Biomedical subjects

Ji Zhang

Publications and source records attributed to Ji Zhang.

At least 19 recordsLinked to original sources

PubMed2026

Prospective clinical validation of targeted long-read sequencing for preimplantation genetic testing of α-thalassaemia.

BACKGROUND: Preimplantation genetic testing for monogenic disorders (PGT-M) can prevent transmission of severe α-thalassaemia, but conventional workflows remain limited by family-specific assay design for direct variant detection, dependence on additional family samples for haplotype construction, and labour-intensive multi-step procedures across several platforms. Targeted long-read sequencing-based PGT-M for α-thalassaemia (tlrPGT-α-thal) integrates direct variant detection and haplotype linkage analysis within a single assay, but prospective clinical validation is lacking. METHODS: This prospective clinical study enrolled 103 families at high risk of transmitting α-thalassaemia at a reproductive medicine centre between August 2024 and March 2025. All families underwent blinded parallel analysis using both conventional NGS-based PGT-M (comparator) and tlrPGT-α-thal. RESULTS: In the primary concordance analysis, tlrPGT-α-thal was fully concordant with conventional NGS-based PGT-M (507/507, 100.0%; exact 95% CI, 99.3-100.0). Direct variant detection was successful in 501/507 embryos (98.82%; 95% CI, 97.4-99.6), haplotype linkage was established in 505/507 embryos (99.61%; 95% CI, 98.6-100.0), and one meiotic recombination event was identified. Among 93 families proceeding to embryo transfer, 57 pregnancies underwent invasive prenatal diagnosis, and all were concordant with the corresponding tlrPGT-α-thal results. Of the 26 comparator-inconclusive embryos, tlrPGT-α-thal resolved 6 complex cases, including cases with incomplete pedigrees or insufficient informative SNPs. Among the remaining 20 embryos with HBA-region aneuploidies, genotype and parental origin could be determined in 12. CONCLUSIONS: The findings show that tlrPGT-α-thal enables direct detection of diverse α-thalassaemia-causing variants together with efficient haplotype linkage analysis within a single workflow, without requiring family-specific assay design or additional family samples. The method demonstrated high diagnostic accuracy while providing added value in complex scenarios. Taken together, tlrPGT-α-thal represents a simplified and broadly applicable strategy for α-thalassaemia PGT-M.

Humans↗

PubMed2025

GCLC desuccinylation regulated by oxidative stress protects human cancer cells from ferroptosis.

Tumor cells evolve strong antioxidant capacities to counteract the abnormal high level of reactive oxygen species (ROS) in the tumor microenvironment. Glutamate-cysteine ligase catalyzing subunit (GCLC) for synthesis of antioxidant glutathione (GSH) represents the key enzyme to maintain redox homeostasis of tumor cells, however, whether its activity is regulated by posttranslational modifications, such as succinylation, remains to be clarified. Here, we demonstrate the existence of succinylation modification on GCLC by in vitro and in vivo assays. NAD-dependent deacetylase Sirtuin-2 (SIRT2) serves as the desuccinylase and catalyzes GCLC desuccinylation at sites of K38, K126, and K326. Specifically, GCLC directly interacts with SIRT2, which can be substantially enhanced upon ROS treatment. This strengthened association results in GCLC desuccinylation and activation, consequently promoting GSH synthesis and rendering cancer cells resistant to ferroptosis induction. Depletion of SIRT2 decreases total GSH level and meanwhile increases the cellular susceptibility to ferroptosis, which can mostly be rescued by introducing wild-type GCLC, but not its 3K-E mutant. We further demonstrated that histone acetyltransferase P300 serves as the succinyltransferase of GCLC, and their association is remarkably decreased after ROS treatment. Thus, SIRT2-regulated GCLC succinylation represents an essential signaling axis for cancer cells to maintain their redox balance in coping with oxidative stress-induced ferroptosis.

Humans↗

PubMed2003

Phylogenetic changes in the expression of delta opioid receptors in spinal cord and dorsal root ganglia.

