ABSTRACT
Objective:To investigate the value of peripheral blood eosinophils (EOS) in predicting the therapeutic effect of sublingual specific immunotherapy (SLIT) in patients with allergic rhinitis (AR).Methods:From January 2018 to June 2020, 200 patients with AR who received SLIT in Dongguan Kanghua Hospital were evaluated for their symptoms before treatment and 6 months after treatment. The curative effect was evaluated according to the improvement of the total symptom score. The number of eosinophils, percentage of eosinophils in peripheral blood were measured before treatment. The correlation between curative effect and EOS count and EOS percentage was analyzed and the value of these two indicators in predicting the efficacy of SLIT was evaluated.Results:Of the 200 AR patients, 178 patients were confirmed to have completed the treatment course of 6months. 126 effective and 52 ineffective, the effective rates were 70.8%. There was a weak correlation between the number of EOS in peripheral blood and the percentage of EOS in peripheral blood before treatment and the efficacy of SLIT ( r=0.168, P=0.048; r=0.250, P=0.001). The area under the curve of peripheral blood EOS count was 0.380, and the percentage of peripheral blood EOS was 0.355, which were all less than 0.5. Conclusions:There was no significant correlation between the number of peripheral blood EOS count and peripheral blood EOS percentage and the efficacy of SLIT , therefore, both of blood EOS count and blood EOS percentage have no value in predicting the efficacy of SLIT.
ABSTRACT
Sepsis， a common critical disease in the intensive care unit（ICU）， features high morbidity and mortality. At present， it is mainly tackled with western medicine， which may trigger a series of problems like antibiotic resistance， adverse hormonal reactions， and high cost after a long-term use. Therefore， exploring new efficient， safe， and cheap drugs and treatment modes has become the focus of our research at this stage. By virtue of unique advantages including "the concept of holism and individualized treatment based on syndrome differentiation"， Chinese medicine has accumulated quite rich experience in the prevention and treatment of sepsis. In recent years， research on the regulation of Chinese medicine on nuclear transcription factor-κB（NF-κB） signaling pathway in sepsis has kept emerging. On this basis， this paper reviewed the etiology and pathogenesis of sepsis， syndrome differentiation and treatment， NF-κB signaling pathway， and its intervention with Chinese medicine. It has been found that some single Chinese herbs and their extracts， Chinese herbal compounds， and Chinese herbal injections effectively inhibit the expression of such inflammatory factors as NF-κB-mediated tumor necrosis factor-α（TNF-α）， interleukin-1（IL-1）， and IL-6 as well as the related proteins， reduce the systemic inflammatory response and organ injury， and improve the prognosis by regulating the activation of NF-κB signaling pathway and the immune function of macrophages. However， due to the limitations of objective conditions， some studies also have the problems of fuzzy pro-inflammatory anti-inflammatory balance mechanism， unclear pharmacokinetics and low drug safety evaluation， which need to be further studied and explored in order to provide a new theoretical basis and diagnosis and treatment thinking for the treatment of sepsis with traditional Chinese medicine.
ABSTRACT
Objective:To determine the prevalence of renal function decline in the elderly population in a community and risk factors. Methods:Data in the physical examination of the elderly population aged over 60 years old in a community in 2018 were collected and analyzed. Estimated glomerular filtration rate was calculated by modified modification of diet in renal disease （MDRD） formula. Association between renal function decline and risk factors were determined. Results:Among the 9 626 elderly people， the prevalence of renal function decline was 10.71%， which increased with age. Multivariate logistic regression showed that men， age， anemia， abnormal uric acid， hypertension， hyperlipidemia， diabetes， glutamine transaminase， and the history of stroke were the independent risk factors associated with renal function decline. Conclusion:The prevalence of renal function decline in elderly people in a community in Shanghai is relatively high. It is necessary to pay attention to early screening and take effective preventive measures， such as health education， scientific exercise and reasonable diet， chronic disease management and other measures.
