Diagnostic Value of Structural MRI in Spinocerebellar Ataxia Type 3 / 中山大学学报(医学科学版)

ObjectiveTo explore the role of structural MRI in the diagnosis of spinocerebellar ataxia type 3 （SCA3） and further evaluate its correlation with disease severity and disease duration. MethodsWe prospectively enrolled 81 genetically diagnosed SCA3 patients ［59 symptomatic （sym-SCA3） and 22 pre-symptomatic （pre-SCA3）］ and 35 age- and sex-matched healthy controls （HCs）. MRI structural images （3D T1 MPRAGE） and clinical data of all subjects were collected. Three observers with different radiological experience measured the width of the superior， middle and inferior cerebellar peduncle （SCP， MCP and ICP）， the anterior-posterior diameters of the pons and spinal cord at the levels of the foramen magnum and upper edge of the 3rd-5th cervical vertebra. One observer performed the measurements again 2 months later to assess for the intra- and inter-observer reliability， respectively. One-way ANOVA， rank-sum test， ROC curve and Random Forest were used to evaluate the diagnostic value of the above metrics for SCA3， and the correlation between the metrics and clinical variables was analyzed. ResultsNot depending on the radiological experience， the metrics based on morphological MRI showed high intra- and inter-observer reliability， among which bilateral superior and middle cerebellar peduncles performed best. The diameters of bilateral SCP， MCP， ICP， pons and spinal cord （except spinal cord at the level of the upper edge of the 5th cervical vertebra） decreased successively in HCs， pre-SCA3 and sym-SCA3 with a statistical difference （P<0.017）. ROC analysis revealed that the left MCP had the highest diagnostic value for pre-SCA3 （AUC=0.911）， with sensitivity， specificity and a cut-off value of 85.7%， 95.5% and 10.15 mm， respectively. In contrast， the right SCP had the highest diagnostic value for sym-SCA3 （AUC=0.999）， with sensitivity， specificity and a cut-off value of 100%， 98.3% and 2.62 mm， respectively. The Random Forest model based on the above metrics also had high diagnostic efficiency （AUC= 0.970， specificity=93.1%）， and the left MCP contributed the most. Correlation analysis showed that the above metrics had a significantly or moderately negative correlation with the Scale for the Assessment and Rating of Ataxia （SARA） and disease duration （P<0.05）. ConclusionNot depending on radiological experience， measurements of brain structure based on morphological MRI are reliable， which can help diagnose SCA3 and predict disease severity and duration. The left MCP and the right SCP perform best for predicting pre-SCA3 and sym-SCA3， respectively. Therefore， the structural MRI is recommended for assisting the clinical diagnosis of SCA3.

Regulatory Effect of Qingzhenfang on Cellular Immune Function of Patients with Chronic Urticaria / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of Qingzhenfang for plasmoby （chronic urticaria）， and to investigate its effect on cellular immune function. Method:One hundred and thirty-two cases patients were divided into control group and observation group evenly according to random number table. The 60 patients in control group finished the study because of 6 cases of dropout， loss of follow-up and withdrawal， and 62 patients in observation group finished the study. Patients in both groups got Yiebastine tablets， 10-20 mg/time， 1 time/day. Patients in control group additionally got Piminxiao capsule， 4 grains/time， 3 times/day， while patients in observation additionally got Qingzhenfang， 1 dose/day. The treatment continued for 8 weeks in both groups. Before the treatment， and at the second， fourth， and eighth week after treatment， scores of urticaria activity for 7 days （USA7） and total symptom score （TSS） were graded. Before and after treatment， scores of chronic urticaria quality of life scale （CU-Q2oL） and syndrome of rheumatic fever were graded. A follow-up of 3 months was conducted for the patients whose score of USA7 was less than 7 to record the recurrence. Complement 3 and 4 （C3， C4）， CD4⁺， CD8⁺ cells were detected， and Th17/ CD4⁺ and Treg/ CD4⁺， CD4⁺/CD8⁺ and Th17/Treg were calculated. Levels of peripheral blood interleukin-10 （IL-10）， IL-17 and IL-23 were detected， and safety was evaluated after the treatment. Result:At the second， fourth and eighth week after the treatment， scores of USA7， TSS， CU-Q2oL and syndrome of rheumatic fever in observation group were lower than those in the control group （<italic>P</italic><0.01）. Levels of C3， C4， CD4⁺， Treg， CD4⁺/CD8⁺and IL-35 in observation group were higher than those levels detected in control group （<italic>P</italic><0.01）， while levels of CD8⁺， Th17， Th17/Treg， IL-10， IL-17 and IL-23 were lower than those in the control group （<italic>P</italic><0.01）. Recurrence rate was 25.58% （11/43） in observation group， lower than 48.48% （16/33） in control group （<inline-formula><alternatives><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:msup><mml:mrow><mml:mi>χ</mml:mi></mml:mrow><mml:mrow><mml:mn mathvariant="normal">2</mml:mn></mml:mrow></mml:msup></mml:math><graphic specific-use="big" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="alternativeImage/19F4CEA3-4719-4fe6-AFE8-81E481AA497E-M002.jpg"><?fx-imagestate width="3.30199981" height="3.64066648"?></graphic><graphic specific-use="small" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="alternativeImage/19F4CEA3-4719-4fe6-AFE8-81E481AA497E-M002c.jpg"><?fx-imagestate width="3.30199981" height="3.64066648"?></graphic></alternatives></inline-formula>=4.276， <italic>P</italic><0.05）， and the clinical efficacy in observation group was superior to that in control group （<italic>Z</italic>=2.021， <italic>P</italic><0.05）. Conclusion:Yaoyi Qingzhenfang can control the degree of disease and improve the quality of life for patients with chronic urticaria， with superior clinical efficacy. In addition， it can reduce recurrence rate， increase the levels of C3， C4， regulate cellular immune function， and reduce immune inflammatory response， so it is worthy of further clinical research and use.

