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Biomedical subjects

Lei Yang

Publications and source records attributed to Lei Yang.

At least 37 records · Page 2Linked to original sources

A temporal study on the histopathological, biochemical and molecular responses of CCl(4)-induced hepatotoxicity in Cyp2e1-null mice.

Previous study using Cyp2e1-null mice showed that Cyp2e1 is required in CCl(4)-induced liver injury at 24h, what remains unclear are the temporal changes in liver damage and the spectrum of genes involved in this process. We investigated the time-dependent liver changes that occurred at morphological, histopathological, biochemical and molecular levels in both Cyp2e1(+/+) and Cyp2e1(-/-) mice after treating with either corn oil or CCl(4) (1 ml/kg) for 2, 6, 12, 24 and 48 h. A pale orange colored liver, indicative of fatty infiltration, was observed in Cyp2e1(+/+) mice treated with CCl(4) for 24 and 48 h, while the Cyp2e1(+/+) mice treated with corn oil and Cyp2e1(-/-) mice treated with either corn oil or CCl(4) showed normal reddish brown colored liver. Ballooned hepatocytes with multiple vacuoles in their cytoplasm were observed in the livers of Cyp2e1(+/+) mice 24 and 48 h after treating with CCl(4). The levels of serum alanine aminotransferase and aspartate aminotransferase, markers for liver injury, were significantly higher at 12h, peaked at 24h and gradually decreased at 48 h after CCl(4) intoxication. In contrast, this kind of damage was not apparent in the Cyp2e1(-/-) mice treated with CCl(4). Altered expressions of genes related to liver cirrhosis, apoptosis, oxidative stress, xenobiotic detoxification, lipid metabolism, chemsensory signaling or tumorigenesis, structural organization, regeneration and inflammatory response were identified, and the time-dependent changes in expression of these genes were varied. Overall, the present study provides insights into the mechanism of CCl(4)-induced hepatotoxicity in animal models.

Alanine Transaminase↗

Asymmetric heat conduction in nonlinear lattices.

In this Letter, we conduct an extensive study of the two-segment Frenkel-Kontorova model. We show that the rectification effect of the heat flux reported in recent literature is possible only in the weak interfacial coupling limit. The rectification effect will be reversed when the properties of the interface and the system size change. These two types of asymmetric heat conduction are governed by different mechanisms though both are induced by nonlinearity. An intuitive physical picture is proposed to interpret the reversal of the rectification effect. Since asymmetric heat conduction depends critically on the properties of the interface and the system size, it is probably not an easy task to fabricate a thermal rectifier or thermal diode in practice.

Journal Article↗

[The use of minimally invasive injectable graft and internal fixation in tibial plateau fractures].

OBJECTIVE: To value the use of an injectable minimally invasive calcium sulfate cement for displaced tibial plateau fractures. METHODS: Thirteen patients with lateral tibial plateau fractures treated with internal fixation and bone grafting were matched with 13 patients treated using internal fixation and an injectable calcium sulfate cement. The clinical data were retrospectively analyzed. All patients were followed up for a minimum of one year. The peri-operative complication, quality of reduction, maintenance of reduction, function assessment and development of post-traumatic osteoarthritis was compared in both groups. RESULTS: Ten patients in the internal fixation and bone graft group had excellent anatomical reductions as judged on immediate post-operative radiographs but some loss of reduction on follow-up at one year was observed in 8 of the 13 (61%) cases. Twelve patients from the MIIG group had an excellent reduction on immediate post-operative radiographs but 3 (23%)demonstrated some loss of reduction of the plateau at one year follow-up (P < 0.05). CONCLUSIONS: The use of MIIG and internal fixation is associated with more favourable clinical results than conventional treatment with internal fixation and bone grafting for lateral tibial plateau fractures.

Adult↗

2-methoxyestradiol reduces cerebral vasospasm after 48 hours of experimental subarachnoid hemorrhage in rats.

