Physical deviation and precocious puberty among school-aged children in Leshan City: an investigative study.

OBJECTIVE: We investigated physical deviation and precocious puberty among school-aged children in Leshan City, to provide a theoretical basis for the management of precocious puberty in children. METHODS: We selected 12 primary schools of Leshan City using a cluster random sampling method and conducted physical examinations among healthy students aged 4 12 years. A total of 11,000 students were recruited (5502 boys and 5498 girls). We measured body mass index (BMI), and participants were tested for precocious puberty according to the Tanner stages and standard maps. Nutritional status was also evaluated. RESULTS: Obese and overweight children accounted for a high proportion of participants; the prevalence of underweight was the lowest. The prevalence of obesity among boys was higher than that in girls. Precocious puberty was mainly observed in girls, particularly those age 7 years old. The prevalence of precocious puberty among overweight and obese children was higher than that in children with normal weight. CONCLUSION: We identified a significant sex difference in precocious puberty among children in Leshan City. Overweight and obesity may be associated with precocious puberty.

Cisatracurium Retards Cell Migration and Invasion Upon Upregulation of p53 and Inhibits the Aggressiveness of Colorectal Cancer.

Colorectal cancer (CRC) is reported to be the third and fourth, most diagnosed and cause of cancer associated deaths respectively. In 2012 for instance, about 1.4 million new cases were reported, and approximately 700,000 deaths recorded. Survival from CRC is dependent on the stage at which it is diagnosed coupled with appropriate surgical and medical intervention. Cisatracurium is widely used for skeletal muscle relaxation during abdominal surgeries, including bowel and colon surgeries. Recent studies reported that cisatracurium inhibits progression of human cancer cells, however, the mechanisms leading to the inhibition are yet to be completely understood. To elucidate mechanisms resulting particularly in tumor cell growth and metastasis, we developed ex vivo and in in vivo xenograft models of CRC. Cisatracurium caused upregulation of p53 and its down-stream genes and proteins known to regulate proliferation and metastasis in vitro and in vivo. Genomic analyses of CRC following cisatracurium treatment revealed moderate to high DNA damage, while functional analyses demonstrated significant tumor cells growth regression, as well as repression of migration and invasion. Importantly, cisatracurium increased E-Cadherin and CALD-1 but decreased SNAI-1 and SLUG levels in vitro and in vivo. Together, the findings demonstrate that elevation of p53 upon cisatracurium-induced genomic injury, represent a potential mechanism by which cisatracurium result in the suppression of CRC progression and metastasis.

Case-control pharmacogenetic study of HCN1/HCN2 variants and genetic generalized epilepsies.

Epilepsy is a common complex neurological disorder, and some forms are resistant to drug treatment. The HCN1/HCN2 genes encode hyperpolarization-activated cyclic nucleotide-gated channels, which play important roles in the electrophysiology of neurons. We investigated the association between HCN1/HCN2 variants and drug resistance or the risk of genetic generalized epilepsies (GGEs). We used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to assess nine variants of HCN1/HCN2 in 284 healthy participants and 483 GGEs (279 drug-responsive, 204 drug-resistant). Frequencies of HCN2 rs7255568 and rs3752158 G alleles differed in GGEs and in controls (P = .039, P = .027, respectively). The frequency of HCN2 haplotype (CAC) was higher in patients than controls (P = .046). The frequency of the HCN1 rs10462087 CC+CT genotype was lower in patients with childhood absence epilepsy (CAE) than controls (P = .047). Rs7255568 was associated with the risk of CAE (P = .028) and juvenile myoclonic epilepsy (JME) (P = .02). Rs3752158 was associated with the risk of generalized tonic-clonic seizures, JME, and febrile seizures (all P < .05). The frequency of the HCN2 haplotype (CAC) was higher in patients with JME (P = .015) and in those with febrile seizures (P = .024) than in controls. No significant association was found between HCN1/HCN2 alleles, genotypes or haplotypes, and drug resistance in patients. After Bonferroni's multiple comparisons correction, only the HCN2 rs3752158 C allele and GC+CC genotype frequencies in patients with JME were higher than those in controls (19.2% vs 11.6%, odds ratio (OR) = 1.71, 95% CI = 1.18-2.32), P = .004 < 0.05/9; 36% vs 22.2%, OR = 1.62(1.18-2.23), P = .003 < 0.05/9). Our study suggests that HCN2 rs3752158 is involved in the susceptibility to JME.

Fentanyl Promotes Breast Cancer Cell Stemness and Epithelial-Mesenchymal Transition by Upregulating α1, 6-Fucosylation via Wnt/ß-Catenin Signaling Pathway.