MRN complex is an essential effector of DNA damage repair / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Genome stability can be threatened by both endogenous and exogenous agents. Organisms have evolved numerous mechanisms to repair DNA damage, including homologous recombination (HR) and non-homologous end joining (NHEJ). Among the factors associated with DNA repair, the MRE11-RAD50-NBS1 (MRN) complex (MRE11-RAD50-XRS2 in

Selective inhibition of endothelin receptor A improves white matter le-sions in hypertensive rats / 中国病理生理杂志

AIM:To observe whether selective inhibition of endothelin receptor A(ETRA)improves white matter lesions(WMLs),and explore the mechanism.METHODS:Sprague-Dawley rats(n=33)were randomly divided into sham operation group(n=9),treatment group[stroke-prone renovascular hypertensive rats-modified 2 vessel occlu-sion(RHRSP-modified 2VO)+ambrisentan(n=12)]and placebo group[RHRSP-modified 2VO +vehicle(n =12)].Drug and vehicle administration was performed from 17th to 20th week and monitoring of systolic arterial pressure was performed weekly.Morris water maze test was conducted to evaluate the function of cognition.The protein levels of en-dothelin-1(ET-1)in the cortex,corpus callosum and caudate putamen were quantitatively analyzed respectively.The se-verity of WMLs and the relationship between ET-1 and vessels were observed by the method of histopathology.RESULTS:The difference of systolic arterial pressure between treatment group and placebo group was not significant.The animals in treatment group exhibited shorter escape latency(P<0.05),more times of crossing platform(P<0.05), lower level of ET-1 in corpus callosum and caudate putamen(P<0.05),respectively,improved WMLs severity(P<0.05)and lower binding level of ET-1 to vessels compared with the placebo group.CONCLUSION: Selective inhibition of endothelin receptor A improves the severity of WMLs and ameliorates the cognitive function.

Pathological Changes in APP/PS-1 Transgenic Mouse Models of Alzheimer's Disease Treated with Ganoderma Lucidum Preparation / 中国医学科学院学报

Objective To explore the efficacy of ganoderma lucidum preparation(Ling Zhi) in treating APP/PS-1 transgenic mouse models of Alzheimer's disease(AD).Methods APP/PS-1 transgenic mice of 4 months were randomly divided into model group,ganoderma lucidum treatment groups,including high [2250 mg/(kg·d)] and middle [750 mg/(kg·d)] dose groups,i.e.LZ-H and LZ-M groups,and the positive control group(treated with donepezil hydrochloride [2 mg/(kg·d)]).In addition,C57BL/6J wild mice were selected as normal group.The animals were administered for 4 months.Histopathological examinations including hematoxylin-eosin(HE) staining,immunohistochemistry,special staining,and electron microscopy were applied,and then the pathological morphology and structures in different groups were compared. Results The senile plaques and neurofibrillar tangles in the cerebrum and cerebellum were dissolved or disappeared in LZ-H and LZ-M groups.Decrease of amyloid angiopathy was found in LZ-H and LZ-M groups.The immature neurons appeared more in hippocampus and dentate nucleus of LZ-H and LZ-M groups than those in AD model and donepezil hydrochloride groups(hippcampus:F=1.738,P=0.016;dentate nucleus:F=1.924,P=0.026),and these immature neurons differentiated to be neurons.More Purkinje cells loss occurred in AD model mice than that in LZ-H and LZ-M groups(F=9.46,P=0.007;F=9.46,P=0.010).The LZ-H and LZ-M groups had more new neuron stem cells grown up in cerebellum.Electromicroscopic examination showed the hippocampal neurons in LZ-H and LZ-M group were integrated,the nuclear membrane was intact,and the mitochondria in the cytoplasm,endoplasmic reticulum,Golgi bodies,microtubules,and synapses were also complete.The microglial cell showed no abnormality.No toxicity appeared in the pathological specimens of mice treated with ganoderma lucidum preparation.Conclusion The ganoderma lucidum preparation can dissolve and decline or dismiss the senile plaques and neurofibrillar tangles in the brain of AD mice and also reduce the amyloid angiopathy.

