Background Sclera remodeling process in axial elongation is one of the main pathological mechanisms of axial myopia progression.Studies confirmed that transforming growth factor-β1(TGF-β1) participates in the sclera remodeling process,and Smad3 is one of TGF-β1 downstream signal gene transcriptive factors,so to explore its role in sclera remodeling process of myopic eyes is of great significance for pathogenesis and prevention research of myopia.Objective This study was to investigate the expressions of type Ⅰ collagen and Smad3,a TGF-31 downstream target,in sclera of form deprivation myopic (FDM) eyes and explore the impact of TGF-β1-Smad3-type Ⅰ collagen signaling pathway on collagen remodeling in myopic sclera.Methods Seventy-five 1-week-old guinea pigs were randomly divided into normal control group (25 guinea pigs) and FDM group (50 guinea pigs).Monocular FDM was induced by occluding the left eyes of guinea pigs in FDM group with translucent latex balloons for 2,4,6 weeks,respectively,and consecutive occluding for 4 weeks followed by uncovering for 1 week (4/-1 weeks).The refractive power was detected by retinoscopy and axial length was measured with A-type ultrasound.Immunohistochemistry and reverse transcription-PCR were employed to detect the dynamic expressions of type Ⅰ collagen and Smad3 protein ad mRNA in the sclera of guinea pigs with emmetropia and experimental myopia,ard the relationship between collagen Ⅰ and Smad3 levels was analyzed.Results The refraction was hypermetropic in both normal control group and FDM group before occluding of eyes (P＞0.05),and the hypermetropic power was gradually reduced over time in the normal control group.In the FDM group,the refractive power was gradually changed from (+2.09 ± 0.31)D before occluding to (-1.23±0.69),(-4.17±0.59),(-7.07±0.56) and (-4.30±0.58)D,and the axial length was increased from (5.93-±0.39)mm to (6.62±0.36),(7.30±0.34),(7.99--0.32),and (7.21 ±0.36) mm at weeks 2,4,6,and 4/-1 after occluding,respectively,indicating significant differences in refractive power and axial length over time in the FDM group from normal control group and self-control group (all at P＜0.05).The expressions of Smad3 and type Ⅰ collagen protein and mRNA in the sclera of the FDM group was significantly lower than those of the control group and self-control group in various time points (all at P＜0.05).The positive correlation were found in the expression of Smad3 on the myopic sclera with that of type Ⅰ collagen in both protein and mRNA levels (protein:r=0.993,P＜0.05;mRNA:r=0.954,P＜0.05).Conclusions The myopic power and ocular axis increase dependent upon occluding time,and the expressions of Smad3 and type Ⅰ collagen in the sclera are correspondingly weakened in FDM eyes.A consistent expression trend is found between Smad3 and type Ⅰ collage,suggesting Smad3 and type Ⅰ collagen participate in the regulation of sclera remodeling in myopia by TGF-β1-Smad3-Collagen Ⅰ signaling pathway.

Objective To ascertain the utility and difference of sonography with echo-tracking (ET) technique and pulse-Doppler to assess vascular stiffness in rats with hypercholesterolemia and atherosclerosis.Methods Sonography associated with ET technique and pulse-Doppler were used to measure stiffness parameter (β),arterial compliance (AC),distensibility coefficient (DC),one-point pulse wave velocity (PWVβ),resistence index(RI),peak systolic velocity(PSV),end-diastolic velocity(EDV) and EDV/PSV of the aorta in cholesterol-fed SD rats (group T1,n =10,for 4 weeks;group T2,n =10,for 12 weeks) and normal control rats(group C1,n =10;group C2,n =10).All parameters and blood biochemical markers[total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-CH) and highdensity lipoprotein cholesterol (HDL-CH)] among groups were analyzed with ANOVE factor analysis.Correlation was analyzed with Pearson analysis.Light microscopic evaluation were used to demonstrate atherosclerotic changes in the aorta.Results The PWVβ value and PSV of the aorta between group T1 and T2 were significantly different (P =0.001,P ＜0.05).The β,PWVβ values of the aorta in group T1 and T2 were significantly higher than those of group C1 and C2 (P ＜0.05).AC and DC values of the aorta in group T1 and T2 were significantly lower than those of group C1 and C2 (P ＜0.05).Correlation analysis showsed that RI was positively correlated with systolic pressure(P ＜0.05).All parameters had correlated with each other among β,PWVβ,AC,DC,TG,TC,systolic pressure and diastolic pressure.DC and AC were negatively correlated with β and PWVβ,also DC was negatively correlated with TG.Light microscopy confirmed morphologic typical changes of aortic atherosclerosis in group T1 and T2.Conclusions Sonography with the ET method compared with pulse-Doppler is much more sensitive and it can be used to evaluate tissue elastic changes in arterial walls associated with atherosclerosis and hypercholesterolemia.PSV can reflect atherosclerosis of rat's abdominal aorta well,but pulse-Doppler is limited in the diagnosis of earlier atherosclerosis period.

