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The "ability of realistic drawing" especially realistic drawing ability has been an important measure in assessing the spiritual world of humankind; However, several points in individual teaching strategy remain yet to be clarified in the established practice of group teaching how to draw: 1. How does one assess the artist's skill level? 2. Which abilities should be included in the scale used to assess drawing ability? 3. Of these abilities, which ones can be learned in a short time and which ones require a long time? 4. How does drawing ability evolve to reflect quantitative and qualitative changes as the learning time accumulates? This study attempts to answer the four questions posed above in an analytical and quantifiable way by obtaining empirical data from three drawing experts and four student groups with the aim to establish a set of assessment criteria for drawing ability. With a comprehensive and effective set of assessment criteria established for drawing ability, that the contributions from this study could enable teachers to assist learners not only save time on guesswork, but also provide tailored and specific breakthrough teaching strategies.

Abstract Background 1-{4-[Bis(2-chloroethyl)amino]phenyl}-3-[2-methyl-5-(4-methylacridin-9-ylamino)phenyl]urea (BO-1051) is an N-mustard DNA alkylating agent reported to exhibit antitumor activity. Here we further investigate the effects of this compound on radiation responses of human gliomas, which are notorious for the high resistance to radiotherapy. Methods The clonogenic assay was used to determine the IC50 and radiosensitivity of human glioma cell lines (U87MG, U251MG and GBM-3) following BO-1051. DNA histogram and propidium iodide-Annexin V staining were used to determine the cell cycle distribution and the apoptosis, respectively. DNA damage and repair state were determined by γ-H2AX foci, and mitotic catastrophe was measure using nuclear fragmentation. Xenograft tumors were measured with a caliper, and the survival rate was determined using Kaplan-Meier method. Results BO-1051 inhibited growth of human gliomas in a dose- and time-dependent manner. Using the dosage at IC50, BO-1051 significantly enhanced radiosensitivity to different extents [The sensitizer enhancement ratio was between 1.24 and 1.50 at 10% of survival fraction]. The radiosensitive G2/M population was raised by BO-1051, whereas apoptosis and mitotic catastrophe were not affected. γ-H2AX foci was greatly increased and sustained by combined BO-1051 and γ-rays, suggested that DNA damage or repair capacity was impaired during treatment. In vivo studies further demonstrated that BO-1051 enhanced the radiotherapeutic effects on GBM-3-beared xenograft tumors, by which the sensitizer enhancement ratio was 1.97. The survival rate of treated mice was also increased accordingly. Conclusions These results indicate that BO-1051 can effectively enhance glioma cell radiosensitivity in vitro and in vivo. It suggests that BO-1051 is a potent radiosensitizer for treating human glioma cells.

Abstract Background Opioid analgesics such as morphine and meperidine have been used to control moderate to severe pain for many years. However, these opioids have many side effects, including the development of tolerance and dependence after long-term use, which has limited their clinical use. We previously reported that mutations in the mu-opioid receptors (MOR) S196L and S196A rendered them responsive to the opioid antagonist naloxone without altering the agonist phenotype. In MORS196A knock-in mice, naloxone and naltrexone were antinociceptive but did not cause tolerance or physical dependence. In this study we delivery this mutated MOR gene into pain related pathway to confirm the possibility of in vivo transfecting MORS196A gene and using naloxone as a new analgesic agent. Methods The MOR-knockout (MOR-KO) mice were used to investigate whether morphine and naloxone could show antinociceptive effects when MORS196A gene was transfected into the spinal cords of MOR-KO mice. Double-stranded adeno-associated virus type 2 (dsAAV2) was used to deliver the MORS196A-enhanced green fluorescence protein (EGFP) gene by microinjected the virus into the spinal cord (S2/S3) dorsal horn region. Tail-flick test was used to measure the antinociceptive effect of drugs. Results Morphine (10 mg/kg, s.c.) and naloxone (10 mg/kg, s.c.) had no antinociceptive effects in MOR-KO mice before gene transfection. However, two or three weeks after the MOR-S196A gene had been injected locally into the spinal cord of MOR-KO mice, significant antinociceptive effects could be induced by naloxone or morphine. On the other hand, only morphine but not naloxone induced significant tolerance after sub-chronic treatment. Conclusion Transfecting the MORS196A gene into the spinal cord and systemically administering naloxone in MOR-KO mice activated the exogenously delivered mutant MOR and provided antinociceptive effect without causing tolerance. Since naloxone will not activate natural MOR in normal animals or humans, it is expected to produce fewer side effects and less tolerance and dependence than traditional opioid agonists do.

Background: Eosinophil-derived neurotoxin (EDN) is an important biomarker of eosinophilic inflammation., Methods: This study evaluated Montelukast treatment response according to EDN concentration in children with perennial allergic rhinitis (PAR). Fifty-two children with PAR were recruited and took a combination of Montelukast (5mg) and Levocetirizine (5mg) "Mont/Levo Group" or only Montelukast (5mg) "Mont Group" for 4 weeks. All caregivers were instructed to record rhinitis symptoms for 4 weeks. EDN was measured before and after treatment., Results: Daytime nasal symptom scores (DNSS) significantly decreased in both the Mont/Levo ( p  = 0.0001; n  = 20) and Mont Group ( p  < 0.0001; n  = 20), but there were no significant differences between the two groups. EDN concentration also significantly decreased after treatment in both groups ( p  < 0.0001 and  p  < 0.001, respectively). For secondary analysis, children with a high initial EDN concentration (EDN ≥ 53 ng/mL) were placed in the "High EDN Group", while those with a lower initial EDN concentration (EDN < 53 ng/mL) were put in the "Low EDN Group". Both groups experienced significant reductions in DNSS after either treatment regimen ( p  < 0.0001 and  p  = 0.0027, respectively) but the High EDN Group had greater reductions. EDN concentrations in the High EDN Group decreased significantly from either treatment ( p  < 0.0001)., Conclusion: We found that children with AR and a high serum EDN concentration may respond well to Montelukast treatment. A therapeutic strategy using EDN concentrations in patients with AR to evaluate therapeutic response may help improve quality of care.

