Heat shock protein 90 is a new target of antitumor drug, the inhibitor of Hsp90 fight against tumor by destroy and degrade the structure of protein. In recent years, looking for Hsp90 inhibitor is not only via structure modifying of natural products, but also via high throughput screening and computer aided drug design to find and synthesize new kinds of Hsp90 inhibitor. Anyway, Hsp90 inhibitor has considered as an important biology target and to pay more and more attention. This review describes recent developments of small molecule Hsp90 inhibitors.

Objective To explore the effect and its possible mechanism of human umbilical cord mesenchymal stem cells (hUCMSCs) on bacterial growth in bronchoalveolar lavage fluid (BALF) of newborns with ventilator associated pneumonia (VAP).Methods Newborns admitted to neonatal intensive care unit (NICU) in Guangdong Women and Children Hospital Affiliated to Guangzhou Medical University from June 1,2012 to December 31,2012 were reviewed.The inclusion criteria were:(1)Positive BALF culture results.(2) Requirement of mechanical ventilation with tracheal intubation.(3) Diagnosed as ventilator-associated pneumonia.Two pieces of BALF samples of newborn were collected and randornaly divided into experimental and control group.hUCMSCs were added into the experimental group,while the same volume of conditioned medium was added into the control group.Both groups were incubated for six hours in humidified CO2 incubator at 37 ℃,then,bacterial growth was assessed by colony forming unit (CFU) counts.Levels of the antimicrobial peptides (Cathelicidin/LL-37 and human HBD-2) were determined by enzyme-linked immunosorbent assay and Western blot.Paired t-test was used for statistical analysis.Results Among the culture results of 31 newborns,there were Klebsiella pneumoniae (6 cases,19.3％),Stenotrophomonas narrow food aeromonas (6 cases,19.3％),Hemolytic staphylococci (5 cases,16.1％),Escherichia coli (3 cases,9.7％),Bacterial meningitis septicemia Elizabeth Platinum (3 cases,9.7％),Acinetobacter baumannii (3 cases,9.7％),Pseudomonas putida (2 cases,6.4％),Pseudomonas aeruginosa (1 case,3.2％),Staphylococcus aureus (1 case,3.2％) and Enterobacter cloacae (1 ease,3.2％).The CFU counts in experimental group were much less than those in control group [(2.60±0.67) ×104] CFU/ml vs [(1.18±0.32) ×105] CFU/ml,(t=-20.19,P＜0.01).Levels of Cathelicidin/LL-37 and HBD-2 in experimental group were higher than those in control group [Cathelicidin/LL-37:(8.98 ± 3.22) ng/ml vs (3.18 ± 1.57) ng/ml,t =17.79,P ＜ 0.01 ;HBD-2:(379.87±11.74) pg/ml vs (39.89±2.86) pg/ml,t=37.62,P＜0.01].Conclusions hUCMSCs had antimicrobial effect on bacterial growth in BALFs from ventilator associated pneumonia possibly by the secretion of antimicrobial peptides (Cathelicidin/LL-37 and HBD-2).

BACKGROUND: Extensive liver resection or liver transplantation operated on patients with combined hepatic cirrhosis and other complications correlates with high morbidity and mortality.Child-Turcotte-Pugh scoring system is now widely used in the assessment of liver function.This classification scheme includes three clinical indicators and two biochemical indices;however,it seems difficulty on directly evaluating functional status of hepatocytes.OBJECTIVE: To explore the practicability of bioluminescence adenosine triphosphate (ATP) determination assay to assess the functional reserve of residual hepatocytes,DESIGN,TIME AND SETTING: Case contrast study,which was carried out in the Second Affiliated Hospital,Sun Yat-sen University from January 2005 to March 2006.PARTICIPANTS: Thirty-two patients who underwent major extra-and intra hepatic surgery including liver transplantation were randomly divided into three groups based on hepatic cirrhosis grading standard,including normal group (n=7),macronodular cirrhosis group (n=9),and micronodular cirrhosis group (n=16).METHODS: Routine examination and biochemical indexes of liver were performed preoperatively,including glutamic oxalacetic transaminase (GOT) and total bilirubin (TBIL).Liver specimens were delivered by aseptic technique during operation and enzymatic digested.Cell suspension was cultured and centrifuged.Hepatocytes were counted and dispensed cell suspension to be used for ATP extraction and measurement.MAIN OUTCOME MEASURES: ATP content,preoperative biochemical parameters of liver function,and correlation between biochemical parameters and ATP content.RESULTS: The ATP content in the macronodular cirrhosis group was significantly higher than that in the micronodular cirrhosis group and normal group (P=0.000 1,0.004).While,the ATP content in the micronodular cirrhosis group was also significantly higher than that in the normal group (P=0.004).ATP content (mole/cell) wassignificantly positively correlated with serum glutamic oxalacetic transarninase (r=-0.609 3,P=0.000 2) and TBIL (r=0.614 5,P=0.000 2).CONCLUSION: ATP assay can directly evaluate functional reserve of liver parenchyma and reflect high operative risk status (HORS) and course of postoperative recovery in major hepatic resection.