ABSTRACT
Objective To study the correlation between laryngopharyngeal reflux (LPR) and secretory otitis media (SOM).Methods A total of 294 adult patients with reflux-related symptoms were recruited in this study.The patients were evaluated with reflux symptom index (RSI) and reflux finding score (RFS).Tympanometry was conducted to all the patients.The 54 patients with the otitis media effusion with type B tympanograms were tested by auripuncture.Results Among the 294 patients,168 cases showed RSI＜13,in which 128 cases,31 cases and 9 cases had type A,type C,and type B tympanograms,respectively.The other 126 patients showed RSI＞13 in which 52 cases,29 cases and 45 cases had type A,type C,and type B tympanograms,respectively.Among the 294 patiems,172 patients showed RFS＜7,in which 131,32 and 9 cases had type A,type C,and type B tympanograms,respectively.The left 122 patients showed RFS＞7,in which 49,28 and 45 cases had type A,type C,and type B tympanograms,respectively.The ratio of type B tympanograms in the patients with RSI＞13 and RFS＞7 were both significantly higher than those in the patients with RSI＜13 and RFS＜7 (P＜0.05).The RSI scores of patients with type A,C,and B tympanogram were 8.6± 3.8,15.9±7.5,and 23.9±8.6,respectively,and the RFS score were 5.6±2.6,9.6±4.7,and 15.3±6.6,respectively.Compared with type A and C,the patients with type B tympanogram had significantly higher RSI and RFS score (P＜ 0.05).Among the 54 patients of type B tympanograms,those with RSI＜13 were found to have serous fluid,grume fluid,glue fluid as in 6 cases,2 cases,and 1 case,while the patient of the RSI＞ 13 had serous fluid,grume fluid,glue fluid in 13 cases,23 cases,and 9 cases,respectively.The otitis media effusion of the patients with the RSI＜13 were mainly serous,while those with the RSI＞13 were mainly sticky.Conclusion The correlation between LPR and SOM was significant.LPRmay accelerate the progress of SOM.
ABSTRACT
Objective To investigate the clinical efficacy of knife needle microinvasive operation for cervical spondylotic arteriopathy. Method Sixty patients with cervical spondylotic arteriopathy were randomized, in order of admission times, to observation and control groups, 30 cases each. The observation group received three-step knife needle microinvasive operation and the control group, single suboccipital deltoid muscle lysis. The therapeutic effects were compared between the two groups of patients. Result In the two groups of patients the score changed significantly at the end of and three months after treatment compared with before and had a tendency towards gradual increase (P<0.05). The score difference values between pre-treatment and post-treatment and between post-treatment and three-month follow-up were significantly higher in the observation group than in the control group (P<0.05). Repeated measurement analysis integrogram showed significant differences in the scores between the two groups. The total efficacy rate was significantly higher in the observation group (96.7%) than in the control group (76.7%) (P<0.05). Conclusion Knife needle microinvasive operation has clinically a marked therapeutic effect on cervical spondylotic arteriopathy.
ABSTRACT
Bromodomain-containing proteins (BCPs) can specifically recognize acetylated lysine (KAc) in histones and other substrate proteins. Recently, several kinase inhibitors were found to inhibit bromodomains, such as the PLK1 inhibitor BI-2536 and the JAK2 inhibitor TG101209, which bind to BRD4 with IC50 values of 25 nmol·L-1 and 130 nmol·L-1, respectively. To obtain potent BRD4 inhibitors from inhibitor BI-2536, we used dihydroquinoxalin-2(1H)-one to replace the 7,8-dihydropteridin-6(5H)-one in BI2536. By exploring the structure-activity relationships of the new dihydroquinoxalin-2(1H)-one structures, we obtained a novel phenyl side chain series of BRD4 inhibitors. We identified several potent BRD4 inhibitors, especially compounds 16, 22, 28 and 29, which had IC50 values below 100 nmol·L-1 in fluorescence anisotropy (FA) assays, indicating this series of compounds are worth to fruther investigation.
