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Y Y Zhang

Publications and source records attributed to Y Y Zhang.

At least 19 recordsLinked to original sources
PubMed2026

[Analysis of clinical spectrum and genotype characteristics of 9 cases of Fabry disease].

Objective: To investigate the genetic characteristics and clinical phenotypes across different genotypes in patients with Fabry disease. Methods: Clinical data of 9 confirmed FD patients treated from June 2019 to December 2025 at the Affiliated Huai'an No.1 people's Hospital of Nanjing Medical University were retrospectively analyzed. The diagnostic criteria for FD included α-galactosidase A (α-GalA) activity, GLA gene sequencing, globotriaosylsphingosine levels, and renal biopsy findings, supplemented by clinical symptoms and signs. Genetic testing was performed on both the proband and their family members. Proband underwent next-generation sequencing of the GLA gene using the long-range PCR. Family members were verified by conventional PCR combined with Sanger sequencing. Variants were classified according to the 2015 American College of Medical Genetics and Genomics guidelines for sequence variation interpretation. Results: Of the 9 patients, 4 were males and 5 were females. The mean α-Gal A activity was (0.47±0.13) μmol·L-1·h-1 in males and (2.38±0.91) μmol·L-1·h-1 in females. The mean age at diagnosis was (43.0±16.7) years. The main clinical manifestations included renal impairment in 7 cases (proteinuria, chronic kidney disease, or end-stage renal disease), cardiac involvement in 8 cases (myocardial hypertrophy, arrhythmia, etc.), and autonomic nervous system symptoms in 6 cases (hypohidrosis). Pathogenic or likely pathogenic GLA variants were identified in all 9 patients, of which 8 were classified as pathogenic and 1 as a variant of uncertain significance. Three patients underwent family screening: in one case, the variant was possibly inherited from the maternal grandmother; one case was confirmed as a de novo mutation; and in one case, paternal inheritance could not be excluded. Renal biopsy in one patient revealed characteristic myeloid bodies and zebra bodies. Among the 9 patients, 1 received agalsidase α and 8 received agalsidase β, with one case developing infusion-associated reactions after 12 infusions. During the follow-up period, one patient died due to cardiac complications. Conclusions: FD patients exhibit a broad clinical spectrum and diverse genotypes. Atypical presentations should be closely monitored to enable early diagnosis and treatment, thereby improving prognosis.

Humans↗
PubMed2006

Community-acquired pneumonia in Shanghai, China: microbial etiology and implications for empirical therapy in a prospective study of 389 patients.

The aim of this multicenter study was to identify the causative pathogens of community-acquired pneumonia (CAP) in Shanghai, China, and to determine their susceptibility to antimicrobial agents. Pathogens obtained from 389 patients with documented CAP during 2001-2003 were identified by multiple diagnostic tools that included bacterial culture, polymerase chain reaction (PCR), and specific immunological assays. Susceptibility of the bacterial isolates was tested by the broth microdilution method. A specific pathogen was identified in 39.8% (155/389) of the patients: Haemophilus influenzae (n=80), Klebsiella spp. (n=15), Streptococcus pneumoniae (n=12), Staphylococcus aureus (n=6), Moraxella catarrhalis (n=1), other gram-negative organisms (n=9), and atypical pathogens that comprised Mycoplasma pneumoniae (n=42), Chlamydia pneumoniae (n=17), and Legionella pneumophila (n=2). Most H. influenzae isolates were susceptible to ampicillin (88.3%), and all were susceptible to macrolides. Of the S. pneumoniae isolates, 75% (9/12) were susceptible to penicillin, while 25% (3/12) were intermediately susceptible. H. influenzae and atypical pathogens are among the most important pathogens of CAP. Ampicillin, cephalosporins, and the newer fluoroquinolones can be used as empirical therapy for CAP in the Shanghai area. The efficacy of monotherapy with newer macrolides for CAP caused by S. pneumoniae requires further evaluation.

Adolescent↗
PubMed2006

Semen characterization and sperm storage in Cabot's Tragopan.

