ABSTRACT
Phosphodiesterase 4 (PDE4) is an important member of the phosphodiesterase enzyme family that specifically catalyzes the hydrolysis of cyclic adenosine monophosphate (cAMP), activates the downstream phosphorylation cascade pathway by altering cAMP concentration, and is strongly associated with multiple diseases. Inhibition of PDE4 is clinically investigated as a therapeutic strategy in a broad range of disease areas, including respiratory system diseases, autoimmune disorders, central nervous system diseases, and dermatological conditions. However, the incidence of adverse reactions such as nausea and vomiting is relatively high in the marketed PDE4 inhibitors, which has stalled their clinical development. In this review, we provide an overview of the clinical progression and safety issues of the marketed PDE4 inhibitors. We also review the main causes underlying PDE4-mediated adverse effects by combining the structural analysis of the PDE4 protein, the mechanism of action of PDE4 inhibitors, and the related side effect mechanism research, aiming to provide a reference for the development of safe and effective PDE4 inhibitors.
ABSTRACT
Aim To study the reversal effect of albiflorin(AL)on multidrug resistance of human ovarian cancer and the potential mechanism. Methods The drug resistance reversal effect of AL on SKOV3/DDP cells was detected by CCK-8 kit,and the effect of AL on P-glycoprotein(P-gp)function was detected by flow cytometry. The effects of AL on MYC,WWP1 and ABCB1 in SKOV3/DDP cells were detected by RT-qPCR and Western blot. The MYC-knockdown SKOV3/DDP cell line was constructed by RNA interference technology,and its drug resistance,P-gp function and related gene and protein expression changes were investigated. Results AL had a drug resistance reversal effect on SKOV3/DDP cells and a concentration-dependent inhibitory effect on P-gp function. The inhibitory effects of AL 25,50 and 100 μmol·L-1 on ABCB1/P-gp,MYC and WWP1 were gradually enhanced. The inhibitory effect of MYCi975,a MYC inhibitor,on ABCB1/P-gp,MYC and WWP1 was stronger than or equivalent to that of AL 100 μmol·L-1 group. After knockdown of MYC in SKOV3/DDP cells,cell drug resistance,P-gp function,and related gene and protein expression were inhibited. Conclusions The drug resistance reversal effect of AL on SKOV3/DDP cells may be related to the inhibition of P-gp function and the expression of ABCB1/P-gp,MYC and WWP1,which provides an experiment base for the development of AL as a drug resistance reversal agent for the clinical treatment of ovarian cancer.
ABSTRACT
@#Objective To analyze the effect of myocardial protection between modified Del Nido cardioplegia and St. Thomas Hospital Cardioplegia in adult patients with aortic valve and mitral valve replacement. Methods From January 2014 to June 2016, 140 patients underwent aortic valve and mitral valve replacement in our hospital. According to different cardioplegia, the patients were divided into two groups including a modified Del Nido cardioplegia group (70 patients, 37 males, 33 females at mean age of 53.13±9.52 years) and a St. Thomas cardioplegia group (70 patients, 32 males, 38 females, at age of 50.71±9.29 years). We collected clinical data of the patients before operation (T1), 2 h after aortic unclamping (T2), 24 h after operation (T3) and 48 h after operation (T4). Indexes of muscle enzymes including blood center creatine kinase (CK), creatine kinase isoenzyme (CK-MB) concentration and liver function indexes including urea nitrogen (BUN), creatinine (Cr), alanine aminotransferase (ALT), aspartate aminotransferase (AST) concentrations, and compared the postoperative and follow-up clinical data. Results There was no statistical difference in age, weight, gender, ejection fraction baseline data between the two groups (P>0.05). All patients were successfully completed combined valve replacement under cardiopulmonary bypass. The cardiopulmonary time was no statistical difference between the two groups (P>0.05). However, compared with St. Thomas cardioplegia group, modified Del Nido group was less in perfusion (1.19±0.39 vs. 2.99±0.75, P<0.001), shorter in aortic clamping time (P=0.003). No statistical difference was found in defibrillation rate after resuscitation between the two groups (P=0.779). Biochemical indicators were not statistically different at different time points between the two groups (P>0.05). Conclusion Modified Del Nido cardioplegia has the same effect on myocardial protection with St. Thomas cardioplegia in adult patients. It reduces the frequency of reperfusion, and shortens the clamping time. There is no additional injury in the important organs such as liver, kidney. Modified Del Nido cardioplegia myocardial protection ability in adult heart valve surgery is feasible.