Objective To investigate the effects of early intensive therapy on P cell function and long-term glycemic control in newly diagnosed type 2 diabetic patients with different recruiting fasting plasma glucose (FPG) levels.Methods A total of 382 newly diagnosed type 2 diabetic patients with FPG 7.0-16.7 mmol/L were randomly assigned to therapy with insulin in the form of continuous subcutaneous insulin infusion (CSII) or multiple daily injection (MDI) or oral hypoglycemic agents (OHA, by using gliclazide and/or metformin) for initial rapid correction of hyperglycemia.The treatments were stopped after euglycemia had been maintained for 2 weeks.The patients were followed longitudinally on diet alone for 1 year.Intravenous glucose tolerances tests (IVCTTs) were performed and blood glucose, insulin and proinsulin were measured before and after therapy as well as at 1-year follow-up.Homeostasis model assessment ( HOMA) of β cell function and insulin resistance index ( HOMA-β and HOMA-IR ) were calculated.All the patients were stratified on the recruiting FPG: stratum A (7.0 mmol/L≤ FPG < 11.1 mmol/L) , stratum B (11.1 mmol/L≤ FPG ≤ 16.7 mmol/L).Results More patients in stratum A achieved target glycemic control (94.4% vs 89.8% ) and in shorter time [(5.9 ±3.8)d vs(6.9 ±3.6)d, P <0.05] as compared with those in stratum B.B cell function represented by HOMA-β and acute insulin response ( AIR) improved significantly after intensive interventions in both stratum A and B patients.However, the remission rate at 1 year was significantly higher in stratum A patients (47.8% ) than those in stratum B (35.7%, P < 0.05).The patients treated with insulin (especially with CSII) had higher remission rates and better improvement of AIR at 1 year follow-up irrespective of the recruiting FPG (CSII or MDI vs OHA: 57.1% , 51.8% vs 32.8% in stratum A, P <0.05; 44.4% , 38.7% vs 18.6% in stratum B, P <0.05).Conclusions Compared with OHA, early short time intensive insulin treatment had more favorable outcomes on maintaining AIR and prolonged glycemic remission in newly diagnosed type 2 diabetic patients irrespective of the recruiting FPG levels.

This study was aimed to compare the effect of insulin plus rosiglitazone with that of insulin plus metformin on the level of serum N-terminal pro-brain natriuretic peptide (NT-BNP) in patients with type 2 diabetes mellitus, and to find out whether serum NT-BNP can be used as an index for predicting heart failure induced by rosiglitazone in the cases of type 2 diabetes mellitus. Sixty type 2 diabetic patients were recruited and were randomly divided into two groups: group A (n = 30) received insulin plus rosiglitazone (4 mg/d) and group B (n = 30) received insulin plus metformin. The observations covered an 8-weeks' course of treatment. Serum NT-BNP was measured at the beginning and at the end of 8 weeks. The Before-After study revealed that the level of serum NT-BNP did not change apparently in the two groups (P >0.05). There was no remarkable difference in the level of serum NT-BNP between the two groups (P>0.05). There were 3 cases with edema in the group of insulin plus rosiglitazone, but none with heart failure; in these three cases, the mean serum NT-BNP level at the end of the treatment exhibited an increase of 108.99 fmol/ml when compared with that at the beginning. Neither insulin plus rosiglitazone nor insulin plus metformin had apparent effect on the level of serum NT-BNP in the patients with type 2 diabetes mellitus. The question of whether serum NT-BNP is a predictive index of heart failure awaits answers given by more observation on type 2 diabetes mellitus patients using rosiglitazone.
Aged ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; Drug Therapy, Combination ; Female ; Humans ; Hypoglycemic Agents ; therapeutic use ; Insulin ; therapeutic use ; Male ; Metformin ; therapeutic use ; Middle Aged ; Natriuretic Peptide, Brain ; blood ; Peptide Fragments ; blood ; Thiazolidinediones ; therapeutic use

