Expression of Bax/Bcl-2, TGF-ß1, and Type III Collagen Fiber in Congenital Muscular Torticollis.

BACKGROUND This study investigated the expression of Bax/Bcl-2, TGF-ß1 and type III collagen fiber in sternocleidomastoid of congenital muscular torticollis (CMT), and explored the possible mechanisms of fibrosis in sternocleidomastoid of CMT. MATERIAL AND METHODS The localization and expression of Bax, Bcl-2, TGF-ß1, and type III collagen were detected in the control group and experimental group by using immunohistochemical staining method. The RT-PCR assay was used to measure the expression of TGF-ß1 in the control group and experimental group. RESULTS HE staining results showed that the collagen fiber in the experimental group had more abundant hyperplasia compared to the control group (p<0.05). Immunohistochemical staining results showed that the expression of Bax, Bax/Bcl-2, TGF-ß1, and type III collagen in the experimental group was significantly increased compared to the control group (p<0.01). There were positive correlations between expression of Bax/Bcl-2 and TGF-b1, and between expression of TGF-ß1 and type III collagen fiber (p<0.05, r=0.32 and 0.83, respectively). The RT-PCR results showed that the expression of TGF-ß1 mRNA was also significantly elevated in the experimental group compared to the control group (p<0.05). CONCLUSIONS Increased muscular apoptosis may aggravate the formation of muscular fibrosis, which may be involved in the pathogenesis of sternocleidomastoid of CMT.

Comparison of abdominal radiographs and sonography in prognostic prediction of infants with necrotizing enterocolitis.

PURPOSE: The purpose of this study was to investigate the comparison of AR and AUS in predicting prognosis in infants with necrotizing enterocolitis. METHODS: All patients were diagnosed as NEC at the department of general surgery and neonatal surgery, Qilu children's hospital between 1st, Jun, 2010 and 30th, Dec, 2016. The logistic regression analysis and the area under ROC curve (AUC)s were also used to compare the prognostic values of radiograph and sonograph for NEC. RESULTS: Throughout the study period, 86 preterm neonates were hospitalized with diagnosis of definite NEC. Among these patients, 39 infants (45.3%) required surgical treatment. After adjusting for competing sonographic factors, we identified that thick bowel wall (more than 2.5 mm) (p = 0.001, HR: 1.849), intramural gas (pneumatosis intestinalis) (p = 0.017, HR: 1.265), portal venous gas (p = 0.002, HR: 1.824), and reduced peristalsis (p = 0.021, HR: 1.544) were independent prognostic factors associated with NEC. After adjusting for competing radiographic factors, we identified that free peritoneal gas (p = 0.007, HR: 1.472), portal venous gas (p = 0.012, HR: 1.649), and dilatation and elongation (p = 0.025, HR: 1.327). Moreover, we found that the AUROC for AR logistic model was 0.745 (95% CI 0.629-0.812), which was significant lower than the AUS logistic model (AUROC: 0.857, 95% CI 0.802-0.946) for predicting prognosis of NEC. CONCLUSIONS: In conclusion, we found that several radiographic and sonographic parameters were associated with the prognosis of patients with NEC. The AUS model based on the logistic regression analysis was significant superior to the AR model in the prognostic prediction of NEC.

Expression of neurexin and neuroligin in the enteric nervous system and their down-regulated expression levels in Hirschsprung disease.

To investigate the expression levels of neurexins and neuroligins in the enteric nervous system (ENS) in Hirschsprung Disease (HSCR). Longitudinal muscles with adherent mesenteric plexus were obtained by dissection of the fresh gut wall of mice, guinea pigs, and humans. Double labeling of neurexin I and Hu (a neuron marker), neuroligin 1 and Hu, neurexin I and synaptophysin (a presynaptic marker), and neuroligin 1 and PSD95 (a postsynaptic marker) was performed by immunofluorescence staining. Images were merged to determine the relative localizations of the proteins. Expression levels of neurexin and neuroligin in different segments of the ENS in HSCR were investigated by immunohistochemistry. Neurexin and neuroligin were detected in the mesenteric plexus of mice, guinea pigs, and humans with HSCR. Neurexin was located in the presynapse, whereas neuroligin was located in the postsynapse. Expression levels of neurexin and neuroligin were significant in the ganglionic colonic segment of HSCR, moderate in the transitional segment, and negative in the aganglionic colonic segment. The expressions of neurexin and neuroligin in the transitional segments were significantly down-regulated compared with the levels in the normal segments (P < 0.05). Expression levels of neurexin and neuroligin in ENS are significantly down-regulated in HSCR, which may be involved in the pathogenesis of HSCR.

