The clinical implications of mean platelet volume and mean platelet volume/platelet count ratio in locally advanced esophageal squamous cell carcinoma.

As a hallmark of platelet activation, mean platelet volume (MPV) has been identified to be associated with various malignancies. However, the correlation between MPV, mean platelet volume/platelet count ratio (MPR), and esophageal squamous cell carcinoma (ESCC) remains unclear. The aim of this study is to clarify the relevance of MPV and MPR in patients with locally advanced ESCC. Four hundred and fifty-seven cases with newly diagnosed locally advanced ESCC followed by radical surgery and 240 healthy subjects matched for age and gender were included in this study. We retrospectively compared various hematological variables between groups and analyzed the correlation between MPV, MPR, and patients' clinicopathologic characteristics. Preoperative MPV and MPR were found to be significantly decreased in locally advanced ESCC when compared to healthy controls, they were (8.14 ± 1.09 fL vs. 10.23 ± 0.78 fL, P < 0.0001) and (0.03875 ± 0.02645 vs. 0.04463 ± 0.00972, P = 0.001), respectively. In addition, patients with advanced tumor length (≥4 cm) tended to have lower MPV levels (8.03 ± 1.11 fL versus 8.33 ± 1.21 fL, P = 0.005), while there was no difference between other subgroups. Moreover, decreased MPR was significantly correlated with advanced tumor length (P < 0.001) when divided at a median of 0.03420. Decreased MPV and MPR were significantly associated with locally advanced ESCC. Thus, they might be helpful in screening and risk stratification for locally advanced ESCC in combination with other approaches.

[Forensic Analysis for 54 Cases of Suxamethonium Chloride Poisoning].

OBJECTIVES: To observe and analyze the performance of forensic science in the cases of suxa- methonium chloride poisoning, and to improve the identification of suxamethonium chloride poisoning. METHODS: Fifty-four cases of suxamethonium chloride poisoning were collected. The rules of determination of suxamethonium chloride poisoning were observed by the retrospective analysis of pathological and toxicological changes as well as case features. RESULTS: The pathological features of suxamethonium chloride poisoning were similar to the general changes of sudden death, which mainly included acute pulmonary congestion and edema, and partly showed myocardial disarray and fracture. Suxamethonium chloride could be detected in the heart blood of all cases and in skin tissue of part cases. CONCLUSIONS: Suxa-methonium chloride poisoning has the characteristics with fast death and covert means, which are difficult to rescue and easily miss inspection. For the cases of sudden death or suspicious death, determination of suxamethonium chloride should be taken as a routine detection index to prevent missing inspection.

[Clinical significance of low-dose CT performed for three consecutive years in diagnosis of lung nodules in coal mine workers with 20 working years].

Objective: To investigate the clinical significance of low-dose CT (LDCT) in coal mine workers with relatively long working years. Methods: A total of 907 coal mine workers with ≥20 working years were enrolled, among whom there were 863 male and 44 female workers with a mean age of 49.5 years. Digital radiography (DR) was performed for these workers in 2013, and LDCT was performed for three consecutive years from 2014 to 2016. Results: A total of 32 workers were found to have lung nodules by DR in 2013, while in 2014, 269 workers were found to have non-calcified lung nodules by LDCT, and there was a significant difference in the number of workers with lung nodules (χ(2)=233.73, P<0.005) . There was also a significant difference in the detection rate of nodules between the workers with different working years of dust exposure (χ(2)=6.648, P=0.00) . The male workers had a significantly higher detection rate of nodules than the female workers (χ(2)=5.690, P=0.017) . There was no significant difference in the number of nodules between workers with different types of work (χ(2)=16.985, P=0.05) . There were 443 lung nodules in total, among which 71.56% were solid nodules and 55.75% had a size of ≤4mm; malignant nodules were confirmed by surgery in 6 (0.66%) of the 907 workers after baseline LDCT. LDCT reexamination in 2015 and 2016 found new nodules in 8 workers and enlarged nodules in 3 workers, and there was no significant change in the number of nodules with a size of ≤4 mm. Conclusions: It is necessary to perform high-risk population screening for coal mine workers by LDCT. The follow-up strategies for nodules with a size of ≤4mm are the same as those for negative results; annual reexamination is recommended for nodules with a size of >4-8 mm, and clinical treatment should be considered for nodules with a size of >8 mm.

Combination of a free radical scavenger and heparin reduces cerebral hemorrhage after heparin treatment in a rabbit middle cerebral artery occlusion model.

BACKGROUND AND PURPOSE: We sought to investigate the effects of EPC-K1, a free radical scavenger, on reducing heparin-produced cerebral hemorrhage in a rabbit model of middle cerebral artery (MCA) photothrombosis and to investigate whether the combination of EPC-K1 and heparin enhances neuroprotection from cerebral ischemic damage. METHODS: In the heparin-alone group (n=8), heparin was administered intravenously for 24 hours, starting from 3 hours after MCA occlusion. In the EPC-K1-alone group (n=8), EPC-K1 was administered as a bolus injection (10 mg/kg) twice at 3 and 6 hours after MCA occlusion. In the combination group (n=8), EPC-K1 and heparin both were administered as in the single-drug procedures. In the vehicle group (n=10), saline were infused for 24 hours. RESULTS: Heparin prolonged activated partial thromboplastin time by approximately 3 times that of control animals. In the heparin-treated animals, the hemorrhage size was significantly increased (P<0.0001) and neurological symptoms were significantly worse (P<0.01) than in control animals at 48 hours. The combination of EPC-K1 and heparin dramatically reduced heparin-produced cerebral hemorrhage (P<0.0001), with a significant reduction in infarct volume (reduction by 63.2% and 57.2% of heparin-alone and control animals, respectively, P<0.0001) and a significant improvement in neurological symptoms (P<0.01 versus heparin-alone and control animals, respectively). CONCLUSIONS: These data indicate that free radical formation may play a key role in intracerebral hemorrhage exacerbated by heparin treatment and that the combination of a free radical scavenger and heparin augmented neuroprotection from acute brain ischemia. The results of the present study may suggest a potential clinical approach for the treatment of acute stroke.

