Biomedical subjects

Jianhua Zhao

Publications and source records attributed to Jianhua Zhao.

14 recordsLinked to original sources

PubMed2026

Paired Exome-Based Comprehensive Genomic Profiling and Germline Genetic Testing for Unselected Patients With Colorectal Cancer in a Multicenter Prospective Study.

BACKGROUND AND AIMS: Comprehensive genomic profiling (CGP) for tumors and germline genetic testing (GGT) inform precision therapy and clinical management of patients with colorectal cancer (CRC), and evidence is growing in support of universal paired CGP-GGT patient testing. However, the utility of combining CGP and GGT for early-stage CRC (ESC) and early-onset CRC (EOC) is unclear. METHODS: We performed a prospective, multisite study featuring GGT using an 80+ gene next-generation sequencing platform and exome-based CGP among CRC patients (unselected for age, stage, family history) receiving care at Mayo Clinic Cancer Centers between April 1, 2018, and March 31, 2020. RESULTS: A total of 150 CRC patients had GGT and exome-based CGP performed. ESC patients had an enrichment of high microsatellite instability and high tumor mutation burden. High microsatellite instability was also enriched in those with smoking history, and in tumors with mutated BRAF, homologous recombination deficiency, or at least 1 variant in the rat sarcoma virus pathway. Moreover, patients with smoking history were enriched in BRAF and other Tier 1 or 2 variants overall. Sixteen percent of patients harbored a pathogenic germline variant, most frequent being in Lynch syndrome genes. Paired GGT and CGP testing had high rates of clinically significant findings (≈70%) with the most frequent being high tumor mutation burden status. Pathway and mutational signature analysis revealed frequent CGP mutations in DNA repair and cell cycle pathways. CONCLUSION: These data suggest that universal, combined GGT-CGP increases clinical utility for EOC and ESC patients. This is key for EOC patients who tend to experience poorer outcomes. CGP-GGT expedites germline resolution for tumor mutations in hereditary cancer genes, reducing delays and facilitating identification of relevant therapies, clinical trials, and management recommendations.

Colorectal Cancer↗

PubMed2025

Genome sequencing reveals the impact of pseudoexons in rare genetic disease.

PURPOSE: Advancements in sequencing technologies have significantly improved clinical genetic testing; yet, the diagnostic yield remains around 30% to 40%. Emerging technologies are now being deployed to address the remaining diagnostic gap. METHODS: We tested whether short-read genome sequencing could increase the diagnostic yield in individuals enrolled into the UCI-GREGoR research study, who had suspected Mendelian conditions and prior inconclusive testing. Two other collaborative research cohorts, focused on aortopathy and dilated cardiomyopathy, consisted of individuals who were undiagnosed but had not undergone harmonized prior testing. RESULTS: We sequenced 353 families (754 participants) and found a molecular diagnosis in 54 (15.3%) of them. Of these diagnoses, 55.5% were previously missed because the causative variants were in regions not originally interrogated. In 5 cases, they were deep intronic variants, all of which led to abnormal splicing and pseudoexons, as directly shown by RNA sequencing. All 5 of these variants had inconclusive spliceAI scores. In 26% of newly diagnosed cases, the causal variant could have been detected by exome sequencing reanalysis. CONCLUSION: Genome sequencing can overcome limitations of clinical genetic testing, such as the inability to call intronic variants. Our findings highlight pseudoexons as a common mechanism via which deep intronic variants cause Mendelian disease.

Humans↗

PubMed2006

Protective effects of focal ischemic preconditioning and HSP70 expression on middle cerebral artery occlusion in rats.

To systematically evaluate the importance of protein synthesis in ischemic preconditioning (PC)-induced ischemic tolerance (IT), temporary middle cerebral artery occlusion (MCAO) by Longa (20 min) was used for PC (ischemic precondioning). Twenty-four hours of reperfusion was allowed after PC and before permanent MCAO to establish ischemic tolerance (IT) to compare with non-PC (sham-operated) rats (n = 5 for each group). Infarct size and neurological deficits were measured 24 h after PMCAO. Samples of brain were taken for the determination of HSP70 expression by Western blot analysis. The effects of the protein synthesis inhibitor cycloheximide administered just before PC or administered long after PC but just before PMCAO on IT were also determined (n = 5 for each group). Our results showed that hemispheric infarct was significantly reduced (P < 0.01) only if PC was performed after 24 h, and PC significantly (P < 0.05) reduced neurological deficits (similar to reductions in infarct size). Cycloheximide eliminated ischemic PC-induced IT effects on bothbrain injury and neurological deficits if administered before PC but not if administered long after PC but before PMCAO. PC produced no brain injury but did increase HSP70 protein 24 h after PC. Cycloheximide eliminated that effect. The results suggest that PC is a powerful inducer of ischemic brain tolerance as reflected by the preservation of brain tissue and motor function. PC induces IT that is dependent on de novo protein synthesis.

