and caged nanocarbon molecules, such as the well-known corannulene and fullerene C60. However, the operating temperature of the traditional FVP apparatus is limited to ~1250 °C, which is not sufficient to overcome the high energy barriers of some reactions. Herein, we report an ultrahigh-temperature FVP (UT-FVP) apparatus with a controllable operating temperature of up to 2500 °C to synthesize fullerene C60 from a nonaromatic single carbon reactant, i.e., chloroform, at 1350 °C or above. Fullerene C60 cannot be obtained from CHCl3 using the traditional FVP apparatus because of the limitation of the reaction temperature. The significant improvements in the UT-FVP apparatus, compared to the traditional FVP apparatus, were the replacement of the quartz tube with a graphite tube and the direct heating of the graphite tube by impedance heating instead of indirect heating of the quartz tube using an electric furnace. Because of the higher temperature range, UT-FVP can not only synthesize fullerene C60 from single carbon nonaromatic reactants but sublimate some high-molecular-weight compounds to synthesize larger curved PAHs in the future.

C-reactive protein, vitamin B12 and C677T polymorphism of N-5,10-methylenetetrahydrofolate reductase gene are related to insulin resistance and risk factors for metabolic syndrome in Chinese population.

PURPOSE: Metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM) are complex diseases affected by both dietary intake and genetic background. Whether N-5, 10-methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism, high-sensitivity C-reactive protein (hs-CRP) and dietary components folate and vitamin B12 are associated with MS in Asian has not been determined. METHODS: We hypothesized that MTHFR gene C677T, folate, vitamin B12 and hs-CRP are associated with MS and factors related to MS in northern Han Chinese. To test this hypothesis, MTHFR C677T gene polymorphism was determined by PCR-RFLP, serum insulin, folate and vitamin B12 levels by radioimmunoassay, and hs-CRP by immunoturbidimetry in newly diagnosed T2DM patients with MS (118) and without MS (40), and in 55 healthy subjects. RESULTS: Results indicated that MS-associated T2DM accounts for 75% of newly diagnosed T2DM in Han Chinese. Serum hs-CRP was higher and serum vitamin B12 was lower in subjects with TT genotype in comparison with those with CC or CT genotypes. Total T frequency was significantly higher in MS-associated T2DM patients (45.3%) compared to 26.3% in non-MS-associated T2DM patients. MTHFR C677T gene polymorphism and vitamin B12 levels were associated with MS-associated T2DM. CONCLUSION: MTHFR C677T gene polymorphism may contribute to insulin resistance in Han Chinese with MS by increasing hs-CRP and decreasing vitamin B12, and consequently play an important role in development of MS-associated T2DM.

The circulating level of miR-122 is a potential risk factor for endothelial dysfunction in young patients with essential hypertension.

MicroRNAs are key molecules involved in the regulation of endothelial function. They are important risk factors and biomarkers for the development of hypertension related to endothelial dysfunction. However, the gene expression patterns associated with hypertension development related to endothelial dysfunction have not been fully elucidated. We conducted a case-control study of 65 patients with essential hypertension (EH) and 61 controls without EH. Plasma levels of miR-122 and its target protein high-affinity cationic amino acid transporter 1 (CAT-1) were measured by qRT-PCR and ELISA, respectively. miR-122 expression in plasma of patients with EH was significantly higher than that of the control group (p = 0.001), while CAT-1 expression in patients with EH was significantly lower than that in the control group (p = 0.018). miR-122 expression in plasma of young patients with EH was significantly higher than that in young people without EH (p = 0.0004), and CAT-1 expression in plasma of young patients with EH was also significantly lower than that of the control group (p = 0.002). CAT-1 expression in the plasma of young participants was significantly higher than that of individuals aged ≥40 years (p = 0.003), whereas miR-122 expression was significantly lower (p = 0.001). We showed that among patients with EH, the high expression of miR-122 contributed to endothelial dysfunction by suppressing the expression of the CAT-1 protein, which led to a decrease in CAT-1 expression in plasma. Therefore, high expression of miR-122 appears to be a risk factor for endothelial dysfunction in EH, especially in younger patients.

[Analysis of prognostic factors in 300 colorectal cancer patients with liver metastases].

OBJECTIVE: To analyse the clinical characteristics and potential prognostic factors of colorectal cancer patients with liver metastases. METHODS: The clinical and pathological data of 300 colorectal cancer patients with liver metastases were retrospectively reviewed and analyzed. RESULTS: The median survival time of these patients was 19.0 months. The 1-, 2- and 5-year survival rates after liver metastases were 79.0%, 29.0% and 3.0%, respectively. Univariate analysis revealed that performance status (KPS), histological grading, primary tumor, N status, lymphatic and vascular invasion, stage at diagnosis, the number, size and distribution of liver metastases and other accompanied metastases were prognostic factors. Multivariate analysis showed that KPS, lymphatic and vascular invasion, the number and size of liver metastases were independent prognostic factors of colorectal cancer with liver metastases. CONCLUSION: Performance status, lymphatic and vascular invasion, the number and size of liver metastases are independent prognostic factors of colorectal cancer with liver metastases.

