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Fan Li

Publications and source records attributed to Fan Li.

At least 19 recordsLinked to original sources
PubMed2026

Spatial mapping of RNA turnover kinetics in the mouse brain.

Gene regulation requires coordinated control of RNA synthesis and degradation, yet measuring RNA turnover across intact tissues remains challenging. Here we present spatial NT-seq, a method that combines transgenesis-free metabolic RNA labeling with in situ chemical recoding on spatial transcriptomics platforms to co-map newly synthesized and pre-existing RNAs. Applying spatial NT-seq to the mouse brain reveals pronounced regional heterogeneity in RNA turnover and identifies the dentate gyrus as a spatial hotspot marked by coordinated upregulation of basal RNA synthesis and decay. Moreover, spatial NT-seq uncovers rapid, brain region-specific transcriptional and post-transcriptional responses to electroconvulsive stimulation, a clinically relevant treatment for refractory depression. Finally, we leverage computational modeling to identify sequence features and post-transcriptional regulators that shape transcriptome-wide mRNA stability across spatial and cellular contexts in the mouse brain. Together, this integrated 'in vivo timescope' framework provides a spatially resolved view of RNA turnover kinetics and reveals the regulatory architecture of RNA stability in vivo.

Journal Article↗
PubMed2026

Comparative effectiveness of torsemide vs furosemide in the management of heart failure patients: Win-ratio reanalysis of the TRANSFORM-HF trial.

BACKGROUND: Loop diuretics are widely used for managing congestion in patients with heart failure (HF). The TRANSFORM-HF trial is a multicenter randomized study that enrolled heart failure patients, comparing a strategy of torsemide vs furosemide. The time-to-event analysis demonstrated neutral effects on all-cause death at 30 months and the composite of all-cause death and first rehospitalization at 12 months. We evaluated whether a hierarchical win-ratio (WR) framework integrating mortality, recurrent hospitalization, and patient-reported health status provides additional interpretive insight. METHODS: This study is a secondary analysis of the pragmatic, multicenter, open-label, randomized TRANSFORM-HF trial, conducted across 60 US hospitals that randomized 2,859 patients hospitalized with HF to torsemide or furosemide. The primary 12-month hierarchical composite outcome was defined as (1) all-cause mortality, (2) recurrent all-cause hospitalizations, and (3) lack of improvement in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS). The primary statistical method was a WR analysis adjusting covariates via inverse probability weighting. Subgroup analyses evaluated potential heterogeneity across patient demographics and clinical characteristics. RESULTS: In the primary 12-month intention-to-treat analysis, the adjusted WR was 1.07 (95% CI, 0.98-1.16; P = .13), indicating no significant difference between torsemide and furosemide. A supplementary 30-month analysis with extended mortality follow-up yielded a similar estimate (adjusted WR, 1.06; 95% CI, 0.98-1.16; P = .14); hospitalization and KCCQ-CSS components were assessed through 12 months. As-treated sensitivity analyses were consistent with the neutral primary findings. Exploratory subgroup analyses were not adjusted for multiplicity and should be considered hypothesis-generating. CONCLUSIONS: The overall WR comparison between torsemide and furosemide showed no statistically significant difference in the primary 12-month analysis. The WR framework provided an interpretive decomposition across outcome domains but did not establish superiority of either loop diuretic strategy. All findings should be considered exploratory. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03296813, https://clinicaltrials.gov/study/NCT03296813.

Aged↗
PubMed2025

Global Evolution and Transmission Dynamics of Enterovirus D68.

Enterovirus D68 (EV-D68), a serotype of the enterovirus species D, has garnered significant attention due to outbreaks reported in 2014, 2016, and 2018. In this study, 36 Chinese EV-D68 strains were isolated, sequenced, and combined with all EV-D68 VP1 sequences from GenBank to form a data set of 1679 sequences. This data set served as the basis for phylogenetic, evolutionary dynamics, phylogeographic, and key amino acid site mutation analyses of EV-D68. Based on the VP1 region, EV-D68 is classified into four genotypes (A-D), and seven subgenotypes (B1-B3, D1-D4), with B3 and D3 being the predominant subgenotypes. Bayesian skyline plots indicated that genotypes B and D experienced multiple population expansions, aligning with reported EV-D68 outbreaks. Phylogeographic analyses of the B3 subgenotypes revealed sequences from Europe and North America clustering into a single evolutionary branch, suggesting significant transmission between these regions. Additionally, mutation analysis identified VP1-98 as a high-frequency mutation site, differing significantly between the previously prevalent A and C genotypes and the currently prevalent B and D genotypes. However, the functional implications of this mutation require further investigation. This study provides a solid theoretical basis for epidemiological research, disease surveillance, and prevention efforts related to EV-D68.

