The present study investigates the vasodilative action of carbon monoxide on rat pulmonary artery in vitro. After isolation of the pulmonary artery rings (PAR) from Wistar rats, an ACh concentration-response curve was generated; the PARs were incubated with the NOS inhibitor L-NAME (30 micromol/L, n=10) or the heme oxygenase inhibitor ZnPPIX (10 micromol/L)+L-NAME (30 micromol/L, n=10) for 30 min. After that, a second ACh concentration-response curve was elicited. Other isolated PARs were randomly divided into two groups: endothelium-intact group (n=8) and endothelium-denuded group (n=8). The effect of exogenous carbon monoxide (CO) on pulmonary arterial vessel tone was observed. The results showed that ACh induced a concentration-dependent pulmonary vasorelaxation. This relaxation disappeared after endothelium was denuded. The ACh induced relaxation was attenuated after pretreatment with 30 micromol/L L-NAME, and attenuated further after pretreatment with 10 micromol/L ZnPPIX+30 micromol/L L-NAME. Exogenous carbon monoxide relaxed pulmonary artery in both the endothelium-intact group and the endothelium-denuded group. These data suggest that ZnPPIX inhibits ACh induced endothelium-dependent pulmonary artery relaxation and that CO is an endothelium-derived relaxation factor, and exogenous CO can relax pulmonary artery.
Acetylcholine ; pharmacology ; Animals ; Carbon Monoxide ; pharmacology ; Dose-Response Relationship, Drug ; Endothelium, Vascular ; drug effects ; Heme Oxygenase (Decyclizing) ; antagonists & inhibitors ; In Vitro Techniques ; NG-Nitroarginine Methyl Ester ; pharmacology ; Nitric Oxide Synthase ; antagonists & inhibitors ; Protoporphyrins ; pharmacology ; Pulmonary Artery ; drug effects ; Rats ; Rats, Wistar ; Vasodilation ; drug effects

In recent years a huge amount of clinical studies have proved that fluctuant hypertension could aggravate the damage of target organs and increase the incidence of acute cardio-/cerebrovascular events, when compared with stable hypertension [increased mean artery blood pressure (MBP)]. How to prevent and treat fluctuant hypertension and its damage of target organs has become one of the hot and difficult problems in the field of hypertension studies all over the world. Hypertensive patients often suffer from thromboembolic target organ damage. Platelet activation plays a key role in this progress, but its concrete mechanisms have not been clearly clarified. Based on the in-depth discussions on progress of fluctuant hypertension, its relationship with platelet activation and blood stasis syndrome of Chinese medicine (CM) in recent three years, we proposed, under the fluctuant hypertensive state, the prethrombotic state has occurred in the organisms, i.e., a pathological state featured by platelet activation, liable to have vulnerable thrombopoiesis, and accompanied by endothelial dysfunction. Blood stasis syndrome might occupy an important position in CM syndrome typing of fluctuant hypertension. Herbs for activating blood circulation and removing stasis might have an extensive application prospect.
Humans ; Hypertension ; blood ; prevention & control ; Integrative Medicine ; Platelet Activation

OBJECTIVETo study the effect of embelin on proliferation, differentiation and apoptosis of HL-60 cells and explore its possible mechanism.

METHODSDifferent concentration of embelin were used to treat HL-60 cells. Cell growth curve was analysed by MTT assay, cell apoptosis by Annexin V/PI double staining and JC-1 dye. The differentiation of HL-60 cells was evaluated by expression of CD33, CD34, CD11b and CD14. Bone marrow cells (BMC) from nine patients with acute nonlymphocytic leukemia (ANML) were also studied.

RESULTSEmbelin induced differentiation of HL-60 cells with significant increase of CD14 and CD11b expression at 33.97µmol/L for 3 days (P < 0.01). Embelin induced apoptosis of HL-60 cells in a time- and dose-dependent manner, the apoptosis rates were (9.23 ± 0.05)%, (25.86 ± 0.30)% and (39.03 ± 0.07)% respectively at 339.67 µmol/L of embelin for 12-, 24- and 48-hours treatment (P < 0.05); the apoptosis rates were (0.07 ± 0.03)%, (7.43 ± 0.30)%, (14.01 ± 0.01)%, (25.52 ± 0.03)% and (39.15 ± 0.01)% respectively at 10.19, 33.97, 101.90, 339.67 and 1019.02 µmol/L of embelin for 24-hours culture (P < 0.05). Clusters of differentiation antigen on BMC from three acute promyelocytic leukemia patients showed significant changes at 33.97 µmol/L of embelin treatment for 3 days. Embelin induced apoptosis of BMCs from all the nine ANML patients at 33.97 µmol/L for 24 hour.