[Capecitabine combined with cisplatin as first-line therapy in Chinese patients with advanced gastric carcinoma-a phase II clinical study].

OBJECTIVE: To evaluate the effectiveness and safety of the combination chemotherapy of capecitabine (X) with fractionated administration of cisplatin (C) in Chinese patients with advanced gastric cancer (AGC). METHODS: 141 patients with AGC were enrolled between July 2002 and August 2004. All patients had measurable tumor according to the criteria of RECIST, Karnofsky performance status > or = 60, adequate bone marrow, renal and hepatic functions. Prior radiotherapy or adjuvant chemotherapy was not permitted. Patients received oral administration of capecitabine at a dose of 1000 mg/m(2) twice a day on D1-D14, and intravenous infusion of fractionated cisplatin at a dose of 20 mg/m(2)/day on D1-D5. The regimen was repeated every 3 weeks, totally for 6 cycles. RESULTS: Of the 141 evaluable patients, there were 104 men and 37 women, with a median age of 54 years (range, 23 - 80 years). Metastases before chemotherapy were detected in lymph nodes (46.8%), liver (40.4%), lung (5.7%) and other area (10.6%). The median treatment duration was 6 cycles (range, 3 - 6 cycles). The objective response rate (RR) was 36.2% (51/141). The median follow-up period was 17.5 months. The median time to progress (TTP) was 9.0 months, and the median overall survival (OS) was 12.0 months. The most common treatment-related adverse events (grade 3/4) were: hand-foot syndrome (HFS) (2.1%), leucopenia (0.7%), abnormal alanine transaminase elevation (2.8%). There was no treatment-related death. CONCLUSION: Capecitabine combined with fractionated cisplatin is highly effective and well tolerated as a first-line treatment for advanced gastric cancer, with comparable results to 5-Fu plus cisplatin combination therapy.

Gender Affects the Median Effective Dose and 95% Effective Dose of Oxycodone for Blunting the Hemodynamic Response to Tracheal Intubation in Narcotic-Naïve Adult Patients.

BACKGROUND: Intravenous (IV) oxycodone has been used at induction to prevent an intubation reaction. The aims of the current study were to calculate the median effective dose (ED50) and the 95% effective dose (ED95) of an IV bolus of oxycodone that blunts the hemodynamic response to tracheal intubation with propofol according to gender and to observe the adverse events of induction-dose oxycodone. METHODS: Adult patients who required general anesthesia and tracheal intubation were enrolled. Tracheal intubation was performed using unified TD-C-IV video laryngoscopy and an ordinary common endotracheal tube. Dixon's up-and-down method was used to obtain ED50data for women and men separately. The initial dose of oxycodone was 0.2 mg/kg for women and 0.3 mg/kg for men (step size was 0.01 mg/kg). Next, a dose-response curve from the probit analysis was generated to determine the ED50and ED95to blunt the intubation reaction in female and male patients. Adverse events following oxycodone injection were observed for 5 min before propofol injection. RESULTS: Sixty-three patients were analyzed, including 29 females and 34 males. According to the probit analysis, the ED50 and ED95of oxycodone required to blunt the intubation reaction in women were 0.254 mg/kg (95% confidence interval [CI], 0.220-0.328 mg/kg) and 0.357 mg/kg (95% CI, 0.297-2.563 mg/kg), respectively. In men, the ED50 and ED95were 0.324 mg/kg (95% CI, 0.274-0.381 mg/kg) and 0.454 mg/kg (95% CI, 0.384-2.862 mg/kg), respectively. Men required 28% more oxycodone than women for induction (P < 0.01). The most common adverse events were dizziness (87.3%), vertigo (66.7%), sedation (74.6%), and respiratory depression (66.7%). CONCLUSIONS: Oxycodone can be used for induction to prevent intubation reactions. Gender affected the ED50and ED95of oxycodone for blunting the tracheal intubation reaction.

[A randomized trial of irinotecan plus fuorouracil and leucovorin with thalidomide versus without thalidomide in the treatment for advanced colorectal cancer].