Objective:To investigate the efficacy and safety of fecal microbiota transplantation (FMT) in the treatment of irritable bowel syndrome (IBS), and to explore the effects of FMT on the gut microbiota of IBS patients.Methods:From September 2016 to August 2017, at Guangzhou First People′s Hospital, 28 hospitalized IBS patients who underwent FMT treatment were enrolled. Before FMT, four and 12 weeks after FMT, all the IBS patients completed the irritable bowel syndrome quality of life scale (IBS-QOL), irritable bowel syndrome severity scoring system (IBS-SSS) and gastrointestinal symptom rating scale (GSRS). 16S rDNA sequencing was performed before FMT and four weeks after FMT. The effects of FMT on gut microbiota diversity and microbiota structure of IBS patients were analyzed respectively from the level of phylum, family and genus, and linear discriminant analysis effect size (LEfSe) was further used to screen the different bacteria. Paired t test and paired rank sum test were used for statistical analysis. Results:Twelve weeks after FMT, the scores of the six dimensions of IBS-QOL including dysthymia, behavioral disorder, auto imagery, health concerns, eating avoidance, and relationship expansion were all lower than those before FMT (43.750, 22.656 to 56.250 vs. 48.438, 32.031 to 60.938; 37.500, 18.750 to 56.250 vs. 46.429, 21.429 to 62.500; 31.250, 14.063 to 42.188 vs. 31.250, 18.750 to 50.000; 41.667, 27.083 to 56.250 vs. 50.000, 41.667 to 66.667; 54.167, 43.750 to 72.917 vs. 66.667, 58.333 to 83.333; 8.333, 0.000 to 33.333 vs. 16.667, 8.333 to 33.333, respectively), and the differences were statistically significant ( Z=-2.157, -3.429, -2.274, -3.197, -3.042 and -2.329, all P<0.05). Twelve weeks after FMT, the scores of the two dimensions of IBS-QOL including behavioral disorder and relationship expansion were both lower than those of four weeks after FMT (37.500, 18.750 to 56.250 vs. 39.286, 19.643 to 62.500 and 8.333, 0.000 to 33.333 vs. 16.670, 2.083 to 41.667, respectively), and the differences were statistically significant ( Z=-1.998 and -2.110, both P<0.05). Four and 12 weeks after FMT, the scores of IBS-SSS and GSRS were both lower than those before FMT ((190.32±106.51), (201.43±102.48) vs. (245.93±86.10) and 5.50, 4.00 to 9.00 and 5.50, 4.00 to 8.75 vs. 7.00, 6.00 to 9.75), and the differences were statistically significant ( t=4.402 and 3.848, Z=-3.081 and -3.609; all P<0.01). No serious adverse reactions occurred in the patients after FMT. At the phylum level, after FMT the abundance of Verrucomicrobia in the feces of IBS patients was richer than that before FMT (6.74% vs. 0.37%); at the family level, after FMT the abundance of Verrucomicrobiaceae in the feces of IBS patients was richer than that before FMT (6.74% vs. 0.37%); at the genus level, after FMT the abundance of Akkermansia was richer than that before FMT (6.74% vs. 0.37%); and the differences were statistically significant (all Z=-2.589, all P=0.010). The results of LEfSe method indicated that four weeks after FMT the abundance of Akkermansia in the gut microbiota of IBS patients was richer than that before FMT (6.74% vs. 0.37%), and the difference was statistically significant (linear discriminant analysis value=4.5, P=0.049). Conclusions:FMT is safe and effective in the treatment of IBS. The mechanism may be through upregulating the diversity of gut microbiota and changing the structure of gut microbiota of IBS patients.

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OBJECTIVETo understand the prevalence of high risk sex behaviors and HIV infection status among the female sex workers (FSWs) from Vietnam in Yunnan province during a 5 year intervention project and provide evidence for the improvement of the behavior intervention among this population.

METHODSThe survey was conducted annually among Vietnamese FSWs sampled in a county near China-Vietnam border to collect the information about their demographic characteristics, high risk sex behaviors and HIV test results through questionnaire and in-depth interview by bilingual outreach team. The behavior intervention included peer advise, training, lectures, interactive games, free condom distribution. The database was set up with Excel 2003 and the results were analyzed with SPSS 16.0.

RESULTSThe condom use rates among the Vietnamese FSWs at commercial sex in last month were 1.5%, 36.0%, 67.7%, 86.5% and 90.3% (P<0.05) respectively; and the condom use rates at the latest sex were 89.5%,44.8%, 86.6%,92.5% and 99.0% respectively (P<0.05) . The HIV antibody positive rates were 7.5%, 3.6%, 5.9%, 4.0% and 3.1% respectively (P>0.05).

CONCLUSIONThe condom use rate of Vietnamese FSWs at commercial sex increased by more than 90% after the 5 year intervention project. However, the HIV-infection rate was still high. It is necessary to promote condom use among FSWs from Vietnam and their regular sex partners and strengthen the health education among clients.

Ulcerative colitis (UC) is one of types of inflammatory bowel disease with high recurrence. Recent studies have highlighted that microbial dysbiosis as well as abnormal gut immunity are crucial factors that initiate a series of inflammatory responses in the UC. Modulating the gut microbiota-intestinal immunity loop has been suggested as one of key strategies for relieving UC. Many Chinese herbal medicines including some of single herb, herbal formulas and the derived constituents have been reported with protective effect against UC through modulating gut microbiome and intestinal immunity. Some clinical trials have shown promising results. This review thus focused on the current knowledge on using Chinese herbal medicines for treating UC from the mechanism aspects of regulating intestinal homeostasis involving microbiota and gut immunity. The existing clinical trials are also summarized.