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Qi Zhu

Publications and source records attributed to Qi Zhu.

At least 19 recordsLinked to original sources
PubMed2026

Plasma Proteomics Identifies Thousand-and-One-Amino Acid Kinase 3 as a Potential Biomarker of Rheumatoid Arthritis Activity and a Novel Therapeutic Target.

OBJECTIVE: Bone destruction associated with active rheumatoid arthritis (RA) remains a major therapeutic challenge, with a lack of reliable molecular markers reflecting bone injury. This study aims to identify novel biomarkers linked to bone destruction in active RA through proteomic analysis, providing new strategies for precise monitoring and targeted therapy. METHODS: Data-independent acquisition mass spectrometry was used for proteomic quantification and bioinformatic analysis on plasma samples from 160 patients with RA and 40 healthy controls. Key proteins associated with bone destruction were screened by integrating Sharp scores with synovial single-cell RNA sequencing data and subsequently validated in two independent cohorts (N1 = 50 and N2 = 10) using enzyme-linked immunosorbent assay and multiplex immunohistochemistry. Functional studies were conducted using fibroblast-like synoviocytes (FLSs) in vitro and a collagen-induced arthritis (CIA) mouse model in vivo. RESULTS: A total of 4,998 plasma proteins were identified, with 506 showing significant differential expression between active and remitted RA. Thousand-and-one-amino acid kinase 3 (TAOK3) levels were positively associated with Sharp scores and markedly elevated in patients with active RA. Combining TAOK3 with C-reactive protein improved diagnostic accuracy for active RA (area under the curve = 0.915). High TAOK3 expression was also associated with increased relapse frequency. Functional studies showed that TAOK3 knockdown suppressed the tumor-like phenotype of FLSs and down-regulated matrix metalloproteinase 1/2/3 and cathepsin K, whereas TAOK3 overexpression promoted pannus cell-mediated bone erosion, mitigated by TAOK3-targeted inhibitor. In vivo, its inhibition showed therapeutic effects in CIA mice. CONCLUSION: TAOK3 serves as a potential biomarker for bone destruction in active RA and as a therapeutic target for precision monitoring and intervention.

Arthritis, Rheumatoid↗
PubMed2025

MWENA: a novel sample re-weighting-based algorithm for disease classification and data interpretation using extracellular vesicles omics data.

BACKGROUND AND OBJECTIVE: Extracellular vesicles (EVs), considered as a form of liquid biopsy, have gained significant attention in recent years due to their stability and the preservation of disease markers. Research studies underscore the clinical significance of molecules found in EVs, highlighting their role as communicative mediators between cells. However, analyzing this data is challenging due to noisy measurements, having far more variables than samples, and some groups (e.g., disease subtypes or experimental conditions) having much less data than others. We therefore develop an algorithm to address aforementioned challenges for the classification of imbalanced EVs omics data. METHODS AND RESULTS: We propose the EV Meta-Weight Elastic Net Algorithm (MWENA), which utilizes logistic regression with elastic net regularization for the classification and identification of EV signatures, effectively addressing the challenges posed by high-dimensional small sample sizes. To mitigate issues related to class imbalance and high noise levels, MWENA incorporates an automatic sample re-weighting function, which uses a meta-net to adaptively learn generalizable patterns directly from the data itself. We validate the MWENA algorithm on both simulated data and EVs omics data, covering six classification tasks that involve four different types of diseases (pancreatic ductal adenocarcinoma, interstitial lung diseases, colorectal cancer, and ovarian cancer) and three clinical scenarios (disease diagnosis, disease-stage screening, and disease-subtype classification). Compared to other machine learning methods, MWENA demonstrates superiority in identifying small class samples and achieves the highest scores in both sensitivity and G-means. Biological analysis is also performed to further explore the significance of selected signatures as biological markers and their roles in disease mechanisms. CONCLUSIONS: We anticipate that our proposed approach will take a modest step in harnessing EV omics data to discover biomarkers, aiding researchers in gaining a comprehensive understanding of biological processes.