Effect of green tea on reward learning in healthy individuals: a randomized, double-blind, placebo-controlled pilot study.

BACKGROUND: Both clinical and preclinical studies revealed that regular intake of green tea reduced the prevalence of depressive symptoms, as well as produced antidepressant-like effects in rodents. Evidence proposed that disturbed reward learning has been associated with the development of anhedonia, a core symptom of depression. However, the relationship between green tea and reward learning is poorly investigated. Our goal was to test whether chronic treatment with green tea in healthy subjects affects the process of reward learning and subsequently regulates the depressive symptoms. METHODS: Seventy-four healthy subjects participated in a double-blind, randomized placebo-controlled study with oral administration of green tea or placebo for 5weeks. We used the monetary incentive delay task to evaluate the reward learning by measurement of the response to reward trial or no-reward trial. We compared the reaction time of reward responsiveness between green tea and placebo treatment. Furthermore, we selected Montgomery-Asberg depression rating scale (MADRS) and 17-item Hamilton Rating Scale for Depression (HRSD-17) to estimate the depressive symptoms in these two groups. RESULTS: The results showed chronic treatment of green tea increased reward learning compared with placebo by decreasing the reaction time in monetary incentive delay task. Moreover, participants treated with green tea showed reduced scores measured in MADRS and HRSD-17 compared with participants treated with placebo. CONCLUSIONS: Our findings reveal that chronic green tea increased the reward learning and prevented the depressive symptoms. These results also raised the possibility that supplementary administration of green tea might reverse the development of depression through normalization of the reward function.

Inhibition of c-Met activation sensitizes osteosarcoma cells to cisplatin via suppression of the PI3K-Akt signaling.

Osteosarcoma is a common malignant bone tumor. Cisplatin (CDDP) achieves a high response rate in osteosarcoma. However, osteosarcoma usually exhibits cisplatin resistance. Many members of receptor tyrosine kinases (RTKs)(1) have been demonstrated to be overexpressed and constitutively activated in various tumors including osteosarcoma, resulting in malignant progression and insensitivity to chemotherapy. Hepatocyte growth factor receptor (HGFR/c-Met) also appears overexpressed and activated in osteosarcoma cells. Nevertheless, which role of c-Met activation in cisplatin efficacy against osteosarcoma cells remains still elusive. This study found that inhibition of c-Met activity by PHA-665752 or blockade of the interaction of autocrined HGF with c-Met with neutralizing anti-HGF antibody promoted cisplatin efficacy in osteosarcoma cells, while addition of recombinant human HGF (rh-HGF) counteracts cisplatin cytotoxicity. Specifically, we demonstrated that inhibition of c-Met activity led to suppression of the PI3K-Akt pathway, thus enhancing cisplatin chemosensitivity. Our study clearly suggests that inhibition of c-Met activity can effectively sensitize osteosarcoma cells to cisplatin via suppression of the PI3K-Akt signaling.

Short-Term Outcomes of Herbert Screw Fixation for Isolated Olecranon Fractures in Children: A Single-Institution Retrospective Study.