Animals↗

PubMed2006

[A comparative research of multilevel cervical spondylotic myelopathy treated by two different anterior operative methods].

OBJECTIVE: To compare the outcomes of two operative methods, the anterior decompression in subsection and the anterior decompression in one section, which were used to treat multilevel cervical spondylotic myelopathy (CSM). METHODS: Data of multilevel CSM undergoing the anterior decompression in subsection (33 cases, the subsection group) and the anterior decompression in one section (19 cases, the one section group) from July 1999 to January 2004 were retrospectively analyzed. The incidence of perioperative complications and the rate of fusion were evaluated by the postoperative X-ray and MRI examinations, and improvement of the neurological function was evaluated by the JOA score. RESULTS: The incidence of perioperative complications was 36.8% in the one section group, mainly including immigration of the plate and grafts, which was settled by the revision surgery; while the incidence of perioperative compilcations was 12.1% in the subsection group, mainly including the immigration of the titanium mesh. There was a significant difference between the two groups (P < 0.05). 84.2% of the patients in the one section group and 81.8% of the patients in the subsection group developed bony fusion by the end of the follow-up (9-31 mon, averaged 11.2 mon), and there was no significant difference between the two groups (P > 0.05). According to the JOA score, the ratio of the improvement in the neurological function was 70.4% in the subsection group and 64.4% in the one section group. There was no significant difference between the two groups (P > 0.05). CONCLUSION: The anterior decompression in subsection is more rational for the surgical treatment on the multilevel CSM than the anterior decompression in one section. It can provide an equal decompressive effect but a more stable local mechanical environment right after the surgery and can maintain it well, which is critical for the bony fusion.

Aged↗

PubMed2006

[Clinical application of medical grade calcium sulfate as a bone graft substitute].

OBJECTIVE: To investigate the clinical effect of medical grade calcium sulfate(Osteoset) as a bone graft substitute. METHODS: From December 2004 to May 2005, 9 cases of bone defect(limb group) were repaired with Osteoset pellets; bone defect was caused by benign tumor in limbs, including 3 cases of fibroma xanthomas in humerus (1 case) and acetabulum (2 cases), 2 cases of bone cysts in humerus (1) and radius (1), 1 case of nonossifying fibroma, 1 case of ossifying fibroma and 2 cases of osteofibrous dysplasia in femurs. Five cases of lumbar posterolateral fusion (spine group) were treated with Osteoset pellets as autograft volume expander, including 2 cases of lumbar spinal stenosis, 2 cases of lumbar spondylolisthesis and 1 case of lumbar spondylolysis. Radiological method was used to evaluate the repair effect of Osteoset pellets. RESULTS: The mean follow-up time was 6.2 months (3 to 9 months). Osteoset pellets began to be absorbed after 1 to 3 months of operation, and were totally absorbed and replaced by osseous tissue after 4 to 6 months. No local recurrence was detected in limb group and the function of limbs was normal. At 6 months after operation, all patients in spine group got bony fusion. CONCLUSION: Medical grade calcium sulfate (Osteoset) is an ideal bone graft substitute with excellent bone repair effect.

Adolescent↗

PubMed2005

[Molecular mechanism of bone absorption in osteoclast].

The physiological reconstruction of bone is strictly dependent on bone resorption. Bone resorption is believed to be a complicated molecular reaction process that occurs in the microcircumstance of bone tissue. A lot of enzymes and factors take part in this process, yet there are not enough data with reference to the activation of osteoclast, resorption of bone matrix, regulation of bone resorption. In this paper we review the importance of matrix metalloproteinases (MMPs) in transfer of osteoclast and degradation of bone matrix, and the function of receptor activator of NF-kappaB-ligand (RANKL) and osteoprotegerin (OPG) in regulation of bone resorption.

Bone Resorption↗

PubMed2004

Nickel-induced 1,4-alpha-glucan branching enzyme 1 up-regulation via the hypoxic signaling pathway.