The effects of metformin on glucolipid metabolic disorders and liver lipid deposition caused by clozapine in rats / 预防医学

Objective To study the effect of metformin on glucolipid metabolic disorders and liver lipid deposition caused by clozapine in rats.Methods From 1 d to 4 d,Clozapine 5 mg·kg -1 ·d -1 was gavaged,and the dose increased to 25 mg·kg -1 ·d -1 from the 5th day.Metformin 100 mg·kg -1 ·d -1 or 400 mg·kg -1 ·d -1 or simvastatin 1 mg· kg -1 ·d -1 was gavaged from the 15th day.The total period of dosing was 8 weeks.Body mass,fasting blood sugar (FBS) and postprandial 2 hours blood glucose (2hPBG)were measured at baseline,3 d,1 week,2 weeks,4 weeks,6 weeks and 8 weeks.At the end of the 8th week,serum cholesterol (TC),triglyceride (TG),low density lipoprotein (LDL -C), high density lipoprotein (HDL -C),fructosamine (FA)and insulin (IRS)were measured and liver HE staining was done.Results There were no significant differences of the measured indexes between control group and metformin group at the all test points.By the end of the 6th and 8th week,compared with control group,the body mass,FBS,2hPBG,IRS, FA,TC,TG and LDL -C were significantly increased in clozapine group (P <0.05 ),while HDL -C decreased in clozapine group (P <0.05).Compared with clozapine group,body mass,FBS,2hPBG,IRS,FA,TC,TG and LDL -C were significantly decreased by metformin or simvastatin administration (P <0.05),while HDL -C increased(P <0.05).Rat liver cells in clozapine group were not neat around the small blood vessels;there were more white fat cells and hepatocellular lipid calm far away from the blood vessels.However,in other groups,there were moderate white fat cells, and there were not much hepatocellular lipid calm far away from the blood vessels.Conclusion Metformin could effectively prevent and treat weight gain,glucolipid metabolic disorder and liver lipid deposition caused by clozapine.

Association of Ureaplasma urealyticum infection with bronchopulmonary dysplasia in very low birth weight infants with respiratory distress syndrome / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the relationship between Ureaplasma urealyticum (UU) infection in the lower respiratory tract and the incidence of bronchopulmonary dysplasia (BPD) in very low birth weight (VLBW) infants with respiratory distress syndrome (RDS).</p><p><b>METHODS</b>Seventy-three VLBW infants diagnosed with neonatal RDS, who had received at least one dose of pulmonary surfactant, as well as mechanical ventilation, and were hospitalized for over 28 days, were recruited. Endotracheal aspirates were obtained from the lower respiratory tract and examined by real-time PCR to detect UU DNA. The infants were divided into UU infection and non-UU infection groups according to examination results. Clinical characteristics and the incidence of BPD were compared between the two groups.</p><p><b>RESULTS</b>Compared with the non-UU infection group, the UU infection group had a higher rate of maternal vaginal delivery, higher incidence of recurrent nosocomial pulmonary infection and premature rupture of membranes (PROM), and longer durations of PROM, oxygen supplementation, and hospital stay; in addition, the UU infection group had higher plasma IgM level, leukocyte count, and neutrophil count within 3 hours after birth. Among 73 VLBW infants, 45 developed BPD; the incidence of BPD in the UU infection group was 90% (19/21), versus 50% (26/52) in the non-UU infection group (P<0.01).</p><p><b>CONCLUSIONS</b>UU infection in the lower respiratory tract increases the incidence of BPD in VLBW infants with RDS.</p>

Observation of long-term efficacy and life quality in allergic rhinitis treated with acupoint catgut embedding therapy combined with acupuncture-moxibustion therapy / 中国针灸

<p><b>OBJECTIVE</b>To observe the impacts of acupoint catgut embedding therapy and acupuncture-moxibustion therapy on the long-term efficacy and patient's life quality in the treatment of allergic rhinitis.</p><p><b>METHODS</b>Sixty-nine patients were randomized into the combined acupuncture-moxibustion and acupoint catgut embedding therapy group (combined therapy group, 36 cases) and an acupuncture-moxibustion group (33 cases). In the acupuncture-moxibustion group, acupuncture was applied at Yingxiang (LI 20), Shangyingxiang (EX-HN 8), Yintang (GV 29), Shangxing (GV 23), Tongtian (BL 7) and Zusanli (ST 36). Moxibustion was applied at Zusanli (ST 36), Feishu (BL 13), Dazhui (GV 14) and Fengmen (BL 12). In the combined therapy group, on the basis of the treatment as acupuncture-moxibustion group, the catgut embedding therapy was applied at Feishu (BL 13), Fengmen (BL 12), Pishu (BL 20), Shenshu (BL 23), Zhongwan (CV 12) and Qihai (CV 6). The treatment duration was 4 weeks in the two groups. The clinical efficacy of allergic rhinitis and rhinoconjunctivitis quality of life questionnaire (RQLQ) score were observed before and after treatment as well as in the 4-weeks follow-up after the end of treatment respectively.</p><p><b>RESULTS</b>The markedly effective rate was 72.7% (24/33) in the combined therapy group and 48.4% (15/31) in the acupuncture-moxibustion group after treatment. The efficacy was similar between the two groups (P > 0.05). It was 57.6% (19/33) in the combined therapy group and was 22. 6% (7/31) in the 4-week follow-up after treatment, indicating the long-term efficacy in the combined therapy group was superior to that in the acupuncture-moxibustion group (P<0. 05). Scores of RQLO after treatment and in 4-week follow-up after treatment in both groups were improved as compared with those before treatment (all P < 0.05). In 4-week follow-up, the improvements in sleep and affection in the combined therapy group were superior to the acupuncture-moxibustion group (3.27 +/- 3.23 vs 4.61 +/- 3.56, 3.48 +/- 3.67 vs 5.81 +/- 4.15, both P < 0.05).</p><p><b>CONCLUSION</b>The acupoint catgut embedding therapy combined with acupuncture-moxibustion therapy are safe and effective in the treatment of allergic rhinitis and display the more roles in the long-term efficacy.</p>

