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Biomedical subjects

Rui Xu

Publications and source records attributed to Rui Xu.

At least 19 recordsLinked to original sources

Engineered Transformer Base Editor with Enhanced Editing Efficiency.

Canonical cytosine base editors (CBEs) achieve precise C-to-T conversions without inducing DNA double-strand breaks (DSBs), yet their clinical potential remains hampered by substantial off-target (OT) mutations. The recently developed transformer base editor (tBE) significantly reduces both genomic and transcriptomic OT mutations by using a cleavable deoxycytidine deaminase inhibitor (dCDI) domain. However, the modest base editing efficiency limits its broader applications. Here, through rational deaminase engineering and fusion of a uracil DNA glycosylase inhibitor (UGI) domain, we developed the engineered tBE (etBE). The etBE exhibited substantially enhanced editing efficiencies compared with the parental tBE (up to 35.11-fold improvement), while maintaining high editing fidelity and background levels of OT mutations. As a therapeutic proof-of-concept, dual adeno-associated virus (AAV)-mediated delivery of etBE targeting proprotein convertase subtilisin/kexin type 9 (PCSK9), a well-established therapeutic target for cardiovascular diseases, was evaluated in a humanized mouse model. The treatment achieved efficient in vivo base editing (up to 35.13%), resulting in substantial reductions in plasma PCSK9 protein (24%) and low-density lipoprotein cholesterol (LDL-C) levels (33%), while inducing only minimal OT mutations. Collectively, etBE represents a highly efficient and specific base editing platform with enormous potential for both basic research and clinical applications.

CRISPR‐Cas9↗

Mitochondrial genomic characteristics and phylogenetic analysis of Cunninghamella elegans (Mucorales: Cunninghamellaceae).

Cunninghamella, a filamentous fungal genus with important biomedical and biochemical value, lacks any fully annotated mitochondrial genome to date. Herein, we presented the first complete mitogenome of Cunninghamella elegans, a circular 41,552 bp molecule (GC 27.86%) encoding 14 conserved protein-coding genes, 2 rRNA genes, 24 tRNA genes, and 6 non-conserved ORFs. Structural comparison with related species (Absidia glauca and Gongronella sp. w5) revealed dynamic evolution in intron and repeat elements. Phylogenetics places C. elegans within Cunninghamellaceae, with Gongronella as its closest relative. This reference mitogenome will underpin future evolutionary and taxonomic investigations of this industrially and medically significant lineage.

Cunninghamella elegans↗

Decoding age-stratified clinical and molecular heterogeneity in male breast cancer through multiomic profiling.

OBJECTIVE: Age-associated molecular heterogeneity is well described in female breast cancer but remains insufficiently characterized in male breast cancer (MBC). We profiled age-stratified clinical and molecular differences between younger (&#x2264;55 years) male breast cancer (YMBC) and older (>55 years) male breast cancer (OMBC). METHODS: We retrospectively analyzed 347 patients with MBC diagnosed at Fudan University Shanghai Cancer Center by integrating clinicopathological data, RNA sequencing, and whole-exome sequencing (WES). Survival, differential expression, and mutational signature analyses were performed. Tumor microenvironment features were inferred using xCell and ESTIMATE, and weighted gene co-expression network analysis (WGCNA) was conducted to identify age-associated co-expression modules. Candidate therapeutics were prioritized using the Genomics of Drug Sensitivity in Cancer (GDSC) resource and evaluated using patient-derived organoids (PDOs). RESULTS: Compared with OMBC, YMBC more frequently had human epidermal growth factor receptor 2 (HER2)-positive status (14.91% vs. 4.02%) and triple-negative tumors (4.92% vs. 1.78%), and had worse 5-year recurrence-free survival (hazard ratio=2.19, P=0.018). Transcriptomic analyses indicated enrichment of neural-related programs and reduced immune-related signaling in YMBC, and xCell/ESTIMATE supported lower immune infiltration. Consistently, WGCNA identified age-associated modules linking neural-related programs with reduced immune infiltration. Immunohistochemistry supported increased perineural invasion and lower CD8+ T cell infiltration in YMBC. GDSC-guided prioritization with PDO testing nominated sepantronium bromide (YM155) as a candidate vulnerability in YMBC. WES showed a higher NBPF10 mutation frequency in YMBC (54.5% vs. 14.3%, P<0.05). CONCLUSIONS: Integrated multi-omics profiling revealed age-stratified clinical and molecular heterogeneity in MBC. YMBC patients demonstrated inferior recurrence-free survival, neural signaling enrichment, an immune-cold microenvironment, and enriched NBPF10 mutations. These findings support age as a meaningful stratification variable in MBC risk assessment and treatment planning, and highlight the need for caution when considering treatment de-escalation in younger patients, while nominating YM155 as a candidate agent for prospective evaluation.