ABSTRACT
Spinal cord injury [SCI] is one of the most common causes of severe incapacity and has been associated with high health care expenditures. The present study designed to assess the effect of acetylcholine in rat brain [cortex] promotes early recovery of SCI by inhibiting monoamine oxidase enzyme. Male adult wistar rats [200-250 gram in body weight] were kept in isolated cages with 12-day and dark cycle, and were offered regular food and water [as and when required] during the day. Protocol was approved by ethics committees of Soochow University. Rats were distributed into two groups: 1] Test group: SCI group, treated with acetylcholine; 2] Control group [SCI group, not treated with acetylcholine]. SCI was induced by clipping between T12 and T13 vertebra. Rats were surrendered by decapitation, and the cortex was removed and was stored at ?80 degree C for investigation. Acetylcholine inhibited acetylcholinesterase enzyme and MAO isoform [MAO-A or -B] in the cerebral cortex. Motor function of rats after inducing SCI was tested using rotarod test, and retention time was measured at different RPM speed [low [10rpm], medium [15] and high/fast [25]] in both the groups. In the rotarod test, the rats with treated with acetylcholine had significantly more retention time as compared to control rats SCI at all rotations [10, 15 and 25 rpm]. Whereas, the rats of the control group had significantly lesser retention time as compared to rats with treated with acetylcholine at all rotations [10, 15 and 25 rpm] [p=0.003]. Our study results showed significant improvement in activity of cholinergic and monoaminergic transmission, which thereby improve motor function in rats with SCI after treatment with acetylcholine. This study results suggested, that there is need to target MAO enzyme in brain for developing effective treatment for SCI. The finding of this study gives the new idea to researchers to develop therapy for treatment of SCI based on MAO enzyme target
ABSTRACT
Objective To explore the application of plastic pancreatic stents and/or nasal biliary drainage for choledocholithiasis patients having DSBC during Endoscopic Retrograde Cholangiopancreatography (ERCP).Methods Retrospective analysis on clinical data of 57 ERCP cases aiming at choledocholithiasis patients having DSBC from January 2010 to December 2015 has been carried out. According to the guide wire cannulation in an operation, patients are divided into three groups, i.e. plastic pancreatic stents group, nasal biliary drainage group, and plastic pancreatic stents + nasal biliary drainage group, so as to observe the success rate of operation and the occurrence rate of postoperative complications, such as pancreatitis or hyperamylasemia, as well as to compare the differences between the three groups.Results Out of the 57 patients receiving ERCP, 13 patients are in the plastic pancreatic stents group, with two successful operations (15.4%), one case of hyperamylasemia (7.7%), two cases of postoperative pancreatitis (15.4%), one case of fever (7.7%) and one case of hemorrhage (7.7%); 20 patients are in the nasal biliary drainage group, with 20 successful operations (100.0%), no occurrence of hyperamylasemia or postoperative pancreatitis or other complications including hemorrhage and fever; 24 patients are in the plastic pancreatic stents + nasal biliary drainage group, with 19 ERCP operations succeeded at the first attempt (79.2%) and 5 ERCP operations succeeded at the second try (20.8%), as well as 4 cases of hyperamylasemia (16.7%), 2 cases of hemorrhage (8.3%) , no occurrence of fever cases and postoperative pancreatitis. In comparison between the three groups, the occurrence of postoperative pancreatitis and successful rate of operation show a significant difference.Conclusion By adopting plastic pancreatic stents and/or nasal biliary drainage for patients having a dififcult selective biliary cannulation during ERCP, the success rate of operation can be improved, and the occurrence of pancreatitis can also be reduced.
ABSTRACT
The ALIPORC full-text database is targeted at a specific full-text database of acupuncture literature in the Republic of China. Starting in 2015, till now, the database has been getting completed, focusing on books relevant with acupuncture, articles and advertising documents, accomplished or published in the Republic of China. The construction of this database aims to achieve the source sharing of acupuncture medical literature in the Republic of China through the retrieval approaches to diversity and accurate content presentation, contributes to the exchange of scholars, reduces the paper damage caused by paging and simplify the retrieval of the rare literature. The writers have made the explanation of the database in light of sources, characteristics and current situation of construction; and have discussed on improving the efficiency and integrity of the database and deepening the development of acupuncture literature in the Republic of China.
