Research into the correlation between positional skull deformation and motor performance of infants aged under 4 months.

OBJECTIVE: To investigate the correlation between positional skull deformation (PD) and motor performance of infants under 4 months of age. METHODS: Infants aged under 4 months were enrolled in the children's healthcare and the premature infants follow-up Clinic of the Second Affiliated Hospital of Army Military Medical University. The cranial vault asymmetry (CVA) and cephalic index (CI) were calculated in all infants, and the infant motor performance test (TIMP) was used to evaluate the infant motor performance. The motor performances of infants with different types and degrees of PD were compared, so were the incidences of PD in infants with different motor performance levels. RESULTS: Overall, 2118 infants were recruited and divided according to the types of PD and TIMP scores. The comparison of TIMP scores within different types of PD at different months of age showed that, regardless of the types of PD, TIMP scores of infants with PD were lower than those of normal infants. In particular, the difference in TIMP scores was statistically significant (P < 0.05) in infants with dolichocephaly, plagiocephaly,dolicho-plagiocephaly and brachy-plagiocephy. In addition, the comparison of CVA values of infants with different TIMP score levels at different months of age showed that the CVA values of the extremely low-level group were significantly higher than those of the medium-level and high-level group, especially in the 3-month-old and 4-month-old groups, which showed significant statistical differences (P < 0.05). CONCLUSIONS: PD and motor performance of infants aged under 4 months seem to interact and influenc each other. The more serious the severity of PD were,the worse the motor performance of infants. Conversely, the incidence of PD increased in infants with poor motor performance.

Analysis of cranial type characteristics in term infants: a multi-center study.

BACKGROUND: Positional head deformity (PHD) is defined as a change in the shape of an infant's skull due to an external force. In certain cases, it can lead to cosmetic deformities or even neurological issues due to its impact on the developing nervous system. Therefore, we conducted this study to investigate the incidence and characteristics of PHD in term infants in China and preliminarily establish a localized diagnostic reference standard. METHODS: Overall, 4456 term infants from three medical institutions in Chongqing were and divided and analyzed according to their age. Cranial vault asymmetry (CVA) and cephalic index (CI) were calculated in all infants. The current international diagnostic criteria were used to understand PHD incidence and analyze the CVA and CI distribution. RESULTS: According to the current international standards, the total detection rate of PHD in Chongqing's term infants was 81.5%, with brachycephaly alone being the most frequent (39.4%), followed by brachycephaly with plagiocephaly (34.8%) and plagiocephaly alone (6.2%). The detection rates of dolichocephaly were low: alone, 0.9% and combined with plagiocephaly, 0.2%. According to age, plagiocephaly (44.5%) and brachycephaly (82.0%) were the most frequent in the 2-3-month group. The 75th/90th/97th and 3rd/10th/25th/75th/90th/97th percentiles of CVA and CIs were 0.4/0.7/1.0 and 76.4/78.8/82.3/91.1/94.6/99.2%, respectively. CONCLUSIONS: According to the current international standards, the PHD detection rate among term infants in Chongqing was high. Therefore, a new diagnostic standard for Chinese infants was proposed where CVA ≥ 0.4 cm indicates plagiocephaly, CI ≥ 91% indicates brachycephaly, and CI ≤ 82% indicates dolichocephaly.

A comparative study between traditional head measurement and structured light three-dimensional scanning when measuring infant head shape.

BACKGROUND: This study aimed to evaluate the correlation and consistency between traditional head measurement and structured light three-dimensional (3D) scanning parameters when measuring infant skull shape. METHODS: A total of 76 infants aged 3 months to 2.5 years old were included in the study. Head circumference (HC) was measured with a tape measure. The transverse, anteroposterior, and oblique diameters were measured using a spreading caliper, and the cranial vault asymmetry index (CVAI) and a cranial index (CI) of symmetry were calculated; 76 cases were measured successfully. The above indexes were measured using a structured light 3D scanning system (71 cases were measured with success). Thus, in the end, the valid data of 71 cases were analyzed, and the measurements of the two approaches were compared. RESULTS: The 95% confidence interval of traditional head measurement and structured light 3D scanning was between 0.633 and 0.988. Pearson's correlation coefficient indicated a high correlation between the two methods (r=0.793-0.980). The correlation coefficients of the transverse diameter, anteroposterior diameter, and HC, and the CI of symmetry were higher than 0.9. The lowest correlation coefficient for the CVAI was 0.793. The P values of the above measurement data were all <0.001, which indicated that they were closely related. A Bland-Altman plot indicated reasonable consistency between the two methods. CONCLUSIONS: Both traditional head measurement and structured light 3D scanning are suitable for the measurement of infant head shape. However, while traditional head measurement using a spreading caliper is economical and simple, making it suitable for general screening at a basic level, structured light 3D scanning can deliver additional parameters, which is useful for infants with an abnormal head shape. The latter is also convenient for designing a customized helmet for skull correction when needed.