Enterovirus Infections↗
PubMed2006

Development of hepatitis C virus vaccine using hepatitis B core antigen as immuno-carrier.

AIM: To develop hepatitis C virus (HCV) vaccine using HBcAg as the immuno-carrier to express HCV T epitope and to investigate its immunogenicity in mice. METHODS: We constructed the plasmid pTrc-core(NheI) using gene engineering technique, constructed the pcDNA3.1-core(NheI)-GFP plasmid with GFP as the reporter gene, and transfected them into Hela cells. The expression of GFP was observed under confocal microscopy and the feasibility of using HBcAg as an immuno-carrier vaccine was studied. pTrc-core gene with a synthetic T epitope antigen gene of HCV (35-44aa) was fused and expressed in the plasmid pTrc-core-HCV (T). For the fusion of the HBcAg-T protein, sucrose, density gradient centrifugation was used, and its molecular weight and purity were analyzed by SDS-PAGE. Then balb/c mice were immunized by the plasmid with the HBcAg (expressed by pTrc-core) protein as control. The tumor regression potential was investigated in mice and evaluated at appropriate time. After three times of immunization, the peripheral blood and spleen of vaccinated mice were collected. HBcAb was detected by ELISA, and nonspecific T lymphocyte proliferation and response of splenocytes were respectively examined by MTT assay. T cell subset of blood and spleen were detected by FACS. RESULTS: GFP was successfully expressed. Tumor regression trial showed that no tumor formation was found in the group receiving immunization, while tumor xenograft progression was not changed in the control group. Strong nonspecific lymphocyte proliferation response was induced. FACS also showed that the ratio of CD8+ T cells in the experimental group was higher than the controls, but the serum HBcAb in experimental group was similar to the control. CONCLUSION: HBcAg can be used as an immuno-carrier of vaccine, the fusion of HBcAg-T protein could induce stronger cellular immune responses and it might be a candidate for therapeutic vaccines specific for HCV.

Animals↗
PubMed2006

[Expressions of Bcl-2 and Caspase-3 in the internal organs of rats when tetramine was administered].

OBJECTIVE: To find whether Bcl-2 and Caspase-3 take part in the pathophysiological mechanism of tetramine toxification. METHODS: Sixty Sprague-Dawley rats were divided into normal control group, the sham poisoned group, high dose poisoned group, low dose poisoned group. High dose poisoned group were administered 1.0 mg/kg weight body tetramine by mouth, however low dose poisoned group was administered tetramine 0.1 mg/kg weight body by mouth. The rats of the sham poisoned group were administered water, and rats of normal control group were given nothing. Bcl-2 and Caspase-3 were detected by immunohistochemistry staining and the results were assessed by image analysis system. RESULTS: The expressions of Bcl-2 and Caspase-3 in all organs were similar, ie, Bcl-2 and Caspase-3 expressed obviously in all organs of high dose poisoned group; in all organs of low dose poisoned group, they were hardly detected at 30 min after administration, however, at 3 h after administration, they could be detected obviously; Bcl-2 got to peak at 6 h-3 d after administration and Caspase-3 got to peak at 24 h-3 d after administration. CONCLUSION: Bcl-2 and Caspase-3 take part in the pathophysiological procedure of tetramine poisoned rats.

Animals↗
PubMed2006

Polydesigns and causal inference.

In an increasingly common class of studies, the goal is to evaluate causal effects of treatments that are only partially controlled by the investigator. In such studies there are two conflicting features: (1) a model on the full cohort design and data can identify the causal effects of interest, but can be sensitive to extreme regions of that design's data, where model specification can have more impact; and (2) models on a reduced design (i.e., a subset of the full data), for example, conditional likelihood on matched subsets of data, can avoid such sensitivity, but do not generally identify the causal effects. We propose a framework to assess how inference is sensitive to designs by exploring combinations of both the full and reduced designs. We show that using such a "polydesign" framework generates a rich class of methods that can identify causal effects and that can also be more robust to model specification than methods using only the full design. We discuss implementation of polydesign methods, and provide an illustration in the evaluation of a needle exchange program.

