A series of 2-methoxyestradiol (2-MeO-E2) RGD peptide conjugates with coupling RGD peptides to 3- position or 17-position of 2-MeO-E2 through space linker were synthesized. Their antiangiogenic properties were preliminarily evaluated by cell migration scratch assays against HUVECs. Compound 26c binding RGDV peptide showed the best inhibitory effect. In addition, all 2-MeO-E2 RGD peptide conjugates exhibited obvious activity. These results demonstrate that conjugates with RGD peptides represent a promising means for targeting angiogenesis in cancer therapy.

Objective To explore the death types of PC12 cells injured by a high concentration of zinc, and effects of inosine on the types of zinc-induced cell death. Methods MTT assay was used to assess the viability of PC12 cells treated with different concentrations of zinc chloride (50, 100,200,400 μmoL/L) or inosine (0.1,0.5, 1.0, 2.0 mmol/L) for 12 h. Hoechst 33342 / PI double staining, Annexin-V binding assay and DNA agarose gel electrophoresis were employed to investigate the death forms of PC12 cells with treatment of 200 μmol/L zinc chloride or 2.0 mmol/L inosine for 12 h. Results Zinc at 100 μ mol/L and more reduced cell viability significantly. After treatment with 200 μmoL/L zinc,56.5, 24.4 and 19.1% of total PC12 cells were necrotic, survival and apoptotic. Inosine, from the concentration of 0.5 mmol/L, markedly increased cell viability of zinc-induced PC12 cells. However, additional exposure to 2.0 mmol/L inosine, necrotic, survival and apoptotic cells were 27.9, 33.8 and 38.4% of the total PC12 cells that were injured by zinc.Conclusion The viability of PC12 cells decreases when the concentration of zinc increases, and inosine protects zinc-induced PC12 cells at a dose-dependent manner. A high concentration of zinc causes both necrosis and apoptosis, and inosine attenuates necrosis, but not apoptosis, of zinc-injured PC12 cells.

Objective To understand the situation of iodized salt consumption at the household level and non-iodized salt distribution in those areas with low iodized salt coverage.Methods In 2010,iodized salt was monitored in 31 provinces and Xinjiang Production and Construction Corps in accordance with the Monitoring Program of the National Iodine Deficiency Disorders (Trial) (hereinafter referred to as the Program) requirements.Under the jurisdiction of counties (cities,districts,banners) with more than 9 townships (towns,street offices),based on the location of east,west,south,north and center,9 townships (town,district offices) were selected using simple random sampling method; 4 administrative villages (neighborhoods) were selected in each township (town,district office); and 8 residents in each administrative village (neighborhood) were selected.Under the jurisdiction of counties (cities,districts,banners) with less than 9 townships (towns,street offices),based on the location of east,west,south,north and center,1 township(town,district office) was selected using simple random sampling method; 4 administrative villages(neighborhoods) were selected in each township(town,district office);and 15 residents in each administrative village(neighborhood) were selected.Iodized salt coverage rate,qualification rate of iodized salt and consumption rate of qualified iodized salt were calculated in various provinces.The salt samples were tested by semi-quantitative method on the spot and then tested with quantitative method in laboratories.The standard of qualified iodized salt was set as 20-50 mg/kg and that of non-iodized salt was set as ＜ 5 mg/kg (GB/T 13025.7-1999).Results In 2010,a total of 2862 counties(districts,cities and banners) and 14 divisions of Xinjiang Production and Construction Corps,reported the monitoring results,and the monitoring coverage rate was 99.79％(2876/2882).A total of 826 696 copies of edible salt samples were tested,the coverage rate of iodized salt was 98.63％,the consumption rate of qualified iodized salt was 97.95％,and the coverage rate of qualified iodized salt was 96.63％.At province level,only in Tibet iodized salt coverage rate was ＜ 90％.At county level,2755 counties qualified iodized salt coverage rate was ≥90％,and 33 counties iodized salt coverage rate was ＜ 80％.The counties with qualified iodized salt coverage rate of 90％ or more accounted for 96.63％(2785/2882) of the total counties.Conclusions The counties where non-iodized salt coverage is higher than 20％ mainly distributed in the western or coastal areas and adjacent areas with higher iodine.These areas need policy and funding support from governments at all levels to reducc the gap between these areas and other areas.

OBJECTIVETo describe the mortality of esophageal cancer (EC) in China during 2004 - 2005, and its trends over past 30 years.