Male breast cancer↗

BIOCARD framework: integrating fecal bile acids, lipids, and metabolites to assess response to a cardiovascular health intervention.

Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality, particularly in under-resourced populations. Although nutritional interventions are important for CVD prevention, their outcomes are commonly evaluated using conventional clinical and behavioral indicators, which may not fully capture early molecular responses. In this study, we developed the BIOCARD framework, an exploratory fecal multi-omics platform integrating bile acids, lipids, and metabolites to evaluate intervention outcomes related to cardiovascular health. Fecal samples were collected from caregiver-child participants enrolled in a 10-week randomized controlled trial comparing a multicomponent garden-based intervention (SHA) with an education-only control group (MSP). Fecal polar metabolites, lipids, and bile acids were analyzed by UHPLC-HRMS-based approaches and integrated with conventional health indicators. Traditional clinical indicators in the present study showed limited sensitivity for detecting intervention-related differences. In contrast, fecal multi-omics analyzes revealed intervention-associated differences in metabolites, lipids, and bile acids, with children showing more apparent molecular variation than parents. Network analysis further revealed associations between selected molecular features and cardiovascular-related indicators, including blood pressure, body fat, skin carotenoids, and Healthy Eating Index scores. Together, these findings suggest that the BIOCARD framework may serve as an exploratory molecular approach to complement traditional outcome measures and improve the evaluation of nutritional interventions for cardiovascular health.

Humans↗

Cerebellar iTBS enhances gait adaptation by modulating cortical sensorimotor network dynamics: a randomized controlled trial.

Gait adaptation enables individuals to maintain locomotor stability under persistent perturbations. Although the cerebellum is critical for sensory prediction error-based (SPE) adaptation, how cerebellar neuromodulation reshapes cortical sensorimotor networks to enhance gait adaptation remains unclear. This study investigated the behavioral effects and underlying cortical neurodynamic mechanisms of cerebellar intermittent theta-burst stimulation (iTBS) on gait adaptation. Thirty-two healthy adults received either active or sham cerebellar iTBS. Participants performed a split-belt treadmill adaptation task before and after intervention. Cortical responsiveness was evaluated using TMS-evoked EEG over primary motor cortex (M1), while resting-state EEG was analyzed to assess spectral power and directional functional connectivity. Compared to sham, cerebellar iTBS significantly enhanced gait adaptation, evidenced by a faster adaptation rate (p&#x202f;=&#x202f;0.035) and enhanced Early Adaptation SLS (p&#x202f;=&#x202f;0.011), without altering initial perturbation responses or post-adaptation outcomes. The iTBS increased TMS-evoked &#x3b1; (p&#x202f;=&#x202f;0.031) and &#x3b3; (p&#x202f;=&#x202f;0.022) power in M1, while the &#x3b1; power was correlated with faster adaptation (r&#x202f;=&#x202f;0.526, p&#x202f;=&#x202f;0.002). Furthermore, iTBS strengthened PPC-to-M1 directed connectivity in the &#x3b2; (p&#x202f;=&#x202f;0.025) and &#x3b3; (p&#x202f;=&#x202f;0.013) bands. Enhanced parieto-motor directionality were positively associated with adaptation rate (&#x3b2;: r&#x202f;=&#x202f;0.515, p&#x202f;=&#x202f;0.003; &#x3b3;: r&#x202f;=&#x202f;0.463, p&#x202f;=&#x202f;0.009). These findings suggest that cerebellar iTBS facilitates gait adaptation by modulating cortical responsiveness and directional sensorimotor network connectivity, providing multi-level neurodynamic evidence for the cerebello-cortical modulation during gait adaptation and offering a strong physiological rationale for targeted neuromodulation in gait rehabilitation strategies.

