In the research on cancer theranostics, most environment-sensitive drug delivery systems can only achieve unidirectional and irreversible responsive changes under pathological conditions, thereby improving the targeting effect and drug release performance of the delivery system. However, such irreversible changes pose potential safety hazards when the dynamically distributed delivery system returns to the blood circulation or transports to the normal physiological environment. Intelligent reversible drug delivery systems can respond to normal physiological and pathological microenvironments to achieve bidirectional and reversible structural changes. This feature will help to precisely control the drug release of the delivery system, prolong the blood circulation time, improve the targeting efficiency, and avoid the potential safety hazards of the irreversible drug delivery system. In this review, we describe the research progress of intelligent reversible drug delivery system from two main aspects: controlled drug release and prolonged blood circulation time/enhanced cellular internalization of drug.

Objective: To optimize the prescription and preparation process of "Hugan I" Orally Disintegrating Tablets, and investigate its efficacy against acute liver injury in mice. Methods: Single factor method was used for disintegrants, lubricants, and fillers screening. Taking the appearance, hardness, friability and disintegration time of the tablets as the comprehensive evaluation index, the dosage of disintegrant, micro-silica gel and magnesium stearate was selected as the investigation factor. The Box-Behnken response surface method was used to optimize the orally disintegrating tablets. Acetaminophen (APAP, 500 mg/kg) was used to replicate acute liver injury model by one-time high-dose intragastric administration to investigate the effects of orally disintegrating tablets on the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum, the content of glutathione (GSH) and malondialdehyde (MDA) and morphological changes in liver tissue. Results: The optimal prescription was as following: dry paste powder 22.00%, microcrystalline cellulose 18.00%, sorbitol 20.00%, mannitol 16.00%, Aspartame 0.50%, citric acid 0.50%, disintegration agent L-HPC 20.00%, micro-powder silica gel 2.50% and magnesium stearate 0.50%. The hardness of the orally disintegrating tablets was 4-7 kg, the mean disintegration time was about 50 s, and the mean friability was around 0.85%. Compared with the model group, there were significant differences (P < 0.01) in Biphenyl diester control group, "Hugan I" Decoction group and "Hugan I" Orally Disintegrating Tablets group, and the levels of ALT and AST in the serum of the mice were significantly decreased, The content of MDA in the liver tissue was decreased, which improved the damage of APAP to liver tissue. Conclusion: The formulation of the "Hugan I" Orally Disintegrating Tablet is feasible and easy to operate, which achieves the same effect with "Hugan I" Decoction that effectively prevent liver damage caused by acetaminophen with no significant differences.

OBJECTIVEAcupuncture has a definite therapeutic effect on chronic obstructive pulmonary disease (COPD), and the cholinergic anti-inflammatory pathway (CAP) has been shown to be involved in regulation of inflammation. In this study, we investigated whether electro-acupuncture (EA) affects the CAP in COPD.

METHODSSprague-Dawley rats were induced into COPD through exposure to cigarette smoke combined with lipopolysaccharide. EA treatment was applied at Zusanli (ST36) and Feishu (BL13) points for 30 min/d for 7 d. Seventy-two rats were randomly divided into six study groups, including normal, normal + EA, normal + α-bungarotoxin (α-BGT) (the antagonist of the nicotinic acetylcholine receptor α7 subunit (α7nAChR)) + EA, COPD, COPD + EA, and COPD + α-BGT + EA. Lung function, pathology and vagus nerve discharge were tested. The levels of acetylcholine (ACh), acetylcholinesterase (AChE), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in bronchoalveolar lavage fluid (BALF) and lung tissue were measured by enzyme-linked immunosorbent assay. The mRNA and protein expression and immunoreactivity of α7nAChR and its postreceptor inflammation signal pathway, including janus kinase 2 (JAK2), signal transducers and activators of transcription 3 (STAT3), nuclear factor-κB (NF-κB), were observed by quantitative reverse transcription-polymerase chain reaction, Western blot and immunohistochemistry.

RESULTSCompared with normal rats, there were a significant decline in lung function and discharge of the vagus nerve (P < 0.01), a marked sign of lung inflammation and an increase of ACh, AChE, IL-6 and TNF-α level in BALF or lung tissue (P < 0.05, P < 0.01) and higher expression of α7nAChR, JAK2, STAT3 and NF-κB (P < 0.05, P < 0.01) in the COPD rats. In rats receiving EA, the lung function and vagal discharge were enhanced (P < 0.01), lung inflammation was improved and the levels of ACh, AChE, IL-6 and TNF-α were decreased (P < 0.01). Further, the expression of α7nAChR, JAK2, STAT3 and NF-κB was downregulated (P < 0.05, P < 0.01). However, the above effects of EA were blocked in rats injected with α-BGT (P < 0.01).

