Pepole pay more attention to the medicinal value and health function of Monascus day by day,however,the existence of citrinin restricted the further development of Monascus products heavily. How to ruduce the content of citrinin is a problem need to be solved urgently.Briefly introduced the toxicity,the biosynthetic pathway,and the relative standards of citrinin in monascus. According to the research progress on citrinin,the strategies of citrinin control were described from the three aspects of fermentation technology,mutation breeding,and genetic engineering. The expectation about the direction of citrinin in the future was also discussed.

OBJECTIVETo evaluate the clinical efficacy and safety of phosphodiesterase 5 (PDE-5) inhibitors for erectile dysfunction (ED) in patients with diabetes mellitus and provide some evidence for the clinical treatment of the disease.

METHODSWe searched MedMed, EMbase, Cochrane Library, CNKI, Wan Fang Data, VIP and ZADL for randomized controlled trials on PDE-5 inhibitors for ED in diabetic men and evaluated the methodology of the included trials with the Jadad scale. We used the erectile function domain in the IIEF (IIEF-EF), IIEF questions (IIEF-Q) 3 and 4, SEP-2 and -3, and Global Assessment Questions (GAQ) as the main evaluation indexes and employed the Review Manager 5. 1. 0 software for meta analysis.

RESULTSA total of 13 studies were included, which were all high quality trials with Jadad score > 3. The IIEF-EF scores in 10 of the included studies were subjected to meta analysis using the random-effect model (REM), with a weighted mean difference (WMD) of 5.64 (95% CI 4.41 - 6.83, P < 0.001). The fixed-effect model (FEM) analysis of the IIEF-Q scores in 6 of the studies showed the WMD to be 0.96 (95% CI 0.83 -1.08, P < 0.001) for IIEF-Q3 and 1.11 (95% CI 0.98 - 1.25, P < 0.001) for IIEF-Q4. FEM analysis of the SEP-2 scores showed WMD = 17.67 (95% CI 12. 38 - 22. 97, P < 0.001) in 2 of the studies, and that of the SEP-3 scores WMD = 23.64 (95% CI 17. 49 - 29.79, P < 0.001) in 5 of the studies. The GAQ scores in 11 of the studies were subjected to REM analysis, with OR = 6. 20 and 95% CI 3.65 - 10.52 (P < 0.001). REM analysis was performed on the adverse reactions in 11 of the studies, with OR = 7.43 and 95% CI 4.11 - 13.44 (P < 0.001).

CONCLUSIONPDE-5 inhibitors can effectively and safely improve erectile function in patients with diabetes mellitus.

AIM: To evaluate the safety of the laser peripheral iridoplasty ( LPIP ) for the early-stage chronic primary angle-closure glaucoma ( ECPACG) .
METHODS:Sixty-five eyes of 36 patients with ECPACG received LPIP. At preoperative and postoperative, patients were examined with intraocular pressure ( IOP ) , anterior chamber, optical coherence tomography ( OCT) , visual acuity, visual field, fundus and complications. The mean follow-up was 18. 2±6. 7mo (ranged 12~24mo).
RESULTS: The preoperative average IOP were 23. 8±5.6mmHg, postoperative 1wk, 1, 3, 6, 12mo and in the last follow-up time the average IOP were 18. 7±3. 8, 17. 9±3. 2, 17. 6±3. 5, 18. 4±3. 7, 18. 6±3. 7, and 18. 6±7. 8mmHg. There was statistical difference comparing with preoperative (P<0. 05, decreasing average 6. 5±3. 1mmHg compared with the preoperative, the difference was statistically significant (t=5. 32, P<0. 05). Postoperative 1wk, 1, 3, 6mo, the trabecular-iris angle ( TIA500 ) and the angle opening distance at 500μm ( AOD500 ) had the statistical difference comparing with preoperative ( P <0.05). At Postoperative 1a and the last follow-up time, the TIA500 and AOD500 did not have statistical difference comparing with preoperative (P>0. 05). The postoperative visual acuity, visual field, fundus had not changed. There were no complications found.
CONCLUSION:LPIP is safe, and has the short time effect in the treatment of ECPACG. With elapse of time, the effect of LPIP is weakened. We can repeat the treatment.

The achievements inspection and the drive standard of our country' universities and colleges is unscientific.The inspection result and the incentive mechanism have a lot of questions.Based on some medical university,the author analyzed the indicator system's construction,proposed displaying school culture guidance value,construcing the easy and feasible achievements inspection indicator system and completing measures and so on to better inspection feedback.