Background: Rectal carcinoma (RC), one of the most common malignancies globally, presents an increasing incidence and mortality year by year, especially among young people, which seriously affects the prognosis and quality of life of patients. At present, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters and serum carbohydrate antigen 19-9 (CA19-9) and CA125 Levels have been used in clinical practice to evaluate the T stage and differentiation of RC. However, the accuracy of these evaluation modalities still needs further research. This study explores the application and value of these methods in evaluating the T stage and differentiation degree of RC., Aim: To analyze the diagnostic performance of DCE-MRI parameters combined with serum tumor markers (TMs) in assessing pathological processes and prognosis of RC patients., Methods: A retrospective analysis was performed on 104 RC patients treated at Yantai Yuhuangding Hospital from May 2018 to January 2022. Patients were categorized into stages T1, T2, T3, and T4, depending on their T stage and differentiation degree. In addition, they were assigned to low (L group) and moderate-high differentiation (M + H group) groups based on their differentiation degree. The levels of DCE-MRI parameters and serum CA19-9 and CA125 in different groups of patients were compared. In addition, the value of DCE-MRI parameters [volume transfer constant (Ktrans), rate constant (Kep), and extravascular extracellular volume fraction (Ve) in assessing the differentiation and T staging of RC patients was discussed. Furthermore, the usefulness of DCE-MRI parameters combined with serum CA19-9 and CA125 Levels in the evaluation of RC differentiation and T staging was analyzed., Results: Ktrans, Ve, CA19-9 and CA125 were higher in the high-stage group and L group than in the low-stage group and M + H Group, respectively ( P < 0.05). The areas under the curve (AUCs) of the Ktran and Ve parameters were 0.638 and 0.694 in the diagnosis of high and low stages, respectively, and 0.672 and 0.725 in diagnosing moderate-high and low differentiation, respectively. The AUC of DCE-MRI parameters (Ktrans + Ve) in the diagnosis of high and low stages was 0.742, and the AUC in diagnosing moderate-high and low differentiation was 0.769. The AUCs of CA19-9 and CA-125 were 0.773 and 0.802 in the diagnosis of high and low stages, respectively, and 0.834 and 0.796 in diagnosing moderate-high and low differentiation, respectively. Then, we combined DCE-MRI (Ktrans + Ve) parameters with CA19-9 and CA-125 and found that the AUC of DCE-MRI parameters plus serum TMs was 0.836 in the diagnosis of high and low stages and 0.946 in the diagnosis of moderate-high and low differentiation. According to the Delong test, the AUC of DCE-MRI parameters plus serum TMs increased significantly compared with serum TMs alone in the diagnosis of T stage and differentiation degree ( P < 0.001)., Conclusion: The levels of the DCE-MRI parameters Ktrans and Ve and the serum TMs CA19-9 and CA125 all increase with increasing T stage and decreasing differentiation degree of RC and can be used as indices to evaluate the differentiation degree of RC in clinical practice. Moreover, the combined evaluation of the above indices has a better effect and more obvious clinical value, providing important guiding importance for clinical condition judgment and treatment selection., Competing Interests: Conflict-of-interest statement: There is no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Considering the differences in pH between bacterial infection microenvironment and normal tissues, a series of pH-responsive drug-release amphiphilic polyurethane copolymers (DPU-g-PEG) have been prepared in this work. Fourier transform infrared (FT-IR) spectroscopy and 1 H NMR was selected to detect the structure of the condensed polymers. The DPU-g-PEG amphiphilic copolymers could form stable micelles with a hydrophilic shell of polyethylene glycol (PEG) and a hydrophobic core of polylactic acid (PLA). We loaded a model drug called triclosan onto DPU-g-PEG micelles and studied how pH affects their particle size, Zeta potential, and drug release performance. The results revealed that when exposed to acidic conditions, the surface potential of DPU-g-PEG micelles changed, the micelles' particle size increased, and the drug release performance was significantly enhanced. These results suggested that the micelles prepared in this study can release more antibacterial substances at sites of bacterial infection. Meanwhile, we also investigated the impact of different ratios of soft and hard segments on the properties of micelles, and the results showed that the pH responsiveness of micelles was strongest when the ratio of soft segments (PLLA diol + PEG 2000): 1,6-hexamethylene diisocyanate (HDI): 2,6-Bis-(2-hydroxy-ethyl)-pyrrolo[3,4-f]isoindole-1,3,5,7-tetraone (DMA) = 1: 1.2: 0.2. Furthermore, the results of inhibition zone test, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) all confirmed the antibacterial activity of triclosan-load DPU-g-PEG micelles. In conclusion, the DPU-g-PEG micelles produced in this study have the potential to be used as intelligent drug delivery systems in the biomedical field.

Prenatal exposure to methamphetamine (METH) is an issue of global concern due to its adverse effects on offspring, particularly its impact on liver health, an area still not fully understood. Inulin, a recognized prebiotic, is thought to potentially ameliorate these developmental disorders and toxic injuries in progeny. To investigate the effects of prenatal METH exposure on the liver and the role of gut microbiota, we established a murine model, the subjects of which were exposed to METH prenatally and subsequently treated with inulin. Our findings indicate that prenatal METH exposure causes liver damage in offspring, as evidenced by a decreased liver index, histopathological changes, diminished glycogen synthesis, hepatic dysfunction, and alterations in mRNA profiles. Furthermore, it impairs the antioxidant system and induces oxidative stress, possibly due to changes in cecal microbiota and dysregulation of bile acid homeostasis. However, maternal inulin supplementation appears to restore the gut microbiota in offspring and mitigate the hepatotoxic effects induced by prenatal METH exposure. Our study provides definitive evidence of METH's transgenerational hepatotoxicity and suggests that maternal inulin supplementation could be an effective preventive strategy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. No potential conflict of interest was reported by the authors., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of the study is to examine the associations between mandatory access prescription drug monitoring programs (PDMPs), pain management clinic (PMC) laws, and doctor shopping (DS) laws with adolescent nonmedical use of prescription medications (NUPM)., Methods: We linked 2011-2015 Youth Risk Behavior Survey data on 364,103 adolescents across 40 states with PDMP, PMC laws, and DS laws. We conducted a 2-way fixed effects logistic regression model to examine the associations between state drug laws and adolescent self-reported NUPM., Results: We found some evidence that implementation of a mandatory access PDMP was associated with a decrease in nonmedical use of prescription drugs at the P = 0.079 level (average marginal effect: -0.017, 95% confidence interval = -0.036 to 0.002), while there were no associations with the implementation of PMC and DS laws., Conclusions: Our findings suggest that current state drug laws to combat NUPM are inadequate for adolescents., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 American Society of Addiction Medicine.)

This study aimed to investigate the clinical, radiological, and pathological characteristics of pathologies involving the buccal fat pad (BFP) and to explore the treatment protocols. The cases of 109 patients with primary pathologies involving the BFP (pBFP) diagnosed between January 2013 and September 2021 were assessed. The patients' clinical presentations and radiological and histopathological findings were analysed retrospectively, and their treatment outcomes were evaluated. The 109 pBFP were categorized as benign tumours (n = 17), malignant tumours (n = 29), vascular malformations (n = 38), and inflammatory masses (n = 25). Of the 17 benign tumours, seven were lipomas, five were pleomorphic adenomas, three were solitary fibrous tumours, and two were other tumours. The 29 malignant tumours included five adenoid cystic carcinomas, six mucoepidermoid carcinomas, three synovial sarcomas, and 15 other tumours. Of the 38 vascular malformations, 37 were venous and one was arteriovenous. Regarding the inflammatory masses, the lesions appeared after cosmetic facial botulinum toxin injection in 13 cases and after other cosmetic facial procedures in five. The upper body of the BFP was the most frequently involved site (79/109), while other frequently involved sites were the lower body (67/109) and the masseteric (41/109), temporal (32/109), and pterygopalatine (30/109) extensions., (Copyright © 2023 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Limb-girdle muscular dystrophy recessive 1 (LGMDR1), previously known as LGMD2A, is a specific LGMD caused by a gene mutation encoding the calcium-dependent neutral cysteine protease calpain-3 (CAPN3). In our study, the compound heterozygosity with two missense variants c.635 T > C (p.Leu212Pro) and c.2120A > G (p.Asp707Gly) was identified in patients with LGMDR1. However, the pathogenicity of c.635 T > C has not been investigated. To evaluate the effects of this novel likely pathogenic variant to the motor system, the mouse model with c.635 T > C variant was prepared by CRISPR/Cas9 gene editing technique. The pathological results revealed that a limited number of inflammatory cells infiltrated the endomyocytes of certain c.635 T > C homozygous mice at 10 months of age. Compared with wild-type mice, motor function was not significantly impaired in Capn3 c. 635 T > C homozygous mice. Western blot and immunofluorescence assays further indicated that the expression levels of the Capn3 protein in muscle tissues of homozygous mice were similar to those of wild-type mice. However, the arrangement and ultrastructural alterations of the mitochondria in the muscular tissues of homozygous mice were confirmed by electron microscopy. Subsequently, muscle regeneration of LGMDR1 was simulated using cardiotoxin (CTX) to induce muscle necrosis and regeneration to trigger the injury modification process. The repair of the homozygous mice was significantly worse than that of the control mice at day 15 and day 21 following treatment, the c.635 T > C variant of Capn3 exhibited a significant effect on muscle regeneration of homozygous mice and induced mitochondrial damage. RNA-sequencing results demonstrated that the expression levels of the mitochondrial-related functional genes were significantly downregulated in the mutant mice. Taken together, the results of the present study strongly suggested that the LGMDR1 mouse model with a novel c.635 T > C variant in the Capn3 gene was significantly dysfunctional in muscle injury repair via impairment of the mitochondrial function., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Whilst admission to dental school in many jurisdictions requires applicants to shadow dentists or undertake work experience at a dental practice, little is known about the impacts on professional learning when dental students work part-time as dental assistants whilst concurrently studying dentistry. This paper explores what, how and from whom dental students who work as dental assistants acquire professional knowledges during employment., Methods: This study draws on a qualitative analysis of interviews with sixteen senior dental students who have extra-curricular part-time employment as dental assistants in private dental practices., Results: Analysis produced four themes that relate to students learning in the professional environment: students learn about the responsibilities, rhythms and routines of practice, as well as patient communication and interactions. Students embedded in the dental team noticed and related to the dispositions and the work of dentistry. Students learned from all members of the dental team including clinical and non-clinical staff (reception, administration, laboratory and sterilisation)., Discussion: Students used their experiences in a practice setting to further their professional education. The ability to "read" a situation and formulate an appropriate response requires the integration of complex and actionable professional knowledges., Conclusion: This research study presents insight into the ways dental students employed as dental assistants are embedded in and learn from the dental team in a critically evaluative manner. Students professionally notice and make sense of complex practice environments whilst undertaking university studies to learn about practice routines, rhythms and responsibilities as well as advancing confidence in relating with patients. This study provides a stimulus for further research about the contribution of workplace experiences to dental education., (© 2022 The Authors. European Journal of Dental Education published by John Wiley & Sons Ltd.)

