Multiple myeloma (MM) is a hematological malignancy caused by the clonal expansion ofbone marrow plasmacytes.It accounts for 10 ％ of all hematological malignancies.The proteasome,an intracellular enzyme complex that degrades ubiquitin-tagged proteins to regulate protein levels within the cell,plays an important role in maintaining cellular homeostasis.Proteasome inhibitors proved to be significantly effective in the clinical treatment of MM.In recent years,the application of the proteasome inhibitor has led to increased survival rates in MM patients.Bortezomib is the first proteasome inhibitor that has been approved by the US Food and Drug Administration due to its ability to reversibly inhibit the 26 s proteasome functions.Despite the fact that Bortezomib improves medical treatment,many patients experience difficulty responding to this drug and some patients who do respond eventually relapse.These results have led researchers to investigate new proteasome inhibitors with mechanisms different from those of Bortezomib.Some drugs that bind to the active site of the proteasome and irreversibly inhibit the complex have recently been developed and are currently being tested in advanced clinical trials.Here,we will elaborate on the proteasome inhibitors targeting MM and focus on newly discovered inhibitors that may overcome the resistance to Bortezomib.

Objectives: To analyze the strategies of the diagnosis and treatment in patients with the pulmonary infection after renal transplantation. Methods: A retrospective analysis was made on 28 cases of pulmonary infections among 285 patients undergoing renal transplantation. Results: The morbidity of pulmonary infection was 9.82%(28/285). The majority pathogens of pulmonary infection in this study were pseudomonas, staphylococcus epidermidis, canadida and cytomegalovirus. Chest X ray was important in the diagnosis, but there was no specificity to determine the pathogens. The mortality in 28 pulmonary infection patients was 32.1%(9/28). Most of the patients suffered from pulmonary infection within 4 months after the operation, and the postoperative period from 2 months to 4 months was a high risk time window for death caused by pulmonary infections. Conclusions: The morbidity and mortality of pulmonary infections, especially severe pneumonia, in patients with renal transplantation, are higher than healthy people. Treatment following clinical epidemiology and strategy of microbiology play a very important role to reduce the mortality in those patients.

In this article we built formula database of health food containing Gardeniae Fructus with Traditional Chinese Medicine Inheritance Support System (V2.0). And on this basis, use data mining method such as association rules of the software, to analyze commonly used formula raw materials or materials combination of formula containing Gardeniae Fructus and raw material application having assisted function formula to protect chemical liver injury. The result shows that of the 71 health food formulas containing Gardeniae Fructus, most used materials are Gardeniae Fructus, Lycii Fructus, Angelica Sinensis Radix, Poria and so on. Commonly used materials combination mostly are Gardeniae Fructus and Lycii Fructus, Gardeniae Fructus and Angelica Sinensis Radix, Gardeniae Fructus and Poria, Gardeniae Fructus and Paeonia. There are nearly 18 healthcare functions of the health food containing Gardeniae Fructus, and most of these are assisted functions to protect chemical liver injury, and then immune modulating function. Of 23 formulas containing Gardeniae Fructus having assisted function formula to protect chemical liver injury, Gardeniae Fructus usually combined with traditional Chinese medicine which nourishs blood and liver such as Pueraria, Lycii Fructus, Hawthorn, Paeonia and Turnjujube. Analyzing formula raw materials application of health food containing Gardeniae Fructus contributes a lot to the further development and utilization.
Chemical and Drug Induced Liver Injury ; drug therapy ; Data Mining ; methods ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Food, Organic ; Fruit ; chemistry ; Gardenia ; chemistry ; Medicine, Chinese Traditional ; methods

Adult ; Aged ; Biomarkers, Tumor ; biosynthesis ; genetics ; Carcinoma, Hepatocellular ; metabolism ; Cell Cycle Proteins ; biosynthesis ; genetics ; Cyclin-Dependent Kinase Inhibitor p27 ; Female ; Humans ; Liver Cirrhosis ; metabolism ; Liver Neoplasms ; metabolism ; Male ; Middle Aged ; Retinoblastoma Protein ; biosynthesis ; genetics ; Tumor Suppressor Proteins ; biosynthesis ; genetics

OBJECTIVETo investigate prevalence of human immunodeficiency virus (HIV) infection and risk factors for its transmission among injection drug users (IDUs) in Liangshan Yizu Autonomous Prefecture of Sichuan Province, China.

METHODSA community-based survey was conducted to investigate demographic characteristics, pattern and frequency of sharing injection equipment, and sexual behaviors in IDUs. Blood samples were also collected from them to detect for antibodies against HIV and syphilis.

RESULTSA total of 379 subjects were recruited with informed consent for study through community outreach and peer recruiting methods. Their prevalence of HIV infection was 11.3% (43/379). Ethnicity, frequency of sharing syringes and cotton swab during the past three months and syphilis infection associated with HIV infection by univariate analysis using chi-square test. Multivariate logistic regression analysis showed odds ratio of frequency of sharing syringes for HIV infection during the past three months was 2.28 (95% CI 1.18 - 4.43), and that for syphilis infection 3.10 (95% CI 1.48 - 6.48).