Objective To investigate the effects of penehyclidine hydrochloride (PHC) on acute lung injury induced by blunt chest trauma-hemorrhagic shock and resuscitation in rats.Methods Forty male SpragueDawley rats,aged 8 weeks,weighing 250-300 g,were randomly assigned into 4 equal groups (n =10 each) using a random number table:sham operation group (S group),blunt chest trauma combined with hemorrhagic shock and resuscitation group (group THSR),PHC for prevention group (group P1)and PHC for treatment group (group P2).ALI was induced by dropping a 300 g weight onto a precordial protective shield to direct the impact force away from the heart and toward the lungs in anesthetized rats in THSR,P1 and P2 groups.Blood was withdrawn via the femoral artery 5 min later until MAP was decreased to 35-45 mmHg within 15 min and maintained at this level for 60 min,followed by resuscitation.In P1 group,PHC 2 mg/kg was injected intravenously at 30 min before blunt chest trauma.In P2 group,PHC 2 mg/kg was injected intravenously at 60 min after hemorrhagic shock.At 6 h after the model was established,arterial blood samples were obtained for blood gas analysis and for measurement of concentrations of interleukin-6 (IL-6) and interleukin-1β (IL-1β) in serum by ELISA.Oxygenation index (OI) was calculated.The animals were sacrificed and bronchoalveolar lavage fluid (BALF) was collected for determination of white blood cell count and protein concentrations.Lungs were removed for examination of pathological changes and ultrastructure and for determination of Toll-like receptor (TLR4) and phosphor-p38 mitogen activated protein kinase (p-p38MAPK) expression (by Western blot).Results Compared with group S,PaO2 and OI were significantly decreased,PaCO2,protein concentrations in BALF,white blood cell count,and IL-6 and IL-1β concentrations in serum were increased,and TLR4 and p-p38MAPK expression was up-regulated in THSR,P1 and P2 groups.Compared with group THSR,PaO2 and OI were significantly increased,PaCO2,protein concentrations in BALF,white blood cell count,and IL-6 and IL-lβ concentrations in serum were decreased,TLR4 and p-p38MAPK expression was down-regulated in P1 and P2 groups.No significant differences were found in the parameters mentioned above between P1 and P2 groups.Conclusion PHC can mitigate acute lung injury induced by blunt chest trauma-hemorrhagic shock and resuscitation in rats,and inhibited activation of TLR4/ p38MAPK signaling pathway and attenuated inflammatory responses are involved in the mechanism.

0.05).The expression rate of p53 protein in patients with cervical lymph nodes metastasis(≥4cm)was 81.8%(9/11),in cervical lymph nodes metastasis (

BACKGROUNDThere are few researches for the healing of metaphyseal fractures; moreover, the animal models to study the metaphyseal fractures are usually made by the oscillating saw osteotomy without reliable fixation, which is not in accordance with our current clinical practice. In this study, we established a new model to observe the healing process of metaphyseal fractures.

METHODSEighteen New Zealand rabbits were used in the study. The fracture model was created by splitting the medial tibial plateau in rabbits, then reset, and fixed with compression screws. At 1, 2, 3, 4, 6, and 8 weeks postoperatively, the tibial specimens were collected; firstly, a general observation and an X-ray examination of the specimens was done, and then they were embedded in methylmethacrylate and cut into sections with hard tissue slicer. The sections were stained with Giemsa reagent and examined under light microscopy.

RESULTSThere was no fracture displacement in the tibial specimens of all time points, except for one showing a collapse. No external callus formation could be observed by X-ray and general examination. After 1 week of the operation, the fracture gap was filled by mesenchymal tissue; 2 weeks postoperatively, a large number of woven bones were formed; from the third week onwards, the woven bone began to turn into lamellar bone, and new trabecular structure began to form. In all of the slices, no obvious chondrocytes formed in fracture areas; thus, there was no endochondral ossification.

CONCLUSIONSThis model was an ideal fracture animal model and suitable for the study of metaphyseal fracture healing. The X-ray and histological images demonstrated that metaphyseal fracture healing was a process of direct bone healing through intramembranous bone formation under the conditions of minor trauma, good reduction, and firm fixation.