Temporomandibular joint osteoarthrosis (TMJ-OA) frequently causes mild, moderate, or severe condylar morphological changes. A novel condylar remodelling scoring system (CRSS) based on three-dimensional cone beam computed tomography images is proposed, which is used to grade condylar morphological changes. In the CRSS, the condyle is divided into 10 regions by 11 reference points. For each increase in the number of regions involved in TMJ-OA, one point is subtracted from the full score of 10. The intra-class correlation coefficients for intra- and inter-observer agreement (range 0.656-0.898 and 0.841-0.906, respectively) indicated that the CRSS had good reliability. Cephalometric analysis showed that the condyles with severe morphological changes were prone to present with a retrognathic and clockwise rotating mandible, shorter ramus height, reduced mandibular length, larger mandibular angle, and maxillary retrusion. Qualitative CRSS evaluation and quantitative volumetric analysis were performed to evaluate the stability of severe TMJ-OA in its natural course (343 condyles). The continuous cortex group showed no remarkable changes with an average follow-up of 2 years. In the discontinuous cortex group, most (74.4%) converted into a continuous cortex during follow-up (mean 2 years)., (Copyright © 2022 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Non-muscle invasive bladder cancer (NMIBC) is a major type of bladder cancer with a high incidence worldwide, resulting in a great disease burden. Treatment and surveillance are the most important part of NIMBC management. In 2018, we issued "Treatment and surveillance for non-muscle-invasive bladder cancer in China: an evidence-based clinical practice guideline". Since then, various studies on the treatment and surveillance of NMIBC have been published. There is a need to incorporate these materials and also to take into account the relatively limited medical resources in primary medical institutions in China. Developing a version of guideline which takes these two issues into account to promote the management of NMIBC is therefore indicated. We formed a working group of clinical experts and methodologists. Through questionnaire investigation of clinicians including primary medical institutions, 24 clinically concerned issues, involving transurethral resection of bladder tumor (TURBT), intravesical chemotherapy and intravesical immunotherapy of NMIBC, and follow-up and surveillance of the NMIBC patients, were determined for this guideline. Researches and recommendations on the management of NMIBC in databases, guideline development professional societies and monographs were referred to, and the European Association of Urology was used to assess the certainty of generated recommendations. Finally, we issued 29 statements, among which 22 were strong recommendations, and 7 were weak recommendations. These recommendations cover the topics of TURBT, postoperative chemotherapy after TURBT, Bacillus Calmette-Guérin (BCG) immunotherapy after TURBT, combination treatment of BCG and chemotherapy after TURBT, treatment of carcinoma in situ, radical cystectomy, treatment of NMIBC recurrence, and follow-up and surveillance. We hope these recommendations can help promote the treatment and surveillance of NMIBC in China, especially for the primary medical institutions., (© 2022. The Author(s).)

Objective: To explore the application value of white light image (WLI), endoscopic ultrasonography (EUS) and magnifying endoscopy with narrow band imaging (ME-NBI) in the endoscopic treatment of early gastric cancer (EGC), and to provide basis for decision-making in clinical diagnosis and treatment., Methods: The clinicopathological data of EGC patients who underwent endoscopic submucosal dissection (ESD) at West China Hospital, Sichuan University between December 2013 and October 2020 were included. The accuracy, sensitivity, specificity, positive predictive value and negative predictive value of EGC invasive depth were compared between WLI and EUS. The role of ME-NBI in predicting the differentiation types of EGC was analyzed., Results: A total of 280 patients (291 lesions) were enrolled in the study. Among them, 199 patients (207 lesions) received EUS and 160 patients (168 lesions) received ME-NBI. The overall accuracy of WLI in diagnosing the invasive depth of EGC was 87.0%, significantly higher than that of EUS (46.4%, P <0.001). When WLI was combined with EUS, the diagnostic accuracy (87.4%) was not significantly improved. The overall accuracy of determining the differentiation degree of EGC with ME-NBI was 92.3% (155/168), and the accuracy of determining undifferentiated EGC with ME-NBI was significantly lower than that of differentiated EGC (41.2% vs. 98.0%, P <0.001)., Conclusion: In the evaluation of indications for endoscopic treatment of EGC, WLI showed better performance in predicting the invasive depth of EGC, while EUS demonstrated limited value. ME-NBI showed better accuracy for predicting the differentiation degree of most EGC, especially for differentiated EGC., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

A 46-year-old woman was admitted for repeated abdominal distention and constipation for more than 10 years and further deterioration for 5 years. Colonoscopy showed, in the sigmoid colon, nodular neoplasm protruding into the cavity, resulting in local intestinal stenosis, through which the endoscopy could not pass. Pathological findings of the biopsy sample revealed changes caused by intestinal endometriosis. The patient underwent multiple endoscopic dilatation treatments in our hospital and the interval between recurrences of intestinal stenosis was extended from 6 months to 4 years. Intestinal endometriosis can cause repeated intractable stenosis caused by the infiltration of ectopic glands in the intestinal wall, which usually requires surgical intervention. Herein, we report a case of severe intestinal stenosis caused by endometriosis in the sigmoid colon. Good results have been achieved through endoscopic dilatation treatment. This case suggests that endoscopic dilation has good application value in the treatment of this kind of disease, which needs further exploration and promotion., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

The application of artificial intelligence in medicine has gradually received attention along with its development. Many studies have shown that machine learning has a wide range of applications in stomatology, especially in the clinical diagnosis and treatment of maxillofacial cysts and tumors. This article reviews the application of machine learning in maxillofacial cyst and tumor to provide a new method for the diagnosis of oral and maxillofacial diseases.