Biometry↗
PubMed2006

Protective effect of total flavones of rhododendra on ischemic myocardial injury in rabbits.

This study was to investigate the effect of total flavones of rhododendra (TFR) on ischemic myocardial injury in rabbits. Rabbit ischemic myocardial injury was induced by occluding the anterior descent of the left artery (LAD). The ECG was recorded; the plasma creatine kinase (CK), nitric oxide (NO) and endothelin-1 (ET-1) levels were measured using spectrophotometry, Griess method and radioimmunoassay, respectively. The myocardial ischemic size and infarction size were determined by dual staining with Evan's blue and Nitroblue tetrazolium reductionest (N-BT). A typical ECG S-T segment elevation and an increase of plasma CK activity were observed 6 and 24 hours after the induction of ischemia. These changes were inhibited in rabbits treated with either TFR (30, 60 mg/kg) or ginkgo biloba extract (EGB) for 7 days, indicating a protective effect of TFR on ischemic myocardial injury. The myocardial ischemic size and infarction size were 40.7 +/- 3.6% and 36.8 +/- 3.6% respectively in the control group, while TFR (60 mg/kg) pretreatment for 7 days significantly reduced both myocardial ischemic size (32.40 +/- 5.38%, p < 0.05) and infarction size (28.7 +/- 5.8%, p < 0.05). In addition, the occlusion of LAD resulted in an increase of ET-1 and a decrease of NO levels in the plasma, effects that were inhibited by TFR treatment, suggesting a possible mechanism for the protective effect of TFR against myocardial ischemic injury.

Animals↗
PubMed2006

[Retrospective analysis of autopsy on 49 cases of medical tangles in perinatal period].

Medical tangles caused by the death of women and infants in perinatal period are very normal in the forensic appraisal. The author collected and analyzed 49 cases of these tangles from many aspects, such as sex and age of the dead, hospital,information of autopsy, fault of medical action and so on,and discovered the normal causes of death, medical action's effects and the causes of tangle. It would be useful to the forensic appraisal, settlement and prevention of these medical tangles.

Adult↗
PubMed2006

[Relationship between the injury time and DNA fragmentation and its quantity in rat brain].

OBJECTIVE: To observe the changes of DNA fragmentation and its quantity along with the time of injury in nerve cells after brain contusion. METHODS: The model of brain contusion caused by free drop hammer was established. TUNEL and Feulgen's DNA staining conjoined with image analysis technique were used for exploration. RESULTS: With the gradually rising of DNA fragmentation, DNA quantity was declining in the brain tissue after contusion. CONCLUSION: TUNEL and Feulgen's DNA staining conjoined with image analysis technique could be utilized in the timing of brain injury and provide a new approach for this issue.

Animals↗
PubMed2006

[Observation the electroporation of blood cells in vitro by scanning electron microscope].

OBJECTIVE: To observe changes on cell membrane in blood cells after they were been electrified. METHODS: Blood were electrified for 5, 10, 20, 30 s, 1 min respectively, and Scanning electron microscope was used to detect the changes on their cell membranes. RESULTS: Pores were detected both on electrified erythrocytes and leukocytes with round or ellipse shapes. The erythrocytes often have one or more pores while the leukocytes often have more pores looked like cribble. The rates of perforated cells were increased with the prolonging time of electrification, 5 s with 6% and 1 min increased to 40%. CONCLUSIONS: Alternating current can cause the cell perforating, and the rates of perforated cell were increased with the prolonging time of electrification.

Adult↗
PubMed2006

[The relationship of injury timing with the change of neuronal apoptosis and the expression of caspase-3 after brain contusion].

