Biomedical subjects

Nan Zhang

Publications and source records attributed to Nan Zhang.

At least 19 recordsLinked to original sources

PubMed2026

Integrative multi-omics profiling of insomnia-related molecular features reveals microbiome, immune, and therapy-relevant heterogeneity in colorectal cancer.

Emerging evidence implicates insomnia as a potential risk factor in carcinogenesis, potentially involving systemic inflammation, circadian disruption, and microbiome alterations. However, the molecular associations linking insomnia-related features to colorectal cancer (CRC), particularly with respect to tumor biology, immune microenvironmental states, and therapy-relevant phenotypes, remain largely unexplored. Multi-omics integration of genomic, transcriptomic, and microbiome data from 3,026 CRC patients across seven independent cohorts, including a large, well-annotated Clinical Omics study of Colorectal Cancer in China (COCC) cohort, enabled insomnia-based molecular classification through unsupervised non-negative matrix factorization (NMF) clustering. The insomnia subtype (IS) was biologically characterized via pathway enrichment, immune deconvolution, microbial profiling, and single-cell transcriptomics. Furthermore, an insomnia score (ISscore) was developed and validated in multiple cohorts for risk stratification and assessment of treatment-response-related indicators in CRC. Unsupervised clustering revealed two distinct molecular subtypes (IS1/IS2), with IS2 demonstrating significantly poorer survival. IS2 exhibited marked activation of EMT/angiogenesis pathways versus cell cycle activation in IS1. The IS2 microenvironment showed increased immunosuppression-related infiltration and exhausted T cell signatures, together with intratumoral microbiome variation characterized by depletion of Ruminococcaceae UCG-002 and enrichment of Hungatella/Selenomonas. The ISscore system stratified survival risk and was associated with computational indicators of immunotherapy response. Single-cell analysis nominated PPIA-BSG as a potential cell-cell communication signal involving high-ISscore tumor cells, CXCL12+ endothelial cells, and CLEC9A+ dendritic cell subsets. This multi-omics characterization of insomnia-CRC interplay suggests that insomnia-related molecular features are associated with an immunologically distinct and microbiome-altered tumor ecosystem. The ISscore provides a reproducible framework for capturing insomnia-related molecular heterogeneity, supporting risk stratification and future evaluation of therapy-relevant phenotypes.IMPORTANCEChronic insomnia affects millions, but it is not typically considered a cancer risk factor. Our study, analyzing vast biological data from over 3,000 colorectal cancer patients, uncovers a potential link between a person's predisposition to insomnia and their risk of developing this disease. This suggests that the biological pathways related to sleep may play a role in cancer development. Understanding this connection opens up new avenues for identifying individuals at higher risk and developing novel prevention strategies for colorectal cancer.

colorectal cancer↗

PubMed2026

Metal-Organic Framework-Based and Metal-Organic Framework-Derived Nanomaterials for Cancer Theranostics and Antibacterial Applications: Advances, Challenges, and Perspectives.

Metal-organic frameworks (MOFs), constructed through coordination-driven self-assembly of metal ions/clusters and organic linkers, have emerged as a uniquely versatile class of porous nanomaterials with broad biomedical potential. Despite substantial clinical progress, both oncological treatment and antimicrobial intervention remain constrained by inadequate tumor-targeting selectivity, multidrug resistance, immunosuppressive tumor microenvironments, and the global proliferation of antibiotic-resistant pathogens, limitations that conventional nanocarrier platforms have addressed only in part. MOF-based and MOF-derived nanomaterials, distinguished by tunable pore architecture, structurally and compositionally adaptable metal nodes, high surface areas, and stimulus-responsive degradability, offer a rational framework for overcoming these barriers. This review systematically examines the synthetic strategies underlying MOF-based and MOF-derived nanomaterials, including pyrolysis, chemical etching, composite modification, and functional group introduction, and their structural determinants of performance. In cancer theranostics, we critically evaluate their roles as multimodal imaging contrast agents, stimulus-responsive drug delivery carriers, and platforms for combination therapies encompassing photodynamic, photothermal, chemodynamic, and immunomodulatory modalities. In antibacterial applications, we analyze the mechanistic basis of MOF-based and MOF-derived activity, including physical membrane disruption, reactive oxygen species-mediated oxidative stress, and sustained metal ion release, alongside strategies targeting biofilm formation and antibiotic resistance. Multifunctional platforms that concurrently integrate cancer theranostic and antibacterial capabilities are further discussed. This review also addresses the principal barriers to clinical translation, encompassing large-scale manufacturing, long-term biosafety, and regulatory approval, and proposes future directions incorporating artificial intelligence-assisted design and materials genomics, underscoring the transformative potential of MOF-based and MOF-derived nanomaterials as next-generation precision nanomedicines. This review establishes a unified mechanistic framework grounded in the intrinsic physicochemical properties of MOF-derived nanomaterials, systematically integrating their applications in cancer theranostics and antibacterial therapy. Critically, it bridges fundamental advances with translational reality by incorporating a rigorous assessment of regulatory pathways, scalable manufacturing constraints, and clinical implementation barriers, and offers a comprehensive, practice-oriented reference for the rational design and responsible translation of MOF-based and MOF-derived nanomaterials.