OBJECTIVE: To evaluate the efficacy, side-effects and quality of life in the advanced colorectal cancer patients treated by irinotecan plus fuorouracil and leucovorin with thalidomide or without thalidomide. METHODS: Eligible patients were randomly assigned to the treatment group and control group in a 1:1 ratio. In the treatment group, 32 evaluable patients were treated with irinotecan 180 mg/m2 i. v. on day 2, fuorouracil 400 mg/m2 bolus on day 1, 2 at a dose of 1200 mg/m2 civ. for 43 hours; leucovorin 200 mg/m2 i. v. on day 1, 2; thalidomide 300 mg, orally on day 1 - 14, two weeks as a cycle. In the control group, the regimen was the same as in the treatment group except oral intake of thalidomide. RESULTS: The response rate was 28.1% in the treatment group vs. 15.2% in the control group (P = 0.2034) with a median TTP of 3.8 months vs. 2. 5 months (P = 0.1312). Furthermore, there was no statistically difference either between two groups regarding to adverse effects. CONCLUSION: Irinotecan plus fuorouracil and leucovorin without oral intake of thalidomide is as effective and tolerable as irinotecan plus fuorouracil and leucovorin combined with oral thalidomide for advanced colorectal cancer.

[10-hydroxy-camptothecin plus fluorouracil/leucovorin for the treatment of patients with advanced colorectal cancer].

OBJECTIVE: To evaluate the maximum tolerated dose and dose-limiting toxicity (DLT) of 10-hydroxy-camptothecin (10-HCPT) in HFL regimen for the treatment of advanced colorectal cancer (CRC). METHODS: 18 advanced CRC patients, 13 males and 3 females, aged 33 - 70, were randomly assigned to 6 groups to be treated with 10-HCPT 4, 6, 8, 10, 12, or 14 mg/m(2), and 5-fluoro-uracil (5-FU) 425 mg/m(2), and leucovorin (LV) 20 mg/m(2), all administered intravenously on days 1 - 5 with 4 weeks as one cycle. The efficacy and side-effect were evaluated. RESULTS: There were two patients with grade IV myelosuppression in the 10, 12, and 14 mg/m(2) groups each. The most dose-associated adverse reactions were myelosuppression and GI dysfunction. The DLT was myelosuppression, and the maximum tolerable dose of 10-HCPT is 10 mg/m(2) on days 1 - 5. CONCLUSION: HFL regimen is well tolerated in the patients with advanced CRC. The dosing regimen recommended in clinic trial is 8 mg/m(2).

Anesthetic considerations for patients with acute cervical spinal cord injury.

Anesthesiologists work to prevent or minimize secondary injury of the nervous system and improve the outcome of medical procedures. To this end, anesthesiologists must have a thorough understanding of pathophysiology and optimize their skills and equipment to make an anesthesia plan. Anesthesiologists should conduct careful physical examinations of patients and consider neuroprotection at preoperative interviews, consider cervical spinal cord movement and compression during airway management, and suggest awake fiberoptic bronchoscope intubation for stable patients and direct laryngoscopy with manual in-line immobilization in emergency situations. During induction, anesthesiologists should avoid hypotension and depolarizing muscle relaxants. Mean artery pressure should be maintained within 85-90 mmHg (1 mmHg = 0.133 kPa; vasoactive drug selection and fluid management). Normal arterial carbon dioxide pressure and normal blood glucose levels should be maintained. Intraoperative neurophysiological monitoring is a useful option. Anesthesiologists should be attentive to postoperative respiratory insufficiency (carefully considering postoperative extubation), thrombus, and infection. In conclusion, anesthesiologists should carefully plan the treatment of patients with acute cervical spinal cord injuries to protect the nervous system and improve patient outcome.

[Influence of breast carcinoma cells on normal endothelial cells: experimental study with a co-culture system].

OBJECTIVE: To study the influence of breast carcinoma cells on normal endothelial cells. METHODS: Human endothelial cells were isolated from umbilical cord blood. Medium Z-MCF-7-EC was established and was used to co-culture the normal endothelium cells (ECs) and human breast cancer cells of the line MCF-7. Normal endothelial cells cultured by itself were used as control. Light microscopy and transmission electron microscopy were used to observe the morphology of the 2 kinds of endothelial cells. Expression of the genes ESM, IGFBP-3, alphavbeta3, VE-C, and Tie-2-2 was analyzed by semi-quantitative RT-PCR using a house-keeping gene beta(2m) as inner reference gene. RESULTS: The ECs co-cultured with MCF-7 breast cancer cells were abnormal in shape with increased size of nucleus and nucleolus, increased size ratio of nuclear to nucleoplasm, increased depth of surface fenestration, loosed and distorted endoplasm, increased size of cell-cell junctions, decreased number of surface microvilli, and tubules formed by ECs. The expression values of the genes ESM, IGFBP-3, alphavbeta3, VE-C, and Tie-2-2 in the ECs co-cultured with MCF-7 breast cancer cells were all up-regulated in comparison with those in the controls (P < 0.01, P < 0.05, P < 0.01, P < 0.01, and P < 0.05 respectively). CONCLUSION: Breast cancer cells promote formation of new vessels with endothelial cells different from the normal ECs in character and behavior.