2-Methoxyestradiol (2ME2), a naturally occurring metabolite of estradiol, is known to have antiproliferative, antiangiogenic, and antiproapoptotic activities. Mechanistically, 2ME2 has been shown to downregulate hypoxia-inducible factor 1alpha (HIF-1alpha). We hypothesized that hypoxia in the major cerebral arteries might activate a unique signaling pathway, hypoxia-inducible factor-1alpha (HIF-1alpha), to produce or enhance cerebral vasospasm after subarachnoid hemorrhage (SAH). Sprague-Dawley male rats (n = 70) were randomly divided into 5 groups: Sham operated, SAH without treatment, SAH treated with vehicle (DMSO), SAH treated with two HIF-1alpha inhibitors, 2ME2, and D609 (positive control of 2ME2). SAH model was produced by middle cerebral artery perforation. 2ME2 and D609 were administered intraperitoneal at 1 h after SAH; rats were sacrificed after 48 h of SAH. Thick blood clot was observed around basilar artery under arachnoids in all animals except Sham group; severe morphological vasospasm was observed in basilar arteries in SAH and SAH+DMSO rats, and the mild vasospasm in rats treated with 2ME2 and D609; 2ME2 and D609 reduced the activity of HIF-1alpha in the basilar arteries by HIF-1alpha DuoSet ELISA; reduce the expression of HIF-1alpha, VEGF, BNIP3 and PCNA in basilar arteries by Western blotting and immunohistochemical staining. In addition, it decreased the mortality and improved the neurological deficits. In conclusion, 2ME2 is a powerful agent to reduce cerebral vasospasm by inhibiting HIF-1alpha activity and the expression of VEGF as its downstream, suppressing endothelium and VSMCs apoptosis via BNIP3 pathway, and attenuating vasoproliferation.

2-Methoxyestradiol↗

[Percutaneous reduction and fixation of osteoporotic fractures for the proximal humerus in a geriatric population].

OBJECTIVE: To appraise the value of clinical treatment of percutaneous reduction and fixation of osteoporotic fractures for the proximal humerus in a geriatric population. METHODS: Postoperation complication, mortality in hospital and within the first three months postoperation, operation time, blood transfusion requirement, the functional outcome of the shoulder had been analysed and observed in 37 cases for open and closed fixation. RESULTS: Closed reduction provided the benefit of obtaining and holding adequate reduction without the soft-tissue dissection of open reduction and internal fixation. The general complication and mortality in the first three months postoperation in the open reduction and internal fixation cases were more severe than the percutaneous cases. CONCLUSIONS: Open operation increases the risk of the geriatric population with osteoporotic proximal humerus fracture; percutaneous reduction and fixation may be preferable.

Aged↗

[Application of diffusion tensor imaging fractography in minimally invasive surgery of brain tumors].

OBJECTIVE: To investigate the effects and prospect of application of diffusion tensor imaging (DTI) fractography in minimally invasive surgery of brain tumors. METHODS: DTI fractography was performed in 52 patients with malignant brain tumors. Based on the DTI fractography results, 34 of the 52 patients underwent operation under neuro-navigation, and 18 of the 52 patients underwent operation routine minimally invasive craniotomy and tumor resection without neuro-navigation. RESULTS: The rate of total tumor resection was 86.5% (45/52). The mortality was 1.9% (1/52). The disability rate was 11.5% (6/52). No case needed the second operation. CONCLUSION: DTI fractography has raised the minimally invasive neurosurgery to the level of protecting the nuclei and nerve tracts and guiding intra-operative management of infiltration of deep-seated tumors, especially when combined with neuro-navigation and interventional MRI.

Adolescent↗

The development and regulation of occupational exposure limits in China.

Of the 700 million workers in China, approximately 200 million workers are potentially exposed to industrial hazards. Although the promulgation and implementation of occupational exposure limits (OELs) in China began in the mid-1950, a systematic approach was not formalized until the formation of the Subcommittee of Occupational Health Standards Setting (SOHSS) in 1981. More recently, the 2002 Occupational Disease Prevention and Control Act of the People's Republic of China created the legislative framework for the development and enforcement of OELs. The SOHSS, whose members are primarily health professionals, is the organization responsible for the development of recommended standards, under the auspices of the Ministry of Health. The philosophy of OEL development of the SOHSS consists of a two-step approach: (1) an initial health-based recommended standard is established based on scientific data, and (2) a final law-based standard takes into consideration both socioeconomic and technological feasibility. Governmental agencies such as the Centers for Diseases Control and Prevention and the Institutes of Public Health Supervision at the state, provincial or municipal levels are charged with the responsibilities of the enforcement of OELs. The process and challenges in the enforcement of OELs are discussed. A comparison is made between selected Chinese OELs and those in other countries. The OELs for benzene and industrial dusts (including silica) are discussed in some detail.