Theranostic Nanomedicine↗

PubMed2026

Graded Mulberry Leaf Supplementation Shapes Gut Microbiota, Reprograms Intestinal Metabolism, and Maintains Intestinal Chemical-Immune Barrier Homeostasis in Amur Sturgeon: A Multi-Omics Study.

Mulberry leaf contains abundant phytochemicals with antioxidant and immunomodulatory activities. However, systematic insight into its dose-dependent regulatory effects on the intestinal health of Amur sturgeon remains limited. In the present study, multi-omics approaches, including 16S rRNA gene sequencing, untargeted metabolomics, transcriptomics, together with RT-qPCR, were applied to investigate graded dietary mulberry leaf supplementation in Acipenser schrenckii. Juvenile sturgeons were fed four experimental diets containing 0%, 2%, 4% and 6% mulberry leaf over a 10-week feeding trial. Dietary mulberry leaf caused no adverse impacts on growth performance or intestinal digestive capacity. Although the overall structure of the intestinal microbiota remained stable, beneficial bacterial taxa were enriched in a dose-dependent manner. Intestinal metabolism underwent hierarchical remodelling: low inclusion levels supported basal nutrient metabolism, medium inclusion strengthened antioxidant capacity, and high inclusion reprogrammed lipid metabolism and immune function. Mulberry leaf reinforced the intestinal chemical barrier by balancing redox homeostasis and reducing mucosal epithelial permeability. Moreover, intestinal immunity was modulated through three sequential phases: initial innate immune priming, B-cell homing, and the establishment of sustained immune tolerance. In conclusion, mulberry leaf maintains intestinal chemical-immune barrier homeostasis in a dosage-tunable manner, supporting its potential application as a functional aquafeed ingredient.

Amur sturgeon (Acipenser schrenckii)↗

PubMed2026

Long-acting reversible contraception, condom use and sexually transmitted infections in developing countries: a multi-country serial cross-sectional analysis using demographic and health surveys.

INTRODUCTION: Unintended pregnancy and sexually transmitted infections (STIs) are major public health issues in developing countries. While long-acting reversible contraception (LARC) effectively prevents unintended pregnancy, there is limited evidence from large multinational studies on its association with condom use and STI-related outcomes. This study aimed to investigate the association between LARC use, condom use and STIs among women in developing countries. METHODS: This serial cross-sectional study extracted data from Demographic and Health Surveys (DHS), a series of nationally representative household surveys conducted in developing countries. The analysis included women aged 15 to 49 years, with data on contraceptive methods and demographics. Generalised linear mixed effect models (GLMMs) were used to estimate adjusted prevalence ratios (aPRs) for condom use and self-reported STI-related outcomes, comparing LARC users with both non-LARC users and oral contraceptive users. Subgroup analyses were conducted at the individual level and at the country level. RESULTS: Data from 2 171 884 women across 31 countries were analysed. Overall, the prevalence of self-reported STI-related outcomes was 7.4%, 3.9% of participants used LARC, and 7.5% of participants reported consistent condom use. LARC users were significantly less likely to use condoms compared with non-LARC users (aPR=0.40, 95% CI 0.30 to 0.53) and compared with oral contraceptive users (aPR=0.61, 95% CI 0.48 to 0.78). LARC use was associated with a higher prevalence of STI-related outcomes compared with non-LARC users (aPR=1.19, 95% CI 1.10 to 1.28) and compared with oral contraceptives users (aPR=1.14, 95% CI 1.05 to 1.24). Associations were stronger in low-Human Development Index (HDI) countries, especially among younger women (15-19 years), but were not significant in high-HDI countries. Country-level heterogeneity was observed. CONCLUSIONS: LARC use is associated with reduced condom use and higher self-reported STI prevalence, particularly among younger women and in lower HDI developing countries. These findings support integrating STI prevention into LARC services and promoting dual-method use to prevent both unintended pregnancies and STIs.