Extracellular Vesicles↗
PubMed2006

Expression modification of uncoupling proteins and MnSOD in retinal endothelial cells and pericytes induced by high glucose: the role of reactive oxygen species in diabetic retinopathy.

Uncoupling proteins (UCPs) are mitochondrial transporters present in the inner membrane of mitochondria. They belong to the family of anion mitochondrial carriers. UCPs could act as proton carriers activated by metabolites and create a shunt between complexes of the respiratory chain and ATP synthase. The increased leakiness of the mitochondrial inner membrane to protons may be to minimize superoxide production by limiting the maximum Deltamu(H+). The purpose of this study was to detect UCP expression in retinal capillary cells and their modification in high levels of glucose. The role of reactive oxygen species (ROS) of mitochondria and UCPs in pathogenesis of diabetic retinopathy was investigated. Bovine retinal capillary endothelial cells and pericytes were cultured with selective culture media, respectively. Passage cells were cultured in three different glucose concentrations (5, 23, 30 mM) until passage four. ROS changes in mitochondria of these cells in different glucose concentrations were detected with scanning laser confocal microscopy (SLCM). The mitochondria membrane potential (Deltapsi), cell death rate and apoptosis rate were measured with flowing cytometry. UCP expression in retinal capillary cells was detected by immunocytochemistry. Expression and modification of MnSOD and uncoupling proteins (UCPs) in different concentrations of glucose were detected by means of semi-quantitative RT-PCR. ROS in mitochondria of both endothelial cells and pericytes increased as the glucose concentration of media increased. Deltapsi and cell death rate of endothelial cells increased also. ROS was correlated to Deltapsi and cell death rate positively in endothelial cells. No difference in Deltapsi and cell death rate among different glucose levels was found in pericytes. Apoptosis rate of endothelial cells and pericytes in high glucose levels was higher than that in lower glucose levels. UCP1 and UCP2 were expressed in cultured retinal capillary cells whereas UCP3 was not. At high levels of glucose, expression of UCP1, UCP2 and MnSOD increased to accommodate ROS production compensatively. The compensative mechanism disappeared when glucose concentration was too high (30 mM). The results of this study showed that increasing mitochondrial ROS could be induced by high glucose concentration. Those proteins related to antioxidation mechanism, such as MnSOD and UCPs, could exert compensative action to a certain extent. This compensative action was insufficient when the glucose concentration was too high.

Animals↗
PubMed2006

[Differences of Angiotensin II receptor expression between systemic and pulmonary circulation in children with left-to-right shunt congenital cardiac lesions].

OBJECTIVE: It has been shown that angiotensin converting enzyme inhibitors (ACEI) can reduce the ratio of pulmonary and systemic circulation blood flow (Qp/Qs) and thus decrease the blood flow of left-to-right shunt in children with left-to-right shunt congenital cardiac lesions. This suggests that there are differences in the expression of Angiotensin II receptors between systemic and pulmonary circulation. This study aimed to explore the differences of Angiotensin II receptors type 1 and type 2 (AT1 and AT2 receptors) expression between systemic and pulmonary circulation in children with left-to-right shunt congenital cardiac lesions. METHODS: Lung and skeletal muscular tissues were obtained from 20 children with left-to-right shunt congenital cardiac lesions by biopsy during operation. The specimens were stained by immunohistochemistry techniques for AT1 and AT2 receptors. The technique of morphometric analysis was used to measure the immunoreactivity of AT1 and AT2 receptors (expressed by IOD values) of pulmonary, skeletal muscular and pleural small vascular wall the diameter of which was 15-100 microm. RESULTS: The immunoreactivities of AT1 and AT2 receptors of pulmonary small vascular walls [(124 +/- 95)x10(3) and (85 +/- 62)x10(3) respectively] were significantly lower than those of skeletal muscular [(219 +/- 156)x10(3) and (155 +/- 139)x10(3) respectively] and those of pleural small vascular walls [(279 +/- 191)x10(3) and (175 +/- 128)x10(3) respectively] in children with left-to-right shunt congenital cardiac lesions (P < 0.05). CONCLUSIONS: The expression of AT1 and AT2 receptors in small vascular walls of systemic circulation was higher than that of pulmonary circulation in children with left-to-right shunt congenital cardiac lesions.