Cancer pain is a common and severe complication of human breast cancer, and relieving pain is fundamental strategy in the treatment. Fentanyl, as an opioid analgesic, is widely used in breast cancer patients. However, little is known about its effects on stemness and epithelial-mesenchymal transition (EMT) of breast cancer cells. Aberrant protein glycosylation is involved in cancer malignancy. The α1, 6-fucosylation is an important type of glycosylation, and the elevated α1, 6-fucosylation catalyzed by fucosyltransferase VIII (FUT8) is found in many tumors. However, whether 1, 6-fucosylation is involved in regulating stemness and EMT, and stimulated by fentanyl is not clear. In this study, we found that fentanyl induced stemness and EMT in MCF-7 and MDA-MB-231 breast cancer cells by analysis of sphere formation, expression of stemness markers (Sox2, Oct4) and EMT markers (N-cadherin, E-cadherin and Vimentin). Results also showed that fentanyl upregulated FUT8 gene and protein expression by qPCR, Western blot and immunofluorescent staining, as well as α1, 6-fucosylation level by Lectin blot and Lectin fluorescent staining. Furthermore, decreased or blocked α1, 6-fucosylation by FUT8 siRNA transfection or LCA Lectin blockage reduced stemness and EMT. Additionally, fentanyl activated the key molecules and target genes in Wnt/ß-catenin signaling pathway. LGK-974 (an inhibitor of Wnt ligands) suppressed fentanyl-mediated upregulation of α1, 6-fucosylation, stemness and EMT. The results of tumor xenograft demonstrated that fentanyl enhanced tumor growth, α1, 6-fucosylation, stemness and EMT. Taken together, our study reveals that fentanyl upregulated FUT8 expression, which increased α1, 6-fucosylation level through activation of Wnt/ß-catenin signaling pathway, thereby, induce stemness and EMT of breast cancer cells. This study suggest a potential side effect of fentanyl in the treatment of cancer, which may guide the safety of fentanyl in the clinical application.

Pharmacogenetic and case-control study on potassium channel related gene variants and genetic generalized epilepsy.

Potassium channels are the targets of antiepileptic drugs (AEDs), which play important roles in the etiology of epilepsy. KCNA1 and KCNA2 encode mammalian Kv1.1 and Kv1.2 channels, which are essential roles in the initiation and shaping of action potentials. KCNV2 encodes Kv8.2, which is a regional overlap with Kv2 subunits as functional heterotetramers. In our study, we aim to investigate whether variants of KCNA1, KCNA2, and KCNV2 genes influence susceptibility to genetic generalized epilepsies (GGEs) and the efficacy of AEDs. Seven hundred sixty-seven subjects (284 healthy controls, 279 drug-responsive, and 204 drug-resistant GGE patients) were enrolled in our study. Eight variants of KCNA1, KCNA2, and KCNV2 were assessed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry method. Results showed that there were no statistically significant correlations between the 8 variants of KCNA1, KCNA2, and KCNV2 and the risk/drug resistance of GGEs. In conclusion, our study suggests that KCNA1, KCNA2, and KCNV2 variants may not be involved in the risk/drug resistance of GGEs. Further multicenter, multiethnic, and large sample size pharmacogenetic and case-control studies are warranted to confirm our negative results.

Long non-coding RNAs: a rising biotarget in colorectal cancer.

Colorectal cancer (CRC) is a common gastrointestinal cancer, with a high incidence and high mortality. Long non-coding RNAs (lncRNAs) are involved in the development, invasion and metastasis, early diagnosis, prognosis, the chemoresistance and radioresistance of CRC through interference with mRNA activity, directly combining with proteins to regulate their activity or alter their localization, influencing downstream gene expression by inhibiting RNA polymerase and regulating gene expression as competing endogenous RNAs. Recent progress in next generation sequencing and transcriptome analysis has revealed that tissue and cancer-type specific lncRNAs could be useful prognostic markers. Here, the CRC-associated lncRNAs from recent studies until October 2016 are reviewed and multiple studies that have confirmed CRC-associated lncRNAs are summarized. This review may be helpful in understanding the overall relationships between the lncRNAs involved in CRC.

Comparison of age-related changes between corneal and ocular aberration in young and mid-age myopic patients.

AIM: To study the dynamic character of aberration between the cornea and the ocular with aging, and to evaluate the symmetry of the aberrations between right and left eye in order to supply the data for clinic to do the refractive surgery reasonably. METHODS: This is a comparative case series study. 82 normal cases (164 eyes) including 37 females (74 eyes) and 45 males (90 eyes) were recruited through the routine examinations, Topolyzer and wavefront analysis. The average age was 25.9±5.0 years old (range 18 to 49 years old), and the mean spherical equivalent (SE) is -3.82±2.21D (range -1.00 to -6.00D). The changes of aberrations regarding age, the relationship between anterior corneal and total aberrations were analyzed, as well as the symmetry between right and left eyes by using Zernike terms. RESULTS: The Z(3) (1), RMS3 of corneal aberrations, Z(3) (1), Z(4) (0) , RMS3 and RMS4 of ocular aberrations had a positive correlation with age. The zernike terms both in corneal and whole eye were significantly correlated between right and left eyes. CONCLUSION: The corneal horizontal coma, ocular horizontal coma and ocular spherical aberrations become to increase at the age of more than 40 years old. The dynamic change of aberration with aging, balance between corneal and ocular, and the symmetric character between left eye and right eye should be designed carefully in the treatment nomogram before the refractive surgery.