CONCLUSIONEA treatment can reduce the lung inflammatory response and improve lung function in COPD, which may be related to its involvement in the regulation of CAP.

Objective To observe the clinical efficacy and safety of Qishen Tongluo granules in the treatment of diabetic nephropathy (DN) in stage Ⅲ.Methods One hundred and four patients with DN in stage Ⅲ were randomly divided into control and treatment groups with 52 cases per group.Control group was given potassium choride tablets 100 mg per time,qn,orally.Treatment group was given Qishen Tongluo granule 20 g per time,bid,orally.Two groups were treated for 12 weeks.The clinical efficacy,fasting plasma glucose (FPG),hemoglobin A1 c (HbA1c),homostasis model assessment of insulin resistance index (HOMA-IR),urinary albumin excretion rate (UAER),serum creatinine (SCr) and adverse drug reactions (ADR) were compared between two groups.Results After treatment,the total effective rates of treatment and control groups were 86.54％ (45 cases/52 cases) and 69.23％ (36 cases/52 cases) with significant difference (P ＜ 0.05).After treatment,the main indexes in treatment and control groups were compared:FPG were (6.54±0.68) and (7.16 ±0.74) mmol · L-1,HbA1c were (7.18 ±0.72)％ and (7.62-± 0.79)％,HOMA-IR were (4.71 ±1.06) and (5.65±1.10),UAERwere (58.34 ±16.52) and (82.15±19.05) mg· 24 h-1,SCr were (85.60 ± 15.69) and (94.25 ± 16.77) μmol · L-1,the differences were statistically significant (all P ＜0.01).The adverse drug reactions in two groups were nausea,abdominal discomfort,lack of appetite and dizziness.The total incidences of ADR were 9.62％ and 13.46％ without significant difference (P ＞ 0.05).Conclusion Qishen Tongluo granules have a definitive clinical efficacy and safety in the treatment of DN in stage Ⅲ,which can effectively improve the renal function and insulin resistanc,and reduce blood glucose.

Objective: The HPLC method was established for assessment of quality of Lasiosphaera seu Calvatia (LSC) based on the determined indicator of ergosterol. The contents of ergosterol in 42 batches of LSC were comparatively analyzed. Methods: The contents of ergosterol in LSC from different origins were determined by HPLC. The conditions were as follows: BDS Hypersil C18 column (250 mm × 4.6 mm, 5 μm); flow rate: 1.0 mL/min; detection wavelength: 282 nm; column temperature: 30 ℃; injection volume: 20 μL; mobile phase: acetonitrile (A): 0.1% formic acid (B) as the mobile phase gradient elution: 0-15 min, 95% A, 15-50 min, 100% A. Results: The HPLC method to determine the ergosterol content of puffball was established.The ranges of ergosterol contents among different samples was 0.009 9%-0.150 3%. Conclusion: The contents of ergosterol in different LSC are obviously different, and the quality of commercial LSC is not coincident. So the quality control of LSC a needs further normalization and standardization. The data in this paper would provide a reasonable reference for the quality control of LSC.

OBJECTIVETo investigate the incidence, molecular features and clinical significance of CCAAT/enhancer binding protein alpha (CEBPA) gene mutation in patients with acute myeloid leukemia (AML).

METHODSMutation analysis of the entire coding region of CEBPA gene in 206 de novo AML patients was performed by using polymerase chain reaction (PCR) followed by sequence analysis and fragment length analysis.

RESULTSOf 206 AML patients, 31 (15%) had CEBPA gene mutations, including 23 with double mutations (duCEBPA) and 8 with single mutation (siCEBPA). CEBPA gene mutations presented mainly in M2 subtype or intermediate risk patients. As compared with those with wild type CEBPA gene, patients with mutated CEBPA gene were of higher white blood cell counts [20.92(0.86-351.43)× 10(9)//L vs 8.17(0.47-295.2) × 10(9)/L, P=0.003], higher hemoglobin levels [97.5(51-128) g/L vs 80.5(13-153) g/L, P=0.015] and lower platelet counts [27.5(5-81)× 10(9)//L vs 44(3-548)× 10(9)/L, P=0.004]. Patients with CEBPA gene mutation had higher complete remission (CR) rate than those with wild type (P=0.009). While co-existing of NPM1 and siCEBPA mutations was observed in M5 subtype (2/8, 25%), NPM1 gene mutation was not present in any patients with duCEBPA mutation (0/23, 0%). Dynamic tracking analysis showed that CEBPA mutations disappeared at CR, and the same mutations re-appeared at relapse. When compared to sequence analysis, the coincidence rate of CEBPA mutations detected by fragment length analysis was 100% (54/54).