To assess the validity of rodent models for investigating the role of delta opioid receptors (DOR) in analgesia, the distribution of DOR binding and mRNA were compared between rodent and primate spinal cord and dorsal root ganglia (DRG), using receptor autoradiography and in situ hybridization, respectively. In mouse and rat spinal cord, [(125)I]-deltorphin-labeled DOR binding sites were detected throughout the gray matter. In contrast, in primate and particularly in human spinal cord, DOR binding was mainly present in laminae I-II, with little to no binding in deeper layers. Accordingly, in rodent spinal cord, DOR mRNA was expressed by a large number of neurons distributed throughout the ventral and dorsal horns, whereas in the primate, DOR expression was significantly lower, as evidenced by a moderate number of labeled cells throughout the gray matter in monkey and by only few labeled cells in human, mainly in Clarke's column and lamina IX. Major species differences in DOR expression were also observed in primary afferent cells bodies. In rat DRG, intense DOR mRNA hybridization was primarily observed over large ganglion cells immunopositive for neurofilament 200. In contrast, in monkey and human DRG, DOR mRNA was primarily detected over small and medium-sized ganglion cells. These results demonstrate major differences in the expression and distribution of DOR in the spinal cord and DRG between mammalian species. Specifically, they point to a progressive specialization of DOR toward the regulation of primary somatosensory, namely nociceptive, inputs during phylogeny and suggest that the effects of DOR agonists in rodents may not be entirely predictive of their action in humans.

Animals↗

PubMed2003

Estimate of standard deviation for a log-transformed variable using arithmetic means and standard deviations.

Analyses of study variables are frequently based on log transformations. To calculate the power for detecting the between-treatment difference in the log scale, we need an estimate of the standard deviation of the log-transformed variable. However, in many situations a literature search only provides the arithmetic means and the corresponding standard deviations. Without individual log-transformed data to directly calculate the sample standard deviation, we need alternative methods to estimate it. This paper presents methods for estimating and constructing confidence intervals for the standard deviation of a log-transformed variable given the mean and standard deviation of the untransformed variable. It also presents methods for estimating the standard deviation of change from baseline in the log scale given the means and standard deviations of the untransformed baseline value, on-treatment value and change from baseline. Simulations and examples are provided to assess the performance of these estimates.

Confidence Intervals↗

PubMed2003

Component plane presentation integrated self-organizing map for microarray data analysis.

We describe a powerful approach, component plane presentation integrated self-organizing map (SOM), for the analysis of microarray data. This approach allows the display of multi-dimensional SOM outputs of microarray data in multiple sample specific presentations, providing distinct advantages in visual inspection of biological significances of genes clustered in each map unit with respect to each RNA sample. Beneficial potentials of the approach are highlighted by processing microarray data from yeast cells as well as human breast malignancies.

Gene Expression Profiling↗

PubMed2003

First direct reductive amination of mucochloric acid: a simple and efficient method for preparing highly functionalized alpha,beta-unsaturated gamma-butyrolactams.

[reaction: see text] The first direct reductive amination of mucochloric acid (1) has been accomplished. Reaction of 1 with various alkyl, aryl, and benzylamines, followed by reduction in the same pot, provides an efficient method of obtaining N-benzyl-3,4-dichloro-1,5-dihydro-pyrrol-2-one and N-aryl (or alkyl)-3,4-dichloro-1,5-dihydro-pyrrol-2-ones.

Amination↗

PubMed2003

Induction of CB2 receptor expression in the rat spinal cord of neuropathic but not inflammatory chronic pain models.

Cannabinoids have been considered for some time as potent therapeutic agents in chronic pain management. Central and systemic administration of natural, synthetic and endogenous cannabinoids produce antinociceptive and antihyperalgesic effects in both acute and chronic animal pain models. Although much of the existing data suggest that the analgesic effects of cannabinoids are mediated via neuronal CB1 receptors, there is increasing evidence to support a role for peripheral CB2 receptors, which are expressed preferentially on immune cells. As yet, little is known about the central contribution of CB2 in neuropathic pain states. We report here that chronic pain models associated with peripheral nerve injury, but not peripheral inflammation, induce CB2 receptor expression in a highly restricted and specific manner within the lumbar spinal cord. Moreover, the appearance of CB2 expression coincides with the appearance of activated microglia.

Animals↗

PubMed2003

Is survival possible without arachidonate metabolites in the brain during systemic infection?

The central nervous system mediates a coordinated set of biological responses during systemic immune stimuli. These responses are essential for the organism to eliminate invading pathogens and restore health. Coincidentally, centrally produced prostaglandins play a determinant role in activating the neuronal circuits involved in the control of autonomic functions.

Arachidonic Acid↗

PubMed2003

[Quantitative analysis of mixed hematopoietic chimersim based short tandem repeats loci after nonmyeloablative stem cell transplantation].

