Humans ; Lung Neoplasms ; therapy ; Medicine, Chinese Traditional ; methods ; trends

Given the vital role of vasculature in solid tumors, the potential of vascular disrupting therapy in the treatment of triple-negative breast cancer (TNBC) is promising. In this study, we prepared the acid-sensitive liposome PPD/CA4P/Lip-Rap loaded with the vascular disrupting agent CA4P and the anti-angiogenic drug rapamycin (Rap) to explore the potential of the vascular disrupting strategy in TNBC. PPD/CA4P/Lip-Rap was characterized by ¹H NMR, dynamic light scattering, and transmission electron microscopy. Its drug loading and acid sensitivity were determined. The particle size of PPD/CA4P/Lip-Rap is 161.53 ± 1.89 nm, the zeta potential is -20.03 ± 0.9 mV and it demonstrated good drug release on acidic sensitivity responses. CCK-8 experiments proved that Rap can enhance the ability of CA4P to destroy tumor vascular endothelial cells. Rap can kill marginal residual tumor cells, suppress tumor recurrence. Nanocarriers can further enhance the therapeutic effect. Western blot (WB) showed that Rap decreased the expression of hypoxia-inducible factor-1α (HIF-1α) via the mTOR/p70S6K and mTOR/4E-BP1 pathways. Thus, tumor hypoxia activation and angiogenesis were inhibited. PPD/CA4P/Lip-Rap can effectively destroy tumor vessels, inhibit tumor angiogenesis and recurrence, and provide a new strategy for the treatment of TNBC by targeting disruption of tumor vessels.

Objective To investigate the relationship between serum adiponectin and metabolic syndrome(MS) in children and adolescents with obesity and nonalcoholic fatty liver disease(NAFLD).Methods Four elementary schools and 4 middle schools were selected from Haidian district in Beijing with representative cluster sampling.Two hundred and eighty obese children(obese group),65 obese children with NAFLD(NAFLD group) and 264 normal weight children(healthy control group) aged 7 to 18 years were recruited from the 8 schools with uncompletely randomized sampling.Data including questionnaire,anthropometric measurements,B type ultrasonographic examination for liver were collected and fasting blood laboratory assay were determined.Variables including triglyceride(TG),adiponectin,alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were skewed distribution and natural logarithmical transformations were performed.Chi-square test for category and multiple binary Logistic regression analysis were used to statistical analysis.Results Body mass index(BMI) and waist circumference(WC) in obese group and NAFLD group were higher than those in healthy control group.All the chi-square tests for trend among the 3 groups were statistically significant(P

Objective Using CT perfusion (CTP) technique,to investigate the graft perfusion changes in patients with hepatic artery stenosis (HAS) with or without ischemic-type biliary lesions (ITBL) after orthotopic liver transplantation (OLT).Methods Thirteen recipients with HAS received CTP scan of the liver,including 8 with ITBL and 5 without ITBL.For all patients,the diagnosis of HAS was made by CTA,and the diagnosis of ITBL by percutaneous transhepatic cholangiography.CT perfusion indices were obtained,including hepatic artery perfusion (HAP),portal vein perfusion (PVP),total liver perfusion (TLP) and hepatic perfusion index (HPI).Results Of the 13 patients with HAS,mean HAP in patients with and without ITBL was 59.8 and 35.1 ml·min-1 ·100 ml-1 (P =0.021,two-tailed paired Student t test) ; mean PVP was 125.4 and 166.2 ml·min-1·100 m1-1 (P =0.016) ; mean TLP was 185.2 and 201.3 ml· min-1 · 100 ml-1 (P =0.306) ; and mean HPI was 33.6 and 18.2 (P =0.005),respectively.Conclusion Using CTP technique,liver perfusion changes were reflected by measuring CTP indices noninvasively.Compared to those without ITBL in this study,HAP and HPI in patients with ITBL were higher and PVP was lower,which may be contributed to biliary inflammation.