ABSTRACT
The purpose of the experiment was to study the efficacy of edaravone in enhancing flap viability after ischemia/reperfusion (IR) and its mechanism.Forty-eight adult male SD rats were randomly divided into 3 groups:control group (n=16),IR group (n=16),and edaravone-treated IR group (n=16).An island flap at left lower abdomen (6.0 cm×3.0 cm in size),fed by the superficial epigastric artery and vein,was created in each rat of all the three groups.The arterial blood flow of flaps in IR group and edaravone-treated IR group was blocked for 10 h,and then the blood perfusion was restored.From 15 min before reperfusion,rats in the edaravone-treated IR group were intraperitoneally injected with edaravone (10 mg/kg),once every 12 h,for 3 days.Rats in the IR group and control group were intraperitoneally injected with saline,with the same method and frequency as the rats in the edaravone-treated IR group.In IR group and edaravone-treated IR group,samples of flaps were harvested after reperfusion of the flaps for 24 h.In the control group,samples of flaps were harvested 34 h after creation of the flaps.The content of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) were determined,and changes in organizational structure and infiltration of inflammatory cells were observed by hematoxylin-eosin (HE) staining,apoptotic cells of vascular wall were marked by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay,and the apoptotic rate of cells in vascular wall was calculated.The ultrastructural changes of vascular endothelial cells were observed by transmission electron microscopy (TEM).Seven days after the operation,we calculated the flap viability of each group,and marked vessels of flaps by immunohistochemical staining for calculating the average number of subcutaneous vessels.The results showed that the content of MDA,the number ofmulticore inflammatory cells and apoptotic rate of cells in vascular wall in the edaravone-treated IR group were significantly lower than those in the IR group.The activity of SOD,flap viability and average number of subcutaneous vessels in the edaravone-treated IR group were significantly higher than those in the IR group.All the differences were statistically significant.The ultrastructure injury of vascular endothelial cells in the edaravone-treated IR group was slighter than that in IR group.It was concluded that edaravone can significantly enhance IR flap viability and protect flap vessels,which is related to scavenging oxygen free radicals,reducing the consumption of SOD,reducing the extent of lipid peroxidation and inflammation,and protecting functional structure of vessels in the early stages of reperfusion.
ABSTRACT
<p><b>OBJECTIVE</b>To explore the feasibility of preparation of a mouse model of orthotopic colon cancer by injecting tumor cell suspension into mesenteric triangle of the cecum.</p><p><b>METHODS</b>Twenty SPF 8-week old BALB/c mice (male:female = 1:1) were used in this study. The mouse caecum was exposed by laparostomy, and suspension of mouse colon adenocarcinoma CT26. WT cells was injected into the mesenteric triangle of cecum for preparation of a mouse model of orthotopic colon cancer.</p><p><b>RESULTS</b>Mouse orthotopic colon cancer was developed by injection of tumor cell suspension into mesenteric triangle of the cecum showing a successful rate of 100%, without intestinal obstruction, and the liver, spleen, diaphragm and mesenteric lymph nodes metastasis rates were high in all the 20 experimental mice.</p><p><b>CONCLUSIONS</b>The establishment of mouse models of orthotopic colon cancer by injection of tumor cell suspension into the mesenteric triangle is a simple, rapid, and easy to master procedure, causing less damage to the colon wall, safe and with less trauma to the mice. This method may provide an ideal mouse model of orthotopic colon cancer for the study of pathogenesis as well as liver metastasis mechanisms of colon cancer.</p>
Subject(s)
Animals , Female , Male , Mice , Adenocarcinoma , Pathology , Cecal Neoplasms , Pathology , Cecum , Colonic Neoplasms , Pathology , Disease Models, Animal , Feasibility Studies , Liver Neoplasms , Lymphatic Metastasis , Mice, Inbred BALB C , Neoplasm Transplantation , MethodsABSTRACT
HSP90, which is the biomarker of cell stress and endogenous protective protein, functions as a molecular chaperone. Many client proteins of HSP90, including EGFR, Met, Raf-1, IKK and p53, play important roles in the occurrence and development of tumor. Binding of HSP90 inhibitors triggers the deactivation of HSP90, resulting in client protein degradation, and hence inhibits the tumor growth by blocking multiple targets involved in signaling of tumor proliferation. This review summarizes recent development of small molecule inhibitors bound to N-terminal of HSP90.