Background: The aim of this study was to assess the clinical and radiological outcomes of closed reduction with percutaneous Herbert screw fixation in children with isolated olecranon fractures. Methods: We retrospectively reviewed the records of children treated at our center for isolated olecranon fractures (Mayo type IIA) with closed reduction and percutaneous Herbert screw fixation. The related indices and data of the group were collected for comparative analysis after an average follow-up of 6-8 months. The Herbert screws were removed by a second operation. Results: Overall, 14 patients with an average age at the time of injury of 11.36 (range 10-14) years were included. All patients had good radiological and clinical outcomes at 6-8 months postoperatively; all had normal elbow ranges of motion and showed complete bone healing on radiographs. There were no foreign body irritation, implant migration, or osteoarthritis cases. Premature epiphyseal closure was noted in six patients. The average QuickDASH score was 1.58. Conclusions: Fixation of olecranon fractures with Herbert screws is a safe and easy method in young patients, leading to good functional and radiological results. Nonetheless, determination of the effects of this treatment method on the olecranon ossification center requires long-term follow-up.

Postoperative avascular necrosis of the femoral head in pediatric femoral neck fractures.

This study aimed to evaluate the relevant factors of postoperative avascular necrosis of the femoral head (AVN) in children with femoral neck fracture. This study retrospectively analyzed the clinical data of 28 children with femoral neck fractures treated at our center between July 2016 and January 2019. The average age was 9.3 (range, 4.4-14) years with 75% male participants. Fracture classification was based on the Delbet classification: there were four, seven, 15, and two cases of type I, II, III, and IV fractures, respectively. Displacement degree was based on the Garden classification. Sixteen cases had insignificant displacement (Garden types I and II), six had medium displacement (Garden type III), and six had significant displacement (Garden type IV). There were six early (≤24 hours) and 22 delayed (>24 hours) surgeries. Twenty-three patients had satisfactory reduction, and five had unsatisfactory reduction. The mean postoperative follow-up period was 15.7 (range, 12-36) months. Follow-up was evaluated using the Ratliff scoring standards. The correlation between age, fracture classification, displacement degree, surgery timing, reduction quality, and other factors and AVN occurrence was statistically analyzed. Among 28 children, AVN was found in six cases. There were statistically significant differences in displacement degree (P = 0.001) and reduction quality (P = 0.001), while the occurrence of AVN did not significantly differ with sex (P = 0.117), age distribution (P = 0.218), fracture classification (P = 0.438), surgery timing (P = 0.255), and mechanism of injury (P = 0.436). The results of logistic regression analysis showed that displacement degree was a relevant risk factor (P = 0.049, odds ratio [OR] = 8.391, 95% confidence interval [CI]: 1.004-70.117), while reduction quality was not (P = 0.075, OR = 14.536, 95% CI: 0.757-278.928). Although the development of AVN in children with femoral neck fractures may be related to many factors, the results of this research suggest that there is a significant correlation between displacement degree and AVN occurrence.

A novel Xp11.22-22.33 deletion suggesting a possible mechanism of congenital cervical spinal muscular atrophy.

BACKGROUND: Congenital cervical spinal muscular atrophy (CCSMA) is a rare, nonprogressive, neurogenic disorder characterized by symmetric arthrogryposis and motor deficits mainly confined to upper extremities. Since its first proposal by Darwish et al. 39 years ago, only few cases have ever been reported. Vascular insult to the anterior horn of cervical spinal cord during fetal development was speculated to be the cause, however, the exact pathogenesis is still not well understood. METHODS: In this study, whole-exome sequencing (WES) and copy number variation (CNV) analysis were conducted on a definitive CCSMA patient, confirmed by the clinical manifestations and other supplementary examinations. RESULTS: On physical examination, the patient was mainly characterized by symmetric, congenital, nonprogressive contractures, hypotonia, and muscle weakness mainly confined to the upper limbs, which were further supported by MRI and electromyography. Neuromuscular biopsy of the deltoid muscle demonstrated the type 1 myofiber predominance without any infiltration of inflammatory cells. The WES and CNV analysis unveiled a de novo Xp11.22-22.33 deletion. On further examination of the genes contained within this segment, we recognize UBA1 gene as the most likely pathogenic gene. Ubiquitin-like modifier activating enzyme 1 is encoded by UBA1 gene (MIM 314370) located in Xp11.3 and is a critical protein that plays a vital role in ubiquitin-proteasome system and autophagy. It is well documented that UBA1 gene mutation causes X-linked infantile spinal muscular atrophy (XL-SMA), which manifests phenotypes of arthrogryposis, hypotonia, and myopathic face. Type 2 XL-SMA, which follows a nonprogressive and nonlethal course is very similar to the presentations of CCSMA. CONCLUSION: The phenotypic similarities between this CCSMA case and XL-SMA prompt us to hypothesize a possible connection between UBA1 gene deficit and the pathogenesis of CCSMA. Our study is the first to demonstrate that CCSMA might have a genetic etiology, thus, expanding our insights into the underlying cause of CCSMA.