OBJECTIVE: To establish a method for quantitative analysis of mixed hematopoietic chimerism (MC) based on STR loci. METHODS: Using STR technique combined with PCR, we analyzed the peripheral blood samples collected from 3 nonmyeloablative stem cell transplantation recipients every 15 days after transplantation. RESULTS: The quantitative results coincided with the qualitative results of DNA electrophoresis and with the clinical outcomes. When the result of electrophoresis showed only donor's allele type we could still find out the recipient's specific allele. CONCLUSION: The quantitative analysis using STR-PCR can detect more subtle changes in the evidence of engraftment. It is a more efficient method for detect the hematopoietic chimerism post transplantation.

Chimera↗

PubMed2003

[Correlation between mutation of GyrA and ParC genes and quinolone resistance in Neisseria gonorrhoeae].

OBJECTIVES: To investigate the correlation between mutation of GyrA and ParC genes and quinolone resistance in Neisseria Gonorrhoeae. METHODS: The gene fragments of quinolone resistance-determining region (QRDR) in GyrA and ParC genes in 20 Neisseria gonorrhoeae strains clinically isolated in Wuxi, China, were sequenced, and the susceptibility of the 20 strains to quinolone was examined by agar diffusion method. RESULTS: The mutations at the Asp95 point in GyrA gene were found in 20 strains. Of the 19 stains examined, 16 had mutations at the 86, 87, 88, 91 points in ParC genes. CONCLUSIONS: The mutations of Asp95 in GyrA gene and Asp86, Ser87, Ser88, Glu91 in ParC gene contribute to quinolone resistance in Neisseria Gonorrhoeae.

Base Sequence↗

PubMed2002

Reinvestigation of mucohalic acids, versatile and useful building blocks for highly functionalized alpha,beta-unsaturated gamma-butyrolactones.

[reaction: see text] Mucohalic acids (mucochloric acid (1, 3,4-dichloro-5-hydroxy-5H-furan-2-one) and mucobromic acid (2, 3,4-dibromo-5-hydroxy-5H-furan-2-one)) are inexpensive, commercially available starting materials with multiple functional groups. These compounds have been modified by way of reduction followed by Suzuki cross-coupling reactions involving arylboronic acids to afford highly functionalized alpha,beta-unsaturated gamma-butyrolactones in excellent yield. The synthetic utility of these building blocks was effectively demonstrated through preparation of the antiinflammatory drug Vioxx.

4-Butyrolactone↗

PubMed2002

Development of a catalytic enantioselective conjugate addition of 1,3-dicarbonyl compounds to nitroalkenes for the synthesis of endothelin-A antagonist ABT-546. Scope, mechanism, and further application to the synthesis of the antidepressant rolipram.

The enantioselective synthesis of endothelin-A antagonist ABT-546 has been accomplished via the discovery and development of a highly selective catalytic asymmetric conjugate addition of ketoesters to nitroolefins. Employing just 4 mol % bis(oxazoline)-Mg(OTf)(2) complex with an amine cocatalyst, we obtained the product nitroketone with 88% selectivity at the aryl-bearing stereocenter and in good yield on scales ranging to 13 mol. The effects of ligand structure, metal salt, and solvent on the reaction are described. Particularly important to the reaction is the water content. While water is necessary during the generation of the catalyst, the water must be then removed to maximize stereoselectivity and reactivity. The reaction has been extended to other dicarbonyl substrates, and a variety of substitution patterns are tolerated on the nitroolefin partner. The reaction has also been employed in the synthesis of the antidepressant rolipram. Investigations relating to the mechanism of the reaction are also described.

Alkenes↗

PubMed2002

[Detection of Mycoplasma hyorhinis in gastric cancer using bio-chip technology].