Child↗
PubMed2006

[Interventional approach to the treatment of aneurysms of the perimembranous ventricular septal defects].

OBJECTIVES: To explore applicable protocol for the positioning of ventricular septal defect (VSD) occluder and the selection of the device by retrospective analysis of transcatheter closure approach to the aneurysms of the perimembranous VSD. METHODS: Thirty-five cases of perimembranous VSD with septal aneurysm (19 males and 16 females) from May, 2004 to May, 2005 were included, with a mean age of 5.3 y and mean weight of 17.6 kg. Their angiographic and ultrasound data, and interventional processes were analyzed. Seven segments of the aneurysms were assessed: the diameter of the defect on the left ventricle, the diameter of the defect on the right ventricle, the thickness of ventricular septum, the distance from the farthest end of the aneurysm to the defect, the diameter of the widest part of the aneurysm and the distance between the two farthest orifices on the aneurysm. RESULTS: Sixteen cystiform aneurysms and nineteen tubiform ones were identified with left ventricular angiography. The diameters of the orifices of aneurysms and the diameters of the VSDs ranged from 1.5 mm to 4.1 mm and 2.7 mm to 11.9 mm, separately, with the mean of 2.9 mm and 4.3 mm. From the echocardiography, the distances of the rim of defect to the aortic valve ranged from 2.0 mm to 7.0 mm, with the mean of 4.3 mm. All the interventions were successfully done with symmetrical devices from 4 mm to 14 mm. The left disc of the device was positioned at the defect surface from the left ventricle in 29 cases, and was released at the left side of the orifice in 3 cases. CONCLUSIONS: The positioning of the left disc is mostly determined by the condition for the correct formation of the right disc in the right ventricle after deploying. Generally the defect surface in the left ventricle is most ideal to release the left disc of the device. If the body of aneurysm was too long for the right disc to restore its configuration, the left disc should be released on the left side of the orifice. The selection of device size is determined by the placement of the left disc. When the left disc is to be released at the defect surface in the left ventricle, the device size should be equal to or 1 to 2 mm larger than the diameter of the defect on the left ventricle. When the left disc is to be deployed on the left side of an orifice, the device size should be equal to or 1 mm larger than the defect diameter on the left ventricle when there is a single orifice. In the case of multiple orifices, the minimal size of the device which can cover all the orifices should be selected.

Adolescent↗
PubMed2005

Losartan blocks the excitatory effect of peripheral hypertonic stimulation on vasopressinergic neurons in hypothalamic paraventricular nucleus in rats: electrophysiological and immunocytochemical evidence.

The effect of peripheral hypertonic stimulation on the neurons of hypothalamic paraventricular nucleus (PVN) was investigated in the present study with both electrophysiological and immunocytochemical methods. The discharge frequency of the neurons with phasic activity in PVN could be increased by intraperitoneal (i.p.) injection of hypertonic saline (HS, 1.5M NaCl) (from 2.8 +/- 0.5 Hz to 5.4 +/- 0.9 Hz, P<0.001). The Fos expression in PVN could be enhanced (from 21.2 +/- 12.9 to 217.3 +/- 38.5 Fos-positive neurons, P<0.001) by i.p. HS and the majority of AVP-positive neurons expressing Fos (91.7 +/- 3.6%) was in magnocellular subdivision of PVN. After intracerebroventricular (i.c.v.) injection of losartan, angiotensin II type 1 (AT1) receptor antagonist (5 microg/microl), the excitatory effect of peripheral hypertonic stimulation on PVN neurons with phasic activity was inhibited significantly, and the number of the neurons co-expressing Fos and AVP in PVN decreased significantly (P<0.001) as well. The result demonstrated that the vasopressinergic neurons in PVN could be excited by peripheral hypertonic stimulation, and this excitation might be mediated by angiotensin II fibers projecting from subfornical organ to PVN.