CONCLUSIONEmbelin can inhibit proliferation and induce differentiation and apoptosis of HL-60 cells. The mechanism may be related to mitochondrial apoptosis pathway. Embelin at subtoxic concentration doesn't promote leukemia BMC differentiation, but at 339.67 µmol/L induces apoptosis of these cells.

Apoptosis ; drug effects ; Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; HL-60 Cells ; Humans ; Leukemia, Promyelocytic, Acute ; metabolism

Myeloproliferative neoplasm is a clonal hematopoietic stem cell disease, which is often complicated by coagulation dysfunction, manifested as thrombosis and bleeding tendency. The mechanism of coagulation dysfunction in myeloproliferative neoplasm is unclear, which may be the result of multiple factors, such as proliferation and activation of leukocyte, abnormality of platelet and its receptors, JAK2V617 F mutation, vWF consumption and drugs. High-risk patients should be assessed to prevent and reduce adverse events.

BACKGROUNDBladder recurrent disease is still a challenge in the treatment of upper tract urothelial carcinoma (UTUC). This controlled study aims to investigate the efficacy of early clipping of the distal ureter prior to nephroureterectomy (NU) to prevent bladder recurrence after UTUC.

METHODSPatients with clinical diagnosis of UTUC were subjected to open trans-peritoneal NU and were randomly divided into two groups. One group received modified NU: clipping the distal ureter prior to NU; while the other group underwent traditional standard NU. Subsequent bladder recurrence was the primary endpoint.

RESULTSFrom January 2007 to December 2009, 85 eligible cases were enrolled in this study. Modified NU and standard NU were performed on 42 and 43 patients, respectively. Operation time ((215.73 ± 21.26) minutes vs. (220.19 ± 15.35) minutes), blood loss ((105.15 ± 11.32) ml vs. (110.12 ± 9.07) ml), transfusion event (11.20% vs. 9.78%), and the in-patient time (10.0 days vs 9.5 days) were not significant between the two groups. After a median follow-up of 28 months (5 - 60), six (14.3%) cases who received modified NU had bladder recurrence, which was significantly lower compared with 15 (34.9%) patients from the group that underwent standard NU (P = 0.026). In univariate and multivariate analysis, tumor grade (HR 4.33, 95%CI 2.66 - 6.30, P = 0.01) and operation type (HR 2.35, 95%CI 1.53 - 3.48, P = 0.041) were independent risk factors for subsequent bladder recurrence after UTUC.

CONCLUSIONSClipping the distal ureter at the beginning of NU significantly reduces bladder recurrence after UTUC. It is reasonable to conclude that clipping the distal portion of ureter trans-peritoneal is an effective surgical procedure for the treatment of UTUC.

Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; prevention & control ; Nephrectomy ; methods ; Ureter ; surgery ; Urinary Bladder Neoplasms ; surgery

OBJECTIVESTo investigate the oncologic outcomes of surveillance, retroperitoneal lymph node dissection (RPLND) and primary chemotherapy in patients with clinical stage Ia nonseminomatous germ cell testicular tumors (CS Ia NSGCT) and to analyze risk factors for relapse.

METHODSPatients with CS Ia NSGCT were retrospectively reviewed. Totally 72 patients were enrolled and grouped according to three different treatment after orchiectomy, among them 33 cases in surveillance group, 24 cases in RPLND group and 15 cases in primary chemotherapy group. Disease progressive free survival and disease specific survival were compared using Kaplan-Meier analysis. Cox regression analysis was used to confirm variables those were associated with disease progression.