Subject(s)
Humans , Antineoplastic Agents , Chemistry , HSP90 Heat-Shock Proteins , Neoplasms , Signal TransductionABSTRACT
The tumor hospital has its unique resources superiority.To collect and utilize the information from tumor patients,information from their diagnosis and treatment,and biological specimens,through clinical epidemiology methods and design,would facilitate the deep development in the management and research at tumor hospitals in the new circumstances.Nantong Tumor Hospital,a first rate 3A hospital,and also one of the earliest-run specialized tumor hospitals in prefecture-level cities,possesses own basis for clinical epidemiological research,medical follow-up,and application of biobanking.In this paper we report the specific work plan and work contents,including:to establish a hospital-based cancer registry system for serving clinical epidemiology; to set up a follow-up system for clinical cases with tumor,in order to assess the effect of factors on tumor treatment and to analyse their survival rates; to build a biobank of tumor cases with perfect epidemiological information and background,fitting in with the needs of the development of translational medicine.The bottleneck problems in the work are also discussed.
ABSTRACT
The paper is aimed at studying the diversity of endophytic fungi community from Paris polyphylla var. yunnanensis, and to provide a scientific basis for the utilization value of the endophytic fungi as bioactive material resources. In the present study, endophytic fungi were isolated from roots, rhizomes and leaves of wild P. polyphylla var. yunnanensis collected from Baoshan, Heqing county and Songming city of Yunnan province, and identified and classified by morphological methods together with its ITS sequence analysis. Seven and forty-nine strains of endophytic fungi were isolated from P. polyphylla var. yunnanensis. They were identified belonging to 41 genus. In these 41 genus, 3 genus exist in root only, 12 genus only exist in rhizome and 8 genus only exist in leaf. There was difference in endophytic fungi isolated from different sample sites. Endophytic fungi diversity from rhizomes of Heqing site was the highest. Endophytic fungi similarity coefficient was low among different sites and tissues. Based on these results, it is reasonable to propose that endophytic fungi of P. polyphylla var. yannanensis from different tissue and different sample sites has a certain difference which is possibly relate to their different habitats, different structure and composition of each tissue.
Subject(s)
Biodiversity , Endophytes , Classification , Genetics , Fungi , Classification , Genetics , Liliaceae , Microbiology , Molecular Sequence Data , Phylogeny , Plant Leaves , Microbiology , Plant Roots , Microbiology , Plant Stems , MicrobiologyABSTRACT
As an extension of the structure-based drug discovery, fragment-based drug discovery is matured increasingly, and plays an important role in drug development. Fragments in a small library, with lower molecular mass and high "ligand efficiency", are detected by SPR, MS, NMR, X-ray crystallography technologies and other biophysical methods. Then they are considered as starting points for chemical optimization with the guidance of structural biology methods to get good "drug-like" lead and candidate compounds. In this article, we reviewed the current progress of fragment-based drug discovery and detailed a number of examples to illustrate the novel strategies.
Subject(s)
Computer-Aided Design , Crystallography, X-Ray , Drug Discovery , Methods , Ligands , Magnetic Resonance Spectroscopy , Peptide Fragments , Chemistry , Protein Conformation , Small Molecule Libraries , Surface Plasmon ResonanceABSTRACT
Sodium-glucose co-transporters are a family of glucose transporter found in the intestinal mucosa of the small intestine (SGLT-2) and the proximal tubule of the nephron (SGLT-1 and SGLT-2). They contribute to renal glucose reabsorption and most of renal glucose (about 90%) is reabsorbed by SGLT-2 located in the proximal renal tubule. Selectively inhibiting activity of SGLT-2 is an innovative therapeutic strategy for treatment of type 2 diabetes by enhancing urinary glucose excretion from the body. Therefore SGLT-2 inhibitors are considered to be potential antidiabetic drugs with an unique mechanism. This review will highlight some recent advances and structure-activity relationships in the discovery and development of SGLT-2 inhibitors including O-glycoside, C-glycoside, C, O-spiro glycoside and non glycosides.