Introduction: To explore the function of interleukin 1α (IL-1α) in bladder cancer (BCa)., Material and Methods: Immunohistochemistry (IHC) was used to test the protein expression of IL-1α in BCa tissues. The relationship between IL-1α and clinical characteristics was analyzed by the Kaplan-Meier curve method. The gene and protein expression was tested by reverse transcription quantitative polymerase chain reaction (RT-q-PCR) and western blot, respectively. Colony formation and MTT assays were used to detect the potential of proliferation in vitro , and scratch and transwell chamber assays were used to detect the potential of invasion in vitro . Markers of proliferation such as Ki-67 and proliferating cell nuclear antigen (PCNA) and markers of invasion such as MMP-2 and MMP-9 were detected by western blot. Xenograft study was used for the in vivo experiment., Results: We found that IL-1α was highly expressed in BCa patients while highly expressed IL-1α was significantly related to short overall survival and progression-free survival in BCa as well. Moreover, knockdown of IL-1α might inhibit the ability of cancer cells to proliferate and invade or migrate both in vitro and in vivo ., Conclusions: Our findings suggested that IL-1α might be a therapy target for BCa malignant progression., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2020 Termedia & Banach.)

Objectives: Adolescent Screening, Brief Intervention, and Referral to Treatment (SBIRT) in primary care is a key strategy to prevent, identify, and respond to substance use problems and disorders, including opioid and other drug addictions. Despite substantial investment in recent years to increase its implementation, few studies have reported on recent levels of SBIRT implementation among pediatricians. We aimed to assess self-reported use of the SBIRT framework with adolescent patients among Massachusetts pediatricians, and describe trends since an earlier survey., Methods: We analyzed responses to a cross-sectional survey mailed in 2017 to a representative sample of pediatricians in Massachusetts. We computed response frequencies for all SBIRT practice questions. We used the chi-square test to compare current data to data collected in 2014, as we found no demographic differences between the 2 samples., Results: Nearly all pediatricians in the 2017 sample (n = 160) reported annual screening of their adolescent patients (99%). The majority reported giving positive reinforcement (87%), brief advice (92%), counseling (90%), and referral to treatment (66%) in response to screen results. Compared with 2014, a significantly higher proportion of pediatricians in 2017 referred patients who screened positively for problematic alcohol use, but perceived barriers to screening and follow-up remain, such as insufficient time to screen and patient refusal to return., Conclusions: Among respondents to a Massachusetts pediatrician survey, we found high rates of delivering SBIRT in accordance with published guidelines, though barriers remain. Whether the content of the counseling adheres to guidelines is unknown.

Background: Cartilaginous endplate (CEP), a thin layer of hyaline cartilage located between the vertebral endplate and nucleus pulposus, transports the nutrient into the disc. The objective of this study was to evaluate the influence of T140 (polyphemusin II-derived peptide) on the CEP cell growth, apoptosis, and the matrix formation via the stromal cell-derived factor-1 (SDF-1)/cysteine X cysteine (CXC) receptor-4 (CXCR4) signaling pathway., Methods: Sprague-Dawley rats were euthanized by cervical dislocation and dissected for the isolation and the appraisal of CEP cells that were extracted from the endplate in rat intervertebral discs and were then added with different concentrations of reagents (SDF-1 and T140). The effect of T140 on CEP cell proliferation and apoptosis were analyzed. The messenger RNA (mRNA) and protein expressions of CXCR4, prominin-1, proteoglycans, type II collagen, B-cell lymphoma-2 (Bcl-2), and Bcl-2 associated X protein were analyzed by reverse transcription quantitative polymerase chain reaction and Western blot analysis., Results: T140 promoted the proliferation of CEP cells and inhibited the apoptosis of CEP cells. Additionally, T140 suppressed the mRNA and protein expression of CXCR4, prominin-1, and Bcl-2 associated X protein, and increased the mRNA and protein expression of proteoglycans, type II collagen, and Bcl-2., Conclusions: T140 promotes the proliferation and matrix formation and inhibits the apoptosis of CEP cells by blocking the SDF-1/CXCR4 signaling pathway in vitro, which provides a certain therapeutic effect on the degeneration of intervertebral discs., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Protein kinase CK2 alpha (CK2α) is involved in the development of multiple malignancies. Overexpression of Y-box binding protein 1 (YBX1) is related to tumor proliferation, drug resistance, and poor prognosis. Studies have demonstrated that both CK2 and YBX1 could regulate the PI3K/AKT pathway. In addition, we predicted that CK2 might be the upstream kinase of YBX1 through the Human Protein Reference Database (HPRD). Herein, we hypothesize that CK2 may interact with YBX1 and they regulate the PI3K/AKT signaling pathway together. Expressions of CK2α and YBX1 in cancer cell lines were evaluated by immunoblotting. The results showed that CK2α could regulate the expression of YBX1 at the transcriptional level, which is dependent on its enzymatic activity. Synergistic effects of PI3K/AKT pathway inactivation could be observed through combined inhibition of CK2α and YBX1, and YBX1 was required for CK2α-induced PI3K/AKT pathway activation. Further results demonstrated that CK2α could interact with YBX1 and PI3K/AKT antagonist decreased cell resistance to doxorubicin induced by co-activation of CK2α and YBX1. These results indicated that combined inhibition of CK2α and YBX1 showed synergistic effects in inactivating the PI3K/AKT signaling pathway and may be one of the mechanisms involved in tumor growth and migration.

Aims: Intracerebral hemorrhage (ICH) is a devastating type of stroke without specific treatment. Activator protein 1 (AP-1), as a gene regulator, initiates cytokine expression in response to environmental stimuli. In this study, we investigated the relationship between AP-1 and neuroinflammation-associated brain injury triggered by ICH., Methods: Intracerebral hemorrhage mice were developed by autologous blood or collagenase infusion. We measured the dynamics of AP-1 in mouse brain tissues during neuroinflammation formation after ICH. The effects of the AP-1 inhibitor SR11302 on brain injury and neuroinflammation as well as the underlying mechanisms were investigated in vivo and in vitro., Results: AP-1 was significantly upregulated in mouse brain tissue as early as 6 hours after ICH, accompanied by elevations in proinflammatory factors, including interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α. Inhibition of AP-1 using SR11302 reduced neurodeficits and brain edema at day 3 after ICH. SR11302 ablated microglial IL-6 and TNF-α production and brain-infiltrating leukocytes in ICH mice. In addition, SR11302 treatment diminished thrombin-induced production of IL-6 and TNF-α in cultured microglia., Conclusions: Inhibition of AP-1 curbs neuroinflammation and reduces brain injury following ICH., (© 2019 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)

Background: Current research has identified several risk factors for refractory benign esophageal strictures (RBES), but research is scarce on the prediction of RBES in benign esophageal strictures patients. Meanwhile, the long-term outcomes of RBES remain unclear. The aim of this study was to develop and validate a model to determine the progression of RBES in patients with benign esophageal strictures. And we also explored the long-term outcomes and safety in patients with RBES., Aim: To develop and validate a model to determine the progression of RBES in patients with benign esophageal strictures, based on the demographic data and endoscopic findings., Methods: A total of 507 benign esophageal stricture patients treated by dilation alone or in combination with stenting were retrospectively enrolled between January 2009 and February 2018. The primary outcome was to establish a risk-scoring model predicting RBES in benign esophageal strictures. The secondary outcome was to explore the clinical effectiveness and adverse events in patients with RBES., Results: In the study, age, etiology, and number and length of strictures were the independent risk factors for the refractory performance of benign esophageal strictures. According to risk factors of benign esophageal strictures, a risk-scoring model for predicting RBES in benign esophageal strictures was established: The risk score ranged from 0 to 8 points, and the risk scores were divided into low risk (0-2 points), intermediate risk (3-5 points), and high risk (6-8 points). The proportions of RBES in the corresponding risk categories were 1.0%, 12.2%, and 76.0%, respectively. Among 507 patients, 57 had RBES (39 males; median age, 60 years). The success rate of dilation treatment (51.2%, 21/41) was higher than that of stent placement (37.5%, 6/16)., Conclusion: In this study, 11.3% (57/507) patients had RBES at our hospital. The risk-scoring model predicting RBES in benign esophageal strictures could predict the long-term outcome of patients with strictures ahead., Competing Interests: Conflict-of-interest statement: All authors declare no conflicts of interest.