RESULTSAll 72 patients were followed-up at mean 62 months (12 - 175 months), 6 patients had evidence of relapse. Both the 5-year disease specific survival and 5-year overall survival rate were 100%. For surveillance, chemotherapy and RPLND, cumulative 5-year PFS rates were 84.0%, 93.3% and 100%, respectively. Relapse rate was higher in surveillance group than in RPLND group (17.8% vs. 0, χ² = 3.99, P = 0.04). Patients with the history of cryptorchidism also have higher relapse rate than without (37.5% vs. 4.7%, χ² = 10.02, P = 0.01). In the surveillance cohort, relapse rates were significantly higher in patients with a predominant component of embryonal carcinoma (3/6 vs. 7.4%, χ² = 6.93, P = 0.04) and for those over 13 years of age (23.1% vs. 5.3%, χ² = 4.33, P = 0.04). On multivariate analysis, treatment mode of patients (OR = 0.08, 95% CI: 0.06-0.36, P = 0.03) and patients with a history of cryptorchidism (OR = 25.3, 95% CI: 6.57-78.42, P = 0.04) were independent predictors of relapse.

CONCLUSIONSSurveillance, RPLND and adjuvant chemotherapy could be reliable strategies in compliant stage Ia nonseminoma patients and achieve satisfactory overall survival. Relapse rate is relatively higher for patients with surveillance. Those who are older or have a history of cryptorchidism experience a higher risk of relapse.

Adolescent ; Adult ; Aged ; Chemotherapy, Adjuvant ; Child ; Child, Preschool ; Humans ; Infant ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasms, Germ Cell and Embryonal ; therapy ; Orchiectomy ; Postoperative Period ; Retrospective Studies ; Risk Factors ; Survival Rate ; Testicular Neoplasms ; therapy ; Treatment Outcome ; Young Adult

OBJECTIVETo investigate the effects of fosinopril sodium pre-treatment combined with ischemic postconditioning on rat serum and myocardial oxidative stress and proinflammatory cytokines post ischemia/reperfusion.

METHODSSixty Sprague-Dawley rats were randomly divided into sham group (n = 15), ischemia/reperfusion group (30 minutes in situ occlusion of the left anterior descending artery followed by 1 hour reperfusion, n = 15), IPoC group (30 minutes occlusion of the left anterior descending artery followed by 3 cycles of 10 seconds of reperfusion/10 seconds of ischemia before 1 hour reperfusion, n = 15) and fosinopril sodium group [pretreated with fosinopril sodium (0.9 mg×kg(-1)×d(-1) for 14 days) followed by IPoC protocol at 2 h after the last gavage, n = 15]. The arterial blood and heart samples were extracted after 1 hour reperfusion. Serum CK-MB and cTnT levels were detected by colorimetric method, myocardial infarction size was measured by nitrotetrazolium blue chloride staining, SOD content was examined by colorimetric method, MDA content was detected using thiobarbituric acid method, serum levels of Interleukin-1α (IL-1α), Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were examined by radioimmunoassay, IL-1α, IL-6 and TNF-α levels of myocardial tissue were detected by ELISA.

RESULTSCompared with I/R group, myocardial enzymes and infarction size were significantly decreased (P < 0.05, P < 0.01), serum SOD content was increased and MDA content was decreased (all P < 0.01), serum and myocardial levels of IL-1α, IL-6 and TNF-α were significantly reduced (P < 0.05, P < 0.05, P < 0.01) in IPoC group. Compared with IPoC group, fosinopril sodium pretreatment further reduced infarction size and myocardial enzyme CK-MB (P < 0.05), increased SOD content (P < 0.05) while reduced serum IL-6 and myocardial tissue TNF-α (P < 0.05, P < 0.01).

CONCLUSIONPretreatment with fosinopril sodium enhanced the protective effect of IPoC on rat myocardium underwent I/R injury, possibly by reducing oxidative stress and early inflammatory reaction.

Animals ; Creatine Kinase, MB Form ; blood ; Fosinopril ; therapeutic use ; Interleukin-1alpha ; blood ; Interleukin-6 ; blood ; Ischemic Preconditioning, Myocardial ; methods ; Malondialdehyde ; blood ; Myocardial Reperfusion Injury ; metabolism ; pathology ; prevention & control ; Myocardium ; metabolism ; pathology ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; blood ; Troponin T ; blood ; Tumor Necrosis Factor-alpha ; blood

Aged ; Antineoplastic Agents ; administration & dosage ; Cystectomy ; Humans ; Infusions, Intra-Arterial ; Male ; Neoplasm Recurrence, Local ; Pelvic Neoplasms ; drug therapy ; Urinary Bladder Neoplasms ; surgery

OBJECTIVETo identify the antimicrobial resistance of commercial lactic acid bacteria present in microbial foods and drug additives by analyzing their isolated strains used for fermentation and probiotics.

