Objective:To study the thickness distribution palatal bone in adolescents and provide a clinical reference for implanting mini-screws.Methods:Cone-beam CT head scan data of palate of 20 adolescent orthodontic patients were measured with NNT Viewer software.60 points of the palate bone on one side were designed as 1 -10 in sagittal direction and as A -F in transvers direction with incisive foramen as the point of A and 0,the distance between each 2 adjacent points was 2 mm.The bone thickness of the 60 points were measured and statistically analyzed.Results:There were no significant differences among B2,B3,C2,C3,D3,E3,E4,F4 and F5(P >0.05).Statistically significant difference was found between F3 and B2 or B3,C2,C3,D3,E3,E4,F4 and F5(P ＜0.05).There was significant difference between D3 and D4(P ＜0.05).Conclusion:The appropriate areas for implanting mini-screws in palate may be about 2 -4 mm near the palatal suture and 4 -6 mm behind incisor canal,and 8 -10 mm near the palatal su-ture,6 -8 mm behind incisor canal.Those regions are safe for implanting mini-screws and can provide about 6 mm bone tissue sup-port.

The development trend, countries, institutions, co-authors, and subjects in MEDLINE-covered papers were analyzed by Excel, Ucinet and SciMAT respectively in order to understand the current situation in studies on precision medicine, which showed that precision medicine is in a rapid development stage, the impact power of pa-pers on precision medicine published in United States of America is high, the source journals published in United States of America are the core journals in precision medicine, the academic level of papers on precision medicine published in United States of America is high. Co-authors analysis showed that the co-authors network is of the small world effect. Subject evolution analysis revealed that the subjects involved in studies on precision medicine are increasingly rich with genomics, drug treatment and oncology accounted a large proportion. Analysis of the evo-lution in genomics, drug treatment and oncology displayed that the subjects involved in studies on precision medi-cine have experienced macro-stage, micro-stage, and combined macro- and micro-stage.

Objective To investigate the expression of cathepsin B in photoaging skin and its signifi-cance.Methods Skin specimens were obtained from the right forearm(sun-exposed sites)and buttock (unexposed sites)of 6 healthy volunteers with informed consent and subjected to immunohistochemistry for the detection of cathepsin B expression.Primary human fibroblasts derived from the prepuce of children aged 3 to 6 years were cultured in vitro;after 10 to 15 passages,cells were divided into four groups to be treated with methoxsalen of 50 mg/L for 24 hours followed by ultraviolet A(UVA)exposure(premature senescence group),phosphate buffered saline(PBS)only(control group),UVA exposure only(UVA group),methoxsalen only(methoxsalen group).Then,the protein and mRNA expressions of cathepsin B were detected by Western blot and RT-PCR,respectively,in these fibroblasts 1,2,3 weeks after the treatment.Results Cathepsin B was observed in both exposed and unexposed sites of all volunteers,and the average absorbence of cathepsin B was significantly lower in exposed sites than in unexposed sites(0.2130±0.7997 vs 0.4520±0.5921,t=5.37,P<0.05).Decreased protein expression of cathepsin B was also noted in the premature senescence group compared with the other three groups.Moreover,the gray ratio between cathepsin B protein and glyceraldehyde phosphate dehydrogenase(GAPDH)in premature senescence group reduced from 28.099±O.054 before treatment to 25.1 03±0.102 in week 1 and 17.693±0.099 in week 3 after UVA exposure.RT-PCR revealed that the mRNA expression level of cathepsin B in fibroblasts of premature senescence group decreased by 36 percent compared with that in the control group.Conclusions The expression of cathepsin B decreases in photoaged skin as well as in UVA-exposed fibroblasts in a time-dependent manner,which may be associated with the self-repair of photoaged skin.