Effects of feeding patterns after hospital discharge on increase rates of growth indices in preterm and low-birth-weight infants within 3 months after birth / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the effects of post-discharge formula (PDF) for preterm infants, breast milk (BM) and term infant formula (TF) on increase rates of body weight, length and head circumference in preterm and low-birth-weight infants (PLBWIs) from discharge to 3 months after birth, and to provide a reference for the choice of feeding pattern for PLBWIs.</p><p><b>METHODS</b>A total of 407 PLBWIs discharged from the newborn departments of ten hospitals in Guangzhou City and Foshan City in Guangdong Province, China were chosen for this study. According to feeding pattern, they were assigned to three groups: PDF-fed (n=258), BM-fed (n=58) and TF-fed (n=91). Their body weight, length and head circumference were measured at 3 months after birth, and the increase rates of growth indices relative to baseline values (at birth) were calculated and compared.</p><p><b>RESULTS</b>At 3 months after birth, the PDF-fed group had significantly greater body weight, length and head circumference than the BM-fed and TF-fed groups (P<0.05). The increase rates of body weight and length were significantly higher in the PDF-fed group than in the BM-fed and TF-fed groups (P<0.05).</p><p><b>CONCLUSIONS</b>Compared with those fed with BM and TF after discharge, the PDF-fed PLBWIs have higher increase rates of body weight and length and show greater body weight and length at 3 months after birth. However, further study is needed to investigate the long-term effects.</p>

Expression of SOCS3 and Pyk2 and their correlation in non-small cell lung cancer / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the expression of SOCS3 and Pyk2 and their correlations in non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>The expression of SOCS3 and Pyk2 was detected in 100 cases of NSCLC, human bronchial epithelial cells (HBE) and 6 lung cancer cell lines by immunohistochemistry and immunofluorescence staining. The methylation status of SOCS3 was investigated in A549 cells by methylation-specific PCR. A549 cells were either treated with a demethylation agent 5-aza-2'-deoxycytidine (5-aza) or transfected with three SOCS3 mutants with various functional domains deleted. Besides, the cells were pretreated with a proteasome inhibitor β-lactacystin where indicated. The effects of SOCS3 on Pyk2 expression, Pyk2 Tyr 402 and ERK1/2 phosphorylations were assessed by Western blot. RT-PCR was used to estimate Pyk2 mRNA levels. Transwell experiments were performed to evaluate cell migration.</p><p><b>RESULTS</b>SOCS3 (43.0%, 43/100) and Pyk2 (65.0%, 65/100) were expressed in NSCLC. A significant negative correlation was found between SOCS3 and Pyk2 in both NSCLC tissues and cell lines. SOCS3 was aberrantly methylated and 5-aza restored SOCS3 expression. Transfection studies indicated that exogenous SOCS3 interacted with Pyk2, and both Src homology 2 (SH2) and kinase inhibitory region (KIR) domains contributed to Pyk2 binding. Furthermore, SOCS3 was found to inhibit Pyk2-associated ERK1/2 activity in A549 cells. SOCS3 possibly promoted degradation of Pyk2 in a SOCS-box-dependent manner and interfered with cell migration.</p><p><b>CONCLUSIONS</b>The data indicates that SOCS3 definitely plays roles in regulating Pyk2 signaling, and cell motility. Decreased SOCS3 induced by methylation may confer a migration advantage to A549 cells.</p>

