To investigate whether accelerated blood clearance (ABC) phenomenon could be induced after repeated injection of mitoxantrone thermosensitive liposomes, LC-MS/MS and enzyme linked immunosorbent assay (ELISA) were used to measure the concentration of mitoxantrone and the anti-polyethylene glycol (PEG) IgM levels in rat plasma, separately. The drug was rapidly cleared away after the second administration. The anti-PEG IgM was detected after the first dose which was neutralized quickly after the second dose. It is proved that repeated administration of mitoxantrone thermosensitive liposomes in rat caused the ABC phenomenon.

Animals ; Antineoplastic Agents, Phytogenic ; pharmacology ; Calmodulin ; drug effects ; physiology ; Cell Communication ; drug effects ; Cyclic AMP ; physiology ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Neoplasms ; pathology ; physiopathology ; Signal Transduction ; drug effects ; Tumor Cells, Cultured

Objective To investigate the role of calreticulin (CRT) in the pathogenesis of rheumatoid arthritis (RA) by analyzing its expression in the sera,synovial fluid and synovial membrane in patients with RA.Methods Levels of CRT in the sera from patients with RA,osteoarthritis (OA),systemic lupus erythematosus (SLE),other autoimmune diseases and health control (HC) were detected by enzyme linked immunosorbent assay (ELISA) and Western bloting.CRT levels in synovial fluid from RA and OA patients were measured by ELISA.Pathological methods were employed to analyze the expression and localization of CRT in synovial membrane.ANVOA,SNK-q test were used for statistical analysis.Results CRT was found to be significantly up-regulated in sera from RA [(4.8±2.4) ng/ml] than that from in OA [(3.6±0.9)ng/ml],SLE [(4.0±1.5) ng/ml],other autoimmune diseases [(3.9±0.8) ng/ml] and HC [(3.7±0.6) ng/ml].Only the monomer form of CRT in the serum could be detected.Pathological results showed that in RA synovium,CRT was mainly expressed in the lining and sublining layers,endothelial cells and perivascular areas； while in OA,only few CRT staining was seen in perivascular areas and the synovial lines.Conclusion In RA,increased levels of CRT are detected in the sera.In addition,high expression of CRT is observed in synovium and its distribution are different from OA.Our results suggest that CRT may be involved in RA joint inflammation and pannus formation.CRT may become a potential serological marker in the diagnosis of RA.

Objective To explore the clinical value of serum κ/λ ratio in the differential diagnosis of multiple myeloma (MM) and primary nephritic,and to explore its relationship with MM other laboratory markers.Methods We obtained 88 cases of MM patients with serotyping by immunofixation and 109 cases of primary nephritic patients.In accordance with the composition of protein M in immunofixation electrophoersis (IFE),88 patients were divided into 4 groups:IgGκ,IgGλ,IgAκ and IgAλ.In addition,45 serum samples of health examination were collected as control samples.The levels of serum IgG,IgA,IgM,light chain κ and λ in each group were tested by immune turbidimetry,and κ/λ ratio was calculated.The levels of serum β2-microglobin (β2-MG),albumin (ALB),serum urea (BUN),creatinine (CRE),and M protein percentage were also detected.Results (1) In MM group,there was no significant difference of sex and International Staging System (ISS) stages between each type(P ＞ 0.05),while there was significant difference in age distribution between each type (P ＜ 0.05).(2) Compared to control,the levels of se-rum light chain κ,κ/λ ratio,and matched Ig were significantly higher and the level of light chain λ and other Ig were significantly lower in κ typed MM patients,while the levels of serum light chain λ were significantly higher and the levels of serum light chain κ,and κ/λ ratio were significantly lower in λ typed MM patients(P ＜0.01).The levels of light chain κ,λ,and IgG in primary nephritic patients were significantly lower than control(P ＜0.01),while there was no significant difference in κ/λ ratio between two group (P ＞ 0.05).There were also significant difference of light chain,Ig,BUN and CRE levels between MM patients and primary nephritic patients (P ＜ 0.05).(3) The κ/λ ratio correlated with serum ALB (r =-0.264,P =0.013) and β2-MG (r =0.235,P =0.040) levels in MM.Conclusions Serum levels of light chain κ,λ,and κ/λ ratio have great significance in the differential diagnosis of multiple myeloma and primary nephritic.The κ/λ ratio correlated with several tumor markers in MM progresses,rendering it as a promising method for diagnosis and prognosis monitoring of MM.