Objective:To investigate the effect of cyclin D1 (CCND1) negatively regulated by miRNA-541 (miR-541-5p) on the proliferation and migration of colon cancer cells as well as its related mechanism.Methods:Expression levels of miR-541-5p in colon cancer cell lines HT29, SW480, SW620, HCT116 and enterocyte line HIEC of the normal people as well as cancer tissues and pericarcinomatous normal tissues of 112 patients undergoing the colon cancer surgery from the First Affiliated Hospital of Hebei North University between April 2017 and March 2020 were detected by using quantitative real-time polymerase chain reaction(qRT-PCR). The potential target gene of miR-541-5p was predicted by using TargetScan, and was verified by using dual luciferase reporter gene assay, qRT-PCR and Western blot. Expression level of CCND1 was detected in colon cancer cell lines and tissues. Cells with the lowest expression level of miR-541-5p were divided into miR-NC group (the transfected control plasmid), miR-541-5p group (the transfected miR-541-5p mimics), miR-541-5p+CCND1 group (the co-transfected miR-541-5p mimics and CCND1). Effect of miR-541-5p and CCND1 on proliferation and migration ability of colon cancer cells was detected by using cell counting kit-8 (CCK8) and Transwell method. The xenograft model of colon cancer in nude mice was constructed to observe the effect of miR-541-5p on tumor growth.Results:The relative expression level of miR-541-5p in colon cancer tissues was lower than that in pericarcinomatous normal tissues (0.45±0.06 vs. 1.00±0.12, t = 43.385, P < 0.01). The relative expression level of miR-541-5p was 0.46±0.03, 0.67±0.04, 0.57±0.06, 0.17±0.02, 1.00±0.15, respectively in colon cancer cell lines HT29, SW480, SW620, HCT116 and enterocyte line HIEC of the normal people, and the difference was statistiacally significant ( F = 5.621, P < 0.01); the relative expression level of miR-541-5p in all colon cancer cell lines was lower than that in enterocyte line HIEC of the normal people. HCT116 cells were selected to make the subsequent experiments. The predicted results of TargetScan showed that 3'UTR of CCND1 might have sites complementary to those of miR-541-5p. Dual luciferase reporter gene assay showed that CCND1 was the target gene of miR-541-5p, and miR-541-5p negatively regulated the expression of CCND1. CCK-8 method showed that cell proliferation rate of HCT116 was (2.00±0.16)%, (0.89±0.08)%, (2.56±0.23)%, respectively in miR-NC group, miR-541-5p group, miR-541-5p+CCND1 group, and the difference was statistically significant ( F = 6.715, P < 0.01); among HCT116 cells with the overexpression of miR-541-5p, the transfected CCND1 chould reverse the inhibitory effect of miR-541-5p on cell proliferation. Transwell results showed that the overexpression of miR-541-5p inhibited the cell migration ability of HCT116, while the co-transfection of miR-541-5p mimics and CCND1 could reverse the inhibitory effect. In the colon cancer nude mice xenograft model, the tumor mass and size of nude mice in miR-541-5p group was decreased compared with that in the control group (all P < 0.05). Conclusions:miR-541-5p inhibits cell proliferation and migration of colon cancer cells via negatively regulating CCND1, and inhibits tumor growth in xenograft model of colon cancer in nude mice, thereby acting as a tumor suppressor in colon cancer.

OBJECTIVETo examine the prevalence of obesity phenotypes and cardiometablic disorders (CDs) among children aged 6- 17 in Beijing from 2004 to 2013.

