Risk Factors of Bleeding-related Perioperative Cardiac Arrest / 中国医学科学院学报

Objective To reveal the incidence,mortality,and risk factors of bleeding-related perioperative cardiac arrest(POCA). Methods We carried out a single-center retrospective case-control study which enrolled all the POCA cases reported from January 2010 to September 2020 in the patient safety incident reporting system of Peking Union Medical College Hospital.For the screening of risk factors,the patients were respectively assigned into the POCA group and the control group at a ratio of 1∶3 according to the same sex,age,American Society of Anesthesiologists(ASA)physical status,and type of surgery in the same month.Potential risk factors for POCA were first selected by univariate analysis.The significant risk factors were then checked based on the clinical experience and further included in the multivariate Logistic regression model. Results Totally 16 bleeding-related POCA cases were collected from the patient safety incident reporting system among the study period,with an overall incidence of 0.36/10 000.The blood loss volume of POCA group and control group was(7 037.50±5 477.70)ml and(375.63±675.14)ml,respectively(P<0.001),and 14(87.5%)patients suffering from bleeding-related POCA died within three days after anesthesia.According to the univariate analysis,patients' body mass index[(21.79±3.57)kg/m2 vs.(24.26±3.91)kg/m2,P=0.043],hemoglobin level[(113.44±31.08)g/L vs.(131.75±19.70)g/L,P=0.039],and alanine aminotransferase level[(17.31±7.73)U/L vs.(26.91±24.73)U/L,P=0.022]were significantly lower in the POCA group than in the control group.Further Logistic regression analysis showed that smaller body mass index and lower preoperative hemoglobin level were independently associated with the occurrence of bleeding-related POCA. Conclusions Bleeding-related POCA rarely occurred but had high mortality.Adequate precautions should be taken for the patients who are to receive surgeries with high risk of intraoperative massive bleeding.Elevating preoperative hemoglobin level might decrease the incidence of bleeding-related POCA.

Ovatodiolide isolated from Anisomeles indica induces cell cycle G2/M arrest and apoptosis via a ROS-dependent ATM/ATR signaling pathways.

Ovatodiolide was isolated from the traditional Chinese medicinal herb Anisomeles indica, possesses anti-bacterial and anti-inflammatory properties; however, the anti-cancer activity and its mechanisms have been limitedly reported. This study aimed to examine the effect and molecular action of ovatodiolide in lung cancer cells. Cell cycle distribution and reactive oxygen species (ROS) generation were measured by flow cytometry. Apoptosis was detected by propidium iodide/annexin V staining and TUNEL assay. DNA damage was investigated by comet assay and γ-H2AX staining. Caspase activity was determined using caspase fluorometric kits. Moreover, protein levels were examined by western blot. Ovatodiolide provoked reactive oxygen species generation and DNA damage, as well as inhibited cell growth and induced apoptosis in human lung cancer A549 and H1299 cell lines. DNA damage-related molecules, ATM/ATR and CHK1/CHK2 were activated by ovatodiolide. Moreover, ovatodiolide-mediated G2/M arrest was associated with the decrease of Cyclin B1 and CDC25C levels, and increase of p21WAF1/CIP1 expression. Additionally, ovatodiolide-triggered apoptosis was through both intrinsic and extrinsic pathways characterized by the elevating PUMA, Bax, and DR5 proteins, decreasing Bcl-2 and Mcl-1, and activating caspase-8, caspase-9 and caspase-3. Caffeine, an ATM/ATR inhibitor, rescued ovatodiolide-mediated cell cycle arrest and apoptosis, but not reactive oxygen species generation. Nevertheless, antioxidant N-acetyl-cysteine completely blocked ovatodiolide-mediated molecular events, G2/M arrest, and apoptosis. These observations suggest that ovatodiolide stimulates reactive oxygen species generation, causes oxidative stress and DNA damage; subsequently, provokes DNA damage signaling pathways, eventually leads to block cell cycle at G2/M phase and trigger apoptosis in lung cancer A549 and H1299 cells.

Persistent elevation of paraoxonase-1 specific enzyme activity after weight reduction in obese non-diabetic men with metabolic syndrome.