METHODSThe Third National Retrospective Sampling Survey of Death Causes in 2004 - 2005 was covered 142 660 482 person years (72 970 241 person years in male, 69 690 241 person years in female; 47 899 806 person years in urban, 94 760 676 person years in rural). All death records of EC cases were selected. Crude, age-adjusted mortality, the proportion to all cancer deaths, and age-standardized death rate by Chinese standard population (CASR) and world standard population (WASR) were calculated. The statistic indexes of mortality were compared with those of previous retrospective death surveys in 1973 - 1975 and 1990 - 1992.

RESULTSDuring 2004 - 2005, the crude death rate of EC was 15.21/100 000 (21 694/142 660 482), CASR was 9.98/100 000, EC death accounted for 11.19% (21 694/193 841) and ranked fourth of all cancer death causes. The CASR of male (14.32/100 000, 15 067 cases) was higher than that of female (5.75/100 000, 6627 cases). In rural areas, there were 16 437 deaths caused by EC with CASR of 12.01/100 000, it was higher than in urban areas (CASR was 6.48/100 000, 5257 deaths). There were little different of EC mortality among Eastern, Central and Western areas in China. EC crude death rate in Eastern was the highest with rate of 16.67/100 000 (8761/52 556 694) and the lowest rate was 12.92/100 000 (5209/40 322 563) in Western area. EC crude death rate was increased by age increasing and reached the peak with mortality of 180.55/100 000 (1984/1 098 885) at age group of 80-. The CASR of EC was reduced by 41.64% compared with the first survey (CASR was 17.10/100 000) in 1973 - 1975, and reduced by 33.56% compared with the second survey (CASR was 15.02/100 000) in 1990 - 1992.

CONCLUSIONAlthough the EC mortality has dropped obviously in the past three decades, it is still the main cancer burden, especially in rural areas. EC prevention and control should be focused on the rural high risk areas in China in future.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cause of Death ; trends ; Child ; Child, Preschool ; China ; epidemiology ; Data Collection ; Esophageal Neoplasms ; epidemiology ; mortality ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Young Adult

OBJECTIVETo study the role of cAMP in repair of hemisection of spinal cord in rats models.

METHODSRats models of spinal cord hemisection were made and cAMP were injected once in the motor cortex or continuously input in the lesion area or in the subarachnoid cistern for 3 d. NFs, GFAP, CSTs and spinal axons in the lesion areas were observed by immunohistochemistry and hind limb movements were evaluated in BBB scales.

RESULTSMany regenerated axons were presented in the lesion areas in cAMP groups though no continuous long regenerated axons traversed the lesion area when cAMP was input in the motor cortex or in the local lesion area. In control group, no regenerated axon were presented in the lesion areas. When cAMP was input in the subarachnoid cistern, only few-labelled CST axon survived and presented in the lesion area comparing no labelled CST axon presented in the lesion area. More NFs and less GFAP were distributed and extended in the lesion area in the cAMP groups. All the rats restored to normally walk 4-5 weeks after operations and no significance existed between cAMP groups and control groups comparing the BBB scales of hind limb movements.

CONCLUSIONcAMP injected in the brain cortex or continuously input in the lesion area can induce the axonal regeneration.

Administration, Topical ; Animals ; Cyclic AMP ; administration & dosage ; physiology ; Hindlimb ; physiopathology ; Male ; Nerve Regeneration ; drug effects ; Rats ; Rats, Sprague-Dawley ; Spinal Cord Injuries ; drug therapy ; physiopathology

OBJECTIVETo explore the expression and significance of secretions of hypothalamus-pituitary-adrenal (HPA) axis in human hypertrophic scar.

METHODSHypertrophic scar tissues obtained from 12 patients with deep-partial thickness burn or full-thickness burn and normal skin tissues from the same 7 patients with hypertrophic scar were harvested for determination of gene expression of corticotrophin-releasing hormone (CRH), CRH receptor 1 (CRH-R1), pro-opiomelanocortin (POMC), melanocortin receptor 2 (MC-2R), and glucocorticoid receptor α (GR-α) by real-time fluorescence quantitative PCR. After addition of corresponding antibodies, distribution differences of CRH, CRH-R1, adrenocorticotropic hormone (ATCH), MC-2R, and GR-α were observed with immunohistochemical staining. Data were processed with t test.

RESULTSThe mRNA expression of CRH, CRH-R1, POMC, and GR-α in hypertrophic scar was respectively 3.1 ± 0.8, 0.05 ± 0.03, 0.020 ± 0.007, and 0.0030 ± 0.0010, which were significantly lower than those in normal skin (20.6 ± 4.7, 0.30 ± 0.12, 0.060 ± 0.020, and 0.0200 ± 0.0070, with t values from 2.10 to 4.75, P values all below 0.05). There was no statistical difference in MC-2R mRNA expression between hypertrophic scar and normal skin (t = 1.48, P = 0.15). Immunohistochemical observation showed CRH, CRH-R1, ACTH, MC-2R, and GR-α in hypertrophic scar were located in basal layer of epidermis, fibroblast of dermis, and tube wall of sweat gland. Expressions of these indexes could also be observed in sebaceous gland and hair follicle besides above-mentioned structures.