Animals ; Fracture Healing ; physiology ; Fractures, Bone ; diagnostic imaging ; pathology ; Rabbits ; Radiography

OBJECTIVETo study into the genetic polymorphism of DC-SIGN and DC-SIGNR's exon 4 in Chinese hepatitis C patients and its relationship with HCV infection susceptibility.

METHODSPatients with hepatitis C (n=300, group A) and healthy subjects (n=520, group B) were genotyped and analysed for the repeat sequence of polymorphism of DC-SIGN and DC-SIGNR's exon 4 using PCR and DNA sequencing.

RESULTSThe distribution of genotypes and alleles in DC-SIGN's exon 4 in the two groups did not differ significantly (P > 0.05). The difference of allele frequency in DC-SIGNR's exon 4 between the two groups was also not significant (P > 0.05). However, 9/5 genotype distribution frequency of DC-SIGNR's exon 4 in patients with hepatitis C was significantly higher than that in the healthy subjects (P < 0.05).

CONCLUSIONThere is no significant correlation between the genetic polymorphism of DC-SIGN's exon 4 and HCV infection susceptibility. 9/5 genotype distribution frequency of DC-SIGNR's exon 4 in patients with hepatitis C is significantly higher and may be associated with HCV infection susceptibility.

Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group ; genetics ; Blood Donors ; Case-Control Studies ; Cell Adhesion Molecules ; genetics ; Child ; Exons ; Female ; Genetic Predisposition to Disease ; Genotype ; Hepatitis C, Chronic ; ethnology ; genetics ; Humans ; Lectins, C-Type ; genetics ; Male ; Middle Aged ; Polymorphism, Genetic ; Receptors, Cell Surface ; genetics ; Young Adult

Thyroid cancer is the one of the most common endocrine tumors. The biological behaviors and prognoses of the thyroid cancer of different histological types remarkably differ. The highly invasive thyroid cancer responds poorly to traditional therapies. Recent research advances in the molecular mechanisms of the pathogenesis of thyroid cancer have revealed the roles of many genetic and epigenetic variations such as gene mutation, abnormal gene amplification, and abnormal gene methylation in the development of thyroid cancer, which provides new insights in the molecular diagnosis, prognosis, and target therapy of the thyroid cancer.
Carcinoma ; genetics ; Humans ; Mutation ; Signal Transduction ; Thyroid Neoplasms ; genetics

To optimize the culture environment and protocol of hematopoietic cells' expansion, avoiding the fluctuation caused by medium changing in stirred culture and concentration gradient in static culture, the hematopoietic cells from cord blood (CB) were cultured in a stirred bioreactor connected with a cell retention system, which is a gravity sedimentation settler designed for hematopoietic cell. Total cells expanded 11.5 and 18.6 fold respectively in the twice perfusion stirred cultures, in which CFU-Mix was expanded 23.2 and 20.4 fold, CFU-GM 13.9 fold and 21.5 fold, BFU-E 8.0 fold and 6.9 fold, CD34+ cells 17.1 fold and 15.4 fold. After 12-day culture, it was obtained that 1082 x 10(6) total cells, 6.31 x 10(6) CFU-GM, 6.2 x 10(6) CFU-Mix and 23 x 10(6) CD34+ cells from 267 x 10(6) CB mononuclear cells (MNC) in the first culture, and 1080 x 10(6) total cells, 4.65 x 10(6) CFU-GM, 11.0 x 10(6) CFU-Mix, and 25.0 x 10(6) CD34+ cells from 180 x 10(6) CB MNC. These two cultures met to the clinical scale. Due to the optimized dissolved oxygen (DO) and stable culture environment, the rate of stem/progenitor cells to total cells in the perfusion culture was higher than that in T-flask cell-retention feeding culture. But the cell growth was inhibited in the later phase of perfusion culture, when the cell density is high. The inhibition should be attribute to the high cell density itself. The perfusion culture environment in bioreactor with optimal DO and pH controlling is more favorable for stem/progenitor cells' maintenance and expansion, and the expanded cells' number has reached a clinical scale. But the high cell density in the later phase of perfusion culture caused inhibition to mature hematopoietic cell's growth.
Bioreactors ; Cell Culture Techniques ; methods ; Cells, Cultured ; Fetal Blood ; cytology ; Hematopoietic Stem Cells ; cytology ; Humans

OBJECTIVEMany studies have demonstrated that low levels of insulin-like growth factor-I (IGF-I) may be associated with the hypoxic-ischemic brain damage (HIBD) and that IGF-I has a neuroprotective effect. The role of IGF-II, a structurally and functionally homologous polypeptide with IGF-I, is unclear in HIBD. This study was designed to observe the changes of serum and cerebrospinal fluid (CSF) IGF-II levels in neonates with hypoxic-ischemic encephalopathy (HIE) and to investigate its effects on HIE.