To investigate whether accelerated blood clearance (ABC) phenomenon could be induced after repeated injection of mitoxantrone thermosensitive liposomes, LC-MS/MS and enzyme linked immunosorbent assay (ELISA) were used to measure the concentration of mitoxantrone and the anti-polyethylene glycol (PEG) IgM levels in rat plasma, separately. The drug was rapidly cleared away after the second administration. The anti-PEG IgM was detected after the first dose which was neutralized quickly after the second dose. It is proved that repeated administration of mitoxantrone thermosensitive liposomes in rat caused the ABC phenomenon.
Animals ; Antineoplastic Agents ; administration & dosage ; blood ; pharmacokinetics ; Chromatography, High Pressure Liquid ; Immunoglobulin M ; blood ; Liposomes ; administration & dosage ; blood ; pharmacokinetics ; Male ; Metabolic Clearance Rate ; Mitoxantrone ; administration & dosage ; blood ; pharmacokinetics ; Polyethylene Glycols ; administration & dosage ; chemistry ; pharmacokinetics ; Rats ; Rats, Wistar ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry

OBJECTIVETo observe the clinical effects of Qiyao Xiaoke Capsule (QXC) on patients with type 2 pre-diabetes.

METHODSTotally 116 pre-diabetes patients were randomly assigned to the Chinese medicine group (CM, 76 cases) and the blank control group (BC, 40 cases) in the ratio of 2: 1. All patients received proper diet control, health education, and exercises, and so on. Besides, patients in the CM group took QXC (0.4 g/pill), 6 pills each time, three times a day. But patients in the BC group were intervened by life style alone. The fasting blood glucose (FBG), postprandial blood glucose (PBG), insulin (FINS, 2h INS), glycosylated hemoglobin (HbAlc), blood lipids (TG, TC, HDL-C, and LDL-C), and efficacy of CM symptoms were observed in the two groups before and after intervention. The sequelae were observed at the end of the treatment and at follow-ups.

RESULTSAfter treatment FBG, PBG, and HbA1c decreased in all patients of the two groups (P<0.05, P<0.01), with 2 h PBG decreased more significantly. But there was no statistical difference between the two groups (P>0.05). The two methods could improve the secretion of FINS. Especially 2 h INS decreased more significantly in the CM group, showing statistical difference when compared with the BC group (P<0.05). The two methods could improve the metabolism of blood lipids. CM could significantly lower TG and elevate HDL-C, showing statistical difference when compared with before treatment (P<0.05). After treatment the CM symptoms were obviously improved, showing statistical difference when compared with the BC group (P<0.05). The normalization rate was better in the CM group than in the BC group at the end of the treatment and at follow-ups (P<0.05).

CONCLUSIONSQXC combined life style intervention could improve fasting and postprandial insulin secretion of type 2 pre-diabetes patients, regulate glycolipid metabolism, correct the insulin resistance state, and improve the symptoms of qi-yin insufficiency. It could postpone or hinder the occurrence and development of type 2 diabetes. It was more effective and durable than changing the life style alone.

Adult ; Diabetes Mellitus, Type 2 ; prevention & control ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Life Style ; Male ; Middle Aged ; Phytotherapy ; Prediabetic State ; drug therapy

BACKGROUNDNitroglycerin (NTG) is one of the few immediate treatments for acute angina. Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme in the human body that facilitates the biological metabolism of NTG. The biological mechanism of NTG serves an important function in NTG efficacy. Some reports still contradict the results that the correlation between ALDH2 gene polymorphisms and NTG and its clinical efficacy is different. However, data on NTG measurement by pain relief are subjective. This study aimed to investigate the influence of ALDH2 gene polymorphism on intervention with sublingual NTG using noninvasive hemodynamic parameters of cardiac output (CO) and systemic vascular resistance (SVR) in Northern Chinese Han population.

METHODSThis study selected 559 patients from the Affiliated Hospital of Qingdao University. A total of 203 patients presented with coronary heart disease (CHD) and 356 had non-CHD (NCHD) cases. All patient ALDH2 genotypes (G504A) were detected and divided into two types: Wild (GG) and mutant (GA/AA). Among the CHD group, 103 were wild-type cases, and 100 were mutant-type cases. Moreover, 196 cases were wild-type, and 160 cases were mutant type among the NCHD volunteers. A noninvasive hemodynamic detector was used to monitor the CO and the SVR at the 0, 5, and 15 minute time points after medication with 0.5 mg sublingual NTG. Two CO and SVR indicators were used for a comparative analysis of all case genotypes.

RESULTSBoth CO and SVR indicators significantly differed between the wild and mutant genotypes at various time points after intervention with sublingual NTG at 5 and 15 minutes in the NCHD (F = 16.460, 15.003, P = 0.000, 0.000) and CHD groups (F = 194.482, 60.582, P = 0.000, 0.000). All CO values in the wild-type case of both NCHD and CHD groups increased, whereas those in the mutant type decreased. The CO and ΔCO differences were statistically significant (P < 0.05; P < 0.05). The SVR and ΔSVR changed between the wild- and mutant-type cases at all-time points in both NCHD and CHD groups had statistically significant differences (P < 0.05; P < 0.05).

CONCLUSIONALDH2 (G504A) gene polymorphism is associated with changes in noninvasive hemodynamic parameters (i.e. CO and SVR) after intervention with sublingual NTG. This gene polymorphism may influence the effect of NTG intervention on Northern Chinese Han population.