ABSTRACT
<p><b>OBJECTIVE</b>To prepare a specific polyclonal antibody against full-length SUN5 for detecting the expression of SUN5 in human germ cells.</p><p><b>METHODS</b>Bioinformatic methods were used to compare the full-length SUN5 and its variant SUN5β, and a short peptide was designed based on the differential region to prepare SUN5 antibody. The prepared antibody was used to detect the expression of SUN5 in Ntera-2 cells and in human germ cells by Western blotting and immunofluorescence assay.</p><p><b>RESULTS</b>The short peptide was correctly synthesized and SUN5 antibody was obtained and purified. Western blotting showed that the prepared antibody was capable of recognizing full-length SUN5 in Ntera-2 cells, and SUN5 expression was localized on the nuclear membrane and in the cytoplasm as shown by immunofluorescence assay. Using this antibody, we detected SUN5 expression in the spermatocytes, round spermatids and sperms in human germ cells.</p><p><b>CONCLUSION</b>We successfully prepared SUN5-specific antibody. SUN5 is expressed in the spermatocytes, round spermatids and sperms in human germ cells, suggesting its important role in spermatogenesis.</p>
Subject(s)
Humans , Male , Antibodies , Chemistry , Blotting, Western , Cytoplasm , Metabolism , Fluorescent Antibody Technique , Nuclear Envelope , Metabolism , Proteins , Allergy and Immunology , Metabolism , Spermatids , Metabolism , Spermatocytes , Metabolism , Spermatogenesis , Spermatozoa , MetabolismABSTRACT
Objective To investigate the health literacy about infectious diseases in urban and rural residents in Huai'an city and to provide suggestions for the intervention of health literacy in the residents.Methods Using multi -stage stratified cluster random sampling method,4000 residents aged 15 -69 years old from 8 counties were selected and investigations were carried out by Chinese Residents Health Literacy Questionnaire (2012).Results The awareness rate of health literacy about infectious diseases was 20.62%,which was slightly higher than the national level.The awareness rate of urban residents was higher than that of rural residents (63.38% vs.67.12% respectively),male residents higher than female residents (68.78% vs.62.75% respectively)and people over15 and less 30 years old higher than other age groups.There were significant differences of awareness rate among different education levels and different occupations (P<0.05 ).The awareness rates of"tuberculosis infection","the correct treatment of cough and sneeze"were relatively low. Conclusion Effective measures should focus on different groups of people,especially for the elderly,women and people with low level of education.
ABSTRACT
Objective To investigate the association of B?-fibrinogen gene-455G/A polymorphism and plasma fibrinogen levels with Henoch-Schoenlein purpura(HSP) in children.Methods Sixty-seven children(including 40 boys and 27 girls) with HSP were served as HSP group,age ranging from 5-14 years,with the average age of 9 years.Seventy healthy controls(including 37 boys and 33 girls) were served as healthy controls.Age ranging from 5-13 years,with the average age of 9 years.The B?-fibrinogen gene-455G/A polymorphism was detected in all subjects by polymerase chain reaction-restrictive fragment length polymorphism technique with restrictive enzyme HaeⅢ.Results There were a greater proportion of individuals with the AA,GA,GG genotype in the HSP group comparied with those of the healthy controls(?2=29.5 P0.05].Conclusions The B?-fibrinogen gene-455G/A mutation is correlated with HSP in children,A allele is susceptibility gene of HSP in children.The plasma fibrinogen level is related to HSP in children.