CONCLUSIONFrequency of sharing syringes during the past three months associated with syphilis and HIV infection.

Adolescent ; Adult ; China ; epidemiology ; Disease Transmission, Infectious ; Female ; HIV Infections ; epidemiology ; transmission ; Humans ; Logistic Models ; Male ; Needle Sharing ; adverse effects ; Prevalence ; Sexual Behavior ; Substance Abuse, Intravenous ; virology

ObjectiveTo explore the effect of Qingfei Jiangmai decoction （QJD） on the content of mercapturic acids in urine in healthy people amid PM_2.5 （particles 2.5 microns or less in size） pollution. MethodA total of 84 healthy students of 18-30 years old in Beijing were recruited and they were randomized into the test group （42 in total， with 1 dropout） and control group （42 in total， with 3 dropouts）. During the pollution， the test group and the control group respectively took QJD granules and placebo for 7 days （1 bag/time， 2 times/day）， and another 7-day intervention with the same drugs was performed at an interval of 4 weeks. The time-activity patterns were recorded during the intervention. On-line solid phase extraction-liquid chromatography/tandem mass spectrometry （SPE-LC-MS/MS） was performed to detect the content of PM_2.5-related metabolites S-phenylmercapturic acid （SPMA）， 3-hydroxypropylmercapturic acid （3-HPMA）， 3-hydroxy-1-methylpropylmercapturic acid （HMPMA）， N-acetyl-S-（2-nitrile ethyl）-L-cysteine （CEMA）， and N-acetyl-S-（2-hydroxy ethyl）-L-cysteine （HEMA） in urine before and after intervention. Statistical analysis was followed. ResultThe content of CEMA， HEMA， 3-HPMA， and HMPMA in the test group was all higher after the intervention than before the intervention， with the significant difference in HEMA （P<0.05）. After intervention， content of HEMA and SPMA was significantly higher in the test group than in the control group （P<0.05）， and the difference in HEMA （Z=-3.614， P<0.01） and HMPMA （Z=-1.988， P<0.05） before and after invention in the test group was significantly larger than that in the control group. After the intervention， HEMA in the test group was significantly higher than that in the control group （F=7.597， P<0.01）. ConclusionDuring PM_2.5 pollution， QJD can increase the excretion of HEMA， a metabolite of ethylene oxide， in the urine of healthy people in Beijing， and enhance the detoxification process of toxic components in PM_2.5， which is of great value in preventing and treating haze-related illnesses.

OBJECTIVETo investigate the efficacy of repeat transurethral resection of tumor in patients with non-muscle invasive bladder cancer.

METHODSFrom March 2004 to August 2008, 462 patients (350 males, 112 females, aged from 35 to 83 years old) with non-muscle invasive bladder cancer, were evaluated according to tumor stage, grade and muscle or no muscle tissue in initial transurethral resected sample. One hundred and twenty-five patients underwent repeat transurethral resection of bladder tumor within 4 to 6 weeks after initial resection. Of these 125 patients 49 were Ta, 76 were T1, 58 were low grade carcinoma, 67 were high grade carcinoma and 30 were not found presence of muscle tissue in initial resected sample in patients with T1 stage.

RESULTSOf the 125 cases, 34.4% (43/125) had residual tumor and 65.6% (82/125) had no tumor on repeat transurethral resection. Of 43 cases with residual tumor 35 had non-muscle invasive tumor including 15 in Ta and 20 in T1. The patients with high grade carcinoma had more residual tumor than those with low grade carcinoma (P < 0.05). The patients with muscle tissue in initial transurethral resected sample had fewer residual tumor than those without (P < 0.05). Twelve cases (9.6%) were understated at initial resection. Six cases (4.8%) had bladder perforation and 7 (5.6%) had bleeding during repeat transurethral resection. All cases were followed up for 3 to 56 months (median 26 months), 37.2% (16/43) patients with residual tumor in repeat transurethral resection had recurrence while only 12.2% (10/82) without residual tumor in repeat transurethral resection did (P < 0.05).

CONCLUSIONSRoutine repeat transurethral resection is advised to non-muscle invasive bladder cancer patients with T1 tumor or high grade carcinoma or no muscle tissue in initial transurethral resected sample within 4 to 6 weeks after initial resection. Repeat transurethral resection could increases the stage accuracy.

Adult ; Aged ; Aged, 80 and over ; Electrosurgery ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Reoperation ; Retrospective Studies ; Treatment Outcome ; Urinary Bladder Neoplasms ; surgery ; Urologic Surgical Procedures ; statistics & numerical data

OBJECTIVETo understand the relationship between the HIV-1 viral sequence variation and host factors associated with HIV-1 disease progression.

METHODSEnv and gag fragments of HIV-1 were amplified with PCR, cloned and sequenced. Bioinformatics was employed to find the genetic variation, N-linked glycosylation, hypermutation etc. Host gene polymorphism was analysed by using restricted fragment length polymorphism (RFLP).