METHODSData were obtained from two cross-section surveys, which were conducted in 2004 and 2013. In 2004, by using stratified cluster sampling design, 20 primary or middle schools were selected from 7 districts (Xicheng, Dongcheng, Chaoyang, Haidian, Daxing, Pinggu, and Yanqing) in Beijing, and 20 554 school children aged 6-17 were recruited, with weight, height, waist circumference and blood pressure measured. Fasting plasma glucose (FPG), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) were measured in 962 subjects from one school. In 2013, by using the same sampling design, 7 211 students from two districts (Haidian and Dongcheng) were surveyed with weight, height, waist circumference and blood pressure measured, and fasting plasma glucose and lipid profile (TC, TG, HDL-C, LDL-C) were measured for 1 344 subjects in the same school measured in 2004. Student's-t test was used to analyze the difference in body mass index(BMI), WC, and waist to height ratio (WHtR) among children between 2004 and 2010. Chi-square test was used to analyze the difference of hypertension, impaired fasting glucose(IFG), dyslipidemia, and metabolic disorders clustering between 2004 and 2010, and among different types of obesity; logistic regression model was used to analyze the association between three types of obesity and risks of cardiovascular metabolic disorders.

RESULTSIn boys, BMI ((20.3 ± 4.4) vs (19.4 ± 4.2) kg/m(2), t=11.18, P<0.001), WC ((70.6 ± 12.8) vs (66.7 ± 11.8) cm, t=17.20, P<0.001) and WHtR (0.451 ± 0.064 vs 0.437 ± 0.059, t=11.64, P<0.001) were significantly higher in 2013 than those in 2004. Similarly in girls, BMI ((18.9 ± 3.6) vs (18.7 ± 3.7) kg/m(2), t=12.21, P<0.001), WC ((64.5 ± 9.6) vs (63.0 ± 9.3) cm, t=8.15, P<0.001) and WHtR (0.430 ± 0.047 vs 0.423 ± 0.047, t=14.13, P<0.001) were also significantly higher in 2013 than those in 2004. The prevalence of combined obesity rose from 8.27% (1 697/20 526) in 2004 to 10.74% (774/7 209) in 2013, and central obesity from 3.08% (632/20 526) to 4.44% (320/7 209). The prevalence of hypertension (10.78%(313/1 344) vs 4.29% (42/962), χ(2)=36.76, P<0.001), IFG(49.54%(664/1 344) vs 6.45%(63/962), χ(2)=506.61, P<0.001), high TC(11.53%(155/1 344) vs 5.03%(49/962), χ(2)=28.31, P< 0.001), high TG(7.51%(101/1 344) vs 3.59%(35/962), χ(2)=29.59, P<0.001) were significantly higher in 2013 than those in 2004. Subjects with combined obesity had higher risks of hypertension (OR=5.88, 95% CI: 4.42-7.82), high TG (OR=7.12, 95%CI: 4.35-11.64), low HDL-C (OR=3.04, 95%CI: 1.55-5.95), high LDL-C (OR=2.27, 95% CI: 1.22-4.02), CDs≥2 (OR=3.07, 95% CI: 2.09-4.50), comparing to children without obesity.

CONCLUSIONThe prevalence of types of obesity and obesity-related metabolic disorders, except for low HDL-C and high HDL-C, were significantly higher in 2013 than those 2004 among chlildren aged 6-17 year in Beijing. Children with combined obesity had higher prevalence of metabolic disorders.

Adolescent ; Beijing ; Blood Glucose ; analysis ; Blood Pressure ; Body Mass Index ; Body Weight ; Cardiovascular Diseases ; epidemiology ; Child ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Cross-Sectional Studies ; Dyslipidemias ; epidemiology ; Female ; Humans ; Hypertension ; epidemiology ; Lipids ; blood ; Logistic Models ; Male ; Obesity, Abdominal ; epidemiology ; Pediatric Obesity ; epidemiology ; Phenotype ; Prevalence ; Triglycerides ; blood ; Waist Circumference