METHODSAntimicrobial susceptibility of 41 screened isolates was tested with disc diffusion and E-test methods after species-level identification. Resistant strains were selected and examined for the presence of resistance genes by PCR.

RESULTSDistribution of resistance was found in different species. All isolates were susceptible to chloramphenicol, tetracycline, ampicillin, amoxicillin/clavulanic acid, cephalothin, and imipenem. In addition, isolates resistant to vancomycin, rifampicin, streptomycin, bacitracin, and erythromycin were detected, although the incidence of resistance to these antibiotics was relatively low. In contrast, most strains were resistant to ciprofloxacin, amikacin, trimethoprim/sulphamethoxazole, and gentamycin. The genes msrC, vanX, and dfrA were detected in strains of Enterococcus faecium, Lactobacillus plantarum, Streptococcus thermophilus, and Lactococcus lactis.

CONCLUSIONAntibiotic resistance is present in different species of probiotic strains, which poses a threat to food safety. Evaluation of the safety of lactic acid bacteria for human consumption should be guided by established criteria, guidelines and regulations.

Anti-Bacterial Agents ; pharmacology ; Cultured Milk Products ; microbiology ; Dairy Products ; Drug Contamination ; Drug Resistance, Multiple, Bacterial ; Food Microbiology ; Humans ; Lactobacillaceae ; drug effects ; Microbial Sensitivity Tests ; Pharmaceutical Preparations ; Probiotics

OBJECTIVETo compare the oncology outcomes and anal function among laparoscopic partial, subtotal and total intersphincteric resection(ISR) for low rectal cancers.

METHODSFrom June 2011 to February 2016, a total of 79 consecutive patients with low rectal cancers underwent laparoscopic ISR with hand-sewn coloanal anastomosis at our department. According to the distal tumor margin, partial ISR (internal sphincter resection at the dentate line) was used to treat tumors with distance <1 cm from the anal sphincter (n=28), subtotal ISR was adopted for the tumors locating between the dentate line and intersphincteric groove (n=34), and total ISR (resection at the dentate line) was applied in the treatment of intra-anal tumors (n=17). Anal function was evaluated by a standardized gastrointestinal questionnaire, Wexner incontinence score and Kirwan's classification. Metaphase oncological results and postoperative anal function were compared among three groups, and.

RESULTSOther than the distance of tumor low margin to dentate line (P=0.000) and serum CEA level (P=0.040), no significant differences were noted in baseline data among 3 groups (all P>0.05). The median follow up was 21(8-61) months. The 3-year disease-free survival rates in laparoscopic partial, subtotal and total ISR groups were 91.1%, 88.9%, 88.2% (P=0.901) and the 3-year local relapse-free survival rates were 91.1%, 72.9%, 80.2%(P=0.658), whose all differences were not significant. Thirty-eight patients who did not receive neoadjuvant chemoradiotherapy and underwent ileostomy closure for at least 24 months completed the evaluation of anal function, including 14 cases in partial group, 15 cases in subtotal group and 9 cases in total group. Of 38 patients, 73.7%(28/38) was classified as good function (Wexner incontinence score ≤10) and no patient adopted a colostomy because of severe fecal incontinence(Kirwan classification=grade 5). Furthermore, there were no significant differences in Wexner incontinence score and Kirwan classification among 3 groups (all P>0.05). However, patients with chronic anastomotic stoma stenosis showed worse anal function than those without stenosis [Wexner incontinence score: 18(9-20) vs 6(0-18), P=0.000; Kirwan grading: 3(2-4) vs. 2(1-4), P=0.002].

CONCLUSIONSAs the ultimate sphincter-saving technique, laparoscopic ISR can result in better oncologic outcomes and better anal function for patients with low rectal cancers. The different procedures of ISR may not affect the efficacy, but chronic anastomotic stoma stenosis deteriorates incontinence status.