Subject(s)
Animals , Humans , Benzhydryl Compounds , Chemistry , Pharmacology , Diabetes Mellitus, Type 2 , Drug Therapy , Glucosides , Chemistry , Pharmacology , Hypoglycemic Agents , Chemistry , Pharmacology , Molecular Structure , Monosaccharides , Chemistry , Pharmacology , Sodium-Glucose Transporter 1 , Metabolism , Sodium-Glucose Transporter 2 , Metabolism , Structure-Activity RelationshipABSTRACT
To obtain higher potency and specificity, a series of 7-alkoxy analogues of illudalic acid was synthesized on the base of structure-activity relationship (SAR). All of these compounds exhibited submicromolar inhibition of the enzyme when tested against human leukocyte common antigen-related phosphatase (LAR) (for example, for 15e, IC50 = 180 nmol x L(-1)). They represent the most potent small-molecule inhibitors of LAR so far. These analogues also display excellent selectivity for LAR over other protein tyrosine phosphatases (PTPs) except for the highly homologous PTPsigma. The compound 15f is of 120-fold selectivity for LAR versus PTP-1B inhibition. The development of potent enzyme-specific inhibitors is so important that they may serve both as tools to study the role of LAR and as therapeutic agents for treatment of type II diabetes.
Subject(s)
Coumarins , Chemistry , Pharmacology , Enzyme Inhibitors , Chemistry , Pharmacology , Inhibitory Concentration 50 , Molecular Structure , Receptor-Like Protein Tyrosine Phosphatases, Class 2 , Structure-Activity RelationshipABSTRACT
<p><b>OBJECTIVE</b>Pseudomonas aeruginosa is a ubiquitous and opportunistic pathogen that uses the type III secretion system (TTSS) to inject effector proteins directly into the cytosol of target cells to subvert the host cell's functions. Specialized bacterial chaperones are required for effective secretion of some effectors. To identify the chaperone of ExoS, the representative effector secreted by the TTSS of P. aeruginosa, we analyzed the role of a postulated chaperone termed Orf1.</p><p><b>METHODS</b>By allelic exchange, we constructed the mutant with the deletion of gene Orf1. Analysis of secreted and cell-associated fractions was performed by SDS-PAGE and Western blotting. Using strain expressing in trans Orf1, tagged by V5 polypeptide and histidine, protein-protein interaction was determined by affinity resin pull-down assay in combination with MALDI-TOF. The role of Orf1 in the expression of exoS was evaluated by gene reporter analysis.</p><p><b>RESULTS</b>Pull-down assay showed that Orf1 binds to ExoS and ExoT. Secretion profile analysis showed that Orf1 was necessary for the optimal secretion of ExoS and ExoT. However, Orf1 had no effect on the expression of exoS.</p><p><b>CONCLUSION</b>Orf1 is important for the secretion of ExoS probably by maintaining ExoS in a secretion-competent conformation. We propose to name Orf1 as SpcS for "specific Pseudomonas chaperone for ExoS".</p>
Subject(s)
ADP Ribose Transferases , Genetics , Metabolism , Bacterial Toxins , Genetics , Metabolism , Base Sequence , Blotting, Western , DNA Primers , Electrophoresis, Polyacrylamide Gel , Kinetics , Molecular Chaperones , Genetics , Metabolism , Protein Binding , Pseudomonas aeruginosa , Metabolism , Spectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationABSTRACT
Fragile histidine triad(FHIT) gene is a tumor suppressor gene that locates on chromosome 3p14.2.FHIT can induce cell apoptosis and inhibit cell growth by activating caspase,inhibiting PI3K-Akt-survivin signal pathway and phosphorylation of I?B-?,and binding with microtube.The inactivation of FHIT is closely related with carcinogenesis.The advances in research on the structure,biological function,relationship between inactivation and carcinogenesis,and gene therapy of FHIT are reviewed in this paper.