Interleukin 7 and its receptor promote cell proliferation and induce lymphangiogenesis in non-small cell lung cancer / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the mechanism of interleukin 7/interleukin 7 receptor (IL-7/IL-7R) in promoting cell proliferation and inducing lymphangiogenesis of non-small cell lung cancer (NSCLC) in vivo and in vitro.</p><p><b>METHODS</b>Immunohistochemical study for IL-7, IL-7R, cyclin D1 and vascular endothelial growth factor-D (VEGF-D) was carried out in NSCLC tissues from 95 patients. The relationship between IL-7/IL-7R expression and various parameters was analyzed. The mechanism of IL-7/IL-7R in promoting cell proliferation and inducing lymphangiogenesis was studied by methylthiazolyldiphenyl-tetrazolium bromide, fluorescence-activated cell sorting, reverse transcriptase-PCR, Western blot, co-immunoprecipitation, chromatin immunoprecipitation and nude mice experiments with xenograft tumors.</p><p><b>RESULTS</b>IL-7 (63.2%, 60/95), IL-7R (61.1%, 58/95), cyclin D1 (52.6%, 50/95) and VEGF-D (58.9%, 56/95) showed that high level of expression in NSCLC. IL-7/IL-7R over-expression correlated with cyclin D1 expression (P < 0.01, P < 0.01), VEGF-D expression (P < 0.01, P < 0.01), increased lymphovascular density (P = 0.005, P = 0.013), advanced clinical stage (P = 0.008, P = 0.005) and presence of lymph node metastasis (P < 0.01, P < 0.01). IL-7/IL-7R could promote proliferation of A549 cell, increase cyclin D1 and VEGF-D expression, and enhance c-Fos/c-Jun expression and phosphorylation, resulting in formation of heterodimer. Furthermore, IL-7/IL-7R could induce binding of c-Fos/c-Jun to cyclin D1/VEGF-D promoters and regulate their transcription. IL-7/IL-7R could also promote proliferation and lymphangiogenesis of lung cancer xenograft tumors.</p><p><b>CONCLUSIONS</b>IL-7/IL-7R promotes c-Fos/c-Jun expression and activity in NSCLC. This further facilitates cyclin D1 expression and accelerates proliferation of cells and VEGF-D-induced lymphovascular formation.</p>

The effect of birth weight and early growth on body fat composition and insulin sensitivity / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the effect of birth weight and early growth on body fat composition and insulin sensitivity.</p><p><b>METHODS</b>The birth and growth data of 258 children of 6 to 7 years old in Guangzhou were collected from Jun.2009 to Feb. 2010. Physical and laboratory examination were preformed, which included body weight, body height and body fat composition index (body mass index (BMI), percentage of body fat (PBF), waist circumference to height ratio (WtHR), etc). Fasting blood glucose and insulin were measured. The homeostasis model assessment model for insulin resistance index (HOMA-IR) was calculated. According to birth weight, the children were divided into three groups from light to heavy: BW-I, BW-II, BW-III group. Then according to change in weight SDS between 0 and 36 months, the children were divided into three groups: changers up (CU), non-changers (NC), changers down (CD) group. The effect of birth weight and early growth on body fat composition and insulin sensitivity were analyzed.</p><p><b>RESULTS</b>Change in weight SDS between 0 and 36 months was higher in BW-I group (1.06 ± 1.29) than in the BW-II group (-0.19 ± 0.94) and BW-III group (-0.10 ± 1.20) (all P values < 0.01). Birth weight of the CU group ((2.90 ± 0.47) kg) was lower than that of the NC group ((3.22 ± 0.34) kg) and the CD group ((3.57 ± 0.37) kg) (all P values < 0.01). The body fat composition index of BMI, PBF and WtHR were higher in the BW-III group ((16.35 ± 2.13) kg/m(2), (17.03 ± 5.88)%, (0.479 ± 0.033)) than in the BW-I group ((15.46 ± 2.06) kg/m(2), (14.06 ± 5.25)%, (0.459 ± 0.032)) and BW-II group ((15.47 ± 1.58) kg/m(2), (14.09 ± 5.01)%, (0.460 ± 0.025)) (P < 0.01), while there was no significant difference between the BW-I group and the BW-II group (P > 0.05). The body fat composition index of BMI, PBF and WtHR were higher in the CU group ((16.44 ± 2.20) kg/m(2), (16.51 ± 5.78)%, (0.473 ± 0.034)) than in the NC group ((15.62 ± 1.74) kg/m(2), (14.49 ± 5.30)%, (0.463 ± 0.030)) and the CD group ((15.26 ± 1.85) kg/m(2), (14.24 ± 5.54)%, (0.462 ± 0.031)) (all P values < 0.05). In the CU group, BMI, PBF and WtHR were higher in the BW-III-CU group ((18.76 ± 2.56) kg/m(2), (22.19 ± 8.28)%, (0.512 ± 0.029)) than in the BW-I-CU group ((16.04 ± 2.14) kg/m(2), (15.54 ± 5.28)%, (0.467 ± 0.034)) and BW-II-CU group ((16.70 ± 1.36) kg/m(2), (17.12 ± 4.44)%, (0.474 ± 0.017)) (all P values < 0.05), while there was no significant difference between the BW-I-CU group and the BW-II-CU group (P > 0.05). HOMA-IR was higher in the CU group (1.27 ± 0.44) than in the NC group (1.08 ± 0.31) and the CD group (1.00 ± 0.36) (all P values < 0.01). In the CU group, HOMA-IR was higher in the BW-III-CU group (1.69 ± 0.48) than in the BW-I-CU group (1.21 ± 0.41) and the BW-II-CU group (1.27 ± 0.44) (all P values < 0.01), while there was no significant difference between the BW-I-CU and BW-II-CU group (P > 0.05).</p><p><b>CONCLUSION</b>According to birth weight tertile, both lower birth weight individuals with more weight change-up growth postnatal early and higher birth weight individuals had greater body fat composition in childhood. They were high-risk people of insulin resistance.</p>