Carcinogens, Environmental↗

Preparation of roxithromycin-polymeric microspheres by the emulsion solvent diffusion method for taste masking.

Microspheres of roxithromycin with Eudragit S100 and silica were prepared by the emulsion solvent diffusion method to mask the bitter taste of the antibiotic. The effect of different polymers and drug-polymer ratios on the taste masking and the characteristics of the microspheres were investigated. It was found that Eudragit S100 was the best for masking the unpleasant taste of roxithromycin among the six kinds of polymers investigated. The results of DSC, X-ray diffraction and IR showed that there were several combinations of roxithromycin and Eudragit S100. The influence of other formulation factors, i.e. dichloromethane-acetone ratios and silica-polymer ratios on the properties of the microspheres were also examined. In conclusion, the results of the present study will be helpful for the preparation of oral forms of roxithromycin with an acceptable taste.

Acetone↗

Geographical effects on cascading breakdowns of scale-free networks.

Cascading breakdowns of real networks have resulted in severe accidents in recent years. In this paper, we study the effects of geographical structure on the cascading phenomena of load-carrying scale-free networks. Our essential finding is that when networks are more geographically constrained, i.e., more locally interconnected, they tend to have larger cascading breakdowns. Explanations are provided in terms of the effects of cycles and the distributions of betweenness over degrees.

Journal Article↗

Xenopus laevis is a potential alternative model animal species to study reproductive toxicity of phytoestrogens.

This study investigated effects of phytoestrogen quercetin on the gonadal development in Xenopus laevis. X. laevis at Nieuwkoop and Faber stage 46/47 were exposed to 50, 100 and 200 microg/L quercetin till 1 month postmetamorphosis. Gonads from frogs at 1 and 3 months postmetamorphosis were examined in gross morphology and histology. The highest dose of quercetin as well as estradiol (E2) significantly increased the percentages of phenotypic females. Exposure to quercetin at all doses induced abnormal testes with certain ovarian characteristics to some degree in gross morphology, including ovotestes. The abnormality rate exceeded 10% in each quercetin treatment. Histologic examination revealed that some abnormal testes exhibited intersexuality with testicular structure and ovarian structure or oocytes interspersed in testicular structure at 1 month postmetamorphosis. At 3 months postmetamorphosis, testicular abnormalities were more obvious, such as necrosis or apoptosis of spermatogonia, occurrence of developed or undeveloped oocytes, delay of the development of seminiferous tubes without or less late stage spermatocytes. The results have shown that quercetin cannot only feminize but also impair testicular development of X. laevis, i.e. X. laevis is sensitive to phytoestrogen. It is suggested that X. laevis might be an alternative model species to study reproductive toxicity of phytoestrogens.

Animals↗

[Inhibition of ACh on the delayed rectifier-like potassium current in acutely isolated cerebral cortical neurons of rats].