Using the mouse Affymetrix gene chip, we found that 1,4-alpha-glucan branching enzyme 1 (GBE1) was one of the most up-regulated genes following nickel exposure. This result was confirmed by Northern blot in two mouse cell lines, four mouse tissues, and three human cell lines. We further found that this gene was also up-regulated by cobalt, hypoxia, the iron chelator (deferoxamine, or DFO), and the prolyl hydroxylase (PH) inhibitor (dimethyloxalyglycine, DMOG), suggesting that hypoxia inducible factor-1alpha (HIF-1alpha) was involved in the up-regulation of this gene. Experiments using HIF-1alpha +/+ and HIF-1alpha -/- mouse cells demonstrated this gene was up-regulated through a HIF-1alpha-dependent hypoxic signaling pathway. Because the hypoxic signaling pathway is believed to be important in the initiation and progression of carcinogenesis, it is important to study genes regulated by this pathway.

1,4-alpha-Glucan Branching Enzyme↗

PubMed2004

Correlation between serum vascular endothelial growth factor and endostatin levels in patients with breast cancer.

Serum vascular endothelial growth factor (VEGF) and endostatin levels were detected in 59 patients with breast cancer before surgery and at 3 weeks after surgery. Pre-operatively, their levels were significantly elevated and correlated with each other. Post-operatively, VEGF level decreased significantly and endostatin remained at a high level. Patients with both normalized VEGF and elevated endostatin following surgery had a lower risk of relapse than patients whose VEGF failed to normalize. Univariate and multivariate analyses showed a correlation between elevated VEGF level and short free-relapse survival. These findings suggest a new angiogenesis balance is formed in the patients after surgery and such a resultant balance may be beneficial for the prognosis of breast cancer, which deserves more extensive study.

Adult↗

PubMed2004

Nickel-induced down-regulation of serpin by hypoxic signaling.

Nickel (Ni) carcinogenesis is thought to involve gene chip silencing by epigenetic mechanisms. Serpina3g, a member of the mouse serpin family, was among the most down-regulated genes (32-fold) in response to Ni exposure of mouse cells based on the Affymetrix gene chip. Serpina3g down-regulation was controlled by a hypoxia inducible factor (HIF) mechanism. The exposure of cells to cobalt (Co), hypoxia, the iron chelator deferoxamine, and the proline hydroxylase inhibitor dimethyloxalylglycine (DMOG) also down-regulated serpina3g transcription to similar extents as soluble Ni exposure. These results support the mounting experimental evidence that water-soluble Ni compounds have a predominant effect on hypoxia signaling because of their ability to interfere with Fe homeostasis in the cell. Trichostatin A (TSA) and 5-azacytidine (5-AzaC) reactivated the Ni-silenced serpina3g gene, indicating that its silencing by Ni involved either a direct or indirect epigenetic mechanism. Analysis of the chromatin state of the serpina3g promoter by the ChIP assay revealed that exposure of mouse fibroblast cells to Ni resulted in the methylation of H3 lysine 9 within its promoter, as well as a decrease in the phosphorylation of serine 10 of H3 and a marked decrease in the acetylation of H3 and H4. Serpina3g gene expression returned to basal levels following Ni removal, suggesting that the observed silencing was a dynamic and reversible process.

Animals↗

PubMed2003

Effective normalization method for sample-position-dependence effect in photoacoustic spectrometry.

Sample position dependence effect in photoacoustic (PA) spectrometry has been reported by several scientists. This effect must be taken into account in a PA application that requires a quantitative theoretical treatment. In this work, we experimentally investigated PA signal magnitude varying with sample-to-window distance in an MTEC Model 300 Photoacoustic Detector, which has a fixed empty (gas) volume in addition to the sample-to-window-distance-dependent gas volume. An operative method was introduced to obtain the coefficient, which considered the sample-to-window distance and the additional gas volume. With this coefficient, the one-dimensional PA model, developed by Aamodt, Murphy, and Parker, can be employed to quantitatively process PA experimental data, no matter what the sample-to-window distance is. Quantitative measurements of thermal effusivities of two samples were performed to prove this effective normalization method.

Acoustics↗

PubMed2002

The initial evaluation of non-peptidic small-molecule HDM2 inhibitors based on p53-HDM2 complex structure.

Peptidic Mouse Double Minute (MDM2) inhibitors have been demonstrated to effectively inhibit the interaction between p53 and MDM2, thus providing a therapeutic strategy for some tumors. However, there is no report on non-peptidic inhibitors. In this study non-peptidic HDM2 (the human homologue of MDM2) inhibitors were obtained by computer-aided design and subsequently synthesized by chemical method. Bio-evaluation showed that some of these inhibitors have affinity with HDM2, and can cause death of some tumor cells which express wild-type p53. Cellular assays showed that one of these compounds, syc-7, can activate the p53 pathway in some of these tumor cell lines, and further induce apoptosis. The results suggest that developing non-peptidic small-molecule HDM2 inhibitors is a promising way for new antitumor drug discovery.