CONCLUSIONSDecreasing expression of active material of HPA axis may be related to formation of hypertrophic scar.

Adolescent ; Adrenocorticotropic Hormone ; metabolism ; Adult ; Child ; Cicatrix, Hypertrophic ; metabolism ; Female ; Glucocorticoids ; metabolism ; Humans ; Hypothalamo-Hypophyseal System ; metabolism ; Male ; Pituitary-Adrenal System ; metabolism ; Young Adult

OBJECTIVETo study the effect of melatonin on proliferation and apoptosis of fibroblasts in human hypertrophic scar and its mechanism.

METHODSFibroblasts from human hypertrophic scar were isolated and cultured with DMEM medium containing 10% FBS, and then they were divided into control (C, added with ethanol), low concentration (LC, added with 1 × 10(-5) mmol/L melatonin), middle concentration (MC, added with 1 × 10(-3) mmol/L melatonin), and high concentration (HC, added with 1 mmol/L melatonin) groups according to the random number table. After being cultured for 24 hours, cell morphologic change was observed under microscope; XTT-PMS assay was used to examine cell proliferative activity; cell cycle and apoptosis were assessed with flow cytometry after double staining of FITC and PI, and the levels of cyclin E, p53, and Fas mRNA were determined with fluorescence quantitative RT-PCR. Data were processed with analysis of variance and LSD test.

RESULTS(1) Fibroblasts in C group were spindle-shaped with growth in colonies. Along with the increase in melatonin concentration, fibroblasts in LC, MC, and HC groups gradually dispersed, deformed and atrophied, with shrunk cellular membrane, and decrease in ratio of nucleus and cytoplasm. (2) Proliferative activity of fibroblasts in LC, MC, and HC groups decreased along with an increase in melatonin concentration (1.49 ± 0.15, 1.24 ± 0.20, and 0.92 ± 0.09), which were lower that in C group (1.79 ± 0.10, F = 67.61, P < 0.05). Cell ratios of S and G2/M phases in LC, MC, and HC groups decreased along with an increase in melatonin concentration, which were all lower than those in C group [(10.6 ± 1.1)%, (6.1 ± 1.2)%, (3.2 ± 0.8)% vs.(16.9 ± 1.3)%, F = 286.10, P < 0.05; (13.5 ± 1.1)%, (9.8 ± 1.0)%, (6.0 ± 0.7)% vs. (16.7 ± 1.6)%, F = 162.69, P < 0.05]. Apoptotic rates in early and late stages of LC, MC, and HC groups increased along with an increase in melatonin concentration, all higher than those in C group (with F value respectively 424.05, 236.44, P values all below 0.05). The expressions of cyclin E mRNA in LC, MC, and HC groups decreased along with an increase in melatonin concentration, which were lower than that in C group (1.58 ± 0.21, 0.90 ± 0.20, and 0.24 ± 0.12 vs. 2.90 ± 0.30, F = 266.79, P < 0.05), while the expressions of p53 mRNA and Fas mRNA showed opposite tendency (with F value respectively 10.11, 12.03, P values all below 0.05).

CONCLUSIONSMelatonin can inhibit proliferation and induce apoptosis of fibroblasts in hypertrophic scar through regulating the gene expressions of cyclin E, p53, and Fas.

Adult ; Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Cicatrix, Hypertrophic ; metabolism ; pathology ; Cyclin E ; metabolism ; Female ; Fibroblasts ; drug effects ; metabolism ; pathology ; Humans ; Male ; Melatonin ; pharmacology ; Oncogene Proteins ; metabolism ; Tumor Suppressor Protein p53 ; metabolism ; fas Receptor ; metabolism

OBJECTIVE: To explore the genetic basis for a Chinese pedigree where three siblings were affected with Parkinson's disease. METHODS: Multiple ligation-dependent probe amplification (MLPA) and next-generation sequencing (NGS) were employed to detect the causative mutation. Sanger sequencing of cDNA was also used for verify the effect of mutation on the transcription of RNA. RESULTS: Heterozygous deletion of exon 3 of the PARK2 gene was detected by MLPA, while a heterozygous splice site variant c.619-3G>C was detected by NGS. Both mutations were shown to result in aberrant transcripts of the PARK2 gene (loss of exons 3 and 6, respectively) by Sanger sequencing of cDNA. Both mutations have co-segregated with the disease in the pedigree. CONCLUSION Compound heterozygous mutations of the PARK2 gene probably underlie the disease in this pedigree. Identification of the splice site variant c.619-3G>C has expanded the mutation spectrum of the PARK2 gene.
Asian Continental Ancestry Group ; China ; DNA Mutational Analysis ; Exons ; Heterozygote ; Humans ; Mutation ; Parkinson Disease ; genetics ; Pedigree ; Ubiquitin-Protein Ligases ; genetics