Action Potentials↗
PubMed2005

Association of genetic polymorphism in GH gene with milk production traits in Beijing Holstein cows.

Associations were analysed between polymorphisms of the growth hormone gene (GH-MspI) (localized in intron 3) and milk production traits of Beijing Holstein cows (a total of 543 cows). Polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method was used for identification of various genotypes. Frequencies of genotypes were 0.77, 0.21 and 0.02 for A/A, A/B and B/B, respectively. The frequency of the GH A allele is 0.875. The results of the least squares means show that in all three lactations, the GH A/A cows yielded more milk (P less than 0.01 for lactation I and P less than 0.05 for lactations II and III), whereas A/B cows showed higher milk fat content than A/A individuals (P less than 0.05 for lactations I and II, and P less than 0.01 for lactation III). The A/A cows yielded more fat than A/B individuals (P less than 0.01 only in lactation I). The A/A cows yielded more milk protein than A/B individuals (P less than 0.01 for lactations I, II, and III). The A/A cows produced milk of higher protein content than of A/B individuals (P less than 0.05 only in lactation II).

Animals↗
PubMed2005

Role of protein kinase C on the alteration of retinal endothelin-1 in streptozotocin-induced diabetic rats.

Activation of protein kinase C (PKC) has been implicated in the pathogenesis of diabetic retinopathy. The purpose of this study was to investigate the role of PKC on the alteration of retinal endothelin-1 in 2-week streptozotocin (STZ)-induced diabetic rats. The measurement of retinal PKC activities from membranous and cytosolic fractions was conducted by ELISA. Retinal tissues were analysed for the expression of endothelin-1 (ET-1), endothelin-3 (ET-3), endothelin-A (ET-A), and endothelin-B (ET-B) mRNA by means of semi-quantitative RT-PCR. Retinal vasculature isolated by trypsin digest technique was immunostained for ET-1. We followed the alteration of retinal ET-1 after intravitreal injection of a general PKC inhibitor, GF109203X, in 2-week diabetic rats. Retinal PKC specific activities were significantly increased by 37% (P=0.027) in the membranous fraction in diabetic rats compared with normal rats, whereas PKC specific activities in the cytosolic fraction were unchanged. The retina from the diabetic rats showed increased ET-1 mRNA expression after 2 weeks, while no changes were found for ET-3, ET-A and ET-B. ET-1 immunoreactivity was also increased in the retinal vasculature of diabetic rats. Retinal ET-1 expression was decreased after intravitreal injection of GF109203X (10(-5), 10(-6), 10(-7) M) in a dose-dependent manner. The results from this study showed that the enhanced ET-1 expression associated with the activation of PKC has occurred in early diabetes, and PKC inhibitor could reverse the up regulation of ET-1.

Animals↗
PubMed2005

Sequence-specific assignment of 1H-NMR resonance and determination of the secondary structure of Jingzhaotoxin-I.

Jingzhaotoxin-I (JZTX-I) purified from the venom of the spider Chilobrachys jingzhao is a novel neurotoxin preferentially inhibiting cardiac sodium channel inactivation by binding to receptor site 3. The structure of this toxin in aqueous solution was investigated using 2-D 1H-NMR techniques. The complete sequence-specific assignments of proton resonance in the 1H-NMR spectra of JZTX-I were obtained by analyzing a series of 2-D spectra, including DQF-COSY, TOCSY and NOESY spectra, in H2O and D2O. All the backbone protons except for Gln4 and more than 95% of the side-chain protons were identified by d alphaN, d alphadelta, d betaN and d NN connectivities in the NOESY spectrum. These studies provide a basis for the further determination of the solution conformation of JZTX-I. Furthermore, the secondary structure of JZTX-I was identified from NMR data. It consists mainly of a short triple-stranded antiparallel beta-sheet with Trp7-Cys9, Phe20-Lys23 and Leu28-Trp31. The characteristics of the secondary structure of JZTX-I are similar to those of huwentoxin-I (HWTX-I) and hainantoxin-IV (HNTX-IV), whose structures in solution have previously been reported.

Amino Acid Sequence↗
PubMed2005

[The change of angiotensin II receptors in children with left-to-right shunt].