OBJECTIVE: To determine the prevalence of Mycoplasma hyorhinis in archived paraffin-embedded gastric cancer tissue and to find whether Mycoplasma hyorhinis infection can influence gene expression level in gastric cancer cells. METHODS: A high-dense tissue microarray containing 105 gastric cancer samples, 101 benign margin samples and 62 non-cancerous gastric disease samples resected during operation was constructed. PD4, a specific anti-Mycoplasma-hyorhinis Mab, was used to detect the infection rate in all the samples in the tissue microarrays immunohistochemically. Then, cDNA microarray was used to pinpoint differentially the expressed genes between gastric cancer cell line MGC803 samples with and without Mycoplasma hyorhinis infection. RESULTS: The infection rate of M. hyorhinis was 54.1% 53/98 in gastric cancer samples, 51.7% 45/87 in benign margin samples, and 15.8 % 9/57 in non-cancerous disease samples respectively. The difference of infection rates between gastric cancer and non-cancerous gastric disease was statistically significant (P = 0.001). Highly differentiated adenocarcinomas had more opportunity (84.6%) to be infected with M. hyorhinis than poorly differentiated ones (45.9%)(P < 0.05). Intestinal type of gastric cancers (according to Lauren's classification) got the infection more often than diffused type. About 409 gene expression alterations were detected in 48 000 sites from two gastric cancer cell lines and the expression levels of some genes correlating with cell apoptosis and cell adhesion were down regulated after Mycoplasma hyorhinis infection. CONCLUSION: The infection rate of M. hyorhinis is significantly higher in gastric cancer than in other gastric diseases, thus indicating the association between Mycoplasma infection and gastric cancer. Mycoplasma hyorhinis infection influences the gene expression level in gastric cancer cell line MGC803, which indicates that the infection could have something to do with the process of gastric cancer. The question whether M.hyorhinis has oncogenic potential remains to be elucidated.

Adult↗

PubMed2002

A note on ANOVA assumptions and robust analysis for a cross-over study.

Analysis of variance (ANOVA) methods are usually applied to analyse continuous data from cross-over studies. The analysis, however, may not have appropriate type I error when certain assumptions are violated. In this paper, we first clarify a conventionally minimum set of assumptions that validate the F-tests of ANOVA models for cross-over studies. We then provide a practical verification/remedy procedure based upon the theoretical developments. By applying the verification/remedy procedure, more robust analysis results can be expected from the ANOVA models.

Analysis of Variance↗

PubMed2002

Improvement of aspirin-intolerant asthma by montelukast, a leukotriene antagonist: a randomized, double-blind, placebo-controlled trial.

Leukotriene antagonists block the proinflammatory actions of leukotrienes (LT) and have been introduced as new treatments for asthma. Conventional therapy with glucocorticosteroids does not inhibit the biosynthesis of leukotrienes. We therefore tested whether addition of the leukotriene receptor antagonist montelukast was of therapeutic benefit in a group of aspirin-intolerant patients with asthma of whom 90% already were treated with moderate to high doses of glucocorticosteroids. Under double-blind conditions, 80 aspirin-intolerant patients with asthma were randomized to receive 4 wk oral treatment of either 10 mg of montelukast or placebo once daily at bedtime. Pulmonary function was measured as forced expiratory volume in 1 s (FEV(1)) once a week in the clinic and daily as morning and evening peak expiratory flow rate (PEFR). Asthma symptoms and use of rescue bronchodilator were also recorded daily. Asthma specific quality of life (QoL) was assessed before and after the treatments. The group receiving montelukast showed a remarkable improvement of their asthma, whereas the group given placebo showed no change. Thus, from equal baseline values, the mean difference between the groups over the 4-wk treatment period was 10.2% for FEV(1) and 28.0 L for morning PEFR (p for both < 0.001). The improved pulmonary function in the group receiving montelukast occurred at the same time as 27% less bronchodilator was used (p < 0.05), and it was associated with fewer asthma symptoms than in the group given placebo, including 1.3 nights more of sleep per week and 54% fewer asthma exacerbations (p < 0.05). There was also an improvement in asthma-specific QoL (p < 0.05). The therapeutic response to montelukast was consistent across patients with different baseline characteristics and did not correlate with baseline urinary LTE(4). Addition of a leukotriene receptor antagonist such as montelukast improves asthma in aspirin-intolerant patients over and above what can be achieved by glucocorticosteroids.

Acetates↗

PubMed2002

Genomic gains and losses are similar in genetic and histologic subsets of rhabdomyosarcoma, whereas amplification predominates in embryonal with anaplasia and alveolar subtypes.