Objective To investigate the activation state of and expressions of surface co-stimulatory molecules on peripheral CD4+ T cells from patients with pemphigus and healthy human controls.Methods Ninety patients with pemphigus including 24 patients with first-onset pemphigus,51 with quiescent pemphigus and 15 with recurrent pemphigus,as well as 30 healthy human controls were enrolled in this study.Peripheral blood samples were obtained from these subjects followed by lymphocyte isolation.Flow cytometry was performed to detect the expressions of CD69,intercellular adhesion molecule-1 (ICAM-1),inducible co-stimulatory molecule (ICOS),CD40 ligand (CD40L) and OX40 on CD4+ T cells.Statistical analysis was done by Mann-Whitney test using Graphpad 5.0 software.Results The expression rate of CD69 on peripheral CD4+ T cells from the healthy human controls was significantly lower than that from patients with pemphigus,patients with first-onset pemphigus,patients with quiescent pemphigus,and patients with recurrent pemphigus ((1.26 ± 0.19)％ vs.(2.46 ± 0.19)％,(2.77 ± 0.40)％,(2.15 ± 0.25)％ and (2.36 ± 0.35)％,all P ＜ 0.05).The patients with pemphigus also showed a significant increase in the expression rates of ICAM-1,CD40L and OX40 compared with the healthy human controls ((55.88 ± 1.67)％ vs.(47.75 ± 2.52)％,P＜ 0.05; (2.23 ± 0.22)％ vs.(0.73 ± 0.07)％,P＜ 0.01; (2.55 ± 0.29)％vs.(0.62 ± 0.17)％,P ＜ 0.01).No significant differences were observed between patients with different stages of pemphigus in the expression rates of CD69,ICAM-1,CD40L or OX40 (all P ＞ 0.05).The percentage of ICOS-expressing CD4+ T cells was significantly up-regulated in only patients with first-onset pemphigus as compared to the healthy controls ((3.73 ± 0.60)％ vs.(2.39 ± 0.16)％,P ＜ 0.05).Conclusions The peripheral blood CD4+ T cells from patients with pemphigus are in a relatively active state with up-regulated surface expressions of many costimulatory molecules,suggesting that CD4+ T cells are involved in the initiation and progression of pemphigus by interacting with B cells through co-stimulatory molecules.

This paper is aim to investigate the pharmacokinetics and absolute bioavailability of neoline in Beagle dogs, and provide a theoretical basis for further study. Ethyl acetate was used for liquid-liquid extracting after 10% ammonia alkalizing. The method of UPLC-Q-TOF-MS was established for the determination of neoline plasma concentrations. Beagle dogs were orally or intravenously administered with neoline for pharmacokinetic and absolute bioavailability study. Good linear relationship of neoline was found over the range of 0.1-4 mg x L(-1) (R2 = 0.9982) and 2-100 microg x L(-1) (R2 = 0.9945). Intra-and inter-day precision, expressed as the relativestandard (RSD) were less than 5.0%. Accuracy, expressed as the relative error (RE) was within 90.0%-115%. The recovery of neoline in dog plasma was more than 80%. After 6 mg x kg(-1) for ig and 1 mg x kg(-1) for iv administration of neoline, the main pharmacokinetic parameters were analyzed with Winnonlin software. t(1/2) were (313.88 +/- 63.18), (236.33 +/- 229.84) min, and AUC(0-infinity) were (58,027.40 +/- 14,132.69), (473,578.02 +/- 82,333.08) min x microg x L(-1) for ig and iv administration respectively. The absolute bioavail ability was (73.15 +/- 10.29) %. The method of UPLC-Q-TOF-MS described in the report was sensitive, reliable and specific, and suitable for pharmacokinetic study of neoline in Beagle dog. The high absolute bioavailability of neoline in dog suggested good absorption of neline which was worth of further investigation.
Aconitine ; analogs & derivatives ; chemistry ; pharmacokinetics ; Animals ; Biological Availability ; Dogs ; Drug Stability ; Female ; Male