Humans↗

PubMed2026

Integrated landscape of salivary metagenome and multi-biofluid metabolome characterizes a microbial-metabolic axis in upper gastrointestinal cancer progression.

BACKGROUND: Upper gastrointestinal cancer (UGIC) imposes a major global health burden, yet the stage-specific molecular changes along the microbial-metabolic axis remain limited understood. We aimed to delineate this molecular landscape across UGIC progression and evaluate its potential as non-invasive methods for precision screening. RESULTS: Derived from a multi-center population-based UGIC screening program, we enrolled 420 individuals, stratified into normal, low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), and UGIC (n = 105 per group). Integrated salivary metagenomics and paired salivary/plasma metabolomics were performed to capture local and systemic dysregulation. We uncovered distinct stage-specific divergence during UGIC progression: profound remodeling of the salivary microbiota (104 differential species) and salivary metabolomics (80 differential metabolites) initiated early at the LGIN stage, whereas plasma metabolic dysregulation (40 differential metabolites) peaked significantly later at the HGIN stage. Integrative analysis revealed salivary microbiota related more closely with salivary metabolome than plasma metabolome. Moreover, statistical evidence suggested that dysbiotic salivary microbiota was associated with altered lysine- and tryptophan-related catabolic pathways converging on Acetyl-CoA-related metabolic nodes, supporting a potential metabolic mechanism in precancerous lesions. Finally, the discriminative model integrating metagenomic and metabolomic markers demonstrated promising diagnostic performance in distinguishing these precancerous lesions (LGIN: area under the curve [AUC] = 0.83; HGIN: AUC = 0.77) and UGIC (AUC = 0.76) from normal. CONCLUSION: This study characterizes a stage-specific microbial-metabolic axis that facilitates the comprehensive understanding of UGIC pathogenesis. These multi-biofluid signatures offer a promising non-invasive triage strategy for detecting precancerous lesions and optimizing endoscopic resource allocation. Video Abstract.

Female↗

PubMed2025

Efficient site-specific integration of kilobase-length DNA fragments in plant cells via Kp03 recombinase.

Targeted insertion of large DNA sequences into plant genomes remains a major challenge in synthetic biology. Here, we evaluate the large serine recombinase Kp03 for site-specific integration of DNA fragments in rice and Arabidopsis. In transient protoplast assays, Kp03 mediates efficient insertion of donor DNA up to 27.3 kilobases (kb), with plasmid integration efficiencies reaching 99.1% for fragments up to 3.4 kb. Truncation experiments reveal that a minimal 15-bp attB sequence is necessary for integration. As a proof of concept, Kp03 successfully incorporates a 3.4-kb donor DNA into the rice genome at a locus containing this minimal attB sequence. Moreover, in rice callus, combining Kp03 with the NM-PE genome editing system to install a 26-bp attB site enables targeted integration of a 3.4-kb donor at the desired genomic locus. These findings establish Kp03 as a versatile tool for plant genome engineering, with broad applications for synthetic biology.

Oryza↗

PubMed2025

Proteomic-based identification of novel EV-derived protein antibodies biomarkers for melioidosis diagnosis.