Humans↗

Dual signal-enhanced immunochromatographic test strip based on Au@PtNPs: From sensitive detection of thiamethoxam to multiplex pesticide screening in vegetables.

Immunochromatographic test strip (ICTS) is a rapid analytical technique widely used in environmental and food detection owing to its merits of simple operation and short analysis time. Herein, three-dimensional nanoflower-structured gold&#x2011;platinum nanoparticles (Au@PtNPs) were synthesized via a seed-growth method. Compared with conventional gold nanoparticles (AuNPs), Au@PtNPs exhibited stronger signal intensity, excellent catalytic performance, and efficient antibody binding efficiency. Colorimetric Au@PtNPs-ICTS and catalytic colorimetric Au@PtNPs-ICTS were developed for the sensitive detection of thiamethoxam (THI) in vegetables. The limits of detection (LODs) for colorimetric Au@PtNPs-ICTS and catalytic colorimetric Au@PtNPs-ICTS quantitative analysis were 0.18&#xa0;ng/mL and 0.093&#xa0;ng/mL, respectively, representing approximately 3-fold and 6-fold improvement compared to AuNPs-ICTS (0.56&#xa0;ng/mL). Furthermore, highly sensitive detection of multiple pesticide residues (chlorpyrifos, acetamiprid, and imidacloprid) was achieved by replacing the corresponding target antigens and antibodies, which further verified the universality of this immunochromatographic strategy.

Thiamethoxam↗

A New Threat Emerges: The First Detection of GVIII Genotype IBV in China and the Urgent Need for Molecular Surveillance.

In 2025, an infectious bronchitis virus (IBV) strain of the GVIII genotype was identified and isolated from a poultry farm in Hebei Province, China, representing the first documented detection of this IBV genotype within the country to date. Nucleotide homology analysis revealed that the S1 gene of this isolate shares 62.2%-96.9% sequence identity with previously reported GVIII-type strains from other countries. Comprehensive phylogenetic analysis of the complete genome indicated that this strain originated from a single recombination event: Its S gene may have been derived from the GVIII-1 lineage strain IBV/Ck/USA/CA/21-1883, while the remaining genomic regions were likely acquired from the GI-19 lineage strain SD. Pathogenicity evaluation demonstrated that infected flocks exhibited reduced body weight gain, with 40% of chickens showing signs of diarrhea. Necropsy findings included hemorrhagic lesions at the proventriculus-gizzard junction and within the bursa of Fabricius. Moreover, 85% of infected hens developed severe oviduct hypoplasia, and 90% showed a reduction in follicular number. The isolate described in this study constitutes the first detection of a GVIII genotype IBV strain in China, although its route of introduction remains undetermined. The emergence of this strain highlights the necessity for sustained molecular surveillance of IBV and the development of genotype-matched vaccines.

Animals↗

Alternating diacetylene copolymer utilizing perfluorophenyl-phenyl interactions.

The symmetric diacetylenes, 2,4-hexadiynylene dibenzoate 4 and 2,4-hexadiynylene bis(pentafluorobenzoate) 5, as well as the unsymmetric 6-(pentafluorobenzoyloxy)hexa-2,4-diynyl benzoate 6 were prepared and investigated with respect to their reactivity toward topochemical polymerization in the crystalline state. The 1:1 cocrystal 4.5 was successfully polymerized to the corresponding poly(diacetylene) copolymer 7, as evidenced by solid-state (13)C NMR and Raman spectroscopy, as well as single-crystal structure analysis of the monomer-polymer cocrystal. Thus, perfluorophenyl-phenyl interactions were utilized as complementary supramolecular synthons in the cocrystallization of two different diacetylene monomers and their unprecedented conversion into a strictly alternating diacetylene copolymer.

Journal Article↗

[Surgical treatment for bilateral traumatic optic neuropathy through intranasal endoscopic approach].