The effects of vasoactive intestinal peptide on RANKL-induced osteoclast formation.

BACKGROUND: Congenital pseudarthrosis of the tibia is a rare disease characterized by an imbalance in bone remodeling. Vasoactive intestinal peptide (VIP) has been proven to modulate bone resorption and the formation of osteoclasts. This study aimed to explore the effects of VIP on the homeostasis of bone metabolism in diverse in vitro systems. METHODS: Bone marrow-derived macrophages (BMMs) were differentiated into tartrate-resistant acid phosphatase-positive cells through incubation with receptor activator of nuclear factor κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). In vitro resorption pit detection was carried out to assess the effects of VIP on osteoclastic activity. Rat osteosarcoma cell line ROS 17/2.8 was cultured alone or co-cultured with rat BMMs in the presence or absence of VIP at various concentrations. The expression levels of RANKL, RANK, OPG, NF-κB, IL-6, ERK, CAII, and GAPDH were determined by qRT-PCR and WB assay. RESULTS: VIP was observed to repress osteoclast differentiation without affecting the number of osteoclast precursor cells. Furthermore, the modulation of the RANKL/osteoprotegerin (OPG), nuclear factor-κB (NF-κB), and extracellular signal-regulated kinase (ERK) signaling pathways were involved in the inhibitive influence of VIP upon bone erosion. Additionally, VIP affected the expression levels of osteoclastic factors including RANKL, OPG, and interleukin-6 in osteoblast cells. Furthermore, the expression levels of RANKL and RANK were increased, while OPG expression was reduced after treatment with VIP in the co-culture of ROS 17/2.8 and rat BMMs. ERK and NF-κB signal pathways were demonstrated to be involved in the effect of VIP in the co-culture system. CONCLUSIONS: VIP plays a critical role in bone remodeling and might serve as a potential target in the development of treatments for congenital pseudarthrosis of the tibia.

A systematic review and meta-analysis of naproxen for prevention heterotopic ossification after hip surgery.

BACKGROUND: The aim of this study was to assess the efficacy of naproxen in preventing heterotopic ossification (HO) after hip surgery (total hip arthroplasty [THA] and hip arthroscopy). METHODS: Using databases (PubMed, EMBASE, and Web of Science), we conducted an electronic, systematic search of randomized controlled trials (RCTs) comparing naproxen versus placebo on HO after hip surgery. The risk ratio (RR) of the dichotomous data, weighted mean difference (WMD) of continuous data, and 95% confidence intervals (CIs) were calculated to assess the effects of naproxen in patients with hip surgery. RESULTS: A total of 4 studies including 269 patients were analyzed. Risk of bias was relatively high in allocation concealment and blinding. Compared with control group, administration naproxen was associated with a significantly reduction of the occurrence of HO at final follow-up after hip surgery (P < .05). What's more, naproxen was associated with a reduction of the Brooker I and II HO (P < .05). However, there was no significant difference between the Brooker III HO between naproxen and control groups (P > .05). Furthermore, there was no significant difference between the complications (P > .05) between naproxen and control groups. CONCLUSION: Naproxen has a beneficial role in reducing the total occurrence of HO, Brooker I and II HO after hip surgery. However, conclusions are limited due to the lack of high-quality studies. More high quality studies may help in a more reliable therapy for HO.

Application of abdominal sonography in diagnosis of infants with necrotizing enterocolitis.