The semen quality of Cabot's Tragopan, the dependence of sperm yields on frequency of semen collection, and the duration of sperm storage in females were investigated. The results are as follows: 1) The average duration of the period in which Cabot's Tragopan can produce an ejaculate was about 70 d. The ejaculate volume ranged from 15 to 100 microL. The average concentration of the ejaculate was 2.31 x 10(9) mL(-1). There were 11.69 (+/- 0.77)% abnormal spermatozoa per ejaculate. Three of 11 males yielded more than 50 microL of semen per collection most of the time. 2) The ejaculate volumes, the concentration, the total number of sperm per ejaculate, and the daily sperm output were all markedly affected by the frequency of semen collection (P < 0.01). However, no significant difference was detected in characters between the 2 groups with relatively low collection frequency (P > 0.05) except the daily sperm output (P < 0.01). The highest frequency of semen collection did not yield more sperm. 3) The average duration of the period in which the female laid fertilized eggs after single insemination was 19.85 +/- 3.08 d (range 9 to 32 d, n = 7). This value was affected by the rhythm of egg laying and varied among individuals. All of the results will facilitate design of the optimal artificial insemination strategy and help to achieve the ultimate aim of ex situ conservation.

Animals↗
PubMed2006

Functional alpha(1)-adrenoceptor subtypes in human submandibular glands.

alpha(1)-Adrenoceptor has been discovered to exist in many human tissues and mediates important physiological functions. The purpose of this study was to detect the expression, distribution, and function of alpha(1)-adrenoceptor subtypes in human submandibular glands. alpha(1A)- and alpha(1B)-Adrenoceptor mRNAs were identified by reverse-transcription/polymerase chain-reaction (RT-PCR), and their proteins were detected by Western blotting. No expression of the alpha(1D)-adrenoceptor mRNA and protein was found. By in situ hybridization and immunohistochemistry, alpha(1A)- and alpha(1B)-adrenoceptor mRNAs and proteins were shown to be widespread in both ductal and acinar cells. By confocal microscopy, phenylephrine (stimulating both alpha(1A)- and alpha(1B)-adrenoceptors) or A61603 (alpha(1A)-selective agonist) induced an increase in intracellular calcium by 2.33 +/- 0.18-fold and 1.81 +/- 0.43-fold, respectively, while 5-methylurapidil (alpha(1A)-selective antagonist) partly blocked calcium mobility stimulated by phenylephrine. The results indicated that functional alpha(1A)- and alpha(1B)-adrenoceptors were expressed in human submandibular glands, and might contribute to the regulation of saliva synthesis and secretion.

Adrenergic alpha-1 Receptor Agonists↗
PubMed2006

Effects of phenylephrine on transplanted submandibular gland.

Autotransplantation of the submandibular gland is a potential treatment for severe kerato-conjunctivitis sicca. However, one of the major barriers to this procedure is that secretions from the transplanted gland decrease shortly after the operation, which may lead to obstruction of Wharton's duct, or even to transplantation failure. Using a rabbit model, we investigated whether phenylephrine could improve the secretion from the transplanted gland. We found that phenylephrine treatment significantly reversed the decrease in salivary secretion after transplantation, enhanced the expressions of alpha1A-, alpha1B-, and alpha1D-adrenoceptor mRNA, and ameliorated atrophy of acinar cells. Furthermore, phenylephrine also induced translocation of aquaporin-5 from the cytoplasm to the apical membrane, and increased the levels of phospho-ERK1/2, ERK1/2, phospho-PKCzeta, and PKCzeta in the transplanted gland. These results indicate that phenylephrine treatment moderates structural injury and improves secretory function in the transplanted submandibular gland through promoting alpha1-adrenoceptor expression and post-receptor signal transduction.

Adrenergic alpha-Agonists↗
PubMed2004

T-helper and T-cytotoxic cell subsets monitoring during active cytomegalovirus infection in liver transplantation.

OBJECTIVE: The objectives of this study was to analyze the peripheral blood T-lymphocyte subsets of the Th1-related versus Th2-related cytokines of CD4+ cells, and the Tc1 versus Tc2 cytokines of CD8+ cells liver transplant recipients with versus without active cytomegalovirus (CMV) infection. METHODS: Isolated peripheral blood mononuclear cells (PBMC) were stimulated using PMA/Ionomycin/Monensin. Interleukin (IL)-4 and interferon gamma (IFN-gamma) production by CD4+ and CD8+T cells were determined using fluorescence-activated cell sorter (FACS) analysis. RESULTS: The ratios of CD4/CD8 were significantly lower among active CMV-infected patients. The levels of Th2 and Tc2 cytokines (IL-4) were similar between CMV-infected and uninfected patients. However, the levels of Th1-type and Tc1-type cytokines (IFN-r) were significantly lower among active CMV-infected patients. CONCLUSIONS: Low levels of Th1-type cytokines seem to correlate with active CMV infection in liver transplant recipients.