OBJECTIVE: This study was aimed to explore the necessity of nasal endoscopic operation for bilateral traumatic optic neuropathy. METHODS: Four patients with complete blind resulted from traumatic impairment of bilateral optic nerves were selected to receive a combined treatment of nasal endoscopic optic nerve decompression (NEOND) with all-around medication. RESULTS: The vision of all patients was improved except one who lost vision immediately after trauma. Thirty days after injury, patient 1 was treated with NEOND, and the vision of left eye was restored to 1.5, however, the vision of right side was just from light perception (LP) to hand motion (HM). Patient 2 was treated with NEOND 3 days after injury, and the vision was improved from LP to 0. 2 in left side, no change in right eye. The operation of patient 3 was performed 6 days after injury, but no improvement was observed in both visions. Patient 4 received NEOND 28 days after injury, the vision was improved in both sides with left eye from NLP to 0. 8 and right eye from NLP to 0.2. CONCLUSIONS: NEOND can be regarded as an effective treatment for bilateral traumatic blindness, even delayed NEOND may be effective. Both gradual vision loss and residual vision should be the indications for an effective NEOND, but immediate blindness after injury might be the index for poor result of NEOND.

Adult↗

[Effects of losartan, ramipril and their combination on left ventricular remodeling and function in spontaneous hypertensive rats].

OBJECTIVE: To evaluate the effects of losartan, an angiotensin receptor blocker, ramipril, an angiotensin converting enzyme inhibitor, and their combination on left ventricular remodeling and diastolic function in SHR at the same level of blood pressure. METHODS: Sixty-two SHRs and 20 WKYs were divided randomly into 5 groups: WKY-control group, SHR-control group, SHR-ramipril group, SHR-losartan group, and SHR-combination group. Twelve weeks after feeding, 6 rats from each group were randomly selected to undergo hemodynamic examination and then killed to undergo further examinations, and 24 weeks after the remaining rats underwent the same examinations. The hemodynamic examination included the systolic blood pressure (SBP) of the caudal artery, left ventricular systolic pressure (LVSP), left ventricle end diastolic pressure (LVEDP), maximum uprising velocity of left ventricle pressure (dP/dtmax), and maximum declining velocity of left ventricle pressure (-dP/dtmax), and tau. Then the hearts were taken out to measure the weight of heart, undergo pathological examination, measure the intracellular free calcium concentrations, hydroxyproline concentration, interstitial collagen volume fraction (CVF), perivascular collagen area/luminal area (PVCA/LA), the mRNA expression of SR Ca(2+)-ATPase, phospholamban and L-type calcium channel, and the protein levels of SR Ca(2+)-ATPase. The myocardial ultrastructure was analyzed by electron microscopy. RESULTS: The speed, extent, and sustained time of blood pressure decrease were better in the combination group than in the other 2 treatment groups. Twelve and 24 weeks after treatment the levels of LVM/BW in the combination group were significantly lower than those of the control group, however, without significant differences among the 3 treatment groups. The values of LVSP, LVEDP, and tau 12 and 24 weeks after treatment in the 3 treatment groups were all significantly lower and the levels of -dP/dtmax significantly higher than those of the control group (all P < 0.01). The values of CVF in the myocardium and PCVA/VA of the heart wall arteriole 12 and 24 weeks after in the 3 treatment groups were significantly lower than those of the control group, and the CVF in the myocardium 12 weeks after in the combination group was significantly than that of the ramipril group. Microscopy showed that the degree of myocardial fibrosis in the 3 treatment groups were significantly milder than those of the control group, and the ultrastructure improvement improved along with the lapse of time in the sequence of combination group > losartan group > ramipril group. The concentrations of hydroxyproline in cardiac muscle cells of the 3 treatment 12 and 24 weeks after were significantly than those of the control group and decreased gradually time-dependently. The expression of Ca(2+)-ATPase mRNA 24 weeks after of the ramipril, losartan, and combination groups were 53.5%, 72.9%, and 76.7% higher than that of the control group, and the Ca(2+)-ATPase protein expression of the 3 treatment groups were 28.9%, 33.3%, and 49.3% higher than that of the control group. The expression of L-type Ca(2+) channel mRNA of the 3 treatment groups were 51.8%, 76.8%, and 98.2% than that of the control group. CONCLUSION: Both losartan and ramipril reverse LVH and left ventricular diastolic dysfunction. A combination of these two drugs is more effective than single drug treatment for improvement of myocardial fibrosis and ultrastructure. All three-treatment groups can raise calcium-handling proteins mRNA and protein expressions, which may be the underlying molecular mechanisms for their therapeutic effects.