OBJECTIVE: To explore the change of AT1 and AT2 receptors in children with left-to-right shunt. METHODS: Lung tissue was obtained from 20 children with left-to-right shunt by biopsy during operation, and lung tissue from 5 children by autopsy was used as control. The above specimens were stained by immunohistochemistry techniques for detecting AT1 and AT2 receptors. Histomorphometric study was done to measure the IOD value of pulmonary small vascular wall via the staining of AT1 and AT2 receptors, and the diameter of these vessels was 15-100 microm. RESULTS: The IOD values of pulmonary small vascular walls obtained from via the staining of AT1 and AT2 receptors in children with left-to-right shunt were higher than the IOD values in control group (P=0.000). CONCLUSION: The expression of AT1 and AT2 receptors in pulmonary small vascular walls in children with left-to-right shunt was higher than that of the control. It may provide a sound rationale for the pharmacological management of children with left-to-right shunt by use of ACEI or AT1 receptor antagonist.

Child, Preschool↗
PubMed2005

[Effect of changji' an oral liquid on activated signal alterative intensity in algesthesia domain in patients with diarrhea type irritable bowel syndrome due to gan-pi disharmony].

OBJECTIVE: To observe the effect of Changji' an (CJA) oral liquid on the activated signal alterative intensity (ASAI) in intracranial algesthesia domain in patients with diarrhea type irritable bowel syndrome (IBS) due to Gan-Pi disharmony. METHODS: Twenty-four patients were randomly divided into 2 groups, 14 in the treated group and 10 in the control group, they were administrated with CJA and placebo respectively. The sensory threshold and score in the two groups recorded by rectal inflation test were compared and analyzed. The change of ASAI in intracranial algesthesia domain was analyzed by functional magnetic resonance imagine (fM-RI) during rectum being inflated with 30 ml, 60 ml, 90 ml and 120 ml of gas respectively. RESULTS: The initial sensory thresholds in the two groups were insignificantly different, but significant difference did show between the two groups in urgent defecation threshold and pain threshold after treatment (P < 0.05). Comparison in visual simulative scores between the two groups after treatment at rectal inflated for 30 ml showed no significant difference, but it showed significant difference when the inflation was over 30 ml (P < 0.05). In the treated group, the ASAI in insula cortex when rectal inflation being 90 ml or 120 ml and that in thalamus when rectal inflation being 120 ml were significantly decreased (P < 0.05). But in the control group, it changed insignificantly after treatment. CONCLUSION: The treatment of CJA on Gan-Pi disharmony caused diarrhea type IBS might be effected by regulating the ASAI in intracranial insula cortex and thalamus.

Adult↗
PubMed2004

Microfluidic PicoArray synthesis of oligodeoxynucleotides and simultaneous assembling of multiple DNA sequences.

Large DNA constructs of arbitrary sequences can currently be assembled with relative ease by joining short synthetic oligodeoxynucleotides (oligonucleotides). The ability to mass produce these synthetic genes readily will have a significant impact on research in biology and medicine. Presently, high-throughput gene synthesis is unlikely, due to the limits of oligonucleotide synthesis. We describe a microfluidic PicoArray method for the simultaneous synthesis and purification of oligonucleotides that are designed for multiplex gene synthesis. Given the demand for highly pure oligonucleotides in gene synthesis processes, we used a model to improve key reaction steps in DNA synthesis. The oligonucleotides obtained were successfully used in ligation under thermal cycling conditions to generate DNA constructs of several hundreds of base pairs. Protein expression using the gene thus synthesized was demonstrated. We used a DNA assembly strategy, i.e. ligation followed by fusion PCR, and achieved effective assembling of up to 10 kb DNA constructs. These results illustrate the potential of microfluidics-based ultra-fast oligonucleotide parallel synthesis as an enabling tool for modern synthetic biology applications, such as the construction of genome-scale molecular clones and cell-free large scale protein expression.

Base Sequence↗
PubMed2004

Structure--activity relationships of hainantoxin-IV and structure determination of active and inactive sodium channel blockers.