Prevalence of positional skull deformities in 530 premature infants with a corrected age of up to 6 months: a multicenter study.

BACKGROUND: Positional deformities (PD) are common during early infancy. Severe cases may result in facial abnormalities and be associated with delayed neurological development in infants. The earlier the detection of PD, the better the intervention effect and the lower the cost of treatment. Currently, there are many studies on PD in Europe and the United States. However, in China, there is little data on the basic metrics and incidence of PD. Premature infants have a high risk of PD. However, there are few studies on PD in premature infants globally, and none in Asia. This study aimed to investigate PD and its characteristics inpremature infants to help its early detection and intervention and thus improve the quality of life for premature infants. METHODS: We analyzed 530 preterm infants who visited the outpatient departments at Xinqiao Hospital of Army Medical University and Maternal and Child Health Care Hospitals of Wanzhou and Yongchuan Districts in Chongqing from September 1, 2016, to August 31, 2017. The head shape data measured by a simple manual method were recorded. The diagonal difference (DD) between the transcranial diagonals and the cranial index (CI) was calculated. PD and its incidences indifferent gestational ages and corrected age groups were analyzed. RESULTS: According to previously defined international diagnostic criteria, the incidence of plagiocephaly, brachycephaly, and dolichocephaly were 51.1, 85.1, and 3.0% respectively, and those of right and left plagiocephalywere69.4 and 30.6%, respectively. The incidence of PD was highest among infants with a gestational age of < 32 weeks and decreased as the gestational age increased. As the corrected age (CA) increased, the incidence of plagiocephaly and dolichocephaly decreased, and the incidence of brachycephaly increased. CONCLUSIONS: PD incidence is high among preterm infants. As gestational age decreased, PD incidence and severity increased. Therefore, healthcare providers should implement early PD detection and intervention to prevent the adverse outcomes. The extremely high incidence of brachycephaly and extremely low incidence of dolichocephaly in this study are likely to be due to the variance of cranial metrics caused by cultural differences. The Chinese standards for infant cranial measurements must be established.

Aspirin Inhibits Cancer Metastasis and Angiogenesis via Targeting Heparanase.

Purpose: Recent epidemiological and clinical studies have suggested the benefit of aspirin for patients with cancer, which inspired increasing efforts to demonstrate the anticancer ability of aspirin and reveal the molecular mechanisms behind. Nevertheless, the anticancer activity and related mechanisms of aspirin remain largely unknown. This study aimed to confirm this observation, and more importantly, to investigate the potential target contributed to the anticancer of aspirin.Experimental Design: A homogeneous time-resolved fluorescence (HTRF) assay was used to examine the impact of aspirin on heparanase. Streptavidin pull-down, surface plasmon resonance (SPR) assay, and molecular docking were performed to identify heparanase as an aspirin-binding protein. Transwell, rat aortic rings, and chicken chorioallantoic membrane model were used to evaluate the antimetastasis and anti-angiogenesis effects of aspirin, and these phenotypes were tested in a B16F10 metastatic model, MDA-MB-231 metastatic model, and MDA-MB-435 xenograft model.Results: This study identified heparanase, an oncogenic extracellular matrix enzyme involved in cancer metastasis and angiogenesis, as a potential target of aspirin. We had discovered that aspirin directly binds to Glu225 region of heparanase and inhibits the enzymatic activity. Aspirin impeded tumor metastasis, angiogenesis, and growth in heparanase-dependent manner.Conclusions: In summary, this study has illustrated heparanase as a target of aspirin for the first time. It provides insights for a better understanding of the mechanisms of aspirin in anticancer effects, and offers a direction for the development of small-molecule inhibitors of heparanase. Clin Cancer Res; 23(20); 6267-78. ©2017 AACR.

[Efficacy of sleep position correction for treating infants with positional plagiocephaly].