Antigens, CD↗
PubMed2003

Association of estrogen receptor alpha and vitamin D receptor gene polymorphisms with bone mineral density in Chinese males.

Osteoporosis is a common health problem not only in females but also in males, however, studies of osteoporosis in males are relatively rare compared to those in females. This is especially true in genetics studies. We evaluated the effects of PvuII and XbaI polymorphisms in the estrogen receptor alpha (ER-alpha) gene and ApaI polymorphism in the vitamin D receptor (VDR) gene on BMD variation in a random sample of 352 unrelated males from 401 Chinese nuclear families. BMD was measured at the lumbar spine (L1-L4) and hip (femoral neck, trochanter, intertrochanteric region). Raw BMD values were adjusted by age, age(2), height, and weight as covariates. We found no significant results for the 3 individual markers on BMD variation, however, ER-alpha haplotype analyses yielded some interesting results. Carriers of haplotype pX had a 4.98% lower BMD at the trochanter (P = 0.02) and 3.55% lower BMD at the lumbar spine (P = 0.09) than non-carriers. PX subjects had a 3.42% higher BMD at the trochanter and 3.26% higher BMD at the lumbar spine than others (P = 0.07 and P = 0.10, respectively). Such results were highly comparable with the significant or nearly significant interactions between ER-PvuII and ER-XbaI on BMD values at the trochanter (P = 0.03) and spine (P = 0.11). No significant results were observed for the interactions between ER-PvuII and VDR-ApaI, between ER-XbaI and VDR-ApaI, and between any of ER-alpha haplotypes and VDR-ApaI locus. Our results suggest that the ER-alpha haplotypes, not individual markers, may be associated with BMD variation at some skeletal sites in our Chinese male samples.

Absorptiometry, Photon↗
PubMed2002

[Hairpin probes for teal-time assay of restriction endonucleases].

New fluorogenic probes for restriction endonucleases based on molecular beacons were developed. These hairpin probes were single-stranded oligonucleotides that had stem-and-loop structure and carried 5'- fluorophor moiety and 3'-quencher moiety. Their stem sequences were designed as recognition sites for restriction endonucleases and loop sequences were unrelated nucleotides. Upon cleavage by endonuclease, these probes became fluorescent and thus could trace the enzyme activity continuously. Two probes were designed for BglII and NcoI, respectively, and each was labeled with a fluorophor of different color. The results showed that the two probes could specifically assay for the corresponding enzymes either individually or simultaneously in a real-time mode. Considering the simplicity, quantification and high throughput, these probes could be extended to other applications such as drug screening, protein-nucleic acid interaction study and searching for small molecule DNA cleavage agents.

Bacterial Proteins↗
PubMed2001

Overexpression of cellular glutathione peroxidase rescues homocyst(e)ine-induced endothelial dysfunction.

Homocyst(e)ine (Hcy) inhibits the expression of the antioxidant enzyme cellular glutathione peroxidase (GPx-1) in vitro and in vivo, which can lead to an increase in reactive oxygen species that inactivate NO and promote endothelial dysfunction. In this study, we tested the hypothesis that overexpression of GPx-1 can restore the normal endothelial phenotype in hyperhomocyst(e)inemic states. Heterozygous cystathionine beta-synthase-deficient (CBS((-/+))) mice and their wild-type littermates (CBS((+/+))) were crossbred with mice that overexpress GPx-1 [GPx-1((tg+)) mice]. GPx-1 activity was 28% lower in CBS((-/+))/GPx-1((tg-)) compared with CBS((+/+))/GPx-1((tg-)) mice (P < 0.05), and CBS((-/+)) and CBS((+/+)) mice overexpressing GPx-1 had 1.5-fold higher GPx-1 activity compared with GPx-1 nontransgenic mice (P < 0.05). Mesenteric arterioles of CBS((-/+))/GPx-1((tg-)) mice showed vasoconstriction to superfusion with beta-methacholine and bradykinin (P < 0.001 vs. all other groups), whereas nonhyperhomocyst(e)inemic mice [CBS((+/+))/GPx-1((tg-)) and CBS((+/+))/GPx-1((tg+)) mice] demonstrated dose-dependent vasodilation in response to both agonists. Overexpression of GPx-1 in hyperhomocyst(e)inemic mice restored the normal endothelium-dependent vasodilator response. Bovine aortic endothelial cells (BAEC) were transiently transfected with GPx-1 and incubated with dl-homocysteine (HcyH) or l-cysteine. HcyH incubation decreased GPx-1 activity in sham-transfected BAEC (P < 0.005) but not in GPx-1-transfected cells. Nitric oxide release from BAEC was significantly decreased by HcyH but not cysteine, and GPx-1 overexpression attenuated this decrease. These findings demonstrate that overexpression of GPx-1 can compensate for the adverse effects of Hcy on endothelial function and suggest that the adverse vascular effects of Hcy are at least partly mediated by oxidative inactivation of NO.