BACKGROUND: Paraoxonase-1 (PON1) is an esterase associated with the high-density lipoprotein (HDL) in serum. To date, there have been few reports about circulating PON1 protein concentration and specific activity in subjects with metabolic syndrome (MetS). More importantly, it is unknown whether weight loss could alter PON1 protein expression or specific activity in obese non-diabetic men with MetS. METHODS: We prospectively enrolled a total of 40 obese non-diabetic men with MetS. Among them, 22 subjects finished the 3-month course of weight loss program and complied for longer follow-ups post-weight loss at the 3rd, 12th, and 18th month from the beginning of the program. Twenty-six healthy volunteers served as controls. Serum circulating PON1 concentration was measured by an enzyme linked immunosorbent kit (ELISA) and PON1 activity was measured by an automated PON1 activity assay. RESULTS: Obese non-diabetic men with MetS (n=40) had a higher PON1 protein concentration (31.0 ± 11.3 vs. 24.8 ± 9.7 µg/ml, p=0.025) but lower specific enzyme activity (7.5 ± 4.0 vs. 11.2 ± 7.2 mU/µg, p=0.023) than those of the controls. Multivariate regression analysis of baseline PON1 specific activity revealed that adiponectin was a significant positive predictor (p=0.044) while monocyte chemotactic protein-1 (MCP-1) was a negative predictor (p=0.031). After a 3-month weight loss program, obese MetS men (n=22) had a significant weight reduction (95.8 ± 9.0 to 86.3 ± 10.4 kg, with a 9.9 ± 5.4% decrease, p<0.001). PON1 protein decreased significantly after weight loss and kept declining through the 3rd month till the 18th month follow-up. PON1 specific enzyme activity (baseline 7.5 ± 2.6 mU/µg) increased significantly after weight loss and kept increasing through the 12th month till the 18th month follow-ups (11.8 ± 6.4 mU/µg, p=0.001 vs. baseline). CONCLUSIONS: Weight loss by a 3-month diet and exercise program time-sequentially increased PON1 specific enzyme activity in obese non-diabetic men with MetS.

C-reactive protein gene polymorphism 1009A>G is associated with serum CRP levels in Chinese men: a TCVGHAGE study.

BACKGROUND: Increased concentrations of high-sensitivity CRP (hs-CRP) are associated with increased risk of cardiovascular disease. This increase might be caused by low-grade inflammation, but a number of studies have suggested that serum CRP concentrations are under genetic control. Since the relation between CRP concentration and cardiovascular diseases occurs across ethnicities, we determined whether CRP gene variants affect fasting hs-CRP concentrations in a cohort of Chinese men. METHODS: High-sensitivity CRP concentrations were measured in 369 Chinese men. Six polymorphisms were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing within the CRP gene: 969T>C, 1009A>G, and a 3-allele polymorphism 1440C>A>T in the 5' UTR (promoter region), 2667G>C in exon 2, and 3872A>G and 5992T>A in the 3' UTR. RESULTS: In a group of participants (n=328) whose fasting serum hs-CRP concentrations were within the 5th to 95th percentile, we found that the genetic polymorphism 1009A>G was significantly associated with fasting serum hs-CRP concentrations (GG vs. AG or AA genotypes, CRP concentrations 0.072+/-0.062 vs. 0.176+/-0.166 and 0.166+/-0.185 mg/dl, mean+/-S.D., both P=0.023). Furthermore, subjects carrying the 1009G bearing haplotype exhibited the lowest CRP concentrations (P=0.05). CONCLUSION: The CRP 1009A>G genotypes and associated haplotypes were associated with lower fasting serum hs-CRP concentrations in a group of elderly Chinese men.

Lactate dehydrogenase, not vascular endothelial growth factor or basic fibroblast growth factor, positively correlates to bone marrow vascularity in acute myeloid leukemia.

BACKGROUND: Angiogenesis has been extensively studied in acute myeloid leukemia (AML). Lactate dehydrogenase (LDH), a common biochemical marker for tumor burden and anaerobic glycolysis, is a poor prognostic factor for AML. Regulated by hypoxia-induced factor, both vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are responsive to cancer-related angiogenesis. To study the roles of serum LDH, VEGF and bFGF in AML angiogenesis, we investigated bone marrow vascularity in untreated AML patients, and analyzed its relationship to serum LDH, VEGF and bFGF levels. METHODS: Eighteen (11 males, 7 females; mean age, 57.7 years) de novo, untreated AML patients were enrolled. Bone marrow vascularity was evaluated by staining bone marrow core biopsy tissue with endothelial cell marker CD31 or CD34. Serum LDH was determined with the Wroblewski-La Due method. Serum VEGF and bFGF were determined with enzyme-linked immunoassay. The relationship of LDH, VEGF and bFGF level to bone marrow vessel numbers was examined by linear regression. RESULTS: Log LDH significantly correlated to AML bone marrow vascularity (r = 0.61; p = 0.007). VEGF and bFGF concentrations did not correlate with AML angiogenesis. CONCLUSION: These results suggest that serum LDH, but not VEGF and bFGF concentrations, can be used as a simple parameter for predicting vessel formation in AML bone marrow.