The purpose of this study was to explore the diagnostic significance of abdominal sonography (AUS) in infants with Necrotizing enterocolitis (NEC) admitted to a neonatal intensive care unit to better evaluate the ability of AUS to differentiate necrotizing enterocolitis from other intestinal diseases.All patients diagnosed with NEC at the Department of General Surgery and Neonatal Surgery, Qilu Children's Hospital between 1st, Jun, 2010 and 30th, Dec, 2015. The logistic regression analysis and the area under receiver operating characteristic (ROC) curve (AUCs) were also used to identify the sonographic factors for diagnosing NEC.For the entire cohort of 91 patients, we divided these patients into suspected NEC (n = 35) group and definite NEC (n = 56) group. After adjusting for competing sonographic factors, we identified that thick bowel wall (more than 2.5 mm) (P = .013, OR: 1.246), intramural gas (pneumatosis intestinalis) (P = .002, OR:1.983), portal venous gas (P = .022, OR:1.655) and reduced peristalsis (P = .011, OR:1.667) were independent diagnostic factors associated with NEC. We built a logistic model to diagnose NEC according to the results of multivariable logistic regression analysis. We found the AUROC for thick bowel wall (more than 2.5 mm), intramural gas (pneumatosis intestinalis), portal venous gas and reduced peristalsis were significantly lower than the AUROC for the logistic model was 0.841 (95% CI: 0.669 to 0.946).We found that thick bowel wall (more than 2.5 mm), intramural gas (pneumatosis intestinalis), portal venous gas and reduced peristalsis were independent diagnostic factors associated with NEC. The logistic model was significantly superior to the single sonographic parameter for diagnosing NEC.

Rapamycin inhibits proliferation and induces autophagy in human neuroblastoma cells.

Objective To investigate the effect of Rapamycin on proliferation and autophagy in human neuroblastoma (NB) cell lines and to elucidate the possible mechanism. Methods NB cells were treated with different concentrations of Rapamycin. Cell counting kit-8 (CCK-8) was used to measure proliferation, and flow cytometry (FCM) was used to analyze the cell cycle. EM was used to observe cell morphological changes. Western blotting (WB) was performed to detect the expression of Beclin-1, LC3-I/II, P62, mammalian target of Rapamycin (mTOR), and p-mTOR. Results Rapamycin inhibited the spread of NB cells in a dose- and time-dependent manner and arrested the cell cycle at the G0/G1 phase. EM showed autophagosomes in NB cells treated with Rapamycin. The WB results showed that the expression levels of Beclin-1 and LC3-II/LC3-I were significantly elevated in NB cells treated with Rapamycin, while the expression levels of P62, mTOR, and p-mTOR proteins were significantly reduced compared with the control cells (P<0.05). Conclusion Rapamycin inhibits cell proliferation and induces autophagy in human NB cell lines. The mechanism may be related to suppression of the mTOR signaling pathway.

Small Molecule-Modified Hole Transport Layer Targeting Low Turn-On-Voltage, Bright, and Efficient Full-Color Quantum Dot Light Emitting Diodes.

For an organic-inorganic hybrid quantum dot light-emitting diode (QD-LED), enhancing hole injection into the emitter for charge balance is a priority to achieve efficient device performance. Aiming at this, we employ N,N'-bis(3-methylphenyl)-N,N'-bis(phenyl)benzidine (TPD) as the additional hole transport material which was mixed with poly(9-vinylcarbazole) (PVK) to form a composite hole transport layer (HTL) or was employed to construct a TPD/PVK bilayer structure. Enabled by this TPD modification, the green QD-LED (at a wavelength of 515 nm) exhibits a subband gap turn-on voltage of 2.3 V and a highest luminance up to 56 157 cd/m2. Meanwhile, such TPD modification is also beneficial to acquire efficient blue and red QD-LEDs. In particular, the external quantum efficiencies (EQEs) for these optimized full-color QD-LEDs are 8.62, 9.22, and 13.40%, which are 3-4 times higher than those of their pure PVK-based counterparts. Revealed by the electrochemical impedance spectroscopy, the improved electroluminescent efficiency is ascribable to the reductions of recombination resistance and charge-transfer resistance. The prepared QD-LEDs surpass the EQE values achieved in previous reports, considering devices with small-molecule-modified HTLs. This work offers a general but simple and very effective approach to realize the low turn-on-voltage, bright, and efficient full-color QD-LEDs via this solution-processable HTL modification.