Aged ; Aldehyde Dehydrogenase ; genetics ; Aldehyde Dehydrogenase, Mitochondrial ; Asian Continental Ancestry Group ; Female ; Hemodynamics ; drug effects ; genetics ; physiology ; Humans ; Male ; Middle Aged ; Nitroglycerin ; pharmacology ; Polymorphism, Genetic ; genetics

OBJECTIVEUsing olfactory event related potentials (OERP) and magnetic resonance to evaluate olfactory function in patients with posttraumatic anosmia.

METHODSTwenty four patients with posttraumatic anosmia were reviewed retrospectively. A thorough medical history, physical examination, nasal endoscopy, T&T olfactory testing, olfactory event-related potentials, brain computed tomography scan and magnetic resonance image of olfactory pathway were performed in all patients.

RESULTSSubjective olfactory testing indicated 20 of 24 patients were birhinal anosmia, 2 with right nostril anosmia and left impairment, 2 with left anosmia and right normal. No OERP were obtained in 24 (20 were birhinal, 4 was monorhinal), except 4 cases with single nostril. Magnetic resonance imaging revealed the injures to the olfactory bulbs (100%), rectus gyrus (91.7%), orbital gyrus (67%), olfactory tracts (8%) and temporal lobes (8%).

CONCLUSIONSOERP can objectively evaluate posttraumatic olfactory function, and magnetic resonance of olfactory pathway can precisely identify the location and extent of injures.

Adult ; Craniocerebral Trauma ; complications ; Evoked Potentials ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Olfaction Disorders ; etiology ; pathology ; physiopathology ; Retrospective Studies

Objective To learn the prevalence of overweight and obesity among city residents in Wenzhou city.Methods Byusing multistage stratified cluster sampling method,a total of 10 449 residents aged 18 years and above were selected forquestionnaires interview,physical examination and laboratory testing ,analyzed the prevalence and risk factors of overweightand obesity among city residents.Results The crude prevalence rates of overweight and obesity were 32.60% and7.70%,and the age -adjusted rate were 27.50% and 6.51%.The multivariate logistic regression analysis showed that age(OR =1.01,95%CI:1.01 -1.02)and drinking (OR =1.14,95%CI:1.02 -1.27)were risk factors of overweight andobesity,while high degree of education(OR =0.87,95%CI:0.84 -0.91)and active physical exercise (OR =0.75,95%CI:0.57 -0.98)were protective factors of overweight and obesity.The prevalence rates of hypertension,diabetes,dyslipidemia and hyperuricemia were much higher among adults with overweight and obesity,compared with that of normalweight adults (P <0.01).Conclusion Prevalence of overweight and obesity is high in Wenzhou City.Intervention shouldbe actively carried out for the prevention and control of overweight and obesity.

To characterize the genomic sequence and arrangement of WU polyomavirus (WU virus) identified in clinical specimens collected from children with acute respiratory infections in Beijing, China, the sequences of capsid proteins VP1, VP2, and the large tumor antigen (LTAg), as well as the 5'-terminal sequence of WU virus, were amplified from the clinical specimen with ID number of BJF5276 which was determined as WU virus positive by PCR amplification. The PCR amplicons were sequenced, and genomic sequence analysis was performed by using the software DNAStar. In addition, VP2 coding-region sequences were amplified from other 21 clinical specimens identified as WU virus positive to investigate the gene diversity of WU virus. The genomic sequence of WU virus BJF5276 with accession number of HQ218321 in GenBank was 5,229 base pairs in length with 3 major coding domain sequences (CDS) sited on one strand coding for capsid proteins VP2, VP3 and VP1, and two CDS sited on the complementary strand coding for small tumor antigen (STAg) and LTAg; These 22 VP2 CDS sequences including 5 sequences submitted to GenBank were compared with 64 corresponding sequences downloaded from GenBank by MegAlign of DNAStar software, indicated that these sequences coming from children in Beijing shared high homology (over 98.8%) with those from GenBank. Phylogenetic analysis of these VP2 CDS by using Neighbor-joining (NJ) analyses with 2,000 bootstraps (Mega 4.0) showed that 20 sequences out of 22 belonged to clade Ia, and other 2 of them belonged to clade III, including 1 clustered in IIIa and 1 in a novel cluster proposed as IIIc. In conclusion, the genomic sequence of WU polyomavirus detected from clinical specimens from children in Beijing is closely related to other WU polyomaviruses in the feature of genomic coding region arrangement. Overall variation of VP2 CDS was very low, and there were different clades circulating in Beijing with a dominant clade Ia, which is different from dominated Ib circulating in other parts of the world reported previously, and a novel clade IIIc was proposed.
Acute Disease ; Child, Preschool ; China ; Female ; Genome, Viral ; Humans ; Infant ; Male ; Molecular Sequence Data ; Phylogeny ; Polyomavirus ; classification ; genetics ; isolation & purification ; Respiratory Tract Infections ; virology ; Viral Proteins ; genetics