Animals↗
PubMed2001

Surveillance of bacterial resistance among isolates in Shanghai in 1999.

We report here surveillance data on the bacterial resistance of clinical isolates from 11 Shanghai hospitals in 1999, for guidance in the clinical use of antibacterial agents. Of the 14,855 strains collected, 5130 (34.5%) were Gram-positive cocci and 9725 (65.5%) were Gram-negative bacilli. The most common organisms in descending order of frequency, were: Escherichia coli (16%), coagulase-negative staphylococci (CNS; 14.3%), Klebsiella spp. (12.3%), Staphylococcus aureus (11.5%), Pseudomonas aeruginosa (9.2%), Acinetobacter spp. (8.1%), and Enterococcus spp. (6.6%). Methicillin-resistant strains accounted for 64% and 77% of S. aureus and CNS, respectively. The methicillin-sensitive strains were susceptible to most agents tested, while most methicillin-resistant strains were resistant to these agents. No vancomycin-resistant staphylococci were identified. Vancomycin-resistant strains accounted for 3.6% of Enterococcus fecalis and 1.7% of E. fecium. E. coli strains resistant to piperacillin, gentamicin, and fluoroquinolones accounted for 50% or more of the strains, and the resistance rates of Klebsiella spp., Enterobacter spp., Citrobacter spp., and Acinetobacter spp. to third-generation cephalosporins had increased markedly compared with rates in recent years. Resistance rates of P. aeruginosa to ceftazidime and imipenem (27% and 20%, respectively) had also increased compared with rates in recent years. A national strategy on the limited and prudent use of antibiotics is urgently needed.

Anti-Bacterial Agents↗
PubMed2001

Frequency of spontaneous mutations in an avian hepadnavirus infection.

In this study, we measured the frequency of revertants of a cytopathic strain of the duck hepatitis B virus that bears a single nucleotide substitution in the pre-S envelope protein open reading frame, resulting in the amino acid substitution G133E. Cytopathic virus mixed with known amounts of a genetically marked wild-type virus was injected into ducklings. Virus outgrowth was accompanied by a coselection of wild-type and spontaneous revertants during recovery of the ducklings from the acute liver injury caused by death of the G133E-infected cells. The frequency of individual revertants in the selected noncytopathic virus population was estimated by determining the ratio of each revertant to the wild-type virus. Spontaneous revertants were found to be present at frequencies of 1 x 10(-5) to 6 x 10(-5) per G133E genome inoculated. A mathematical model was used to estimate that the mutation rate was 0.8 x 10(-5) to 4.5 x 10(-5) per nucleotide per generation.

Animals↗
PubMed2001

Heparin reacts with and inactivates nitric oxide.