Melioidosis, caused by Burkholderia pseudomallei (Bp), is a life-threatening disease characterized by diverse clinical manifestations and limited diagnostic capabilities. Extracellular vesicles (EVs) have emerged as critical carriers of novel antibody targets for serodiagnosis. In this study, we established a Bp-infected BEAS-2B cell model (Bp/BEAS-2B) and isolated EV from both Bp and Bp/BEAS-2B cells to generate EV proteome, identifying potential antigenic biomarkers for melioidosis diagnosis. Bioinformatics analysis identified PPEP and POMCR proteins as candidate antigens, with BLF1 and omp A serving as positive controls. Using a self-developed IgM-ELISA, serum samples from 43 melioidosis patients and 47 healthy volunteers were analyzed to detect antibodies against these antigens. Anti-POMCR IgM demonstrated exceptional diagnostic performance, with an AUC of 0.9872 (95% CI: 0.9713-1.003), sensitivity of 93.02% and specificity of 97.92% at a cutoff value of OD450 = 0.118. Similarly, IgM against PPEP, BLF1, and omp A also showed high diagnostic accuracy, with AUC values of 0.969, 0.9621, and 0.976, respectively. The accuracy of anti-POMCR and anti-PPEP were 96.43% and 95.54%, respectively, equivalent to anti-omp A (93.75%) and anti-BLF1 (91.96%). Antibodies to EV-derived proteins effectively differentiated melioidosis patients from other bacterial infections and healthy volunteers, highlighting their clinical potential as diagnostic tools for melioidosis.

Humans↗

PubMed2025

Causal relationship between white matter structural connectivity and epilepsy.

White matter structural connectivity has recently been linked to epilepsy pathogenesis, yet its causal role remains unclear. This study used Mendelian randomization (MR) to investigate the causal relationship between white matter structural connectivity and epilepsy. GWAS summary statistics for white matter structural connectivity were sourced from the UK Biobank, while epilepsy data were obtained from FinnGen R10 and the International League Against Epilepsy (ILAE). Our MR analysis revealed significant causal links between white matter structural connectivity and epilepsy risk. Increased connectivity between the right hemisphere visual and salience/ventral attention networks (RH Vis to RH Sal/VentAttn WMSC) was associated with higher epilepsy risk in FinnGen_R10_FE_STRICT (OR = 2.25, 95 % CI = 1.43-3.56, p < 0.01, FDR P = 0.019). Conversely, increased connectivity between left and right hemisphere salience/ventral attention networks (LH Sal/VentAttn to RH Sal/VentAttn WMSC) was linked to reduced epilepsy risk in FinnGen_R10_GE_STRICT (OR = 0.17, 95 % CI = 0.07-0.46, p < 0.01, FDR P = 0.033). A total of 15 nominally significant associations were identified across datasets. These findings suggest a causal relationship between white matter structural connectivity and epilepsy, offering insights into disease mechanisms and potential therapeutic targets.

Humans↗

PubMed2025

Metagenomic and Transcriptomic Datasets of Plateau Brown Frogs (Rana kukunoris) from the Helan Mountains.

Global climate change has become a primary driving factor behind the biodiversity crisis in amphibians, making it crucial to understand how climate change affects species and their potential responses. The plateau brown frog (Rana kukunoris) is often regarded as an ideal ecological indicator species, yet research on its environmental adaptation mechanisms based on transcriptomic and microbiomic studies remains limited. Therefore, this study investigates the adaptation strategies of the plateau brown frog to environmental changes, providing extensive transcriptomic and the first comprehensive metagenomic dataset from two distinctly different environmental regions (eastern and western slopes of the Helan Mountains). We gathered transcriptomic data from three tissues (blood, liver, and muscle), resulting in 294,962 unigenes and 570,192 transcripts. Metagenomic sequencing identified major bacterial groups, including Firmicutes, Proteobacteria, Bacteroidetes, Spirochetes, and Actinobacteria. In summary, the results of this study can be used to further explore the associations among microbiota, host, and environment, which are crucial for comprehending the mechanisms of environmental adaptation in this species and contributing to the conservation of amphibian biodiversity.

Animals↗

PubMed2025

Clinical and Multiorgan Proteomics Characteristics of the Diverse Fatal Phase in Super Elderly Patients With SARS-CoV-2 Infection: A Descriptive Study.