Objective: To explore the effect on the recovery of gastrointestinal function after cesarean section treated with transcutaneous electrical acupoint stimulation at Zusanli (ST 36) on the basis of routine treatment., Methods: A total of 110 primiparas after cesarean section were randomized into an observation group and a control group, 55 cases in each one. The conventional treatment was applied in the two groups, after operation, transcutaneous electrical acupoint stimulation at Zusanli (ST 36) was used immediately in the observation group, the skin electrode of disposable anti-magnetic buckle was attached to Zusanli (ST 36) and the corresponding part of the inner lower leg, with disperse-dense wave, 30 Hz/60 Hz and 15-20 mA. The treatment was given for 30 min every time, once every 8 h, until the end of the first bowel movement. The recovery of gastrointestinal function after cesarean section (the restoring time of borborygmus, the time of first anal exsufflation and the first defecation time), the time of secretion of foremilk, complications (abdominal distension, abdominal pain, nausea etc.), hospital stays after operation and the satisfaction of primiparas after bowel movement were compared between the two groups., Results: The observation group was superior to the control group in the restoring time of borborygmus, the time of first anal exsufflation, the first defecation time and the time of secretion of foremilk ( P <0.01, P <0.05). In the observation group, the incidence of postoperative complications such as abdominal pain, abdominal distension and nausea was 3.6% (2/55), which was lower than 16.4% (9/55) in the control group ( P <0.05). Compared with the control group, the observation group had shorter hospital stays ( P <0.01). The satisfaction of effect was 89.1% (49/55) in the observation group, which was superior to 72.7% (40/55) in the control group ( P <0.05)., Conclusion: Transcutaneous electrical acupoint stimulation at Zusanli (ST 36) can speed up the recovery of gastrointestinal function after cesarean section, reduce complications such as abdominal pain, abdominal distension, shorten hospital stays, promote patient nutrition intake and lactation, and improve comfort level and satisfaction of primiparas.

In cancers with tumor-infiltrating lymphocytes (TILs), monoclonal antibodies (mAbs) that block immune checkpoints such as CTLA-4 and PD-1/PD-L1 promote antitumor T-cell immunity. Unfortunately, most cancers fail to respond to single-agent immunotherapies. T regulatory cells, myeloid derived suppressor cells (MDSCs), and extensive stromal networks within the tumor microenvironment (TME) dampen antitumor immune responses by preventing T-cell infiltration and/or activation. Few studies have explored combinations of immune-checkpoint antibodies that target multiple suppressive cell populations within the TME, and fewer have studied the combinations of both agonist and antagonist mAbs on changes within the TME. Here, we test the hypothesis that combining a T-cell-inducing vaccine with both a PD-1 antagonist and CD40 agonist mAbs (triple therapy) will induce T-cell priming and TIL activation in mouse models of nonimmunogenic solid malignancies. In an orthotopic breast cancer model and both subcutaneous and metastatic pancreatic cancer mouse models, only triple therapy was able to eradicate most tumors. The survival benefit was accompanied by significant tumor infiltration of IFNγ-, Granzyme B-, and TNFα-secreting effector T cells. Further characterization of immune populations was carried out by high-dimensional flow-cytometric clustering analysis and visualized by t-distributed stochastic neighbor embedding (t-SNE). Triple therapy also resulted in increased infiltration of dendritic cells, maturation of antigen-presenting cells, and a significant decrease in granulocytic MDSCs. These studies reveal that combination CD40 agonist and PD-1 antagonist mAbs reprogram immune resistant tumors in favor of antitumor immunity., (©2019 American Association for Cancer Research.)

Bladder cancer (BC) has been regarded as the most common malignancy of the urinary system worldwide. With lack of investigations for molecular pathogenesis underlying that develop BC, the therapeutic efficacy of several therapeutic approaches existing is still unsatisfactory. Here, our study aimed to explore the potentially biological function of MAN1B1 on BC. In this study, MAN1B1 expression level in BC tissues and normal tissues was analyzed based on The Cancer Genome Atlas (TCGA) data and correlation between its expression and prognosis was determined using Kaplan-Meier analysis. Knockout of MAN1B1 was performed using silencing RNA and the efficacy of MAN1B1 knockout was identified using quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis. The BC cells proliferation was assessed by Cell Counting Kit-8 (CCK8) assay, and then the cells apoptosis was detected by Annexin V-fluorescein isothiocyanate (Annexin V-FITC)/propidium iodide (PI) staining and flow cytometry following MAN1B1 knocked down by small interfering RNA. Protein kinase B (AKT) signaling was evaluated by detecting related markers, namely AKT, p-AKT, 4E-BP-1 and Bax using western blot assay. As a result, the MAN1B1 expression was higher in BC tissues than those in normal tissues, besides, its overexpression was associated with poor prognosis. Moreover, MAN1B1 reduction by silencing RNA approach resulted in BC cells proliferation suppression and BC cells apoptosis promotion. Finally, AKT signaling activity was inhibited by MAN1B1 silencing. Taken together, these results unraveled that MAN1B1 may act on an oncogenic action in BC, which improved the likelihood of MAN1B1 taking on a promising prognostic biomarker and a potential target for treating BC., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Immune-checkpoint inhibition (ICI) has revolutionized treatment in cancers that are naturally immunogenic by enabling infiltration of T cells into the tumor microenvironment (TME) and promoting cytotoxic signaling pathways. Tumors possessing complex immunosuppressive TMEs such as breast and pancreatic cancers present unique therapeutic obstacles as response rates to ICI remain low. Such tumors often recruit myeloid-derived suppressor cells (MDSCs), whose functioning prohibits both T-cell activation and infiltration. We attempted to sensitize these tumors to ICI using epigenetic modulation to target MDSC trafficking and function to foster a less immunosuppressive TME. We showed that combining a histone deacetylase inhibitor, entinostat (ENT), with anti-PD-1, anti-CTLA-4, or both significantly improved tumor-free survival in both the HER2/neu transgenic breast cancer and the Panc02 metastatic pancreatic cancer mouse models. Using flow cytometry, gene-expression profiling, and ex vivo functional assays, we characterized populations of tumor-infiltrating lymphocytes (TILs) and MDSCs, as well as their functional capabilities. We showed that addition of ENT to checkpoint inhibition led to significantly decreased suppression by granulocytic MDSCs in the TME of both tumor types. We also demonstrated an increase in activated granzyme-B-producing CD8 + T effector cells in mice treated with combination therapy. Gene-expression profiling of both MDSCs and TILs identified significant changes in immune-related pathways. In summary, addition of ENT to ICI significantly altered infiltration and function of innate immune cells, allowing for a more robust adaptive immune response. These findings provide a rationale for combination therapy in patients with immune-resistant tumors, including breast and pancreatic cancers., (©2018 American Association for Cancer Research.)

Objective: To assess the accuracy of endoscopic ultrasound (EUS) and magnifying endoscopy with narrow-band imaging (ME-NBI) in evaluating the invasion depth of early esophageal carcinoma., Methods: Patients who underwent endoscopic resection for early esophageal cancer from March 2013 to October 2017 were enrolled. The EUS and ME-NBI results were compared with the pathology results., Results: A total of 392 lesions from 333 patients were assessed, including 83 mild and moderate dysplasia, 72 severe dysplasia, 235 squamous cell carcinoma, and 2 adenosquamous carcinoma. About 308 lesions were given EUS only, 7 had ME-NBI only, 77 underwent both EUS and ME-NBI. EUS resulted in a 43.9% accuracy for the 385 lesions, with poor consistency ( Kappa =0.1) with the pathology results. But higher accuracy (68.2%) was found for lesions infiltrating into the submucosa of the lesions, compared with 40.5% for lesions contained within the mucosa ( P =0.001). ME-NBI resulted in a 72.6% accuracy for the 84 lesions, with a medium consistency ( Kappa =0.4). The accuracy for lesions contained within the mucosa was 91.0%, compared with 16.7% for lesions infilrtrating into the submucosa ( P =0.001). EUS and ME-NBI for the 77 lesions demonstrated an accuracy of 42.9% for the EUS and 84.3% for the ME-NBI ( P =0.001)., Conclusions: ME-NBI has higher accuracy than EUS in evaluating the invasion depth of early esophageal carcinoma., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).)