Effects of heparanase inhibition by RNA interference on proliferation, invasiveness and apoptosis of lung cancer cells / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the effects of heparanase expression inhibition on the proliferation, invasiveness and apoptosis of human lung adenocarcinoma cell line A549 cells.</p><p><b>METHODS</b>Recombinant eukaryotic expression plasmid pshRNA-Hpa targeting human heparanase gene was constructed. A549 cells were cultured in DMEM and transfected with pshRNA-Hpa. The expression of heparanase mRNA and protein were examined by RT-PCR and Western blot. The proliferation, invasiveness and apoptotic rates of A549 cells were determined by MTT method, matrigel invasion assays and flow cytometry respectively.</p><p><b>RESULTS</b>The expression levels of heparanase mRNA and protein were down-regulated in A549 transfected with pshRNA-Hpa. The number of cells penetrating matrigel and the proliferation ability of A549 cells transfected with pshRNA-Hpa were reduced significantly compared to the control cells. The apoptotic rate of A549 cells transfected with pshRNA-Hpa was 12.53% +/- 0.34%, being significantly higher than that of the control cells (both P < 0.01). Western-blot showed that inhibition of heparanase expression led to reduced Akt phosphorylation.</p><p><b>CONCLUSIONS</b>The recombinant plasmid pshRNA-Hpa effectively inhibited the expression of heparanase, thus suppressing the proliferation and invasion and inducing apoptosis of A549 cells. The effects may be due to the down-regulation of Akt phosphorylation level.</p>

Clinical observation on TCM treatment according to syndrome differentiation in relieving acute radio-reaction in nasopharyngeal carcinoma patients / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of traditional Chinese medicine (TCM) treatment according to syndrome differentiation on acute radio-reaction (ARR) in nasopharyngeal carcinoma (NPC) patients.</p><p><b>METHODS</b>One hundred and ninety-five NPC patients who received radiotherapy (RT) for the first time were randomly assigned to two groups: the control group (89 cases) was treated by RT alone for 7 weeks and the treatment group (106 cases) was treated by RT combined with oral taking TCM from starting of RT till 5 weeks after RT. The overall changes in total ARR score and ARR in different locations were observed weekly and compared.</p><p><b>RESULTS</b>The total ARR score in the treatment group was significantly lower than that in the control group (P<0.05). And the ARR scores of different organs, including skin, oropharyngeal mucosa, salivary glands, larynx, car, upper digestive tract, and central nervous system, in the treatment group were all lower than those of the corresponding organs in the control group. In addition, the ARR scores in both groups showed an ascending trend in the first 7 weeks and a descending trend from the 8th to the 10th week after beginning RT.</p><p><b>CONCLUSION</b>TCM treatment could relieve the ARR in the NPC patients without any affection on the efficacy of RT.</p>

Expression of p120ctn and its significance in non-small cell lung cancer / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the expression of p120(ctn) in non-small cell lung cancer (NSCLC) and its correlation with the clinical and pathologic parameters.</p><p><b>METHODS</b>Immunohistochemistry (S-P method) was used to detect the expression of p120(ctn) in 143 NSCLC cases. The variation of protein expression was further analyzed in 36 cases by Western blot. The correlation with clinical and pathologic parameters was studied.</p><p><b>RESULTS</b>Immunohistochemically, normal bronchial cells showed membranous expression for p120(ctn), while NSCLC was characterized by cytoplasmic or diminished membranous staining. The rate of abnormal p120(ctn) expression was 79.7% (114/143). There was a significant correlation between abnormal expression of p120(ctn) and tumor differentiation, clinical stage, lymph node metastasis and poor prognosis (< 0.05), but not histologic typing. Western blot showed that the total amount of p120(ctn) in normal bronchial cells was significantly higher than that in NSCLC. The p120(ctn) isoform 1 (120,000) and isoform 3 (100,000) were expressed in normal lung tissue, while there was a reduced expression or absence of isoform 1 in NSCLC.</p><p><b>CONCLUSION</b>The expression of p120(ctn) is abnormal in NSCLC; p120(ctn) may serve as a useful prognostic marker for NSCLC.</p>

Clinical significance of heparanase and basic fibroblast growth factor expression in human non-small cell lung cancer / 中华病理学杂志

<p><b>OBJECTIVE</b>To assess protein and mRNA expression levels of heparanase and basic fibroblast growth factor (bFGF) genes in human non-small cell lung cancer (NSCLC) and their roles in tumor invasion, metastasis and prognosis.</p><p><b>METHODS</b>A total of 115 paraffin-embedded and 45 fresh-frozen tissue specimens of NSCLC were studied by immunohistochemistry, Western Blot and in situ hybridization to evaluate the protein and mRNA expression status of heparanase and bFGF genes. The data was analyzed by SPSS statistical software.</p><p><b>RESULTS</b>Both human heparanase and bFGF were highly expressed in NSCLC cells, in contrast to none or a low expression in normal lung tissue. Expression of heparanase also showed a significantly higher than that in the normal tissue by Western blot (P = 0.041). Immunohistochemistry showed that heparanase expression was both cytoplasmic and membranous. The agreement between heparanase and bFGF was significant. A significant correlation was found between the expression of either protein and TNM stage, vascular invasion, lymphatic metastasis and microvascular density (MVD). Co-expression of the two proteins demonstrated an even higher correlation with the tumor stage and MVD. In addition, expression of bFGF correlated with tumor cell differentiation. Data of a multivariate analysis indicated that tumor cell differentiation, vascular invasion, lymphatic metastasis and expression of bFGF were identified as significant prognostic parameters.</p><p><b>CONCLUSIONS</b>Both heparanase and bFGF may play important roles in tumor angiogenesis, metastasis, and prognosis of NSCLC.</p>