Angiotensin II Type 1 Receptor Blockers↗

A general procedure for the enantioselective synthesis of the minor tobacco alkaloids nornicotine, anabasine, and anatabine.

The minor tobacco alkaloids nornicotine, anabasine, and anatabine from Nicotiana tobacum are known to possess nicotinic receptor agonist activity, although they are relatively less potent than S-(-)-nicotine, the principal tobacco alkaloid. Previous pharmacological investigations and structure-activity studies have been limited owing to the lack of availability of the optically pure forms of these minor alkaloids. We now report a 2-step synthetic procedure for the enantioselective synthesis of the optical isomers of nornicotine and anabasine, and a modified procedure for the synthesis of anatabine enantiomers. These procedures involve initial formation of the chiral ketimine resulting from the condensation of either 1R, 2R, 5R-(+)- or 1S, 2S, 5S-(-)-2-hydroxy-3-pinanone with 3-(aminomethyl)pyridine followed by enantioselective C-alkylation with an appropriate halogenoalkane or halogenoalkene species, N-deprotection, and base-catalyzed intramolecular ring closure, to form the appropriate, chirally pure minor tobacco alkaloid. Using this approach, the R-(+)- and S-(-)-enantiomers of the above minor tobacco alkaloids were obtained in good overall chemical yield and excellent enantomeric excess.

Alkaloids↗

Introduction of unsaturation into the N-n-alkyl chain of the nicotinic receptor antagonists, NONI and NDNI: effect on affinity and selectivity.

N-n-octylnicotinium iodide (NONI) and N-n-decylnicotinium iodide (NDNI) are selective nicotinic receptor (nAChR) antagonists mediating nicotine-evoked striatal dopamine (DA) release, and inhibiting [3H]nicotine binding, respectively. This study evaluated effects of introducing unsaturation into the N-n-alkyl chains of NONI and NDNI on inhibition of [3H]nicotine and [3H]methyllycaconitine binding (alpha4beta2* and alpha7* nAChRs, respectively), (86)Rb+ efflux and [3H]DA release (agonist or antagonist effects at alpha4beta2* and alpha6beta2*-containing nAChRs, respectively). In the NONI series, introduction of a C3-cis- (NONB3c), C3-trans- (NONB3t), C7-double-bond (NONB7e), or C3-triple-bond (NONB3y) afforded a 4-fold to 250-fold increased affinity for [3H]nicotine binding sites compared with NONI. NONB7e and NONB3y inhibited nicotine-evoked 86Rb+ efflux, indicating alpha4beta2* antagonism. NONI analogs exhibited a 3-fold to 8-fold greater potency inhibiting nicotine-evoked [3H]DA overflow compared with NONI (IC50 = 0.62 microM; Imax = 89%), with no change in Imax, except for NONB3y (Imax = 50%). In the NDNI series, introduction of a C4-cis- (NDNB4c), C4-trans-double-bond (NDNB4t), or C3-triple-bond (NDNB3y) afforded a 4-fold to 80-fold decreased affinity for [3H]nicotine binding sites compared with NDNI, whereas introduction of a C9 double-bond (NDNB9e) did not alter affinity. NDNB3y and NDNB4t inhibited nicotine-evoked 86Rb+ efflux, indicating antagonism at alpha4beta2* nAChRs. Although NDNI had no effect, NDNB4t and NDNB9e potently inhibited nicotine-evoked [3H]DA overflow (IC50 = 0.02-0.14 microM, Imax = 90%), as did NDNB4c (IC50 = 0.08 microM; Imax = 50%), whereas NDNB3y showed no inhibition. None of the analogs had significant affinity for alpha7* nAChRs. Thus, unsaturated NONI analogs had enhanced affinity at alpha4beta2*- and alpha6beta2*-containing nAChRs, however a general reduction of affinity at alpha4beta2* and an uncovering of antagonist effects at alpha6beta2*-containing nAChRs were observed with unsaturated NDNI analogs.

Aconitine↗

Expression and clinical significance of TAp73alpha, p53, PCNA and apoptosis in hepatocellular carcinoma.