The Efficacy of Naikan Therapy on Male Offenders: Changes in Perceived Social Support and Externalized Blame.

Naikan is a contemplative self-observation practice that originated from Japanese Shin Buddhism and is utilized for rehabilitating prison inmates in many countries. Although some investigations have provided initial evidence for its efficiency in decreasing recidivism, there is still a need for further investigation of the effectiveness of Naikan on other outcomes through more controlled studies. The present study aimed to investigate the efficacy of Naikan therapy on male offenders' perceived social support and externalized blame. Ninety-two male offenders were randomly assigned to either the experimental group or to the waiting group. All participants were evaluated by the Multidimensional Scale of Perceived Social Support and the Externalization subscale of the Test of Self-Conscious Affect before and after Naikan therapy. The results suggested that participants who received Naikan therapy showed higher levels of perceived social support and lower levels of externalized blame after Naikan therapy than before.

Transumbilical Single-Incision Laparoscopic Surgery in Children with Conventional Instruments: Our Early Experience.

OBJECTIVE: Laparoscopic surgery is the current accepted approach in most pediatric surgical centers. In an attempt to further minimize the surgical trauma and improve cosmetic outcome, new techniques with a single incision through the umbilicus have been proposed and we believe they will become the standard choices for pediatric surgery. This report describes our initial experience with transumbilical single-incision laparoscopic surgery (TSILS) in children with conventional instruments. MATERIALS AND METHODS: A retrospective review of 82 pediatric patients who underwent TSILS in children with conventional instruments from January 2011 to June 2015 was performed. The operations included 56 appendectomies, 9 cholecystectomies, and 17 spermatic vein ligations. RESULTS: The average age by procedure was 6.2 years for appendectomy (range of 3-14 years); 12.4 years for cholecystectomy (range of 10-14 years); and 12.8 years for spermatic vein ligation (range of 11-14 years). The average operative time was 32 minutes for appendectomy (range of 25-56 minutes); 54 minutes for cholecystectomy (range of 35-95 minutes); and 23 minutes for spermatic vein ligation (range of 17-41 minutes). The average length of staying in hospital was 3 days (range of 2-5 days). All of the operations in 82 cases were successful. None required conversion to open or conventional laparoscopic surgery. There was no obvious wound pain. In addition, there were no wound infections on umbilicus and any other intraoperative complications. There was no obvious scar at patients' umbilicus after postoperative follow-up for 2-4 weeks. CONCLUSIONS: TSILS is a safe and viable technique that may be used successfully in pediatric surgery. Additionally, excellent cosmetic results are obtained as evidenced by imperceptible umbilical scarring.

Breastfeeding and the risk of childhood Hodgkin lymphoma: a systematic review and meta-analysis.

PURPOSE: Numerous observational epidemiological studies have evaluated associations between breastfeeding and the risk of childhood Hodgkin lymphoma; however, the existing results are inconsistent. We therefore conducted a systematic review and meta-analysis. METHODS: Medical literature was searched in the Pubmed and Embase databases to identify all English-language relevant studies up to April 10, 2013. Reference lists were thereafter hand-searched for additional articles. Studies that reported relative risk ratios (RRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were included. This meta-analysis was conducted in accordance with the guidelines for the meta-analysis of observational studies in epidemiology. RESULTS: We finally included 10 case-control studies in our meta-analysis, involving 1,618 childhood Hodgkin lymphoma cases and 8,181 controls. Overall, we did found a borderline significant association between breastfeeding and reduced risk of childhood Hodgkin lymphoma comparing ever breastfed children to never breastfed children (pooled OR =0.79; 95%CI, 0.58-1.08; P=0.13), with limited evidence for between-study heterogeneity (P =0.12, I2 = 35.70%). CONCLUSION: There is limited evidence for an inverse association between breastfeeding and risk of childhood Hodgkin lymphoma.