In this investigation, we selected PAX3/FKHR and PAX7/FKHR fusion transcript-positive and -negative alveolar rhabdomyosarcomas (ARMSs) and embryonal rhabdomyosarcomas (ERMSs) with and without anaplastic features, to ascertain genomic imbalance differences and/or similarities within these histopathologic and genetic rhabdomyosarcoma (RMS) variants. Comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) studies were performed on 45 rhabdomyosarcoma specimens consisting of 23 ARMSs and 22 ERMSs (12 ERMS cases were included from an earlier study). The anaplastic variant of RMS has not previously been subjected to CGH analysis. Overall, the most prominent imbalances were gain of chromosomes or chromosomal regions 2/2q (40%), 7/7q (31%), 8/8p (53%), 11/11q (31%), 12q13-15 (49%), 13q14 (22%), and 20/20p (31%), and loss of 1p36 (27%), 3p14-21 (22%), 9q21-22 (33%), 10q22-qter (18%), 16q (27%), 17p (22%), and 22 (22%). These gains and losses were distributed equally between ARMS and ERMS histologic subtypes (excluding 7/7q and 11/11q gain that were observed chiefly in ERMS), demonstrating that these entities are similar with respect to recurrent genomic imbalances. Moreover, genomic imbalances were also evenly distributed among the ARMS fusion transcript subtypes, providing evidence for a genetic kinship despite the absence of a fusion transcript in some cases. Genomic amplification was detected in 26% and 23% of the ARMS and ERMS cases, respectively (with nearly all of the latter subset exhibiting anaplastic features). One amplicon, involving 15q25-26, corresponds to the locus of the insulin-like growth factor type I receptor (IGF1R) gene. Amplification of IGF1R was confirmed molecularly in the cases exhibiting a 15q25-26 amplicon. In summary, these results indicate that genomic gains and losses involve alike chromosomes with similar frequencies within the histopathologic and genetic subtypes of rhabdomyosarcoma, that genomic amplification is frequent not only in the alveolar histologic subtype of rhabdomyosarcoma but also in ERMS with anaplasia, and that amplification of IGF1R possibly plays a role in the development or progression of a subset of rhabdomyosarcomas.

Adolescent↗

PubMed2002

Effect of montelukast, a once-daily leukotriene receptor antagonist, on peak expiratory flow variability.

BACKGROUND: Peak expiratory flow (PEF) is an important measure of airway functin in asthma. PEF variability (PEFvar) assessment is described in asthma treatment guidelines as another means of evaluating patient status and response to therapy. OBJECTIVE: The goal of this study was to determine the clinical effect of oral montelukast, a leukotriene receptor antagonist, on PEFvar in asthmatic patients and to assess the relationship of PEFvar with other clinical measures. METHODS: This was a retrospective analysis of data from a multicenter, randomized, double-blind, placebo-controlled, parallel-group study, details of which have been published previously. Eligible patients had chronic stable asthma, had a forced expiratory volume in 1 second (FEV1) that was 50% to 85% of the predicted value, used inhaled beta-agonists, had at least 15% improvement in absolute FEV1 after inhaled beta-agonist administration, and showed a minimal predefined level of daytime asthma symptoms. Treatment consisted of a 2-week, single-blind, placebo run-in period followed by a 12-week, double-blind treatment period (montelukast 10 mg or matching placebo once daily at bedtime). RESULTS: Six hundred eighty-one patients (age range, 15-79 years) were randomized to treatment at 50 centers. Baseline PEFvar was 11.44% +/- 6.55% and 10.62% +/- 6.48% in the montelukast and placebo groups, respectively. PEFvar decreased 20.1% and 7.5% from baseline in the montelukast and placebo groups, respectively. The between-group difference was significant (P < 0.001). PEFvar had low correlation with other clinical measures. CONCLUSIONS: Over 12 weeks of treatment, montelukast significantly reduced PEFvar compared with placebo, indicating improved asthma control. The relative reduction in PEFvar was similar in patients with different degrees of variability at baseline. PEFvar did not correlate highly with other outcome variables and may measure different aspects of the disease.

Acetates↗

PubMed2002

Proenkephalin A gene products activate a new family of sensory neuron--specific GPCRs.

Several peptide fragments are produced by proteolytic cleavage of the opioid peptide precursor proenkephalin A, and among these are a number of enkephalin fragments, in particular bovine adrenal medulla peptide 22 (BAM22). These peptide products have been implicated in diverse biological functions, including analgesia. We have cloned a newly identified family of 'orphan' G protein--coupled receptors (GPCRs) and demonstrate that BAM22 and a number of its fragments bind to and activate these receptors with nanomolar affinities. This family of GPCRs is uniquely localized in the human and rat small sensory neuron, and we called this family the sensory neuron--specific G protein--coupled receptors (SNSRs). Receptors of the SNSR family are distinct from the traditional opioid receptors in their insensitivity to the classical opioid antagonist naloxone and poor activation by opioid ligands. The unique localization of SNSRs and their activation by proenkephalin A peptide fragments indicate a possible function for SNSRs in sensory neuron regulation and in the modulation of nociception.

Amino Acid Sequence↗