Expression of tumor necrosis factor alpha mRNA in adipose cell of intrauterine growth retarded rats and its relation to insulin resistance / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the association between the expression of turnor necrosis factor alpha (TNF-alpha) mRNA in fat tissue of intrauterine growth retarded (IUGR) rats and insulin resistance, and the long-term effects of early different nutritional diet.</p><p><b>METHODS</b>The IUGR rat model was established by food restriction of pregnant rats. A total of 32 newborn IUGR rats were randomly divided into 4 groups: IUGR model (S/N) group, IUGR high caloric diet (A) group, IUGR high caloric and high protein diet (B) group, IUGR high protein diet (C) group. Only the mother rats were given those different diets individually, and all IUGR newborn pups were lactated for 3 weeks. From the beginning of the 4(th) week, all IUGR pups were weaned and fed with normal diet till the end of the experiment. Eight normal birth weight newborn rats were used as the control group fed with the normal diet. Weight, perirenal fat weight, fasting glucose and insulin concentration and quantified TNF-alpha mRNA expression in adipose cell were measured at the 48(th) week. The insulin sensitive index (ISI) and the relation index between TNF-alpha mRNA and fat weight, fat weight/body weight (fw/bw) ratio and ISI were calculated.</p><p><b>RESULTS</b>ISI of IUGR model group, IUGR A and B groups was lower than normal control group, while perirenal fat weight, fw/bw and the expression of TNF-alpha mRNA in adipose cells were all significantly higher (P < 0.05 or 0.01). There were no significant differences in these indexes between IUGR C group and normal control groups (P > 0.05). A positive correlation was found between TNF-alpha mRNA and fat weight and fw/bw (r(1) = 0.755, r(2) = 0.782, P = 0.000). Significant inverse associations between ISI and TNF-alpha mRNA (r = -0.556, P = 0.000) and fw/bw (r = -0.513, P = 0.02) were also found.</p><p><b>CONCLUSION</b>The occurrence of insulin resistance in IUGR rats is possibly associated with central obesity and accumulation of the abdominal fat and adipose cell over-expression of TNF-alpha. The adipose TNF-alpha may be an important pathogenic factor of insulin resistance of IUGR. High protein diet is a reasonable nutritional intervention. Because it promotes the skeleton muscle catch-up growth but not fat catch-up growth, it can avoid the occurrence of central obesity and insulin resistance in IUGR rats.</p>

The effects of pregnancy malnutrition on the development of insulin resistance in rat offspring / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the effects of pregnancy malnutrition on the occurrence of insulin resistance (IR) in rat offspring during adult stage and to find out the relationship between TNF-alpha and IR; and to find out a reasonable early nutritional intervention measure for the prevention of IR, through giving different diets to offspring.</p><p><b>METHODS</b>An IUGR model was built by maternal nutrition restriction. 80 newborn IUGR female pups were randomly divided into 4 groups, the mother rats were given the following diet respectively for 3 weeks after delivery, pups were fed by mother milk: (1) The IUGR (intrauterine growth retardation) rat model was used and the animals were divided into: IUGR control group (group S/N) fed with normal diet, (2) IUGR high-caloric diet group (group A), (3) IUGR high-protein and high-caloric diet group (group B) and (4) IUGR high-protein isocaloric diet group (group C). Each group had 20 pups and another 20 normal female pups were fed with normal diet as the normal control group (group C/N). All pups were weaned at the 4th week of age and fed with normal diet till the end of the experiment. At the 12th week (adulthood) and 48th week (senility) of life, body weight and length, the fasting blood glucose, insulin concentration, TNF-alpha of adipose tissue and body weight were measured. Body mass index (BMI), ISI (insulin sensitive index), IRI (insulin resistant index) and HBCI (beta cell insulin excretion index) and their correlation to TNF-alpha were calculated.</p><p><b>RESULTS</b>At 12th week and 48th week of life, the insulin sensitivity of IUGR model group was significantly lower than group C/N, although there was no significant difference of body weight between these two groups. TNF-alpha was negatively correlated with ISI, positively correlated with IRI and no relation to HBCI. Group A and B was fatter and developed more severe IR. There were no significant differences in ISI, IRI, HBCI and TNF-alpha between group C and group C/N.</p><p><b>CONCLUSIONS</b>IUGR offspring of pregnancy malnutrition mother rats showed IR at the age of 12th week. TNF-alpha was closely related to the occurrence of IR in IUGR pups. IUGR pups fed with high caloric diet or high protein and caloric diet at the early postnatal period amplified the metabolic abnormality. The high protein isocaloric diet is effective early nutritional intervention measure for the prevention of occurrence of IR at adulthood.</p>