Objective To compare the regulating effect of electrically stimulating different parts of the auri-cle on the cardiac vagus nerve in rats, and to explore the basic neural mechanism. Methods The tragus, concha auriculae and helix of 24 male Sprague-Dawley rats were stimulated at different intensities ( 0-16 mA) and with differ-ent durations ( 0-15 min) and any changes in the heart rate were observed. One week later, the rats were randomized into a tragus injection group, a concha auriculae injection group, a helix injection group and a control group, each of 6. The rats of the first three groups were injected with 2 μL of cholera toxin subunit B conjugate AF555 ( CTB-AF555) at the right auricle, while the control group was injected with the same amount of aseptic phosphate-buffered saline at the right tragus. Five days later, all of the rats were sacrificed and their right superior and inferior ganglia and the whole bulbus medullae were resected to observe the fluorescent labeling sites. Results The rats'heart rate declined with longer and more intense stimulation of the tragus or concha auriculae, but not with stimulation of the he-lix. With stimulation of the same duration, a significant decrease was observed in the heart rate when the tragus and concha auriculae were stimulated at 10, 12, 14 or 16 mA compared with when the helix was stimulated at the same intensities. The heart rate when the concha auriculae was stimulated at 12 mA was significantly slower than when the tragus was stimulated at the same intensity. At identical stimulus intensities, the heart rate slowed significantly more when the tragus was stimulated for 6 to 15 minutes and the concha auriculae for 4 to 15 minutes compared with stimu-lating the helix for the same length of time. And compared with stimulating the tragus for 6 to 10 minutes, the heart rate decreased significantly more when the concha auriculae was stimulated for the same length of time. All of the rats in the tragus and concha auriculae injection groups displayed nerve tracer in their superior and inferior ganglia. In the tragus injection group, CTB-AF555 was observed in the nucleus tractus solitarius ( NTS) of 3 of the 6 rats. In the concha auriculae injection group it was observed in 4 of the 6. In the helix injection group, CTB-AF555 was observed in the nucleus of the spinal tract in 5 of the 6 rats, but no nerve tracer was found in their superior or inferior ganglia or in the NTS. Conclusion Electrical stimulation of the tragus and concha auriculae can regulate the functioning of the cardiac vagus nerve, but stimulating the helix cannot. This is partly because the nerve signals in tragus or concha auriculae stimulation and the cardiac sensory nerve signal are integrated in the inferior ganglion and then analyzed and processed in the bulbar center to monitor the heart.

Objective:To investigate the mechanisms of effects of high fat and high fructose diet on rat aging.Methods:Adult male SD rats were divided into normal diet(ND) group and high fat and high fructose diet(HFHFD) group. After treatment for 48 weeks, these rats were sacrificed and the blood, liver, and brain tissues were collected. Serum triglyceride(TG), total cholesterol(TC), low density lipoprotein-cholesterol(LDL-C), high density lipoprotein-cholesterol(HDL-C) levels were determined by automatic biochemical analyzer. The serum levels of interluekin-2(IL-2), IL-6, and advanced glycation end products(AGEs) were measured using enzyme linked immunosorbent assay. The expressions of p16, p21, and p53 genes in the liver and brain tissues were detected by real-time quantitative PCR and western blot.Results:After 48 weeks treatment, there were significant differences in body weight and fasting plasma glucose between two groups. Serum TG, TC, and LDL-C in HFHFD group were significantly higher than those in the ND group( P<0.05), with an increase trend in HDL-C but without statistical difference. Compared with ND group, the level of IL-2 in HFHFD group was significantly decreased while the levels of IL-6 and AGEs were significantly increased(all P<0.05). The levels of p16 and p21 mRNA expressions as well as p53 and p21 protein expressions in liver and brain in HFHFD group were markedly increased compared with ND group(all P<0.05). Conclusion:Long-term high fat and high fructose diets accelerate the aging process of rats, which may be related to the damage of the immune system and the changes of cell senescence related gene expressions in liver and brain tissues.