Cerebral hemorrhage due to heparin limits its neuroprotective effects: studies in a rabbit model of photothrombotic middle cerebral artery occlusion.

We investigated the efficacy of heparin on cerebral ischemic damage in a rabbit model of middle cerebral artery (MCA) photothrombosis and in the same model, cerebral hemorrhage induced by heparin as its side effect was also investigated. Using a photothrombosis model in rabbits, 38 animals were divided into four groups, heparin low-dose I and II, heparin high-dose and vehicle. In heparin low-dose I (n=10) or II (n=7), heparin was administered for 23.5 or 22 h, respectively, starting 30 or 120 min after the start of photo-irradiation to induce thrombosis. In high-dose (n=7), heparin was administered 30 min after the start of photo-irradiation for 23.5 h. In the vehicle treated group (control), 14 animals were infused continuously with saline for 23.5 h. Heparin at low and high doses prolonged Activated partial thromboplastin time (aPTT) by about 3 and 10 times compared with control group. The results show that cerebral hemorrhage was present in all animals, gross hemorrhage was observed in one animal each of the heparin low-dose I and high-dose groups, and in three animals of the heparin low-dose II group, while no gross hemorrhage was observed in control group. In heparin low-dose I, the size of cerebral infarction was significantly (P<0.01) reduced and neurological deficits were significantly (P<0.01) improved. In contrast, in heparin high-dose, the infarct size significantly increased, especially in the cortex (P<0.0001), and neurological deficits were significantly (P<0.01) worsened. In heparin low-dose II, the size of cerebral hemorrhage significantly (P<0.001) increased compared with the control group. In conclusion, using a photothrombotic model in the rabbit MCA, we have investigated the antithrombotic benefits and hemorrhagic risks associated with heparin. Of unique feature of our model is the fact that in a single animal model, we could evaluate doses of heparin which reduce cerebral infarction and doses which can promote cerebral hemorrhage. This model can be extended to determine both benefits and risks of antithrombotic agents.

Spectroscopic studies on the interaction of efonidipine with bovine serum albumin.

Efonidipine hydrochloride is an antihypertensive and antianginal agent with fewer side effects and is better tolerated in the treatment of hypertension with renal impairment. Its interaction with bovine serum albumin (BSA) is of great use for the understanding of the pharmacokinetic and pharmacodynamic mechanisms of the drug. The binding of efonidipine to BSA was investigated by fluorescence spectroscopy and circular dichroism. BSA fluorescence was quenched by efonidipine, due to the fact that efonidipine quenched the fluorescence of tryptophan residues mainly by the collision mode. The thermodynamic parameters DeltaH0 and DeltaS0 were 68.04 kJ/mol and 319.42 J x mol-1 x K-1, respectively, indicating that the hydrophobic interactions played a major role. The results of circular dichroism and synchronous fluorescence measurements showed that the binding of efonidipine to BSA led to a conformational change of BSA. The fraction of occupied sites (theta) for the 8-anilino-1-naphthalein-sulfonic acid (ANS)-BSA system is 85%, whereas for the NZ-105-BSA system, it is 53%, which suggests that the interaction of ANS with BSA is stronger than that of NZ-105 with BSA. Binding studies in the presence of ANS indicated that efonidipine competed with ANS for hydrophobic sites of BSA. The effects of metal ions on the binding constant of the efonidipine-BSA complex were also investigated. The presence of metal ions Zn2+, Mg2+, Al3+, K+, and Ca2+ increased the binding constant of efonidipine-BSA complex, which may prolong the storage period of NZ-105 in blood plasma and enhance its maximum effects.

Spectroscopic studies on the interaction of efonidipine with bovine serum albumin

Efonidipine hydrochloride is an antihypertensive and antianginal agent with fewer side effects and is better tolerated in the treatment of hypertension with renal impairment. Its interaction with bovine serum albumin (BSA) is of great use for the understanding of the pharmacokinetic and pharmacodynamic mechanisms of the drug. The binding of efonidipine to BSA was investigated by fluorescence spectroscopy and circular dichroism. BSA fluorescence was quenched by efonidipine, due to the fact that efonidipine quenched the fluorescence of tryptophan residues mainly by the collision mode. The thermodynamic parameters ÄH0 and ÄS0 were 68.04 kJ/mol and 319.42 J·mol-1·K-1, respectively, indicating that the hydrophobic interactions played a major role. The results of circular dichroism and synchronous fluorescence measurements showed that the binding of efonidipine to BSA led to a conformational change of BSA. The fraction of occupied sites (è) for the 8-anilino-1-naphthalein-sulfonic acid (ANS)-BSA system is 85 percent, whereas for the NZ-105-BSA system, it is 53 percent, which suggests that the interaction of ANS with BSA is stronger than that of NZ-105 with BSA. Binding studies in the presence of ANS indicated that efonidipine competed with ANS for hydrophobic sites of BSA. The effects of metal ions on the binding constant of the efonidipine-BSA complex were also investigated. The presence of metal ions Zn2+, Mg2+, Al3+, K+, and Ca2+ increased the binding constant of efonidipine_BSA complex, which may prolong the storage period of NZ-105 in blood plasma and enhance its maximum effects.