In recent researches, high expression of nesfatin-1/nucleobindin-2 (NUCB2) is linked to poor prognosis in prostate and colon cancer due to the enhancement in proliferation, migration, and invasion. However, the role of nesfatin-1 in bladder cancer is not clear. In this study, we examined the expression of NUCB2 in bladder cancer using immunohistochemistry and observed that its high expression was associated with recurrence and metastasis. In addition, the transwell assay and wound healing assay showed that cell migration and invasion were decreased with NUCB2 knockdown in T24 and 5637 cells. In vivo, tumor growth and metastasis were inhibited with shRNA treatment in T24 cells. Those results showed that NUCB2 played an important role in bladder cancer and could be considered a potent prognostic factor in bladder cancer.

BACKGROUND Alteration of DNA methylation of tumor suppressor genes (TSGs) is one of the most consistent epigenetic changes in human cancers. DNMTs play several important roles in DNA methylation and development of cancers. Regarding DNMTs protein expressions, little is known about the clinical significance and correlation with promoter methylation status of TSGs in human pituitary adenomas. MATERIAL AND METHODS We analyzed the protein expression of 3 DNMTs using immunohistochemistry and assessed DNA hypermethylation of RASSF1A, CDH13, CDH1, and CDKN2A (p16) in 63 pituitary adenomas. We examined associations between DNMTs expression and clinicopathological features or promoter methylation status of TSGs. RESULTS Overexpression of DNMTs was detected in pituitary adenomas. Frequencies of DNMT1 overexpression were significantly higher in macroadenomas, invasive tumors, and grade III and IV tumors. DNMT3A was frequently detected in invasive tumors and grade IV tumors. In addition, DNMT1 and DNMT3A were frequently detected in high-methylation tumors. Furthermore, in multivariate logistic regression, the significant association between DNMT1 or DNMT3A and high-methylation status persisted after adjusting for clinicopathological features. CONCLUSIONS Our findings suggested that tumor overexpression of DNMT1 and DNMT3A is associated with tumor aggressive behavior and high-methylation status in pituitary adenomas. Our data support a possible role of DNMT1 and DNMT3A in TSG promoter methylation leading to pituitary adenoma invasion and suggest that inhibition of DNMTs has the potential to become a new therapeutic approach for invasive pituitary adenoma.

Background: Although triptorelin is increasingly used in China for biochemical castration, its effects on primary prostate cancer symptoms remain unclear. This study aimed to assess the prevalence of lower urinary tract symptoms (LUTS) in Chinese prostate cancer patients and the effectiveness of triptorelin on LUTS., Methods: In this 48-week multicenter, non-interventional, prospective study, we enrolled patients with locally advanced or metastatic prostate cancer. Patients received triptorelin (15 mg) intramuscularly at baseline and at weeks 12, 24, and 36 with symptom assessment using the International Prostate Symptoms Score (IPSS). The primary endpoints were the prevalence of LUTS at baseline per IPSS categories and the percentage of patients with moderate to severe LUTS (IPSS > 7) at baseline, having at least a 3-point reduction of IPSS score at week 48., Results: A total of 398 patients were included; 211 (53.0%) and 160 (40.2%) among them had severe and moderate LUTS, respectively. Of the patients with IPSS scores available at baseline and at week 48 (n = 213), 81.2% achieved a reduction in IPSS of at least 3 points. Of the patients with moderate to severe LUTS at baseline and IPSS scores available at baseline and at week 48 (n = 194), 86.6% achieved a total IPSS reduction of at least 3 points., Conclusions: The vast majority of Chinese patients with locally advanced or metastatic prostate cancer scheduled to receive triptorelin as part of their standard treatment have severe or moderate LUTS. Triptorelin therapy resulted in sustained improvement of LUTS in these patients.

Objective: To investigate the efficacy of inhalational sevoflurane anesthesia induction on inhibiting the stress response to endotracheal intubation in pediatric patients with congenital heart disease (CHD)., Patients and Methods: Forty ASA physical status I/II pediatric patients scheduled for interventricular septal defect repair or interatrial septal defect repair, were randomly divided into two groups (20 each): intravenous induction group (Group C) and inhalational sevoflurane anesthesia induction group (Group D). In group C, anesthesia was induced with midazolam, pipecuronium bromide and fentanyl, and the children were examined by radial artery monitoring after the consciousness extinction. Also, they were endotracheally intubated after muscle relaxation. In group D, anesthesia was induced with inhalation of 8% sevoflurane and 6 L/min oxygen, and the children were examined by radial artery monitoring after the consciousness extinction and were endotracheally intubated 4 min later. Before anesthesia induction (T0), consciousness extinction (T1), endotracheal intubation (T2), endotracheal intubation (T3), and after endotracheal intubation (T4), 1 and 3 min after intratracheal intubation (T5,6), HR and bispectral index (BIS) were monitored. The MAP of T2-T6 points was recorded. Ulnar vein blood samples were taken for determination of Endothelin (ET) and Thromboxane A2(TXA2) in the points of consciousness extinction, and 5 and 10 min after endotracheal., Results: All the children were well examined by endotracheal intubation. Compared with the baseline value at T0, there was no significant difference of HR in group D, but the HR of group C was decreased at T2, T3, T4 and T6. The BIS of the two groups were decreased at T1-T6 (p<0.05). Compared with the values at T2, they were increased at T5 and T6 in group C, and increased at T6 in group D (p<0.05). Compared with group C, the MAP of group D was decreased at T5, and the BIS of the two groups was decreased at T2-T6 (p<0.05). There were no significant differences of ET and TXA2 between groups., Conclusions: It is well inhibited the endotracheal intubation stress response in children with congenital heart diseases using sevoflurane inhalational anesthesia induction.

FMS-like tyrosine kinase-3 (FLT3) tyrosine kinase inhibitors (TKI) have been tested extensively to limited benefit in acute myeloid leukemia (AML). We hypothesized that FLT3/internal tandem duplication (ITD) leukemia cells exhibit mechanisms of intrinsic signaling adaptation to TKI treatment that are associated with an incomplete response. Here, we identified reactivation of ERK signaling within hours following treatment of FLT3/ITD AML cells with selective inhibitors of FLT3. When these cells were treated with inhibitors of both FLT3 and MEK in combination, ERK reactivation was abrogated and anti-leukemia effects were more pronounced compared with either drug alone. ERK reactivation was also observed following inhibition of other tyrosine kinase-driven cancer cells, including EGFR-mutant lung cancer, HER2-amplified breast cancer, and BCR-ABL leukemia. These studies reveal an adaptive feedback mechanism in tyrosine kinase-driven cancers associated with reactivation of ERK signaling in response to targeted inhibition. Cancer Res; 77(20); 5554-63. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Quantitative modeling of microscopic genes regulatory mechanisms in an individual cell is a crucial step towards understanding various macroscopic physiological phenomena of cell populations. Based on the regulatory mechanisms of genes zeb1 and cdh1 in the growth and development of breast cancer cells, we propose a kinetic model at the level of single cell. By constructing the effective landscape of underlying stationary probability for the genes expressions, it is found that (i) each breast cancer cell has three phenotypic states (i.e., the stem-like, basal, and luminal states) which correspond to three attractions of the probability landscape. (ii) The interconversions between phenotypic states can be induced by the noise intensity and the property of phenotypic switching is quantified by the mean first-passage time. (iii) Under certain conditions, the probabilities of each cancer cell appearing in the three states are consistent with the macroscopic phenotypic equilibrium proportions in the breast cancer SUM159 cell line. (iv) Our kinetic model involving the TGF-β signal can also qualitatively explain several macroscopic physiological phenomena of breast cancer cells, such as the "TGF-β paradox" in tumor therapy, the five clinical subtypes of breast cancer cells, and the effects of transient TGF-β on breast cancer metastasis.