OBJECTIVE: To investigate and analyze the changes of neuronal-apoptosis and the expression of caspase-3 for finding out a new method of injury timing after brain contusion in human. METHODS: The tissue was stained by TUNEL for apoptosis and by immunohistochemistry for caspase-3. Image analysis technique was employed. RESULTS: The nerve cells stained positive by TUNEL and Caspase-3 immunohistochemistry were distributed in the penumbra and central area. Both these areas were in striking contrast with the distal area or those of control group. The positive staining was more prominente in penumbra area than in central area (P < 0.05). The changes of TUNEL staining and expression of Caspase-3 in penumbra area gradually increased with the survival period after injury; they were parallel to each other. There were linear relationships between the time of injury in 48 hours and the increase in the mean of integral optical density (IOD), the coefficient of correlation (r) being 0.93 and 0.69 for the two staining methods, and two linear regression formulae were induced, respectively. CONCLUSION: Observations on the increasing of neuronal apoptosis and Caspase-3 expression in relation with the survival period after injury could be utilized in the timing of brain contusion.

Adolescent↗
PubMed2006

[Spatial variability of temperature in semi-aerobic landfilling structure].

The study indicated that the semivariogram function of temperature in semi-aerobic landfilling structure could be well modeled by the linear with sill model. The correlation range of the profile was 3.5 m, and the sill value was 83.6. The unmeasured temperature values were interpolated with Kriging method, and the temperature isoline showed that high temperature region located at 3 to approximately 5.5 m in the vertical direction of the middle part, while low temperature area laid in 0 to approximately 1 m on the two sides of the landfill structure and substrate. The weighted average temperature of the profile was 59.80 degrees C, which could be regarded as the indicator of landfilling structure' s formation.

Models, Theoretical↗
PubMed2006

[Analysis of genetic characteristics of wild-type measles viruses in Jilin Province 2005].

OBJECTIVE: To investigate the know gene types of main wild type measles virus strains and take measures to control measles in Jilin Province. METHODS: Genetic characterization of 9 measles viruses isolated from 72 throat swabs or urine specimens of measles patients using CDW(150) cells line was studied in Jilin Province in 2005. RESULTS: Sequence analysis of 450 nucleotides of COOH-terminal of nucleoprotein (N) genes of 9 isolates indicated that all were members of H(1) genotype, in which there are 7 strains of H1a and 2 strains of H1b, the H1a subgroup differed from H1b by 2.0% approximately 3.5% at the nucleotide level in the COOH-terminal of the N gene. CONCLUSIONS: The H(1) genotype of wild-type measles viruses should be the main epidemic strain and main pathogen that caused measles outbreaks and sporadic cases in Jilin Province.

China↗
PubMed2005

The effect of antigen targeting sequences on antibody responses to hepatitis E virus DNA vaccines in rats and sheep.

Expression of the capsid (PORF2) protein of hepatitis E virus (HEV) in mammalian cells results in heterogeneous intracellular processing with a mixture of stable and rapidly degraded forms, which might be expected to influence immune responses to DNA immunisation. Plasmids encoding the N-terminal 22 or 50 amino acids of PORF2 (Sig1 or Sig3, respectively) fused at the N-terminus of the ORF2.1 antigen of HEV (amino acids 394-660 of PORF2) were examined for processing in vitro and antibody responses in vivo, in both rats and sheep. Unmodified ORF2.1 is an unstable cytosolic protein and Sig1-ORF2.1 is a stable membrane-associated protein, whereas Sig3-ORF2.1 demonstrated heterogeneous processing analogous to that of full-length PORF2. After DNA immunisation, Sig1-ORF2.1 demonstrated a 30-fold enhancement of antibody responses in rats compared to untargeted ORF2.1, increasing to more than 200-fold after boosting with recombinant protein, but was ineffective in sheep. In contrast, Sig3-ORF2.1 did not give a significant effect in rats, but demonstrated 4-5-fold enhancement of antibody responses in sheep, and this enhancement was maintained after boosting with recombinant protein. These results suggest that Sig3 in particular may have promise as a targeting molecule for DNA vaccines in large animals.

Amino Acid Sequence↗
PubMed2005

Analysis of recursive gene selection approaches from microarray data.