AIM: To study the prognostic role of TAp73alpha, p53, proliferating cell nuclear antigen (PCNA) and apoptosis in patients with hepatocellular carcinoma (HCC) after surgical tumor ablation. METHODS: Forty-seven human resected HCC tissues and 42 adjacent non-cancerous tissues were studied with 10 normal liver tissues as control group. TAp73alpha, p53, and PCNA were detected with Elivision immunohistochemistry. Terminal deoxynucleotidyl transferase (TdT)-mediated d-UTP-biotin nick-end labeling (TUNEL) method was used to detect the apoptosis cells. All clinical and pathological materials were analyzed by SPSS10.0 statistical package. RESULTS: TAp73alpha overexpressed in HCC tissues (36.2%) when compared with adjacent non-cancerous tissues (2.38%, P<0.005) and normal liver tissues (0, P<0.01). Mutant type p53 (mt-p53) overexpressed in HCC tissues (38.3%) when contracted with adjacent non-cancerous tissues (16.7%, P<0.05) and normal liver tissues (0, P<0.01). Proliferation index (PI) level in HCC tissues was significantly higher than that in adjacent non-cancerous tissues (30.34%+/-4.46% vs 27.88%+/-5.89%, t, P = 0.028). Apoptosis index (AI) level in HCC tissues was higher than that in adjacent non-cancerous tissues (8.62%+/-2.28% vs 7.38%+/-2.61%, t, P = 0.019). Expression of TAp73alpha was associated with lymph node metastasis and mt-p53, with r = 0.407 and 0.265, respectively. Expression of mt-p53 was associated with Edmondson's stage and AFP, with r = 0.295 and -0.357, respectively. In Kaplan-Meier univariant analysis, TAp73alpha, AFP, TNM stage, portal vein invasion, liver membrane invasion and HBsAg correlated with prognosis (log rank, P = 0.039, 0.012, 0.002, 0.000, 0.014, 0.007, respectively). Multivariant Cox regression analysis showed that TAp73alpha, AFP, TNM stage, portal vein invasion, liver membrane invasion and age were independent factors of prognosis. CONCLUSION: These results suggest that TAp73alpha can be used as a prognostic indicator of patients with HCC undergoing surgical tumor ablation. AFP, TNM, portal vein invasion, liver membrane invasion and age also have a potency of predicting the prognosis of HCC.

Adult↗

[Comparison of instrumented posterior fusion with instrumented circumferential lumbar fusion in the treatment of lumbar stenosis with low degree lumbar spondylolisthesis].

OBJECTIVE: To compare and evaluate instrumented posterior fusion with instrumented circumferential lumbar fusion in the treatment of lumbar stenosis with low degree lumbar spondylolisthesis. METHODS: From April 1998 to April 2003, 45 patients who suffered from lumbar stenosis with low degree lumbar spondylolisthesis were divided into 2 groups (A and B) at random. The patients in group A (n = 24, average age 54 years old) were performed decompressive laminectomy, intertransverse process arthrodesis with bone grafting and transpedicle instrumentation of solid connection (SOCON) system. The patients in group B (n = 21, average age 53 years old) were performed the same procedure as group A except adding posterior lumbar interbody fusion (PROSPACE). The main levels of lumbar spondylolisthesis in 2 groups was L(4 - 5) or L(5)-S(1). All cases were classified as degree 1 to degree 2. All patients in the two groups received preoperative myelography or CTM, and were diagnosed lateral recess stenosis and(or) central lumbar canal stenosis. RESULTS: All the patients were followed up from 12 to 72 months. In group A, the results showed that the preoperative clinical symptoms disappeared completely in 12 of 24 patients, pain relief was seen in 91.7% (22/24), anatomical reduction rate was 91.7%. No infection or neurologic complication occurred in this series. In group B, the results showed that the preoperative clinical symptoms disappeared completely in 13 of 21 patients, pain relief was seen in 90.5% (19/21), anatomical reduction rate was 95.2%. Four cases of infection or neurologic complication occurred in this series. Two groups had no significant difference in follow-up clinical outcome and anatomical reduction rate. But group A had better intraoperative circumstances and postoperative outcome than group B, group B had better postoperative parameters in X-ray of angle of slipping and disc index than group A. CONCLUSIONS: The best surgical treatment method of lumbar stenosis with low degree lumbar spondylolisthesis is complete intraoperative decompressive laminectomy, reduction with excellent transpedicle system instrumentation and solid fusion after bone grafting. The use of cage should be conformed to strict indications.

