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Chang Lu

Publications and source records attributed to Chang Lu.

14 recordsLinked to original sources
PubMed2025

New Genetic Loci Implicated in Cardiac Morphology and Function Using Three-Dimensional Population Phenotyping.

BACKGROUND: Cardiac remodeling occurs in the mature heart and is a cascade of adaptations in response to stress, which are primed in early life. A key question remains as to the processes that regulate the geometry and motion of the heart and how it adapts to stress. METHODS: We performed spatially resolved phenotyping using machine learning-based analysis of cardiac magnetic resonance imaging in 47 549 UK Biobank participants. We analyzed 16 left ventricular spatial phenotypes, including regional myocardial wall thickness and systolic strain in both circumferential and radial directions. In up to 40 058 participants, genetic associations across the allele frequency spectrum were assessed using genome-wide association studies with imputed genotype participants, and exome-wide association studies and gene-based burden tests using whole-exome sequencing data. We integrated transcriptomic data from the GTEx project and used pathway enrichment analyses to further interpret the biological relevance of identified loci. To investigate causal relationships, we conducted Mendelian randomization analyses to evaluate the effects of blood pressure on regional cardiac traits and the effects of these traits on cardiomyopathy risk. RESULTS: We found 42 loci associated with cardiac structure and contractility, many of which reveal patterns of spatial organization in the heart. Whole-exome sequencing revealed 3 additional variants not captured by the genome-wide association study, including a missense variant in CSRP3 (minor allele frequency 0.5%). The majority of newly discovered loci are found in cardiomyopathy-associated genes, suggesting that they regulate spatially distinct patterns of remodeling in the left ventricle in an adult population. Our causal analysis also found regional modulation of blood pressure on cardiac wall thickness and strain. CONCLUSIONS: These findings provide a comprehensive description of the pathways that orchestrate heart development and cardiac remodeling. These data highlight the role that cardiomyopathy-associated genes have on the regulation of spatial adaptations in those without known disease.

Humans↗
PubMed2025

Identification of a PRDM1-regulated T cell network to regulate atherosclerotic plaque inflammation.

BACKGROUND: Inflammation is a key driver of atherosclerosis, yet the mechanisms sustaining inflammation in human plaques remain poorly understood. This study uses a network-based approach to identify immune gene programs involved in the transition from low- to high-risk (rupture-prone) human atherosclerotic plaques. METHODS: Expression data from human carotid artery plaques, both stable (low-risk, n = 16) and unstable (high-risk, n = 27), were analyzed using Weighted Gene Co-expression Network Analysis (WGCNA). Bayesian network inference, operated on the eigengene values from the WGCNA, further extended the WGCNA analysis, and similarity to the signature of T cell subsets was validated in single-cell RNA sequencing data of human plaques, and a loss-of-function study in a mouse model of atherosclerosis. In silico drug repurposing was performed to identify potential therapeutic targets. RESULTS: Our analysis revealed a distinct gene module with a prominent T cell signature, particularly in unstable plaques. Key regulatory factors, RUNX3, IRF7 and in particular PRDM1, were significantly downregulated in plaque T cells from symptomatic versus asymptomatic patients, indicating a protective role. Additionally, as PRDM1 is downstream of IRF7, we opted for PRDM1 as a key target. T cell-specific Prdm1 deficiency in Western-type diet fed Ldlr knockout mice featured accelerated plaque progression. Finally, as PRDM1 targeting drugs are not yet available, we performed in silico drug repurposing, identifying EGFR inhibitors as promising therapeutic candidates. CONCLUSIONS: This study highlights a PRDM1-regulated T cell network that distinguishes high-risk from low-risk plaques and demonstrates the regulatory role of T cell PRDM1 in controlling atherosclerosis, positioning this pathway as a promising therapeutic target.

Plaque, Atherosclerotic↗
PubMed2006

High-throughput and real-time study of single cell electroporation using microfluidics: effects of medium osmolarity.

Electroporation has been widely accepted as an important tool for the delivery of exogenous molecules into cells. Previous mechanistic studies have been carried out by observing either the average behavior from a large population of cells or the response from a small number of single cells. In this study, we demonstrated a novel microfluidic method with high throughput (up to 30 Hz) for real-time studies of single cell electroporation events. Electroporation occurred when cells flowed through a section of a microfluidic channel defined by special geometry. A CCD camera was used to monitor the response of cells starting from the onset of the electroporation. We studied the swelling of Chinese hamster ovary cells and the rupture of cell membrane during electroporation using this technique. We applied buffers with different osmolarities to investigate the effects of medium osmolarity, based on results from a population of single cells. We were able to establish the distributions of the rates of swelling and membrane rupture in the cell population. We also explored establishing the correlation between the property (the cell diameter) and the behavior (the swelling rate) of single cells. Our results indicated that the processes of swelling and rupture occurred more rapidly in the hypotonic or hypertonic buffers than in the isotonic buffer. Statistical analysis did not reveal strong linear correlation between the cell size and the swelling rate. These proof-of-concept studies reveal the potential of applying microfluidics to study electroporation of a cell population at single cell level in real time with high throughput. The limitations associated with this approach were also addressed.