This study aims to identify the risk factors associated with clinical outcomes and the proteomic changes in organs related to fatal SARS-CoV-2 infection within the super-elderly population. This retrospective analysis included all elderly individuals with COVID-19 admitted to the Second Medical Center of PLA General Hospital from December 2022 to January 2023. The follow-up period ended on March 30, 2023. During this time, epidemiological, demographic, laboratory, and outcome data were analyzed descriptively. Proteomic sequencing was performed on super-elderly patients who died from COVID-19 at different stages of the disease. A total of 352 elderly COVID-19 patients, with a mean age of 89.84 ± 8.54 years, were included in this study. During a median follow-up period of 98 days, 79 patients died. Deceased patients were older and more likely to have cardiovascular and cerebrovascular diseases, with a lower prevalence of lipid-lowering therapy. The number of deaths in the acute and post-acute phases were 34 and 45, respectively. Proteomics data suggest that the immune systems of patients who died in the acute phase underwent a more rapid and severe onslaught. Patients in the post-acute phase showed higher levels of viral genome replication and a more robust immune response. However, the over-activation of the immune system led to systemic organ dysfunction. Effective management of comorbidities may improve the prognosis of COVID-19 in super-elderly patients. The continuous replication of the SARS-CoV-2 virus and its subsequent impact on the immune system are critical determinants of survival time in this demographic.

Humans↗

PubMed2007

Synthesis and SAR of [1,2,4]triazolo[1,5-a]pyrimidines, a class of anticancer agents with a unique mechanism of tubulin inhibition.

The synthesis and SAR of a series of triazolopyrimidines as anticancer agents are described. Treatment of 5-chloro-6-(trifluorophenyl)-N-fluoroalkyl [1,2,4]triazolo[1,5-a]pyrimidin-7-amine with an alcohol, a thiol, or an alkylamine provided the corresponding final compounds. A clear SAR requirement has been established for optimal activity. A (1S)-2,2,2-trifluoro-1-methylethylamino group or an achiral 2,2,2-trifluoroethylamino group is required at the 5-position to achieve high potency. On the phenyl ring, both fluoro atoms, at the positions ortho to the triazolopyrimidine core, are needed for optimal activity. At the position para to the triazolopyrimidine core, on the phenyl ring, the best activity is achieved with an oxygen linkage followed by a three-methylene unit, and an alkylamino or a hydroxy group. The mechanism of action for this series of triazolopyrimidines was shown to be unique in that they promoted tubulin polymerization in vitro, but did not bind competitively with paclitaxel.1 Instead, they inhibit the binding of vincas to tubulin. Selected compounds were studied further, and it was shown that these compounds were able to overcome resistance attributed to several multidrug resistance transporter proteins. Lead compounds were shown to inhibit tumor growth in several nude mouse xenograft models, with high potency and efficacy, when dosed either orally or intravenously.

Administration, Oral↗

PubMed2006

Purification and characterization of cathepsin L from the muscle of silver carp (Hypophthalmichthys molitrix).

Cathepsin L in silver carp musle was purified to 48.4-fold by acid-heat treatment and ammonium sulfate fractionation, followed by a series of chromatographic separations. The molecular mass of the purified enzyme was 30 kDa determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The purified enzyme was activated by dithiothreitol and cysteine while it was substantially inhibited by E-64 and insensitive to PMSF and pepstatin A, suggesting that the purified enzyme belongs to a family of cysteine proteinase. Consistent with this conclusion, Zn2+, Cu2+, Co2+, Ni2+, and Fe2+ could strongly inhibit the activity of this enzyme. The optimal pH and temperature were 5.0 and 55 degrees C, respectively. The enzyme catalyzed the hydrolysis of Z-Phe-Arg-MCA with a parameter of K(m) (8.27 microM) and K(cat) (28.7 s(-1)) but hardly hydrolyzed Z-Arg-Arg-MCA, Arg-MCA, and Boc-Val-Leu-Lys-MCA. The microstructure analysis by scanning electron microscopy showed that this proteinase is capable of destroying the network structure of silver carp surimi gels. The enzyme exhibited a higher hydrolytic activity on surimi protein at 65 degrees C than at 40 degrees C.