OBJECTIVE: To investigate the efficacy of 2-month course of sleeping position correction in the treatment of positional plagiocephaly in infants aged <8 months. METHODS: A total of 73 infants with positional plagiocephaly between January 2015 and June 2016 were divided into treatment group (n=46) and control group (n=27) according to parents' wishes. The treatment group received sleeping position correction, while the control group received sleep curve mattress. The oblique diameters A and B in the two groups were measured and the cranial vault asymmetry (CVA) was calculated before and after treatment. The severity of positional plagiocephaly based on CVA was compared between the two groups before and after treatment. The Gesell Developmental Scale was used to determine the developmental quotients (DQs) in the motor, adaptive, language, and social domains in the two groups before and after treatment. RESULTS: Before treatment, there were no significant differences in oblique diameters A and B, CVA, and DQs in the four specific domains between the two groups (P>0.05). After 2 months of treatment, the treatment group had a significantly greater oblique diameter B and a significantly smaller CVA than the control group (P<0.05); there were no significant differences in DQs in the four specific domains between the two groups (P>0.05). After treatment, both groups had significant improvements in oblique diameters A and B, CVA, and DQs in the motor and adaptive domains (P<0.01); moreover, the treatment group showed a significant improvement in the DQs in the social domain (P<0.01). There was no significant difference in the severity of positional plagiocephaly between the two groups before and after treatment (P>0.05). CONCLUSIONS: For infants with positional plagiocephaly, sleeping position correction has better efficacy and is more convenient and economical than the sleep curve mattress, so it holds promise for clinical application.

JG6, a novel marine-derived oligosaccharide, suppresses breast cancer metastasis via binding to cofilin.

Cofilin, an actin-binding protein which disassembles actin filaments, plays an important role in invasion and metastasis. Here, we discover that JG6, an oligomannurarate sulfate, binds to cofilin, suppresses the migration of human breast cancer cells and cancer metastasis in breast cancer xenograft model. Mechanistically, JG6 occupies actin-binding sites of cofilin, thereby disrupting cofilin modulated actin turnover. Our results highlight the significance of cofilin in cancer and suggest JG6, a cofilin inhibitor, to treat metastatic cancer.

O-GlcNAcylation of cofilin promotes breast cancer cell invasion.

O-GlcNAcylation is a post-translational modification that regulates a broad range of nuclear and cytoplasmic proteins and is emerging as a key regulator of various biological processes. Previous studies have shown that increased levels of global O-GlcNAcylation and O-GlcNAc transferase (OGT) are linked to the incidence of metastasis in breast cancer patients, but the molecular basis behind this is not fully known. In this study, we have determined that the actin-binding protein cofilin is O-GlcNAcylated by OGT and mainly, if not completely, mediates OGT modulation of cell mobility. O-GlcNAcylation at Ser-108 of cofilin is required for its proper localization in invadopodia at the leading edge of breast cancer cells during three-dimensional cell invasion. Loss of O-GlcNAcylation of cofilin leads to destabilization of invadopodia and impairs cell invasion, although the actin-severing activity or lamellipodial localization is not affected. Our study provides insights into the mechanism of post-translational modification in fine-tuning the regulation of cofilin activity and suggests its important implications in cancer metastasis.

Extensive crosstalk between O-GlcNAcylation and phosphorylation regulates Akt signaling.

O-linked N-acetylglucosamine glycosylations (O-GlcNAc) and O-linked phosphorylations (O-phosphate), as two important types of post-translational modifications, often occur on the same protein and bear a reciprocal relationship. In addition to the well documented phosphorylations that control Akt activity, Akt also undergoes O-GlcNAcylation, but the interplay between these two modifications and the biological significance remain unclear, largely due to the technique challenges. Here, we applied a two-step analytic approach composed of the O-GlcNAc immunoenrichment and subsequent O-phosphate immunodetection. Such an easy method enabled us to visualize endogenous glycosylated and phosphorylated Akt subpopulations in parallel and observed the inhibitory effect of Akt O-GlcNAcylations on its phosphorylation. Further studies utilizing mass spectrometry and mutagenesis approaches showed that O-GlcNAcylations at Thr 305 and Thr 312 inhibited Akt phosphorylation at Thr 308 via disrupting the interaction between Akt and PDK1. The impaired Akt activation in turn resulted in the compromised biological functions of Akt, as evidenced by suppressed cell proliferation and migration capabilities. Together, this study revealed an extensive crosstalk between O-GlcNAcylations and phosphorylations of Akt and demonstrated O-GlcNAcylation as a new regulatory modification for Akt signaling.

The role of polymeric immunoglobulin receptor in inflammation-induced tumor metastasis of human hepatocellular carcinoma.