Although heparin is a well-known anticoagulant, in some cases it promotes a prothrombotic state and does so through both antibody-dependent and antibody-independent platelet activation. In this study, heparin was found to reverse the antiplatelet effect of an NO donor. S-nitroso-glutathione (SNO-Glu), with an EC(50) of 1.8 U/mL. Ultraviolet/visible spectral analysis and the Griess assay showed that increasing heparin concentrations on a dose-dependent basis eliminated acidified NO(x) species. Since heparin is a heterogeneous mixture of glycosaminoglycans, the effects of six different heparin disaccharides were compared with various substitutions on the hexose rings to determine which functional group(s) of the polysaccharide interact with acidified NO(x). Among the six disaccharides tested, only types I-S and II-S had the effect, suggesting that the sulfamino-group at the C2 position of the glucosamine moiety was critical for the elimination of acidified NO(x) species. Mass spectrometry experiments gave results consistent with these observations, indicating that only the I-S and II-S heparin disaccharides were modified upon treatment with NaNO(2)/HCl. Negative-ion electro-spray ionization MS and tandem MS analyses of the native compounds and their deuterium-labeled analogs confirmed that the reaction products from nitrosation of these N-sulfated disaccharides had eliminated the C2-sulfamino-moiety and replaced it with methoxide derived from the solvent. Participation of the 6-sulfato-substituent appears to facilitate the elimination reaction. These data show that heparin can impair the antiplatelet properties of nitric oxide by interacting with the nitrosating species, and suggest that heparin-like glycosamino-glycans may interact with endothelium-derived nitric oxide in vivo to regulate the bioactivity of this important antiplatelet and vasorelaxant substance.

Anticoagulants↗
PubMed2001

[Site-directed mutagenesis at disulfide bond Cys206-Cys210 of prochymosin (chymosin)].

During the work of site-directed mutagenesis at disulfide bond Cys206-Cys210 of prochymosin, it was found that the corresponding template sequence had the potential to form a loop-stem structure with free energy of -16.1 kcal/mol, which prevent the template from pairing with primer and, in turn, the synthesis of the mutated DNA strand. Rapid annealing can overcome this difficulty. Five expression plasmids of prochymosin muants with deletion of Cys206-Cys210 (C206A, C210A, C206A/C210A, C210S and C206S/C210S) were constructed. Except for C206A they were expressed at high level in E. coli amounting to 50% of the total cellular proteins. Renaturation of the mutant prochymosin indicated that Cys206-Cys210 is dispensable for correct refolding of prochymosin. However, the amino acid residues at Cys206 and/or Cys 210 play a critical role in determining the renaturation. Among the five mutants the reactivation efficiency of C206A/C210A were about 4.5-fold, 20-fold and 30-fold higher than that of C206S/C210S, C210A and C210S respectively. C206A can not correctly refold at all. CD spectra in the far UV region indicate that C206A/C210A and C206S/C210S chymosin analogs have a secondary structure almost identical to that of the wild-type chymosin. Fluorescence spectroscopic analysis revealed that mutant chymosins have the same emission maximum at 333 nm as the wild-type chymosin but their fluorescence intensities at 333 nm are much higher than that of the wild-type chymosin. Considering that the mutants and the wild-type chymosin exhibit almost the same specific activity, it is reasonable to conclude that the mutant proteins assume a native active information with a perturbance around some tryptophan residues.

Chymosin↗
PubMed2001

Postantibiotic effects of eleven antimicrobials on five bacteria.

AIM: To investigate the postantibiotic effects (PAE) of different classes of antimicrobials against five different types of bacteria. METHODS: Minimal inhibitory concentrations (MIC) were determined by twofold macrodilution in broth. The antimicrobial agents were eliminated by washing method after the bacteria were exposed to antimicrobials for 1 h or 2 h. Growth curves were followed by viable counts, and then the PAE were calculated. RESULTS: Macrolides induced PAE of 3.10 h to 4.15 h on S aureus, and 1.85 h to 3.3 h against S pneumoniae, which were longer than PAE induced by other tested antimicrobials (P<0.01). Macrolides induced PAE of 1 h to 4 h against H influenzae, with azithromycin producing the longest PAE of 4 h. Ciprofloxacin and amikacin induced PAE of 1.38 h to 2.00 h on E coli and K pneumoniae, which were longer than that of beta-lactams, piperacillin, cefazolin, or cefotaxime, with PAE of 0.1 h to 0.5 h (P<0.01). CONCLUSION: Different classes of antimicrobials induce different periods of PAE. As an important pharmacodynamic parameter, PAE provide reference data for the determination of the optimal dosing regimen and reasonable use of antimicrobials.

Escherichia coli↗
PubMed2001

[Characteristics of alpha2-adrenoceptor mediated contractile response in isolated aortae of rats].