Effects of early nutrition intervention on IGF1, IGFBP3, intestinal development, and catch-up growth of intrauterine growth retardation rats / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the effects of early nutritional intervention on the serum insulin-like growth factor-1 (IGF1), insulin-like growth factor binding protein 3 (IGFBP3), intestinal development, and catch-up growth of intrauterine growth retardation (IUGR) rats by giving the IUGR new born rats different protein level diet.</p><p><b>METHODS</b>IUGR rat model was built by starvation of pregnant female rats. Twenty-four IUGR pups and 8 normal pups were divided randomly into 4 groups: normal control group (C group); IUGR control group (S group), IUGR low-protein diet group (SL group), and IUGR high-protein diet group (SH group). Detected the serum IGF1, IGFBP3, body weight, body length, intestinal weight length, intestinal villi height (VH), crypt depth (CD), villi absorbing area (VSA), mucous thickness (MT), and disaccharidase at the 4th week.</p><p><b>RESULTS</b>(1) The SH group showed the fastest catch-up growth, serum IGF1, IGFBP3, VH, and VSA were significantly higher than those of normal control group and IUGR control group. The intestinal weight and length, and the activities of lactase and saccharase of the SH group also reached the normal control group level. (2) The SL group kept on small size, the serum IGF1, IGFBP3, and most of intestinal histological indexes were all significantly lower than other groups. (3) IGF1, IGFBP3 were positively correlated to intestinal VH, VSA, saccharase, body weight and length.</p><p><b>CONCLUSIONS</b>The serum IGF1 was a sensitive index to the catch-up growth. The early nutritional intervention of high-protein diet after birth is helpful for the catch-up growth of IUGR through promoting the intestinal development and the absorption of nutrition.</p>

Effect of different early nutritional interventions on catch-up growth of rats with intrauterine growth retardation / 中华儿科杂志

<p><b>OBJECTIVE</b>About 20 - 50% individuals with intrauterine growth retardation (IUGR) could not achieve catch-up growth and remain small in size till adulthood. There are few reports on the relation between intestinal development and body catch-up growth of IUGR. Studies showed that early "nutritional programming" would results in long-term effects on the body growth and organic function, and gastrointestinal development is closely related to the body development as well. The authors aimed to study the effect of early nutritional interventions on serum IGF1, IGFBP3, intestinal development and catch-up growth of pups with IUGR by using diets with different protein and caloric levels during the first four weeks of life.</p><p><b>METHODS</b>An IUGR rat model was established by maternal nutrition restriction during pregnancy. Thirty-two IUGR female pups were divided randomly into 4 groups (8 pups in each group) and eight normal female pups as control. The groups and interventions were (1) Normal control group (C group); (2) IUGR control group (S group), (3) IUGR low-protein diet group (SL group); (4) IUGR high-protein diet group (SH group); (5) IUGR high-caloric group (SA group). The serum IGF1, IGFBP3, body weight, body length, and intestinal weight, length, intestinal villi height (VH), crypt depth (CD), villi absorbing area (VSA), mucous thickness (MT) were measured at the 4(th) week of life.</p><p><b>RESULTS</b>(1) At the 4(th) week, the serum IGF1 (724.0 +/- 153.5 ng/ml), IGFBP3 (9.69 +/- 3.13 ng/ml), and VH (416.9 +/- 46.3 microm), VSA (115.9 +/- 24.0 x 10(3) microm(2)), MT (583.9 +/- 68.5 microm) in the SH group were significantly higher than those of normal control group (539.4 +/- 198.4 ng/ml, 4.77 +/- 2.98 ng/ml and 322.1 +/- 25.8 microm, 85.8 +/- 17.8 x 10(3) microm(2), 480.0 +/- 61.5 microm) and IUGR control group (P < 0.05). The intestinal weight (1.91 +/- 0.16 g) and length (80.67 +/- 9.47 cm) in the SH group was not significantly different from the normal control group (2.24 +/- 0.22 g and 74.77 +/- 9.06 cm, P > 0.05). The SH group showed the fastest catch-up growth. Their body weights (40.14 +/- 11.03 g) at the 3(rd) week and body lengths (23.61 +/- 0.49 cm) at the 4(th) week of life reached the normal ranges of the control group (44.65 +/- 5.36 g and 23.10 +/- 1.42 cm, P > 0.05). (2) The serum IGF1 (346.7 +/- 85.3 ng/ml), IGFBP3 (1.4 +/- 0.21 ng/ml), body weight (21.41 +/- 3.54 g) and body length (15.96 +/- 1.29 cm) and the most of intestinal indexes in the SL group were markedly lower than other groups at the 4(th) week of life (P < 0.05).</p><p><b>CONCLUSION</b>The serum IGF1 was a sensitive marker to reflect the catch-up growth and nutritional status, and IGF1 was positively correlated with the intestinal development and body growth. When given different nutritional interventions during the first four weeks of life, high protein diet is more helpful for the IUGR catch-up growth by promoting the intestinal development and the absorption of nutrition.</p>