Specific RNAs can function as sinks for endogenous miRNAs, known as competing endogenous RNAs (ceRNAs). Here, we confirm a miR-124 mediated ceRNA crosstalk between LAMC1 and CD151 in hepatocellular carcinoma (HCC). miR-124 negatively regulates LAMC1 expression through two miRNA binding sites within its 3' untranslated region (3'UTR) and suppresses migration and invasion of HCC cells through regulating LAMC1. The wild type LAMC1 miRNA response elements (MREs) facilitate expression of CD151, and this regulation is miR-124 dependent. In clinical hepatic tissues, LAMC1 and CD151 mRNAs exhibit positive correlation. Importantly, LAMC1 MREs promote HCC malignancy by absorbing miR-124 and by assisting CD151 expression. We conclude that LAMC1 mRNA acts as a trans regulator to stimulate CD151 expression by competing for miR-124 binding in HCC cells. © 2017 IUBMB Life, 69(8):595-605, 2017., (© 2017 International Union of Biochemistry and Molecular Biology.)

Objective: To investigate the causes of 30-day unplanned revision surgery following one-stage posterior vertebral column resection (PVCR) for severe spinal deformity and the methods of prevention and management. Methods: A total of 112 severe deformity patients underwent one-stage PVCR for surgical treatment in the 306(th) Hospital of People's Liberation Army from May 2010 to December 2015 were retrospectively reviewed. Six patients required reoperation within 30 days after PVCR, including 2 males and 4 females with average age of 21 years (ranging from 12 to 38 years). Four cases were congenital kyphoscoliosis, 1 was post-laminectomy kyphoscoliosis and 1 was post-tuberculous angular kyphosis. Three cases associated with preoperative neurologic deficit (Frankel C in 1 patient and D in 2 patients). The causes, management and outcomes of unplanned revision surgery within 30 days after PVCR were recorded. Results: The total incidence of unplanned revision surgery within 30 days following PVCR was 5.4% (6/112). There was 1 case due to cerebrospinal fluid leak, 5 cases with varying degrees of new neurologic deficits, the causes were as followed: dural buckling in 1 case, residual bone compression in 1 case, epidural hematoma compression in 2 cases, spinal subdural hematoma in 1 case. All the 6 cases underwent surgical exploration again, including further dural repair, decompression and hematoma clearance. After unplanned reoperation, 6 cases recovered completely. The average follow-up time after surgery was 30.8 months (ranging from 10 to 60 months). The major curve at coronal plane was improved from preoperative 87.7° to 34.2°, with a mean correction of 61.0% at final follow-up; the sagittal kyphosis curve was improved from preoperative 119.5° to 45.5°, with a mean correction of 61.9% at final follow-up. Two patients' neurological status improved from Frankel D to Frankel E, one patient's neurological status improved from Frankel C to Frankel E. Conclusions: One-stage PVCR could be an effective method for treatment of severe spinal deformity. The causes of 30-day unplanned reoperation after PVCR are as followed: cerebrospinal fluid leak, dural buckling, residual bone compression and hematoma compression. Timely surgical exploration can gain good clinical outcomes.

All- trans retinoic acid (ATRA) has been very successful in the subtype of acute myelogenous leukemia known as acute promyelocytic leukemia due to targeted reactivation of retinoic acid signaling. There has been great interest in applying this form of differentiation therapy to other cancers, and numerous clinical trials have been initiated. However, ATRA as monotherapy has thus far shown little benefit in nonacute promyelocytic leukemia acute myelogenous leukemia. Here, we review the literature on the use of ATRA in combination with chemotherapy, epigenetic modifying agents and targeted therapy, highlighting specific patient populations where the addition of ATRA to existing therapies may provide benefit. Furthermore, we discuss the impact of recent whole genome sequencing efforts in leading the design of rational combinatorial approaches., Competing Interests: Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.

From January 2013 to January 2015, 19 patients of traumatic hemothorax with hemorrhagic shock were treated in our department by thoracoscopic surgery combined with autologous blood transfusion. This study retrospectively analyzed the therapeutic effect and shared our experience. The average amount of blood transfused back was 662.41 ml ± 269.15 ml. None of the patients developed transfusion reaction and were all discharged uneventfully. Thoracoscopic surgery combined with autologous blood trans- fusion is effective in the rescue of patients with progressive hemothorax and hemorrhagic shock. When corresponding indications are well managed, treatment for these patients is quicker, safer, and more effective.

Calcitonin may relieve pain by modulating central serotonin activity. Calcitonin partly reversed the hypersensitivity to pain induced by ovariectomy. This suggests that the anti-nociceptive effects of calcitonin in the treatment of osteoporosis may be mediated by alterations in neural serotonin transporter (SERT) activity., Introduction: This study used a rat model of osteoporosis to evaluate the role of the cerebral serotonin system in the anti-nociceptive effect of calcitonin, a drug used to treat post-menopausal osteoporosis., Methods: Osteoporosis was induced in rats by ovariectomy (OVX). Rats were then randomized to the following four groups: sham operation, OVX, OVX plus calcitonin, or OVX plus alendronate., Results: OVX led to alterations in bone micro-architecture; alendronate strongly reversed this effect, and calcitonin moderately reversed this effect. OVX increased hyperalgesia (determined as the time for hind paw withdrawal from a heat source); calcitonin reduced this effect, but alendronate had no effect. OVX increased the expression of c-Fos (a neuronal marker of pain) in the thalamus; calcitonin strongly reversed this effect, and alendronate moderately reversed this effect. OVX also reduced SERT but increased 5-HT1A receptor expression and activity; calcitonin aggravated this effect, but alendronate had no effect on recovery of SERT/5-HT1A activity and expression., Conclusions: Our study of a rat model of osteoporosis suggests that OVX-induced enhancement of the serotonergic system may protect against hyperalgesia. However, the anti-nociceptive effects of calcitonin in osteoporosis may be mediated by decreased neural SERT activity and increased activation of 5-HT1 receptors in the thalamus.

The aim of this study was to investigate the expression of vascular adhesion molecule (VCAM)-1 in the maternal serum, cord blood, and placental tissue of pregnant women from Xingtai, Hebei, with gestational hypertension (GH) combined with fetal growth restriction (FGR). A total of 108 patients with GH combined with FGR (GH-FGR), 60 patients with GH alone (GH), and 50 healthy pregnant women (control) were recruited to this study. VCAM- 1 expression was detected in the maternal serum and cord blood by enzyme-linked immunosorbent assay, and in the placental tissue by immunohistochemistry. VCAM-1 expression was significantly higher in the maternal serum of patients with GH-FGR (164.38 ± 60.35) and GH alone (103.85 ± 54.47) than in the serum of the control population (46.70 ± 21.79; P < 0.05). On the other hand, VCAM-1 expression in the cord blood of GH-FGR (163.19 ± 69.46), GH (149.82 ± 58.20), and control (128.89 ± 43.59) subjects was not significantly different (P > 0.05). Moreover, the VCAM-1 expression rates were significantly higher and lower in the vascular endothelial and trophoblastic cells of the placenta of patients with GH-FGR (74.71 and 56.1%) and GH (72.98 and 55.36%), respectively, compared to those in the control subjects (46.48 and 95.11%). Therefore, we concluded that VCAM- 1 plays an important role in the development and generation of GH. Additionally, the low VCAM-1 expression in the trophoblastic cell could be correlated to the pathogenesis and progression of GH., Competing Interests: The authors declare no conflict of interest.