Objective To study the consumption rate of qualified iodized salt at household level based on the salt surveillance results from 2004 to 2011,and to provide a scientific basis for setting up appropriate control strategies to iodine deficiency disorders.Methods Iodized salt monitoring results in Hainan Province from 2004 to 2011 were collected with retrospective method.Coverage rate of iodized salt,qualified rate of iodized salt and consumption rate of qualified iodized salt were calculated at the provincial,city(county) levels and on geographic distribution (coastal,plains and mountains).Qualified iodized salt criteria was set as (35 ± 15)mg/kg,unqualified iodized salt criteria was set as 5 to ＜ 20 mg/kg or ＞ 50 mg/kg,and criteria of non-iodized salt was set as ＜ 5 mg/kg.Results From 2004 to 2011,at provincial level,the median of iodized salt was raised from 30.25 mg/kg to 32.14 mg/kg; the iodized salt coverage rate,the qualified rate of iodized salt and the consumption rate of qualified iodized salt was raised from 77.81％ (4780/6143) to 96.06％ (5890/6132),90.48％ (4325/4780) to 98.72％(5815/5890),and 70.41％(4325/6143) to 94.83％(5815/6132),respectively.From 2004 to 2011,at city (county) level,the proportion of iodized salt coverage rate that higher than 90.00％,of qualified rate of iodized salt that higher than 95.00％ and of consumption rate of qualified iodized salt that higher than 90.00％ was raised from 44.45％(8/18) to 88.89％(16/18),16.67％(3/18) to 100.00％(18/18),and 22.22％(4/19) to 88.89％(16/18),respectively.The iodized salt coverage rate in the coastal and plain townships was raised from 70.55％(1440/2041) to 95.02％(1869/1967),and 75.36％ (1762/2338) to 96.24％(2331/2422),respectively.The iodized salt coverage rate in mountainous townships maintained at 89.46％ (1578/1764)-97.46％ (1690/1734) in the 8 years.There were 2 counties where the iodized salt coverage rate was less than 90％.There were 9 and 4 townships,where the iodized salt coverage rate was less than 90％ in coastal and plain townships,respectively,in 2011.Conclusions The rate of qualified iodized salt has been raised in Hainan Province,but part of coastal and plain townships (towns) are still serious in non-iodized salt problem.Comprehensive intervention on iodine deficiency disorders should be strengthened in these areas.

Objective To investigate the effect of rosuvastatin on the morphine tolerance in rats and the underlying mechanism.Methods Forty-eight male Sprague-Dawley rats,weighing 200-250 g,were randomly divided into 6 groups (n =8 each):control group (group C),morphine tolerance group (group MT),rosuvastatin control group (group RC),rosuvastatin 0.4 mg/kg group (group R1),rosuvastatin 2.0 mg/kg group (group R2)and rosuvastatin 10.0 mg/kg group (group R3).Morphine tolerance was induced by subcutaneous injection of morphine 10.0 mg/kg at 8:00 and 16:00 everyday for 5 consecutive days.The equal volume of normal saline was given in groups C and RC.Normal saline 10 ml/kg was injected through a gastric tube into stomach everyday at 30 min after subcutaneous injection of normal saline or morphine for 5 consecutive days in groups C and MT.Rosuvastatin 10,0.4,2.0 and 10.0 mg/kg were injected through a gastric tube into stomach everyday at 30 min after subcutaneous injection of normal saline or morphine for 5 consecutive days in groups RC,R1,R2 and R3,respectively.The paw withdrawal latency to nociceptive thermal stimulation was measured 1 day before (T1) and 1 day after morphine tolerance was induced (T2).The percentage of maximal possible effect (MPE) was calculated.The rats were sacrificed after the last measurement of pain threshold and the L5 segment of the spinal cord was removed for determination of the expression of extracellular signal-regulated kinase (ERK) and phosphorylated ERK (p-ERK)(by Western blot) and contents of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) (by ELISA).Results Compared with group C,MPE was significantly decreased at T2 and the expression of p-ERK and contents of IL-1β and TNF-α were increased in groups MT and R1 (P ＜ 0.05).Compared with group MT,MPE was significantly increased at T2 and the expression of p-ERK and contents of IL-1β and TNF-α were decreased in groups RC,R2 and R3 (P ＜ 0.05).There was no significant difference in the indicators mentioned above between groups R2 and R3,and in the expression of ERK between the six groups (P ＞ 0.05).Conclusion Rosuvastatin can attenuate the morphine tolerance in rats by inhibiting the phosphorylation of ERK and decreasing the level of IL-1β and TNF-α.