MOTIVATION: Finding a small subset of most predictive genes from microarray for disease prediction is a challenging problem. Support vector machines (SVMs) have been found to be successful with a recursive procedure in selecting important genes for cancer prediction. However, it is not well understood how much of the success depends on the choice of the specific classifier and how much on the recursive procedure. We answer this question by examining multiple classifers [SVM, ridge regression (RR) and Rocchio] with feature selection in recursive and non-recursive settings on three DNA microarray datasets (ALL-AML Leukemia data, Breast Cancer data and GCM data). RESULTS: We found recursive RR most effective. On the AML-ALL dataset, it achieved zero error rate on the test set using only three genes (selected from over 7000), which is more encouraging than the best published result (zero error rate using 8 genes by recursive SVM). On the Breast Cancer dataset and the two largest categories of the GCM dataset, the results achieved by recursive RR are also very encouraging. A further analysis of the experimental results shows that different classifiers penalize redundant features to different extent and this property plays an important role in the recursive feature selection process. RR classifier tends to penalize redundant features to a much larger extent than the SVM does. This may be the reason why recursive RR has a better performance in selecting genes.

Algorithms↗
PubMed2005

Comparative evaluation of tigecycline and vancomycin, with and without rifampicin, in the treatment of methicillin-resistant Staphylococcus aureus experimental osteomyelitis in a rabbit model.

OBJECTIVES: Staphylococcus aureus is the most common organism isolated in osteomyelitis. Methicillin-resistant S. aureus (MRSA) infections are particularly difficult to treat. We evaluated the efficacy of tigecycline and vancomycin with and without rifampicin in a rabbit model of MRSA osteomyelitis. METHODS: A 28 day antibiotic therapy with a subcutaneous injection of tigecycline (14 mg/kg twice daily), with and without oral rifampicin (40 mg/kg twice daily); or subcutaneous administration of vancomycin (30 mg/kg twice daily), with and without oral rifampicin (40 mg/kg twice daily) were compared. Osteomyelitis was induced with an intramedullary injection of 10(6) colony-forming units of MRSA. Infected rabbits were randomly divided into six groups: tigecycline, tigecycline with oral rifampicin, vancomycin, vancomycin with oral rifampicin, and no treatment control and tigecycline bone penetration groups. Treatment began 2 weeks after infection. After 4 weeks of therapy, the rabbits were left untreated for 2 weeks. Rabbits were then euthanized, and the tibias were harvested. The bones were cultured, and bacterial counts of MRSA were performed. RESULTS: Rabbits that received tigecycline and oral rifampicin therapy (n=14) showed a 100% infection clearance. Rabbits treated with tigecycline (n=10) showed a 90% clearance. Rabbits treated with vancomycin and oral rifampicin (n=10) also showed a 90% clearance. Rabbits treated with vancomycin (n=11) showed an 81.8% clearance. Untreated controls (n=15) demonstrated only a 26% clearance. For the tigecycline bone penetration group, the bone concentrations of tigecycline in the infected tibia were significantly higher than the non-infected ones. CONCLUSIONS: Tigecycline may be an effective alternative to vancomycin in the treatment of MRSA osteomyelitis.

Animals↗
PubMed2005

Several recombinant capsid proteins of equine rhinitis a virus show potential as diagnostic antigens.

Equine rhinitis A virus (ERAV) is a significant pathogen of horses and is also closely related to Foot-and-mouth disease virus (FMDV). Despite these facts, knowledge of the prevalence and importance of ERAV infections remains limited, largely due to the absence of a simple, robust diagnostic assay. In this study, we compared the antigenicities of recombinant full-length and fragmented ERAV capsid proteins expressed in Escherichia coli by using sera from experimentally infected and naturally exposed horses. We found that, from the range of antigens tested, recombinant proteins encompassing the C-terminal region of VP1, full-length VP2, and the N-terminal region of VP2 reacted specifically with antibodies present in sera from each of the five experimentally infected horses examined. Antibodies to epitopes on VP2 (both native and recombinant forms) persisted longer postinfection (>105 days) than antibodies specific for epitopes on other fragments. Our data also suggest that B-cell epitopes within the C terminus of VP1 and N terminus of VP2 contribute to a large proportion of the total reactivity of recombinant VP1 and VP2, respectively. Importantly, the reactivity of these VP1 and VP2 recombinant proteins in enzyme-linked immunosorbent assays (ELISAs) correlated well with the results from a range of native antigen-based serological assays using sera from 12 field horses. This study provides promising candidates for development of a diagnostic ERAV ELISA.

Animals↗