In order to investigate the characteristics of vascular alpha(2)-adrenoceptor (alpha(2)-AR) and its relation to alpha(1)-AR, isolated Wistar rat (10 weeks) aortae were used as a model for testing contractile function in vivo. It was found that both alpha(1) and alpha(2)-AR (mainly alpha(1)-AR) mediated the contractile response. While alpha(1)-AR enhanced the contractile response mediated by alpha(2)-AR, alpha(2)-AR had no effect on that mediated by alpha(1)-AR. When alpha(1)-AR was irreversibly blocked and the activity of alpha(2)-AR remained intact, the contractile response mediated by alpha(2)-AR was no longer observed. The contractile response only reappeared in the presence of KCl of the threshold level, and the extent of the maximum contraction decreased, compared with control (with alpha(1)-AR being intact). The results show that there exists a functional alpha(2)-AR in rat aorta, however, the contractile effect of which depends on the stimulation of alpha(1)-AR.

Adrenergic alpha-Antagonists↗
PubMed2000

Analysis of a nucleotide-binding site of 5-lipoxygenase by affinity labelling: binding characteristics and amino acid sequences.

5-Lipoxygenase (5LO) catalyses the first two steps in the biosynthesis of leukotrienes, which are inflammatory mediators derived from arachidonic acid. 5LO activity is stimulated by ATP; however, a consensus ATP-binding site or nucleotide-binding site has not been found in its protein sequence. In the present study, affinity and photoaffinity labelling of 5LO with 5'-p-fluorosulphonylbenzoyladenosine (FSBA) and 2-azido-ATP showed that 5LO bound to the ATP analogues quantitatively and specifically and that the incorporation of either analogue inhibited ATP stimulation of 5LO activity. The stoichiometry of the labelling was 1.4 mol of FSBA/mol of 5LO (of which ATP competed with 1 mol/mol) or 0.94 mol of 2-azido-ATP/mol of 5LO (of which ATP competed with 0.77 mol/mol). Labelling with FSBA prevented further labelling with 2-azido-ATP, indicating that the same binding site was occupied by both analogues. Other nucleotides (ADP, AMP, GTP, CTP and UTP) also competed with 2-azido-ATP labelling, suggesting that the site was a general nucleotide-binding site rather than a strict ATP-binding site. Ca(2+), which also stimulates 5LO activity, had no effect on the labelling of the nucleotide-binding site. Digestion with trypsin and peptide sequencing showed that two fragments of 5LO were labelled by 2-azido-ATP. These fragments correspond to residues 73-83 (KYWLNDDWYLK, in single-letter amino acid code) and 193-209 (FMHMFQSSWNDFADFEK) in the 5LO sequence. Trp-75 and Trp-201 in these peptides were modified by the labelling, suggesting that they were immediately adjacent to the C-2 position of the adenine ring of ATP. Given the stoichiometry of the labelling, the two peptide sequences of 5LO were probably near each other in the enzyme's tertiary structure, composing or surrounding the ATP-binding site of 5LO.

Adenosine Triphosphate↗
PubMed2000

Selective cyclooxygenase-2 inhibitors: heteroaryl modified 1,2-diarylimidazoles are potent, orally active antiinflammatory agents.

A series of heteroaryl modified 1,2-diarylimidazoles has been synthesized and found to be potent and highly selective (1000-9000-fold) inhibitors of the human COX-2. 3-Pyridyl derived COX-2 selective inhibitor (25) exhibited excellent activity in acute (carrageenan induced paw edema, ED(50) = 5.4 mg/kg) and chronic (adjuvant induced arthritis, ED(50) = 0.25 mg/kg) models of inflammation. The relatively long half-life of 25 in rat and dog prompted investigation of the pyridyl and other heteroaromatic systems containing potential metabolic functionalities. A number of substituted pyridyl and thiazole containing compounds (e.g., 44, 46, 54, 76, and 78) demonstrated excellent oral activity in every efficacy model evaluated. Several orally active diarylimidazoles exhibited desirable pharmacokinetics profiles and showed no GI toxicity in the rat up to 100 mg/kg in both acute and chronic models. The paper describes facile and practical syntheses of the targeted diarylimidazoles. The structure-activity relationships and antiinflammatory properties of a series of diarylimidazoles are discussed.

Administration, Oral↗