OBJECTIVE: To analyze the features of drowning victims with psychiatric disorders to support further investigation on such cases. METHODS: One hundred and five archives of drowning victims with psychiatric disorders from January 2010 to June 2014 in Harbor Public Security Subbureau, Shanghai Public Security Bureau were reviewed. The decedents' general information, autopsy findings, case investigation data and disease histories were statistically analyzed. RESULTS: Of the 105 cases, 104 were suicides. Most decedents were poorly educated. Most suicides occurred in warm climate, and the corpses were usually found within 2 days. Most decedents had no suicide history and notes, but had abnormal mental or behavior changes before suicide. Depression, depression status and schizophrenia were the main types of psychiatric disorders, and only 9 decedents had received regular therapies before their deaths. CONCLUSION Mental disorder is a high risk factor in the drowning victims. Guardians should be aware of psychotic abnormal behaviors, especially during warm climate seasons.
China/epidemiology* ; Depression/epidemiology* ; Depressive Disorder/epidemiology* ; Drowning/psychology* ; Female ; Humans ; Male ; Mental Disorders/psychology* ; Psychotic Disorders ; Retrospective Studies ; Risk Factors ; Schizophrenia ; Seasons ; Suicide/statistics & numerical data*

The Z-drugs (zolpidem, zopiclone, and zaleplon), as the innovative hypnotics, have an improvement over the traditional benzodiazepines in the management of insomnia. Z-drugs have significant hypnotic effects by reducing sleep latency and improving sleep quality, though duration of sleep may not be significantly increased. As benzodiazepines, Z-drugs exert their effects through increasing the transmission of γ-aminobutyric acid. Z-drugs overdose are less likely to be fatal, more likely would result in poisoning. Z-drugs can be detected in blood, urine, saliva, and other postmortem specimens through liquid chromatography-mass spectrometry techniques. Zolpidem and zaleplon exhibit significant postmortem redistribution. Z-drugs have improved pharmacokinetic profiles, but incidence of neuropsychiatric sequelae, poisoning, and death may prove to be similar to the other hypnotics. This review focuses on the pharmacology and toxicology of Z-drugs with respect to their adverse effect profile and toxicity and toxicology data in the field of forensic medicine.
Acetamides/poisoning* ; Azabicyclo Compounds/poisoning* ; Drug Overdose ; Forensic Medicine/trends* ; Forensic Toxicology/trends* ; Humans ; Hypnotics and Sedatives/poisoning* ; Piperazines/poisoning* ; Pyridines/poisoning* ; Pyrimidines/poisoning* ; Sleep Initiation and Maintenance Disorders/drug therapy* ; Zolpidem

Depression is a heterogeneous disease.The heterogeneity of depression is mainly manifested in morbidity,pathogenesis,clinical manifestation,treatment and prognosis.Heterogeneity of depression has brought great difficulties to the treatment.In the field of the study and treatment of depression has not to receive attention.This paper reviews the influencing factors,clinical manifestations and possible mechanisms of depression heterogeneity,and focus on how to design a more effective individualized scheme for depressive heterogeneity from the perspective of "precision medicine".

Objective To observe the abdominal ultrasonic manifestations of children with Langerhans cells histiocytosis (LCH).Methods Imaging features of histopathologically proved LCH in 28 children were retrospectively analyzed.Results Among 28 eases,multi system involvement was found in 25 cases,while only liver and bile duct involvement were detected in 3 cases.Different degrees of enlarged liver,inhomogeneous echo of liver parenchyma,scattered or diffuse hypoechoic regions were found in all 28 cases.Uneven thickening and echo enhancement of the bile duct wall,as well as local expansion or stricture of bile duct cavity were found in 13 cases.Splenomegaly was found in 17 cases,swelling of the pancreas was found in 5 cases,varying degrees of ascites were found in 13 cases,and hepatic hilar lymphadenectasis were found in 14 cases.Conclusion There are specific ultrasonographic manifestations of LCH in children,which may be helpful to improving diagnostic accuracy of LCH.