The modulation of ACh on delayed rectifier-like potassium currents (I(K)) was studied in freshly dissociated cerebral cortical neurons using the whole-cell patch-clamp technique. Wistar rats between 10- and 14-day old of both sexes were used. After rats were decapitated, their brains were quickly removed, iced, and then manually cut into 400 mum slices. Slices were then incubated for 0.5 h at 32 degrees C in a buffered artificial cerebrospinal fluid (ACSF) bubbled with 95% O2, 5% CO2. Slices were then removed into buffered ACSF containing protease (0.5 mg/ml) at 32 degrees C. After 30 min of enzyme digestion, tissue was rinsed three times in the buffered saline. Then the enzyme-treated slices were mechanically dissociated with a graded series of fire-polished Pasteur pipettes. The cell suspension was then plated into a 35 mm dish and placed on the stage of a Olympus inverted microscope. For whole-cell recordings of currents, standard voltage-clamp techniques were used. Neurons were held at -80 mV, and the I(K) was evoked by 2 000 ms depolarizing voltage commands to potential between -40 mV and +60 mV in 10 mV steps applied at a frequency of 0.5 Hz. It was found that the inhibitory effect of ACh (0.1, 1, 10, 100 mumol/L) on I(K) was dose-dependent. It was also found that ACh affected the activation process of I(K) significantly, i.e., the activation curve of I(K) was characterized by half-activation potential of (-41.8+/-9.7) mV and a slope factor of (30.7+/-7.2) mV in the cortical neurons and they were changed to (-122.4+/-38.6) mV and (42.4+/-7.0) mV, respectively, after giving ACh (10 mumol/L). Tubocurarine (100 mumol/L) antagonized the inhibitory effect of ACh on I(K), and the drop of currents varied from the control value of (36.5+/-7..8)% to (16.9+/-13.8)% (n=8, P<0.01). 4-DAMP (10 mumol/L) blocked the inhibitory effect of ACh on I(K), and the currents reduced from the control value of (36.5+/-7.8)% to (26.8+/-4.7) % (n=6, P<0.05). Pirenzepin did not antagonize the inhibition of ACh on I(K) (n=7, P>0.05). Chelerythrine (20 mumol/L) blocked the inhibitory effect of ACh on I(K) and the currents reduced from the control value of (36.5+/-7.8)% to (11.7+/-17.3)% (n=6, P<0.05). On the contrary, PDBu (10 mumol/L) strengthened the inhibition of ACh on I(K) and the drop of currents changed from the control value of (36.5+/-7.8)% to (59.2+/-14.0)% (n=5, P<0.05). PDBu abolished the antagonism of chelerythrine on ACh in cortical neurons. It is suggested that the ACh-induced depolarization of neurons in the cortex is attributed to the inhibition of I(K) that is most likely evoked by the activation of nicotinic ACh receptors and muscarinic M3 receptor via protein kinase C (PKC) signal transduction pathway.

Acetylcholine↗

Study of the preparation of sustained-release microspheres containing zedoary turmeric oil by the emulsion-solvent-diffusion method and evaluation of the self-emulsification and bioavailability of the oil.

The purpose of this study was to design a sustained-release formulation of an oily drug. The sustained-release microspheres with self-emulsifying capability containing zedoary turmeric oil (ZTO) were prepared by the quasi-emulsion-solvent-diffusion method. The micromeritic properties, the efficiency of emulsification and the drug-release behavior of the resultant microspheres were investigated. The bioavailability of the microspheres was compared with conventional ZTO self-emulsifying formulations for oral administration using 12 healthy rabbits. An HPLC method was employed to determine the concentration of germacrone in plasma, which was used as an index of ZTO. Spherical and compacted microspheres with average diameters of 100-600 microm have been prepared, and their release behavior in distilled water containing 1.2% (w/v) of polysorbate-80 can be controlled by the ratio of polymer/Areosil200 in the microspheres. The resultant emulsions with mean droplet sizes of 200-500 nm are produced when the microspheres are immersed in phosphate buffer (pH 6.8) under gentle agitation. The stability and the droplet size of the resultant emulsions are also affected by the polymer/Areosil200 ratio in the formulation, while the amount of talc has a marked effect on the self-emulsifying rate. The plasma concentration-time profiles with improved sustained-release characteristics were achieved after oral administration of the microspheres with a bioavailability of 135.6% with respect to the conventional self-emulsifying formulation (a good strategy for improving the bioavailability of an oily drug). In conclusion, the sustained-release microspheres with self-emulsifying capability containing ZTO have an improved oral bioavailability. Our study offers an alternative method for designing sustained-release preparations of oily drugs.

Administration, Oral↗

Multinuclear copper complexes of pyridylmethylamide ligands.