RESULTSSignificant difference was found in genetic divergence between Env PCR dominant and clonal sequences (0.1 and 0.06, respectively) in non-treated group, but no significant difference was found in the HAART treated group. V3 GPGQ accounted for the most part in both treated and nontreated groups, rare V3 loop such as GPGH, GQGR and GLGR was found in treated group, V3 substitutions of I/V (position 12) and Y/H (position 21) was associated with the relatively rapid progression (RRP). Glycosylation was significantly higher in RRP than in TP for Env region, GA substitution in RRP was also significantly higher than that in TP group. SDF1-3primeA and CCR2 V64I gene frequency was higher in TP than in RRP, but the difference was not significant.

CONCLUSIONDisease progression was associated with V3 AA change, glycosylation and GA substitution in env gene. SDF1-3primeA, CCR2 V64I and CX3CR1 V249I/M280T was not associated with disease progression significantly.

Adult ; Disease Progression ; Female ; Genetic Variation ; Glycosylation ; HIV Infections ; pathology ; virology ; HIV-1 ; classification ; genetics ; isolation & purification ; metabolism ; Humans ; Male ; Phylogeny ; Polymorphism, Genetic ; Receptors, Chemokine ; genetics ; env Gene Products, Human Immunodeficiency Virus ; genetics ; metabolism ; gag Gene Products, Human Immunodeficiency Virus ; genetics ; metabolism

OBJECTIVETo assess bone health in epileptic children who have been treated with topiramate (TPM) or carbamazepine (CBZ).

METHODSSixty-three epileptic children who received TPM or CBZ treatment and 36 eileptic children who did not receive any drug treatment (control group) were enrolled. Bone mineral density (BMD) at lumbar vertebrae (L1-L4) and radius-ulna was evaluated by the dual-energy X-ray absorptiometry method. Biochemical indices of bone metabolism, including serum calcium, phosphorus and alkaline phosphatase contents were measured.

RESULTSThe serum calcium content was higher in the TPM group (2.41+/-0.17 mmol/L), but it was lower in the CBZ group (2.15+/-0.26 mmol/L) than that (2.26+/-0.11 mmol/L) in the control group (p<0.05). The serum phosphorus content in both the TPM (1.55+/-0.17 mmol/L) and the CBZ groups (1.52+/-0.26 mmol/L) was significantly lower than that in the control group (1.70+/-0.30 mmol/L) (p<0.05). There were no significant differences in the serum content of alkaline phosphatase between three groups. BMD was significantly reduced in both the TPM and the CBZ groups when compared to the control group (p<0.05).

CONCLUSIONSTPM and CBZ may result in alterations in serum contents of calcium, phosphorus and alkaline phosphatase as well as BMD reduction.

Adolescent ; Alkaline Phosphatase ; blood ; Anticonvulsants ; adverse effects ; Bone Density ; drug effects ; Bone and Bones ; drug effects ; metabolism ; Calcium ; blood ; Carbamazepine ; adverse effects ; Child ; Child, Preschool ; Epilepsy ; drug therapy ; metabolism ; Female ; Fructose ; adverse effects ; analogs & derivatives ; Humans ; Male ; Phosphorus ; blood

OBJECTIVETo investigate the effect of chemically synthetic small interfering RNA (siRNA) targeting connective tissue growth factor (CTGF) on the synthesis and secretion of extracellular matrix (ECM) in hepatic stellate cells (HSC).

METHODSChemically synthetic siRNA targeting CTGF was transfected into HSC T6 (an active HSC line in rats) by oligofectamine package, and untreated HSC T6 were used as control. Total RNA and protein of the cells, after their incubation with siRNA for 24, 48 and 72 hours, were extracted, and the supernatants were collected. The expressions of CTGF and type I and III collagen genes were detected by means of reverse transcription-polymerase chain reaction (RT-PCR) and/or Western blot. Contents of hyaluronic acid and type III pro-collagen in the supernatants were determined by radioimmunoassay.

RESULTSThe expression of CTGF at mRNA and protein level and type I and III collagen at mRNA levels were markedly down-regulated in siRNA-transfected HSCs. The contents of hyaluronic acid and type III pro-collagen in the supernatants decreased by 46%+/-7%, 52%+/-7%, 53%+/-7% and 29%+/-18%, 29%+/-7%, 27%+/-5%, compared with those of the blank control at 24, 48 and 72 hours.

CONCLUSIONSChemically synthetic anti-CTGF siRNA can significantly inhibit CTGF gene expression in HSC, and markedly reduce the synthesis and secretion of ECM including type I and III collagen and hyaluronic acid. The siRNA-directed suppression of CTGF gene in HSC was maintained for 72 hours. This suggests that chemically synthetic siRNA may be a potential in preventing and treating liver fibrosis and may have a promising future for development

Cell Line ; Connective Tissue Growth Factor ; Extracellular Matrix ; metabolism ; Gene Targeting ; Humans ; Immediate-Early Proteins ; genetics ; Intercellular Signaling Peptides and Proteins ; genetics ; Liver ; cytology ; metabolism ; RNA, Small Interfering ; genetics