CONCLUSIONCEBPA gene mutation is a recurring genetic change in AML patients and has a certain correlation with clinical and laboratory features. It could be reliably used as a potential marker for minimal residual disease follow up. The prognostic significance of co-existing of siCEBPA with NPM1 mutations in patients with AML-M5 subtype needs further investigation.

Adolescent ; Adult ; Aged ; CCAAT-Enhancer-Binding Proteins ; genetics ; DNA Mutational Analysis ; Female ; Gene Expression Regulation, Leukemic ; Genotype ; Humans ; Leukemia, Myeloid, Acute ; genetics ; therapy ; Male ; Middle Aged ; Mutation ; Polymorphism, Restriction Fragment Length ; Prognosis ; Young Adult

OBJECTIVETo investigate a potential relationship between Solute carrier family 30 (zinc transporter) member 8 (SLC30A8) rs13266634 variant and efficacy of rosiglitazone or repaglinide in treating newly diagnosed Chinese type 2 diabetes patients.

METHODSA total of 209 diabetic patients without any antihyperglycemic history were recruited and treated with repaglinide or rosiglitazone randomly for 48 weeks (104 and 105 patients, respectively). Anthropometric measurements and clinical laboratory tests were carried out before and after the treatment. An non-synonymous variant rs13266634 was genotyped by matrix-assisted laser desorption ionization-time of flight mass spectroscopy.

RESULTSNinety-one patients in repaglinide group and ninety-three patients in rosiglitazone group completed the study. Δ value of homeostasis model assessment of beta cell function (HOMA-B) and Δ value of fasting proinsulin levels were statistically significant between three genotype groups (P=0.0149 and 0.0246, respectively) after rosiglitazone treatment. However, no genotype association was observed in the repaglinide or rosiglitazone group with other parameters.

CONCLUSIONThe SLC30A8 variant was associated with the efficacy of insulin sensitizer monotherapy on insulin secretion in patients with newly diagnosed type 2 diabetes mellitus in Shanghai, China.

Carbamates ; therapeutic use ; Cation Transport Proteins ; genetics ; China ; Diabetes Mellitus, Type 2 ; drug therapy ; genetics ; Female ; Gene Frequency ; Humans ; Hypoglycemic Agents ; therapeutic use ; Male ; Middle Aged ; Piperidines ; therapeutic use ; Polymorphism, Single Nucleotide ; Thiazolidinediones ; therapeutic use ; Zinc Transporter 8

OBJECTIVETo investigate the relationship between the vascular endothelial growth factor A gene (VEGFA) rs9369425 single nucleotide polymorphism (SNP) and type 2 diabetes in Chinese Han population.

METHODSOne thousand eight hundred and ninety two type 2 diabetes patients and 1808 controls with normal glucose were recruited in this study. Phenotypes including body mass index, waist, waist hip ratio, plasma glucose and serum insulin levels of blood obtained both at 0 and 120 minute during standard 75-gram glucose oral glucose tolerance tests, were analyzed. Insulin resistance and beta cell function were assessed by homeostasis model assessment (HOMA-IR and HOMA-B). Genotyping was performed by time-of-light mass spectrum using a Sequenom platform.

RESULTSThe frequencies of minor allele G in the diabetic patients and controls were 10.8% and 11.3% respectively. No significant difference of allele distribution was detected between the cases and controls (P=0.5086). No significant difference (P>0.05) was detected on the association between rs9369425 SNP and clinical phenotypes.

CONCLUSIONVEGFA rs9369425 was not associated with type 2 diabetes in Chinese Han population. Whether there is association in any other loci in this gene remained to be investigated.

Alleles ; Asian Continental Ancestry Group ; ethnology ; genetics ; Blood Glucose ; metabolism ; Diabetes Mellitus, Type 2 ; genetics ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Glucose Tolerance Test ; Humans ; Insulin Resistance ; genetics ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; genetics ; Population Groups ; genetics ; Vascular Endothelial Growth Factor A ; genetics

OBJECTIVETo study the clinical effificacy of electroacupuncture (EA) on treating knee osteoarthritis (KOA) of Shen ()-Sui () insuffificiency (SSI) syndrome type.