BACKGROUND: Expression of the polymeric immunoglobulin receptor (pIgR), a transporter of polymeric IgA and IgM, is commonly increased in response to viral or bacterial infections, linking innate and adaptive immunity. Abnormal expression of pIgR in cancer was also observed, but its clinical relevance remains uncertain. METHODS: A human hepatocellular carcinoma (HCC) tissue microarray (n = 254) was used to investigate the association between pIgR expression and early recurrence. An experimental lung metastasis model using severe combined immune-deficient mice was applied to determine the metastatic potential of Madin-Darby canine kidney (n = 5 mice per group) and SMMC-7721 (n = 12 mice per group) cells overexpressing pIgR vs control cells. RNA interference, immunoprecipitation, and immunoblotting were performed to investigate the potential role for pIgR in the induction of epithelial-mesenchymal transition (EMT). In vitro studies (co-immunoprecipitation, immunoblotting, and migration, invasion, and adhesion assays) were used to determine the mechanisms behind pIgR-mediated metastasis. All statistical tests were two-sided. RESULTS: High expression of pIgR was statistically significantly associated with early recurrence in early-stage HCC and in hepatitis B surface antigen-positive HCC patients (log-rank P = .02). Mice injected with pIgR-overexpressing cells had a statistically significantly higher number of lung metastases compared with respective control cells (Madin-Darby canine kidney cells: pIgR mean = 29.4 metastatic nodules per lung vs control mean = 0.0 metastatic nodules per lung, difference = 29.4 metastatic nodules per lung, 95% confidence interval = 13.0 to 45.8, P = .001; SMMC-7721 cells: pIgR mean = 10.4 metastatic nodules per lung vs control mean = 2.2 metastatic nodules per lung, difference = 8.2 metastatic nodules per lung, 95% confidence interval = 1.0 to 15.5, P = .03). Furthermore, high expression of pIgR was sufficient to induce EMT through activation of Smad signaling. CONCLUSIONS: pIgR plays a role in the induction of EMT. Our results identify pIgR as a potential link between hepatitis B virus-derived hepatitis and HCC metastasis and provide evidence in support of pIgR as a prognostic biomarker for HCC and a potential therapeutic target.

Unprecedented citrinin trimer tricitinol B functions as a novel topoisomerase IIα inhibitor.

Fifteen citrinin derivatives (1-4, 6-16), including two unprecedented citrinin trimers tricitrinols A (3) and B (4), were isolated from Penicillium citrinum HGY1-5. The six-membered ring A system is essential for the cytotoxicity of active dimers (1, 2, and 5) and trimers (3 and 4). Tricitrinol B (4) showed extensive cytotoxicity in 17 tumor cells with comparable low-micromolar IC(50) values (1-10 µM) and potential antimultidrug resistance capabilities. Tricitrinol B (4) induced cell apoptosis in HL60 and HCT116 cells via mainly extrinsic pathways and G2/M arrest. Further antitumor mechanism study and computational docking analysis indicated that tricitrinol B (4) works as an intercalating topoisomerase IIα (topo IIα) poison, which inhibits the enzyme activity of topo IIα by interfering predominantly with the topo IIα-mediated poststrand-passage cleavage/religation equilibrium over with the prestrand-passage one and induced DNA damage. Tricitrinol B (4) represents a novel class of topo IIα-inhibitory skeletons for developing new chemotherapeutic agents.

Marine-derived oligosaccharide sulfate (JG3) suppresses heparanase-driven cell adhesion events in heparanase over-expressing CHO-K1 cells.

AIM: To elucidate the detailed mechanisms underlying the appreciable effects of JG3, a novel marine-derived oligosaccharide, on cell migration using a Chinese hamster ovary (CHO) cell line stably over-expressing heparanase. METHODS: A retrovirus infection system was used to establish a CHO-K1 cell line stably transfected with heparanase. Immunocytochemistry was used to assess cell morphology. Flow cytometry was selected to analyze the activation of beta1-integrin, and Western blotting was used to analyze the downstream effects on the cell adhesion pathway. An affinity precipitation assay was used to determine activation of the small GTPases, Rac1, and RhoA. RESULTS: JG3 abolished heparanase-driven formation of focal adhesions and cell spreading. Although JG3 failed to block the heparanase-triggered activation of beta1-integrin or the phosphorylation of Src, the oligosaccharide caused a significant dephosphorylation of FAK and subsequent inactivation of Erk. Furthermore, JG3 was found to arrest the activation of Rac1. CONCLUSION: All these findings help form an alternative view to understand the mechanisms underlying the inhibitory effects of JG3 on cell motility.Acta Pharmacologica Sinica (2009) 30: 1033-1038; doi: 10.1038/aps.2009.97; published online 22 June 2009.