Animals↗

PubMed2006

A search for principles of disability using experimental impairment of Drosophila melanogaster.

The results of life table experiments to determine the effects of artificial impairment (leg amputation) in 7500 Drosophila melanogaster adults revealed that the extent to which life expectancy was reduced in impaired individuals was conditional on: (1) leg location and number amputated--front leg had greatest impact and the number of legs amputated directly correlated with mortality impact; (2) age of amputation--the greatest relative reduction in remaining life expectancy occurred when young flies were impaired; (3) vial orientation--mortality in impaired flies was the least when vials held upside-down (most friendly environment) and the greatest when they were right-side up (least friendly environment); and (4) sex--male mortality was increased more than female mortality in nearly all impairment treatments. These results were used to formulate a set of general principles of disability that would apply not only to humans but to all organisms.

Amputation, Surgical↗

PubMed2006

Single-molecule analysis of dynein processivity and stepping behavior.

Cytoplasmic dynein, the 1.2 MDa motor driving minus-end-directed motility, has been reported to move processively along microtubules, but its mechanism of motility remains poorly understood. Here, using S. cerevisiae to produce recombinant dynein with a chemically controlled dimerization switch, we show by structural and single-molecule analysis that processivity requires two dynein motor domains but not dynein's tail domain or any associated subunits. Dynein advances most frequently in 8 nm steps, although longer as well as side and backward steps are observed. Individual motor domains show a different stepping pattern, which is best explained by the two motor domains shuffling in an alternating manner between rear and forward positions. Our results suggest that cytoplasmic dynein moves processively through the coordination of its two motor domains, but its variable step size and direction suggest a considerable diffusional component to its step, which differs from Kinesin-1 and is more akin to myosin VI.

Amino Acid Sequence↗

PubMed2006

Identification of the angiogenesis signaling domain in pleiotrophin defines a mechanism of the angiogenic switch.

Neoplasms progress through genetic and epigenetic mutations that deregulate pathways in the malignant cell that stimulate more aggressive growth of the malignant cell itself and/or remodel the tumor microenvironment to support the developing tumor mass. The appearance of new blood vessels in malignant tumors is known as the "angiogenic switch." The angiogenic switch triggers a stage of rapid tumor growth supported by extensive tumor angiogenesis and a more aggressive tumor phenotype and its onset is a poor prognostic indicator for host survival. Identification of the factors that stimulate the angiogenic switch thus is of high importance. Pleiotrophin (PTN the protein, Ptn the gene) is an angiogenic factor and the Ptn gene has been found to be constitutively expressed in many human tumors of different cell types. These studies use a nude mouse model to test if Ptn constitutively expressed in premalignant cells is sufficient to trigger an angiogenic switch in vivo. We introduced an ectopic Ptn gene into "premalignant" SW-13 cells and analyzed the phenotype of SW-13 Ptn cell tumor implants in the flanks of nude mice. SW-13 Ptn cell subcutaneous tumor implants grew very rapidly and had a striking increase in the density of new blood vessels compared to the SW-13 cell tumor implants, suggesting that constitutive PTN signaling in the premalignant SW-13 cell implants in the nude mouse recapitulates fully the angiogenic switch. It was found also that ectopic expression of the C-terminal domain of PTN in SW-13 cell implants was equally effective in initiating an angiogenic switch as the full-length PTN whereas implants of SW-13 cells in nude mice that express the N-terminal domain of PTN grew rapidly but failed to develop tumor angiogenesis. The data suggest the possibility that mutations that activate Ptn in premalignant cells are sufficient to stimulate an angiogenic switch in vivo and, since these mutations are frequently found in human malignancies, that constitutive PTN signaling may be an important contributor to progression of human tumors. The data also suggest that the C-terminal and the N-terminal domains of PTN equally initiate switches in premalignant cells to cells of a more aggressive tumor phenotype but the separate domains of PTN signal different mechanisms and perhaps signal through activation of a separate receptor-like protein.

