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 screen and determine the regions of copy number variation (CNV) associated with hepatocellular carcinoma (HCC) using SNP array and fluorescence quantitative PCR.

METHODSThe CNV from HCC cell line TJ3ZX-01 was analyzed using GeneChip Human Mapping 500K SNP array. According to the data obtained by SNP array analysis, four candidate amplification regions were verified in 41 primary HCC samples by fluorescence quantitative PCR.

RESULTSFour regions of copy number amplification at 1q21.2, 1q22 approximately 23.1, 7p22.1 and 22q13.1 were detected by SNP array analysis. The four candidate amplicons occurred in 56.1% (23/41) of HCC samples at 1q21.2; 80.5% (33/41) at 1q22 approximately 23.1; 75.6% (31/41) at 7p22.1 and 31.7% (13/41) at 22q13.1 analyzed with sequence tagged site (STS) markers by quantitative PCR.

CONCLUSIONIn four candidate amplification regions selected by SNP array analysis and detected by fluorescence quantitative PCR, three amplification regions show increased copy number in more than 50.0% HCC tissues. This result indicates that these amplification regions are associated with pathogenesis of hepatocellular carcinoma.

Carcinoma, Hepatocellular ; genetics ; pathology ; Cell Line, Tumor ; Chromosomes, Human, Pair 1 ; genetics ; Chromosomes, Human, Pair 22 ; genetics ; Chromosomes, Human, Pair 7 ; genetics ; DNA Copy Number Variations ; genetics ; Female ; Humans ; Liver Neoplasms ; genetics ; pathology ; Male ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; Polymerase Chain Reaction ; methods ; Polymorphism, Single Nucleotide ; Sequence Tagged Sites

OBJECTIVETo investigate the risk factors and management of anastomotic leakage after radical resection for rectal cancer and preservation of anal sphincter.

METHODSThe clinical data of 190 rectal cancer patients, undergone sphincter preserving procedures from Jan. 2004 to Jan. 2006, were analyzed retrospectively.

RESULTSThe incidence of anastomotic leakage among the 190 rectal cancer patients was 7.9% (15 patients). The leakage occurred from 2 to 17 days postoperatively and the average time of appearance was 5.8 days. Thirteen cases of anastomotic leakage were healed by conservative therapy. The treatment included nutritional support, catheter drainage of abdominal abscesses and the use of antibiotics. Healing time ranged from 10 to 60 days and the mean time was 21.8 days. The other 2 patients were healed by abdominal perineal resection and loop colostomy of transverse colon respectively. The complication of anastomotic leakage was associated with age (10.2% in older than 60 years versus 3.2% in younger than 60 years), physical status (20.7% in poor condition patients versus 5.6% in good condition patients), bowel obstruction (19.1% with obstruction versus 6.5% without obstruction), anastomotic procedure (12.2% in Parks' anastomosis versus 6.7% Dixon anastomosis), anastomotic location (9.2% for outside of peritoneal anastomosis versus 2.7 for inside of peritoneal anastomosis). The rates of anastomotic leakage in staple-line manual reinforce group and postoperative anorectal drainage group were significantly decreased than those in control groups (1.9% versus 11.4% and 2.9% versus 10.7%)(P<0.05).

CONCLUSIONSElderly patients, poor general condition, preoperative tumor obstruction, outside of peritoneal anastomosis are independent risk factors for the development of anastomotic leakage. Manual staple-line reinforce after stapled anastomosis and postoperative placement of drainage in rectum may be effective in decreasing the rate of anastomotic failure. Early and active conservative approach should be considered as the main treatment of anastomotic leakage.

Adult ; Age Factors ; Aged ; Aged, 80 and over ; Anastomosis, Surgical ; adverse effects ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Postoperative Complications ; prevention & control ; Rectal Neoplasms ; surgery ; Retrospective Studies ; Risk Factors ; Young Adult

OBJECTIVETo observe the morphological changes and the regenerating ability of the fungiform papillae and taste buds after 60Co radiation with clinical doses in rats.

METHODSThe heads, faces and necks of 30 SD rats were radiated with a large dose and one time of 60Co in the clinical radiation. The general living condition and the number and shape of the fungiform papillae and taste buds of the tongues were observed after the radiation in rats.

RESULTSIn the group of 60Co radiation, the animals had wilting, decreasing appetite, losing weight. The heads, faces and necks of animals appeared redness, peeling of hair, increasing of secretions in 5 days after the 60Co radiation. The changes reached the summit in 10 days and the general living condition of the animals recovered in 60 days. The fungiform papillae and taste buds of the animals appeared degeneration, atrophy and collapsing in 5 days after the 60Co radiation. The injuries reached the summit in 10-20 days and the fungiform papillae and taste buds regenerated partially, and the some atrophied fungiform papillae and taste buds were not regenerated in 60 days.

CONCLUSIONThe damage to fungiform papillae and taste buds of tongue following the 60Co radiation with the clinical doses was very serious. The damaged fungiform papillae and taste buds can regenerate partially, but not completely.

Animals ; Radiation Injuries, Experimental ; pathology ; Rats ; Rats, Sprague-Dawley ; Regeneration ; Taste Buds ; pathology ; radiation effects ; Tongue ; pathology ; radiation effects