ABSTRACT
Objective To investigate the effects of exogenous fragile histidine triad(FHIT) gene on apoptosis of human glioma cell line U87. Methods By the method of liposome transfection,plasmids pcDNA3.1/myc-His(-)B-FHIT and pcDNA3.1/myc-His(-)B were transfected into glioma cell line U87.U87 cells were divided into three groups: U87-FHIT group,U87 cells transfected by plasmids pcDNA3.1/myc-His(-)B-FHIT;U87-vector group,U87 cells transfected by plasmids pcDNA3.1/myc-His(-)B;and blank control group,U87 cells without transfection.The expression of exogenous FHIT protein was detected by Western blot and immunofluorescence staining.The effects of FHIT on the growth characteristics of U87 were observed by MTT and flow cytometry. Results Growth inhibitory rate and apoptosis rate of the cells in U87-FHIT group were significantly higher than those in U87-vector group and blank control group(P
ABSTRACT
Cerebral arteriovenous malformation is a common cerebrovascular disease.Its exact pathogenesis remains unclear.At present,it is thought that this disease is caused by kinds of factors,including congenital and acquired factors.
ABSTRACT
<p><b>BACKGROUND</b>Schwannoma is the tumor arising mainly from the cranial and spinal nerves. Bilateral vestibular schwannoma is the hallmark of neurofibromatosis type 2 (NF2). The NF2 gene has been cloned with comprehensive analysis of its mutations in schwannoma. However, most studies focused on vestibular schwannoma. There are differences in proliferation of tumor cell and ultrastructure between vestibular and spinal schwannomas. It is unknown whether genetic alterations in vestibular schwannoma are different from those in non-vestibular schwannoma. We analyzed the loss of heterozygosity (LOH) on chromosome 22 in patients with sporadic schwannoma including vestibular and spinal schwannomas and correlated this genetic alteration with tumor proliferation.</p><p><b>METHODS</b>In 54 unrelated patients without clinical NF1 or NF2, 36 patients had sporadic vestibular schwannoma, and 18 dorsal spinal root schwannoma. Four highly polymorphic linkage to NF2 gene microsatellite DNA markers (D22S264, D22S268, D22S280, CRYB2) were used to analyze LOH. The proliferative index was evaluated by Ki-67 and proliferative cell nuclear antigen (PCNA) immunostaining. Student's t test was used to analyze the difference of the proliferative index between schwannoma with LOH and that without LOH. The difference of the frequency of LOH in vestibular and spinal schwannomas was investigated by the chi-square test.</p><p><b>RESULTS</b>Twenty-three schwannomas (42.6%, 23/54) showed allele loss. The frequency of LOH in vestibular schwannoma was significantly higher than that in spinal schwannoma (chi2 = 5.14, P < 0.05). The proliferative index of schwannoma with LOH was significantly higher than that without LOH (tki-67 = 2.97, P = 0.0045; tPCNA = 2.93, P = 0.0051).</p><p><b>CONCLUSIONS</b>LOH on chromosome 22 is a frequent event in the tumorigenesis of sporadic schwannoma. And, there is a correlation between LOH on chromosome 22 and proliferative activity in schwannoma. The frequency of LOH in vestibular schwannoma is significantly different from that in spinal schwannoma.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Cell Proliferation , Chromosomes, Human, Pair 22 , Genes, Neurofibromatosis 2 , Loss of Heterozygosity , Neurilemmoma , Genetics , Pathology , Neuroma, Acoustic , Genetics , Spinal Cord Neoplasms , Genetics , Spinal Nerve RootsABSTRACT
<p><b>OBJECTIVE</b>To study the clinical features and treatments of jugular foramen neurinomas. The approximate approach and proper exposure regions of jugular foramen tumour were discussed in this paper.</p><p><b>METHODS</b>Fourteen cases of jugular foramen neurinomas were diagnosed by CT, MRI, DSA and 3D-CT reconstruction preoperatively. The tumours were resected by far lateral infra-temporal approach. The classification and relative operative approaches were discussed.</p><p><b>RESULTS</b>Among 14 patients, total removal were achieved in 8 cases, subtotal removal in 4 cases and partial removal in the other 2 cases. All patients got good recovering. No serious complications correlating the approaches occurred except one case of facial paralysis.</p><p><b>CONCLUSION</b>The far later infratentorial approach was suggested to be more suitable for surgery upon neurinomas of jugular foramen.</p>