Copper complexes of a family of pyridylmethylamide ligands HL(Ph), HL(Me3) and HL(Ph3) were synthesized and characterized [HL(Ph) = 2-phenyl-N-(2-pyridylmethyl)acetamide; HL(Me3) = 2,2-dimethyl-N-(2-pyridylmethyl)propionamide; HL(Ph3) = 2,2,2-triphenyl-N-(2-pyridylmethyl)acetamide]. The reaction of copper(II) salts with the HL family and triethylamine in methanol yields copper(II) complexes [Cu4(L(Ph))4(OH)2](ClO4)2 (1), [Cu2(HL(Me3))2(OMe)2(MeOH)2](OTf)2 (2) and [Cu2(HL(Ph3))2(OMe)2(MeOH)2](OTf)2 (3). The complexes have different nuclearity owing to varying steric properties of the ligands used. Complex 1 self-assembles in the presence of excess base to form a tetranuclear complex. Complexes 2 and 3 are binuclear and are bridged by a pair of methoxide ligands. Steric encumbrance of the ligands in 2 and 3 prevent cluster formation.

Amides↗

Acute myelogenous leukemia-derived SMAD4 mutations target the protein to ubiquitin-proteasome degradation.

Disruption of transforming growth factor-beta (TGFB1/TGF-beta) signaling contributes to the formation of human hematological malignancies. Smad4, a tumor suppressor, functions as an essential intracellular signal transducer of the TGF-beta signaling pathway. Recent studies have demonstrated that some tumor-derived mutations of Smad4 are associated with protein instability; however, the precise mechanism by which mutated Smad4 proteins undergo rapid degradation remains to be elucidated. A missense mutation of the SMAD4 gene in the Mad homology 1 (MH1) domain (c.305C>T, Pro102Leu) and one frameshift mutation resulting in termination in the Mad homology 2 (MH2) domain (c.1447_1448insAATA, Delta483-552) have been identified in acute myelogenous leukemia. It is not known whether protein instability of these SMAD4 mutants is one of the contributors to TGF-beta signaling disruption in acute myelogenous leukemia. Here we report that these two acute myelogenous leukemia-derived SMAD4 mutants are degraded rapidly when compared to their wild-type counterpart. We have demonstrated that both mutated proteins exhibit enhanced polyubiquitination (or polyubiquitylation) and proteasomal degradation. Importantly, we found that beta-transducin-repeat-containing protein 1 (beta-TrCP1), an F-box protein in the ubiquitin E3 ligase Skp1-Cullin-F-box protein (SCF) complex, directly interacts with and acts as a critical determinant for degradation of both mutated SMAD4 proteins. In addition, small interference RNA (siRNA)-triggered endogenous beta-TrCP1 suppression increased the protein expression level of both overexpressed SMAD4 mutants and endogenous mutated SMAD4 protein in acute myelogenous leukemia cells. These data suggest that mutated SMAD4 proteins undergo rapid degradation in acute myelogenous leukemia cells via SCF(beta-TrCP1) E3 ligase-mediated protein ubiquitination (or ubiquitylation) and subsequent proteasomal degradation.

Animals↗

Effect of an acidulated fluoride etchant on bonding between titanium and two luting materials.

Adhesive bonding between resin and titanium is useful for resin-bonded prostheses. The purpose of this study was to investigate the efficacy of an etchant, consisting of ammonium hydrogen fluoride (AHF) and phosphoric acid (PA), in titanium bonding. Cast specimens of commercially pure titanium were air-abraded with alumina and etched for 30 s, after which a primer (ALP) was applied. An acrylic rod was bonded to the specimen with one of the two luting agents being examined (Super-Bond QUICK and Panavia F2.0). Shear bond strengths were determined following 10,000 thermocycles. When Panavia F2.0 was applied, neither the etchant nor the ALP primer showed significant effect on bond strength. The postthermocycling bond strength of Super-Bond QUICK was significantly improved with the use of an etchant and ALP primer. Although microscopic observation revealed that considerable numbers of submicron pits were created on the specimens etched using AHF with PA, no significant difference in bond strength was detected in the application of AHF, with or without PA. The present findings suggested that the improved bonding durability was due to the micromechanical retention between the resin and the microscopically roughened titanium surface.