ABSTRACT
<p><b>OBJECTIVE</b>Human Parvovirus B19 (HPV B19) is a small (23 nm), non-enveloped DNA virus found in 1974. It has been proved that HPV B19 is associated with a variety of childhood diseases, such as erythema infectious, transient aplastic crisis, aplastic anemia, idiopathic thrombocytopenic purpura and arthropathy, etc. There have been no any effective vaccines to prevent HPV B19 infection so far. The HPV B19 genome is composed of 5.6 kb single strand DNA. This genome encodes a nonstructural protein NS1, two structural proteins VP1 and VP2. Most neutralizing linear epitopes of HPV B19 cluster in the VP1 unique and VP1-VP2 junction regions. Only proteins encoded by genes of the VP1 unique and VP1-VP2 junction regions can stimulate bodies to produce protective antibodies. Aim of the present study was to get the VP1 unique region gene of HPV B19 and to analyze the genetic diversity so as to further study its function and application.</p><p><b>METHODS</b>The VP1 unique region gene of HPV B19 was amplified from the serum of a child with idiopathic thrombocytopenic purpura by PCR. The purified PCR product was cloned into pGEM-T easy vector and transfected into the host strain E. coli (DH5 alpha). Positive clones were chosen and then the target gene was sequenced.</p><p><b>RESULTS</b>The target gene sequence of HPV B19 VP1 unique region was amplified and cloned successfully. It had 705 nucleotides. Compared with the relevant sequences published in Genbank, the sequencing results were revealed with two nucleotides changes in the HPV B19 VP1 unique region, but their coding amino acid were not changed.</p><p><b>CONCLUSION</b>It is suggested that genetic diversity exists in the VP1 unique region of HPV B19. Construction of the recombinant plasmid of HPV B19 VP1 unique region gene might benefit to further study.</p>
Subject(s)
Child , Humans , Capsid Proteins , Genetics , DNA, Viral , Chemistry , Genetics , Genetic Variation , Mutation , Parvovirus B19, Human , Genetics , Polymerase Chain Reaction , Sequence Analysis, DNAABSTRACT
Objective To explore the application of laparoscopy in non-traumatic acute abdominal emergency. Methods The authors retrospectively analyzed 201 cases of emergency laparoscopy between March 1999 and May 2002. Results All the 201 patients were unequivocally diagnosed during operation. Laparoscopic operations were successfully completed in 190 cases (139 cases of acute appendicitis, 21 cases of acute cholecystitis, 19 cases of upper gastrointestinal tract perforation, 10 cases of intestinal obstruction and 1 case of common bile duct stones accompanied with acute cholecystitis), with a success rate of 94.5% (190/201). The remaining 11 patients underwent a conversion to open surgery. Conclusions Emergency laparoscopic exploration can not only clarify a diagnosis for acute abdominal emergency with unknown causes but also simultaneously offer a therapeutic method in at least 90% of cases.
ABSTRACT
Objective To evaluate laparoscopic hepatectomy for the treatment of primary liver cancer. Methods Nine patients with primary liver cancers at segment Ⅱ, Ⅲ, Ⅴ, Ⅵ and at the edge of the liver underwent laparoscopic partial hepatectomy with hand-assist devices, harmonic scalpel, and Endo-GIA. Results All operations were successful including resection of tumors involving both Ⅱ and Ⅲ segments, and irregular segmentectomy, and 2 cases with additional laparoscopic splenectomy. Surgery lasted for 80～145 min. Intraoperative bleeding was 150～700 ml, with no postoperative complications. Patients were followed-up for 5～25 months with intrahepatic tumor recurrence on 3rd, 4th and 13rd month in one each respectively. Conclusion Hand-assisted laparoscopic partial hepatectomy is a safe and feasible approach for primary liver cancer in clinically selected patients.
ABSTRACT
Objective To explore the clinical effects of unilateral placement of plastic stents by ERCP for nonresectable Bismuth type IV hilar cholangiocarcinoma.Methods A prospective study was conducted in 42 patients with nonresectable Bismuth type IV hilar cholangiocarcinoma,who had unilateral insertion of plastic stents in the recent 4 years,All of the patients had successful insertion of single plastic stent by ERCP manipulation.Early results (less than 30 days) of procedure-related complications,mortality,long-term results (greater than 30 days) and survival were observed.Results All of the 42 patients had successful drainage.Mean total bilirubin value decreased from (332.3?163.4)?mol/L to (30.6?18.5)?mol/L,and complete resolution of jaundice was achieved in 61.9% (26/42)of the patients.Early comlications included papilla bleeding due to EST in 4 of 42 patients (9.5%) and acute cholangitis in 10 of 42 patients (23.8%).No procedure-related death occurred.All of the patients needed to have their stents replaced periodically,and the median duration up to the first stent replacement was 65 d,and without significant differences between the two groups in stent insertion to the left and right hepatic duct.Median duration of stent patency was 5.15 months,and median patient survival was 6.5 months,but also no significant differences were found between the two groups.Conclusions Unilateral plastic stent insertion is safe and feasible,can achieve adequate drainage for relatively long time,and can improve life quality and survival for patients with nonresectable hilar cholangiocarcinoma.