Objective: To clone mouse rod opsin promoter (ROP) and establish transgenic mice harboring mouse rod opsin promoter and enhanced green fluorescent protein(mROP-EGFP) fusion gene. Methods: Mouse ROP was cloned from C57BL/6 mouse genomic DNA by polymerase chain reaction (PCR). Expression vector of mROP-EGFP fusion gene were constructed by recombination DNA technique. It was identified by restriction endonucleases digestion and confirmed by DNA sequencing. After Not I restriction endonuclease digestion, the coding elements were microinjected into male pronuclei of mice zygotes to generate transgenic mice. The pups were evaluated by PCR at genomic DNA level and mated with normal mouse. Expression of GFP in retina of transgenic mice was detected by fluorescent microscope. Results: 2. 1 kb mouse rod opsin promoter fragment was amplified from mice genome DNA. Expression vector pmROP-EGFP was constructed successfully. Following microinjection of coding sequence of pmROP-EGFP, 3 pups were verified to integrate the mROP-EGFP fusion gene in their genomic DNA by PCR assay, named C57-TgN (mROP-EGFP )SMMU21, C57-TgN (mROP-EGFP)SM-MU26 and C57-TgN(mROP-EGFP) SMMU27. They could express GFP in retina. Conclusion: 2. 1 kb mouse rod opsin promoter is cloned and expression vector pmROP-EGFP is constructed. mROP-EGFP fusion gene transgenic mice are established, which harboring mROP-EGFP gene and expressing GFP in their retina. This is valuable for studying the development of brain and retina, pathogenesis of retina disorder and retina transplanting.

Objective: To evaluate the prognostic value of kinetic changes in minimal residual disease (MRD) status, as well as its relationship with risk stratification, therapeutic response and treatment in patients with newly-diagnosed multiple myeloma (MM) . Methods: A total of 135 patients with newly-diagnosed MM were screened, and 105 patients who achieved VGPR or more as the best responses were included into this study. The MRD status was determined by multiparameter flow cytometry (MFC) at multiple intervals after two cycles of treatment until clinical relapse, death, or last follow-up. The statistical methods included Kaplan-Meier analysis, Cox regression, etc. Results: ①In all 135 patients, 57.8% (78/135) patients achieved MRD negativity (MRD^-) after treatment. In 105 patients who achieved VGPR and thus included in this study, the MRD^- rate was 72.4% (76/105) , with a median interval of 3 months from starting treatment to achievement of MRD^- status. ②The 2-year PFS rate of patients with MRD^- status was significantly higher than that of MRD⁺ status (62.2% vs 41.3%, P=0.001) , while MRD persistence (MRD⁺) was an independent factor for poor prognosis (multivariate analysis for PFS: P=0.044, HR=3.039, 95%CI 1.029-8.974) . ③Loss of MRD^- status (i.e., MRD reappearance) showed inferior outcomes compared with MRD sustained negative ones, the PFS was 18 months versus not reach (P<0.001) and the OS was not reach for both (P=0.002) . ④The 2-year PFS and OS rates of patients with duration of MRD^-status≥12 months were significantly higher than those of the control group (PFS: 77.7% vs 36.7%, P<0.001; OS: 96.4% vs 57.9%, P<0.001 respectively) . Duration of MRD^- status was associated with a marked reduction in risk of relapse or death (univariate analysis for PFS: P<0.001, HR=0.865, 95%CI 0.815-0.918; for OS: P=0.001, HR=0.850, 95%CI 0.741-0.915 respectively) . ⑤Moreover, even in patients carrying high-risk cytogenetic abnormalities (CA) or ineligible for ASCT, MRD negativity remained its prognostic value to predict PFS (high-risk CA medianPFS: not reach vs 19 months, P=0.006; ineligible for ASCT medianPFS: not reach vs 25 months, P=0.052 respectively) . ⑥Last, treatment with the bortezomib-based regimens contributed to prolonged MRD^- duration (median MRD^- duratio: 25 months vs 10 months, P=0.034) . Conclusion Our findings supported MRD⁺ status as an independent poor prognostic factor in MM patients, which implicated that duration of MRD^- status also played a significant role in evaluation of prognosis, while loss of MRD^-status might serve as an early biomarker for relapse. Therefore, monitoring of MRD kinetics might more precisely predict prognosis, as well as guide treatment decision, especially for when to start retreatment in relapsed patients.