Objective To evaluate the role of expression of phosphodiesterase 4B (PDE4B) in the spinal cord in inflammatory responses in a rat model of neuropathic pain and the relationship with extracellular signal-regulated kinase (ERK).Methods Sixty healthy male Sprague-Dawley rats,weighing 180-220 g,in which intrathecal catheters were implanted at L5,6 interspace,were used.The location of catheters was confirmed 6 days later.The rats were randomly divided into 5 groups (n =12 each):sham operation group (group Sham),normal saline (NS) group,vehicle group (group Ⅴ),mismatch siRNA group (group siR-M),and PDE4B-siRNA group (group siR-B).Neuropathic pain was induced by ligation of L5 spinal nerve (SNL).In Sham group,the L5 spinal nerve was only exposed,but not ligated.Immediately after ligation and on 1,3,5,and 7 days after ligation,10 μl NS,10 μl NS,LipofectaminTM RNAiMAX,PDE4B-siRNA (2 μg/10 μl) encapsulated in mismatch siRNA and PDE4B-siRNA (2 μg/10 μl) encapsulated in LipofectaminTM RNAiMAX were injected intrathecally in Sham,NS,V,siR-M,and siR-B groups,respectively.The mechanical pain threshold was measured at 1 day before and 2,4,6 and 8 days after operation.After behavioral testing on 8th day after operation,the rats were sacrificed and the lumbar segment of the spinal cord was removed for determination of PDE4B protein,ERK and phosphor-ERK (p-ERK)expression,and TNF-α,IL-1β and IL-6 levels.Results Compared with Sham group,the mechanical pain threshold was significantly decreased at 2,4,6 and 8 days after operation in NS,V,siR-M and siR-B groups (P ＜0.05),and no significant change was found in the mechanical pain threshold at 2,4,6 and 8 days after operation (P ＞ 0.05) and the expression of p-ERK and PDE4B protein,and levels of TNF-α,IL-1β and IL-6 were increased at 2,4,6 and 8 days after operation in V and siR-M groups (P ＜ 0.05).Compared with NS group,the mechanical pain threshold was significantly increased,and the expression of p-ERK and PDE4B protein and levels of TNF-α,IL-1β and IL-6 were decreased at 2,4,6 and 8 days after operation (P ＜ 0.05),and no significant change was found in the parameters mentioned above in V and siR-M groups (P ＞ 0.05).Conclusion Up-regulation of the expression of PDE4B protein in the spinal cord is involved in the development of neuropathic pain in rats,which may be related to promoted phosphorylation of ERK in the spinal cord and enhanced inflammatory responses.

Objective To evaluate the role of phosphodiesterase 4B (PDE4B) in lipopolysaccharide (LPS)-induced release of inflammatory factors in rat microglias.Methods The pri mary cultured microglial cells were randomly divided into 5 groups (n =24 each) using a random number table:control group (group C),LPS group,vehicle group,mismatch small interfering RNA (siRNA) group and PDE4B-siRNA group.The cells were incubated for 48 h in C and LPS groups.The cells were transfected with lipofectaminTM RNAiMAX 1 μl for 48 h in vehicle group.In mismatch siRNA and PDE4B-siRNA groups,mismatch siRNA 2 μl and PDE4B-siRNA 2 μl were added to 100μl serum-free culture medium (final concentration of siRNA 20 nmol/L),respectively,lipofectaminTM RNAiMAX 1 μl was added simultaneously and the cells were then transfected for 48 h.The expression of PDE4B protein and mRNA was determined by Western blot and real-time PCR,respectively.The cells were cultured for 24 h in serum-free culture medium containing LPS 100 ng/ml in LPS,vehicle,mismatch siRNA and PDF4B-siRNA groups.Then the release of TNF-α and IL-1β was measured by ELISA and the expression of extracellular signalregulated protein kinase (ERK) and phosphorylated ERK (p-ERK) was detected by Western blot.Results Compared with C group,the expression of PDE4B protein and mRNA was significantly down-regulated in group PDE4BsiRNA (P ＜ 0.05),no significant changes were found in LPS,vehicle and mismatch siRNA groups (P ＞ 0.05),and the release of TNF-α and IU1β was increased and the expression of p-ERK was up-regulated in the other four groups (P ＜ 0.05).Compared with LPS group,the release of TNF-α and IL-1β was decreased and the expression of p-ERK was down-regulated in PDE4B-siRNA group,and no significant changes were found in vehicle and mismatch siRNA groups (P ＞ 0.05).There was no significant difference in ERK expression between the five groups (P ＞ 0.05).Conclusion PDF4B can promote LPS-induced release of inflammatory factors in rat microglias and activation of ERK is involved in the mechanism.

Adolescent ; Atrioventricular Block ; diagnosis ; therapy ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male

Peptide cyclization, a pivotal approach to modifying linear precursors of proteins and pepticles, has been used to enhance their biological activities and serum stabilities. Recently, sortase A (SrtA) from Staphyloccus aureus becomes a promising new technology for efficiently incorporating site specific modifications into proteins, conjugating the cell surface and cyclizing the linear peptides. In this study, we constructed two recombinant expression systems, one with chitin binding domain and the other with six-histidine tag and chitin binding domain on the N-terminal of SrtA, separately. The results of enzymatic kinetics indicate that the two recombinant tags do not impair the transpeptidase activity of SrtA compared with the standard reaction reported under the same reaction condition. The two synthesized peptides with N-ternimal three glycines and C-terminal penta-amino acid motif, LPETG, were cyclized using immobilized and recycled SrtA. The SrtA-based cyclization promises to represent a simple method for easy and efficient enzymatic synthesis of large cyclic peptides.
Aminoacyltransferases ; metabolism ; Bacterial Proteins ; metabolism ; Cyclization ; Cysteine Endopeptidases ; metabolism ; Enzymes, Immobilized ; metabolism ; Kinetics ; Peptides ; metabolism ; Peptides, Cyclic ; biosynthesis ; Staphylococcus aureus ; enzymology