METHODSSerum and CSF IGF-II levels in 41 neonates with HIE were measured by radioimmunoassay in the acute phase (postnatal age 12-24 hrs) and the convalescence phase (postnatal age 10-12 days). The 41 HIE neonates included 10 cases of mild, 12 moderate, and 19 severe HIE. Serum samples of 10 normal neonates were used as controls.

RESULTSIn the acute phase, serum IGF-II levels in the Mild HIE group (203.28 +/- 40.09 ng/mL) and the Moderate HIE group (192.33 +/- 39.66 ng/mL) were not significantly reduced, but were obviously reduced in the Severe HIE group (116.72 +/- 39.50 ng/mL) compared with normal controls (229.38 +/- 43.39 ng/mL) (P<0.01). During the convalescence phase, serum IGF-II levels in the Mild HIE group (285.53 +/- 49.44 ng/mL) and in the Moderate HIE group (278.69 +/- 51.34 ng/mL) increased significantly (P < 0.01); CSF IGF-II levels increased in the Mild HIE group from 27.23 +/- 7.82 ng/mL (acute phase) to 81.58 +/- 9.77 ng/mL (convalescence phase) (P < 0.01) and also increased in the Moderate HIE group from 23.43 +/- 7.79 ng/mL (acute phase) to 78.48 +/- 10.44 ng/mL (convalescence phase) (P < 0.01). The patients from the severe HIE group whose neurological symptoms or signs were improved in the convalescence showed higher serum and CSF IGF-II levels than in the acute phase (254.08 +/- 48.50 ng/mL vs 122.21 +/- 46.26 ng/mL; 69.42 +/- 10.20 ng/mL vs 15.05 +/- 7.03 ng/mL; P < 0.01). A positive correlation was found between the serum and CSF IGF-II levels in the HIE group (r=0.69, P < 0.01).

CONCLUSIONSIGF-II levels in serum and CSF are associated with the pathogenesis and the prognosis of neonatal HIE.

Female ; Humans ; Hypoxia-Ischemia, Brain ; metabolism ; Infant, Newborn ; Insulin-Like Growth Factor II ; analysis ; cerebrospinal fluid ; Male

OBJECTIVETo explore the effect of electroacupuncture (EA) on the pathomorphology of the sciatic nerve and the role of P2X3 receptors in EA analgesia.

METHODSThe chronic constriction injury (CCI) model was adopted in this study. A total of 32 rats were randomly divided into four groups: sham CCI, CCI, CCI plus contralateral EA (CCI + conEA) and CCI plus ipsilateral EA (CCI + ipsEA). Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured. EA began at day 7 after the CCI operation and was applied to the Zusanli (ST 36) and Yanglingquan acupoints (GB 34). At day 14, the pathomorphologic changes of the operated sciatic nerve were demonstrated by hematoxylin and eosin staining. In addition, dorsal root ganglion (DRG) neurons isolated from rats were examined by electrophysiological recording to determine if the P2X3 receptor agonists, adenosine 5'-triphosphate disodium (ATP) and α,β-methylen-ATP (α,β-meATP) evoked inward currents.

RESULTSPain thresholds in the CCI group were obviously decreased post CCI surgery (P<0.01). In the EA groups, thermal and mechanical threshold values were increased after the last EA treatment (P<0.05, P<0.01). There was no significant difference in light microscopic examination among the four groups (P>0.05). Current amplitude after application of ATP and α,β-meATP in DRG neurons were much larger in the CCI group compared to those obtained in sham CCI (P<0.05). ATP and α, β-meATP invoked amplitudes in the CCI + EA groups were reduced. There was no signififi cant difference between the CCI + conEA group and the CCI + ipsEA group (P>0.05).

CONCLUSIONEA analgesia may be mediated by decreasing the response of P2X3 receptors to the agonists ATP and α,β-meATP in the DRG of rats with CCI. No pathological changes of the sciatic nerve of rats were observed after EA treatment.

Adenosine Triphosphate ; analogs & derivatives ; pharmacology ; Animals ; Constriction, Pathologic ; Electroacupuncture ; Ganglia, Spinal ; drug effects ; metabolism ; pathology ; Hyperalgesia ; pathology ; Ion Channel Gating ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Reaction Time ; drug effects ; Receptors, Purinergic P2X3 ; metabolism ; Sciatic Nerve ; injuries ; metabolism ; pathology ; Staining and Labeling