Adrenal Gland Neoplasms↗

PubMed2006

Long-term persistence of hepatitis B surface antigen and antibody induced by DNA-mediated immunization results in liver and kidney lesions in mice.

DNA-mediated immunization has been recognized as a new approach for prevention and treatment of hepatitis B virus (HBV) infection. However, the side effects of this approach have not been well described. Here we report that DNA-mediated immunization by intramuscular injection of plasmid DNA encoding HBV surface antigen (HBsAg) induced long-term persistence of HBsAg and HBsAg-specific antibody (anti-HBs) in the sera of the immunized BALB/c mice and resulted in liver and kidney lesions. The lesions persisted for 6 months after injection. Lesions were also found in normal mice injected with the sera from immunized mice, and in HBV-transgenic mice injected with anti-HBs antibody, or sera from immunized mice. Furthermore, lesions were accompanied by deposition of circulating immune complex (CIC) of HBsAg and anti-HBs antibody in the damaged organs. These results indicate that long-term persistence of HBsAg and anti-HBs in the immunized mice can result in deposited CIC in liver and kidney, and in development of lesions. The use of DNA containing mammalian replication origins, such as the plasmids used in this study, is not appropriate for human vaccines due to safety concerns relating to persistence of DNA; nevertheless, the safety of DNA-mediated immunization protocols still needs to be carefully evaluated before practical application.

Animals↗

PubMed2006

Improved technique of mouse heterotopic heart graft retransplantation.

Research on chronic graft failure requires a graft retransplantation model to elucidate the affects of early transplant episodes on long-term graft survival. Prolonged ischemic time is the major hurdle for this retransplant model. Here we describe a novel technique of mouse heart retransplantation, with a shortened retransplant ischemic time and higher success rate. The primary heart transplant employed an allogeneic abdominal heart-transplant technique (Balb/C to C57BL/6 mice). Thirty to 60 days later, the graft was reharvested and retransplanted into the second syngeneic recipient (Balb/C mice) by using cervical heterotopic heart transplantation with a cuff technique. The total ischemic time of retransplant was reduced to within 35 min with the cuff technique, and a greater retransplant success rate (90.6%) was achieved. This heart retransplantation technique is a novel, useful tool in transplantation research.

Animals↗

PubMed2006

Diphenhydramine as an adjunct to sedation for colonoscopy: a double-blind randomized, placebo-controlled study.

BACKGROUND: Intravenous benzodiazepines in combination with opiates are used to achieve moderate sedation for colonoscopy. Although effective, these agents have potential adverse effects, such as respiratory depression and hypotension. Diphenhydramine hydrochloride possesses central nervous system depressant effects that theoretically could provide a synergistic effect for sedating patients. OBJECTIVE: The objective was to assess the efficacy of adding diphenhydramine hydrochloride as an adjunct to improve sedation and to reduce the amount of standard sedatives used during colonoscopy. DESIGN: We conducted a prospective, randomized, double-blind, placebo-controlled study. SETTING: The study was conducted in a university hospital with an active GI fellowship training program. PATIENTS: The study group comprised 270 patients undergoing screening/diagnostic/therapeutic colonoscopy were enrolled. INTERVENTIONS: Patients were randomized to receive either 50 mg of diphenhydramine or placebo, given intravenously 3 minutes before starting conscious sedation with intravenous midazolam and meperidine. MAIN OUTCOME MEASUREMENTS: The main outcome measure was anesthetic effect as assessed by the endoscopy team and by the patient; quantity of adjunctive sedatives to achieve adequate sedation. RESULTS: Of 270 patients, data were analyzed for 258 patients, with 130 patients in the diphenhydramine group and 128 patients in the placebo group. There was a 10.1% reduction in meperidine usage and 13.7% reduction in midazolam usage in favor of the diphenhydramine group. The mean evaluation scores as judged by the faculty, the fellows, and the nurses were statistically significant in favor of the diphenhydramine group. In addition, patient scores for overall sedation and pain level favored the group that received diphenhydramine. CONCLUSIONS: Intravenous diphenhydramine given before initiation of standard sedation offers a significant benefit to conscious sedation for patients undergoing colonoscopy.

Colonoscopy↗