Animals↗
PubMed2006

Electroporation of mammalian cells in a microfluidic channel with geometric variation.

Electroporation has been widely used to load impermeant exogenous molecules into cells. Rapid electrical lysis based on electroporation has also been applied to analyze intracellular materials at single-cell level. There has been increasing demand to implement electroporation in a microfluidic format as a basic tool for applications ranging from screening of drugs and genes to studies of intracellular dynamics. In this report, we have developed a simple technique to electroporate mammalian cells with high throughput on a microfluidic platform. In our design, electroporation only happened in a defined section of a microfluidic channel due to the local field amplification by geometric variation. The time of exposure of the cells to this high field was determined by the velocity of the cells and the length of the section. The change in the cell morphology during electroporation was observed in real time. We determined that electroporation of Chinese hamster ovary cells occurred when the local field strength was increased to approximately 400 V/cm. The internalization of membrane-impermeant molecules (SYTOX green) with cell viability preserved was also carried out to demonstrate transient electropermeabilization. The influence of the operational parameters of the device on cell viability was determined. A large percentage of cells remained viable after electroporation when the parameters were tuned. We also studied rapid cell lysis when the field intensity was in the range of 600-1200 V/cm. The rupture of cell membrane happened within 30 ms when the field strength was 1200 V/cm. Given the simplicity, high throughput, and high compatibility with other devices, this microfluidic electroporation technique may increase the application of microfluidic systems in screening of drugs and biomolecules and chemical cytometry.

Animals↗
PubMed2006

A microfluidic flow-through device for high throughput electrical lysis of bacterial cells based on continuous dc voltage.

Interest in electrical lysis of biological cells on a microfludic platform has increased because it allows for the rapid recovery of intracellular contents without introducing lytic agents. In this study we demonstrated a simple microfluidic flow-through device which lysed Escherichia coli cells under a continuous dc voltage. The E. coli cells had previously been modified to express green fluorescent protein (GFP). In our design, the cell lysis only happened in a defined section of a microfluidic channel due to the local field amplification by geometric modification. The geometric modification also effectively decreased the required voltage for lysis by several folds. We found that local field strength of 1000-1500 V/cm was required for nearly 100% cell death. This threshold field strength was considerably lower than the value reported in the literature, possibly due to the longer duration of the field [Lee, S.W., Tai, Y.C., 1999. Sens. Actuators A: Phys. 73, 74-79]. Cell lysis was detected by both plate count and fluorescence spectroscopy. The cell membrane was completely disintegrated in the lysis section of the microfluidic device, when the field strength was higher than 2000 V/cm. The devices were fabricated using low-cost soft lithography with channel widths considerably larger than the cell size to avoid clogging and ensure stable performance. Our tool will be ideal for high throughput processing of bacterial cells for chemical analysis of intracellular contents such as DNA and proteins. The application of continuous dc voltage greatly simplified the instrumentation compared to devices using electrical pulses for similar purposes. In principle, the same approach can also be applied for lysis of mammalian cells and electroporative transfection.

Cell Culture Techniques↗
PubMed2006

[Screw-rod technique in treating cervical spinal cord injury without fracture and dislocation].

OBJECTIVE: To evaluate the efficacy of screw-rod technique in treating cervical spinal cord injury without fracture and dislocation. METHODS: The screw-rod technique was used to treat 38 patients with cervical spinal cord injury without fracture and dislocation. The JOA scores before and after the surgery were evaluated. RESULTS: No severe complication occurred. The JOA scores were increased by 4.1, 6.7, 7.8, and 8.1 respectively at 0 th, 4 th, 12 th and 24 th weeks after the operation. Neurological deficits were improved one year after the operation in 1 patient. CONCLUSION: Treating cervical spinal cord injury without fracture and dislocation with screw-rod technique can achive an efficient and safe clinical outcome.

Adult↗
PubMed2006

[Diagnosis and treatment of cauda equina syndrome secondary to lumbar disc herniation].

OBJECTIVE: To discuss the diagnosis and treatment of cauda equina syndrome. METHODS: Thirty-four cases of cauda equina syndrome from 1993 to 2005 were analysed retrospectively. Its clinical representation, pathology character and clinical outcome were observed. RESULTS: At follow-ups of 3 to 102 months after the treatment (averagely 43 months), the muscle strength and function of the constrictor began to resume to different degrees. Muscle strength resumed gradually one week after the operation, resumed faster 3 months after the operation, and resumed completely more one year later. Function of the constrictor began to resume 3 days after the operation, and resumed mostly six months or so after the operation. Sense resumed slowly. CONCLUSION: Clinical outcome of cauda equina syndrome is good. Resumption after the operation obviously correlates to the time of operation. One week after the operation, the kinetic function resumes best, function of the constrictor resumes well and the sense function of the saddle area resumes not very well.