Hainantoxin-IV (HNTX-IV) can specifically inhibit the neuronal tetrodotoxin-sensitive sodium channels and defines a new class of depressant spider toxin. The sequence of native HNTX-IV is ECLGFGKGCNPSNDQCCKSSNLVCSRKHRWCKYEI-NH(2). In the present study, to obtain further insight into the primary and tertiary structural requirements of neuronal sodium channel blockers, we determined the solution structure of HNTX-IV as a typical inhibitor cystine knot motif and synthesized four mutants designed based on the predicted sites followed by structural elucidation of two inactive mutants. Pharmacological studies indicated that the S12A and R26A mutants had activities near that of native HNTX-IV, while K27A and R29A demonstrated activities reduced by 2 orders of magnitude. (1)H MR analysis showed the similar molecular conformations for native HNTX-IV and four synthetic mutants. Furthermore, in the determined structures of K27A and R29A, the side chains of residues 27 and 29 were located in the identical spatial position to those of native HNTX-IV. These results suggested that residues Ser(12), Arg(26), Lys(27), and Arg(29) were not responsible for stabilizing the distinct conformation of HNTX-IV, but Lys(27) and Arg(29) were critical for the bioactivities. The potency reductions produced by Ala substitutions were primarily due to the direct interaction of the essential residues Lys(27) and Arg(29) with sodium channels rather than to a conformational change. After comparison of these structures and activities with correlated toxins, we hypothesized that residues Lys(27), Arg(29), His(28), Lys(32), Phe(5), and Trp(30) clustered on one face of HNTX-IV were responsible for ligand binding.

Amino Acid Sequence↗
PubMed2004

Blood-retinal barrier breakdown induced by activation of protein kinase C via vascular endothelial growth factor in streptozotocin-induced diabetic rats.

PURPOSE: To investigate (1) the mechanism of blood-retinal barrier breakdown induced by protein kinase C (PKC) activation (2) the relationship between PKC activation and vascular endothelial growth factor (VEGF) in 2-week streptozotocin-induced diabetes. METHODS: Retinal PKC activities, retinal and vitreous concentration of VEGF protein were conducted by enzyme-linked immunoabsorbent assay (ELISA). Retinal VEGF mRNA expression was analyzed by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). Blood-retinal barrier breakdown was quantified using the Evans blue technique. Alteration of retinal VEGF and blood-retinal barrier were observed after intravitreal injection of PKC inhibitor, GF109203X, in 2-week diabetic rats. RESULTS: Two weeks of diabetes in rats resulted in elevation of retinal PKC specific activities, retinal and vitreous VEGF, and retinal vascular permeability. Retinal VEGF and retinal vascular permeability were decreased after intravitreal injection of GF109203X (10(-5), 10(-6) mol/L) in a dose-dependent manner. CONCLUSIONS: The results from this study showed that enhanced expression of VEGF and PKC in early diabetes and the blood-retinal barrier breakdown of early diabetic retinopathy induced by PKC activation may be partly due to the upregulation of VEGF. PKC inhibitor could reverse the blood-retinal barrier breakdown.

Animals↗
PubMed2004

[The effects of octreotide on portal hemodynamics in patients with liver cirrhosis].

OBJECTIVE: To compare the portal hemodynamic effects of different doses of somatostatin analogue octreotide (sandostatin) with beta-blocker (propranolol) on prevention of early variceal re-bleeding in patients with cirrhotic portal hypertension. METHODS: Thirty patients of cirrhosis with moderate to severe esophageal varices were randomly allocated into three groups. 10 patients in group A were given propranolol 10-20 mg orally three times a day for 7 days; 10 patients in group B were administrated octreotide 0.05 mg subcutaneously two times a day for 3 days, while 10 patients in group C received octreotide 0.1 mg subcutaneously two times a day for 3 days. The postprandial vessel diameter, maximal and average flow velocity (Vmax/V) and flow volume of portal vein (PV), splenic vein (SV) and superior mesenteric vein (SMV) were measured before and after therapy by using Echo-Doppler technology. RESULTS: There was a trend of decrease of the vessel diameter in all the three groups, but with no significant difference. However, the average velocity and flow volume of PV were significantly diminished in the propranolol group (P < 0.05), while there was no statistical change of them in SV and SMV groups. In octreotide 0.05 mg and 0.1 mg group, the average velocity and flow volume of PV, SV and SMV were significantly decreased (P > 0.05). Besides, octreotide 0.1 mg group but not 0.05 mg group was more active in decreasing flow volume of PV as compared with the propranolol group, while both octreotide groups were superior to the propranolol group in decreasing flow volume of SV and SMV. CONCLUSIONS: Octreotide may have potential prophylactic effect in prevention of early variceal re-bleeding in cirrhotic patients with portal hypertension.