OBJECTIVE: To compare the clinical features and follow-up results of systemic lupus erythematosus (SLE) between boys and girls. METHODS: A retrospective analysis was performed for the clinical data of 79 children (18 boys and 61 girls), aged ≤14 years, who were diagnosed with SLE from 2008 to 2018. The boys and the girls were compared in terms of initial and major clinical symptoms, injury of organs/systems, related laboratory markers, and follow-up results. RESULTS: As for the initial and non-initial symptoms, fever had the highest incidence rate in the boys, while facial erythema had the highest incidence rate in the girls. The boys tended to develop renal injury and hematological damage (P<0.05), with a significantly higher incidence rate of proteinuria than the girls (P<0.05), while the girls tended to develop joint pain (P<0.05). There were high abnormal rates (>80%) of anti-nuclear antibody, dsDNA, complement C3, and erythrocyte sedimentation rate in both boys and girls (P>0.05). The boys had a significantly higher disease activity than the girls at the first visit and in year 9 of follow-up (P<0.05). A one-month to ten-year follow-up showed that among the boys, 3 were lost to follow-up, 1 died, 7 were well controlled but required oral administration of large doses of hormones or immunosuppression, 2 progressed to chronic renal failure, and 1 developed lupus encephalopathy. Among the girls, 3 were lost to follow-up; 5 died; 34 were well controlled, among whom 5 were maintained on oral prednisone acetate with a dose of <10 mg, 1 was withdrawn from the drug for 1 year, and 2 were withdrawn from the drug for 2 years; 4 developed lupus encephalopathy; 1 developed depression and anxiety and had suicidal tendency in the 7th year after disease onset; 2 experienced impaired vision, blurred vision, and chloropsia; 1 developed a vascular necrosis of both femoral heads in the 3rd year of hormone administration. CONCLUSIONS There are differences in clinical features, several laboratory markers, and prognosis between boys and girls with SLE. Boys tend to have a high severity at disease onset, develop renal injury and hematological damage, and have poor long-term prognosis, while girls tend to have joint involvement.

BACKGROUNDChai Lai Prescription is a Chinese herbal compound which is used to sooth the liver, strengthen the spleen and harmonize the stomach for descending adverse Qi. We initiated the study to investigate its mechanism of treating in vitro rabbit reflux esophagitis models.

METHODSAdult male Japanese white rabbits, weighing 1.8-2.2 kg, were divided into five groups of three each, which were: normal control group (Krebs buffer, pH7.4), esophagitis model group (Krebs buffer, pH5.8), esophagitis model proup+low-dose Chinese herbal medicine protection group (0.6 mg × ml(-1)× kg(-1)), esophagitis model group+moderate-dose Chinese herbal medicine protection group (6 mg × ml(-1)× kg(-1)), esophagitis model group+high-dose Chinese herbal medicine protection group (60 mg × ml(-1)×kg(-1)). The RT-PCR method was used to test the influence of Chai Lai Prescription on IL-1 and IL-6 in in vitro rabbit models of esophagitis. We treated the in vitro models with different doses of Chinese herbal medicine.

RESULTSEsophageal mucosa were filled with various liquids. IL-6 and IL-1β mRNA expression was increased in rabbit esophageal mucosa stimulated with acid. Chinese herbal medicine significantly reduced the levels of IL-6 and IL-1β mRNA expression in the in vitro cultured rabbit esophageal mucosa. Using Chinese herbal medicine to treat in vitro models of RE, we found that the IL-6 and IL-1β mRNA expression levels went down, near to or lower than the normal control levels, compared with the group treated with acidified buffer solution.

CONCLUSIONSChai Lai Prescription lowered the IL-1β and IL-6 cytokine mRNA levels and protected the esophageal mucosa in the in vitro models of reflux esophagitis, suggesting that the traditional Chinese herbal compound may be able to treat reflux esophagitis by inhibiting the its inflammatory mediators.

Animals ; Drugs, Chinese Herbal ; therapeutic use ; Esophagitis, Peptic ; drug therapy ; metabolism ; Interleukin-1beta ; genetics ; Interleukin-6 ; genetics ; Male ; Rabbits