METHODSA total of 245 patients (279 knees) of KOA-SSI were randomly assigned to two groups by lottery: 141 knees in the treatment group and 138 knees in the control group. The treatment group was managed with EA at the dominant points of Neixiyan (Ex-LE4) and Waixiyan (Ex-LE5) as well as the conjugate points of Xuanzhong (GB39) and Taixi (KI3) for 30 min, once a day, with 15 days as one course; 2 courses were applied with a 5-day interval in between. The control group was treated with intra-articular injection of 2 mL hyaluronic acid into the affected joint every 7 days for 5 times in total. The clinical effects on the patients in different stages were observed, and their symptom scores of knee and contents of cytokines, including interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), prostaglandin E(2alpha) (PGE(2alpha)) and matrix metalloproteinases-3 (MMP-3), in the knee joint fluid were measured before and after treatment.

RESULTSThe study was completed in 235 patients (263 knees); four patients (7 knees) in the treatment group and six patients (9 knees) in the control group dropped out. Comparison of therapeutic effects (excellent and effective rates) between the two groups showed insignificant differences (P>0.05). Symptom scores of knee and contents of cytokines in the knee flfluid after treatment were lowered signifificantly in the patients of stage I-III in both groups (P<0.05 or P<0.01). However, the lowering of the total symptom score of knee in the patients of stage III in the treatment group was more signifificant (P<0.05).

CONCLUSIONSEA could effectively alleviate the clinical symptoms in KOA patients of stage III, showing an effect superior to that of hyaluronic acid. EA also shows action in suppressing the secretion of IL-1, IL-6, TNF-alpha, PGE(2alpha) and MMP-3 in the knee flfluid.

Aged ; Cytokines ; metabolism ; Electroacupuncture ; adverse effects ; methods ; Female ; Humans ; Male ; Matrix Metalloproteinase 3 ; metabolism ; Middle Aged ; Osteoarthritis, Knee ; diagnostic imaging ; enzymology ; therapy ; Radiography ; Syndrome ; Synovial Fluid ; enzymology ; Treatment Outcome

OBJECTIVETo compare the significance of the application of three diagnostic criteria of metabolic syndrome (MS), issued by the National Cholesterol Education Program Adult Treatment Panel II (ATPIII) in 2005, International Diabetes Federation (IDF) in 2005 and Chinese Diabetes Society (CDS) in 2004, in type 2 diabetes mellitus pedigrees.

METHODSTotally,4468 subjects (including spouses) from 715 type 2 diabetic pedigrees were selected in this study. Complete laboratory data, including blood pressure, lipid profile and plasma glucose, were collected. The prevalence rates of MS and the unity of three criteria were analyzed.

RESULTSThe prevalence rates of MS were 44.94% (2008/4468), 37.87% (1692/4468) and 23.86% (1066/4468) according to the ATPIII, IDF and CDS criteria respectively. It subsequently increased in second-degree relatives, spouses, first-degree relatives and probands (ATP III: 23.78% (117/492), 35.77% (318/889), 45.40% (1077/2372) and 69.37% (496/715); IDF: 20.53% (101/492), 31.61% (281/889), 38.74% (919/2372) and 54.69% (391/715); CDS: 8.94% (44/492), 16.99% (151/889), 25.08% (595/2372) and 38.60% (276/715); ATPIII: chi2 = 266.359, IDF: chi2 = 155.950, CDS: chi2 = 165.087, respectively, P < 0.01). The prevalence rates of MS, as defined by the ATP III and IDF criteria, were higher in females than in males (ATP III: 47.47% (1156/2435) and 41.91% (852/2033); IDF: 43.00% (1047/2435) and 31.73% (645/2033); chi2 = 13.871 and 60.169, respectively, P < 0.01), and was lower in females than in males as defined by the CDS criterion (22.38% and 25.63%, respectively, chi2 = 6.423, P = 0.011). The agreement in the diagnosis of MS using ATPIII and IDF, ATPIII and CDS, IDF and CDS was 92.93%, 75.56% and 77.21% respectively. Kappa index were 0.855, 0.484 and 0.478 respectively (P < 0.01).

CONCLUSIONATP III criterion showed the highest prevalence of MS and the percent of risk factor aggregation which best reflected the characteristics of MS in familial type 2 diabetic pedigrees.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cholesterol ; Diabetes Mellitus, Type 2 ; diagnosis ; epidemiology ; Female ; Humans ; Male ; Metabolic Syndrome ; diagnosis ; Middle Aged ; Pedigree ; Prevalence ; Reference Standards ; Young Adult