Adult↗
PubMed2005

Mucormycosis spondylodiscitis after lumbar disc puncture.

Vertebral osteomyelitis due to mucormycosis is a rare but fulminant and fatal disease. Only one case has been reported in literature, with postmortem diagnosis. The present paper reports a female case of mucormycosis spondylodiscitis and vertebral osteomyelitis after lumbar disc puncture and radio frequency nucleoplasty. She subsequently underwent two surgical debridements, continuous local irrigation and drainage, together with local and systemic Amphotericin B treatments. The infection was controlled 4 months after the second debridement; however, there was no improvement in the neurological function at the most recent follow-up, 16 months after the surgery. The experience of this patient, though a single case, supports early recognition, surgical debridement, systemic and local antifungal treatment, closed irrigation and drainage as the keys to successful treatment.

Antifungal Agents↗
PubMed2005

Relationship between polymorphism of class II transactivator gene promoters and chronic hepatitis B.

AIM: To investigate the relationship between the polymorphism of class II transactivator (CIITA) gene promoters and chronic hepatitis B (CHB). METHODS: Genomic DNA was prepared from peripheral blood leukocytes. Promoters I, III and IV of gene were analyzed respectively with polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) in 65 patients with CHB, 26 patients with acute hepatitis B (AHB) and 85 normal controls. RESULTS: No abnormal migration was found in PCR-SSCP analysis of the three promoters in the three groups. Also, no sequential difference was observed at the three promoters among the CHB patients, AHB patients and normal controls. CONCLUSION: No polymorphism in promoters I, III and IV of CIITA gene exists in CHB patients, ABH patients and normal controls, suggesting that the promoter of CIITA gene might be a conserved domain.

Acute Disease↗
PubMed2005

[Surgical treatment of thoracic vertebral angioma with extraosseous extension causing spinal cord compression].

OBJECTIVE: To evaluate the therapeutical effect of surgical treatment for thoracic angioma with extraosseous extension which causes spinal cord compression and neurological dysfunction. METHODS: We retrospectively analyzed 5 cases of thoracic vertebral body angioma with extraosseous extension and spinal cord compression. The operation were performed through anterior approach to resect the involved vertebral body and intracanal angioma in 5 patients. Bone graft and internal fixation were also completed in the meantime. Two patients accepted radiotherapy for 2 periods of treatment postoperatively, and the other 3 patients didn't accept the other supportive therapy. RESULTS: The blood loss during the operation was 1000 mL to 1500 mL. All the patients recovered their neurological function rapidly after the operation. The patients were followed up for 1 to 4 years, and no patient recurred. The bone graft was solidly fused in all patients. No hardware failure occurred. CONCLUSION: The surgical treatment for thoracic vertebral body and extraosseous angioma with spinal cord compression is effective, reliable, and workable. Good long-term result can be obtained.

Adult↗
PubMed2003

[Primary anterior internal fixation for the surgical management of thoracolumbar spinal tuberculosis].

OBJECTIVE: To discuss the effect of primary anterior debridement, interbody autografting, and anterior internal fixation on the surgical management of thoracolumbar spinal tuberculosis. METHODS: Ninety-one cases of thoracolumbar spinal tuberculosis were treated with primary anterior debridement, interbody autografting, and anterior internal fixation. RESULTS: All cases were treated without any recurrence after follow-up for an average of 13 months. Spinal fusion occurred in 3.7 months on average with 20 degree of kyphosis correction achieved after surgery and 95.5% of the patients obtained good results. CONCLUSION: Primary anterior debridement, interbody autografting, and anterior internal fixation for the surgical management of thoracolumbar spinal tuberculosis are safe and effective and play an important role in reconstruction of spinal stability.

Debridement↗
PubMed2002

[Anterior decompression and reconstruction in the treatment of thoraco-lumbar burst fractures].

OBJECTIVE: To describe the clinic results and advantages of anterior decompression and reconstruction in the treatment of thoraco-lumbar burst fractures. METHODS: Sixty-seven cases with the thoraco-lumbar fractures accompanied with the compression of the spinal cord were treated by anterior decompression and internal fixation. The Frankel impair scale of preoperation and postoperation was observed. RESULTS: The follow-up was 30.1 month in average. All postoperation spinal alignments were good. No secondary kyphnosis occurred; in 95.4% of the patients, the Frankel score rose more than one degree. CONCLUSION: Anterior decompression is complete and anterior reconstruction is strong, and both are fit to spinal biomechanical characteristics.

Adolescent↗