Boron Compounds↗

Natural course of silicosis in dust-exposed workers.

To provide a scientific basis for determining the health surveillance period of dust-exposed workers, data of a retrospective cohort study was re-analyzed with emphasis on natural course of silicosis. 33640 workers exposed to silica dust who were employed for at least 1 year from 1972 to 1974 in twenty Chinese mines or pottery factories were included as subjects, and were followed up till December 31, 1994. The cohort included subjects from 8 tungsten mines, 4 tin mines and 8 pottery factories. Our results showed that the mean latency of silicosis, for all the cases of the cohorts, was 22.9 +/- 9.8 y. 52.2 % of silicosis was diagnosed approximately 9.1 +/- 5.7 y after the dust exposure had ceased. The progression rates of silicosis from stage I to II and from stage II to III were 48.2 % and 18.5 %, and the duration was 4.1 +/- 0.2 and 6.8 +/- 0.2 y, respectively. The survival times of silicosis stage I , II and III, from the year of diagnosis to death, were 21.5, 15.8 and 6.8 years, respectively. There was 25 % of the silicosis patients whose survival time was beyond 33 y. The mean death age of all silicosis cases was 56.0 y. The death age increased to 65.6 y in the middle of 1990s. Among dust-exposed workers, subjects who became suspected case (0+ ) accounted for 15.0 %. 48.7 % of the suspected silicosis cases developed to silicosis, and the average year from the time of being suspected of the disease to the first stage of silicosis was 5.1 y. The natural characteristics, as mentioned above, varied with different mines and factories. We are led to conclude that silicosis is chronic in nature, but progress quickly. As a serious occupational disease it significantly reduces the life span of exposed workers. The study of its natural history is of importance for the development of health surveillance criteria for dust-exposed workers.

Cohort Studies↗

Isl1Cre reveals a common Bmp pathway in heart and limb development.

A number of human congenital disorders present with both heart and limb defects, consistent with common genetic pathways. We have recently shown that the LIM homeodomain transcription factor islet 1 (Isl1) marks a subset of cardiac progenitors. Here, we perform lineage studies with an Isl1Cre mouse line to demonstrate that Isl1 also marks a subset of limb progenitors. In both cardiac and limb progenitors, Isl1 expression is downregulated as progenitors migrate in to form either heart or limb. To investigate common heart-limb pathways in Isl1-expressing progenitors, we ablated the Type I Bmp receptor, Bmpr1a utilizing Isl1Cre/+. Analysis of consequent heart and limb phenotypes has revealed novel requirements for Bmp signaling. Additionally, we find that Bmp signaling in Isl1-expressing progenitors is required for expression of T-box transcription factors Tbx2 and Tbx3 in heart and limb. Tbx3 is required for heart and limb formation, and is mutated in ulnar-mammary syndrome. We provide evidence that the Tbx3 promoter is directly regulated by Bmp Smads in vivo.

Animals↗

Comparison of four fluoride etchants in bonding between titanium and a self-curing luting agent.

The purpose of the present study was to investigate the efficacy of four different fluoride etchants in titanium bonding. The etchants were aqueous solutions of 5 wt% sodium fluoride (NaF), ammonium fluoride (NH4F), sodium hydrogen fluoride (NaFHF), and ammonium hydrogen fluoride (NH4FHF). Cast specimens of commercially pure titanium were air-abraded with alumina, etched for 30 seconds, and then primed with a phosphate primer. An acrylic rod was bonded to the specimen with a tri-n-butylborane-initiated self-curing luting agent. Shear bond strengths were determined before and after 10,000 thermocycles. Regarding pre-thermocycling bond strength, there were no significant differences among the etchants. After thermocycling, there was a decrease in bond strength for all groups. Nonetheless, the bond strengths of NaFHF and NH4FHF were significantly higher than those of NaF, NH4F, and non-etched control. In terms of bonding durability between resin and titanium, it was significantly improved when the titanium surface was microscopically roughened with alumina blasting and etching using NaFHF or NH4FHF.

Ammonium Compounds↗