Background: Research suggests that an 8-week mindfulness-based cognitive therapy (MBCT) course may be effective for generalised anxiety disorder (GAD)., Aims: To compare changes in anxiety levels among participants with GAD randomly assigned to MBCT, cognitive-behavioural therapy-based psychoeducation and usual care., Method: In total, 182 participants with GAD were recruited (trial registration number: CUHK&#95;CCT00267) and assigned to the three groups and followed for 5 months after baseline assessment with the two intervention groups followed for an additional 6 months. Primary outcomes were anxiety and worry levels., Results: Linear mixed models demonstrated significant group × time interaction (F(4,148) = 5.10, P = 0.001) effects for decreased anxiety for both the intervention groups relative to usual care. Significant group × time interaction effects were observed for worry and depressive symptoms and mental health-related quality of life for the psychoeducation group only., Conclusions: These results suggest that both of the interventions appear to be superior to usual care for the reduction of anxiety symptoms., (© The Royal College of Psychiatrists 2016.)

FMS-like tyrosine kinase 3 (FLT3)-mutant acute myeloid leukemia (AML) portends a poor prognosis, and ineffective targeting of the leukemic stem cell (LSC) population remains one of several obstacles in treating this disease. All-trans retinoic acid (ATRA) has been used in several clinical trials for the treatment of nonpromyelocytic AML with limited clinical activity observed. FLT3 tyrosine kinase inhibitors (TKIs) used as monotherapy also achieve limited clinical responses and are thus far unable to affect cure rates in AML patients. We explored the efficacy of combining ATRA and FLT3 TKIs to eliminate FLT3/internal tandem duplication (ITD)(+) LSCs. Our studies reveal highly synergistic drug activity, preferentially inducing apoptosis in FLT3/ITD(+) cell lines and patient samples. Colony-forming unit assays further demonstrate decreased clonogenicity of FLT3/ITD(+) cells upon treatment with ATRA and TKI. Most importantly, the drug combination depletes FLT3/ITD(+) LSCs in a genetic mouse model of AML, and prolongs survival of leukemic mice. Furthermore, engraftment of primary FLT3/ITD(+) patient samples is reduced in mice following treatment with FLT3 TKI and ATRA in combination, with evidence of cellular differentiation occurring in vivo. Mechanistically, we provide evidence that the synergism of ATRA and FLT3 TKIs is at least in part due to the observation that FLT3 TKI treatment upregulates the antiapoptotic protein Bcl6, limiting the drug's apoptotic effect. However, cotreatment with ATRA reduces Bcl6 expression to baseline levels through suppression of interleukin-6 receptor signaling. These studies provide evidence of the potential of this drug combination to eliminate FLT3/ITD(+) LSCs and reduce the rate of relapse in AML patients with FLT3 mutations.

Spiradiclis pengshuiensis Bo Pan & R. J. Wang (Rubiaceae) is described as a new species from Chongqing in SW China. It is morphologically compared with Spiradiclis pauciflora L. Wu & Q. R. Liu because of their similarities in habit, pubescent surface, small leaf laminas and subglobose capsules. Its conservation status is evaluated as "VU" according to the IUCN categories and criteria.

Background: Hydrogen sulfide (H2S) is a newly discovered gas transmitter. It is synthesized by cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (MPST). Endogenous hydrogen sulfide has never been studied in bladder cancer., Purpose: We evaluated H2S production and its synthases expression levels in transitional cell carcinoma (urothelial cell carcinoma of bladder [UCB]) of human bladder tissue and cell lines., Materials and Methods: Immunostaining was performed in urothelial cell lines and bladder specimens from 94 patients with UCB of different stages/grades. The expression levels/activities of CBS, CSE, and MPST of specimens and cell lines were analyzed by image semiquantity assay, western blot, and a sulfur-sensitive electrode. We tried to find the correlation between hydrogen sulfide and its synthases with tumor stage in UCB. All experiments were repeated at least 3 times., Results: Immunoreactivity for CBS, CSE, and MPST was detected in malignant uroepithelium and muscular layer of all tissues examined and cultured cells. The expression levels of CBS, CSE, and MPST were associated with UCB stage/grade. Muscle-invasive bladder cancer samples showed the highest production of H2S (52.6±2.91 nmol/[mg·min]) among all tested samples and EJ cells (transitional cell carcinoma, grade IIIshowed the highest production of H2S among all tested cell lines (53.3±7.02nmol/[mg·min])., Conclusions: Protein levels and catalytic activities of CBS, CSE, and MPST increased with the increase of malignant degrees in human bladder tissues and human UCB cell lines. Our findings may promote the application of these novel enzymes to UCB diagnosis or treatment., (Copyright © 2016 Elsevier Inc. All rights reserved.)

There have been a number of clinical trials testing the efficacy of FMS-like tyrosine kinase-3 (FLT3) tyrosine kinase inhibitors (TKI) in patients with acute myeloid leukemia (AML) harboring a constitutively activating mutation in FLT3. However, there has been limited efficacy, most often because of inadequate achievement of FLT3 inhibition through a variety of mechanisms. In a previous study, TTT-3002 was identified as a novel FLT3 inhibitor with the most potent activity to date against FLT3 internal tandem duplication (FLT3/ITD) mutations. Here, the activity of TTT-3002 is demonstrated against a broad spectrum of FLT3-activating point mutations, including the most frequently occurring D835 mutations. The compound is also active against a number of point mutations selected for in FLT3/ITD alleles that confer resistance to other TKIs, including the F691L gatekeeper mutation. TTT-3002 maintains activity against patients with relapsed AML samples that are resistant to sorafenib and AC220. Studies utilizing human plasma samples from healthy donors and patients with AML indicate that TTT-3002 is only moderately protein bound compared with several other TKIs currently in clinical trials. Tumor burden of mice in a FLT3 TKI-resistant transplant model is significantly improved by oral dosing of TTT-3002. Therefore, TTT-3002 has demonstrated preclinical potential as a promising new FLT3 TKI that may overcome some of the limitations of other TKIs in the treatment of FLT3-mutant AML. Cancer Res; 74(18); 5206-17. ©2014 AACR., (©2014 American Association for Cancer Research.)

Purpose: Our previous data have shown that emodin azide methyl anthraquinone derivative (AMAD) triggered mitochondrial- dependent cell apoptosis involving caspase-8-mediated Bid cleavage, and induced proteasomal degradation of HER2/neu by blocking Her2/neu binding to Hsp90. In the present study, we futher investigated the effect of this compound on the cell cycle and related molecular mechanisms in HER2/neu-overexpressing MDA-MB-453 breast cancer cells., Methods: The cell cycle distribution was tested by flow cytometry. The expression of cell cycle-related proteins was determined by Western blot analysis; DNA agarose gel electrophoresis was used to examine the apoptosis of MDAMB- 453 cells induced by emodin AMAD., Results: After MDA-MB-453 cells were treated with different concentrations of emodin AMAD for 24 hrs, cells were arrested in G0/G1 phase, and the expression of G0/G1 related proteins c/Myc, Cyclin D1, CDK4 and p-Rb changed. DNA fragmentation appeared on the agarose gel in a concentration- dependent manner., Conclusion: Emodin AMAD induced G0/G1 arrest in Her2/ neu-overexpressing MDA-MB-453 cancer cells. This G0/G1 arrest was associated with decreasing protein expression of c-Myc, Cyclin D1, CDK4, and p-Rb.