Antineoplastic Agents↗

PubMed2002

Preparation and degradation characteristic study of bone repair composite of DL-polylactic acid/hydroxyapatite/decalcifying bone matrix.

OBJECTIVE: To explore the preparative method and study the degradation characteristics of bone repair composite of DL-polylactic acid (PDLLA)/hydroxyapatite(HA)/decalcifying bone matrix (DBM) in vitro. METHODS: An emulsion blend method was developed to prepare the composite of PDLLA/HA/DBM in weight ratio of PDLLA:HA:DBM = 1.5-2:1-1.5:1. The dynamic changes of weight, biomechanical property and pH value of PDLLA/HA/DBM and PDLLA in phosphate buffered saline (PBS, pH 7.4) were studied respectively through degradation tests in vitro. RESULTS: Without being heated, PDLLA, HA and DBM could be synthesized with the emulsion blend method as bone composite of PDLLA/HA/DBM, which had both osteoconductive and osteoinductive effects. The diameter of the aperture was 100-400 microm and the gap rate was 71.3%. During degradation, the pH value of PDLLA solution decreased lightly within 2 weeks, but decreased obviously at the end of 4 weeks and the value was 4.0. While the pH value of PDLLA/HA/DBM kept quite steady and was 6.4 at the end of 12 weeks. The weight of PDLLA changed little within 4 weeks, then changed obviously and was 50% of its initial weight at the end of 12 weeks. While the weight of PDLLA/HA/DBM changed little within 5 weeks, then changed obviously and was 60% of the initial weight at the end of 12 weeks. The initial biomechanical strength of PDLLA was 1.33 MPa, decreased little within 3 weeks, then changed obviously and kept at 0.11 MPa at the end of 12 weeks. The initial biomechanical strength of PDLLA/HA/DBM was 1.7 MPa, decreased little within 4 weeks, then changed obviously and kept at 0.21 MPa at the end of 12 weeks. CONCLUSIONS: The emulsion blend method is a new method to prepare bone repair materials. As a new bone repair material, PDLLA/HA/DBM is more suitable for regeneration and cell implantation, and the environment during its degradation is advantageous to the growth of bone cells.

Biocompatible Materials↗

PubMed2002

[The analysis of medical-related cost for in-patients with injuries in Ningxia region].

OBJECTIVE: To understand socio-economic losses of inpatients and deaths caused by injuries in 2000 in Ningxia and to estimate their extent of harmfulness. METHODS: Eight of 35 local hospitals totaling 5 876 inpatients were recruited with two-stage sampling in Ningxia in 2000. All medical cost incurred during their hospitalizations for injuries, cardiovascular and cerebrovascular diseases, respiratory disease, cancer and communicable diseases, losses in labor time were analyzed, and years of potential life lost (YPLL), working years of potential lost (WYPLL), valued years of potential life lost (VYPLL) due to these diseases were estimated for the residents in Ningxia with corrected human capital method. RESULTS: The study showed that indirect economic losses due to hospitalization for injuries accounted for 24 million yuan, higher than those for other diseases. YPLL, WYPLL and VYPLL due to injuries were also higher than those in other diseases. CONCLUSIONS: Injury has caused serious threat to their health of the residents in Ningxia and brought heavy burden for the society and economy. It has become an important public health problem and its prevention and control should be strengthened as soon as possible.

Adolescent↗

PubMed1999

Biomechanical experiment and clinical report of modified patellectomy for polar fracture of the patella.

OBJECTIVE: To study the influence of polar patel-lectomy and the site of reanchored the patellar tendon on femoral quadriceps extensing force. METHODS: The experiment was designed by using 5 lower limbs of cadavers for extracorporal biodynamic test. The maximal fixing force of the double stainless steel wire (0.4 mm in diameter) reanchoring the patellar ligament to the patellar cortical edge was measured. Clinically 21 patients with polar fractures were treated by removing the small fragments and reanchoring the patellar ligament to the cortical edge of the patella using the wires. RESULTS: Resection of the lower 1/4 part of the patella and the patellar ligament reanchored to cortical edge of the patella would not increase femoral quadriceps contracting force arm. But if the patellar tendon reanchored near the joint surface, much more extending force would be needed than the former (P<0.001). The maximal fixing force of the wires is 67.4 kg (60.9-72.5 kg). All the patients using this modified procedure gained satisfactory functional recovery. CONCLUSIONS: The modified partial patellecomy is a simple and effective procedure for choice.

Journal Article↗