[Clinical evaluation on the cornea flap with different thickness after LASIK].

OBJECTIVE: To investigate morphologically the different changes of cornea tissue between thick and thin cornea flap with confocal microscope, and to compare visual function between thick and thin cornea flap after LASIK. METHODS: 70 cases (70 eyes) who had received LASIK were divided into the thin cornea flap group (36 eyes, group A) and the thick cornea flap group (34 eyes, group B). The age was (23 +/- 5) years old, spherical equivalent diopter (SE) were ( - 4.76 +/- 2.30) D and (- 3.03 +/- 2.20) D. Inspection items included visual acuity (VA), refraction, wave-front analysis, contrast sensitivity analysis (KONTRASTOMETER BA4, Germany) during pre-and post-LASIK, at the same time, all eyes were examined by confocal microcopy (HRT III, Germany). Using Moria 90 microm and 130 microm keratome with Allegretto Excimer laser machine. RESULTS: Refraction: there was no difference between the two groups. Post-LASIK 3 to 6 months: group A (0.35 +/- 0.21) D; group B (0.45 +/- 0.69) D (P > 0.05). Comparison results by confocal microscope. The thickness of cornea flap: group A (107.37 +/- 20.5) microm, group B (149 +/- 25.2) microm (P < 0.05). The thickness of wrinkle: group A (63.71 +/- 15.8) microm; group B (48.16 +/- 20.7) microm (P < 0.05). The thickness of acellular area: group A (69.93 +/- 15.8) microm; group B (55.63 +/- 23.7) microm (P < 0.05). The thickness of activation cornea cells: group A (60.15 +/- 30.9) microm; group B (51.86 +/- 27.9) microm (P < 0.05). The density of anterior stromal: group A (825.14 +/- 156.9) mm2; group B (853.54 +/- 126.8) mm2 (P < 0.05). There were significant differences on the thickness of cornea flap, the thickness of wrinkle, the thickness of acellular area, the thickness of activation cornea cells, the density of anterior stromal, but there was no difference on posterior stromal (P > 0.05). Wavefront analysis:there was no difference between two groups in Z3(-3), Z3(-1), Z3(1), Z3(3), Z4(0), RMS3, RMS4, RMS5, RMS6, RMSh (P > 0.05) pre-and post-operation. Contrast sensitivity analysis: there was also no difference between two groups (P > 0.05) pre-and post-LASIK 1-6 month. CONCLUSIONS: From the point of confocal microscope view, morphologic changes of cornea was significant with different thick flap. It is not cicatricial healing between the cornea flap and stromal. The cell injury of cornea tissue in the thin cornea flap was severe than that of in the thick cornea flap even though there was no significant difference between thin and thick cornea flap group in clinical refraction correction, wavefront and contrast sensitivity.

[Comparison of retaining or removing negative vertical coma in wavefront guided LASIK for myopia and astigmatism].

OBJECTIVE: To investigate the efficacy and safety of wavefront guided (WG) LASIK for the myopia and astigmatism. METHODS: This study is a randomized control trial. 42 cases (78 eyes) were collected in the study through the routine examinations and wavefront analysis, which were divided into two groups (A and B). The value of Z (3, -1) being less than -0.15 microm was evaluated as Group A (24 cases, 45 eyes); The value of Z (3, -1) being more than +0.15 microm was as Group B (18 cases, 33 eyes). Both A and B were also divided into two subgroups (test and control). WG-LASIK was performed in tested groups, and classic LASIK was performed in control group. Visual quality, wavefront examination, and CSF were analyzed after surgery 3-6 months compared with that of preoperation. RESULTS: In the earlier period of post-operation time, diopters of the two groups were both slightly overcorrected, and then began to decrease slightly later and the diopters of both tested and control groups were corrected perfectly. RMSh of tested group increased higher than that of control group when Z (3, -1) was negative and the CSF in control group was better than that in test group after WG-LASIK in Group A. RMSh of tested group increased lower than that of control group when Z (3, -1) was positive and the CSF in tested group was better than that in control group after WG-LASIK in Group B. CONCLUSIONS: These results suggest that retaining negative vertical coma and removing positive vertical coma were beneficial to the visual function after the WG-LASIK, which could save the corneal tissue reasonably in order to improve visual quality effectively.