Seasonal and geographical variation in diapause and cold hardiness of the Asian corn borer, Ostrinia furnacalis.

Asian corn borer, Ostrinia furnacalis (Guenée), is a key corn pest in the Asian-Western Pacific countries. It overwinters as full-grown larvae in plant stalks or in a spun-silk covering located in the plant debris in the temperate regions of China. Supercooling point (SCP) and survival rate after low sub-zero temperature treatment were assessed for field-collected populations in the laboratory using a cool bath with a 1°C/min cooling rate until -40°C. Mean SCPs were varied among geographical populations, with a significant decline from -22.7°C of Haikou, the multivoltine tropical population in the south, to -28.5°C of Gongzhuling, the univoltine temperate population in the northeast of China. In addition, there was more than 1°C difference in SCP between Gongzhuling univoltine and bivoltine populations that were from the same geographic origin. Mean SCPs of the Guangzhou population fluctuated over the year, with significantly lower SCPs in winter than in other seasons, which correlated with a significantly higher proportion of diapausing larvae in winter than in other seasons. Over 41% of overwintering larvae from the northeast population could withstand to be supercooled for a few minutes to the low sub-zero temperature of -40°C, but only 6.7% of their southern counterparts did so. The findings from this study suggest that O. furnacalis mostly takes advantage of freeze avoidance as diapausing larvae for overwintering in the southern region, whereas it exhibits freeze tolerance in diapause in the northeastern region.

Micro-vascular medicine and proteomics.

A new technique is sweeping the world, and changing the course of human work and life. It is impacting upon models, methods and the development of medical research. In the development of this new technique, a huge quantity of experimental research and clinical practice has proved that many human diseases have a close relationship to pathological changes that take place in the microvascular system. It has been proven that the microvascular system is the target for studying disease development and the treatment of disease. Many studies have shown that successful pathogenesis and pathological research must be aimed at understanding the key proteins in cells, organs and systems, as well as investigating their interaction, and finding out how these proteins change under disease conditions. This paper reviews the current status of microvascular medicine and proteomics.

Small-size circulating endothelial microparticles in coronary artery disease.

OBJECTIVES: Several recent lines of evidence indicate that endothelial microparticles are a new biomarker that can be used to monitor endothelial dysfunction in coronary artery disease (CAD). However, data concerning the detection of small microparticles (diameter <0.5 µm) are lacking. The aim of this study was to detect small-size endothelial microparticles (SEMPs) in CAD patients to monitor endothelial dysfunction. METHODS: In total, 19 CAD patients and 14 healthy subjects were recruited. The absolute numbers and percentages of CD31(+)/CD42b- SEMPs and CD62E(+) SEMPs were determined by flow cytometry. Clinical parameters were also recorded. RESULTS: The mean percentage of CD62E(+) SEMPs was higher in the CAD patient group than in the healthy subject group. The area under the receiver operating characteristic curve of the percentage of CD62E(+) SEMPs was 0.795, and the cut-off value was 1.35. There was no correlation between the percentage of CD62E(+) SEMPs and various clinical parameters. CONCLUSION: The percentage of CD62E(+) SEMPs is a potential biomarker for monitoring endothelial function in CAD.

Circulating CD62P small microparticles levels are increased in hypertension.

The study aims to find a new biomarker in hypertension. Our study is the first time to demonstrate that the CD62P small microparticle (diameter is <0.5 um) was a new microparticle population and a new biomarker in hypertension.

[Clinincal application of self-made eccentric traction belt in the treatment of distal radial fractures].

OBJECTIVE: To observe the curative effect of self-made eccentric traction belt as a manipulative reduction tool in the treatment of the distal radial fracture. METHODS: From February 2011 to June 2012,62 patients with distal radial closed fractures were treated by manipulative reduction with self-made wristlet-eccentric traction belt and combined with the small splint and plaster external fixation. Among them, 59 cases were Colles fractures, 2 were Smith fractures, 1 was Barton fracture. After the reduction, lateral X-ray imaging was used to evaluate curative effect immediately. RESULTS: All the patients obtained excellent and good reduction in standard of fractures, only 1 case didn't. According to functonal assessment of Dienst, the results were excellent in 49 cases, good in 11, fair in 1, and poor in 1. CONCLUSION: Self-made wristlet-eccentric traction belt as a manipulative reduction tool to treat distal radius fractures, can make fractures close to the anatomic reduction, and can significantly improve the manual reduction success rate.