Adolescent↗

Expression of fragile histidine triad in primary hepatocellular carcinoma and its relation with cell proliferation and apoptosis.

AIM: To evaluate the expression of fragile histidine triad (FHIT) gene protein, product of a candidate tumor suppressor, and to investigate the relationship between FHIT, cell apoptosis and proliferation, and pathological features of primary hepatocellular carcinoma (HCC). METHODS: Forty-seven HCC and ten normal liver specimens were collected during surgical operation between 2001 and 2003. FHIT and proliferating cell nuclear antigen (PCNA) expression were detected by immunohistochemistry, and apoptotic level was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay on the tissue sections. RESULTS: All normal liver tissues showed a strong expression of FHIT, whereas 28 of 47 (59.6%) carcinomas showed a significant loss or absence of FHIT expression (P = 0.001). The proportion of reduced FHIT expression in those carcinomas at stages III-IV (70.6%) and in those with extrahepatic metastasis (86.7%) showed an increasing trend compared with those at stages I-II (30.8%, P = 0.013) and those without metastasis (46.9%, P = 0.010) respectively. Apoptotic incidence in advanced TNM stage carcinoma and those with positive FHIT expression was higher than that in early stage carcinoma (P = 0.030) and in those with negative FHIT expression (P = 0.044) respectively. The proliferating potential of hepatocellular carcinoma was associated with FHIT expression (P = 0.016) and the aggressive feature (P = 0.019). Kaplan-Meier analysis demonstrated that the survival time of these 47 patients correlated with TNM stage, FHIT expression and metastasis. CONCLUSION: There is marked loss or absence of FHIT expression, as well as abnormal apoptosis-proliferation balance in HCC. FHIT may play an important role in carcinogenesis and development of HCC.

Acid Anhydride Hydrolases↗

Survey of clustering algorithms.

Data analysis plays an indispensable role for understanding various phenomena. Cluster analysis, primitive exploration with little or no prior knowledge, consists of research developed across a wide variety of communities. The diversity, on one hand, equips us with many tools. On the other hand, the profusion of options causes confusion. We survey clustering algorithms for data sets appearing in statistics, computer science, and machine learning, and illustrate their applications in some benchmark data sets, the traveling salesman problem, and bioinformatics, a new field attracting intensive efforts. Several tightly related topics, proximity measure, and cluster validation, are also discussed.

Algorithms↗

[Study on early fibrinolytic therapy to avoid acute myocardial infarction].

OBJECTIVE: To investigate the frequency of aborted AMI and clinical characteristics of the patients received prompt fibrinolytic therapy. METHODS: 1120 patients with AMI were divided into two groups, true AMI group and aborted AMI group. Aborted AMI was defined as maximal creatine kinase-MB < or = 2 x upper limit of normal coupled with the presence of resolution of chest pain and 50% of ST-segment deviation within 2 hours after onset of therapy. We compared some characteristic of two groups such as the fibrinolytic time after symptom onset and the frequency of aborted AMI. RESULTS: The reopening ratio of infarct was 80.5%. 7.1% of the patients escaped myocardial necrosis. Aborted AMI was highest frequency within the first hour (22.0%) than other time groups (P < 0.01); There were no significant differences in the frequency of Aborted AMI in UK group, SK group and rt-PA group (7.0%, 6.7%, 7.1%, P > 0.05); The rate of Killip III/IV, major arrhythmias, angina pectoris and mortality at 30 day in aborted AMI patients compared with those who had true AMI was 3.9% versus 17.1%, 18.0% versus 30.0%, 1.3% versus 8.0%, 0 versus 6.0%, respectively (P < 0.01). CONCLUSION: Prompt fibrinolytic therapy improved the likelihood of aborted AMI and clinical outcomes. The frequency of aborted AMI has no relationship with fibrinolytic drug, but closely related to the starting time of treatment from symptom onset.

Adult↗