Adult↗
PubMed2004

[Activation of adenylate cyclase influences the sensitivity of acute promyelocytic leukemia cell lines to ATRA].

OBJECTIVE: To explore the molecular mechanism of APL cell resistance to ATRA. METHODS: The ATRA sensitive and resistant APL cell lines, NB4 and NB4-R1, were used as in vitro models. The effects of specific inhibitors and activators of adenylate cyclase (AC) and phosphodiesterase (PDE) on ATRA-induced differentiation was evaluated by cell morphology, cell surface antigen expression and nitroblue-tetrazolium (NBT) reduction assays. RESULTS: SQ22536, a specific antagonist of AC, could dramatically block ATRA-induced NB4 cell differentiation. When ATRA + SQ22536 group compared with ATRA group, the positivity of CD11b decreased from (95.9 +/- 2.5)% to (60.3 +/- 7.1)%, while the A(540) in NBT reduction assay decreased from 0.585 +/- 0.092 to 0.170 +/- 0.028 (P < 0.05). Forskolin, an agonist of AC, could overcome the resistance of NB4-R1 cells to ATRA. When ATRA + forskolin group compared with ATRA group, the positivity of CD11b increased from (34.3 +/- 5.3)% to (94.6 +/- 2.4)%, while the A(540) in NBT reduction assay increased from 0.110 +/- 0.028 to 0.395 +/- 0.049 (P < 0.05). In contrast, the specific antagonist and agonist of PDE, 3-isobutyl-1-methylxanthine (IBMX) and calmodulin, exerted little impact on ATRA treatment. CONCLUSIONS: The defaults in the initiation of AC activation may contribute to the resistance to ATRA in some APL cells.

Adenine↗
PubMed2003

Comparison of information obtained by operative note abstraction with that recorded on a standardized data collection form.

BACKGROUND: The Ischemic Optic Neuropathy Decompression Trial compared optic nerve decompression surgery with careful follow-up for treatment of patients with nonarteritic ischemic optic neuropathy. Surgeons submitted a standardized data collection form and operative notes for 123 patients randomized to and undergoing surgery. The purpose of this study was to see whether operative notes have sufficient and reliable data to avoid development of a surgery data collection form in future trials. METHODS: We abstracted data from Ischemic Optic Neuropathy Decompression Trial patient operative notes, calculated the proportion of completed responses, and compared abstracted responses with those originally recorded on corresponding case report forms. RESULTS: Variables used to identify persons, dates, or eye (left/right) were reported 100% of the time on operative notes and with excellent agreement with those recorded on the case report form (median agreement, 100%; range, 95% to 100%). Categoric variables, used to establish the characteristics of surgical steps, were also reported reliably on operative notes (median agreement, 84%; range, 0 to 100%). Open-ended variables tended to be reported more frequently on operative notes (exact agreement, 57% and 34%, respectively, for complications and postoperative medications). Quantitative variables were infrequently reported but correlated well with values reported on the data collection forms (Pearson correlation coefficients, 0.78, 0.79, 0.94, 0.96). For many variables, disagreements were minor and often were related to interpretation of the operative notes by the abstractor. CONCLUSION: In our trial, operative note abstraction adequately documented surgery date and surgeon and provided more complete information than the standardized report form with respect to complications but did not provide complete information for other variables.

Abstracting and Indexing↗